Comprehensive Textbook Of Echocardiography Volume 1

Vol. 1 Comprehensive Textbook of Echocardiography

.

Vol. 1 Comprehensive Textbook of Echocardiography

Editor

Navin C Nanda MD

Distinguished Professor of Medicine and Cardiovascular Disease and Director, Heart Station/Echocardiography Laboratories University of Alabama at Birmingham and the University of Alabama Health Services Foundation The Kirklin Clinic, Birmingham, Alabama, USA President, International Society of Cardiovascular Ultrasound

Under the Aegis of The International Society of Cardiovascular Ultrasound and The Indian Academy of Echocardiography

®

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD New Delhi • London • Philadelphia • Panama

®

Jaypee Brothers Medical Publishers (P) Ltd Headquarters Jaypee Brothers Medical Publishers (P) Ltd 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 Email: [email protected] Overseas Offices J.P. Medical Ltd 83, Victoria Street, London SW1H 0HW (UK) Phone: +44-2031708910 Fax: +02-03-0086180 Email: [email protected]

Jaypee-Highlights. Medical Publishers Inc City of Knowledge, Bld. 237 Clayton, Panama City, Panama Phone: +1 507-301-0496 Fax: +1 507-301-0499 Email: [email protected]

Jaypee Brothers Medical Publishers (P) Ltd 17/1-B Babar Road, Block-B Shaymali, Mohammadpur Dhaka-1207, Bangladesh Mobile: +08801912003485 Email: [email protected]

Jaypee Brothers Medical Publishers (P) Ltd Shorakhute, Kathmandu Nepal Phone: +00977-9841528578 Email: [email protected]

Jaypee Medical Inc. The Bourse 111 South Independence Mall East Suite 835, Philadelphia, PA 19106, USA Phone: +1 267-519-9789 Email: [email protected]

Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2014, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/ editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. Inquiries for bulk sales may be solicited at: [email protected] Comprehensive Textbook of Echocardiography (Vol. 1) First Edition: 2014 ISBN 978-93-5090-634-7 Printed at:

Dedicated to My late parents Balwant Rai Nanda MD and Mrs Maya Vati Nanda My wife Kanta Nanda MD Our children Nitin Nanda, Anita Nanda Wasan MD and Anil Nanda MD Their spouses Sanjeev Wasan MD and Seema Tailor Nanda, and our grandchildren Vinay and Rajesh Wasan, and Nayna and Ria Nanda

Contributors Masood Ahmad M  D FRCP (C) FACP FACC  

FAHA FASE

Division of Cardiology Department of Internal Medicine University of Texas Medical Branch Galveston Texas, USA

Dheeraj Arora DNB PDCC MNAMS Institute of Critical Care and Anesthesia Medanta The Medicity Gurgaon, Haryana, India

Mohammad Al-Admawi MD King Faisal Specialist Hospital and Research Center Heart Center Riyadh, Saudi Arabia

Bader Almahdi MD

Manreet Basra MBBS

Monodeep Biswas MBBS MD

Professor of Medicine University at Buffalo School of Medicine and Biological Sciences New York, USA

Division of Cardiology Geisinger-Community Medical Center, and The Wright Center for Graduate Medical Education Scranton, Pennsylvania, USA

Charles E Beale MD Department of Medicine Division of Cardiovascular Diseases Stony Brook University Medical Center Stony Brook, New York, USA

Roy Beigel MD The Heart Institute, Cedars Sinai Medical Center, Los Angeles, California, USA The Leviev Heart Center Sheba Medical Center, Affiliated to the Sackler School of Medicine Tel Aviv University, Tel Aviv, Israel

Steven Bleich MD Department of Medicine Division of Internal Medicine University of Alabama at Birmingham Birmingham, Alabama, USA

O Julian Booker MD Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Eduardo Bossone MD PhD FCCP FESC FACC

Echocardiography and Vascular Lab Assistant Professor of Medicine New York University School of Medicine New York, New York, USA

Via Principe Amedeo Lauro (AV), Italy Heart Department, University of Salerno, “Scuola Medica Salernitana” Salerno, Italy Department of Cardiac Surgery IRCCS Policlinico San Donato, Milan, Italy

Division of Cardiology Department of Medicine University of Texas Medical Branch Galveston, Texas, USA

Kunal Bhagatwala MBBS

Luis Bowen MD

Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Department of Medicine University of Alabama at Birmingham Birmingham, Alabama, USA

Neeraj Awasthy FNB

Aditya Bharadwaj MD

Gerald Buckberg MD

Department of Cardiology Loma Linda University and VA Medical Centers Loma Linda, California, USA

Department of Cardiothoracic Surgery David Geffen School of Medicine University of California-Los Angeles Los Angeles, California, USA

Heart Center, St Christopher’s Hospital for Children and Section of Cardiology Department of Pediatrics, Drexel University College of Medicine Philadelphia, Pennsylvania, USA

Aarti H Bhat MBBS

Michael J Campbell MD

Assistant Professor Division of Pediatric Cardiology Seattle Children’s Hospital and University of Washington Seattle, Washington, USA

Department of Pediatrics Division of Pediatric Cardiology Duke University Medical Center Durham, North Carolina, USA

Piers Barker MD

Nicole Bhave MD

    FRCP FACC

Department of Pediatrics Division of Pediatric Cardiology Duke University Medical Center Durham, North Carolina, USA

University Health Network Toronto General Hospital University of Toronto Toronto, Ontario, Canada

Professor Emeritus Division of Cardiology UC-Irvine School of Medicine Irvine, California, USA

King Faisal Specialist Hospital and Research Center Heart Center Riyadh, Saudi Arabia

Ahmed Almomani MBBS

Fortis Escorts Heart Institute New Delhi, India

Rula Balluz MD MPH

Ricardo Benenstein MD

Premindra PAN Chandraratna MD

viii

Comprehensive Textbook of Echocardiography

Leon H Charney

Michele D’ Alto MD PhD

Daniel Forsha MD

Division of Cardiology New York University Medical Center New York, New York, USA

Department of Cardiology Second University of Naples: Monaldi Hospital, Naples, Italy

Department of Pediatrics Division of Pediatric Cardiology Duke University Medical Center Durham, North Carolina, USA

Farooq A Chaudhry M  D FACP FACC

David Daly MD

FASE FAHA

Professor of Medicine Director, Echocardiography Laboratories Associate Director, Mount Sinai Heart Network, Icahn School of Medicine at Mount Sinai, Zena and Michael A Wiener Cardiovascular Institute and Marie-Josée and Henry R Kravis Center for Cardiovascular Health New York, New York, USA

Preeti Chaurasia MD Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama

Reema Chugh MD FACC Consultant in Cardiology/Specialist in Adult Congenital Heart Disease and Heart Disease in Pregnancy Kaiser Permanente Medical Center Panorama City, California, USA

Krishnaswamy Chandrasekaran MD Mayo Clinic, Scottsdale, Arizona, USA Rochester, Minnesota, USA

Michael Chen MD University of Washington Seattle, Washington DC, USA

HK Chopra MD Moolchand City Hospital New Delhi, India

Department of Medicine University of Alabama at Birmingham Birmingham, Alabama, USA

Hisham Dokainish M  D FRCPC Associate Professor of Medicine McMaster University Director of Echocardiography and Medical Diagnostic Units Hamilton Health Sciences Hamilton, Ontario, Canada

Maximiliano German Amado Escañuela MD Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Bahaa M Fadel MD King Faisal Specialist Hospital and Research Center Heart Center Riyadh, Saudi Arabia

Naveen Garg MBBS Dip. Cardiology Fellow, Noninvasive Cardiac Lab Indraprastha Apollo Hospitals New Delhi, India

Luna Gargani MD Institute of Clinical Physiology National Research Council Pisa, Italy

Eleonora Gashi DO MPhil

Robert P Gatewood Jr MD FACC

Division of Cardiology Fondazione Cardiocentro Ticino Lugano, Switzerland

Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Honorary Consultant Imperial and King's Colleges, London, UK

University of Illinois Hospital & Health Science System Jesse Brown VA Medical Center Chicago, Illinois, USA

Francesco Faletra MD

Francesco Ferrara MD

David Cosgrove MD

Leon J Frazin MD

Fellow, Division of Cardiology Allegheny General Hospital Pittsburgh, Pennsylvania, USA

Heart Department, University of Salerno “Scuola Medica Salernitana” Salerno, Italy Department of Internal Medicine and Cardiovascular Sciences University “Federico II” of Naples Naples, Italy

Director, Division of Clinical Cardiology Program Director, Cardiovascular Fellowship, Lenox Hill Hospital New York, USA

Department of Cardiology Loma Linda University and VA Medical Centers, Loma Linda California, USA

Senior Cardiology Fellow Lenox Hill Hospital Non-Invasive Cardiology New York, New York, USA

Abid Ali Fakhri MD

Cecil Coghlan MD

Neil L Coplan MD FACC

Gary P Foster MD

Brandon Fornwalt MD PhD Assistant Professor of Pediatrics Department of Pediatrics University of Kentucky Lexington, Kentucky, USA

Chief of Cardiac Services Kaleida Heath; Clinical Associate Professor of Medicine University at Buffalo School of Medicine and Biological Sciences Buffalo Cardiology and Pulmonary Associates, Main Street Williamsville New York, USA

Shuping Ge MD FAAP FACC FASE Chief, Section of Cardiology St Christopher’s Hospital for Children Associate Professor of Pediatrics Drexel University College of Medicine Philadelphia, Pennsylvania, USA Acting Chair, Pediatric Cardiology Deborah Heart and Lung Center Browns Mills, New Jersey, USA

Contributors

ix

Gopal Ghimire MD DM MRCP

Donald Hagler MD

Rachel Hughes-Doichev MD FASE

Division of Cardiovascular Diseases University of Alabama at Birmingham Birmingham, Alabama, USA

Mayo Clinic Rochester, Minnesota, USA

Temple University School of Medicine Pittsburgh, Pennsylvania, USA

Stephanie El-Hajj MD

Arzu Ilercil MD

Nina Ghosh MD

Department of Internal Medicine Louisiana State University Health Sciences Center Baton Rouge, Louisiana, USA

Associate Professor of Medicine Department of Cardiovascular Sciences University of South Florida Tampa, Florida, USA

Kamran Haleem MD

Trevor Jenkins MD

Division of Cardiovascular Medicine Brigham and Women’s Hospital Harvard Medical School Francis Street Boston, Massachusetts, USA

Edward Gill MD Professor of Medicine and Cardiology, University of Washington Seattle, Washington DC, USA

Rohit Gokhale MBBS University at Buffalo Buffalo, New York, USA

Aasha S Gopal MS MD FACC FAHA FASE Associate Professor of Medicine Stony Brook University Stony Brook, New York, USA Director, Advanced Echocardiography St Francis Hospital, Washington Blvd Roslyn, New York, USA

Willem Gorissen Clinical Market Manager Toshiba Medical Systems Europe Zoetermeer, The Netherlands

Luis Gruberg MD FACC Department of Medicine Division of Cardiovascular Diseases Stony Brook University Medical Center Stony Brook, New York, USA

Rakesh Gupta MD JROP Healthcare New Delhi, India

Fadi G Hage MD Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA Section of Cardiology, Birmingham Veteran’s, Administration Medical Center Birmingham, Alabama, USA

Yale University New Haven, Connecticut, USA

Dan G Halpern MD St Luke’s-Roosevelt Hospital Center Columbia University, College of Physicians and Surgeons New York, New York, USA

Rachel Harris MD MPH Morehouse School of Medicine Section of Cardiology Assistant Professor Echo Lab Co-Director Grady Memorial Hospital Atlanta, Georgia, USA

Christine Henri MD Department of Cardiology Heart Valve Disease Clinic CHU Sart Tilman, University of Liège, Belgium

Julien IE Hoffman MD Department of Pediatrics University of California San Francisco, California, USA

Brian D Hoit MD Director of Echocardiography Harrington Heart & Vascular Center University Hospitals of Cleveland Texas, USA

Steven J Horn MD FACC FASE FASNC SUNY Buffalo Buffalo, New York, USA

Ming Chon Hsiung MD Cardiologist Cheng Hsin General Hospital Taipei, Taiwan

Harrington Heart and Vascular Institute University Hospital Case Medical Center, Cleveland Ohio, USA

Madhavi Kadiyala MD Saint Francis Hospital, Roslyn New York, USA

Arshad Kamel MD Department of Medicine University of Alabama at Huntsville Huntsville, Alabama, USA

Abdallah Kamouh MD University of Buffalo Buffalo, New York, USA

Poonam Malhotra Kapoor MD All India Institute of Medical Sciences New Delhi, India

Kanwal K Kapur MD DM Cardiology, Sr Consultant and Chief Noninvasive Cardiology Indraprastha Apollo Hospitals New Delhi, India Department of Noninvasive Cardiology Indraprastha Apollo Hospitals New Delhi, India

Nidhi M Karia MBBS Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Jarosław D Kasprzak MD Chair and Department of Cardiology Biegański Hospital Medical University of Lodz Lodz, Poland

x

Comprehensive Textbook of Echocardiography

Martin G Keane MD FACC FAHA FASE

Arthur J Labovitz MD

Gerald R Marx MD

Professor of Medicine Cardiology Section Director of Echocardiography Temple University School of Medicine Parkinson Pavilion, Suite North Broad Street, Philadelphia Pennsylvania, USA

Professor of Medicine Chair, Department of Cardiovascular Sciences University of South Florida Tampa, Florida, USA

Associate Professor Harvard School of Medicine Senior Associate Cardiology Boston Children’s Hospital Boston, Massachusetts, USA

Jennifer K Lang MD

Wilson Mathias Jr MD

University at Buffalo Buffalo, New York, USA

Heart Institute (InCor) The University of São Paulo School of Medicine and Fleury Group São Paulo, Brazil

Tuğba Kemaloğlu Öz MD Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Anant Kharod MD Department of Medicine University of Alabama at Birmingham Birmingham, Alabama, USA

Jennifer Kiessling MD Division of Cardiovascular Diseases, University of Alabama at Birmingham Birmingham, Alabama, USA

Allan L Klein M  D FRCP(C) FACC

Roberto M Lang MD University of Chicago Medical Center Chicago, Illinois, USA

Fabrice Larrazet MD PhD Department of Cardiology HÔpital Saint Camille Bry sur Marne, France

Steve W Leung MD Assistant Professor of Medicine Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky, USA

   FAHA FASE

Angele A A Mattoso MD Heart Institute (InCor) The University of São Paulo School of Medicine, São Paulo, Brazil and Santa Izabel Hospital, Salvador, Bahia

Sula Mazimba MD MPH Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Anjlee M Mehta MD Fellow, Division of Cardiology Dartmouth-Hitchcock Heart and Vascular Center Lebanon, New Hampshire, USA

Director, CV Imaging Research and Pericardial Center Professor of Medicine, Cleveland Clinic Heart and Vascular Institute Department of Cardiovascular Medicine Cleveland, Ohio, USA

Sachin Logani MD

Smadar Kort MD FACC FASE

Javier López MD PhD

Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Professor of Medicine State University of New York Stony Brook Director Non Inavasive Cardiac Imaging Director Echocardiography Diretor Valve Center, Stony Brook Medicine Stony Brook, New York, USA

Hospital Clinico Universitario de Valladolid, Spain

Yatin Mehta MD MNAMS FRCA FAMS

Itzhak Kronzon M  D FASE FACC FACP

Department of Medicine Division of Cardiovascular Diseases Stony Brook University Medical Center, Stony Brook New York, USA

    FIACTA FTEE FICCM

Judy R Mangion MD Division of Cardiovascular Medicine Brigham and Women’s Hospital Harvard Medical School Francis Street, Boston Massachusetts, USA

     FESC FAHA

Professor of Cardiology Hofstra University North Shore LIJ, School of Medicine Chief of Noninvasive Cardiac Imaging Lenox Hill Hospital Noninvasive Cardiology New York, New York, USA

Kruti Jayesh Mehta MBBS PGDCC

CN Manjunath MD DM Director, Professor and Head Department of Cardiology Sri Jayadeva Institute of Cardiovascular Sciences and Research Bannergutta Road Bengaluru, Karnataka, India

Institute of Critical Care and Anesthesia Medanta The Medicity Gurgaon, Haryana, India

Julien Magne PhD Department of Cardiology Heart Valve Disease Clinic CHU Sart Tilman, University of Liège, Belgium

Andrew P Miller MD Cardiovascular Associates Birmingham, Alabama, USA

Contributors

Dilbahar S Mohar MD

Ryozo Omoto MD

Eugenio Picano MD PhD

Division of Cardiology UC-Irvine School of Medicine Irvine, California, USA

Professor Emeritus, Saitama Medical University Honorary Director, Saitama Medical University Hospital Moro-Hongou, Moroyama Iruma-Gun, Saitama, Japan

Institute of Clinical Physiology National Research Council Pisa, Italy

Caroline Morbach MD Yale University New Haven, Connecticut, USA

Ahmad S Omran MD FACC FESC FASE

Loma Linda University Medical Center Loma Linda, California , USA Eisenhower Medical Center Rancho Mirage, California, USA

Consultant Cardiologist Head, Non-Invasive Cardiology Lab King Abdulaziz Cardiac Center–Riyadh Health Affairs–Ministry of National Guard Kingdom of Saudi Arabia

Nagaraja Moorthy MD DM

Jatinder Singh Pabla BSc (Hons) MBBS

Hoda Mojazi-Amiri MD

Assistant Professor Department of Cardiology Sri Jayadeva Institute of Cardiovascular Sciences and Research Bengaluru, Karnataka, India

Hirohiko Motoki MD Cardiovascular Research Imaging Fellow, Cleveland Clinic Foundation, Cleveland, Ohio, USA

Bernhard Mumm President and COO TomTec Imaging Systems GmbH, Edisonstr Unterschleissheim, Germany

Rachel Myers RDCS Allegheny General Hospital Pittsburgh, Pennsylvania, USA

Navin C Nanda MD Distinguished Professor of Medicine and Cardiovascular Disease and Director, Heart Station/Echocardiography Laboratories, University of Alabama at Birmingham and the University of Alabama Health Services Foundation The Kirklin Clinic, Birmingham Alabama, USA, President, International Society of Cardiovascular Ultrasound

Elizabeth Ofili MD MPH FACC Morehouse School of Medicine Chief of Section of Cardiology Associate Dean of Clinical Research Professor of Medicine Atlanta, Georgia, USA

xi

Luc A Pierard MD PhD Department of Cardiology Heart Valve Disease Clinic CHU Sart Tilman, University of Liège, Belgium

Atif N Qasim MD MSCE Assistant Professor of Medicine University of California San Francisco, California, USA

       MRCP

Department of Cardiovascular Medicine Northwick Park Hospital, Harrow, UK

Shyam Padmanabhan MD Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Ramdas G Pai MD Professor of Medicine Loma Linda University Medical Center Loma Linda, California, USA

Natesa G Pandian MD Professor, Tufts University School of Medicine, Director, Heart Valve Center Co-Director, Cardiovascular Imaging Center Director, Cardiovascular Ultrasound Research, Tufts Medical Center Boston, Massachusetts, USA

Satish K Parashar MD Metro Heart Institute New Delhi, India

Anita Radhakrishnan MD Fellow, Division of Cardiology Allegheny General Hospital Pittsburgh, Pennsylvania, USA

Peter S Rahko MD Professor of Medicine Division of Cardiovascular Medicine Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA

Rajesh Ramineni MD University of Texas Medical Branch Galveston, Texas, USA

JRTC Roelandt MD Professor of Cardiology Honorary Chairman, Thoraxcentre Erasmus University Medical Centre, Rotterdam The Netherlands

Lindsay Rogers MD

Department of Pediatrics Division of Pediatric Cardiology Vanderbilt University Medical Center Nashville, Tennessee, USA

Heart Center, St Christopher’s Hospital for Children and Section of Cardiology Department of Pediatrics Drexel University, College of Medicine Philadelphia, Pennsylvania, USA

Ashvin K Patel MD

Asad Ullah Roomi MD

University of Wisconsin School of Medicine and Public Health Madison, Wisconsin, USA

Prince Sultan Cardiac Center Military Hospital Riyadh Riyadh, Kingdom of Saudi Arabia

David A Parra MD

xii

Comprehensive Textbook of Echocardiography

José Alberto San Román MD PhD FESCC

Teresa Sevilla MD

Robert J Siegel MD

Hospital Clínico, Universitario de Valladolid, Spain

Hospital Clínico Universitario de Valladolid, Spain

The Heart Institute, Cedars Sinai Medical Center, Beverly Boulevard Los Angeles, California, USA

Emanuele Romeo MD

James Seward MD

Department of Cardiology Second University of Naples Monaldi Hospital, Naples, Italy

Mayo Clinic Rochester, Minnesota, USA

Utpal N Sagar MD Advanced Cardiovascular Imaging Fellow Heart and Vascular Institute Department of Cardiovascular Medicine Cleveland, Ohio, USA

Hamid Reza Salehi MD Research Fellow in Echocardiography Tufts Medical Center Boston, Massachusetts, USA

Ivan S Salgo MD MSc Philips Healthcare Andover, Massachusetts, USA

Giovanni Di Salvo MD King Faisal Specialist Hospital and Research Center Heart Center Riyadh, Saudi Arabia

 Benoy Nalin Shah BSc (Hons) MBBS MRCP

Department of Cardiovascular Medicine Northwick Park Hospital Harrow, UK Cardiovascular Biomedical Research Unit Royal Brompton Hospital London, UK National Heart and Lung Institute Imperial College London, UK

Chetan Shenoy MBBS Fellow in Cardiovascular Disease Tufts Medical Center Boston, Massachusetts, USA

Mark V Sherrid MD

Director, Echocardiography Lab Associate Professor of Medicine New York University Langone Medical Center New York, New York, USA

Director, Echocardiography Laboratory Roosevelt Division Program Director, Hypertrophic Cardiomyopathy Program St. Luke's-Roosevelt Hospital Center Professor, Clinical Medicine Columbia University, College of Physicians and Surgeons New York, New York, USA

Nelson B Schiller MD

Savitri Shrivastava MD DM FACC FAMS

Muhamed Saric MD PhD

Professor of Medicine University of California San Francisco UCSF Division of Cardiology Parnassus Avenue San Francisco, California, USA

Roxy Senior MD DM FRCP FESC FACC Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK National Heart and Lung Institute Imperial College, London, UK Department of Cardiovascular Medicine Northwick Park Hospital, Harrow, UK

Satinder P Singh MD FCCP Professor, Radiology and Medicine—Cardiovascular Disease Chief, Cardiopulmonary Radiology Chief, 3D Lab, Director, Cardiac CT Director, Combined Cardiopulmonary and Abdominal Imaging Fellowship Program University of Alabama at Birmingham Birmingham, Alabama, USA

Siddharth Singh MD MS Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Chittur A Sivaram MD David Ross Boyd Professor Vice Chief of Cardiovascular Section Associate Dean for Continuing Professional Development University of Oklahoma Health Sciences Center Oklahoma City, Oklahama, USA

Sushilkumar K Sonavane MD Assistant Professor Cardiopulmonary Radiology University of Alabama at Birmingham Department Radiology Birmingham, Alabama, USA

Vincent L Sorrell MD

Director Pediatric and Congenital Heart Diseases Fortis Escorts Heart Institute New Delhi, India

Anthony N DeMaria Professor of Medicine, Assistant Chief Division of Cardiovascular Medicine University of Kentucky Lexington, Kentucky, USA

Peter Sidarous MD

Jonathan H Soslow MD

Research Associate UC-Irvine School of Medicine Irvine, California, USA

Department of Pediatrics Division of Pediatric Cardiology Vanderbilt University Medical Center Nashville, Tennessee, USA

Khadija Siddiqui DO

Anna Agnese Stanziola MD

Division of Cardiology Department of Medicine University of Texas Medical Branch Galveston, Texas, USA

Clinical and Surgery Department Division of Respiratory Medicine University “Federico II”of Naples Naples, Italy

Contributors

Sharath Subramanian MD

George Thomas MD

Isidre Vilacosta MD PhD FESCC

Medical College of Wisconsin Milwaukee, Wisconsin, USA

Department of Cardiology Saraf Hospital, Kochi, Kerala, India

Lissa Sugeng MD

Wendy Tsang MD

Hospital Clínico San Carlos Madrid, Spain

Associate Professor Director of Yale Echo Lab and YRCG Echo Corelab Section of Cardiovascular Medicine Division of Medicine Yale University School of Medicine New Haven, Connecticut, USA

Jie Sun MD PhD Heart Center, St Christopher’s Hospital for Children and Section of Cardiology Department of Pediatrics Drexel University College of Medicine Philadelphia, Pennsylvania, USA

Aylin Sungur MD

University Health Network, Toronto General Hospital, University of Toronto Toronto, Ontario, Canada

Jeane M Tsutsui MD

Leon Varjabedian MD

Teena Tulaba RDCS

Karina Wierzbowska-Drabik MD

Allegheny General Hospital Pittsburgh, Pennsylvania, USA

Padmini Varadarajan MD Department of Cardiology Loma Linda University and VA Medical Centers, Loma Linda, California, USA

Azhar Supariwala MD

Mahdi Veillet-Chowdhury MD

Division of Cardiology St Luke’s-Roosevelt Hospital Center New York, New York, USA

Stony Brook University Medical Center Health Sciences Center Stony Brook, New York, USA

Department of Cardiology Loma Linda University and VA Medical Centers Loma Linda, California, USA

Kiyoshi Tamura PhD Hitachi Aloka Medical, Ltd. Imai, Ome-Shi, Tokyo, Japan

Rohit Tandon MBBS MD Dayanand Medical College and Hospital Unit, Hero DMC Heart Institute Ludhiana, Punjab, India

University of Buffalo Buffalo, New York, USA

Heart Institute (InCor), The University of São Paulo School of Medicine and Fleury Group, São Paulo, Brazil

Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham, Alabama, USA

Pooja Swamy MD

Victor Vacanti MD

Colette Veyrat MD Centre National de la Recherche Scientifique Honorary Researcher Department of Cardiovascular Medicine L’Institut Mutualiste de Montsouris Boulevard Jourdan, Paris Cedex, France

IB Vijayalakshmi MD DM (Card) FICC   

FIAMS FIAE FICP FCSI FAMS DSc

Professor of Pediatric Cardiology Sri Jayadeva Institute of Cardiovascular Sciences and Research Bengaluru, Karnataka, India

University of Buffalo Buffalo, New York, USA

Chair and Department of Cardiology Biegański Hospital Medical University of Lodz Lodz, Poland

Timothy D Woods MD Associate Professor of Medicine and Radiology Medical College of Wisconsin Cardiology Division Milwaukee, Wisconsin, USA

Siu-Sun Yao MD FACC Division of Cardiology Valley Health System Ridgewood New Jersey, USA

Elisa Zaragoza-Macias MD MPH Cardiovascular Diseases Fellow University of Washington Seattle, Washington, USA

xiii

Preface Monumental strides have occurred in the evolution of echocardiography since its first introduction in the 1950s. It began with A-mode and M-mode echocardiography which progressed to real time two-dimensional echocardiography in the 1970s after a hiatus of several years. This development completely revolutionized the field of noninvasive cardiac imaging; and within a few years of its introduction, there were hardly any cardiology divisions in any hospital anywhere in the world which did not own an ultrasound machine. The next few years saw the development of continuous and pulsed wave Doppler and color Doppler flow imaging which provided assessment of cardiac hemodynamics to supplement the structural information obtained using two-dimensional echocardiography. Other advances rapidly followed or occurred concurrently. These included stress echocardiography, transesophageal echocardiography, contrast echocardiography and tissue Doppler and velocity vector imaging. More recently, further innovations were introduced such as live/real time three-dimensional echocardiography and both two-and three-dimensional speckle tracking echocardiography which have obviated some of the limitations of the previous techniques and have further enhanced the clinical usefulness of echocardiography. To this day, echocardiography represents the most useful and most costeffective noninvasive modality available for the assessment of various cardiac disease entities. The development of allied noninvasive technologies like magnetic resonance imaging and computed tomography has further added to the information provided by echocardiography and are useful and important additions to the armamentarium of the cardiologists and other patient care providers in the comprehensive assessment and management of cardiac disease. The aim of the current book is to provide an overview of the subject of clinical echocardiography as it is practiced to-day. Given the many advances that have not only been recently introduced but are also ongoing in this field it would be very difficult for anyone to realistically come up with a comprehensive book on echocardiography but an attempt has been made to cover as many topics as possible in this book. In addition, the supplementary information provided by magnetic resonance imaging and computed tomography is also included in this book. The book consists of a total of 85 chapters organized into seven sections. The first section deals with the basics of ultrasound, Doppler, speckle tracking, three-dimensional echocardiography and instrumentation. A short history of echocardiography and Doppler are also included in this section. The second section consists of various aspects of echocardiography and ultrasound examination. M-mode and two- and three-dimensional transthoracic and transesophageal examination, nonstandard planes, various aspects of Doppler assessment including tissue Doppler, velocity vector and speckle tracking imaging, assessment of endothelial function, contrast echocardiography for evaluation of left ventricular endocardial border opacification and myocardial perfusion, transpharyngeal echo, epiaortic echocardiography and both intracardiac and intravascular ultrasound are dealt with in this section. In addition, examination with a small hand-held ultrasound system, peripheral ultrasound, echocardiographic artifacts, quantification techniques in echocardiography and echocardiography training form a part of this section. Valvular heart disease is covered in the next section. It deals with evaluation of mitral valve disease, mitral regurgitation, aortic stenosis including assessment of low gradient stenosis with preserved left ventricular function, aortic regurgitation, aortic disease, tricuspid and pulmonary valves, pulmonary hypertension, infective endocarditis and prosthetic valves. Rheumatic heart disease is also included in this section. Section 4 deals with two- and three-dimensional echocardiographic assessment of systolic and diastolic function of both left and right ventricles. Newer aspects of structure and function to assess cardiac motion, evaluation of left atrial function, ventricular assist devices, pacemakers and intracardiac defibrillators and use of echocardiography for the assessment of cardiac hemodynamics and guidance of therapy are also included in this section. The next section contains chapters covering ischemic heart disease, coronary arteries and coronary flow reserve,

xvi

Comprehensive Textbook of Echocardiography

different aspects of stress echocardiography including three-dimensional stress echocardiography, obstructive and non-obstructive cardiomyopathies, differentiation of ischemic and nonischemic cardiomyopathy, pericardial disorders and tumors and masses. Section 6 deals with congenital heart disease and consists of chapters on fetal cardiac imaging, M-mode and two- and three-dimensional assessment of pediatric congenital heart disease, ventricular function, adult congenital heart disease and acquired heart diseases in childhood. The final section in the book, Section 7, covers systemic diseases, life-threatening conditions, echocardiography in women and the elderly, echocardiography for the electrophysiologist and lung ultrasound. A separate chapter assesses the future of echocardiography and ultrasound. Lastly, two chapters cover the allied techniques of magnetic resonance imaging and cardiac computed tomographic imaging. A very large number of echocardiographic images and other figures illustrate most of the chapters of the book and six DVDs contain numerous movie clips to supplement the images. These represent a major highlight of the book. All chapters in this book are written by well-known experts in the field of echocardiography and ultrasound. Because of the large number of contributors, some overlap of content and chapters do exist in the book. This has been deliberately not excluded because it provides a different perspective to the reader and also serves to reinforce important concepts and echocardiographic findings. Navin C Nanda MD

Acknowledgments I am most grateful to all the contributors from different countries of the world who have taken valuable time off from their busy schedule to prepare chapters for this book. I am also grateful to the faculty, clinical and research fellows, medical residents, and observers, both past and present, from our institution who have directly or indirectly helped in the preparation of this book. Special mention needs to be made of Kunal Bhagatwala, Nidhi M Karia, Steven Bleich, Aylin Sungur, Tuğba Kemaloğlu Öz, Kruti Jayesh Mehta, Maximiliano German Amado Escañuela and Ming Hsuing for their invaluable help. I wish to express my thanks to the International Society of Cardiovascular Ultrasound and the Indian Academy of Echocardiography for agreeing to have the book under their aegis. Special thanks to all the members of the Indian Academy of Echocardiography including the current President Dr ST Yavagal as well as Drs Satish Parashar, HK Chopra and Rakesh Gupta for their unstinting support of this project. I especially appreciate the constant support and encouragement of Shri Jitendar P Vij (Group Chairman) and Mr Ankit Vij (Managing Director) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India, in helping publish this book and also all their associates particularly Ms Chetna Malhotra Vohra (Senior Manager–Business Development) and Ms Saima Rashid (Development Editor) who have been prompt, efficient and most helpful. I also deeply appreciate the help of Lindy Chapman, Administrative Associate at the University of Alabama at Birmingham, who provided excellent editorial and secretarial assistance, and Diane Blizzard, Office Associate, for her help. Last but not least, I appreciate the patience, understanding and support of my wife, Kanta Nanda.

Contents

xix

Contents Volume 1

Section 1: History and Basics 1. History of Echocardiography

3

Fadi G Hage, Anant Kharod, David Daly, Navin C Nanda • • • • • • • • • •

History of Ultrasound  4 The Development of Clinical Cardiac Ultrasound: A-Mode and M-Mode Echocardiography  4 Two-Dimensional Echocardiography  8 Conventional Doppler Ultrasound  9 Color Doppler Ultrasound  11 Contrast Echocardiography  11 Transesophageal Echocardiography  13 Tissue Doppler and Speckle Tracking Imaging  14 Three-Dimensional Echocardiography  14 Perspective  19

2. Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

24

Colette Veyrat • The Preflow Doppler Era: Paucity of Existing Noninvasive Tools  25 • Explosive Emergence of the “Flow Concept”, an Indispensable Mutation from Pressure Measurements, which Prepared the Doppler Flow Era  27 • Return to the Doppler Technique in Search of a Noninvasive Tool Documenting the “Flow Concept”  28

3. Basics of Ultrasound

55

Caroline Morbach, Kamran Haleem, Lissa Sugeng • • • • •

General Physics  55 Imaging by Ultrasound  57 Image Optimization and Equipment  60 Artifacts  61 Doppler Ultrasound  63

4. Doppler Echocardiography—Methodology, Application and Pitfalls George Thomas • • • • •

Doppler in Cardiology  65 Doppler Instrumentation  66 Continuous Wave Doppler  68 Pulsed Wave Doppler  69 Color Doppler  71

65

xx

Comprehensive Textbook of Echocardiography

• • • •

Power Doppler  71 Tissue Doppler  72 The Doppler Methodology  72 Information Derived from Doppler  73

5. Basics of 3D Ultrasound

74

Ivan S Salgo, Wendy Tsang, Nicole Bhave, Roberto M Lang • • • • • •

Evolution of 3D Echocardiography  74 Transducer Technology  76 Beam Forming  77 Rendering  78 Limitations in 3D Image Quality  80 3D Echocardiography Quantification  81

6. Speckle Tracking Acquisition: Basics and Practical Tips

87

Willem Gorissen, Navin C Nanda • • • • • • • • • • • • • •

M-Mode (1D Speckle Tracking)  87 Two-Dimensional Speckle Tracking  88 R-R Interval  91 Standard Views  91 Standardization  91 Two-Dimensional Speckle Tracking Limitation  92 Speckle Tracking Versus Tissue Doppler Imaging  92 Tissue Doppler Imaging Versus Speckle Tracking  92 Three-Dimensional Acquisition  92 Multiview Monitoring During Live Acquisition  97 Multiview Orientation  97 Gain Setting  97 Patient Breath-Hold  98 Arrhythmias  98

7. Instrumentation for Transesophageal Echocardiography Including New Technology

99

Ryozo Omoto, Kiyoshi Tamura • • • • • •

Kinds of Transesophageal Echo (TEE)  99 What Makes Image Quality  104 Artifacts  107 Safety Considerations  110 Current and Future Technologies  112 In the Future  116

Section 2: Echocardiography/Ultrasound Examination and Training 8. M-Mode Examination Kamran Haleem, Caroline Morbach, Lissa Sugeng • Historical Perspective  119 • Underlying Concept  119

119

Contents

xxi

• Color M-Mode  120 • Advantages and Disadvantages of M-Mode  120 • Use of M-Mode  121

9. The Complete Transthoracic Echocardiography

132

Rachel Hughes-Doichev, Anita Radhakrishnan, Abid Ali Fakhri Teena Tulaba, Rachel Myers • • • • • • • • •

Getting Started  132 Echocardiographic Imaging Windows and Planes  135 Imaging Modalities  135 Parasternal Window  137 Apical Window  146 Subcostal Window  155 Suprasternal Notch Window  159 Three-Dimensional Echocardiography  159 Left Ventricle Chamber Quantification and Regional Wall Motion Determination  161

10. The Standard Transthoracic Examination: A Different Perspective

164

Atif N Qasim, Nelson B Schiller • Set-Up and Patient Positioning  164 • Imaged Planes  166

11. Nonstandard Echocardiographic Examination

188

Navin C Nanda, Aylin Sungur, Kunal Bhagatwala, Nidhi M Karia, Tuğba Kemaloğlu Öz • • • • • •

Right Parasternal Examination Planes   188 Right and Left Supraclavicular Examination  189 Left Parasternal and Apical Planes for Examination of Coronary Arteries  190 Examination of Left Atrial Appendage  212 Examination from the Back  216 Abdominal Examination  220

12. Technique and Applications of Continuous Transthoracic Cardiac Imaging

224

Premindra PAN Chandraratna, Dilbahar S Mohar, Peter Sidarous • Feasibility of Continuous Cardiac Imaging  224 • Limitations  237

13. The Basics of Performing Three-Dimensional Echocardiography Steven Bleich, Navin C Nanda, Satish K Parashar, HK Chopra, Rakesh Gupta • • • • • • • • • •

3D Technology  240 3D Examination Protocol  241 Left Parasternal Approach  244 Apical Approach  244 Subcostal Approach  244 Suprasternal Approach  244 Supraclavicular Approach  244 Right Parasternal Approach  246 Color Doppler Imaging  248 Advantages/Disadvantages of 3D Echocardiography  262

240

xxii

Comprehensive Textbook of Echocardiography

14. How to do Three-Dimensional Transthoracic Echocardiography Examination

268

Fabrice Larrazet, Colette Veyrat • • • • • • • • • • • •

History  268 Methods for Data Acquisition  268 Left Ventricular Assessment  270 Reproducibility  272 Regional LV Function  276 Aortic Regurgitation  280 Aortic Annulus  280 Mitral Stenosis  280 Mitral Regurgitation  282 Tricuspid Valve Disease  283 Pulmonic Valve Disease  284 Advances in Pediatric and Fetal Cardiac Pathologies  285

15. Point-of-Care Diagnosis with Ultrasound Stethoscopy

291

JRTC Roelandt • • • • • • • • •

Battery-Powered Ultrasound Imagers  291 The Traditional Physical Examination  292 The New Physical Examination  293 Acute Care Environment  294 Screening  294 Preparticipation Screening of Athletes  295 Imaging in Remote Areas and Developing Countries  295 Training Requirements  295 Future Directions  296

16. Spectral Doppler of the Hepatic Veins

299

Bahaa M Fadel, Bader Almahdi, Mohammad Al-Admawi, Giovanni Di Salvo • • • • • • • •

Imaging of the Hepatic Veins  299 Physiological and Other Factors that Affect Hepatic Venous Flow  302 Doppler Pattern of the Hepatic Veins Versus the Superior Vena Cava  304 Transthoracic Echocardiography  304 Transesophageal Echocardiography  305 Technical Considerations  305 Hepatic Venous Flow in Disease States  305 Limitations, Technical Pitfalls and Artifacts  319

17. Spectral Doppler of the Pulmonary Veins Bahaa M Fadel, Bader Almahdi, Mohammad Al-Admawi, Giovanni Di Salvo • • • • • •

Historical Perspective  325 Imaging of the Pulmonary Veins  325 Physiological Factors that Affect Pulmonary Venous Flow  329 Pulmonary Venous Flow in Disease States  331 Limitations and Technical Pitfalls  342 Artifacts  343

325

Contents

18. Tissue Doppler Imaging

xxiii 349

Hisham Dokainish • Technical Considerations  349 • Development of Tissue Doppler Imaging  350 • Current Clinical Uses of TD Imaging  350

19. Speckle Tracking Echocardiography: Clinical Usefulness

360

Shyam Padmanabhan, Siddharth Singh, Navin C Nanda • • • • • • • •

Cardiac Muscular Anatomy, Cardiac Mechanics  360 What is Strain?  362 Two-Dimensional Speckle Tracking Echocardiography (2D STE)  365 Image Acquisition and Processing  367 Clinical Application of 2D STE  367 Three-Dimensional Speckle Tracking Echocardiography (3D STE)  372 Clinical Applications of 3D STE  373 Limitations of Speckle Tracking Echocardiography  374

20. Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

380

Michael J Campbell, David A Parra, Daniel Forsha, Piers Barker, Jonathan H Soslow • • • •

Application of Velocity Vector Imaging by Age and Disease Group  390 Dyssynchrony, Velocity Vector Imaging Analysis  400 Reproducibility and Correlation Between Vendors  401 Future Directions  404

21. Contrast Echocardiography

416

Jatinder Singh Pabla, Benoy Nalin Shah, Roxy Senior • • • • • • •

What is Ultrasound Contrast?  416 How does Ultrasound Contrast Work?  417 Indications for the Use of Ultrasound Contrast  426 Why Should I Use Ultrasound Contrast Agents?  428 Practical Tips  431 Safety of Ultrasound Contrast Agents  434 Saline Contrast Echocardiography  435

22. Myocardial Perfusion Echocardiography

441

Angele A A Mattoso, Jeane M Tsutsui, Wilson Mathias Jr • Acute Coronary Syndromes  443 • Assessment of Myocardial Viability  443 • Chronic Coronary Artery Disease  443

23. Endothelial Dysfunction Naveen Garg, Kanwal K Kapur • History  450 • Endothelial Functions  450 • Endothelial Dysfunctions  451

449

xxiv

Comprehensive Textbook of Echocardiography

• • • • • • • • • • •

Role of Acetylcholine  451 Shear Stress and Flow-Mediated Dilatation  452 Vasoactive Molecules Involved in Vasoregulation  454 NO Release  455 Methodology for Assessing Endothelial Function  455 Analysis of Shear Stress and Flow-Mediated Dilatation Response  457 Limitations  458 Factors Affecting the Flow-Mediated Dilatation  463 Clinical Utility  465 Other Noninvasive Methods to Assess Endothelial Function  465 Assessment of Endothelial Function and Future Directions  471

24. How to do a Two-Dimensional Transesophageal Examination

480

Andrew P Miller, Navin C Nanda • Patient Selection and Consent  480 • Preparation, Conscious Sedation and Esophageal Intubation  480 • The TEE Examination  481

25. Upper Transesophageal and Transpharyngeal Examination

487

Stephanie El-Hajj, Navin C Nanda, Kunal Bhagatwala, Nidhi M Karia, Fadi G Hage • Technique and Recognition of Vessels  487 • Application  495

26. How to Perform a Three-Dimensional Transesophageal Echocardiogram

507

Elisa Zaragoza-Macias, Michael Chen, Edward Gill • • • •

Three-Dimensional Transesophageal Technology  507 Performing 3D TEE Evaluation  508 Specific Uses of 3D TEE  512 Guidelines and Final Recommendations  514

27. Three-Dimensional Examination to Evaluate Valvular Heart Disease: The Value of an Added Dimension Nina Ghosh, Judy R Mangion • • • • • •

Data Acquisition  515 3D Echo Image Optimization  516 3D Echo of the Mitral Valve  516 3D Echo of the Aortic Valve  520 3D Echo of the Pulmonic Valve  522 3D Echo of the Tricuspid Valve  523

Case Examples of 3D Echo in Valvular Heart Disease  525 • • • • • • •

Case Study 1: Paravalvular Leak Mechanical MV  525 Case Study 2: MV Repair and Aortic Valve Replacement  526 Case Study 3: S/P Cardiac Transplant with Right Heart Failure, Tricuspid Valve Replacement  526 Case Study 4: Flail Middle-Scallop, Posterior Leaflet, MV  526 Case Study 5: Bileaflet MV Prolapse, Moderate to Severe Mitral Insufficiency  527 Case Study 6: Severe Aortic Stenosis, Evaluate for Possible TAVR  527 Case Study 7: Rheumatic Mitral Stenosis  527

515

Contents

xxv

• Case Study 8: S/P Balloon Aortic Valvuloplasty  527 • Case Study 9: Mechanism and Severity of Eccentric Mitral Insufficiency  528 • Case Study 10: Question of Carcinoid Involvement of the Pulmonic Valve  528

28. Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures 531 Muhamed Saric, Ricardo Benenstein • • • • • • •

Fluoroscopy Versus Echocardiography in Guiding Percutaneous Interventions  532 Transseptal Puncture: A Common Element of Many Interventional Procedures  532 Valvular Disease  533 Device Closure of Cardiac Shunts  548 Occlusion of the Left Atrial Appendage  559 Guidance of Electrophysiology Procedures  566 Miscellaneous Procedures  569

29. Three-Dimensional Echocardiography in the Operating Room

577

Ahmad S Omran • • • • • • •

Mitral Valve Disease  577 Aortic Valve Disease  582 Tricuspid Valve Disease  589 Native Valve Endocarditis  597 Prosthetic Valve Dysfunction  605 Cardiac Masses  617 Limitations of 3D TEE, Future Directions  628

30. Epiaortic Ultrasonography

638

Dheeraj Arora, Yatin Mehta • • • • • •

Background for Epiaortic Ultrasonography Examination  638 Indications  638 Epiaortic Probe and Preparation  638 Imaging Views/Planes  639 Role of Epiaortic Ultrasonography in Aortic Pathology  640 Advantages of Three-Dimensions over Two-Dimensions in Epiaortic Ultrasonography  641

31. Intracardiac Echocardiography

643

Krishnaswamy Chandrasekaran, Donald Hagler, James Seward • • • • •

Equipment and the Catheters  643 Imaging Specifications  644 Intracardiac Echocardiography: Clinical Applications  644 Intracardiac Echocardiography during Electrophysiology (EP) Intervention  644 Intracardiac Echocardiography during Structural Intervention  648

32. Intravascular Ultrasound Imaging Sachin Logani, Charles E Beale, Luis Gruberg, Smadar Kort • • • • • • •

Principles of Ultrasound Technology  655 Image Acquisition  655 Intravascular Ultrasound Examination  656 Image Interpretation  657 Utility of Intravascular Ultrasound in Clinical Practice  659 Safety Considerations  661 Future Perspectives  661

655

xxvi

Comprehensive Textbook of Echocardiography

33. Peripheral Vascular Ultrasound

663

Ricardo Benenstein, Muhamed Saric • Ultrasound Diagnosis of Carotid Artery Diseases  663 • Ultrasound Diagnosis of Femoral Access Complications  694

34. Advanced Noninvasive Quantification Techniques in Echocardiography

705

Bernhard Mumm, Navin C Nanda • • • • • •

Technological Background of the Different Advanced Quantification Tools  706 Clinical Applications of Advanced Three-Dimensional Echo Quantification Tools  721 Right Ventricular Quantification  723 Mitral Valve Assessment  725 Aortic Valve Assessment  727 Conclusion and Future Outlook  728

35. Artifacts in Echocardiography

732

Shyam Padmanabhan, Navin C Nanda, Aylin Sungur, Tuğba Kemaloğlu Öz, Kunal Bhagatwala, Nidhi M Karia, Kruti Jayesh Mehta, Rohit Tandon • • • • • • • • • •

Acoustic Shadowing and Acoustic Enhancement  733 Reverberation Artifacts  734 Mirror Image Artifacts  735 Double Image Artifacts  736 Side Lobe Artifact  736 Artifacts Secondary to Use of Electronic Equipment  736 Aliasing  736 Range Ambiguity  736 Artifacts in Three-Dimensional Echocardiography  736 Techniques to Identify and Eliminate Artifacts  737

36. Echocardiography Training

750

Monodeep Biswas, Steven Bleich, Navin C Nanda • • • • •

Training of Noncardiologists  752 Training for Cardiac Sonographers  753 Training in Computed Tomography and Magnetic Resonance Imaging  755 Certification and Maintenance of Proficiency  758 Appropriate Use Criteria  758

Section 3: Valvular Heart Disease 37. Echocardiography in Acute Rheumatic Fever and Chronic Rheumatic Heart Disease IB Vijayalakshmi • • • • • •

Echocardiography in the Diagnosis of Carditis in ARF  765 Chronic Rheumatic Heart Disease  775 Mitral Valve Diseases  775 Mitral Stenosis  776 Mitral Regurgitation  791 Aortic Valve Diseases  802

765

Contents

• • • • •

xxvii

Aortic Stenosis  802 Aortic Regurgitation  806 Tricuspid Valve Diseases  812 Tricuspid Stenosis  812 Tricuspid Regurgitation  813

38. Echocardiographic Assessment of Mitral Valve Disease

826

C N Manjunath, Nagaraja Moorthy, Luis Bowen, Navin C Nanda • • • •

Overview  826 Echocardiographic Assessment of Mitral Stenosis  826 Echocardiographic Assessment of Mitral Regurgitation  847 Assessment of Severity of Mitral Regurgitation  863

39. Mitral Regurgitation

880

Luc A Pierard, Christine Henri, Julien Magne • • • • • • •

Etiology  880 Mechanisms  884 Severity of Mitral Regurgitation  885 Mitral Regurgitation Consequences  889 Sequential Evaluation of Chronic Asymptomatic Mitral Regurgitation  890 Feasibility of Mitral Valve Repair  892 Role of Exercise Echocardiography  892

40. Aortic Stenosis

896

Timothy D Woods, Ashvin K Patel, Sharath Subramanian • • • • • •

Normal Aortic Valve Anatomy  896 Etiology of Aortic Stenosis  897 Echocardiography in Aortic Stenosis  898 Aortic Valve Doppler Examination  904 Use of Stress Echo and Strain in Evaluation of Aortic Stenosis  912 Indications and Appropriateness for Echocardiography in Aortic Valve Stenosis  913

41. Low-Gradient, Severe Aortic Stenosis with Depressed and Preserved Ejection Fraction

919

Eleonora Gashi, Neil L Coplan, Itzhak Kronzon • • • • • • • •

Myocardial Response to Chronic Aortic Stenosis  920 High-Flow, High-Gradient Aortic Stenosis in Setting of Normal Ejection Fraction  920 Low-Flow, Low-Gradient Aortic Stenosis in Setting of Low Ejection Fraction  920 Low-Flow, Low-Gradient Aortic Stenosis in Setting of Normal Ejection Fraction  921 Mechanisms Behind PLFLG-AS  924 Role of Surgical Aortic Valve Replacement (SAVR) in Aortic Stenosis  926 SAVR in Low-Flow, Low-Gradient Aortic Stenosis with Low Ejection Fraction  927 SAVR in Paradoxical Low-Flow, Low-Gradient Aortic Stenosis with Normal Ejection Fraction  927

42. Aortic Regurgitation Arzu Ilercil, Arthur J Labovitz • AR Etiologies  930 • Quantification of AR Severity  936 • Timing of Aortic Valve Surgery  941

930

xxviii

Comprehensive Textbook of Echocardiography

43. Echocardiographic Evaluation of Aortic Disease

945

Martin G Keane • • • • • • •

Echocardiographic Evaluation of the Aorta  945 Aortic Aneurysms  951 Aortic Dissection  954 Common Genetic Syndromes Affecting the Aorta  958 Aortic Atheroma  959 Aortic Trauma and Free Rupture  961 Coarctation of the Aorta  963

44. Transesophageal Echocardiography in the Diagnosis of Aortic Disease

967

Leon J Frazin • The Anatomical Relationship of the Aorta and Esophagus  967 • Imaging the Aorta with Trans­esophageal Echocardiography  967

45. Echocardiographic Examination of the Tricuspid Valve

984

Poonam Malhotra Kapoor, Kunal Bhagatwala, Nidhi M Karia, Navin C Nanda • • • • • • • •

The Anatomy of Tricuspid Valve (TV)  984 M-Mode Echocardiography  984 Two-Dimensional (2D) Transthoracic Examination  986 Two-Dimensional Transeso­phageal Examination  988 Three-Dimensional Examination  988 Tricuspid Regurgitation  990 Tricuspid Stenosis  1004 Tricuspid Valve Prolapse: Flail Tricuspid Valve  1007

46. Echocardiographic Assessment of Pulmonary Valve

1031

Hoda Mojazi-Amiri, Padmini Varadarajan, Ramdas G Pai • • • • • • •

Epidemiology  1031 Pulmonary Stenosis  1032 Pulmonary Regurgitation  1036 Echocardiographic Evaluation  1037 Ross Procedure  1038 Postpulmonary Valve Surgery: Monitoring Sequelae  1039 Other Complementary Techniques for Evaluation of Pulmonary Valves  1040

47. Echocardiography in Infective Endocarditis

1042

Javier López, Teresa Sevilla, José Alberto San Román, Isidre Vilacosta, Maximiliano German Amado Escanuela, Kunal Bhagatwala, Nidhi M Karia, Navin C Nanda • • • •

Echocardiographic Findings in Infective Endocarditis  1043 Special Considerations in Patients with Infective Endocarditis  1047 Role of Echocardiography in the Prognostic Stratification of Infective Endocarditis  1050 Indications of Echocardiography in Infective Endocarditis  1058

48. The Role of Echocardiography in Pulmonary Hypertension

1063

Michele D' Alto, Francesco Ferrara, Emanuele Romeo, Anna Agnese Stanziola, Eduardo Bossone • Conventional Echocardiography  1063 • Nonconventional Echocardiography  1070 • Diagnostic Algorithm in Pulmonary Hypertension  1073

Contents

49. Echocardiographic Assessment of Prosthetic Valves

xxix

1080

Aditya Bharadwaj, Pooja Swamy, Gary P Foster, Padmini Varadarajan, Ramdas G Pai • • • •

Types of Prosthetic Valves  1080 Assessment of Prosthetic Valves  1082 Prosthetic Valve Dysfunction  1087 Other Complementary Imaging Modalities  1092

50. Three-Dimensional Transthoracic and Transesophageal Echocardiographic Evaluation of Prosthetic Valves

1094

Steven Bleich, Navin C Nanda • Three-Dimensional Visualization of Prosthetic Valves  1094 • Three-Dimensional Trans­thoracic Echocardiographic Assessment of Prosthetic Valves  1095 • Three-Dimensional Transeso­phageal Echocardiographic Assessment of Prosthetic Valves  1100

Volume 2

Section 4: Left and Right Ventricles, Left Atrium, Hemodynamics 51. M-Mode and Two-Dimensional Echocardiographic Assessment of Left Ventricular Systolic Function

1115

Anjlee M Mehta, Navin C Nanda • Visual Estimation of Left Ventricular Systolic Function  1115 • M-Mode and Two-Dimensional Transthoracic Echocardiographic Methods for Assessment of Left Ventricular Systolic Function  1116 • Doppler Echocardiographic Methods of Assessment of Left Ventricular Function  1119 • Two-Dimensional Speckle Tracking Echocardiography and Velocity Vector Imaging  1120 • Myocardial Performance Index  1120 • Contrast Echocardiography in the Assessment of Left Ventricular Systolic Function  1121 • Arterial–Ventricular Coupling  1121 • Three-Dimensional Trans­thoracic Echocardiography  1122

52. How to Assess Diastolic Function

1124

Hisham Dokainish • Integrating Echocardiographic Variables for Accurate Diagnosis of Diastolic Function  1130 • Novel Imaging Techniques and Future Directions  1131

53. Evaluation of the Right Ventricle Vincent L Sorrell, Steve W Leung, Brandon Fornwalt • • • • • •

General Overview  1134 Right Ventricle Morphology  1135 Echocardiography  1136 Speckle Tracking  1141 Hemodynamics  1143 Other Imaging Modalities  1144

1134

xxx

Comprehensive Textbook of Echocardiography

54. Three-Dimensional Echocardiographic Assessment of LV and RV Function

1149

Aasha S Gopal • 3D Quantitation of the Left Ventricle  1149 • 3D Quantitation of the Right Ventricle  1165

55. Newer Aspects of Structure/Function to Assess Cardiac Motion

1176

Gerald Buckberg, Navin C Nanda, Julien IE Hoffman, Cecil Coghlan • • • • • • • •

Basic Heart Function  1177 State-of-the-Art  1180 Composite of State-of-the-Art Reports  1181 Novel Mechanical and Timing Interdependence between Torsion and Untwisting  1184 The Normal Heart  1185 The Septum  1194 The Right Ventricle  1198 Other Considerations  1198

56. Echocardiography in Assessment of Complications Related to Permanent Pacemakers and Intracardiac Defibrillators

1210

Ahmed Almomani, Khadija Siddiqui, Masood Ahmad • Normal Echocardiographic Findings in Permanent Pacemakers/Implantable Cardioverter-Defibrillators  1210 • Pacemaker and Implantable Cardioverter-Defibrillator-Related Complications  1212 • Tricuspid Regurgitation  1212 • Masses: Lead Infection and Thrombus  1214 • Myocardial Perforation  1215 • Deleterious Effects of Right Ventricular Apical Pacing on Left Ventricular Function  1217

57. Echocardiographic Evaluation of Ventricular Assist Devices

1222

Peter S Rahko • • • • • • • • • • •

Clinical Uses of Ventricular Assist Devices  1224 Reverse Remodeling  1226 Types of Devices  1226 Preoperative Echocardiographic Evaluation  1229 Immediate Postsurgical Evaluation  1234 Serial Changes in Cardiac Structure and Function  1234 Complications of Left Ventricular Assist Devices  1240 Evidence of Underfilling of the Left Ventricle  1246 Optimizing Left Ventricular Assist Device Settings  1248 Explantation  1249 Percutaneous Continuous Flow Devices  1250

58. Echocardiographic Assessment of Left Atrial Function Utpal N Sagar, Hirohiko Motoki, Allan L Klein • • • •

Anatomy  1255 Physiology  1256 Functional Assessment  1257 Left Atrial Pathophysiology  1259

1255

Contents

59. The Use of Echocardiography to Assess Cardiac Hemodynamics and Guide Therapy

xxxi

1264

Roy Beigel, Robert J Siegel • • • • •

Right Atrial Pressure/Central Venous Pressure  1264 Pulmonary Artery Hemodynamics  1269 Left-Sided Filling Pressures  1273 Additional Parameters for Estimation of Left Atrial Pressure  1279 Stroke Volume, Stroke Distance, Cardiac Output, and Systemic Pulmonary Shunts (QP/QS)  1280

Section 5: Ischemic Heart Disease, Cardiomyopathies, Pericardial Disorders, Tumors and Masses

60. Echocardiography in Ischemic Heart Disease

1289

Chetan Shenoy, Hamid Reza Salehi, Francesco F Faletra, Natesa G Pandian • • • • •

Detection of Ischemia  1289 Role in Acute Coronary Syndromes  1292 Mechanical Complications of Myocardial Infarction  1294 Role of Echocardiography in Chronic Ischemic Cardiomyopathy  1298 Novel Echocardiography Techniques in Ischemic Heart Disease  1301

61. Stress Echocardiography

1306

Azhar Supariwala, Siu-Sun Yao, Farooq A Chaudhry • • • •

Fundamentals of Stress Echocardiography  1306 Types of Stress Echocardiography  1307 Interpretation of Stress Echocardiography  1309 Stress Echocardiography: Future Directions  1319

62. Squatting Stress Echocardiography

1323

Premindra PAN Chandraratna, Dilbahar S Mohar, Peter Sidarous • Squatting Echocardiography  1324

63. Three-Dimensional Stress Echocardiography Rajesh Ramineni, Masood Ahmad • • • • • • • • • • •

Two-Dimensional Stress Echocardiography  1328 Three-Dimensional Transducers  1329 Advantages of Three-Dimensions in Stress Imaging  1329 Three-Dimensional Image Acquisition  1330 Three-Dimensional Stress Protocol  1331 Postacquisition Analysis  1331 Review of Studies Comparing Three-Dimensional Stress Echocardiography to Current Standards  1331 Differences between 2DSE and 3DSE in Wall Visualization  1334 Parametric Imaging in Three-Dimensional Stress Echocardiography  1334 Role of Contraction Front Mapping in RT3DSE  1334 Contrast in Three-Dimensional Stress Testing  1335

1328

xxxii

Comprehensive Textbook of Echocardiography

64. Echocardiographic Assessment of Coronary Arteries—Morphology and Coronary Flow Reserve

1337

Karina Wierzbowska-Drabik, Jarosław D Kasprzak • The Assessment of Coronary Morphology and Flow in Transthoracic and Transesophageal Studies  1337 • Visualization of Coronary Arteries  1337 • Distal Coronary Flow and Coronary Flow Reserve  1340 • Congenital Abnormalities of the Coronary Arteries  1343

65. Echocardiography in Hypertrophic Cardiomyopathy

1348

Dan G Halpern, Mark V Sherrid • • • •

Definitions and Types of Hypertrophy  1349 Mid-Left Ventricular Hypertrophic Cardiomyopathy  1356 Differential Diagnosis  1359 Treatment Strategies in Hypertrophic Cardiomyopathy  1361

66. Echocardiographic Assessment of Nonobstructive Cardiomyopathies

1369

Rohit Gokhale, Manreet Basra, Victor Vacanti, Steven J Horn, Aylin Sungur, Robert P Gatewood Jr, Navin C Nanda • • • • • • • • • •

Cardiomyopathies  1369 Dilated Cardiomyopathy (DCM)  1370 Secondary Findings in Dilated Cardiomyopathy  1372 The Role of Echocardiography in Optimizing Heart Failure  1376 Echocardiography in Assessing Ventricular Remodeling  1379 Findings in Dilated Cardiomyopathy Based on Etiology  1379 Restrictive Cardiomyopathy  1397 Other Infiltrative Cardiomyopathies  1405 Infectious and Metabolic Cardiomyopathies  1405 Carcinoid Heart Disease  1407

67. Echocardiographic Differentiation of Ischemic and Nonischemic Cardiomyopathy: Comparison with Other Noninvasive Modalities 1418 Sula Mazimba, Arshad Kamel, Navin C Nanda, Maximiliano German Amado Escanuela, Kunal Bhagatwala, Nidhi M Karia • • • •

Echocardiographic Assessment of Ischemic and Nonischemic Cardiomyopathy  1419 M-Mode Echocardiography  1419 Two-Dimensional/Three-Dimensional/Doppler Echocardiography  1421 Echocardiographic Distinction between Ischemic Cardiomyopathy and Nonischemic Dilated Cardiomyopathy  1425 • Other Noninvasive Imaging Modalities  1425

68. Pericardial Disease Trevor Jenkins, Brian D Hoit • Acute Pericarditis  1436 • Pericardial Effusion  1436

1435

Contents

• • • • • •

xxxiii

M-Mode and Two-Dimensional Echocardiography  1437 Pericardial Tamponade  1438 Constrictive Pericarditis  1444 Effusive-Constrictive Pericarditis  1448 Congenital Anomalies  1448 Multimodality Imaging of the Pericardium  1450

69. Three-Dimensional Echocardiographic Assessment in Pericardial Disorders 1452 O Julian Booker, Navin C Nanda • Two-Dimensional Transthoracic Echocardiography Versus Three-Dimensional Transthoracic Echocardiography in Pericardial Effusion  1453 • Two-Dimensional Transthoracic Echocardiography Versus Three-Dimensional Transthoracic Echocardiography in Constriction  1456 • Two-Dimensional Transthoracic Echocardiography Versus Three-Dimensional Transthoracic Echocardiography in Pericardial Masses  1458

70. Echocardiographic Assessment of Cardiac Tumors and Masses

1462

Leon Varjabedian, Jennifer K Lang, Abdallah Kamouh, Steven J Horn, Tuğba Kemaloğlu Öz Aylin Sungur, Kruti Jayesh Mehta, Kunal Bhagatwala, Nidhi M Karia Maximiliano German Amado Escañuela, Robert P Gatewood Jr, Navin C Nanda • • • •

Echocardiographic Assessment of Cardiac Tumors and Masses  1462 Primary Benign Cardiac Tumors  1464 Malignant Primary Cardiac Tumors  1484 MICE  1511

Section 6: Congenital Heart Disease 71. Fetal Cardiac Imaging

1527

Aarti H Bhat • • • • • • •

Scope of Fetal Cardiology  1527 Indications for Fetal Cardiac Evaluation  1528 Fetal Physiology  1528 Indications for Fetal Echocardiography  1529 Extracardiac Reasons and Associations for Fetal Heart Disease  1529 Fundamentals of Fetal Cardiac Imaging  1530 Case Studies  1556

72. M-mode and Two-Dimensional Echocardiography in Congenital Heart Disease Neeraj Awasthy, Savitri Shrivastava Part 1: Basics of Imaging and Sequential Segmental Analysis  1562

• • • •

Patient Preparation  1562 Imaging  1563 Dextrocardia  1570 Principles of Sequential Chamber Analysis  1575

1561

xxxiv

Comprehensive Textbook of Echocardiography

Part 2: Left-to-Right Shunts: Atrial Septal Defect, Ventricular Septal Defect, Patent Ductus Arteriosus, and Aortopulmonary Window  1582

• • • • • •

General Features: Shunt Lesions  1582 Atrial Septal Defects  1585 Ventricular Septal Defect  1591 Patent Ductus Arteriosus  1599 Aortopulmonary Window  1602 Gerbode Defect  1603

Part 3: Atrioventricular Septal Defects  1604 Part 4: Congenital Left Ventricular and Right Ventricular Inflow Anomalies  1610

• Congenital Anomalies of Mitral Valve  1610 • Congenital Abnormalities of Tricuspid Valve  1616 Part 5: Left Ventricular Outflow Tract Obstruction  1618

• • • • • •

Valvular Aortic Stenosis  1618 Subvalvular Aortic Stenosis  1624 Supravalvular Aortic Stenosis  1626 Aortic Regurgitation  1628 Sinus of Valsalva Aneurysm  1630 Aortocameral Communications  1632

Part 6: Echocardiographic Anatomy of Tetralogy of Fallot with Pulmonary Stenosis  1633

• Aortic Override  1633 • Double Outlet Right Ventricle  1644 • Truncus Arteriosus  1650 Part 7: Complete Transposition of Great Arteries  1653

• Transposition of Great Vessels (TGA)  1653 Part 8: Atrioventricular and Ventriculoarterial Discordance  1664 Part 9: Pulmonary Veins  1670

• • • •

Normal Flow Pattern of Pulmonary Veins  1670 Anomalies of Pulmonary Veins  1672 Total Anomalous Pulmonary Venous Connection  1673 Anomalies of Systemic Veins  1678

Part 10: Imaging of Coronary Anomalies and Pulmonary Arteries  1684

• Coronary Artery Anomalies  1684 • Coronary Arteriovenous Fistula  1688 • Coronary Aneurysms  1688 Part 11: Echocardiographic Evaluation of Aortic Arch and Its Anomalies  1690

• • • •

Abnormal Formation of Arch  1690 Coarctation of Aorta (CoA)  1692 Interruption of Aortic Arch  1694 Aortic Aneurysm  1695

Part 12: Univentricular Heart and Heterotomy Syndrome  1696

• Univentricular Atrioventricular Connections  1697 • Tricuspid Atresia  1700

Contents

xxxv

• Mitral Atresia and Hypoplastic Left Heart Syndrome  1701 • Heterotaxy Syndrome  1704

73. Real Time 3D Echocardiography for Quantification of Ventricular Volumes, Mass and Function in Children with Congenital and Acquired Heart Diseases 1721 Shuping Ge, Jie Sun, Lindsay Rogers, Rula Balluz • • • •

Left Ventricular Volumes, Ejection Fraction, and Mass  1722 Right Ventricular Volumes, Ejection Fraction, and Mass  1723 Single Ventricular Volumes, Ejection Fraction, and Mass  1725 Three-Dimensional Analysis of Regional Wall Motion, Synchrony, and Strain  1726

74. Three-Dimensional Echocardiography in Congenital Heart Disease

1733

Steven Bleich, Gerald R Marx, Navin C Nanda, Fadi G Hage • • • • • • • • • • •

Shunt Lesions/Septal Defects  1733 Common Atrium  1747 Aortopulmonary Window  1751 Patent Ductus Arteriosus (PDA)  1751 Conotruncal Anomalies  1754 Outflow Tract Obstruction  1766 Aortic Arch Anomalies  1770 Atrial and Atrioventricular Valve Abnormalities  1773 Other Abnormalities  1776 Double Outlet Right Ventricle  1779 Sinus of Valsalva Aneurysm  1784

75. Echocardiography in the Evaluation of Adults with Congenital Heart Disease

1791

Reema Chugh • • • •

Key Concepts of Echocardio­graphy in Adults with Congenital Heart Disease  1793 Simple Congenital Heart Defects in Adults  1798 Valvular Disease  1813 Complex Congenital Heart Defects  1826

76. Echocardiographic Evaluation for Acquired Heart Diseases in Childhood Jie Sun, Rula Balluz, Lindsay Rogers, Shuping Ge • • • • • • • •

Infective Endocarditis  1856 Modified Duke Criteria for the Diagnosis of Infective Endocarditis  1857 Echocardiographic Findings  1857 Complications of Infective Endocarditis  1859 Rheumatic Heart Disease  1859 Jones Criteria, Updated 1992  1859 Kawasaki Disease  1861 Coronary Ectasia and Aneurysms by Echocardiography  1861

1856

xxxvi

Comprehensive Textbook of Echocardiography

Section 7: Miscellaneous and Other Noninvasive Techniques 77. Echocardiography in Systemic Diseases

1867

Mahdi Veillet-Chowdhury, Smadar Kort • • • • • • • • • • •

Systemic Lupus Erythematosus  1867 Rheumatoid Arthritis  1868 Hypereosinophilic Syndrome  1868 Systemic Sclerosis  1869 Renal Disease  1871 Amyloidosis  1872 Carcinoid  1874 Chagas Disease  1875 Sarcoidosis  1876 Thyroid Disorders  1879 Nutritional Deficiency  1880

78. Echocardiography in Women

1886

Jennifer Kiessling, Navin C Nanda, Tuğba Kemaloğlu Öz, Aylin Sungur, Kunal Bhagatwala, Nidhi M Karia • • • • • •

Differences in Echocardiographic Measurements and Technical Considerations  1886 Structural Heart Disease: MVP, Mitral Stenosis, and Mitral Annular Calcification  1888 Ischemic Heart Disease/Stress Echocardiography/Polycystic Ovarian Syndrome  1889 Takotsubo Cardiomyopathy  1899 Congenital Heart Disease  1900 Echocardiography in Pregnancy, Peripartum Cardiomyopathy, Fetal Echocardiography  1902

79. Echocardiography in the Elderly

1921

Gopal Ghimire, Navin C Nanda, Kunal Bhagatwala, Nidhi M Karia • • • • • • • • •

Aortic Atherosclerosis and Penetrating Aortic Ulcer  1921 Aortic Valve Sclerosis  1923 Aortic Stenosis  1924 Aortic Aneurysm  1934 Aortic Dissection  1937 Left Ventricular Mass, Dimensions, and Function  1942 Echocardiography in Stroke Patients: Assessment of Coronary Stenosis  1943 Mitral Annular Calcification  1946 Prosthetic Valves  1948

80. How to do Echo for the Electrophysiologist Chittur A Sivaram • • • • • • •

Echocardiography in Supra­ventricular Tachycardia  1957 Left Atrium  1960 Atrial Septum  1962 Pulmonary Veins  1963 Inferior Vena Cava  1964 Echocardiography in Ventri­cular Tachycardia  1966 Echocardiography in Cardiac Implantable Electronic Devices  1967

1957

Contents

81. Echocardiography in Life-Threatening Conditions

xxxvii

1969

Rachel Harris, Elizabeth Ofili • • • • • • • • • • • •

Chest Trauma  1969 Blunt Chest Trauma  1969 Penetrating Chest Trauma  1972 Acute Mitral Regurgitation  1972 Acute Severe Aortic Regurgitation  1972 Aortic Dissection  1974 Debakey Classification  1974 The Stanford Classification  1974 Pulmonary Thromboembolic Disease  1976 Air Embolism  1977 Hypovolemia  1977 Large Intracardiac Thrombus  1978

82. Lung Ultrasound in Cardiology

1982

Luna Gargani, Eugenio Picano • • • • • • • • •

Physical and Physiological Basis of Lung Ultrasound  1982 Methodology  1983 Pulmonary Interstitial Edema  1984 Pleural Effusion  1985 Pulmonary Embolism  1985 Acute Respiratory Distress Syndrome  1986 Pneumothorax  1986 Cardiopulmonary Ultrasound: An Integrated Approach  1987 Limitations  1987

83. The Future of Echocardiography and Ultrasound

1990

David Cosgrove • • • • • • •

Plane Wave Ultrafast Imaging  1990 Trends in Scanners  1991 Doppler  1993 Microbubbles  1993 Elastography  1994 Light and Sound  1995 Therapeutic Applications of Ultrasound  1996

84. A Primer on Cardiac MRI for the Echocardiographer Madhavi Kadiyala, Aasha S Gopal • • • • • • • •

Quantitative Left and Right Ventricular Assessment  1998 Strain Assessment  1999 Left Ventricular Structure  2000 Myocarditis and Sarcoidosis  2004 Cardiac Hypertrophy  2006 Cardiomyopathies  2008 Velocity Mapping, Flow and Shunt Assessment  2008 Valvular Heart Disease and Prosthetic Valves  2009

1998

xxxviii

Comprehensive Textbook of Echocardiography

• • • •

Pericardial Disease  2014 Normal Variants and Masses  2016 Limitations of Cardiac MRI and CT  2017 Glossary of Cardiac MRI Sequences  2020

85. Cardiac CT Imaging

2023

Satinder P Singh, Sushilkumar K Sonavane • • • • • • • • • • • • •

Challenges for Cardiac Computed Tomography  2024 Radiation Dose  2025 Patient Selection  2027 Technique  2027 Image Postprocessing  2028 Image Analysis  2032 Pitfalls and Artifacts  2034 Diagnostic Accuracy of Coronary Computed Tomography Angiogram  2040 Coronary Plaque  2041 Prognostic Information from Coronary Computed Tomography Angiogram  2042 Cardiac Function  2042 Myocardial Perfusion  2042 How to Improve Accuracy of Computed Tomography Angiogram in Determining Flow Limiting Disease  2044 • Clinical Indications  2044 Index I-i

SECTION 1 HISTORY AND BASICS

Chapters Chapter 1 History of Echocardiography Chapter 2 Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology Chapter 3 Basics of Ultrasound Chapter 4 Doppler Echocardiography—Methodology, Application and Pitfalls

Chapter 5 Basics of 3D Ultrasound Chapter 6 Speckle Tracking Acquisition: Basics and Practical Tips Chapter 7 Instrumentation for Transesophageal Echocardiography Including New Technology

3

CHAPTER 1 History of Echocardiography Fadi G Hage, Anant Kharod, David Daly, Navin C Nanda

Snapshot  History of Ultrasound  The Development of Clinical Cardiac Ultrasound:

A-Mode and M-Mode Echocardiography  Two-Dimensional Echocardiography  ConvenƟonal Doppler Ultrasound  Color Doppler Ultrasound

 Contrast Echocardiography  Transesophageal Echocardiography  Tissue Doppler and Speckle Tracking Imaging  Three-Dimensional Echocardiography  PerspecƟve

INTRODUCTION The development of echocardiography is an interesting story that traverses three centuries and many continents. From the study of ultrasound waves in bats to Nobel Prize winners in physics, to increased military interest in ultrasonography due to the Titanic and World War I, to two- (2D) and three-dimensional (3D) echocardiography, the history of echocardiography highlights human ingenuity and perseverance. This started with A-mode still images derived by a thin ultrasound beam and advanced to M-mode (moving) displays (Figs 1.1 and 1.2). Eventually the technology advanced to allow for 2D examination of the heart in motion (Fig. 1.3). This was followed by the addition of conventional Doppler and color Doppler, the recent introduction of tissue Doppler and speckle tracking imaging, contrast echocardiography, transesophageal echocardiography, 3D transthoracic and transesophageal echocardiographic reconstruction, and ultimately the development of real time, 3D echocardiography (Figs 1.4A to D).1–3 Today, echocardiography is the most frequently utilized imaging modality in cardiology and is at the center of our diagnostic and decision-making algorithms in many, if not most, cardiac pathologies. With current technology,

Fig. 1.1: One-dimensional echocardiography (M-mode). The frontal projection of the heart demonstrates the concept that M-mode is equivalent to extraction of a plug of tissue that corresponds to the width of the beam passing through the heart. The removed plug is shown to the right and contains a portion of the right ventricle (RV), ventricular septum (VS), mitral valve (MV), and left ventricular posterior wall (LVW). A schematic of structure motion along with the ECG is included. (ECG: Electrocardiogram). Source: Reproduced with permission from Nanda NC, Gramiak R. Clinical Echocardiography. St. Louis, MO: C. V. Mosby; 1978: 370.

4

Section 1: History and Basics

Fig. 1.2: Nanda pointing to an M-mode echo tracing on the monitor of one of the earliest echo systems manufactured for clinical use (early 1970s).

echocardiography can provide useful information regarding cardiovascular structure and morphology, cardiac function, and hemodynamics in a noninvasive, versatile, and portable modality that is relatively inexpensive and safe to the patient and physician. This is partly why echocardiography has been the mainstay in cardiac imaging over the last half a century and promises to keep its throne, at least in the near future, because of continued revolutions in this field that will keep it relevant to the practicing physician in the 21st century. This chapter highlights several of the key inventions and historical figures in ultrasonography and echocardiography from the past and present, which have made echocardiography the staple in clinical cardiology that it is today.

HISTORY OF ULTRASOUND Ultrasound, defined as a sound wave with a frequency above the limit of normal human hearing, is a natural phenomenon that is abundant in nature. It was first recognized, as early as the 18th century, that bats, although blind, use ultrasound to detect their prey.4 It is also widely appreciated that whales and dolphins use sonar to navigate and hunt. Humans, by definition, cannot hear ultrasound, but there has been a great interest in developing technologies that can detect ultrasound for various applications. It has been noted that physiotherapists were possibly the first care providers who integrated ultrasound into their practice, using sound as an instrument to treat arthritis and muscle aches.1 In fact, in 1761, Viennese physician Leopold

Fig. 1.3: Two-dimensional (2D) scanning concept (2D echocardiography). Real time 2D images are equivalent to slices of the heart that are removed and observed in motion. This illustration shows the cardiac cavities and valves viewed in the long axis of the left ventricle and the relationship of this plane to a frontal view of the heart. Source: Reproduced with permission from Nanda NC, Gramiak R. Clinical Echocardiography. St. Louis, MO: C. V. Mosby; 1978: 371.

Auenbrugger studied the effects of sound via percussion to diagnose cardiopulmonary problems.1 However, it was the discovery of piezoelectricity in 1880 by Jacques and Pierre Curie that allowed for harnessing the power of ultrasound. Later, Pierre and his wife Marie shared the 1903 Nobel Prize in physics with Antoine Becquerel for the discovery of radioactivity.4 The major stimulus for the development of ultrasound for human use came with the sinking of the Titanic on April 15, 1912, on its maiden voyage when it struck an unseen iceberg. In tandem, there was interest in developing a technology to avert the threat of the German U-boats in sinking allied ships. By 1918, Paul Lavengin, a French physicist, succeeded in developing a sonar system that was capable of producing ultrasound and analyzing returned acoustic echoes.1,4 This led to multiple discoveries that allowed for the use of sonar technology in naval warfare during World War II. After the war, scientists worldwide worked on developing the technology for peaceful purposes.

THE DEVELOPMENT OF CLINICAL CARDIAC ULTRASOUND: A-MODE AND M-MODE ECHOCARDIOGRAPHY The credit for the development of clinical cardiac ultrasound goes mostly to Inge Edler and Hellmuth Hertz.5 Dr Edler, a cardiologist at the University Hospital in

Chapter 1: History of Echocardiography

A

B

C

D

5

Figs 1.4A to D: Progress in echocardiography. The chronology of the books and video textbooks produced by Nanda illustrate the progressive development of echocardiography from M-mode to two-dimensional, conventional and color Doppler, contrast, and two- and three-dimensional transthoracic and transesophageal echocardiography.

Lund, Sweden, was interested in developing a diagnostic method for evaluating patients with mitral stenosis prior to undergoing surgery and identifying patients who have significant mitral regurgitation, which would preclude them from having surgery.6 For this purpose, he collaborated with Dr Hertz, a physicist who graduated from the same university and was studying ultrasound and its applications. Hertz was well known for hailing from a well-established scientific family since his father, Gustav Hertz, won the Nobel Prize in physics in 1925 for his work on the laws governing the impact of an electron upon an atom and his uncle Heinrich Hertz, in whose honor wave frequencies were named in 1930. Visiting a company in Mälmö, Hellmuth Hertz initially tested an ultrasound machine on himself. After seeing signals he thought originated from his posterior wall, Hertz

agreed to work with Edler and they proceeded to borrow a pulse-echo sonar machine from a shipyard for a weekend in 1953 in order to start their experiments.2 Due to the positive results of their experiment, the manager of the shipyard company agreed to lend them the machine for over a weekend to continue their research.6 Siemens was impressed by their work and lent them a reflectoscope for a year in order to perform their work partly due to Hertz’s family connections at the company.1,7 They realized that by using ultrasound they were able to identify the interface between the wall of the heart and its fluid-filled cavity. After studying heart specimens, they proceeded to human studies; it is notable that Hertz’s first human volunteer was himself.2 They documented a signal that moved with cardiac movement, which they originally attributed to the movement of the left atrial wall. Edler then proceeded to

6

Section 1: History and Basics

perform “ultrasound cardiography” on patients on their dying bed and carefully documented the site and angle of the ultrasound beam. After the demise of a patient, he would place an ice pick in the direction of the M-mode beam and dissect the heart to identify the structures that the ultrasound beam traversed. Through this elegant approach, he was able to document that the moving signal was actually arising from the anterior mitral leaflet rather than from the posterior wall of the left atrium. Edler then showed his findings in a movie at the European Congress of Cardiology in Rome in 1960 and published several manuscripts pertaining to ultrasound cardiography.5–6,8–12 Edler also described the use of the movement of the anterior mitral valve leaflet (E–F slope) for the diagnosis of mitral stenosis and for quantitating its severity. Patients with mitral stenosis had a reduced speed of the diastolic downstroke E–F slope of the anterior mitral leaflet.6 Hertz developed inkjet technology in order to record the cardiograms that they obtained, and he was successful in commercially promoting the use of this new technology for multiple applications. In the United States, John Reid, at the University of Pennsylvania, built an ultrasonic reflectoscope, and through a collaboration with Dr Claude Joyner, he repeated the work of Edler on mitral stenosis and published the first manuscript on the use of echocardiography in the United States in 1963.13 At the same time, Dr Harvey Feigenbaum was interested in measuring left ventricular volumes and pressures for the assessment of compliance. He attended the American Heart Association meeting in 1963 in order to examine a machine that was advertised to measure cardiac volumes using ultrasound. When he examined the machine at the meeting, it was apparent that it could not deliver that promise, and he was frustrated. Rather than turning away, he examined the instrument on his own heart, and the company salesman explained how the ultrasound signal is produced. Feigenbaum was intrigued and asked what would happen if there was fluid around the heart, and the salesman answered that the fluid should be echo free.2 He thus realized that this technology can be useful for the diagnosis of pericardial effusion. After returning to Indiana, he borrowed an ultrasound machine from a colleague in neurology, who was using it to detect deviations in the brain caused by intracranial masses, and examined a patient with pericardial effusion and documented the presence of the echo-free space. These observations were then confirmed in the animal laboratory and published in 1965.14

Despite this, there was general skepticism with regard to the clinical utility of echocardiography. Feigenbaum collaborated with Dodge at the University of Alabama in 1968 to develop M-mode echocardiography for the measurement of left ventricular dimensions. However, they were unable to publish their work until years later after their findings were reproduced by other investigators.15–17 In the late 1970s, only three cardiac valves—mitral, aortic, and tricuspid—could be identified by echocardiography. It was believed that the pulmonary valve was inaccessible since it was situated beneath the lung tissue. Dr Navin C Nanda who joined the University of Rochester in upstate New York in early 1971 as a cardiology fellow was not convinced that this was true, and during discussions with a pathologist at the autopsy of a cardiac patient, it became clear that the pulmonary valve was not covered by lung in a majority of patients. Subsequently, he, together with Dr Gramiak, was successful in imaging and identifying the pulmonary valve by M-mode echocardiography (Fig. 1.5).18 This discovery essentially resulted in the birth and development of pediatric echocardiography since all four cardiac valves could now be imaged successfully. This made it possible to diagnose many congenital cardiac disease entities such as dextrotransposition of the great vessels.19,20

Fig. 1.5: Echocardiographic detection and validation of the pulmonary valve. Indocyanine green was injected into the pulmonary artery during cardiac catheterization. The left pulmonary cusp is identified by the dense contrast material filling it. The dense linear bands extending anteriorly during early diastole probably originate in another contrast-filled pulmonary cusp which lies above the plane of study during most of the cardiac cycle. The scattered echoes in front of the left pulmonary cusp are probably in the right ventricular outflow tract as a result of catheter-induced valvular regurgitation. (AV: Aortic valve; ECG: Electrocardiogram; Inj: Injection signal; LA: Left atrium; PCG: Phonocardiogram; PV: Pulmonary valve; RA: Right atrium). Source: Reproduced with permission from Gramiak R, Nanda NC, Shah PM. Echocardiographic detection of the pulmonary valve. Radiology. 1972;102:153–7.

Chapter 1: History of Echocardiography

7

Nanda remembers often being called in the middle of the night to perform echocardiograms on cyanotic newborns to diagnose or rule out dextrotransposition of the great vessels. Early diagnosis was life saving in these newborns since it resulted in enlarging the patent foramen ovale (PFO) or performing atrial septostomy in the cardiac catheterization laboratory to promote improved mixing of pulmonary and systemic circulations. M-mode echo was also used for the first time to assess pulmonary hypertension21 and diagnose a congenital bicuspid aortic valve22 and evaluate intra-atrial baffle dysfunction in transposition of the great vessels (Figs 1.6 and 1.7).23 In its early development, M-mode echo was most commonly used in a clinical setting to detect pericardial effusion and to diagnose mitral stenosis and assess its severity. This was done by measuring the early diastolic slope of the mitral valve M-mode tracing, and it was shown that the slower the diastolic slope, the more severe the stenosis with good correlations with cardiac

catheterization findings. However, when Nanda relooked at this in a large number of patients with M-mode echo and using actual left atrial pressures measured by the transseptal approach in the cardiac catheterization laboratory, no significant correlation was found. He attempted to publish these findings but was unsuccessful because it was believed that this could “destroy” the emerging technique of echocardiography. He was, however, able to publish it as an abstract.24 Subsequent studies by other investigators supported his findings and the mitral diastolic slope was no longer used to assess the severity of mitral stenosis. Two comprehensive books on M-mode echocardiography, one written by Feigenbaum and the other by Nanda and Gramiak, also helped publicize echocardiography and bring into focus the clinical utility of this noninvasive technique.25,26

Fig. 1.6: Pulmonary hypertension and right heart failure. The pulmonary valve echo is from a patient with severe pulmonary hypertension complicated by severe right heart failure. A large “a” dip is observed. The valve opens rapidly, and the amplitude of the opening movement is large. The representation of the right ventricular and pulmonary artery pressure tracings was obtained at cardiac catheterization in this patient. The high right ventricular end-diastolic pressure (38 mm) results in a low gradient (4 mm) across the pulmonary valve in diastole (shaded). (ECG: Electrocardiogram; PA: Pulmonary artery pressure tracing; PV: Pulmonary valve echo tracing; RV: Right ventricular pressure tracing. The scale represents pressures in mm Hg). Source: Reproduced with permission from Nanda NC, Gramiak R, Robinson TI, Shah PM. Echocardiographic evaluation of pulmonary hypertension. Circulation. 1974;50:575–81.

Fig. 1.7: Comparison of normal and bicuspid aortic valve. The aortic root echocardiogram in the upper panel is obtained from a patient with a tricuspid aortic valve. The valve echoes are observed in diastole in the middle of the aortic lumen, and the leaflet images appear symmetric. The lower panel demonstrates an aortic root echogram obtained from a patient with a bicuspid aortic valve. Marked eccentricity of the diastolic cusp signals with respect to the aortic lumen is present. The anterior cusp image is large and practically occupies the whole aortic lumen while the posterior leaflet is miniscule. (AO: Aortic root; ECG: Electrocardiogram; PHONO: Phonocardiogram; RESP: Respirations). Source: Reproduced with permission from Nanda NC, Gramiak R, Manning J, et al. Echocardiographic recognition of the congenital bicuspid aortic valve. Circulation. 1974;49;870–5.

8

Section 1: History and Basics

Although M-mode constituted the real birth of clinical echocardiography, there was general skepticism about the future of echocardiography because the interpretation of the images was nonintuitive. The development of 2D echocardiography constituted a revolution in the field unequalled except with the later introduction of 3D echocardiography. The group at the University of Rochester, led by Gramiak, envisioned the reconstruction of the information embedded in the M-mode to develop 2D and ultimately 3D images of the heart in the early 1970s.27 Although the principles and the techniques used were sound, the application was hampered by the slow processing power of the computers available at that time. Nicolaas Bom of the Netherlands, in 1971, developed the linear array system and was able to visualize moving cardiac images. Bom initially studied electronic engineering and then served in the Navy where he worked with sonar, transducers, and linear array signals. He later graduated from a medical school in Rotterdam and applied his knowledge of sonar to medicine. Having read works by Hertz, Edler, and several others, he realized that their methods were one dimensional and that the majority of the heart could not be visualized with a narrow sound beam. The linear scanner developed by Bom in Rotterdam

was the first real time, 2D scanner that was widely available.28 Current 2D systems are based on the work of Griffith and Henry who developed a mechanical handheld device capable of 2D scanning at the National Institutes of Health.29 The development of real time, 2D echocardiography resulted in an explosive growth in the utility of echocardiography, and it was not long before practically every large hospital with cardiology service owned at least one 2D echo system. Among the several clinical applications, some of the first ones from our group included echocardiographic assessment of intracardiac pacing catheters30, pacemaker perforation31,32, pacing-induced thrombosis, and echocardiographic studies done during sustained ventricular tachycardia (Figs 1.8A and B).33,34 The first article elucidating the differentiation of left ventricular pseudoaneurysms from true aneurysms by 2D echocardiography was published in 1980.35 Other studies included 2D echo features of atrial septal aneurysms,36 2D echo diagnosis of right ventricular infarction,37 myocardial texture recognition by 2D echo, and correlation of 2D echo pattern with histopathology of intracardiac masses (Fig. 1.9).38–39 The first study demonstrating the currently popular technique of posttreadmill exercise echocardiography in the assessment of coronary artery disease was published from our group in 1981.40 It took almost 8 years before another study was published from our echo laboratory showing

A

B

TWO-DIMENSIONAL ECHOCARDIOGRAPHY

Figs 1.8A and B: Pacing catheter perforation. The subcostal four-chamber view shows the temporary pacing catheter (P) passing through the right ventricular (RV) apex (arrow), with the tip located just beyond the epicardial surface. The echo-free space inferior to the cardiac apex represents a portion of the patient’s stomach (S). When the patient swallowed water, contrast echoes appeared in this space, confirming its relationship to the gastrointestinal tract. The prominent echo in the right ventricle originates from a Swan-Ganz catheter (SG). (A: Anterior; AW: Anterior wall; I: Inferior; L: Liver; LA: Left atrium; LV: Left ventricle; MV: Mitral valve; P: Posterior; RA: Right atrium; RB: Reverberation; S: Superior; TV: Tricuspid valve; VS: Ventricular septum). Source: Reproduced with permission from Gondi B, Nanda NC. Real time, two-dimensional echocardiographic features of pacemaker perforation. Circulation. 1981;64:97–106.

Chapter 1: History of Echocardiography

Fig. 1.9: Right ventricular aneurysm due to right ventricular infarction. The right heart apical two-chamber view shows a large aneurysm (AN) that involves the apical region. (A: Anterior; DW: diaphragmatic wall; I: Inferior; L: Left; L: Liver; P: Posterior; R: right; RA: Right atrium; S: Superior). Source: Reproduced with permission from D’Arcy B, Nanda NC. Two-dimensional echocardiographic features of right ventricular infarction. Circulation. 1982;65:167–73.

its temporal reproducibility.41 The first study demonstrating the usefulness of the cold pressor test during real time, 2D echocardiography in the assessment of coronary artery disease came out in 1984.42 The same year saw the publication of a study demonstrating comprehensive evaluation of aortic aneurysm and dissection by 2D echo/conventional Doppler (Figs 1.10 and 1.11).43 Other studies showing the clinical utility of 2D echo in the diagnosis of arrhythmogenic right ventricular dysplasia,44 pulmonary artery branch stenosis,45 and pulmonary artery aneurysms46 were also published in the early 1980s.

CONVENTIONAL DOPPLER ULTRASOUND The Doppler effect is named after the Austrian physicist Christian Doppler who proposed in 1842 that the frequency of a wave to an observer is higher than the emitted frequency if the source is moving toward the observer and lower than the emitted frequency if the source is receding from the observer.47 His theory was ridiculed until it was proved correct 15 years after his death. It was not until 1956 that Dr Satomura, in Japan, first utilized the Doppler theory to examine the movement of cardiac structures.48 In the United States, Rushner in Seattle worked on cardiac Doppler in the 1960s and introduced the technique to Baker,49 who went on to develop the first pulsed Doppler recording device.50 Holen and Hatle then showed how

9

Fig. 1.10: Two-dimensional echocardiographic evaluation of the aorta. The aorta reconstructed from the root level to the abdominal region by assembling Polaroid® images of contiguous segments obtained from multiple transducer positions. (AA: Ascending aorta; ABA: Abdominal aorta; CC: Common carotid; IN: Innominate artery; PA: Pulmonary artery; SC: Subclavian; TA: Transverse aorta; TDA: Thoracic descending aorta). Source: Reproduced with permission from Mathew T, Nanda NC. Two-dimensional and Doppler echocardiographic evaluation of aortic aneurysm and dissection. Am J Cardiol. 1984;54:379–85.

Doppler can be used to derive hemodynamic data using the Bernoulli equation.51–53 These measurements proved quite useful for the assessment of mitral and aortic stenosis and popularized the use of Doppler with echocardiography. In the meantime, Baker had sent a Doppler ultrasound to Nanda to investigate. Nanda recalls placing the probe on his own chest and being initially unable to interpret results. He attended a course on Doppler in Seattle conducted by Baker and became “certified” in Doppler during a time in which only a handful of people were certified. Many other applications of conventional Doppler followed including its usefulness in the assessment of coronary arteries and fetal hemodynamics (Fig. 1.12).54–56 The first book on Doppler echocardiography was published in 1982 by Drs Hatle and Anderson57 followed by a book from Nanda.58 Nanda remembers being invited to go to China in early 1982 and introducing the pulsed Doppler technique to that country at a time when it was just opening up to foreigners. He was given a letter to this effect from the People’s Liberation Army Hospital in Beijing and the Practical Acoustic Association of China, which also stated his lectures had “strengthened the friendship and mutual understanding between USA and China”! Our group was the first to use 2D echo/Doppler in cardiac pacing to

10

Section 1: History and Basics

A

B

Figs 1.11A and B: Two-dimensional echocardiographic evaluation of aortic aneurysm and dissection. (A) Ascending aortic aneurysm. This composite illustration was made by the reconstruction method to show the full extent of the aneurysm. The transverse arch (T) and the descending aorta (DA) are not involved. (B) Aortic dissection (DeBakey type 1). This composite illustration was also made by the reconstruction method. The dissection flap (arrows) can be seen in the ascending aorta (AA), transverse arch (TA), thoracic descending aorta (TDA), and in the abdominal segment (ABA). (AA: Ascending aorta; V: Aortic valve. AV: Aortic valve; PA: Pulmonary artery). Source: Reproduced with permission from Mathew T, Nanda NC. Two-dimensional and Doppler echocardiographic evaluation of aortic aneurysm and dissection. Am J Cardiol. 1984;54:379–85.

Fig. 1.12: Typical Doppler power spectra from the umbilical arteries in a normal pregnancy is shown on the left. Doppler power spectra from a pregnancy with premature rupture of membranes and oligohydramnios is depicted on the right. Source: Reproduced with permission from Maulik D, Saini VD, Nanda NC, Rosenzweig MS. Doppler evaluation of fetal hemodynamics. Ultrasound Med Biol. 1982;8: 705.

maximize cardiac output, minimize mitral regurgitation, and assess atrial capture (Fig. 1.13).59 The incremental value of sequential atrioventricular pacing over regular right ventricular pacing using a prototype continuouswave Doppler system developed by Dr Henry Light of

Fig. 1.13: Usefulness of Doppler echocardiography in cardiac pacing. Peak aortic flow velocity at different atrioventricular (AV) intervals. +, mitral regurgitation present; ++, increased mitral regurgitation; –, mitral regurgitation not evaluated by Doppler. The number in parenthesis indicates the maximum percentage change in peak aortic flow velocity obtained in a given patient as compared to the VVI value or value at the shortest AV interval (in patients in whom VVI values were not available). Note that the maximum percentage change occurred with pacing at AV intervals between 150 and 200 ms. The initials of each patient are given at the right of each Doppler flow velocity curve. Source: Reproduced with permission from Zugibe FT, Nanda NC, Barold SS, Akiyama T. Usefulness of Doppler echocardiography in cardiac pacing. Assessment of mitral regurgitation, peak aortic flow velocity, and atrial capture. PACE. 1983;6:1350–7.

Chapter 1: History of Echocardiography

Fig. 1.14: Doppler echocardiographic studies in sequential AV pacing. In this patient with sequential AV pacing, the Doppler transducer was placed in the suprasternal notch and angled inferiorly and to the left to record blood flow in the proximal descending aorta. The Doppler blood flow patterns (DS) are denoted by triangular waveforms and the height of the triangle represents peak aortic blood flow velocity. When the patient was switched from DVI to VVI mode, a significant decrease occurred in the height and size of the triangles, indicative of significant reduction in the stroke volume and cardiac output (heart rate was kept constant in both pacing modes). The vertical distance between the arrows represents 1 m/s and this scale is common for both VVI and DVI tracings. Source: Reproduced with permission from Nanda NC, Bhandari A, Barold SS, Falkoff M. Doppler echocardiographic studies in sequential atrio-ventricular pacing. PACE. 1983;6:811–14.

England was also shown by us.60 An increase in stroke volume of up to 25% with sequential atrioventricular pacing was demonstrated (Fig. 1.14).

COLOR DOPPLER ULTRASOUND Color Doppler flow imaging was developed in the 1980s, which allowed for the visualization of blood flow noninvasively.61 The first commercially available color Doppler echo machines were developed in Japan where Omoto and his group did some of the early work.62 Nanda realized the potential of color Doppler when he was privately shown a “work-in-progress” system during a scientific meeting in Taiwan. Drs John Kirklin and Gerald Pohost at the University of Alabama agreed to buy two color Doppler systems whenever they were commercially available, prompting Nanda to move to Birmingham from Rochester. Color Doppler was first introduced as a clinical tool to the United States in 1984 at the University of Alabama at Birmingham (Fig. 1.15). His group also pioneered the color Doppler assessment and semiquantitation of mitral,

11

Fig. 1.15: Aloka 880 Color Doppler System. Compliments of Aloka, Tokyo, Japan.

aortic, and tricuspid valvular regurgitation in a reliable and reproducible manner (Figs 1.16 and 1.17).63–65 Some of the initial work also showed the usefulness of color Doppler as an adjunct to 2D echo in the assessment of aortic dissection, aortic valve stenosis, prosthetic heart valves, and fetal hemodynamics (Fig. 1.18).66–69 It was used during supine bicycle exercise to identify the development or worsening of mitral regurgitation as a marker for left main or three-vessel coronary artery disease.70 Color Doppler also began to find application in the evaluation of vessels outside the heart.71 Within only a few years of its introduction, it became an integral part of a clinical echocardiographic examination. Its popularity was further helped by several publications on the subject in the 1980s.72–74

CONTRAST ECHOCARDIOGRAPHY The history of contrast echocardiography dates back to the early days of echocardiography when Joyner noticed the contrast effect using ultrasound following intravenous fluid injection; but, these observations were not published. Gramiak, a radiologist at the University of Rochester, Rochester, New York, borrowed a new ultrasound machine from the cardiology department to try it out. He tested the machine on a patient with aortic regurgitation who was undergoing angiography. During the injection of indocyanine green, he noted the defect in the contrast material caused by the backflow of blood into the ventricle, and Dr Pravin Shah and he developed the technique of contrast echocardiography for the study

12

Section 1: History and Basics

A

B

Figs 1.16A and B: Color Doppler assessment of mitral regurgitation. (A) Maximum RJA/LAA% obtained from analysis of all three two-dimensional echocardiographic planes compared with angiography (all 82 patients). (B) Flow acceleration. A simple example of the generation of flow acceleration can be shown by observing the draining of water from a household bathtub. Flow acceleration or a localized area of high velocity develops as the large body of water moves toward the “hole” or opening in the bottom of the tub through which water flows into the drain. Adjacent to the “hole,” the area of flow acceleration becomes smaller and tends to take the shape and size of the circular “hole.” This finding has clinical significance. For example, in a patient with mitral regurgitation, inspection of the size and shape of the flow acceleration present adjacent to the mitral valve (MV) may provide a good estimate of the size of the anatomical defect in the MV through which the regurgitation is occurring. (AF: Atrial fibrillation; LAA: Left atrial area; NSR: Nnormal sinus rhythm; RJA: Mitral regurgitant area). Source: (A) Reproduced with permission from American Heart Association, Helmcke F, Nanda NC, Hsiung MC, et al. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation. 1987;75:175–83. Source: (B) Reproduced with permission from Nanda NC. Atlas of Color Doppler Echocardiography. Philadelphia, PA: Lea & Febiger; 1989:7. Can Two-Dimensional Echocardiography and Doppler Color Flow Mapping Identify the Need for Tricuspid Valve Repair? H.K. CHOPRA, MD, NAVIN C NANDA, MD, FACC, POHOEY FAN, MD, KANWAL K. KAPUR, MD. RAJENDRA GOYAL, MD, DINYAR DARUWALLA, MD, ALBERT PACIFICO, MD, FACC Birmingham, Alabama

J Am Coll Cardiol 1989;14:1266-74

Tricuspid regurgitation severity was assessed preoperatively with Doppler color flow mapping and these assessments were compared with surgical findings in 90 patients.

The maximal diastolic tricuspid annulus diameter measured with the same two-dimensional imaging planes was ≥ 21 mm/m2 body surface area (mean 26.7 ± 5.2 mm/m2)

Fig. 1.17: Demonstration of the usefulness of tricuspid valve annulus measurement and color Doppler flow mapping for the assessment of tricuspid regurgitation. Source: Reproduced with permission from Chopra HK, Nanda NC, Fan P, et al. Can two-dimensional echocardiography and Doppler color flow mapping identify the need for tricuspid valve repair? J Am Coll Cardiol. 1989;14:1266–74.

of the aortic valve and the aortic root.75 Later work done with Nanda also used contrast injections in the cardiac catheterization laboratory to confirm the detection of pulmonary valve by echocardiography.18 In the 1970s, saline contrast was used for the delineation of intracardiac shunts for the identification of right-sided valves and for better assessment of congenital heart disease.18,76–78 It was also used to identify and assess the severity of right-sided valvular regurgitation.79

Fig. 1.18: Visualization of aortic stenosis (AS) jet. The right parasternal view shows a narrow band of mosaic signals (AS JET) originating from the thickened aortic valve during systole. The mosaic signals indicate the presence of turbulence. The jet is very narrow at its origin (jet width, 6 mm), implying severe aortic stenosis, but later broadens out to completely fill the ascending aorta (AA). (AV: Aortic valve; PA: Pulmonary artery). Source: Reproduced with permission from Fan P, Kapur KK, Nanda NC. Color-guided Doppler echocardiographic assessment of aortic valve stenosis. J Am Coll Cardiol. 1988;12:441–9.

Chapter 1: History of Echocardiography

As recently as 2007, saline contrast was used by us for the first time to identify and validate the echo-free space behind the aorta, examined in the parasternal long-axis view, as the superior vena cava in most instances and only occasionally as the main or right pulmonary artery (Fig. 1.19).80 In the 1980s, commercial contrast agents with miniaturized stable microbubbles were developed. Gelatin-encapsulated nitrogen bubbles were shown to be stable for use with ultrasound enhancement,81 and microbubbles sonicated from human serum albumin were shown to traverse the pulmonary circulation and opacify the left ventricle.82 Some of the early work was pioneered by Drs. Sanjiv Kaul and Steve Feinstein. These observations led to the introduction of multiple contrast agents in the market with variable properties. The first agent approved by the Food and Drug Administration in the United States in 1994 utilized air as the gas component of the microbubbles, as did other agents at that time, which reduced the longevity of the bubbles.78 This is because air can leak out of the thin bubble shell and dissolve in the blood. In the 1990s, perfluorocarbon gases were utilized instead of air to increase the time these bubbles can persist

Fig. 1.19: Validation of the structure behind the aorta as superior vena cava (SVC) by saline contrast echocardiography. Twodimensional transthoracic echocardiographic bubble study. Intravenous injection of agitated normal saline shows contrast echoes first appearing in the bounded echo-free space (arrowhead) and then in the right ventricle (RV, arrow). This suggests that the echo-free space represents the SVC and not the main or right pulmonary artery. (AO: Aorta; LV: Left atrium; RV: Right ventricle). Source: Reproduced with permission from Burri MV, Mahan EF III, Nanda NC, Singh A, et al. Superior vena cava, right pulmonary artery or both: real time two- and three-dimensional transthoracic contrast echocardiographic identification of the echo free space posterior to the ascending aorta. Echocardiography. 2007;24:875–82.

13

in the circulation. These newer agents consisted of smaller and more stable microbubbles that proved to be helpful for the assessment of perfusion as well as enhancement and opacification and direct detection of coronary stenosis (Figs 1.20A and B).78,83,84 The first book to highlight advances in echo imaging using contrast enhancement was published in 1993.85

TRANSESOPHAGEAL ECHOCARDIOGRAPHY Transesophageal echocardiography was envisioned as early as 1971 by Side and Gosling for its use with Doppler,86 but it was first developed with M-mode by Frazin et al. in a classical article in Circulation in 1976.87 The use of this new technique was hampered because of its reliance on large rigid scopes. Hanrath was the first to attach a phased array transducer to the tip of a flexible scope, which ushered in the era of clinical transesophageal echocardiography.88 The technique found popularity because of the superior quality images obtained by the higher frequency probe used and the proximity of the esophagus to cardiac structures. Initially, a monoplane probe was used but subsequently biplane and multiplane probes were developed, and articles and books were published delineating the technique for systematic examination of cardiac structures.89–91 It soon found wide application in the intraoperative setting in the cardiac catheterization laboratory during percutaneous procedures and in the echo laboratory as a valuable adjunct to 2D transthoracic echocardiography. It was found that during a transesophageal examination, important supplementary information could be provided by examining coronary arteries for stenosis and imaging the abdominal structures and vessels for abnormalities with the probe positioned in the stomach (transgastric ultrasonography; Figs 1.21 and 1.22).92,93 Toward the end of the examination with the probe positioned in the upper esophagus, one could evaluate the aortic arch branches and the adjacent veins in detail,94-99 and also with the probe withdrawn into the pharynx, the carotid bulb on both sides, left and right internal carotid arteries, and extracranial segments of the vertebral arteries can be evaluated for stenosis and other abnormalities (transpharyngeal ultrasound; Figs 1.23A and B).100–102 A distinct advantage of the transpharyngeal approach is the parallel orientation of the Doppler beam to the flow in the carotids, which is practically impossible to obtain with the usual external approach from the neck.

14

Section 1: History and Basics

A

B

Figs 1.20A and B: Transesophageal echocardiographic assessment of coronary arteries. Visualization and demonstration of stenosis by contrast echo enhancement. (A) Left panel: Linear flow signals (arrows) are demonstrated in the proximal left anterior descending coronary artery (LAD; without demonstrating the walls) following intravenous injection of Levovist, a contrast agent. Right panel: This LAD segment could not be demonstrated without contrast injection; (B) Left panel: Intravenous injection of Levovist not only demonstrated flow signals in the LAD but also showed an area of flow acceleration and aliasing corresponding to an area of severe stenosis in the proximal LAD on the coronary angiogram. Right panel: A smaller area of flow signals with a smaller flow acceleration persisting from a previous Levovist injection. Contrast enhancement is useful in demonstrating additional segments of the coronary arteries not visualized on routine examination and demonstrating stenoses in these segments. Source: Reproduced with permission from Agarwal KK, Gatewood RP, Nanda NC, et al. Improved transesophageal echocardiographic assessment of significant proximal narrowing of the left anterior descending and left circumflex coronary arteries using echo contrast enhancement. Am J Cardiol. 1994;73:1131–3.

Fig. 1.21: Transesophageal echocardiographic assessment of coronary arteries. A long segment of the circumflex (CX) coronary artery is seen coursing laterally. (LA: Left atrium; LAD: Left anterior descending coronary artery; LM: Left main coronary artery). Source: Reproduced with permission from Nanda NC, Domanski MJ. Atlas of Transesophageal Echocardiography. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007: 31.

TISSUE DOPPLER AND SPECKLE TRACKING IMAGING Since the velocity of blood is much faster than that of the cardiac tissue, usual Doppler imaging filters out slow-

moving objects such as cardiac tissue in order to enhance the images. With tissue imaging, the reverse is done, whereby the fast velocities of the red blood cells are filtered out and the velocity of the tissue is captured. This principle was exploited early on in the history of echocardiography in order to image the velocity of the posterior wall as early as 1972.103 Development in tissue Doppler imaging in the 1990s allowed for imaging the velocity of myocardial motion and for the analysis of myocardial segments independently of each other.104,105 These improvements facilitated the use of tissue Doppler imaging in the assessment of left ventricular diastolic function and in the measurement of strain and strain-rate of the individual myocardial segments. Because of the limitations posed by the angle dependence of the Doppler beam, techniques based on real time, 2D echocardiography such as velocity vector imaging106 and speckle tracking imaging 107 were introduced a few years ago (Fig. 1.24).

THREE-DIMENSIONAL ECHOCARDIOGRAPHY Since 2D echocardiography is not ideal for imaging 3D cardiac structures, several attempts were made over the years to develop 3D echocardiography.108–114 Moritz and Shreve115 introduced the spark gap position-locating approach

Chapter 1: History of Echocardiography

A

15

B

Figs 1.22A and B: Transgastric ultrasound for examination of abdominal structures and vessels. (A) Transgastric examination of the superior mesenteric and renal vessels. Transverse plane imaging. Both the superior mesenteric (SMA) and the left renal arteries (LRA) are visualized arising from the abdominal aorta (AO). The inset shows pulse wave (PW) Doppler velocity waveform obtained from the SMA. (SA: Splenic artery. (B) Schematic representation. Source: Reproduced with permission from Chouinard MD, Pinheiro L, Nanda NC, Sanyal RS. Transgastric ultrasonography: a new approach for imaging the abdominal structures and vessels. Echocardiography. 1991; 9:397–403.

A

B

Figs 1.23A and B: Transpharyngeal ultrasound diagnosis of left carotid bulb and internal carotid artery stenosis. (A) Color Doppler examination demonstrating the ascending pharyngeal (AP) and other branches (arrows) of the left external carotid artery (LEC). The left internal jugular vein (LIJV) is seen adjacent to the left common carotid artery (LCC). (B) Color Doppler-guided pulsed and continuouswave Doppler examination of the proximal left internal carotid (LIC) shows a peak systolic velocity of 1.8 m/s and a peak diastolic velocity approaching 1.0 m/s, indicative of significant stenosis. Note that the Doppler beam is aligned parallel to the flow direction in the proximal LIC. Source: Reproduced with permission from Nanda NC, Gomez, CR, Narayan VK, Tery JB, et al. Transpharyngeal echocardiographic diagnosis of carotid bulb and left internal carotid artery stenosis. Echocardiography. 1999;16:671–4.

(an acoustic spatial locating system) to provide 3D coordinates, but this method was not capable of recording or viewing 3D images. The Nanda group113 used an approach that was able to image the left ventricle in three dimensions by placing a 2D transducer on a mechanical arm that allowed it to rotate around its axis. The transducer was rotated every few degrees in a sequential manner,

and multiple slices of the heart at end systole and end diastole were obtained (Figs 1.25A and B). These were then reconstructed by a computer to obtain 3D images of the left ventricle. The volumes obtained using this method were validated by angiography. This work was further extended by the same group to successfully incorporate Doppler information and color Doppler reconstruction.116,117

16

Section 1: History and Basics

Fig. 1.24: Velocity vector imaging before and after cardiac resynchronization therapy. Velocity vector data obtained from the left ventricular short-axis view. The radial velocities in the lateral wall peak in late systole/early diastole prior to biventricular pacing. After biventricular pacing, the septal and lateral wall radial velocities are synchronous. Thus, cardiac resynchronization therapy (CRT) has improved radial myocardial contraction synchrony. Source: Reproduced with permission from Vannan MA, Pedrizzetti G, Lip P, Gurudevan S, Houle H, Main J, et al. Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging. Description and initial clinical application of a novel method using high-frame rate B-mode echocardiographic images. Echocardiography. 2005;22;823–60.

A Figs 1.25A and B: (A) Three-dimensional reconstruction of transthoracic echocardiographic images by apical axis rotation method. The transducer rotation and different planes intersecting the heart are shown here. The transducer was held manually; (B) Subsequently, the transducer was mounted on a mechanical arm, which permitted only 1° of freedom—rotation about its axis. Source: Reproduced with permission from Ghosh A, Nanda NC, Maurer G. Three-dimensional reconstruction of echocardiographic images using the rotation method. Ultrasound Med Biol. 1982;8:655–61.

B

Chapter 1: History of Echocardiography

17

Later, 3D transesophageal echocardiography was developed by mounting a monoplane probe on a sliding carriage within a casing. By moving the probe up and down the esophagus in small increments, transverse sections at various parallel cardiac levels were obtained and the images were then reconstructed using a computer to provide 3D images.118,119 This technique, developed by the TomTec Company (Munich, Germany), was limited due to the large size of the probe which precluded routine clinical use. The next step was to use a biplane transesophageal echocardiography probe for 3D imaging. In order to determine the probe rotation angle, a protractor mounted on the probe shaft guard was used. The probe was angulated at 90° and manually rotated in a clockwise direction in small increments to provide sequential longitudinal images that were then reconstructed in 3D using both B-mode and color Doppler (Fig. 1.26).120,121 Nanda et al122 then used a multiplane transesophageal echocardiography transducer to reconstruct 3D images by ensuring that the probe remained stationary at a given level and rotating it at 18° intervals at a time (Figs 1.27 and 1.28). Since with this technology the 3D dataset could be sliced in any direction similar to dissecting a piece of tissue, it allowed for the visualization of cardiac structures from any direction and

the understanding of the complex relationship between structures. Several clinical applications ensued from this development (Figs 1.29A to C).123–127 With 3D reconstruction imaging, imaging artifact was common because of the time needed for acquisition of images over several cardiac cycles with patient and/or probe motion during the procedure in addition to changes in heart rate. Live/real time, 3D imaging was thus developed and is currently the 3D technique used in clinical practice. Initial attempts at the development of

Fig. 1.26: Three-dimensional reconstruction of transesophageal echocardiographic longitudinal images. Three-dimensional image of superior vena cava zone, showing three-dimensionally reconstructed longitudinal structures of superior vena cava (SVC), inferior vena cava (IVC), right atrium (RA), left atrium (LA), and right pulmonary artery (RPA). Source: Reproduced with permission from Li ZA, Wang XF, Nanda NC, et al. Three dimensional reconstruction of transesophageal echocardiographic longitudinal images. Echocardiography. 1995;12:367–75.

Fig. 1.27: Three-dimensional reconstruction of multiplane transesophageal echocardiographic images. Sequential multiplanar transesophageal two-dimensional images of the left ventricle were obtained by rotating the probe in small angular increments. These were then reconstructed to obtain a three-dimensional image of the left ventricle. (LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle). Source: Reproduced with permission from Nanda NC, Pinheiro L, Sanyal R, et al. Multiplane transesophageal echocardiographic imaging and three-dimensional reconstruction a preliminary study. Echocardiography. 1992;9:667–76.

18

Section 1: History and Basics

Fig. 1.28: Three-dimensional reconstruction of the left ventricle using sequential planes obtained from multiplane transesophageal examination in an adult patient. The “volume cast” of the left ventricular cavity is shown. Source: Reproduced with permission from Nanda NC, Pinheiro L, Sanyal R, et al. Multiplane transesophageal echocardiographic imaging and three-dimensional reconstruction a preliminary study. Echocardiography. 1992;9:667–76.

A

3D transthoracic echocardiography (TTE) resulted in a stand-alone system which was able to provide B-mode images only.128 A matrix probe was then developed to provide live/real time, B-mode and color Doppler images, therefore, facilitating its use in day-to-day clinical practice.129 These datasets were obtained over four to eight cardiac beats. Further development resulted in real time, 3D imaging in which a dataset was obtained of an entire volume of the heart using only one or more cardiac cycles that could then be dissected along any direction.130 Another important innovation was the development of a single transducer to perform both 2D and live/ real time, 3D studies. Subsequently, the transducer was incorporated in the transesophageal probe and live/real time, 3D transesophageal echocardiography was born. The first clinical study using this technology was published from the University of Alabama at Birmingham in 2007 (Fig. 1.30).131,132 This technique has found popularity in the operating room and cardiac catheterization laboratories for percutaneous procedures.

B

Figs 1.29A and B: Three-dimensional transesophageal echocardiography. (A) Transesophageal three-dimensional reconstruction of the stenotic aortic valve. The aortic valve (AV) shows multiple echo-dense areas indicative of severe thickening and calcification. Although the AV is considerably distorted, three leaflets are easily identified in the systole. The aortic orifice is very small and measured 0.7 cm2 by planimetry; (B) Schematic diagram demonstrating that the maximum dimension of an object (in this case, a cylinder) can be obtained only if the ultrasound beam cuts through its longest dimension (true long axis) when using a multiplane probe. However, when the two-dimensional planes (dotted lines) are stacked together to obtain a three-dimensional image, the object (cylinder), including its long axis, can be viewed completely, even though it is not oriented parallel to the ultrasonic beam as it is rotated from 0° to 180°. As demonstrated here, it is not possible to image the true long axis of an intracardiac mass lesion or defect (such as an atrial septal defect) using multiplane two-dimensional transesophageal echocardiography unless it lies exactly parallel to the ultrasound beam as it is rotated from 0° to 180°. Therefore, the maximum size of a mass or defect may be underestimated by multiplane twodimensional transesophageal echocardiography. On the other hand, with three-dimensional transesophageal reconstruction, multiple sequential two-dimensional images are stacked to reconstruct the entire object in three dimensions, permitting accurate assessment of all its dimensions. (LA: Left atrium; AV: Aortic valve area; RVO: Right ventricular outflow tract). Source: (A) Reproduced with permission from Nanda NC, Roychoudhury D, Chung SM, et al. Quantitative assessment of normal and stenotic aortic valve using transesophageal three-dimensional echocardiography. Echocardiography. 1994;11:617–25. Source: (B) Reproduced with permission from Nanda NC, Abd-El Rahman SM, Khatri G, et al. Incremental value of three-dimensional echocardiography over transesophageal multiplane two-dimensional echocardiography in qualitative and quantitative assessment of cardiac masses and defects. Echocardiography. 1995;12:619–28.

Chapter 1: History of Echocardiography

19

Fig. 1.30: Live/real time, three-dimensional transesophageal echocardiography. Mitral valve ring viewed en face by cropping from the atrial aspect. The arrow points to the en face view of the Duran ring. Source: Reproduced with permission from Pothineni KR, Inamdar V, Miller AP, Nanda NC, Bandarupalli N, Chaurasia P, et al. Initial experience with live/real time, three-dimensional transesophageal echocardiography. Echocardiography. 2007;24:1099–104.

Fig. 1.29C: Transesophageal three-dimensional echocardiographic examination of coronary arteries. There is a tight stenosis (arrow) of the circumflex coronary artery (LCX) imaged in long-axis view in three dimensions. The arrow points to an atrial branch. (AO: Aorta; LA: Left atrium; LMC: Left main coronary artery). Source: Reproduced with permission from Abd El-Rahman SM, Khatri G, Nanda N, et al. Transesophageal three-dimensional echocardiographic assessment of normal and stenosed coronary arteries. Echocardiography. 1996; 13:503–10.

PERSPECTIVE The use of echocardiography over the last decades has changed the practice of cardiology. This modality has successfully evolved with the changing tides of time to continue to be relevant to practicing physicians. It started as a research tool with M-mode whose potential was limited to a handful of pathologies and a future that looked unpromising. Due to the work of multiple investigators with the vision to enhance this field, 2D echocardiography was developed, which helped clinicians in the evaluation of a wide array of diseases ranging from congenital and valvular heart disease to coronary artery disease. Further developments, including the introduction of conventional and color Doppler flow imaging, allowed

for real time visualization of blood flow and opened the era of noninvasive hemodynamic cardiac assessment. With the introduction of 3D echocardiography, the dream of early pioneers of visualizing cardiac structures in a real-life perspective using ultrasound was realized. Echocardiography has become so useful to the clinician that it can be rightfully considered as an extension of clinical cardiac examination, more so because of the development of small, palm-sized handheld echocardiographic machines that can fit into the pocket of a white coat, like a stethoscope.133 We have not reached the end of the road. There is still room for improvement in the resolution of images as well as in the hardware and software used for the various applications. Education regarding the relevance of the newer ultrasound technologies to the cardiologist and echocardiographer is not optimal. Nevertheless, there is still reason to believe that echocardiography will continue to be the chief and most cost-effective cardiac imaging modality for decades to come.

REFERENCES 1. Krishnamoorthy VK, Sengupta PP, Gentile F, et al. History of echocardiography and its future applications in medicine. Crit Care Med. 2007;35(8 Suppl):S309–13. 2. Feigenbaum H. Evolution of echocardiography. Circulation. 1996;93(7):1321–7.

20

Section 1: History and Basics

3. Pandian NG, Roelandt J, Nanda NC, et al. Dynamic threedimensional echocardiography: methods and clinical potential. Echocardiography. 1994;11(3):237–59. 4. Wade G. Human uses of ultrasound: ancient and modern. Ultrasonics. 2000;38(1-8):1–5. 5. Edler I, Hertz CH. The use of ultrasonic reflectoscope for the continuous recording of the movements of heart walls. 1954. Clin Physiol Funct Imaging. 2004;24(3):118–36. 6. Edler I, Lindström K. The history of echocardiography. Ultrasound Med Biol. 2004;30(12):1565–1644. 7. Gowda RM, Khan IA, Vasavada BC, et al. History of the evolution of echocardiography. Int J Cardiol. 2004;97(1): 1–6. 8. Edler I, Gustafson A. Ultrasonic cardiogram in mitral stenosis; preliminary communication. Acta Med Scand. 1957;159(2):85–90. 9. Edler I. Ultrasound cardiography in mitral valve stenosis. Am J Cardiol. 1967;19(1):18–31. 10. Edler I. Ultrasound cardiography. Ultrasonics. 1967;5:72–9. 11. Edler I. Atrioventricular valve motility in the living human heart recorded by ultrasound. Acta Med Scand Suppl. 1961;370:83–124. 12. Edler I. The use of ultrasound as a diagnostic aid, and its effects on biological tissues. Continuous recording of the movements of various heart-structures using an ultrasound echo-method. Acta Med Scand Suppl. 1961;370:7–65. 13. Joyner CR Jr, Reid JM, Bond JP. Reflected ultrasound in the assessment of mitral valve disease. Circulation. 1963;27 (4 Pt 1):503–11. 14. Feigenbaum H, Waldhausen JA, Hyde LP. Ultrasound diagnosis of pericardial effusion. JAMA. 1965;191:711–14. 15. Feigenbaum H, Popp RL, Wolfe SB, et al. Ultrasound measurements of the left ventricle. A correlative study with angiocardiography. Arch Intern Med. 1972;129(3):461–7. 16. Pombo JF, Troy BL, Russell RO Jr. Left ventricular volumes and ejection fraction by echocardiography. Circulation. 1971;43(4):480–90. 17. Popp RL, Harrison DC. Ultrasonic cardiac echography for determining stroke volume and valvular regurgitation. Circulation. 1970;41(3):493–502. 18. Gramiak R, Nanda NC, Shah PM. Echocardiographic detection of the pulmonary valve. Radiology. 1972;102(1): 153–7. 19. Gramiak R, Chung KJ, Nanda N, et al. Echocardiographic diagnosis of transposition of the great vessels. Radiology. 1973;106(1):187–9. 20. Nanda NC, Gramiak R, Manning JA, et al. Echocardiographic features of subpulmonic obstruction in dextro-transposition of the great vessels. Circulation. 1975; 51(3):515–21. 21. Nanda NC, Gramiak R, Robinson TI, et al. Echocardiographic evaluation of pulmonary hypertension. Circulation. 1974;50(3):575–81. 22. Nanda NC, Gramiak R, Manning J, et al. Echocardiographic recognition of the congenital bicuspid aortic valve. Circulation. 1974;49(5): 870–5. 23. Nanda NC, Steward S, Gramiak R, et al. Echocardiography of the intra-atrial baffle in dextro-transposition of the great vessels. Circulation. 1975;51:1130–5.

24. Nanda NC, Gramiak R, Shah PM. Echocardiographic misdiagnosis of the severity of mitral stenosis. Clin Res. 1975;23:199A. 25. Feigenbaum H. Echocardiography. 1st ed. Philadelphia, PA: Lea & Febiger; 1972. 26. Nanda NC, Gramiak R. Clinical Echocardiography. St. Louis, MO: C. V. Mosby; 1978. 27. Gramiak R, Waag RC, Simon W. Ciné ultrasound cardiography. Radiology. 1973;107(1):175–80. 28. Bom N, Lancée CT, Honkoop J, et al. Ultrasonic viewer for cross-sectional analyses of moving cardiac structures. Biomed Eng. 1971;6(11):500–3, 5. 29. Griffith JM, Henry WL. A sector scanner for real time twodimensional echocardiography. Circulation. 1974;49(6): 1147–52. 30. Reeves WC, Nanda NC, Barold SS. Echocardiographic evaluation of intracardiac pacing catheters: M-mode and two-dimensional studies. Circulation. 1978;58(6):1049–56. 31. Gondi B, Nanda NC. Real-time, two-dimensional echocardiographic features of pacemaker perforation. Circulation. 1981;64(1):97–106. 32. Harris JP, Nanda NC, Moxley R, et al. Myocardial perforation due to temporary transvenous pacing catheters in pediatric patients. Cathet Cardiovasc Diagn. 1984;10(4):329–33. 33. Schuster AH, Zugibe F Jr, Nanda NC, et al. Twodimensional echocardiographic identification of pacing catheter-induced thrombosis. Pacing Clin Electrophysiol. 1982;5(1):124–8. 34. Rosenbloom M, Saksena S, Nanda NC, et al. Twodimensional echocardiographic studies during sustained ventricular tachycardia. Pacing Clin Electrophysiol. 1984; 7(1):136–42. 35. Gatewood RP Jr, Nanda NC. Differentiation of left ventricular pseudoaneurysm from true aneurysm with two dimensional echocardiography. Am J Cardiol. 1980;46(5):869–78. 36. Gondi B, Nanda NC. Two-dimensional echocardiographic features of atrial septal aneurysms. Circulation. 1981;63(2): 452–7. 37. D’Arcy BJ, Nanda NC. Two-dimensional echo features of right ventricular infarction. Circulation. 1982;65:167–73. 38. Bhandari AK, Nanda NC. Two-dimensional echocardiographic recognition of abnormal changes in the myocardium. Ultrasound Med Biol. 1982;8(6):663–71. 39. Bhandari AK, Nanda NC, Hicks DG. Two-dimensional echocardiography of intracardiac masses: echo patternhistopathology correlation. Ultrasound Med Biol. 1982;8(6): 673–80. 40. Maurer G, Nanda NC. Two dimensional echocardiographic evaluation of exercise-induced left and right ventricular asynergy: correlation with thallium scanning. Am J Cardiol. 1981;48(4):720–7. 41. Oberman A, Fan PH, Nanda NC, et al. Reproducibility of two-dimensional exercise echocardiography. J Am Coll Cardiol. 1989;14(4):923–8. 42. Gondi B, Nanda NC. Cold pressor test during real time twodimensional echocardiography: usefulness in detection of patients with coronary artery disease. Am Heart J. 1984;107: 278–85.

Chapter 1: History of Echocardiography

43. Mathew T, Nanda NC. Two-dimensional and Doppler echocardiographic evaluation of aortic aneurysm and dissection. Am J Cardiol. 1984;54(3):379–85. 44. Baran A, Nanda NC, Falkoff M, et al. Two-dimensional echocardiographic detection of arrhythmogenic right ventricular dysplasia. Am Heart J. 1982;103(6):1066–7. 45. TInker DD, Nanda NC, Harris JP, et al. Two-dimensional echocardiographic identification of pulmonary artery branch stenosis. Am J Cardiol. 1982;50(4):814–20. 46. Bhandari AK, Nanda NC. Pulmonary artery aneurysms: echocardiographic features in 5 patients. Am J Cardiol. 1984;53(10):1438–41. 47. Reinold E. [”On the colored light of double stars and certain other stars of heaven” and what happened hence]. Ultraschall Med. 2004;25(2):101–4. 48. Satomura S. A study on examining the heart with ultrasonics. I. Principles; II. Instrument. Jpn Circ J. 1956;20:227–8. 49. Rushmer RF, Baker DW, Stegall HF. Transcutaneous Doppler flow detection as a nondestructive technique. J Appl Physiol. 1966;21(2):554–66. 50. Baker DW, Rubenstein SA, Lorch GS. Pulsed Doppler echocardiography: principles and applications. Am J Med. 1977;63(1):69–80. 51. Holen J, Simonsen S. Determination of pressure gradient in mitral stenosis with Doppler echocardiography. Br Heart J. 1979;41(5):529–35. 52. Hatle L, Angelsen BA, Tromsdal A. Non-invasive assessment of aortic stenosis by Doppler ultrasound. Br Heart J. 1980;43(3):284–92. 53. Hatle L, Brubakk A, Tromsdal A, et al. Noninvasive assessment of pressure drop in mitral stenosis by Doppler ultrasound. Br Heart J. 1978;40(2):131–40. 54. Nanda NC, Hodsden J, Santelli S. Pulse Doppler echocardiography of coronary arteries: methodology and clinical usefulness. Am J Cardiol. 1982;49:932. 55. Maulik D, Saini VD, Nanda NC, et al. Doppler evaluation of fetal hemodynamics. Ultrasound Med Biol. 1982;8(6): 705–10. 56. Maulik D, Nanda NC, Saini VD. Fetal Doppler echocardiography: methods and characterization of normal and abnormal hemodynamics. Am J Cardiol. 1984;53(4):572–8. 57. Hatle L, Angelsen B. Doppler Ultrasound in Cardiology— Physical Principles and Clinical Applications. Philadelphia, PA: Lea & Febiger; 1982. 58. Nanda NC, editor. Doppler Echocardiography. New York: Igaku-Shoin Medical Publishers; 1985. 59. Zugibe FT Jr, Nanda NC, Barold SS, et al. Usefulness of Doppler echocardiography in cardiac pacing: assessment of mitral regurgitation, peak aortic flow velocity and atrial capture. Pacing Clin Electrophysiol. 1983;6(6):1350–7. 60. Nanda NC, Bhandari A, Barold SS, et al. Doppler echocardiographic studies in sequential atrioventricular pacing. Pacing Clin Electrophysiol. 1983;6(4):811–14. 61. Omoto R, Yokote Y, Takamoto S, et al. The development of real-time two-dimensional Doppler echocardiography and its clinical significance in acquired valvular diseases. With special reference to the evaluation of valvular regurgitation. Jpn Heart J. 1984;25(3):325–40.

21

62. Kasi C, Namekawa K, Koyano A, et al. Real-time twodimensional blood flow imaging using an autocorrelation technique. IEEE Trans Sonics Ultrason. 1985;SU-32;458–64. 63. Helmcke F, Nanda NC, Hsiung MC, et al. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation. 1987;75(1):175–83. 64. Perry GJ, Helmcke F, Nanda NC, et al. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol. 1987;9(4):952–9. 65. Chopra HK, Nanda NC, Fan P, et al. Can two-dimensional echocardiography and Doppler color flow mapping identify the need for tricuspid valve repair? J Am Coll Cardiol. 1989;14(5):1266–74. 66. Dagli SV, Nanda NC, Roitman D, et al. Evaluation of aortic dissection by Doppler color flow mapping. Am J Cardiol. 1985;56(7):497–8. 67. Fan PH, Kapur KK, Nanda NC. Color Doppler assessment of aortic valve stenosis. J Am Coll Cardiol 1988;12:441–9. 68. Kapur KK, Fan P, Nanda NC, et al. Doppler color flow mapping in the evaluation of prosthetic mitral and aortic valve function. J Am Coll Cardiol. 1989; 13(7):1561–71. 69. Maulik D, Nanda NC, Hsiung MC, et al. Doppler color flow mapping of the fetal heart. Angiology. 1986;37(9):628–32. 70. Zachariah ZP, Hsiung MC, Nanda NC, et al. Color Doppler assessment of mitral regurgitation induced by supine exercise in ischemic heart disease. Am J Cardiol. 1987;59: 1266–70. 71. Jain S, Pinheiro L, Nanda NC, et al. Noninvasive assessment of renal artery stenosis by combined conventional and color Doppler ultrasound. Echocardiography. 1990;7(6): 679–88. 72. Omoto R, editor. Color Atlas of Real-Time Two-Dimensional Doppler Echocardiography. Tokyo, Japan: Shindan-ToChiryo Col; 1984. 73. Nanda NC. Atlas of Color Doppler Echocardiography. Philadelphia, PA: Lea & Febiger; 1989. 74. Nanda NC, editor. Textbook of Color Doppler Echocardiography. Philadelphia, PA: Lea & Febiger; 1989. 75. Gramiak R, Shah PM. Echocardiography of the aortic root. Invest Radiol. 1968;3(5):356–66. 76. Rothbard RL, Nanda NC. Contrast echocardiography. Semin Ultrasound. 1981;2:167–72. 77. Nanda NC, Gramiak R, Manning JA. Echocardiography of the tricuspid valve in congenital left ventricular-right atrial communication. Circulation. 1975;51(2):268–72. 78. Miller AP, Nanda NC. Contrast echocardiography: new agents. Ultrasound Med Biol. 2004;30(4):425–34. 79. Nanda NC, Shah PM, Gramiak R. Echocardiographic evaluation of tricuspid valve incompetence by contrast injections. Clin Res. 1976;24:233A. 80. Burri MV, Mahan EF 3rd, Nanda NC, et al. Superior vena cava, right pulmonary artery or both: real time two- and threedimensional transthoracic contrast echocardiographic identification of the echo-free space posterior to the ascending aorta. Echocardiography. 2007;24(8):875–82. 81. Carroll BA, Turner RJ, Tickner EG, et al. Gelatin encapsulated nitrogen microbubbles as ultrasonic contrast agents. Invest Radiol. 1980;15(3):260–6.

22

Section 1: History and Basics

82. Feinstein SB, Shah PM, Bing RJ, et al. Microbubble dynamics visualized in the intact capillary circulation. J Am Coll Cardiol. 1984;4(3):595–600. 83. Nanda NC, Wistran DC, Karlsberg RP, et al. Multicenter evaluation of SonoVue for improved endocardial border delineation. Echocardiography. 2002;19(1):27–36. 84. Nanda NC, Kitzman DW, Dittrich HC, et al. Imagent Clinical Investigators Group. Imagent improves endocardial border delineation, inter-reader agreement, and the accuracy of segmental wall motion assessment. Echocardiography. 2003;20(2):151–61. 85. Nanda NC, Schlief R, editors. Advances in Echo Imaging Using Contrast Enhancement. Dordrecht, The Netherlands: Kluwer Academic Publishers; 1993. 86. Side CD, Gosling RG. Non-surgical assessment of cardiac function. Nature. 1971;232(5309):335–6. 87. Frazin L, Talano JV, Stephanides L, et al. Esophageal echocardiography. Circulation. 1976;54(1):102–8. 88. Hanrath P, Kremer P, Langenstein BA, et al. [Transesophageal echocardiography. A new method for dynamic ventricle function analysis]. Dtsch Med Wochenschr. 1981; 106(17):523–5. 89. Seward JB, Khandheria BK, Oh JK, et al. Transesophageal echocardiography: technique, anatomic correlations, implementation, and clinical applications. Mayo Clin Proc. 1988;63(7):649–80. 90. Nanda NC, Pinheiro L, Sanyal RS, et al. Transesophageal biplane echocardiographic imaging: technique, planes, and clinical usefulness. Echocardiography. 1990;7(6):771–88. 91. Nanda NC, Domanski M. Atlas of Transesophageal Echocardiography. Baltimore, MD: Williams & Wilkins; 1998. 92. Samdarshi TE, Nanda NC, Gatewood RP Jr, et al. Usefulness and limitations of transesophageal echocardiography in the assessment of proximal coronary artery stenosis. J Am Coll Cardiol. 1992;19(3):572–80. 93. Chouinard MD, Pinheiro L, Nanda NC, et al. Transgastric ultrasonography: a new approach for imaging the abdominal structures and vessels. Echocardiography. 1991;8: 397–403. 94. Agrawal G, LaMotte LC, Nanda NC, et al. Identification of the Aortic Arch Branches Using Transesophageal Echocardiography. Echocardiography. 1997;14(5):461–6. 95. LaMotte LC, Nanda NC, Thakur AC, et al. Transesophageal Echocardiographic Identification of Neck Veins: Value of Contrast Echocardiography. Echocardiography. 1998;15(3): 259–68. 96. Nanda NC, Biederman RW, Thakur AC, et al. Examination of Left External and Internal Carotid Arteries During Transesophageal Echocardiography. Echocardiography. 1998;15(8 Pt 1):755–8. 97. Nanda NC, Thakur AC, Thakur D, et al. Transesophageal Echocardiographic Examination of Left Subclavian Artery Branches. Echocardiography. 1999;16(3):271–7. 98. Nanda NC, Nekkanti R, Melendez A, et al. Transesophageal two-dimensional echocardiographic demonstration of the innominate artery and its branches. Am J Geriatr Cardiol. 2001;10(6):368–70.

99. Aaluri S, Miller AP, Nanda NC, et al. Transesophageal echocardiographic detection of left vertebral artery origin stenosis. Echocardiography. 2002;19(8):695–7. 100. Nanda NC, Gomez CR, Narayan VK, et al. Transpharyngeal Echocardiographic Diagnosis of Carotid Bulb and Left Internal Carotid Artery Stenosis. Echocardiography. 1999; 16(7, Pt 1):671–4. 101. Miller A, Nanda NC, Mukhtar O, et al. Transpharyngeal echocardiographic detection of a left internal carotid artery stent. Echocardiography. 2000;17(8): 739–41. 102. Khanna D, Cheng PH, Nanda NC, et al. Transpharyngeal ultrasound detection of carotid body paraganglioma. Echocardiography. 2004;21(3):299–301. 103. Kostis JB, Mavrogeorgis E, Slater A, et al. Use of a rangegated, pulsed ultrasonic Doppler technique for continuous measurement of velocity of the posterior heart wall. Chest. 1972;62(5):597–604. 104. McDicken WN, Sutherland GR, Moran CM, et al. Colour Doppler velocity imaging of the myocardium. Ultrasound Med Biol. 1992;18(6-7):651–4. 105. Miyatake K, Yamagishi M, Tanaka N, et al. New method for evaluating left ventricular wall motion by color-coded tissue Doppler imaging: in vitro and in vivo studies. J Am Coll Cardiol. 1995;25(3):717–24. 106. Vannan MA, Pedrizzetti G, Li P, et al. Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging: description and initial clinical application of a novel method using high-frame rate B-mode echocardiographic images. Echocardiography. 2005;22(10):826–30. 107. Geyer H, Caracciolo G, Abe H, et al. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr. 2010;23(4):351–69; quiz 453. 108. Dekker DL, Piziali RL, Dong E Jr. A system for ultrasonically imaging the human heart in three dimensions. Comput Biomed Res. 1974;7(6):544–53. 109. Geiser EA, Lupkiewicz SM, Christie LG, et al. A framework for three-dimensional time-varying reconstruction of the human left ventricle: sources of error and estimation of their magnitude. Comput Biomed Res. 1980;13(3):225–41. 110. King D, Al-Bana S, Larach D. A new three-dimensional random scanner for ultrasonic/computer graphic imaging of the heart. In: White DN, Barnes R, editors. Ultrasound in Medicine. New York; 1975: 363–72. 111. Moritz WE, Pearlman AS, McCabe DH, et al. An ultrasonic technique for imaging the ventricle in three dimensions and calculating its volume. IEEE Trans Biomed Eng. 1983;30(8):482–92. 112. Matsumoto M, Matsuo H, Kitabatake A, et al. Threedimensional echocardiograms and two-dimensional echocardiographic images at desired planes by a computerized system. Ultrasound Med Biol. 1977;3(2-3):163–78. 113. Ghosh A, Nanda NC, Maurer G. Three-dimensional reconstruction of echo-cardiographic images using the rotation method. Ultrasound Med Biol. 1982;8(6):655–61.

Chapter 1: History of Echocardiography

114. Handschumacher MD, Lethor JP, Siu SC, et al. A new integrated system for three-dimensional echocardiographic reconstruction: development and validation for ventricular volume with application in human subjects. J Am Coll Cardiol. 1993;21(3):743–53. 115. Moritz WE, Shreve PL. A microprocessor based spatial locating system for use with diagnostic ultrasound. Proc IEEE. 1976;64:966–74. 116. Raqueno R, Ghosh A, Nanda NC. Four-dimensional reconstruction of two-dimensional echocardiographic images. Echocardiography. 1989;6:323–37. 117. Schott JR, Raqueno R, Ghosh A, et al. Four dimensional cardiac blood flow analysis using color Doppler echocardiography. In: Nanda NC, editor. Textbook of Color Doppler Echocardiography. Philadelphia, PA: Lea & Febiger; 1989: 332–41. 118. Wollschlager H, Zeiher AM, Klein H, et al. Transesophageal echo computer tomography: a new method for dynamic 3-D imaging of the heart (Echo-CT). Comp Cardiol IEEE Comp Soc. 1990;39. 119. Pandian NG, Nanda NC, Schwartz SL, et al. Threedimensional and four-dimensional transesophageal echocardiographic imaging of the heart and aorta in humans using a computed tomographic imaging probe. Echocardiography. 1992;9(6):677–87. 120. Li ZA, Wang XF, Nanda NC, et al. Three dimensional reconstruction of transesophageal echocardiographic longitudinal images. Echocardiography. 1995;12:367–75. 121. Li Z, Wang X, Xie M, Nanda NC, Hsiung MC. Dynamic ThreeDimensional Reconstruction of Abnormal Intracardiac Blood Flow. Echocardiography. 1997;14(4):375–82. 122. Nanda NC, Pinheiro L, Sanyal R, et al. Multiplane transesophageal echocardiographic imaging and threedimensional reconstruction. Echocardiography. 1992;9: 667–76.

23

123. Nanda NC, Abd El-Rahman SM, Khatri GK, et al. Incremental value of three-dimensional echocardiography over transesophageal multiplane two-dimensional echocardiography in qualitative and quantitative assessment of cardiac masses and defects. Echocardiography. 1995;12(6):619–28. 124. Nanda NC, Roychoudhury D, Chung SM, et al. Quantitative assessment of normal and stenotic aortic valve using transesophageal three-dimensional echocardiography. Echocardiography. 1994;11(6):617–25. 125. Abd El-Rahman SM, Khatri G, Nanda NC, et al. Transesophageal three-dimensional echocardiographic assessment of normal and stenosed coronary arteries. Echocardiography. 1996;13:503–10. 126. Nanda NC, Khatri GK, Samal AK, et al. Three-Dimensional Echocardiographic Assessment of Aortic Dissection. Echocardiography. 1998;15(8 Pt 1):745–54. 127. Nanda NC, Sorrell VL, editors. Atlas of Three-Dimensional Echocardiography. Armonk, NY: Futura; 2002. 128. Sheikh K, Smith SW, von Ramm O, et al. Real-time, threedimensional echocardiography: feasibility and initial use. Echocardiography. 1991;8(1):119–25. 129. Salgo I, Bianchi M. Going “live” with 3-D cardiac ultrasound. Today Cardiol. 2002;5. 130. Hage FG, Nanda NC. Real-time three-dimensional echocardiography: a current view of what echocardiography can provide? Indian Heart J. 2009;61(2):146–55. 131. Pothineni KR, Inamdar V, Miller AP, et al. Initial experience with live/real time three-dimensional transesophageal echocardiography. Echocardiography. 2007;24(10): 1099–104. 132. Nanda NC, Hsiung MC, Miller AP, et al. Live/Real Time 3D Echocardiography. Oxford, UK: Wiley-Blackwell;2010. 133. Mondillo S, Giannotti G, Innelli P, et al. Hand-held echocardiography: its use and usefulness. Int J Cardiol. 2006;111:1–5.

CHAPTER 2 Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology Colette Veyrat

Snapshot  The Preflow Doppler Era: Paucity of ExisƟng

Noninvasive Tools  Explosive Emergence of the “Flow Concept”, an Indispensable MutaƟon from Pressure Measurements, Which Prepared the Doppler Flow Era

INTRODUCTION In the second half of the 20th century, the investigation of flow dynamics in cardiology represented a breakthrough from both technological and conceptual view points. Most of these new insights were carried out by the growing Doppler ultrasound techniques. Indeed, these new parameters had the merit of introducing numerical values in the discussion of cardiac diseases strategy, but, above all, they provided an approach to a new conceptualization of the cardiovascular system and improved our pathophysiological understanding. This chapter will first briefly recall the procedures clinicians could rely on for the diagnosis and evaluation of cardiac lesions before the Doppler gestation period, in the 1960s. Then the introduction of the cardiac Doppler era, slowly elaborated in several steps by a handful of pioneers in a few sites around the world, laid the foundation for the development from which we benefit today. The history of Doppler is a long series of small advances with multiple hesitant paths, some of them leading to deadlocks, and,

 Return to the Doppler Technique in Search of a

Noninvasive Tool DocumenƟng the “Flow Concept”

suddenly, some exciting breakthroughs! Given these to-and-fro advances, writing the history of the early Doppler era cannot follow a strict chronology, but it rather follows the different streamlines of research, some interrupted like the nondirectional Doppler, some others coming back about 30 years later like tissue Doppler imaging through technological progresses, some finally gaining acceptance as directional flow Doppler, through accompanying improvements in imaging modalities and color coding. Continuous wave Doppler quantitative capabilities also representing a major streamline from the last half of the 1970s will reinforce the Doppler technique as a unique noninvasive tool accepted by cardiologists. In brief, the chapter will outline the successive changes in this flow Doppler era from the 1960s till the last decade before the new millennium. Thus, we chose to emphasize on the first steps of pioneers in the desert land of cardiac Doppler, and on the explosive and fruitful research on flow dynamics which paved the way for their success and guided them during more than 30 years.

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

THE PREFLOW DOPPLER ERA: PAUCITY OF EXISTING NONINVASIVE TOOLS A question often raised by clinicians is, What existed before the flow Doppler era? There were mainly one invasive and three noninvasive procedures.

Existing Invasive Procedures in Cardiology If one looks backward over the 20th century, one might be struck by the immobilism of cardiology which remained mainly clinical during the first half of the century. Apart from the case of Forssmann who passed a catheter into his own right atrium in 1929,1 we may schematically account the 1940s for the starting of a change in cardiac approaches. It was inaugurated by the first attempts to catheterization of the right cavities by Cournand and Range,2 followed in 1950 by left heart catheterization by Zimmerman et al.3 and the development of cinecardioangiography.4 Pressure measurements and angiography had a major impact during the three following decades. Pathology mainly consisted of valvular and congenital defects and possible surgical repair justified the interest in preoperative catheterization, which was considered the gold standard reference in cardiology.

Existing Noninvasive Techniques in Cardiology before Doppler Flow Velocity Procedures. Hopes! Very close to this period, noninvasive imaging was introduced by Edler and Gustafson, who reported the diagnosis of mitral stenosis by ultrasonic imaging.5 The introduction of one-dimensional (1D), guided M-mode echocardiography represented an important step for cardiologists because it was the first time that noninvasive imaging was available. Figure 2.1 shows that very close to the advent of flow Doppler, an important meeting was held entirely relying on 1D echocardiography. Immense hope was raised by this imaging, which appeared appropriate for valvular and congenital lesions, encouraging important studies all around the world. While 1D echo imaging enabled the first visualization of the aortic cusps in 1970,6 some overlap in results obtained in 1975 with two-dimensional (2D) echo imaging weakened the hopes and, furthermore, the confidence in reliability of 1D imaging to assess the severity of aortic stenosis.7

25

THE AMERICAN JOURNAL OF CARDIOLOGY Volume 19

JANUARY 1967

Number 1

CONTENTS Echocardiography. Clinical Application in Mitral Regurgitation Bernard L. Segal, William Likoff and Benedict Kingsley

50

Pre-and Postoperative Evaluation of Mitral Stenosis by Ultrasound Sven Effert

59

Reflected Ultrasound in the Diagnosis of Tricuspid Stenosis 66 Claude R. Joyner JR, E. Berry Hey, JR., Julian Johnson and John M. Reid Echocardiography in Congenital Heart Disease. Preliminary Observations Leslie B. Ultan, Bernard L. Segal and William Likoff

74

Use of Reflected Ultrasound in Detecting Pericardial Effusion Harvey Feigenbaum, Adib Zaky and John A. Waldausen

84

Echocardiography George C. Evans, J. Stauffer Lehman, SR., Bernard L. Segal, William Likoff, Marvin Ziskin and Benedict Kingsley

91

Clinical Application of Ultrasound in the Analysis of Prosthetic Ball Valve Function William L Winters, Jr., Jose Gimenez and Louis A Soloff

97

Another Look at Echocardiography. Concepts in Etiomedical Engineering 108 Benedict Kingsley, George B Flint, Jr., George T Raber and Bernard Segal

Symposium on

Diagnostic Ultrasound BERNARD L. SEGAL. M.D. Guest Editor

Fig. 2.1: 1967: “Symposium on diagnostic ultrasound,” directed by Bernard L. Segal, MD. Ultrasonic images consisted of one-dimensional M-mode echo recordings. Nearly all these topics would now require a flow Doppler exploration. Source: By permission of WC Roberts, MD, and of the American Journal of Cardiology. 1967;19(1), 1, copyright © Elsevier.

The other technique traditionally used for valvular and congenital lesions in laboratories was phonocardiography. The improvement lied in two ways. On one hand, the use of vasoactive drugs during the examination had an impact on the diagnosis (Fig. 2.2A).8 On the other hand, the recent introduction of selective frequencies from low to high bandwidths on the graphic display helped to establish some criteria orientating toward a grading approach to lesions.9 Figure 2.2B shows the graphic inscription in a case of aortic regurgitation with an early beginning before the second sound and the important component of low diastolic frequencies of the murmur orientated toward severe regurgitation due to infective endocarditis (Fig. 2.2B). Finally, a most exciting progress was launched in Japan but remained nearly ignored by the Western medical world for a while. It consisted of the introduction of the Doppler technique in cardiology. It derived from

26

Section 1: History and Basics

A

B

Figs 2.2A and B: Phonocardiography, a noninvasive tool before the Doppler flow era. (A) Effect of amyl nitrite on regurgitant jets: there is a conspicuous decrease of the murmur; (B) Severe aortic regurgitation. No clinical grading was available. Increased low frequency on this selective frequencies recording could suggest severe regurgitation as well as the early occurrence of the diastolic murmur before the second sound fourth frequency line (arrows). (A2: Second sound indicated by an arrow; CAR: Carotid pulse; ECG: Electrocardiogram; 4EICG: Fourth left intercostal space; F2 to F6: Frequencies selected from low (F2) to high and all frequencies (F5 F6); PCG: Phonocardiogram; SD and SS: Systolic and diastolic murmur, chart speed 100 and 250 mm/s from left to right).

Fig. 2.3: Christian Doppler, 1803 to 1853. Institute of Physics, Wien, Austria. Personal document.

Christian Doppler’s principle (Fig. 2.3).10 In particular, the technological breakthrough after World War II enabled the application of Doppler techniques to the cardiovascular system: the frequency shift between an ultrasonic beam emitted to and reflected from a moving target (the vascular red blood cells) is proportional to its motion velocity. The first tool is due to Satomura, a Japanese engineer. In 1956, he used a transcutaneous continuous wave Doppler device.11 The probe involved two piezoelectric quartz crystals one of which was emitting and the other receiving. Much ahead of their time, Nimura’s group used the

“Doppler ultrasound cardiograph” to study heart motion.12 Machii’s group studied the velocity of the mitral valve’s closing and opening motions and that of myocardial wall displacement during the cardiac cycle using a Doppler spectrogram.13 They used continuous wave Doppler with a frequency discriminator, which generated a voltage equal to the frequency recorded by means of an electromagnetic oscillograph. These authors studied heart beats and valve motion. They searched for rough signals originated by walls and valve motion rather than high-pitched flow signals which were also heard, but discarded as possible artifacts at this time. As so, Nimura’s group can be considered as the true pioneer in tissue Doppler. Signals, which were not directional improved with time, and the Japanese used a refined spectral analysis as early as the 1960s (Fig. 2.4). Because deflections were not directional, all events were displayed as positive, thereby cutting off much of their physiological content. This technological innovation, nearly unnoticed at the time, constituted a opened window over the future, as it can be seen with 60 years runback.

Deceptions! Indeed, pressure information did not solve all clinical problems, and clinicians as well as surgeons were often disappointed when pressure and surgical data were discrepant. The increasing surgical repair of cardiac lesions brought to light diagnostic limitations in many clinical situations and possible pitfalls of isolated pressure measurements. Errors were frequent in case of prosthetic

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

Fig. 2.4: The Doppler ultrasound cardiograph. This equipment devised by Satomura in 1956, Japan, was applied to patients by Nimura’s group from 1960. Doppler signal of the mitral valve in a case of hypertensive heart disease (top). The Q-Mc interval and the II-Mo interval are prolonged compared with a healthy subject. (bottom) (I and II: First and second heart sound; Q-Mc: Q-Mitral valve closure interval; II-Mo: Second sound-mitral valve opening interval; sec, second; PCG: Phonocardiogram; ECG: Electrocardiograph). Courtesy: of Professor Y. Nimura, reprinted with permission from the American Heart Journal. 1968;75(1):49–65, “Analysis of a cardiac cycle on the left side of the heart in cases of left ventricular overloading or damage with the ultrasonic Doppler method,” Nimura et al. by permission of Professor Nimura and copyright © Elsevier.

dysfunction in which the feasibility of catheterization was furthermore reduced. Indeed, invasive procedures only enabled a rough approach to lesions. This comes as no surprise since the true finality of the cardiovascular system is to create outputs. Pressures are necessary markers but they only evidence the conditions in which blood flows in vessels. Nevertheless, even if somehow disappointing, this period represents the turning point of modern cardiology. The first 13 reports convey an immense desire to modernize cardiology and are a key for a new conceptual future.

EXPLOSIVE EMERGENCE OF THE “FLOW CONCEPT”, AN INDISPENSABLE MUTATION FROM PRESSURE MEASUREMENTS, WHICH PREPARED THE DOPPLER FLOW ERA In the following paragraph, I will emphasize a mandatory and flourishing step: the intellectual mutation that

27

occurred from the era of invasive pressure measurements to that of flow dynamics measurements. It required the knowledge of pressure and flow relationships. Given the deficiencies of pressure measurements, it became obvious that medicine needed other objective parameters. Several reasons explain the delay in processing flow. Manometers to record pressure data were easily obtained by engineers and were not expensive, whereas recording of flow dynamics required a much more difficult technology. Although in 1936, Kolin reported the first experimental attempt using an electromagnetic flowmeter, this trend of research remained isolated.14 Electromagnetic probes were also highly traumatic since the probes had to be surgically implanted around vessels. About the 1960s, McDonald overstepped a fundamental difficulty: he had computed blood flow in arteries from pressure data using Womersley calculations reported in the 1950s.15,16 McDonald showed that flow was not related to the absolute value of pressure but was related to the pressure gradient between two points (Figs 2.5A and B). Briefly summed, one may observe that pressure traces have the same sign during a phase and that their patterns do not vary within a cavity. In contrast, an obvious difference occurs with flow dynamics: if you imagine two adjacent points of a vessel wall, they are successively reached by a pulse pressure wave initiated by the source of pressure. Pressure is higher at the first point than at the farthest one. This generates a pressure gradient between both points, recorded as a positive vector of flow velocity since the fundamental law of fluid dynamics indicates that flow runs from higher to lower pressure areas. When the farthest point is reached by the pulse pressure wave, the reverse situation occurs: the pressure gradient becomes negative and a negative vector of flow velocity is recorded, accounting for the possibility of a backflow in arteries. This explains the similarity between flow velocity and pressure derivative traces (Figs 2.5A and B). Pressure and flow recordings are related both through the pressure derivative versus time (dP/dt) and through the local pressure gradient versus space (dz/dt), dz being the distance between the two close points aligned on the vessel wall. It is the pulsatile character of the pressure wave that entails the oscillatory pattern of flow velocity. A considerable amount of invasive research in flow studies developed around the 1960s. It consisted of mainly experimental methods requiring still catheterization, but they were less traumatic than surgical insertion of a sutured flow probe. Spencer and Denison pioneered the first clinical applications of the pressure gradient technique

28

Section 1: History and Basics

A Figs 2.5A and B: Relationships between blood flow velocity and pressure gradient. (A, Left) From the top to the fifth line, simultaneous recording of the electrocardiogram, femoral pulse tracing (Mécanogramme), intrafemoral pressure trace (Pression arterielle), pressure derivative (Derivée de pression), and flow velocity of the femoral artery (Flux Artère Fémorale), with (+) positive and (–) negative velocities above the zero line. There is a striking similarity between the pressure derivative and the arterial blood flow velocity recordings, both with negative oscillations. (B, Right) Representation of two close sites of recording on pressure pulse tracings (A), pressure gradient (B) and pressure derivative (C). After McDonald, explanations in text. Source: Reprinted with permission from La Presse Médicale, 1968,41:1943–7, Étude des courbes de flux artériel obtenues par enregistrement transcutané chez le sujet normal, Chiche et al. © B Masson, Paris, 1968.

through pulmonary and aortic pressure catheterizations in 1956 and could derive flow velocity traces during the ejectional phase of the great vessels from their data.17 Another method relied on hot thin film anemometers and thin film techniques, respectively in 1967 by Noble18 and in 1969 by Schultz et al.19 They both pioneered flow velocity distribution in large vessels. Mills et al. and Kolin et al. used another equipment consisting of an electromagnetic velocity catheter tip.20,21 Meanwhile, a series of studies, mainly on experiments or during surgery, were dedicated to vena cava flow investigation from 1956 to 1966.22–24 After a time, sophisticated and refined studies were reported in experiments, showing the growing importance of research on flow. Flow profiles were studied by Taylor and Wade by means of an optical Janus needle with a wide-angled lens.25 When the direction of flow was not constant, it was possible to derive flow at any time within the cardiac cycle, by locating the needle in two positions at right angle to each other. In addition, physicians needed information on the assessment of prosthetic hydraulic performance. Thus, prostheses were studied through experiments involving electromagnetic probes inserted on both sides of the heart and by means of 2D visualization of flow vortices.26–28

Flow paths could also be cinefilmed and correlated with the timing of cusp motion.29 So far, in some studies, models only involved a left ventricular cavity and a mitral valve.28 As for annular flow rates, their specific measurement still required surgical insertion of an electromagnetic probe around the annulus in animals.30,31

RETURN TO THE DOPPLER TECHNIQUE IN SEARCH OF A NONINVASIVE TOOL DOCUMENTING THE “FLOW CONCEPT” Nondirectional Flow Doppler Technique As interesting and new as they might be, signals related to heart motion recorded with Satomura’s first apparatus were not further investigated due to lack of the sophisticated equipment now used for tissue Doppler. Interestingly, Kaneko, a Japanese psychoneurologist, suspected the high-pitched signals heard in the area of the carotid artery to be possible flow signals. He asked Satomura to devise an updated apparatus. Flow signal acquisition mainly relied on some alterations in gain with signals under 120 Hz being filtered to get rid of wall motion. An equipment

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

was designed and studies on peripheral circulation were reported in 1960.32 Practical applications were mostly dedicated to external cerebral arteries and initial recordings appeared more as sound vibrations than as traces. This report and the various invasive procedures used to record flow velocity had nevertheless sensitized physicians to flow recording in the United States. In 1961, Franklin and Rushmer seized on the interest generated by the ultrasonic continuous wave equipment and its usefulness in clinically assessing peripheral arteries.33 They were followed by George and Pourcelot in France in 1965,34 and by Light in the United Kingdom in 1969.35 The latter pioneer investigated the aortic arch for purposes of monitoring aortic velocities as a surrogate for cardiac output in emergency cases. This equipment was later applied to aortic regurgitation by Boughner in 1975.36 At the end of the 1960s, another pioneer, Benchimol also investigated arterial, venous, and coronary vessels in man by means of an ultrasonic nondirectional Doppler catheter tip designed by Stegall in 1967 (Fig. 2.6).37–40 Indeed, an important gap between heart beats and flow had already been bridged by a decisive validation: Kato reported a positive correlation between the magnitude of Doppler frequencies and the number of corpuscles in an experimental model in 1962. This was the rationale for the development of Doppler flowmetry.41 In spite of this fact, at the turning of the 1970s, these few researchers had not succeeded in convincing the scientific community of using the nondirectional Doppler technique for decision making in patients, which was still classically ruled by pressure measurements.

“Directional Doppler Flowmetry”, Final Fundamental Mutation of the Flow Doppler Technique in the 1960s Aware of the reluctance of cardiologists to apply Doppler traces always positive and devoid of physiological meaning to their patients, three engineers at three different sites of the world tackled to detect the direction of flow velocity. In 1966, Kato and Izumi in Japan, followed by McLeod at Cornell University in 1967 and Kalmanson et al in Paris in 1968 reported the first directional flow Doppler apparatuses.42–44 The new Doppler velocity recorder (VUS 135, Sophia, 78200 Mantes-la Jolie, France) had directional capabilities by integrating a phase detector. Flow velocity traces were obtained by analog demodulation and the zero line was obtained by simple deconnexion.

29

Fig. 2.6: Superior vena cava flow velocity recording using nondirectional Doppler catheterization. The three venous components are shown above the zero line including the “A” wave, which is positive when using nondirectional Doppler. Source: Reprinted with permission from the American Journal of Medicine. 1970;48(3):303–9, “Right atrium and superior vena cava flow velocity in man measured with the Doppler-catheter flowmeter-telemetry system,” Benchimol et al. copyright © 1970 Elsevier. From top to bottom, Lead 2 of the ECG, femoral and LV pressures with the scale in mm Hg, phonocardiogram with the first and second sounds, superior vena cava flow velocity with its scale in kilohertz on the left, (S, D, A: Systolic, diastolic, and atrial waves; RA press: Right atrial pressure).

The directional devices were applied to extracranial vessels in Japan. In the United States, Strandness applied the directional equipment to surgical patients.45 As early as 1968, Kalmanson studied peripheral arteries in France.46,47 After the initial report in January 1968, in less than a year, in addition to arterial traces, Kalmanson, a clinician, also described venous traces (Figs 2.7A and B).48 An attempt to determine the cardiac output much ahead of the literature was also reported as early as 1972.49 Congenital defects, namely atrial and ventricular septal defects, were investigated.50,51 Shillingford, as a conceptual scientist, could not ignore this breakthrough. He organized a symposium entitled “The growing edge of the theory and measurement of blood flow” at the Royal Society of Medicine in London, United Kingdom, on April 21, 1969 (Fig. 2.8). Only a handful of about 30 clever scientists acquainted with the cutting edge of these cardiovascular advances attended

30

Section 1: History and Basics

Normal pattern of arterial flow velocity according to the site of recording

B

A

the symposium! The fact that a mere noninvasive clinical method of flow velocity measurement, namely the Doppler directional velocimeter, was admitted for a lecture among articles on invasive and highly sophisticated experimental procedures was also “avant garde”.

Last Conflictual Issue at This Early Period: How to Present the Data, Single or Dual Velocity Trace, Analog Readout or Frequency Spectrum, Hertz or Centimeters per Second? In the first half of the 1970s, the presentation of the directional flow velocity traces generated controversies among the medical community. On one hand, the defenders of separate channels, one for positive signals

The three phases of the venous return

Figs 2.7A and B: Directional Doppler flow velocity. (A) Atlas of peripheral arteries recorded with the directional Doppler equipment in a normal subject (VUS 135). For the first time, arterial recordings show an oscillatory pattern, with possible backflow waves and specific changes for a given arterial location. (B) Venous return at the level of the jugular vein: it is characterized by three waves in relation with the cardiac contraction, two positive (systole and early diastole) and one end diastolic, the “A” wave, negative for the first time. (ECG: Electrocardiogram; FVJ: Jugular venous flow; Les trois phases du retour veineux, the three phases of venous return). Source: Reprinted with permission from La Presse Médicale, 1968;41:1943–7, Étude des courbes de flux artériel obtenues par enregistrement transcutané chez le sujet normal, Chiche et al. © Masson editor, Paris 1968. Source: Reprinted with permission from “Right venous return recorded by transcutaneous route at the level of the internal jugular vein in normal subjects. Physiological interpretation,” Kalmanson et al. Bull Mem Soc Med Hôp Paris. 1968;119(11):873–89, © Masson editor, Paris 1968. Morphologie du flux artériel selon la localisation: arterial flow velocity patterns according to the location.

and the other for negative ones, often presented as positive as well, argued that this separate presentation was mandatory to accurately portray the actual time course of events related to successive positive and negative velocities. Figures 2.9A and B show the obtained brachial artery velocity pattern in a case of aortic regurgitation. On the other hand, Kalmanson was convinced that data needed a simple readout to gain acceptance and should be displayed as a single channel output for both velocity signs successively displayed on each side of the zero line on a strip chart. The single output of Doppler traces finally prevailed and was adopted by all engineers and research groups. Another particularity of the presentation lay in the adoption of a demodulated analog output that better corresponded to previous noninvasive presentations. Also, rather than keeping the hertz units on the vertical axis of

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

31

Royal Society of Medicine, Section of measurement in medicine, Symposium on “THE GROWING EDGE OF THE THEORY AND MEASUREMENT OF BLOOD FLOW” Chairman: Professor J.P. Shillingford To be held on Monday 21st April 1969 in the Wolfson Institute at the Royal Postgraduate Medical School London W 12. 2.00 PM

Wave transmission in arteries

D. Bergel

2.25

Theory and practice in the measurement of arterial impedance

C. Mills

2.40

The propagation constant of the descending thoracic aorta

I. Gabe

2.55

Flow at branches

R. Schroter, M. Sudlow

3.20

Theory of hot film anemometers in oscillatory flow

T. J. Pedley

3.45

Blood velocity measurements using thin film techniques

D. Tunstall Pedoe

Catheter tip electromagnetic velometer for velocity

C. Mills

TEA 4.45

and flow measurement in man 5.0

The Doppler flowmeter

D. Kalmanson

5.30

A new pulsatile blood flowmeter

R.C. Roberts

5.45

The gamma camera

H. Glass

6.5

Radioactive tracer techniques. The last three years

J. Russel Ress

6.30

The catheter tip electromagnetic flowmeter

M. Thomas

in the assessment of treatment DINNER 8.00 PM

Demonstration of techniques of blood flow and results

Fig. 2.8: Program of the symposium on “The growing edge of the theory and measurement of blood flow”, April 21, 1969: it was the first time that the noninvasive directional Doppler flowmeter was presented in a meeting dedicated to invasive procedures. Personal document.

displays, Kalmanson rapidly converted hertz to centimeters per second units on the Doppler traces. All these details contributed to popularize the flow Doppler technique because the single readout was easily understandable and was adopted on the majority of equipments. However, one may judge the intensity of the controversy, evidenced by vigorous exchanges between authors reported in journals.52–55 Controversy on Doppler presentation and graphic modalities including nondirectionality lasted until 1974.

Fundamental Physiological Lessons Drawn from Peripheral Artery Recordings Popularized by Directional Flow Velocity Doppler Using the new directional devices, clinicians had to face new flow velocity characteristics. These were in keeping with Womersley’s mathematical approach and McDonald’s previous studies. It consisted of the discovery

32

Section 1: History and Basics

A

B

Figs 2.9A and B: Two different presentations of directional Doppler, bidirectional versus directional in severe aortic regurgitation. (A) Bidirectional presentation of a brachial artery in a patient with severe aortic regurgitation; top, forward positive flow; middle, reverse shown as positive; bottom, combination of both shown as positive; (B) 1968 Directional Doppler flowmeter: the traces are presented on a single channel for both positive and negative velocities successively. The arrow points to the deep backflow wave from the subclavian artery, much below the zero line (0). Note that the scale is no longer expressed in kHz but in cm/s, as shown on the scale (20 cm/s; D2, lead 2 of the ECG; cm/s, centimeters per second). Source: (A) Reprinted with permission from the American Heart Journal. 1969;78:65–74, “Transcutaneous directional flow detection. A preliminary report”, Strandness et al. by permission copyright © Elsevier.

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

33

of the oscillatory pattern of arteries. Also there were progressive changes that were specific for a given artery and for a given arterial level. Contrasting with the always positive characteristics of pressure recordings, clinicians discovered that there could be backflow within arteries. This new knowledge was unfamiliar to clinicians and entailed reluctance in some of them. It may explain in part the slow acceptance of flow velocity versus pressure data, the latter requiring much less physiological background.

Exploring the Heart Cavities with the Directional Doppler Flow Velocity Device: An Invasive Modality, But a Premiere! (1969–1974) So far, no flow velocity recording had been performed within the heart in man. This step forward was achieved by the design of a directional continuous wave Doppler with a single crystal acting both as the emitter and the receiver and mounted on a catheter tip (VUS 180 and VUS 185 with orientable-tip Sophia France; Fig. 2.10). This enabled reduction of the diameter of the catheter to 2.3 mm. It was first reported by Kalmanson on July 4, 1969, and printed in September of the same year.56 For the first time, flow velocity patterns of tricuspid and mitral annuli in man were described. Again, the specificity of the flow patterns and their progressive changes through the cardiac cavities were demonstrated in keeping with the concepts observed for peripheral flow phenomena. A significant finding was that these velocity patterns changed according to phases of the cardiac cycles, generating features with a specific timing characteristic of systole, diastole, isovolumic contraction, and relaxation, both on the right and left sides as shown in Figures 2.11 and 2.12.57–59 Briefly summed up, the superior vena cava is characterized by a three-wave pattern with two systolic and diastolic positive waves and one end-diastolic negative wave. In the atria, the negative end-diastolic wave tends to become positive when one approaches to the annulus, whereas the systolic component decreases. At the annulus, there are only two positive diastolic waves and no systolic wave. In the ventricle, the diastolic part decreases while a prominent systolic component appears and the pattern turns out to consist of a single systolic wave at the arterial outlet (Fig. 2.11).

Fig. 2.10: The directional Doppler velocimeter Sophia VUS 135 (1968) and VUS 180 (VUS 180), 78200 Mantes la Jolie, France. This equipment, designed by G. Toutain and presented in January 1968, was first used for peripheral examination. In the center of the apparatus, a knob enabled the switch from negative to positive in order to conventionally display forward flow with positive values. The catheter equipment (VUS 180) is connected to the VUS 135 and is shown in front of the image. From 1970, the apparatus was equipped with an orientable catheter tip for transseptal route and left heart exploration. Source: Reprinted with permission from Ann Med Intern. 1969;120:685–700, “Le cathétérisme vélocimétrique du Coeur et des gros vaisseaux par sonde ultrasonique directionnelle à effet Doppler,” Kalmanson et al. © Masson editor, Paris, 1969.

Methodologic Rules Drawn from Phenomenologic Observations of Changes in Intracardiac Doppler Flow Velocity Traces Far from a mere phenomenologic description, new data were the key for a pathophysiological insight. Similar to his physiologic interpretation from newly recorded data, Kalmanson assigned significance to each pathologic change. Pattern alterations were a guide for understanding pathologic anomalies that were regularly reported.60–63 For example, until 1970, mitral regurgitation had never been directly represented by a graphic display showing a negative systolic wave. For the first time, its characteristics were described.59 Importantly, any organic or functional alteration of atrial relaxation, downward displacement of the annular closed floor, ventricular relaxation or filling, and atrial contraction could induce anomalies on

34

Section 1: History and Basics

Schematic representation of the right intracardiac flow velocity traces

Left Heart

Fig. 2.11: Schematic representation of the changes in flow patterns in the right (left) and left (right) heart cavities, each one spatially related to precise locations within the heart and temporally to each phase of the cardiac contraction. There is a three-wave pattern (two positive and one negative) at the inlet, a diastolic double-peaked positive pattern at the annulus which turns out to be a single systolic ejectional wave at the outlet. Note that the ejectional systolic wave, seen as negative in the outflow tract according to the Doppler principle, has been switched to positive by convention. Kalmanson wished to always assign a positive sign to forward flow in order to make it understandable for users and to gain acceptance for this starting procedure. (SVC and IVC: Superior and inferior vena cava; RA: Right atrium; LA and Pulm. Veins: Left atrium and pulmonary veins). Source: Reprinted with permission from CR Acad Sciences. 1969 série D; 269 1097-1100 September 22, “First description and physiological interpretation of flow velocity intracardiac recordings by directional Doppler catheterization,” Kalmanson et al. © Masson editor, Paris 1969, and from Cardiovascular Research. 1972;6(3):309–18, “Retrograde catheterization of left heart cavities in dog by means of an orientable directional Doppler catheter-tip flowmeter; a preliminary report”, Kalmanson et al. © copyright 1972 European Society of Cardiology.

site and in venous return patterns.60 In brief, Kalmanson pioneered a heuristic method systematizing intracardiac flow dynamics from the changes he had observed in flow patterns. Validation of the method was made by comparison with electromagnetic flow probes invasively recorded in experiments.64

One-Dimensional Pulsed Doppler Procedure Takes Off: Return to Transcutaneous Approaches Except for the use of a Doppler catheter tip enabling sampling in the heart, transcutaneous Doppler directional flowmeter was confined to superficial vessels. To sample

into the heart, some clever physicists designed a rangegated pulsed Doppler.65–68 There were two crystals, one emitter and one receiver, which enabled picking up a teardrop sample at any depth along the Doppler beam and was named the “Doppler gate”. Optimal spatial resolution allowed recognition of the sampling site and also noninvasive investigation of the velocity distribution across a vessel diameter. This capability was applied to study small vessels or graft patency by Gould, while there was a return to tissue Doppler with approach to the left ventricular posterior wall by Kostis.69–71 In 1975, there was a true breakthrough with Johnson and Baker’s invention: it consisted of simultaneous 1D imaging combined to pulsed Doppler.72 They applied

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

35

Fig. 2.12: One of the first recordings of the mitral valve flow velocity pattern. Physiological interpretation. On the left, typical normal mitral valve flow velocity with its two-peaked diastolic waves “D” early diastolic (later labeled “E” as on echocardiograms) and “A” end diastolic, no flow velocity in systole (S). The isovolumic contraction (ci) is displayed as a sharp negative deflection. The scale is in cm/s from the zero line. On the right, interpretation of the mitral flow velocity features according to cardiac events. (Ic: Isometric contraction; ECG: Electrocardiogram; LA: Left atrium; LV: Left ventricle; MFV: Mitral flow velocity; MO: Mitral opening; PCG: Phonocardiogram; P: P wave of the ECG; B: End of systole marked by the second sound; ci: Isovolumic contraction S1 S2 S3 S4: Heart sounds). Source: Reprinted with BMJ permission from the British Heart Journal. 1975;37:249–56, “Normal pattern and physiological significance of mitral valve flow velocity recorded using transseptal directional Doppler ultrasound catheterization”, Kalmanson et al. © copyright 1975.

this combination to disturbances generated by heart lesions. This kind of intracardiac stethoscope yielded the “diagnostic era” since it was now possible to relate spectral disturbances to specific valvular or myocardial lesions. Kalmanson added a demodulated analog trace to the time-histogram interval (TIH) with a zero-crossing detector initially designed to reproduce the traces already produced invasively. For the first time, mitral traces were recorded transcutaneously (Fig. 2.13).73 The introduction of imaging contributed to popularize the Doppler technique and several groups reported applications for atrial, septal, and valvular defects either with the TIH or with the analog trace (Fig. 2.14).74–83 To be noted, coincident with this wider acceptance of the procedure by new colleagues, Professor Hugenholtz invited Kalmanson to chair the first session dedicated to

the Doppler technique and more specifically to mitral valve flow dynamics in Amsterdam in June 1976 during the Seventh European Congress of Cardiology. It was the first official recognition of the Doppler flow technique in an international meeting (Fig. 2.15). The pulsed Doppler technique had, however, some limitations, namely its unability to record velocities exceeding the “Nyquist limit,” generating “aliasing,” but its results compared favorably with 1D echo alone for diagnosis. Pulsed Doppler provided crucial information on the progressive flow acceleration proximal to a narrowed orifice. They were consistent with the flow net theory in fluid dynamics, 10 years ahead from its demonstration by color Doppler. Possible assessment of the severity of lesions raised by a step-by-step sampling in heart cavities was however unreliable. Attempts to devise indices of

36

Section 1: History and Basics

Fig. 2.13: One-dimensional echo directional Doppler velocimeter noninvasive recording of mitral valve flow velocity. Placement of the Doppler gate location close to the mitral valve (top left), the typical pattern of the mitral flow velocity is recorded, as seen on the spectral trace (bottom with its zero line) and on the analog output (above, with also its zero line). On the right. S, D, and A are successively displayed as well as the isometric contraction—small negative deflection at the onset of systole. (D2: lead 2 of ECG; M: Mitral valve; P: Doppler gate; PCG: Phonocardiogram; S, D, A: Systole, early diastole, and end-diastole; V: Velocity (cm/s).

Fig. 2.14: One-dimensional echo directional Doppler flowmeter, diagnostic capabilities: differentiation between an infundibular stenosis and a ventricular septal defect (VSD). On the left, the Doppler gate is on the right side of the interventricular septum and records the left-to-right VSD shunt flow velocity with its three characteristic waves: S, D, and A. The onset of the shunt appears within the QRS complex and before the onset of the first sound on the phonocardiogram (small black vertical arrows), whereas on the right, for the stenosis, with the gate in the right ventricle, the onset of the disturbances starts at the end of the first sound. (P: Doppler gate; PCG: Phonocardiogram: Shunt de CIV: Interventricular shunt flow; Infundibulum, infundibular stenosis).

severity on the basis of 1D imaging failed because of frequent changes in the direction of valvular jets out of the scanning line.

they returned to the 2D image to check that the Doppler beam had the same location in the imaged plane. The sound spectrographic display was bidirectional and represented an improvement over the TIH, since it showed distribution of velocity in a sampling volume displaying positive and negative flow velocities above and below the zero line, respectively. In 1977 in the United States, Henry and Griffith reported a similar combination performed on the pulmonary artery, with two successive recordings, imaging and flow trace, using two distinct probes, with a mechanical scanner for the echo probe.85 Baker adapted his 2D equipment from the one he had previously devised for carotid artery imaging.86 It was characterized by a single probe which included both, the scanhead and the Doppler probe. A mechanical 90° sector scanner operated with three equidistant piezoelectric ceramic elements rotated rapidly around a “pivot”. Two of them were used for imaging and the third one for the Doppler function. Also built in was the adjustment system for the Doppler range gate including a lever with one degree liberty that could be tilted to and fro from an axial position and allowed the Doppler beam to be moved in the plane of

Two-Dimensional Imaging Combined to Pulsed Doppler; the “Grading Era” Relying on “Flow Mapping” May Take Off; Refinements of the Doppler Signal Appear It became obvious that Doppler grading lesions would require at least 2D imaging. That is why this phase can be labeled the “grading era” and also the “era of new pathophysiological insights”. Combination of pulsed Doppler with 2D echocardiography, a major breakthrough, was pioneered by Matsuo Kitabatake and Nimura in 1977.84 These authors used a phased array probe generating 2D images with a pulse Doppler capability. Once they had located the site of the Doppler sample on the 2D image, they switched to the Doppler function to record the flow trace. After recording,

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

a m

TUESDAY JUNE 22

Symposium

The mitral valve Room: V/VI Chairmen: D. Kalmanson (Paris, F) M.H. Yacoub (Harefield, GB) A. Experimental and clinical investigations 9:00 Functional anatomy of the mitral apparatus 204 J. K. Perloff (Philadelphia, PA, USA) 9:10 Discussion 9:15 Experimental studies of flow dynamics of the normal and diseased mitral valve 205 E.L. Yellin, S. Laniado, C.S. Peskin, R.W.M. Frater (Bronx, NY, USA) 9:25 Discussion 9:30 An in-vitro study of the flow dynamics of mitral valve prostheses 206 J.T. M. Wright (Liverpool, GB) 9:40 Discussion 9:45 Diagnosis of mitral valve disease, using C. W. Doppler transseptal catheterization 207 C. Veyrat, A. Bernier, D. Kalmanson, C. H. Savier, P. Chiche (Paris, F) 9:55 Non-invasive velocimetric recording of mitral flow using demodulated pulsed Doppler technique associated with echocardiography 208 D. Kalmanson, C. Veyrat, F. Bouchareine, A. Degroote, D.W. Baker (Paris, F and Seattle, Wash., USA) 10:15 Discussion 10:15 Ultrasonic investigation of natural and prosthetic valves 209 R. L. Popp (Stanford, Cal., USA) 10:25 Discussion 10:30

coffee break

Fig. 2.15: Session on the mitral valve, Seventh European Congress of Cardiology, Amsterdam, June 21–25, 1976. For the first time, a session including presentation on directional cardiac Doppler data was authorized in an official international meeting. Personal document.

the sector scan. It was called the “Duplex scanner”. Some applications immediately followed. In 1980, combining a pulsed Doppler flowmeter (Hitachi) and a cross-sectional echocardiograph (Aloka) to check the site of the Doppler gate, Miyatake could pick up turbulent signals related to a jet in several samples along the left atrium shown on a 2D plane. He was the first to confirm previous findings obtained by Johnson and Stevenson with 1D pulsed Doppler in a case of mitral regurgitation.87 In 1981, using the Duplex scanner, Kalmanson studied the trajectory of the jet more precisely and could specify the characteristic criteria defining anterior and posterior mitral valve prolapses. He assigned an anterior location close to the

37

posterior aortic wall to posterior mitral valve prolapse. Conversely, a posterior location along the posterior wall of the atrium was related to anterior mitral valve prolapse, in agreement with angiographic data (Figs 2.16A and B).88 This was confirmed by Miyatake in 1982. This group also detected abnormal right signals in case pulmonary stenosis.89,90 Two-dimensional flow Doppler enabled establishment of a “mapping procedure” according to an objective methodology. In order to take into account, as much as possible, the three-dimensional (3D) configuration of regurgitant jets, namely their length and height in long axis and their width in short-axis views measured in centimeters, we proposed to map abnormal signals with a combination of two orthogonal planes providing 3D semiquantitative indices (Figs 2.17A and B).91–93 Moreover, this mapping procedure provided a pathophysiological insight of the regurgitant lesion. Furthermore, in search of a quantitative evaluation, a new procedure was also proposed from 1983 by measuring the jet area at its origin, corresponding to the “vena contracta,” at the site of the valvular regurgitant or stenosed lesions in the short-axis view (Figs 2.18A and B).94–96 Noninvasive quantification of flow rate became possible, as reported by Sahn’s group.97

Another Breakthrough in the First Half of the 1980s that Definitely Popularizes and Matures the Flow Doppler Technique: Color Doppler Two other developments also took place nearly simultaneously with the introduction of the 2D Doppler: Brandestini designed the first color Doppler consisting of a digital multigated pulsed Doppler that could record the velocity profile along a beam-line at discrete time intervals during the cardiac cycle. The system combined M-mode echo and superimposed color-coded Doppler flow, allowing color visualization of direction and timing of flow within the heart. This was pioneered by Stevenson who applied it to congenital defects.98,99 2D color Doppler was devised simultaneously by Bommer100 and Namekawa.101 Bommer developed a real time, cross-sectional Doppler instrument that continuously sampled Doppler flow throughout an entire 2D echo plane of 64 × 156 sample sites, and produced a real time (60 fields/set) Doppler flow image. This blood flow image was encoded in color to represent the relative velocity and direction of flow,

38

Section 1: History and Basics

A

B

Figs 2.16A and B: Two-dimensional (2D) echo Doppler. Diagnosis of mitral regurgitation related to posterior mitral valve prolapse. A on left, 2D flow Doppler velocimetry, also labeled Scanner-Doppler or Duplex-Scanner, enables following the trajectory of the jet. Here the gate is at the inferior limit of the disturbances in the long-axis view, which spread along the posterior wall of the aorta, impinging on the anterior atrial wall (dotted white line). The spectrum shows negative systolic broadened frequencies corresponding to the regurgitant jet (arrows on respective locations A, B, C); (B): Angiocardiographic confirmation (mitral regurgitation indicated by small black arrows close to the aorta). (AO: Aortic valve; G: Doppler gate; LA: Left atrium; LV: Left ventricle; MV: Mitral valve; Pcg: Phonocardiogram) Source: Reprinted with permission from Ann Cardiol Angeiol. 1981;30(1):27–35, “Contribution of 2D-echo Doppler for diagnosing regurgitation in mitral valve prolapse”, Kalmanson et al. copyright ©1981 Masson.

and superimposed on a simultaneous 2D-echo image to create a color composite image displaying both flow and 2D anatomy in real time. Namekawa developed a 2D Doppler blood flow color imaging system combined with a newly designed autocorrelator. The echo signals were transmitted to a quadrature detector to obtain a pair of Doppler frequencies differing by 90° in phase from each other. This output was supplied to the autocorrelator and injected into a digital scan converter, of which the signals were read out to a color converter. Colors were assigned according to three kinds of information: direction, velocity, and turbulence of blood flow. The new technology was first applied by Omoto on patients operated for cardiac lesions.102 He also implemented the color 2D system to the transesophageal route for surgical purposes.103 This was followed by Miyatake and Nanda’s groups for acquired lesions.104–111 Indeed, jets were more easily displayed with 2D color Doppler. Beat-to-beat variability had to be taken into account to determine “which area” to measure in the long-axis plane.112 “Where to measure” the diseased orifice versus neighboring valvular structures had to be checked in the short-axis plane by a careful examination of the spectral trace showing different displays for the subvalvular,

valvular or postvalvular sites along the trajectory of the jet (Fig. 2.19).113 As for “when to measure”, we showed that the maximal peak pressure gradient was the optimal timing and helped to set up the appropriate triggering timing.114 Finally, following these criteria, color Doppler showed good reliability for grading and also to characterize the type of valvular orifice, three cusps or bicuspid valves at the aortic orifice (Figs 2.20A and B).115,116 As for mitral regurgitation, color Doppler confirmed the interest to couple two orthogonal planes, particularly for mitral valve prolapse (Fig. 2.21, top). Commissurotomy often replaced by interventional procedures required a careful follow-up of patient’s outcome. This time-consuming echo assessment greatly benefited from implementation of color Doppler yielding a rapid check of both cardiac phases (Fig. 2.21, bottom). Importantly, color coding further enabled to take into account a fourth dimension, by averaging regurgitant indices over its duration in the systolic phase (Fig. 2.22).117 In spite of these conspicuous improvements, some cardiologists were still reluctant to move from invasive procedures or echocardiography alone to the 2D color Doppler procedure, compelling authors to plead the Doppler cause till 1987!118

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

39

A

B Figs 2.17A and B: Three-dimensional approach to the mitral and aortic regurgitant jets. (A) Mitral regurgitant jet grading: with the Doppler gate at the mitral valve, mapping of abnormal signals in the left atrium (dotted area) and combination of three measurements in cm, ½ product of length and height in the long-axis view × width in the short-axis view; to obtain the total regurgitant index; (B) Aortic regurgitant jet grading: with the Doppler gate at the aortic orifice, mapping of the abnormal signals in the left ventricular outflow tract (LVOT, dotted area) and combination of three measurements in cm, length and height in the LVOT in the long-axis view × width in the LVOT short-axis view to obtain the total LVOT regurgitant index. (AO: Aortic valve; I: Regurgitant index; L, H, W: Length, height, width; LA, LV, LVOT: Left atrium, left ventricle, left ventricular outflow tract; M: Mitral valve). Source: (A) Reprinted with permission from British Heart Journal. 1984;51(2):130–8, “Pulsed Doppler echocardiographic indices for assessing mitral regurgitation,” Veyrat et al, copyright ©1984, BMJ and the British Cardiovascular Society. Source: (B) Reprinted with permission from the American Heart Journal. 1984;108:507–15, “Calculation of pulsed Doppler left ventricular outflow tract regurgitant index for grading the severity of aortic regurgitation”, Veyrat et al, copyright ©1984 Elsevier. Dotted area, site of abnormal signals.

40

Section 1: History and Basics

A

B Figs 2.18A and B: Two-dimensional mapping at the origin of the jet studied at the valvular orifice to assess the severity of the lesions by planimetry in mm2. Procedures below were elaborated with the Duplex scanner using black and white imaging. (A) Left, aortic stenosis: Having located the site of the aortic cusps and detected the diameter of the stenotic jet in the long-axis view, mapping of the aortic valvular area with the Doppler gate at the orifice in the short-axis view and measurement of the detected abnormal signals in mm2 (dotted area). Source: Reprinted from the British Heart Journal. 1987;57:44–50, “A new noninvasive estimation of the stenotic aortic valve area by pulsed Doppler mapping” Veyrat et al. copyright ©1987, BMJ and the British Cardiovascular Society. Right, aortic regurgitation, with the Doppler gate in the aortic short-axis view, measurement of the aortic valvular orifice area (AVOA) and measurement of the detected abnormal signals in mm2 to determine the regurgitant aortic valvular area RAVA, (dotted area), determination of the ratio RAVA/AVOA to take into account a possible aortic valvular surface area dilatation. Source: Reprinted from Circulation. 1983;68:998–1005, “New indexes for assessing aortic regurgitation with two-dimensional Doppler echocardiographic measurement of the regurgitant aortic valvular area,” Veyrat et al. copyright ©1983 Wolters Kluwer Health. (B) Same procedure as for the aortic stenosis for mitral stenosis. Mitral stenosis, after having located the site of the mitral leaflets and detected the diameter of the stenotic jet at the mitral valve in the long-axis view, mapping of the mitral valvular area (MVA), with the Doppler gate at the orifice in the short-axis view and measurement of the detected abnormal signals in mm2 (dotted area). Source: Reprinted from the European Heart Journal. 1987;8:216–23, “Application of Doppler flow mapping in assessing the severity of mitral stenosis”, Veyrat et al. copyright ©1987 Oxford University Press. (AL, PL: Anterior and posterior mitral leaflets; AO: Aortic valve; AVOA: Circumference of the aortic orifice; DB: Doppler beam; G: Gate; LA: Left atrium; LV: Left ventricle; M: Mitral valve; PA, RA: Pulmonary artery, Right atrium; PW: Posterior wall; RAVA: Measurement of the area of abnormal signals related to the regurgitation; RCC, LCC, NCC: Left, right, and noncoronary cusps; RVOT: Right ventricular outflow tract; S: Septum; T: Tricuspid).

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

41

Fig. 2.19: Trajectory of a jet related to aortic stenosis checking spectral landmarks to choose the right plane of measurement of the aortic valve area. The figure shows three planes in the long-axis view. In all three, there are abnormal systolic spectral signals. The determination of the appropriate plane for measuring the stenotic area relies on a careful analysis of the spectrum below: From left to right, in 1, the Doppler gate is in the left ventricular outflow tract (small thin oblique white arrow points to the red color of accelerating flows on the M-mode trace) no heart sound is recorded, except vibrations related to the atrial contraction transmission, before QRS. In 2, the gate is exactly at the orifice (small oblique white arrow singling out the blue color image appearing between the white echoes on the M-mode trace), the first and second sounds, although decreased, are recorded (vertical white arrows). This is where the area should be measured. In three, the gate is further downstream in the aorta (small white arrow further down the jet on the M-mode recording (mosaic pattern), the first vibration is increased downstream the orifice as an early systolic ejectional click and there is no second sound (A1 A2: First and second heart sounds; ECG: Electrocardiogram; PCG: Phonocardiogram). Source: Reprinted with permission from Angiology. 1990;41(5):352–64, “Quantification of left-sided valvular stenoses by color Doppler imaging of jets”, Veyrat et al. by permission copyright © 1990 Sage.

Another important technological improvement should be noted: the reliable Fast Fourier Transform signal processing definitely replaced the time interval histogram (Figs 2.23A and B).119

“Quantitative” Flow Doppler Era Appears with Continuous Wave Doppler Investigation of the Heart Grading indices drawn from the mapping procedure were only semi-quantitative, except for planimetry of regurgitant and stenosed flow areas.94,96 Many parameters of crucial usefulness were lacking with pulsed Doppler,

such as the measurement of pressure gradients and that of functional valve areas, because of the Nyquist limit. Meanwhile, progress in transducer technology made lower frequency probes available allowing sampling deep into the heart. This was a fundamental reason to return to continuous wave Doppler.120 Indeed, spatial resolution was still lacking, but with a minimal physiological knowledge and training, it was easy to distinguish a regurgitant from a stenosed jet by their timing. A pioneer in this field 10 years earlier was Jarle Holen of Norway. He applied the Bernoulli equation to the calculation of the pressure drop in mitral stenosis and prosthetic valves as early as 1976.121 Calculations derived from ultrasound

42

Section 1: History and Basics

A

B

Figs 2.20A and B: Applications of two-dimensional valvular mapping. (A) Duplex scanner mapping of an aortic regurgitation (black and white image); the Doppler gate is at the aortic orifice in the short-axis view (a finding confirmed by the M-mode trace below), and the time interval histogram (TIH) detects abnormal signals (arrows); (B) Color Doppler mapping: this implementation widens possible recognition of anatomic types of orifices. Top level, the mapping procedure of the aortic stenotic orifice in the short-axis view shows a typical pattern of Monckeberg disease with abnormal signals appearing along the free commissural lines in this trileaflet heavily calcified valve (77 mm2). The imaging is carried out on triggered images (0.160 s after QRS) timed with that of the maximal peak of the stenotic jet. Source: Reprinted with permission from Ultrasound in Medicine and Biology. 1994;20:841–7, Relationship between contour and/or contour/ area ratio at Doppler and left ventricular hypertrophy in patients with significant aortic stenosis”, Veyrat et al. copyright 1994 © Elsevier. Bottom level, schema representing the diagnostic capabilities of color mapping to detect the type (3 or 2 cusps) of the regurgitant aortic orifice. The regurgitation is often central for a tricuspid aortic orifice. To analyze the trajectory of the jet in the LVOT toward LV apex in the long-axis view, we devised a halving line (HL) equidistant from the septum and from the mitral leaflet. Most tricuspid aortic regurgitation of central origin overrides the halving line and move toward the mitral valve. The schema images a bicuspid valve with the most frequent right–left conjoined cusp. The regurgitant jet starts at 10 commissural location, and moves obliquely from its upper location according to a 10–4 commissural line, then abruptly transects the halving line toward the mitral valve in the left ventricular outflow tract as shown on the image. Reverse eccentricity would be noted for bicuspid valve type II (conjoined right coronary–noncoronary cusp). Source: Reprinted with permission from the American Journal of Noninvasive Cardiology. 1993;7:253–8, “Compared locations of the regurgitant aortic jets at their origin and in the left ventricle: a Doppler approach to the underlying type of aortic orifices in adult patients”, Veyrat et al. copyright 1993 © S. Karger AG. 10, 2, 6, location of the normal commissural lines at the aortic orifice. (A, P, I, E: Anterior, posterior, internal, external orientations; AS: Aortic stenosis; AVA: Aortic valvular area; G: Gate; HL: Halving line; LA: Left atrium; LV: Left ventricle; M: Mitral valve; SAX: Short-axis view; TIH: Time interval histogram; Aortic valve; S: Septum RVOT: Right ventricular outflow tract).

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

43

A

B Figs 2.21A and B: Advantages of systematic imaging combining two planes and two cardiac phases to assess severity of valvular lesions. (A) combining two planes for grading mitral regurgitation of the prolapsed anterior leaflet. The long-axis view shows a mitral regurgitant jet impinging the posterior atrial wall which limits its spread and the measurement does not suggest an important regurgitation. On the right, the short-axis wall obviously displays a conspicuous regurgitant jet; (B) combining two cardiac phases to assess results of mitral stenosis postcommissurotomy in the short-axis view: on the left, the crescentic mitral valve pattern is a typical feature of a satisfactory result with good commissural opening (2.1 cm2). On the right, the mitral orifice examined in systole only shows one trivial regurgitant jet at each commissure (small white arrows), confirming a favorable result. (LA: Left atrium; LAX: Long-axis view; LV: Left ventricle; Midsyst: Midsystole; MVA: Mitral valvular area; PS: Parasternal; SAX: Short-axis view). Source: Reprinted with permission from Cardiovascular Imaging. 1990;2(3):119–27, “New methodology for improved quantification of left sided valvular lesions using color flow imaging. Evolution and update of the flow mapping procedure”, Veyrat et al.

were validated against simultaneous invasive pressure measurements. Aware that pressure drop depended on cardiac output, he obtained valve area calculation by combining the ultrasound technique with an invasive measurement of flow rate.122 True quantitative Doppler methods could start, but the complicated equation discouraged cardiologists. From 1978 to 1985, Bjorn Angelsen and Liv Hatle proposed a simplification of the Bernoulli equation as “4V2” that immediately popularized

this Doppler procedure.123–125 The formula is routinely used in all laboratories and its efficiency has been validated in most clinical situations. In 1986, Masuyama proposed several indices derived from the continuous wave Doppler for grading of aortic regurgitation through the study of the slope of the regurgitant flow velocity display (Figs 2.24A and B).126 Finally, Skjaerpe proposed calculation of valve areas using the continuity equation (Fig. 2.25, left).127

44

Section 1: History and Basics

A

B Figs 2.23A and B: Implementation of fast Fourier transform (FFT) to signal processing. (A) The Doppler gate is at the mitral valve; (B) Spectral frequencies shown in systole are related to mitral regurgitation (white arrow). The FFT replaces the time interval histogram on the spectral trace. A complete frequency spectral analysis is performed every 10 ms over selected frequency ranges to provide the equivalent of 256 band pass filters spaced at 100 Hz intervals. Advantages of FFT over TIH consist of three dimensional information, velocity, and time on vertical and horizontal axes, and amplitude on the third axis. The spectrum is color-coded according to the amplitude within the spectrum, red representing the weakest and white the strongest signals. The “Sonocolor” equipment was available in our department as a free generous loan by Merrill Spencer, MD. (ECG: Electrocardiogram; FFT: Fast Fourier transform in kilohertz, with the zero line, positive (F+) and negative (F–) distributed on both sides of the zero line; PCG: Phonocardiogram; T: Time axis).

Fig. 2.22: Color flow mapping helps to take into account the fourth dimension of regurgitation. Checking temporal variations of mitral regurgitation. Three images at different timings in systole of a regurgitant jet. This figure recommends to image the regurgitant jet in early, mid, and late systole to integrate the temporal variations into the calculation of the TRI indice. This patient exhibited important temporal variations from 1 to 3 timings. (LV: Left ventricle; LA: Left Atrium; AO: Aortic valve; LAX: Long-axis view; MR: Mitral regurgitation). Source: Reprinted with permission from the American Journal of Noninvasive Cardiology. 1994;8:1–6, “Four- is better than three-dimensional Doppler grading of mitral regurgitant jets with temporal variations”, Veyrat et al, copyright 1994 © S. Karger AG.

Explosive Streamlines Taking Off from the Mature Flow Doppler Era We can consider the 1980s as a potent cornerstone that prompted users to devise innovations in many parts of the world because the flow Doppler technique had become mature. In order to support their efforts, Merrill Spencer, MD, founded the International Cardiac Doppler Society (1983) for educational purposes with meetings and interlaboratory exchanges worldwide. He himself was involved in the exploration of cerebral circulation,

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

A

45

B

Figs 2.24A and B: Assessment of aortic regurgitation by orificial planimetry and by continuous wave Doppler. (A) In the short-axis view, there is a regurgitant aortic valvular area (RAVA) both in early and end diastole triggered according to the peak continuous wave Doppler velocity (0.520 s) indicative of mild to moderate aortic regurgitation. (CW: Continuous wave Doppler; early-D and end-D: early and end diastole). Source: Reprinted with permission from Cardiovascular Imaging. 1990;2(3):119–127, “New methodology for improved quantification of left sided valvular lesions using color flow imaging. Evolution and update of the flow mapping procedure”, Veyrat et al. (B) Continuous wave Doppler recording of the aortic regurgitant jet, the pressure half-time, devised by Masuyama et al.126 is 0.377 ms and the deceleration is 2.5 mm/s suggesting moderate aortic regurgitation.

B

A

Figs 2.25A and B: Continuity equation to assess the severity of aortic stenosis. (A) As proposed by Skjaerpe et al.127 the subaortic diameter is measured in the long-axis view. Bottom left, the subaortic flow is measured with pulsed Doppler. Bottom right, the peak velocity of the stenotic jet is recorded with continuous wave Doppler showing a mean pressure gradient of 54 mm Hg. The principle relies on the equation of continuity stating that the product of flow area × flow velocity is constant (A × V = A′ × V′) on both sides of an obstruction; (B) Compared results for the assessment of severity of aortic stenosis, using the AVA mapping technique and the continuity equation. A 0.90 correlation coefficient was found with an acceptable standard estimate of error. Both may work complementarily if needed. (AO: Aortic valve; D: Doppler; LA: Left atrium; LV: Left ventricle; m: maximal, mean value; pr.gr: pressure gradient). Source: Reprinted with permission from the European Heart Journal. 1988;9 (Suppl E):93–100, “Doppler flow mapping and its comparison with the continuity equation method for quantifying aortic stenosis”, Kalmanson et al. copyright ©1988 Oxford University Press.

46

Section 1: History and Basics

which interested clinicians as well surgeons. He reported important findings about Doppler signatures of bubble emboli in patients during open heart surgery, with prosthetic valves and stenotic extracerebral arteries. He defined criteria separating embolic signals from artifactual transients.128–130 Although valvular lesions progressively changed from rheumatic to degenerative etiologies, diagnosis and grading of lesions still relied on the flow mapping methods in the majority of cases. However, new concepts started to gain acceptance in search of a more quantitative approach. Calculation of cardiac outputs131,132 opened the way to the quantitation of cardiac shunts and to that of regurgitant fractions (Fig. 2.26).133,134 One of the new concepts was developed by Bargiggia and Recusani, called the “flow convergence” method. It was first studied in patients with mitral prosthesis and in experiments and then applied to native valvular regurgitations.135–137 The method was rapidly popularized as the “proximal isovelocity surface area” by Gardin both for calculation of flow rate138 and for regurgitant as well as stenosed valves.139,140 Gardin further simplified the calculation at the beginning of the millennium.141 The schema shown in Figure 2.27 points out that there were three procedures to cross-check to evaluate valvular lesions (Fig. 2.27).

As for stenoses, clinicians could follow patient outcome under the guidance of Otto’s long-term studies.142–144 Methods involving planimetry of jet area versus the continuity equation compared favourably (Fig. 2.25, right).145 In practice, they appeared complementary and enabled users to avoid possible errors. To sum up, at the turn of the 1990s, the flow Doppler technique made it possible to cross-check several methods in order to obtain the most pertinent results. For example, one could assess a valvular lesion at three levels, beyond the lesion with measurement of the pressure drop with continuous wave Doppler, at the vena contracta by planimetry of the jet area, and below the lesion, by calculating the proximal isovelocity surface area derived from cardiac output calculations (Fig. 2.27). No other noninvasive technique used by clinicians had this advantage. Meanwhile, given some variability in the determination of normal values, age, body size, and other general individual factors were taken into account to define normal values.146 Similarly, to overcome the unavoidable variability of data, relative values appeared preferable to absolute values; for example, recording mitral valve velocities or patterns with comparison with tricuspid velocity or pattern could help to detect if one of both patterns was abnormal, since the general factors should affect them similarly.147 The same applied to the

Fig. 2.26: Regurgitant fraction method to assess the severity of valvular regurgitation. As proposed by Kitabatake for quantification of aortic regurgitation in 1985,134 this schematic view recalls the procedure. Measurements of flow velocity and diameters between the inner walls are performed in respective left and right ventricular outflow tracts on systolic frozen images. Calculations of the stroke volume, one at the subaortic level, the second one at the pulmonary level, leads to the regurgitant fraction calculation obtained from the formula at the bottom of the diagram. (AO: Aortic valve; LA: Left Atrium; LSV: Left stroke volume; M: Mitral valve; Ø: Diameter measured between the inner walls; PA: Pulmonary artery; RA: Right atrium; RVOT: Right ventricular outflow tract; RVS: Right stroke volume; SV: Stroke volume; T: Tricuspid).

Fig. 2.27: Cross-checking three procedures to assess the severity of a valvular lesion. The Doppler procedure is a unique tool as it enables users to combine several procedures in case of uncertain results. This schematic view shows that the assessment may rely on (1) the accelerating flow area (flow convergence137 or PISA method),139 (2) at the orifice through mapping and measurement of area or diameter if difficult,94–96 and (3) by the pressure gradient method and derived indexes from continuous wave Doppler.127,153 (Ø: Diameter measured between the inner walls; CW: Continuous wave).

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

47

Doppler-derived relaxation times.148 Reported analysis of normality from multiple centers also enabled to determine physiological limits, with the awareness of physiological regurgitations.149,150

Return to Noninvasive Hemodynamics with Continuous Wave Doppler Remarkably, in the first period of the technique, we had derived flow from the pressure traces. Conversely from the 1980s, we derived cardiac and arterial pressure gradients from the flow curves recorded using continuous wave Doppler. The formula “4V2” found a series of applications providing a true noninvasive hemodynamic evaluation in valvular and nonvalvular cardiology, diastology, and emergency situations. The first report by Yock and Popp on right-sided ventricular pressure evaluation151 was complemented by Weyman’s group.152 In the same manner, Masuyama proposed to derive the end-diastolic pulmonary pressure from the continuous wave Doppler recording of the regurgitant pulmonary jet.153 Findings were confirmed in a large series by Nishimura and Tajik.154 Bargiggia et al. proposed to determine left ventricular dP/dT from the mitral regurgitant jet.155 Continuous wave Doppler also enabled Chen et al. to study the time constant of left ventricular relaxation.156

Contribution of Pulsed Doppler to “Diastology” Finally, there was a return to pulsed Doppler for examination of the mitral inflow pattern, which resulted in the coinage of the term “diastology.” One decade earlier in 1973, Yellin et al. drew attention to early diastole through the motion of the mitral valve according to atrioventricular pressure flow dynamics and to the isovolumic relaxation period.157 Thereafter, Kitabatake was the first to point out the relationships between transmitral flow velocity and ventricular relaxation.158 For the first time in 1986, Okamoto et al. could feature characteristic changes in transmitral flow patterns according to the increase in left ventricular end-diastolic pressures (Fig. 2.28).159 The finding of diastolic mitral regurgitation in patients with severe aortic regurgitation or cardiomyopathy was further related to increased left ventricular end-diastolic pressures (Fig. 2.29).160 Appleton, Liv Hatle, and Popp finalized the issue gathering together the characteristic features of mitral flow pattern changes.161 Further studies also drew attention

Fig. 2.28: Schematic representation of changes in the mitral flow patterns with increasing left ventricular end-diastolic pressures (LVEDP).159 First schematic diagram singling out the changes in the mitral flow velocity patterns according to LVEDP changes and their reversibility. Mitral flow recording therefore turns out to be a potent indicator of elevated LVEDP and has become a mandatory part of a Doppler examination. More about “diastology” was later codified.159 Source: Reprinted with permissions of Dr Okamoto and from the Journal of Cardiography. 1986;16(4):941–8, “Analysis of mitral inflow velocity pattern in relation to left ventricular end-diastolic pressure”, Okamoto et al, copyright © 1986 Japanese College of Cardiology.

to the “A” wave of the mitral flow pattern.162 Finally, Brun et al. established the relationship between left ventricular early filling wave and relaxation.163 Kitabatake documented these relationships. He established criteria on a spatial and temporal basis derived from the slope of the filling wave with color Doppler: the rate of propagation of peak early filling flow velocity was defined as the distance/time ratio between two sampling points; the point of the maximal velocity around the mitral orifice and the point in the midleft ventricle at which the velocity decreased to 70% of its initial value.164 Re-emergent tissue Doppler processing enabled Nagueh to develop a new ratio combining flow and tissue Doppler in order to explore myocardial function.165 This information was useful as coronary artery disease became prominent and clinicians needed information regarding intracardiac hemodynamics. Interestingly, invasive Doppler exploration of the native coronary arteries166 was followed by a transcutaneous color flow recording in the epicardial arteries in 1993.167 With advancing knowledge in the complexity of flow dynamics, the research possibilities could widen, carried on by recent sophisticated softwares on new equipments. As anticipated by Merrill Spencer when he founded the International Cardiac Doppler Society, it became mandatory that cardiologists should collaborate

48

Section 1: History and Basics

Fig. 2.29: Mitral flow velocity patterns change according to elevated left ventricular end-diastolic pressures (21 mm Hg) in a patient with severe aortic regurgitation. Diastolic mitral regurgitation. Two remarkable findings in this patient: on top left, the mitral flow velocity pattern is typically restrictive (oblique white arrow) with rapid deceleration of the E wave and disappearance of the “A” wave implying diastolic mitral regurgitation. On top right, the tricuspid valve also has a rapid deceleration but the “A” wave is still visible. Comparison of both cardiac sides always provides fruitful information. Bottom row, example of left ventricular end-diastolic pressure overpassing the left atrial pressure (represented here by the pulmonary capillary wedge pressure; vertical black arrow) generating adequate conditions for diastolic mitral regurgitation. Source: Reprinted with permission from the European Heart Journal. 1987;8:878–87. Veyrat et al, copyright © 1987 European Society of Cardiology. (LV (VG): Left ventricle; mm Hg: Millimeters of mercury; PCG IC: Intracardiac phonocardiogram; PWP (CP): Pulmonary capillary wedge pressure).

with physicists and engineers. Together they devised new probes, new transesophageal, intravascular and intracardiac approaches, new tools like contrast agents, and technological improvements such as multidimensional and harmonic imaging. Experimental studies enabled to better specify the changes in velocity profiles of a jet from its origin to its extremity under the effect of entrained fluids around the jet.168 Researchers elaborated refined concepts such as the conservation of momentum, a new basis for quantification of regurgitant jets (Fig. 2.30).169 They contributed to elucidate some factors of errors in investigating patients. For example, pressure gradients could be overestimated in case of valvular stenosis due to the pressure recovery

Fig. 2.30: Assessing valvular lesions as close as possible to the orifice. The schema, adapted from Wranne et al168 illustrates here the changes of an aortic jet velocity in the receiving chamber. The farther from the diseased orifice the measurement of a jet velocity, the greater the decrease in the velocity will be because of fluid entrainment in the receiving chamber, enhancing the clinical advantage of assessment methods proximal to the lesions. Source: Reprinted with permission from Coeur, 1987;18:149–59, “Application de l’échocardiographie Doppler à l’exploration des insuffisances aortiques”, Veyrat et al, copyright © 1987 Masson editor. (AO: Aortic orifice; VG: Left ventricle).

phenomenon.170 Conversely, they evidenced that a regurgitant jet impinging a cardiac wall could reduce its apparent size and generate errors in grading mitral regurgitation related to mitral prolapse (see Fig. 2.21A).171

CONCLUSION Much has been done by scientists all over the world during the last 40 years of the 20th century. This review is not exhaustive. Some valuable scientists may not have been recognized and their contributions not given enough credit because of this explosive field of research. Citated names are related to contributions that majorily impacted the everyday practice in laboratories and addressed a wide spectrum of clinical situations. Nowadays, a complete noninvasive disciplinary is available to investigate patients. Future directions will depend on a pluridisciplinary cooperation. A researcher should have, in addition to a clinical, physiological, and pathophysiological knowledge, a wide open eye toward neighboring disciplines and technologies because many new concepts have arisen from such a connection. Looking backward generates a few reflections. In the past, Daniel Bernoulli and Christian Doppler’s equations

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

and findings were dedicated to a restricted community involving mainly physicists and mathematicians.10,172 The popularization of 4V2 formula for the former, and the change of his last name into a substantive one for the latter, both used daily minute by minute by physicians in their lab, would have been totally unexpected by these scientists. Other similar clever concepts in medicine did not immediately gain acceptance, such as the pressure halftime proposed by Rodbard which appeared superfluous when compared with the Gorlin formula that could be easily used during routine catheterization at the time,173 or the Karliner’s index,174 which lacked an appropriate tool to simplify the concept into a single procedure.175 In brief, there is an optimal timing for a concept to be popularized in medicine depending on the evolution of technology. Finally, flow investigation might be optimized by other physical sources. Indeed, whatever the available technology might be in the future, flow Doppler will remain a remarkable modality prompting users to get to the core of cardiology, upsetting the traditional knowledge prevailing in the first half of the 20th century.

SUMMARY This historical review recalls the impact of audacious pioneers in the Doppler technique, who cleared the way in an unbroken field of cardiology during the last half of the past century. They had to fight to gain acceptance by the scientific community until color coding made the procedure finally widely accepted. At the turning of the new millennium, descriptions of flow events and innovative paradigms from which deviated patterns could be declined according to pathology paved the way toward a promising continuum of progress, pushing back the frontiers of our knowledge. Much has been done over 40 years along with new equipments, but there remains a lot of possible creative trends of research in keeping with the technological progress.

REFERENCES 1. Forssmann W. Die sondierung des rechtenherzens. Klin Wochenschr. 1929;8:2085–7. 2. Cournand AF, Range HS. Catheterization of the right auricle in man. Proc Soc Exp Biol Med. 1941;46:462–6. 3. Zimmerman HA, Scott RW, Becker ND. Catheterization of the left side of the heart in man. Circulation. 1950;1:357–9. 4. Sones FM Jr. Cine-cardio-angiography. Pediatr Clin North Am. 1958;5(4):945–79.

49

5. Edler I, Gustafson A. Ultrasonic cardiogram in mitral stenosis; preliminary communication. Acta Med Scand. 1957;159(2):85–90. 6. Gramiak R, Shah PM. Echocardiography of the normal and diseased aortic valve. Radiology. 1970;96(1):1–8. 7. Weyman AE, Feigebaum H, Dillon JC, et al. Cross-sectional echocardiography in assessing the severity of valvular aortic stenosis. Circulation. 1975;52(5):828–34. 8. Vogelpoel L, Schrire V, Nellen M, et al. The use of amyl nitrite in the differentiation of Fallot’s tetralogy and pulmonary stenosis with intact ventricular septum. Am Heart J. 1959;57(6):803–19. 9. Chiche P, Kalmanson D, Veyrat C. Contribution of phonocardiography to the selection of frequencies for the study of aortic insufficiencies. Sem Hop. 1966;42(38): 2214–32. 10. Doppler C. Uber das farbige licht der Dopplelsterne ùnd einiger anderer Gestirne des Himmels. Abhandlùngen Königlich-Bohmische Gesellschaft. 1843;ser 2:465–82. 11. Satomura S. A study of examining the heart with ultrasonics. Jpn Circ J. 1956;20:227. 12. Yoshida T, Mori M, Nimura Y, et al. Analysis of heart motion with ultrasonic Doppler method and its clinical application. Am Heart J. 1961;61:61–75. 13. Yoshitoshi Y, Sekisguchi H, Machii K, et al. Measurement of the maximal velocity of the mitral valve closure and of anterior ventricular wall movement by ultrasonic Doppler’s method. Digest 6th Int Conf Med Biol Eng Tokyo, Japan; 1965:35–6. 14. Kolin A. An electromagnetic flowmeter. Principle of the method and its application to bloodflow measurements. Proc Soc Exptl Biol Med. 1936; 35: 53–6. 15. McDonald D. Blood flow in arteries. London: Edward Arnold; 1960. 16. Womersley JR. Method for the calculation of velocity, rate of flow and viscous drag in arteries when the pressure gradient is known. J Physiol (Lond). 1955;127(3):553–63. 17. Spencer MP, Denison AB. The aortic flow pulse as related to differential pressure. Circ Res. 1956;4(4):476–84. 18. Noble MI, Gabe IT, Trenchard D, et al. Blood pressure and flow in the ascending aorta of conscious dogs. Cardiovasc Res. 1967;1(1):9–20. 19. Schultz DL, Tunstall-Pedoe DS, Lee G de J, et al. Velocity distribution and transition in the arterial system. In: Wolstenholme GEW, Knight J, eds. Circulatory and Respiratory Mass Transport. London: J and A Churchill; 1969:172–99. 20. Mills C. A catheter-tip electromagnetic velocity probe and its evaluation. Cardiovasc Res. 1967;1:263–73. 21. Kolin A, Ross G, Grollman JH Jr, et al. An electromagnetic catheter flow meter for determination of blood flow in major arteries. Proc Natl Acad Sci USA. 1968;59(3):808–15. 22. Brecher GA. Venous return. New York: Grune and Stratton; 1956. 23. Morgan BC, Abel FL, Mullins GL, et al. Flow patterns in cavae, pulmonary artery, pulmonary vein, and aorta in intact dogs. Am J Physiol. 1966;210(4):903–9.

50

Section 1: History and Basics

24. Pinkerson AL, Luria MH, Freis ED. Effect of cardiac rhythm on vena caval blood flows. Am J Physiol. 1966;210(3):505–8. 25. Taylor DE, Wade JD. The pattern of flow around the atrioventricular valves during diastolic ventricular filling. J Physiol (Lond). 1970;207(2):71P–72P. 26. Wright JT, Temple LJ. An improved method for determining the flow characteristics of prosthetic mitral heart valves. Thorax. 1971;26(1):81–8. 27. Folts JD, Young WP, Rowe GG. Phasic flow through normal and prosthetic mitral valves in unanesthetized dogs. J Thorac Cardiovasc Surg. 1971;61(2):235–41. 28. Bellhouse BJ. Fluid mechanics of a model mitral valve and left ventricle. Cardiovasc Res. 1972;6(2):199–210. 29. Padula RT, Gowan GS Jr, Camishion RC. Photographic analysis of the active and passive components of cardiac valvular action. J Thorac Cardiovasc Surg. 1968;56:790-8. 30. Nolan SP, Dixon SH Jr, Fisher RD, et al. The influence of atrial contraction and mitral valve mechanics on ventricular filing. A study of instantaneous mitral valve flow in vivo. Am Heart J. 1969;77(6):784–91. 31. Folts JD, Young WP, Ravnan ML, et al. Phasic tricuspid flow in chronic unanesthetized dogs. J Appl Physiol. 1973; 34(4):519–22. 32. Kaneko Z, Komuta K, Kotani H, et al. Studies on peripheral circulation with ultrasonics. (I) Abstr. 65th Meet Kinki Psychiat Neurol Soc. (Feb. 21, 1959). Psychiat Neurol Jpn. 1959:61:2140 (in Japanese). 33. Franklin DL, Schlegel W, Rushmer RF. Blood flow measured by Doppler frequency shift of back-scattered ultrasound. Science. 1961;134(3478):564–5. 34. George P, Pourcelot L, Fourcade C, et al. The Doppler effect and measurement of the blood flow. CR Hebd Seances Acad Sci, Ser D, Sci Nat. 1965;261(1):253–6. 35. Light H. Non injurious ultrasonic technique for observing flow in the human aorta. Nature. 1969;2224:1119–21. 36. Boughner DR. Assessment of aortic insufficiency by transcutaneous Doppler ultrasound. Circulation. 1975;52 (5):874–9. 37. Stegall HF, Stone HL, Bishop VS, et al. A catheter-tip pressure and velocity sensor. Proc Twentieth Annual Conference Eng Med Biol. 1967;27:4. 38. Benchimol A, Maia IG, Gartlan JL Jr, et al. Telemetry of arterial flow in man with a Doppler ultrasonic flowmeter. Am J Cardiol. 1968;22(1):75–84. 39. Benchimol A, Stegall HF, Gartlan JL, et al. Right atrium and superior vena cava flow velocity in man measured with the Doppler-Catheter flowmeter-telemetry system. Am J Med. 1970;48(3):303–9. 40. Benchimol A, Stegall HF, Gartlan JL. New method to measure phasic coronary blood velocity in man. Am Heart J. 1971;81(1):93–101. 41. Kato K, Kido Y, Motomiya M, et al. On the mechanisms of generation of detected sound in ultrasonic flowmeter. Memoirs Inst Scient Indust Res Osaka Univ. 1962;19:51–7. 42. Kato K, Izumi T. A new ultrasonic Doppler flowmeter that can detect flow directions. Med Ultrasonics. 1966;5:28–9.

43. McLeod FJ. A directional Doppler flowmeter. Digest 7th Int Conf, Stockholm, Sweden. Med Biol Eng. 1967:213. 44. Kalmanson D, Toutain G, Veyrat C, et al. Enregistrement transcutané du flux artériel et veineux par fluxmètre directionnel à effet doppler. Rapport préliminaire (1). Arch Mal Coeur. 1968;61:291–2. 45. Strandness DH Jr, Kennedy JW, Judge P, et al. Transcutaneous directional flow detection: A preliminary report. Am Heart J. 1969;78(1):65–74. 46. Chiche P, Kalmanson D, Veyrat C, et al. Enregistrement transcutané du flux artériel par fluxmètre directionnel à effet Doppler. Description d’un appareillage et premiers résultats. Bull Mém Soc Méd Hôp Paris. 1968;119:87–95. 47. Chiche P, Kalmanson D, Veyrat C. Etude des courbes de flux artériel obtenues par enregistrement transcutané chez le sujet normal. Pr Med. 1968;41:1943–7. 48. Kalmanson D, Veyrat C, Chiche P. Right venous return registered by transcutaneous route at the level of the internal jugular vein in normal persons. Physiologic interpretation of the curves. Bull Mem Soc Med Hop Paris. 1968;119(11):873–89. 49. Kalmanson D, Savier C, Veyrat C, et al. Transcutaneous determination of an approximate cardiac output value by the Doppler flowmeter. Preliminary results. Poumon Coeur. 1972;28(5):233–4. 50. Kalmanson D, Veyrat C, Derai C, et al. Non-invasive technique for diagnosing atrial septal defect and assessing shunt volume using directional Doppler ultrasound. Correlations with phasic flow velocity patterns of the shunt. Br Heart J. 1972;34(10):981–91. 51. Kalmanson D, Aigueperse J, Veyrat C, et al. Non-invasive technique for diagnosing congenital and acquired ventricular septal defects using directional Doppler ultrasound. Correlations with phasic flow velocity patterns of the shunt. Br Heart J. 1974;36(5):428–45. 52. Alexander RH, Nippa JH, Folse R. Directional transcutaneous assessment of venous inflow. Am Heart J. 1971; 82(1):86–92. 53. Kalmanson D. Directional vs bidirectional Doppler velocimeter. Am Heart J. 1972;83(3):437. 54. Benchimol A, Harris CL, Desser KB. Noninvasive diagnosis of tricuspid insufficiency utilizing the external Doppler flowmeter probe. Am J Cardiol. 1973;32(6):868–73. 55. Kalmanson D, Veyrat C. Letter: Tricuspid incompetence, atrial fibrillation and diagnostic value of Doppler ultrasound. Am J Cardiol. 1974;34(5):619–20. 56. Kalmanson D, Novikoff N, Chiche P, et al. Study and physiologic interpretation of right intracardiac blood velocity curves by directional untrasonic probes with Doppler effect. CR Hebd Seances Acad Sci, Ser D, Sci Nat. 1969;269(12):1097–100. 57. Kalmanson D, Toutain G, Novikoff N, et al. Velocimetric catheterization of the heart and large vessels by directional ultrasonic probe with Doppler effect. Preliminary report. Ann Med Interne (Paris). 1969; 120(11):685–700. 58. Kalmanson D, Toutain G, Novikoff N, et al. Retrograde catheterization of left heart cavities in dogs by means of

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

59.

60.

61.

62.

63.

64.

65. 66.

67. 68.

69.

70.

71.

72. 73.

74.

an orientable directional Doppler catheter-tip flowmeter: a preliminary report. Cardiovasc Res. 1972;6(3):309–18. Kalmanson D, Savier CH, Bernier A, et al. Velocimetric recording of mitral output by transseptal Doppler catheterization. Preliminary report and 1st results in humans. Nouv Presse Med. 1972;1(40):2693–4. Kalmanson D, Veyrat C, Witchitz S, et al. Tricuspid dysfunction: a new physiopathologic entity. Study by means of Doppler velocimetry. Ann Cardiol Angeiol (Paris). 1972;21(5):433–47. Kalmanson D, Bernier A, Veyrat C, et al. Normal pattern and physiological significance of mitral valve flow velocity recorded using transseptal directional Doppler ultrasound catheterization. Br Heart J. 1975;37(3):249–56. Kalmanson D, Veyrat C, Bernier A, Savier CH, et al. Diagnosis and evaluation of mitral valve disease using transseptal Doppler ultrasound catheterization. Br Heart J. 1975;37(3):257–71. Kalmanson D, Veyrat C, Bernier A, Witchitz S, et al. Opening snap and isovolumic relaxation period in relation to mitral valve flow in patients with mitral stenosis. Significance of A2–OS interval. Br Heart J. 1976;38(2):135–46. Reneman RS, Clarke HF, Simmons N, et al. In vivo comparison of electromagnetic and Doppler flowmeters: with special attention to the processing of the analogue Doppler flow signal. Cardiovasc Res. 1973;7(4):557–66. Wells PN. A range-gated ultrasonic Doppler system. Med Biol Eng. 1969;7(6):641–52. Peronneau P, Deloche A, Bui-Mong-Hung, et al. Ultrasonic flowmetry–developments and experimental applications. Eur Surg Res. 1969;1(2):147–56. Baker DW. Pulsed ultrasonic Doppler blood-flow sensing. IEEE Trans Biomed Eng. 1970;17:170–85. Ohtsuki S, Okujima M. M-sequence modulated ultrasonic Doppler flowmeter. IEEE Technical Research Reports 1970; US-70:19. Gould KL, Mozersky DJ, Hokanson DE, et al. A noninvasive technic for determining patency of saphenous vein coronary bypass grafts. Circulation. 1972;46(3):595–600. Kostis JB, Mavrogeorgis E, Slater A, Bellet S. Use of a rangegated, pulsed ultrasonic doppler technique for continuous measurement of velocity of the posterior heart wall. Chest. 1972;62(5):597–604. Hartley CJ, Cole JS. An ultrasonic pulsed Doppler system for measuring blood flow in small vessels. J Appl Physiol. 1974;37(4):626–9. Johnson S, Baker D. The localization of cardiac murmurs. Circulation. 1975;48:810–16. Kalmanson D, Veyrat C, Degroote A, et al. Recording by transcutaneous route of the normal and pathological curves of mitral blood velocity by pulsed emission and demodulated reception Doppler technic associated with echocardiography. Preliminary report. CR Hebd Seances Acad Sci, Ser D, Sci Nat. 1976;282(9):937–40. Stevenson JG, Kawabori I, Guntheroth WG. Differentiation of ventricular septal defects from mitral regurgitation by pulsed Doppler echocardiography. Circulation. 1977; 56(1):14–18.

51

75. Kalmanson D, Veyrat C, Abitbol G, et al. Non-invasive exploration of valvular heart disease using Pulsed Doppler Flowmetry with echography (author’s transl). Nouv Presse Med. 1977;6(32):2849–53. 76. Stevenson JG, Kawabori I, Guntheroth WG. Pulsed Doppler echocardiographic detection of total anomalous pulmonary venous return: resolution of left atrial line. Am J Cardiol. 1979;44(6):1155–8. 77. Stevenson JG, Kawabori I, Guntheroth WG. Noninvasive detection of pulmonary hypertension in patent ductus arteriosus by pulsed Doppler echocardiography. Circulation. 1979;60(2):355–9. 78. Kalmanson D, Veyrat C, Berkman M, et al. Recording of shunt of the interatrial and interventricular septums and tricuspid valve insufficiency by pulse Doppler flowmeters. Nouv Presse Med. 1979;8(16):1350. 79. Veyrat C, Cholot N, Berkman M, et al. Noninvasive diagnosis of ventricular septal defects using echo-pulsed Doppler velocimetry, localization, evaluation of the shunt and the associated lesions. Acta Cardiol. 1979;34(6): 401–15. 80. Pearlman AS, Stevenson JG, Baker DW. Doppler echocardiography: applications, limitations and future directions. Am J Cardiol. 1980;46(7):1256–62. 81. Quinones MA, Young JB, Waggoner AD, et al. Assessment of pulsed Doppler echocardiography in detection and quantification of aortic and mitral regurgitation. Br Heart J. 1980;44(6):612–20. 82. Veyrat C, Cholot N, Abitbol G, et al. Non-invasive diagnosis and assessment of aortic valve disease and evaluation of aortic prosthesis function using echo pulsed Doppler velocimetry. Br Heart J. 1980;43(4):393–413. 83. Waggoner AD, Quinones MA, Young JB, et al. Pulsed Doppler echocardiographic detection of right-sided valve regurgitation. Experimental results and clinical significance. Am J Cardiol. 1981;47(2):279–86. 84. Matsuo H, Kitabatake A, Hayashi T, et al. Intracardiac flow dynamics with bi-directional ultrasonic pulsed Doppler technique. Jpn Circ J. 1977;41(5):515–28. 85. Henry W, Griffith G. A Combined Doppler cross-sectional echocardiographic system for measuring cardiac blood flow velocities in man. In: White, Brown. Ultrasound in Medicine, vol. 3 b. New York: Plenum Press; 1977:1375–6. 86. Barber F, Baker D, Strandness D, et al. Duplex scanner for simultaneous imaging of artery tissues and flow. Ultrasonics Symposium Proceedings I.E.E.E. cat. R 74 1974 CHO-896-1 SU. 87. Miyatake K, Kinoshita N, Nagata S, et al. Intracardiac flow pattern in mitral regurgitation studied with combined use of the ultrasonic pulsed doppler technique and crosssectional echocardiography. Am J Cardiol. 1980;45(1): 155–62. 88. Kalmanson D, Veyrat C, Abitbol G, et al. Contribution of 2D-echo Doppler for diagnosing regurgitation in mitral valve prolapse (author’s transl). Ann Cardiol Angeiol (Paris). 1981;30(1):27–35.

52

Section 1: History and Basics

89. Miyatake K, Nimura Y, Sakakibara H, et al. Localisation and direction of mitral regurgitant flow in mitral orifice studied with combined use of ultrasonic pulsed Doppler technique and two dimensional echocardiography. Br Heart J. 1982;48(5):449–58. 90. Okamoto M, Miyatake K, Kinoshita N, et al. Blood flow analysis with pulsed echo Doppler cardiography in valvular pulmonary stenosis (author’s transl). J Cardiogr. 1981;11(4):1291–301. 91. Veyrat C, Villemot JP, Manin JP, et al. Anatomic and functional evaluation of pure and associated mitral stenoses using the echo-Doppler scanner technique. Ultrasound Med Biol. 1983;9(1):1–17. 92. Veyrat C, Ameur A, Gourtchiglouian C, et al. Calculation of pulsed Doppler left ventricular outflow tract regurgitant index for grading the severity of aortic regurgitation. Am Heart J. 1984;108(3 Pt 1):507–15. 93. Veyrat C, Ameur A, Bas S, et al. Pulsed Doppler echocardiographic indices for assessing mitral regurgitation. Br Heart J. 1984;51(2):130–8. 94. Veyrat C, Lessana A, Abitbol G, et al. New indexes for assessing aortic regurgitation with two-dimensional Doppler echocardiographic measurement of the regurgitant aortic valvular area. Circulation. 1983;68(5):998–1005. 95. Veyrat C, Gourtchiglouian C, Dumora P, et al. A new noninvasive estimation of the stenotic aortic valve area by pulsed Doppler mapping. Br Heart J. 1987;57(1):44–50. 96. Veyrat C, Gourtchiglouian C, Sainte Beuve D, et al. Application of Doppler flow mapping in assessing the severity of mitral stenosis. Eur Heart J. 1987;8(3):216–23. 97. Fisher DC, Sahn DJ, Friedman MJ, et al. The mitral valve orifice method for noninvasive two-dimensional echo Doppler determinations of cardiac output. Circulation. 1983;67(4):872–7. 98. Stevenson J, Brandestini M, Weiler T, et al. Digital multigate Doppler with color echo and Doppler display: diagnosis of atrial septal defect and ventricular septal defect. Circulation. 1979;60(Suppl 2):205. 99. Stevenson JG, Kawabori I, Guntheroth WG. Pulsed Doppler echocardiographic evaluation of the cyanotic newborn: identification of the pulmonary artery in transposition of the great arteries. Am J Cardiol. 1980;46(5):849–54. 100. Bommer WL, Miller L. Real-time two-dimensional colorflow Doppler: enhanced Doppler flow imaging in the diagnosis of cardiovascular disease. Am J Cardiol. 1982;49:944. 101. Namekawa K, Kasai C, Tsukamoto M, et al. Imaging of blood flow using autocorrelation. Ultrasound Med Biol. 1982;8:138. 102. Omoto R, Yokote Y, Takamoto S, et al. Clinical significance of newly-developed real-time intracardiac blood flow imaging system (2-D Doppler). Jpn Circulat J. 1983;47:974. 103. Kyo S, Takamoto S, Matsumura M, et al. Visualization of coronary blood flow by transesophageal Doppler color flow mapping. J Cardiogr. 1986;16(4):831–40. 104. Miyatake K, Okamoto M, Kinoshita N, et al. Clinical applications of a new type of real-time two-dimensional Doppler flow imaging system. Am J Cardiol. 1984;54(7): 857–68.

105. Miyatake K, Okamoto M, Kinoshita N, et al. Mitral regurgitation: detection and quantitative evaluation by twodimensional Doppler echocardiography. Am J Cardiol. 1984;54(7):857–68. 106. Ohwa M, Sakakibara H, Miyatake K, et al. Doppler echocardiographic features of ventricular septal rupture in myocardial infarction. J Cardiogr. 1985;15(3):807–15. 107. Miyatake K, Izumi S, Okamoto M, et al. Semiquantitative grading of severity of mitral regurgitation by real-time twodimensional Doppler flow imaging technique. J Am Coll Cardiol. 1986;7(1):82–8. 108. Miyatake K, Yamamoto K, Park YD, et al. Diagnosis of mitral valve perforation by real-time two-dimensional Doppler flow imaging technique. J Am Coll Cardiol. 1986; 8(5):1235–9. 109. Miyatake K, Izumi S, Shimizu A, et al. Right atrial flow topography in healthy subjects studied with real-time twodimensional Doppler flow imaging technique. J Am Coll Cardiol. 1986;7(2):425–31. 110. Perry GJ, Helmcke F, Nanda NC, et al. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol. 1987;9(4):952–9. 111. Helmcke F, Nanda NC, Hsiung MC, et al. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation. 1987;75(1):175–83. 112. Veyrat C, Legeais S, Gourtchiglouian C, et al. A new quantitative method for quantifying left heart jets by Doppler color imaging. Arch Mal Coeur Vaiss. 1989;82(11):1827–36. 113. Veyrat C, Sainte Beuve D, Gourtchiglouian C, et al. Quantification of left-sided valvular stenoses by color Doppler imaging of jets. Angiology. 1990; 41(5):352–64. 114. Veyrat C, el Yafi W, Gourtchiglouian C, et al. Respective timing of maximal color Doppler jet areas and of peak velocity of jets in left-sided valvular lesions: clinical implications. J Am Soc Echocardiogr. 1991;4(3):258–66. 115. Veyrat C, Gandjbakhch I, Cabrol C, et al. Assessment of number of cusps in aortic lesions by Doppler imaging: surgical correlations. J Thorac Cardiovasc Surg. 1994;107 (1):319–21. 116. Veyrat C, el Yafi W, Gourtchiglouian C, et al. Characteristics of jets in adult bicuspid aortic valve by color Doppler imaging. Arch Mal Coeur Vaiss. 1991;84(12):1803–8. 117. Veyrat C, Bas S, Sebaoun G, et al. Color Doppler grading of mitral regurgitation on the basis of a four-dimensional approach: a pertinent answer to clinical needs. J Cardiovasc Diagn Proceed. 1993;11:189–96. 118. Touche T, Gourgon R. The echocardiogram: with or without cardiac Doppler?. Presse Med. 1987;16(2):51–3. 119. Cannon SR, Richards KL, Rollwitz WT. Digital Fourier techniques in the diagnosis and quantification of aortic stenosis with pulsed-Doppler echocardiography. J Clin Ultrasound. 1982;10(3):101–7. 120. Angelsen BA, Brubakk AO. Transcutaneous measurement of blood flow velocity in the human aorta. Cardiovasc Res. 1976;10(3):368–79. 121. Holen J, Aaslid R, Landmark K, et al. Determination of pressure gradient in mitral stenosis with a noninvasive ultrasound Doppler technique. Acta Med Scand. 1976;199(6):455–60.

Chapter 2: Early Cardiac Flow Doppler Era: A Key for a New Clinical Understanding of Cardiology

122. Holen J, Aaslid R, Landmark K, et al. Determination of effective orifice area in mitral stenosis from non-invasive ultrasound Doppler data and mitral flow rate. Acta Med Scand. 1977;201(1-2):83–8. 123. Hatle L, Brubakk A, Tromsdal A, et al. Noninvasive assessment of pressure drop in mitral stenosis by Doppler ultrasound. Br Heart J. 1978;40(2):131–40. 124. Hatle L, Angelsen B, Tromsdal A. Noninvasive assessment of atrioventricular pressure half-time by Doppler ultrasound. Circulation. 1979;60(5):1096–104. 125. Hatle L, Angelsen BA, Tromsdal A. Non-invasive assessment of aortic stenosis by Doppler ultrasound. Br Heart J. 1980;43(3):284–92. 126. Masuyama T, Uematsu M, Naka M, et al. Continuous wave Doppler echocardiography as a noninvasive evaluation of aortic regurgitation. Circulation. 1986;73(3):460–6. 127. Skjaerpe T, Hegrenaes L, Hatle L. Noninvasive estimation of valve area in patients with aortic stenosis by Doppler ultrasound and two-dimensional echocardiography. Circulation. 1985;72(4):810–18. 128. Spencer MP, Lawrence GH, Thomas GI, et al. The use of ultrasonics in the determination of arterial aeroembolism during open-heart surgery. Ann Thorac Surg. 1969;8(6): 489–97. 129. Spencer MP, Thomas GI, Nicholls SC, et al. Detection of middle cerebral artery emboli during carotid endarterectomy using transcranial Doppler ultrasonography. Stroke. 1990;21(3):415–23. 130. Popa VN, Spencer MP, Lion CL, et al. Power M-Mode Doppler and single-gate spectral analysis using a 2-MHz pulsed-wave Doppler transducer to directly detect cervical internal carotid artery stenosis: use of the continuity principle: report of a novel technique. Stroke. 2007;38(6):1780–5. 131. Goldberg SJ, Sahn DJ, Allen HD, et al. Evaluation of pulmonary and systemic blood flow by 2-dimensional Doppler echocardiography using fast Fourier transform spectral analysis. Am J Cardiol. 1982;50(6):1394–400. 132. Fisher DC, Sahn DJ, Friedman MJ, et al. The mitral valve orifice method for noninvasive two-dimensional echo Doppler determinations of cardiac output. Circulation. 1983;67(4):872–7. 133. Kitabatake A, Inoue M, Asao M, et al. Noninvasive evaluation of the ratio of pulmonary to systemic flow in atrial septal defect by duplex Doppler echocardiography. Circulation. 1984;69(1):73–9. 134. Kitabatake A, Ito H, Inoue M, et al. A new approach to noninvasive evaluation of aortic regurgitant fraction by two-dimensional Doppler echocardiography. Circulation. 1985;72(3):523–9. 135. Bargiggia GS, Tronconi L, Raisaro A, et al. Color Doppler diagnosis of mechanical prosthetic mitral regurgitation: usefulness of the flow convergence region proximal to the regurgitant orifice. Am Heart J. 1990;120(5):1137–42.

53

136. Recusani F, Bargiggia GS, Yoganathan AP, et al. A new method for quantification of regurgitant flow rate using color Doppler flow imaging of the flow convergence region proximal to a discrete orifice. An in vitro study. Circulation. 1991;83(2):594–604. 137. Bargiggia GS, Tronconi L, Sahn DJ, et al. A new method for quantitation of mitral regurgitation based on color flow Doppler imaging of flow convergence proximal to regurgitant orifice. Circulation. 1991;84(4):1481–9. 138. Utsunomiya T, Doshi R, Patel D, et al. Calculation of volume flow rate by the proximal isovelocity surface area method: simplified approach using color Doppler zero baseline shift. J Am Coll Cardiol. 1993;22(1):277–82. 139. Gardin JM. Doppler color flow “proximal isovelocity surface area (PISA)”: an alternative method for estimating volume flow across narrowed orifices, regurgitant valves, and intracardiac shunt lesions. Echocardiography. 1992; 9(1):39–42. 140. Yamachika S, Reid CL, Savani D, et al. Usefulness of color Doppler proximal isovelocity surface area method in quantitating valvular regurgitation. J Am Soc Echocardiogr. 1997;10(2):159–68. 141. Tokushima T, Reid CL, Hata A, et al. Simple method for estimating regurgitant volume with use of a single radius for measuring proximal isovelocity surface area: an in vitro study of simulated mitral regurgitation. J Am Soc Echocardiogr. 2001;14(2):104–13. 142. Otto CM, Pearlman AS, Gardner CL. Hemodynamic progression of aortic stenosis in adults assessed by Doppler echocardiography. J Am Coll Cardiol. 1989;13(3): 545–50. 143. Otto CM, Pearlman AS, Amsler LC. Doppler echocardiographic evaluation of left ventricular diastolic filling in isolated valvular aortic stenosis. Am J Cardiol. 1989;63(5): 313–6. 144. Otto CM, Pearlman AS, Gardner CL, et al. Simplification of the Doppler continuity equation for calculating stenotic aortic valve area. J Am Soc Echocardiogr. 1988;1(2): 155–7. 145. Kalmanson D, Veyrat C, Gourtchiglouian C, et al. Doppler flow mapping and its comparison with the continuity equation method for quantifying aortic stenosis. Eur Heart J. 1988;9 Suppl E:93–100. 146. Gardin JM, Davidson DM, Rohan MK, et al. Relationship between age, body size, gender, and blood pressure and Doppler flow measurements in the aorta and pulmonary artery. Am Heart J. 1987;113(1):101–9. 147. Legeais S, Gaucher S, Veyrat C, et al. Changes in mitral and tricuspid blood flow as a function of aging. Value of a combined study with Doppler echocardiography. Arch Mal Coeur Vaiss. 1990; 83(4):503–10. 148. Larrazet F, Pellerin D, Fournier C, et al. Right and left isovolumic ventricular relaxation time intervals compared in patients by means of a single-pulsed Doppler method. J Am Soc Echocardiogr. 1997;10(7):699–706.

54

Section 1: History and Basics

149. Choong CY, Abascal VM, Weyman J, et al. Prevalence of valvular regurgitation by Doppler echocardiography in patients with structurally normal hearts by two-dimensional echocardiography. Am Heart J. 1989;117(3):636–42. 150. Maciel BC, Simpson IA, Valdes-Cruz LM, et al. Color flow Doppler mapping studies of “physiologic” pulmonary and tricuspid regurgitation: evidence for true regurgitation as opposed to a valve closing volume. J Am Soc Echocardiogr. 1991;4(6):589–97. 151. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation. 1984;70 (4):657–62. 152. Wilkins GT, Gillam LD, Kritzer GL, et al. Validation of continuous-wave Doppler echocardiographic measurements of mitral and tricuspid prosthetic valve gradients: a simultaneous Doppler-catheter study. Circulation. 1986; 74(4):786–95. 153. Masuyama T, Kodama K, Kitabatake A, et al. Continuouswave Doppler echocardiographic detection of pulmonary regurgitation and its application to noninvasive estimation of pulmonary artery pressure. Circulation. 1986;74(3): 484–92. 154. Nishimura RA, Tajik AJ. Determination of left-sided pressure gradients by utilizing Doppler aortic and mitral regurgitant signals: validation by simultaneous dual catheter and Doppler studies. J Am Coll Cardiol. 1988;11(2):317–21. 155. Bargiggia GS, Bertucci C, Recusani F, et al. A new method for estimating left ventricular dP/dt by continuous wave Doppler-echocardiography. Validation studies at cardiac catheterization. Circulation. 1989;80(5):1287–92. 156. Chen C, Rodriguez L, Levine RA, et al. Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation. Circulation. 1992; 86(1):272–8. 157. Yellin EL, Laniado S, Peskin CS, et al. Atrioventricular pressure-flow dynamics and valve motion. In: Iberall AS, Guyton AC, eds. Regulation and Control in Physiological Systems. International Federation of Automatic Control, Pittsburgh, PA, Instrument Society of America; 1973:311–14. 158. Kitabatake A, Inoue M, Asao M, et al. Transmitral blood flow reflecting diastolic behavior of the left ventricle in health and disease–a study by pulsed Doppler technique. Jpn Circ J. 1982;46(1):92–102. 159. Okamoto M, Sakura E, Shimamoto H, et al. Analysis of mitral inflow velocity pattern in relation to left ventricular end-diastolic pressure. J Cardiogr. 1986;16(4):941–8. 160. Veyrat C, Sebaoun G, Fitoussi M, et al. Detection of diastolic mitral regurgitation using pulsed Doppler and its implications. Eur Heart J. 1987;8(8):878–87. 161. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol. 1988;12(2): 426–40.

162. Yamamoto K, Kodama K, Masuyama T, et al. Role of atrial contraction and synchrony of ventricular contraction in the optimisation of ventriculoarterial coupling in humans. Br Heart J. 1992;67(5):361–7. 163. Brun P, Tribouilloy C, Duval AM, et al. Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis. J Am Coll Cardiol. 1992;20(2):420–32. 164. Takatsuji H, Mikami T, Urasawa K, et al. A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography. J Am Coll Cardiol. 1996;27(2):365–71. 165. Nagueh SF, Middleton KJ, Kopelen HA, et al. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997; 30(6):1527–33. 166. Wilson RF, Laughlin DE, Ackell PH, et al. Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man. Circulation. 1985;72(1):82–92. 167. Aragam JR, Main J, Guerrero JL, et al. Doppler color flow mapping of epicardial coronary arteries: initial observations. J Am Coll Cardiol. 1993;21(2):478–87. 168. Wranne B, Ask P, Loyd D. Quantification of heart valve regurgitation: a critical analysis from a theoretical and experimental point of view. Clin Physiol. 1985;5(1): 81–8. 169. Cape EG, Skoufis EG, Weyman AE, et al. A new method for noninvasive quantification of valvular regurgitation based on conservation of momentum. In vitro validation. Circulation. 1989;79(6):1343–53. 170. Levine RA, Jimoh A, Cape EG, et al. Pressure recovery distal to a stenosis: potential cause of gradient “overestimation” by Doppler echocardiography. J Am Coll Cardiol. 1989;13(3): 706–15. 171. Cape EG, Yoganathan AP, Weyman AE, et al. Adjacent solid boundaries alter the size of regurgitant jets on Doppler color flow maps. J Am Coll Cardiol. 1991;17(5): 1094–102. 172. Bernoulli D. Hydrodynamica, sive de Viribus et Motibus Fluidorum commentarii. Opus Academicum. Strasbourg: Dulsecker; 1738. 173. Libanoff AJ, Rodbard S. Atrioventricular pressure halftime. Measure of mitral valve orifice area. Circulation. 1968;38(1):144–50. 174. Mancini GB, Costello D, Bhargava V, et al. The isovolumic index: a new noninvasive approach to the assessment of left ventricular function in man. Am J Cardiol. 1982;50(6): 1401–8. 175. Tei C, Dujardin KS, Hodge DO, et al. Doppler echocardiographic index for assessment of global right ventricular function. J Am Soc Echocardiogr. 1996;9(6):838–47.

CHAPTER 3 Basics of Ultrasound Caroline Morbach, Kamran Haleem, Lissa Sugeng

Snapshot ¾¾ General Physics ¾¾ Imaging by Ultrasound ¾¾ Image Optimization and Equipment

INTRODUCTION This chapter aims to give a quick overview of the physical principles of two-dimensional (2D) ultrasound, image generation, image optimization, and common imaging artifacts. Further, we explain in brief the Doppler effect and the mechanisms of Doppler ultrasound. We kept this theoretical part as short as possible knowing that this book has been written for physicians and sonographers, mainly interested in the clinical use of echocardiography; but, some basic knowledge of the physical fundamentals is crucial to understand how to optimize the ultrasound image and how to identify and avoid artifacts. As ultra­sound technology advances, there are improvements in the ultrasound crystal, electronics, and processing that are specific to manufacturers, which are not discussed here.

GENERAL PHYSICS Sound Waves Sound waves are pressure waves generated by a vibrating object. The human hearing detects sound waves at frequencies between 20 and 20,000 Hz (hertz = cycles per second), whereas ultrasound, which is outside the range of human hearing, has higher frequencies of 1–12,000,000 Hz (1–12 MHz). Ultrasound travelling within a medium

¾¾ Artifacts ¾¾ Doppler Ultrasound

transfers its energy by the vibration of molecules. Its density mainly determines the velocity at which a given medium propagates sound waves. In a solid, where molecules are closer together, propagation velocity is higher than in liquid or gas. As illustrated in Figure 3.1, sound waves have a certain amplitude (A) and propagation velocity (c) that designates the speed of the wave travelling through a medium, which can be calculated as the product of wavelength (λ) and frequency (f): c=λ×f Wavelength is the distance of one cycle measured in meters, and frequency is determined by the number of cycles in 1 second or hertz (Hz). Hence, propagation velocity is measured in m/s. Spatial resolution is dependent on wavelength. The resolution of ultrasound is about half of the wavelength. In soft body tissue, the wavelength at 1,000 Hz is 1.54 m. To achieve a spatial resolution of about 0.5 mm, for example, we need a wavelength of 1 mm and therefore a frequency of 1,540,000 Hz or 1.54 MHz.1,2 In ultrasound machines, a piezoelectric crystal produces sound waves. This is a ceramic crystal that changes its shape when an electric potential is applied to it, and reciprocally, it generates an electric charge when it is mechanically deformed. An echocardiography transducer usually contains one or more such crystals. When electric impulses are applied to the crystal, it

56

Section 1:  History and Basics

Fig. 3.1: Sound wave diagram showing the amplitude (A) of the wave and the cycle length (λ).

vibrates at a determined frequency, in echocardiography usually in the range of 1–12 MHz. The same crystal also detects the returning echoes of the ultrasound waves.1,2

Interactions with Different Material The propagation velocity of ultrasound waves in a given material is constant but it is different in different materials: Material

Propagation Velocity (m/s)

Air

330

Water

1497

Metal

3000–6000

Bone

4080

Fat

1440

Blood

1570

Soft tissue

1540

Sound waves that are emitted by the transducer travel through the body and are partially reflected from a boundary between two tissue structures (the amount of reflected energy depends on the difference in impedance of these two tissues) and are partially transmitted. The transmitted part again is partially reflected and partially transmitted at the next boundary and so on. The reflected sound waves travel back through the body and are detected by the transducer (Fig. 3.2).2,3 As echoes from structures that are farther away from the transducer (yellow bar) need a longer time to travel than those from closer structures (red bar), the time between

Fig. 3.2: Visualization of received ultrasound energy. The gray arrows show ultrasound waves emitted from the transducer. They are partly transmitted and partly reflected by different tissue surfaces. The amount of received ultrasound echoes (colored arrows) is translated into brightness. The more energy is received from a distinct point, the brighter this point is shown on the screen (blue structure reflects the most energy and is shown as the brightest point on the screen). The time lag between emission of the ultrasound wave and dettection of its echo is translated into depth. Ultrasound waves that are reflected by structures that are deeper inside the body (yellow bar) come back to the transducer later than echoes from closer structures (red bar) and are therefore shown on the lower part of the screen.

emission of the ultrasound wave and the reception of its echo can be translated into depth. The deeper the structure, the longer the time lag between emission and reception.2,3 Different structures reflect a different amount of the emitted energy; so for visualization, the strength of a returning echo from any point is shown by the brightness of this point on the screen. The more the reflection, the brighter the point (Fig. 3.2).2,3

Attenuation and Absorption Attenuation is the total energy loss of the ultrasound beam with increasing depth. Emitted ultrasound waves are attenuated when travelling through tissue as part of their energy is reflected, scattered, or diffracted. But most of the attenuation is due to absorption in the tissue.1-4

Chapter 3:  Basics of Ultrasound

This absorption causes heating, which, of course, has to be limited so that the body tissue is not heated to dangerous temperatures. For safety, there is a limitation on the total energy that can be transmitted from ultrasound machines. This is expressed by the mechanical index (MI), which is usually limited to 1.1 (the Food and Drug Administration limit is 1.9).1-4 Absorption is mainly dependent on two factors: (1) the density of the tissue and (2) the frequency of the ultrasound waves. As the density and frequency increase, more absorption occurs. As density of the tissue cannot be changed and the amount of emitted energy is limited for safety reasons, the only variable that can be corrected is frequency. The higher the frequency, the better the spatial resolution, but it results in more absorption and, therefore, waves travel at a lesser depth. So, to visualize structures that are deeper inside the body, we need to use lower frequencies but at the expense of spatial resolution. The frequencies in clinical use are: Depth (cm)

Frequency (MHz)

Adult cardiac ultrasound

10–20

3.5

Pediatric cardiac ultrasound

5–10

5

Vascular ultrasound

2–5

7.5

1–4

10

57

harmonic, three times the fundamental is called the third harmonic, and so on. Modern ultrasound machines can do fundamental imaging (where the transducer detects the same frequency as it emits) or harmonic imaging (where it only detects the harmonic of the emitted frequency). For adult cardiac ultrasound, for example, better tissue penetration of the lower frequency of 1.7 MHz can be combined with the advantages in spatial resolution of 3.5 MHz. Beneath improved depth penetration, the advantage of second harmonic imaging is reduction of side lobe artifacts (see below) and reduction of noise resulting in better contrast resolution of tissue interfaces, especially the endocardial border.1,2 However, with harmonic imaging, some structures like valve leaflets can appear artificially thick so that a very good fundamental image would be preferable, but in most patients, the image quality is much better with harmonic imaging. Figures 3.3A and B show the same image in fundamental and harmonic imaging.1,2

IMAGING BY ULTRASOUND A-Mode and B-Mode

Ultrasound can cause tissue to vibrate at multiples of the emitted frequency. The emitted frequency is called “fundamental”, and the multiples are called “harmonic”, so twice the fundamental frequency is called the second

As mentioned above, the transducer emits and receives ultrasound waves. From the time lag between emission and reception, the distance of the reflecting structure from the transducer can be calculated, and the received energy at a certain time (i.e. from a certain depth) can be displayed as energy amplitude. This is called A-mode. If this amplitude is translated into brightness at a certain point, we call it the B-mode (Fig. 3.4).1,2

A

B

Harmonic Imaging

Figs 3.3A and B: Apical four-chamber view: (A) Fundamental imaging; (B) Harmonic imaging.

58

Section 1:  History and Basics

Fig. 3.4: Scheme of A-, B-, and M-mode. The gray arrows represent from the transducer emitted ultrasound waves that are partially reflected by the different objects. The colored arrows show the reflected ultrasound waves that are received by the transducer. The detected energy of those ultrasound waves is displayed as amplitude at a certain point in A-mode, as brightness of a certain point in B-mode, and as brightness of a certain point over time in M-mode.

A

B

C

Figs 3.6A to C: (A) Linear; (B) Curvilinear; and (C) Sector probe.

M-Mode In M(otion)-mode echocardiography, the B-mode scan line is displayed along a moving sheet of paper or on a screen resulting in a B-mode scan line over time (Fig. 3.4).

2D Ultrasound In A-, B- and M-mode, we only use a single transducer and therefore get one single scan line only. If we put multiple transducers in a row, we can get multiple scan lines next to each other, which results in a 2D image (Fig. 3.5).

Fig. 3.5: Two-dimensional (2D) ultrasound. Multiple transducers in one probe emit and receive ultrasound waves and translate them into B-mode images that are shown next to each other and result in a 2D image.

Transducers and Probes Transducers can either be arranged along a linear array resulting in parallel ultrasound beams creating a near and far field as wide as the probe length or along a curvilinear array resulting in a bigger far field than the width of the probe (Figs 3.6A and B). Using a curvilinear array, the probe width and the width of the ultrasound beam close to the probe can be small but at the cost of reduced lateral resolution in the far field as the scan lines diverge with increasing distance from the probe.2,4 To get a near field that is narrow enough to make it through the intercostal space combined with a far field big enough to show the whole heart, we need ultrasound beams originating from one point in the probe. This can be achieved using a single transducer that changes its direction after every pulse of ultrasound waves that results in a sector image (Fig. 3.6C).2,4 Almost all modern echocardiography machines use phased array technology, where a single piezoelectic crystal is sliced into 256 strips. The pulse generator can activate each of these very thin strips separately in a very rapid sequence, producing a compound ultrasound wave. Varying the electrical activation sequence can change the direction of the compound wave.2,4

Resolution Resolution is a dimension for how close together two different scatterers can be to still be detected and displayed as two different structures.1-4

Chapter 3:  Basics of Ultrasound

Axial Resolution Axial resolution depends on wavelength. As described earlier, the resolution of ultrasound is about half of the wavelength. In structures that are thinner than that, the two interfaces of this structure will be shown as one echo. Additionally, two different objects at different depths will appear as one object if they are less than one wavelength apart (Figs 3.7A to C). Axial resolution can be improved by shortening the wavelength by increasing the frequency (but at the expense of depth due to reduced penetration of the ultrasound waves).

Lateral Resolution Lateral resolution depends on the width of the ultrasound beam. On one hand, there is a limit of object size that can be displayed true to original. One scan line on the display shows an echo at a certain depth and cannot differentiate if the scatterer is smaller than the ultrasound beam or right the ultrasound beam’s width. A scatterer that is smaller than the ultrasound beam’s width will be displayed too big. This is called “smearing” (Figs 3.8A and B). On the other hand, if two different small objects are so close together that they are detected from the same ultrasound beam, then they are displayed as one point on the screen (Fig. 3.8C). Lateral resolution can be improved by narrowing the ultrasound beam by focusing.

Temporal Resolution, Frame Rate The single transducer of a sector probe emits a pulse of ultrasound waves and has to wait for the echoes to build one scan line of the 2D image before changing its position and emitting the next pulse of ultrasound waves for the

A

B

C

Figs 3.7A to C: Axial resolution. (A) Scatterers that are more than half of the wavelength apart will be displayed as two different echoes; (B) Scatterers that are closer together than half of the wavelength will be displayed as one echo; (C) Using a shorter wavelength (higher frequency), the two close scatterers will be displayed as two echoes.

59

next scan line of the 2D image. The sweeping velocity of the transducer, therefore, depends on the time until the echoes from the farthest structures return, which, in turn, depends on propagation velocity (which is more or less stable in soft tissue) and wavelength (required for the desired depth). To build an image with a sector angle of 90° and a depth of 15 cm, for example, we need approximately 200 scan lines, which needs about 40 milliseconds. One complete 2D image consisting of multiple scan lines is called a “frame.” “Frame rate” indicates the number of frames per second. A higher frame rate indicates a higher temporal resolution with more 2D images per second. With a higher frame rate, small structures that are highly mobile are easier to follow. To get a smooth image of the heart’s motion, our eyes need a frame rate of at least 25 frames per second. Frame rates in modern ultrasound machines may be as high as 150/s or as low as 6/s. The frame rate depends on different factors: Depth: the greater the depth, the longer the time until the echoes return to the transducer, and therefore, the slower the sweeping velocity of the transducer. To increase the frame rate, we have to reduce the depth (Figs 3.9A and B). Image line density: the more scan lines form one frame (higher line density), the more precise the image, but slower the sweeping velocity of the transducer. To increase frame rate, we would have to reduce line density but at the cost of spatial resolution. Sector angle: the larger the angle of the sector, the wider the field of view. In consequence, the transducer needs more time to sweep through the complete sector to form one frame, resulting in a lower frame rate. To increase frame rate, one must narrow the sector (Figs 3.10A and B).

A

B

C

Figs 3.8A to C: Lateral resolution. (A and B) Scatterers ≤ the ultrasound beam’s width will be displayed as an echo of the beam’s width; (C) Scatterers that are closer together than the beam’s width will be displayed as one echo.

60

Section 1:  History and Basics

A

B

Figs 3.9A and B: Transthoracic echocardiography, four-chamber view. By reducing the depth, the frame rate increases.

A

B

Figs 3.10A and B: Transesophageal echocardiography, three-chamber view. By reducing the sector, the frame rate increases.

Line Density Line density is a variable that determines how far apart the ultrasound beams are. Maximum lateral resolution can be achieved when the distance between the single ultrasound beams is the same as the ultrasound beams’ width, meaning that all ultrasound beams are in a row without any gaps in between. This, of course, is true only in a linear array with parallel ultrasound beams. In a sector probe, the ultrasound beams diverge with increasing distance from the transducer resulting in a lower line density and therefore a lower spatial resolution deeper inside the body. There is a strong relationship between line density, sector width, and frame rate. As it takes a certain time to emit an ultrasound wave and receive the echoes, at a given depth and frame rate, we can either narrow the sector to

get a high line density or have a lower line density in a larger sector (the same amount of lines in a larger sector). If we want a large sector and a high line density, we get a lower frame rate. There is always a trade-off between those three variables.

IMAGE OPTIMIZATION AND EQUIPMENT The basic components of the ultrasound system are the transducer probe, which emits and receives the ultrasound waves; the transmitter, which creates the pulses sent to the transducer; the receiver, which receives the current generated by the transducer; the amplifier, which amplifies the returning signals; and the central processing unit (CPU), which does all the calculations to display an image on the screen.1-4

Chapter 3:  Basics of Ultrasound

To optimize the ultrasound image, there are several components to adjust. These are discussed below.1-4

Depth The greater the depth, the longer the time until echoes return to the transducer, and therefore less scan lines in a given time. This either results in a lower frame rate or lower line density, which, in turn, reduces resolution. To improve resolution and frame rate, depth should always be adjusted to the minimal possible amount to still display the region of interest.

Sector Width The larger the sector of the image, the more scan lines are needed. This leads to a lower frame rate, or, at a given frame rate, to lower line density because we would have to spread the same amount of scan lines over a larger sector. This, again, would cause worse resolution. To improve the image, the sector should be as small as possible to still cover the region of interest.

Focus The ultrasound waves of a beam are not completely parallel but narrow at a certain distance and diverge again. The ultrasound beam can be manipulated to be the narrowest at a particular depth. As the ultrasound waves are closest, lateral resolution is at its maximum at this level. The focus can be adjusted manually to examine a particular area in more detail.

Gain, Time Gain Compensation The gain button brightens or darkens the image by increasing or decreasing the amplification of the reflected signal in postprocessing. Increasing gain increases signal and noise in the same manner, which results in a brighter image without improved contrast between structures. Modern ultrasound machines apply a time gain compensation (TGC), increasing the gain of the received echo with increasing time from emission (equivalent to increasing gain with increasing depth). As gain increases signal and noise in the same manner, this can only be done up to a certain amount and is usually an automated function of the ultrasound machine.

61

Zoom The zoom is also a function of postprocessing, taking the desired part of the screen and magnifying it. As the original ultrasound image is not affected, there is no improvement in resolution using zoom.

ARTIFACTS Ultrasound artifacts include the appearance of structures that do not exist on one hand, and obscuring of structures that do exist on the other. Both can pose important and decision-making challenges.1-4

Enhancement and Attenuation Different tissues have diverse densities causing varying propagation velocities of ultrasound waves and different absorption. If a structure (e.g. a fluid-filled cyst) absorbs a minimal amount of energy only, the region that lies behind it will receive and reflect more ultrasound than the surrounding tissue at this depth and therefore appear uniformly brighter. This is called “enhancement.” In contrast, if a structure absorbs a big amount of energy, the area beyond will get and reflect less sound and therefore appear darker. This is called “attenuation.” Attenuation and enhancement can be used diagnostically to identify calcific lesions or fluid-filled cysts, for example, but they make assessment of the area beyond impossible either by increasing the brightness up to saturation of the display or by removal of real echoes resulting in a dark display. To overcome this kind of artifact, you have to move the probe and try to find an acoustic window without the artifact causing structure. Alternatively, you can do a transesophageal echocardiogram.

Acoustic Shadowing Acoustic shadowing is the extreme of attenuation. Tissues like air or bone but also prosthetic valves or calcification attenuate the ultrasound beam almost completely and cause an acoustic shadow behind it (Fig. 3.11). Shadowing structures deeper inside the body cause a drop out behind them, and structures close to the probe (like ribs) reduce the effective aperture.

62

Section 1:  History and Basics

Fig. 3.11: Transesophageal echocardiogram. Calcifications of the mitral ring cause an acoustic shadow (red arrows).

Fig. 3.12: Apical four-chamber view. Reverberations (red arrows) caused by mitral valve prosthesis.

Reflection The same mechanism can cause ghost images. Returning high intensity echoes from calcification or the pericardium can be reflected by the transducer, which causes a second echo. This delayed transmission is displayed as a secondary image, a “ghost image,” deeper inside the body (Fig. 3.13). Those reflection artifacts can be recognized as structures twice as far from the transducer as high intensity echoes. When the structure moves, the ghost structure moves twice as far.

Side Lobe Artifacts Fig. 3.13: Short-axis view. Ghost image in the left ventricular cavity (red arrow).

Reverberation Stationary reverberation artifacts, usually immobile curved artifacts on the right edge of the image are caused by echoes from stationary structures like the chest wall. They cause ultrasound to bounce back and forth between the skin and the structure, which increases the time lag of the echoes returning to the transducer. This delay is translated into depth for which reason those stationary structures are displayed farther down the image. Moving reverberations originate from the same phenomenon but are caused by moving structures, typically valve prostheses, causing artifacts in the far field moving the same way as the prosthesis (Fig. 3.12). These kind of artifacts can be overcome by moving the probe.

The ultrasound waves are not only concentrated in the main beam but, mainly originating from interference, the beam is dispersed in side lobes next to the main beam. If ultrasound waves of one of those side lobes hit a reflecting object outside the main beam, the transducer can detect their echoes as well. The system cannot differentiate between echoes from the main beam and echoes from the side lobes and displays them all in the same scan line on the screen. The beam with its side lobes is sweeping back and forth the sector. Coming from the right side, first the left side lobe hits the reflecting object (displaying it in the position of the main beam), then the main beam, and then the right side lobe. This leads to the fact that the one reflecting object is displayed in three different scan lines on the screen, which makes it appear much broader than it is (Fig. 3.14).

Chapter 3:  Basics of Ultrasound

63

The transducer that emits the ultrasound waves is stationary. If the ultrasound waves are reflected by an immobile structure, the returning echoes have the same frequency as the emitted sound waves. If the sound waves hit a structure that is moving toward the transducer (typically blood cells in the blood stream), they are reflected a little earlier. Further, the structure is following the reflected echoes toward the transducer, reflecting the next echo a little closer to the previous one. This shift in the distance of the sound waves, in frequency, can be detected by the ultrasound machine and can be translated into speed and direction of the moving structure.1,2

Pulsed and Continuous Wave Doppler Fig. 3.14: Apical four-chamber view. Side lobe artifact in the lateral wall of the left ventricle (red arrow).

Side lobe artifacts will move with the reflecting object and are increasing and decreasing in intensity the same way. They are most obvious in echo-free cavities and are commonly seen as linear structures.

DOPPLER ULTRASOUND Physical Principles The Doppler effect explains the phenomenon that the sound you hear from a moving source changes depending on your position in relation to the source. The sound of the siren of an oncoming ambulance, for example, is different from the sound after it has passed you. Before it passes you, the tone is a little higher than it is afterward.1,2 Propagation velocity of sound waves in a given medium (like air or water) is constant. From a stationary source, the sound will propagate in all directions with the same velocity. When the source of sound moves in one direction, the next sound wave will be emitted a little further forward than the previous one, causing the crest of the second wave to be a little closer to the previous one. The distance of the crests is equivalent to frequency so that sound waves that are emitted in the direction of the movement have a little higher frequency than sound waves that are emitted in the opposite direction.1,2 If the source of sound is stationary and the observer is moving, we have the same effect. If we are moving toward the source, the crests of the waves will be detected a little earlier; if we are moving away, the crests will be detected a little later, a little farther apart, and consequently a little lower in frequency.1,2

Doppler can either be used as pulsed or as continuous wave Doppler. In pulsed Doppler, a pulse is sent out and the shift in the reflected pulse is received after a certain time. Here as well, time is translated into depth, and we can measure the velocity at a certain depth. The depth can be adjusted manually (using the cursor). For a most accurate measurement, the ultrasound beam should be parallel to the blood flow measured.1,2 Pulsed Doppler is very helpful in measuring the velocity at a certain point. The problem is that there is always a time between the single pulses when no measurement takes place and we miss a part of the motion we are observing. Depending on the sampling frequency, we are missing either a bigger or a smaller part. If the velocity we are measuring exceeds half the pulse repetition frequency (PRF = Nyquist limit), then the movement of the structure cannot be measured correctly.1,2 If, for example, we look at a watch and the moving velocity of the hands is ¼ the PRF (less than half the PRF), we see them at 12, 3, 6, 9, and 12 again. We can be sure, they are moving clockwise. If they are moving exactly at the PRF, we see them at 12, at 6, and again at 12. We can still determine their velocity but we do not know the direction (whether they are moving clockwise or counterclockwise). At ¾ the PRF, we see the hands at 12, then at 9, then at 6, then at 3, and then again at 12. It appears as if they would move counterclockwise although they are moving clockwise. This aliasing is the reason why pulsed Doppler cannot measure high velocities correctly.1,2 However, continuous wave Doppler measures high velocities. The ultrasound beam is transmitted conti­ nuously and the reflected pulses are received continuously. So we can be sure to get all the information about the motion we are observing. As pulses are sent out and

64

Section 1:  History and Basics

Fig. 3.15: Apical four-chamber view. Pulsed wave Doppler measurement of blood flow in the pulmonary vein. Blood flow velocity is displayed in the y-axis and time on the x-axis.

received continuously, there is no information about the time lag between emission of the pulse and reception of its echo, and therefore no information about depth. We can measure the highest velocity along an ultrasound beam, but we do not know exactly where the point of maximal speed is.1,2 High pulse repetition frequency (HPRF) is an attempt to combine the advantages of both techniques. Pulses are sent out in a very high frequency, even before the echoes of the previous ones are returned to the transducer. With increasing frequency, the Nyquist limit is increased as well and higher velocities can be measured, but as it is impossible to tell which echo is from which pulse, the time lag cannot be determined correctly resulting in a partial depth ambiguity.1,2 Similar to M-mode, the shift in frequency of the sound waves (velocity of the blood flow) can be displayed as a function of time. The amount of reflected echoes (amplitude) is translated into brightness; frequency (= velocity) is displayed on the y-axis and time on the x-axis. Figure 3.15 shows a typical flow velocity curve of Doppler measurements.1,2

Color Doppler Color Doppler measures the phase shifts of the returning echoes and translates them into color. Two (or more) pulses are sent out very rapidly. They hit a moving structure (blood cell) so close after each other that the velocity of the structure is still the same when the second

pulse hits it. But as the structure already moved a little before the second pulse hits it, the returning sound waves (of same frequency) are in different phases (crest or valley of the curve or somewhere in-between) when they are detected by the transducer. This shift can be measured and translated into velocity and direction of the moving structure. In color Doppler, velocity and direction of moving structures along an ultrasound beam are displayed as color at a certain depth (according to B-mode images where we display brightness at a certain depth). However, the number of colors our eye can distinguish is limited, and one color has to display a range of velocities because of which color Doppler is only a semi-quantitative method. Common mapping formats are BART (blue away red toward) or RABT (red away blue toward). Velocities slower than the aliasing velocity are displayed in pure red or blue, and higher velocities or turbulences are displayed in yellow-green or mosaic. To build a sector image, we need, like in B-mode, several scan lines next to each other. There are the same rules as in B-mode echocardiography. The larger the sector, the more scan lines we need, and the longer it takes to build one frame, the lower is the frame rate. To improve the image, we should choose a sector as small as possible. In color Doppler, some of the same artifacts as in B-mode ultrasound can occur like mirror or ghost images (see above).

Tissue Doppler The blood flow usually has a much higher velocity and reflects, due to lower density, lower signal amplitudes than tissue. If we filter the higher velocities out, we can display the tissue velocity only (low-pass filter). The movement of the tissue can either be displayed as spectral display or in color (2D or M-mode). Tissue Doppler will be explained in more detail in another chapter.

REFERENCES 1. Anderson B (Editor). Echocardiography: The Normal Examination and Echocardiographic Measurements. 2nd ed. 2007. 2. Armstrong WF, Ryan T (Editors). Feigenbaum’s Echo­ cardiography. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010. 3. Nihoyannopoulos P, Kisslo J (Editors). Echocardiography. London: Springer-Verlag; 2009. 4. Solomon SD (Editor). Contemporary Cardiology: Essential Echocardiography: A Practical Handbook with DVD. Totowa, NJ: Humana Press; 2007.

CHAPTER 4 Doppler Echocardiography— Methodology, Application and Pitfalls George Thomas

Snapshot ¾¾ Doppler in Cardiology ¾¾ Doppler Instrumentation ¾¾ Continuous Wave Doppler ¾¾ Pulsed Wave Doppler ¾¾ Color Doppler

DOPPLER IN CARDIOLOGY Doppler is an integral component of echocardiography.1,2 This enables examiners to differentiate between normal and abnormal flow patterns and to quantify those characteristics. These determinations are helpful to study blood flow. Doppler systems measure the characteristics of disturbed flow: direction, turbulence, and velocity to determine the severity of abnormal hemodynamics.3 Doppler echocardiography provides an accurate assess­ ment of the severity of many cardiac disorders and has therefore assumed an integral role in the clinical evaluation of cardiac patients. Excellent guidelines exist to properly record and quantify Doppler studies.4 According to the Doppler principle, moving blood particles alter the frequency of reflected ultrasound. The magnitude of this Doppler shift relates to the velocity of the blood particles, whereas the polarity of the shift reflects the direction of blood flow toward (positive) or away (negative) from the transducer. The Doppler equation states that the Doppler shift (F) is directly proportional to the velocity of blood particles (v), the transducer frequency (f), and the cosine of the angle of incidence (θ) and is inversely

¾¾ Power Doppler ¾¾ Tissue Doppler ¾¾ The Doppler Methodology ¾¾ Information Derived from Doppler

proportional to the velocity of sound in tissue (c). The Doppler equation can be derived for blood flow velocity. When solving the Doppler equation, an angle of incidence of 0° (cosine = 1.0) is assumed for cardiac applications. Properties of a Good Sonic Reflector

Strong Doppler shifted signals are required for reliable flow measurement. The amplitude of the Doppler shifted signals is largely related to the suitability of the sonic scatterers in the flow. In the case of blood, the sonic scatterers are blood cells and colloidal molecules. Of late, artificially introduced con­ trast agents are used to enhance Doppler signals.5 The proper­ ties of a good reflector are as follows: The scattering material must have an acoustic impedance* different from the fluid. There must be some particles large enough to cause longitudi­ nal scattering. For a given tube size, the longitudinal scattering must have sufficient energy to overcome the Rayleigh (energy wasting) scattering caused by smaller particles. The scattering material must travel at the same velocity as the fluid for good accuracy. *The acoustic impedance (Z) of a material is defined as the pro­duct of density (p) and acoustic velocity (V) of that material, or Z = pV.

66

Section 1:  History and Basics

Apart from flow velocity, another aspect is the detection of abnormal flows or turbulence. The normal flow in a smooth tubing is laminar. Pressure differences can occur anywhere along the path of blood flow. Interaction between blood of higher velocity and lower pressure with blood of lower velocity and higher pressure produces turbulence. The critical number at which turbulence will occur is called the Reynold’s number. As blood velocity increases, from an increase in either ejection force or some obstruction, the critical Reynold’s number is reached, and turbulence occurs. This turbulence may be relatively short in length or may extend considerably if the obstruction is severe. Turbulence generates sound waves (murmurs and bruits) that can be heard with a stethoscope. Because higher velocities enhance turbulence, audible sounds resulting from turbulence become louder whenever blood flow is increased across the valve or vessel. Elevated cardiac outputs, even across anatomically normal valves, can cause physiological murmurs because of turbulence. These types of turbulence may not cause significant ultrasound frequency shifts and may not be detected by Doppler at the conventional frequencies. Such a phenomenon explains the paradox of murmur without Doppler abnormalities. The relation of the degree of obstruction and the rate of flow of the fluid is expressed in Poiseuille’s law. It states that the rate of flow is proportional to the fourth power of the radius of the tube. Currently, Doppler echocardiography consists of four modalities: continuous wave Doppler, pulsed wave Doppler, color Doppler imaging, and power Doppler. Continuous wave and pulsed wave together can be called spectral Doppler. Current ultrasound systems can also apply the Doppler principle to assess velocity within cardiac tissue. The moving target in this case is tissue, such as myocardium, that has higher amplitude of backscatter ultrasound and a lower velocity compared with red blood cells. This new application is under investigation.6

DOPPLER INSTRUMENTATION An oscillator circuit delivering a variable voltage to the piezoelectric ceramic crystals of the transducer produces ultrasound energy. The reflected Doppler ultrasound is passed through the quadrature detector and high-pass filtering. The quadrature detector resolves the frequency shift between the transmitted and received frequencies and thus determines the direction. In pulsed wave Doppler, pulsing is achieved by an electronic transmission gate.

The Doppler Equation Derivation (see Fig. 4.1)

Let the velocity of sound = c Let the velocity of moving object = v Let the frequency of sound = f Let the observed frequency = F So observed wavelength = c/F The wavelength of sound would = c/f The distance traveled by the object in this period = v/f Distance between waves = c/f – v/f = c/F Or, c/F = (c – v)/f Or F = fc/(c – v) Or F – f = fc/(c – v) – f (by arranging the terms and simplifying) Or the change in frequency Δf = fv/(c – v) Because the speed of sound (c) in blood is ~1,560 m/s and the highest velocities (v) of interest in the heart are under 10 m/s, this v can be omitted in the final equation. Thus, Δf = fv/c, meaning that the change in frequency is equal to the fundamental frequency multiplied by the ratio of the velocity of the object and the speed of sound. This is true only if the observation is in line with the moving object. If it is at an angle θ, the relationship is related to the cosine of the angle. Thus, Δf = cos θfv/c. (See Fig. 4.2.) In the case of medical applications, the moving object (blood particle) itself does not emit sound. It reflects the sound emitted by the transducer. Thus, the effect occurs twice—once when received by the blood particles and second after reflection. This will result in adding a factor of 2 to the equation. Thus, Δf = 2cos θfv/c. Thus, the Doppler signal is dependent on: • Blood velocity: as velocity increases, so does the Doppler frequency. • Ultrasound frequency: higher ultrasound frequencies give increased Doppler frequency. But lower ultrasound frequencies have better penetration. • The choice of frequency is a compromise between better sensitivity to flow or better penetration. • The angle of insonation: the Doppler velocity estimation is most accurate when the Doppler ultrasound beam is aligned (cos 0° or cos 180° = 1) to the flow direction. This is of the utmost importance in the use of Doppler ultrasound.

It is also passed through a low-pass filter (determining the highest frequency without aliasing) and the sample and hold unit. High-pass filtering is required to remove

Chapter 4:  Doppler Echocardiography—Methodology, Application and Pitfalls

67

Fig. 4.1: Features of a wave.

Fig. 4.2: Cosine correction. If the Doppler velocity measurement V is done at an angle q, then the actual velocity would be Vcos q.

high amplitude but low-frequency artifacts arising from tissues and movement of the probe (if handheld). Such a procedure will unavoidably lose low-frequency Doppler signals from slowly moving blood, which may be of clinical significance. Next, the demodulated and filtered Doppler frequency shift signals are digitized in the analogue-todigital converter. The continuous analogue Doppler signal is thus converted into a series of discrete digital signals. These are sent through the “FFT” analyzer. This part of a Doppler ultrasound instrument analyzes the spectrum of Doppler frequency shifts using the mathematical method of fast Fourier transform (FFT). The analyzer transforms the Doppler signals into a time-velocity spectral display, showing how the full spectrum of blood-flow velocities varies with time. The FFT analyzer resolves the composite, multifrequency Doppler signal into its component

frequencies and transforms the signal from an amplitudeversus-time (time domain) format into an amplitudeversus-frequency (frequency domain) format. Thus, finally the continuous spectrum of the original analogue Doppler signal is divided into a certain number of frequency intervals. The higher the frequency interval, the better the resolution of the analyzer. The display of the spectral waveform is as follows: X-axis = time; Y-axis = estimated

Reynold’s Number and Poiseuille’s Law

Reynold’s Number The Reynold’s number (Re) predicts the onset of turbulence and is expressed by the equation: Re = (V × D × ρ)/η where V = velocity, D = diameter, ρ = density of blood, and η = viscosity of blood. The Reynold’s number is a dimensionless factor that indicates whether fluid flow will be turbulent. If the Reynolds’s number >2,000, then the flow is turbulent; if the Reynolds’s number is 45%.5,6 Although our laboratory routinely calculates ejection fraction from systolic and diastolic LV volumes obtained by planimetric tracing of the apical views, we habitually inspect the EPSS as a qualitative means of verification of EF. Sinus rhythm is confirmed by the presence of the A-wave, and left atrial function is reflected by its excursion. In systole, the coapted mitral leaflets usually parallel the anterior motion of the cardiac base. The reversal of this motion in mid-systole is confirmatory of mitral valve prolapse.

170

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 10.5: M-mode examination of the left ventricle, speed 100 mm/s. Relaxation of the posterior wall of the left ventricle occurs faster than contraction. This is another sign of normal left ventricular function. Contraction of the interventricular septum and posterior wall of the left ventricle is coordinated, though peak contraction is not simultaneous. Pericardium is the brightest echo structure; its brightness here is normal. In many laboratories, two-dimensional or M-modal linear dimensions of the left ventricle are obtained in this view. The authors prefer planimetric measurements of left ventricular volumes. (LV: Left ventricle; RVOT: Right ventricular outflow tract).

pericardium has a low coefficient of friction and gives the outflow tract the appearance of “sliding” to-and-fro just under the immobile anterior mediastinal structures.7 A posterior collection of pericardial fluid might be imaged as an echo-free space even if it is physiological or trace in amount. A physiological collection of pericardial fluid is recognized by noting that the space between the posterior myocardium and external structures is small and appears only in systole. It is important to realize that the posterior pericardium is the most reflective structure in the heart and producing an intensity standard that can be used to compare other structures. For example, the aortic root and ascending aortic walls should be less reflective (less white) than the pericardium. In turn, the mitral and AVs should be less reflective that the aortic wall. These qualitative relationships are convenient means of identifying abnormal thickening of various structures. In addition to the pericardium and fat pad, other structures that are normally appreciated in the long axis are the coronary sinus and right coronary (seen together in the posterior AV groove), the descending thoracic aorta superior to the sinus posterior to the mid-atrium and the right pulmonary artery crossing under the ascending aorta, superior to the LA.

The M-mode of the LV is useful to confirm that the septum and posterior wall move toward each other in a coordinated fashion (Fig. 10.5). It is also useful to confirm the plausibility of 2D-measured LV mass. For example, if the 2D measurement is in the normal range, the diastolic M-mode cavity diameter and wall thickness are confirmatory if also normal. The RV wall is also sampled during all three M-mode views discussed above. If there is no RV hypertrophy, the RV wall will not exceed a diastolic thickness of 4 mm in any view.

Doppler Imaging

Extracardiac Structures

Calcification

Structures surrounding the heart are important to observe and analyze. Anteriorly, the normal heart, especially with aging, has a fat pad of varying thickness. One of the most common errors in echocardiography is to call a fat pad an “anterior pericardial effusion.” A good way to avoid this error is to observe that the fat pad has fine reticulated echo targets within, whereas an effusion is usually clear and seen in the company of a larger posterior pericardial fluid collection or space. When observing the anterior pericardium that invests the RVOT, note that the healthy

Cardiac skeletal calcification occurs with aging and may be associated with increased risk of atherosclerosis and its complications.8 The normal heart is free of this process, but to establish normality, the areas where calcium is most likely to accumulate should be inspected. These include the posterior mitral annulus, the annulus between the posterior portion and aorta, the aortic annulus, the papillary muscle tips, the AV, the sinuses of Valsalva, and the ST junction, just where the aortic root narrows into the ascending aorta.

Doppler evaluation of the long-axis precordial view is almost always limited to color imaging as the direction of most flow is not ideal for Doppler imaging because it does not flow toward the interrogating transducer. A small color systolic signal of mitral regurgitation is seen in the majority of normal studies and typically occurs at the coaptation point between anterior and posterior leaflets. Aortic regurgitation is unusual in a normal study ( 50% of its starting diameter. This is a sign of normal (0–5 mm Hg) pressure in the right atrium. Spontaneous contrast due to low velocity of the flow in the inferior vena cava is a normal variant. Sometimes an accumulation of ascitic fluid between the liver and the diaphragm can be seen in this view (not present). (IVC: Inferior vena cava; RA: Right atrium). See accompanying Movie clip.

Abdominal Aorta and Inferior Vena Cava The inferior vena cava (IVC) parallel to and to the right of the midline (Figs 10.30A and B), is a centerpiece of cardiac hemodynamics. Characteristically, the normal IVC is less than 2.1 cm and collapses to > 50% of its starting diameter during exaggerated inspiration. The hepatic veins are small and thready; pulsed Doppler of hepatic veins shows systolic dominant inflow with inspiratory exaggeration

(Fig. 10.31). Echocardiographers should always look behind to the IVC for right pleural effusion and on the hepatic side of the diaphragm for ascites. Just to the left of the midline, the abdominal aorta can be imaged in long axis with the probe pointed at 12 o’clock (Fig. 10.32A). In the normal state, the walls are smooth without shadowing from calcification or irregularity from atheroma. Color flow is forward in systole with little if any, back flow (Fig. 10.32B).

184

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 10.31: Pulsed wave (PW) Doppler examination of the flow in the middle hepatic vein. As in any central vein, systolic flow normally (S) exceeds diastolic flow (D) in the hepatic veins. Flow in the hepatic veins varies with respiration, increasing with inspiration, and decreasing or disappearing with expiration. The more pronounced the respiratory variation, the lower the right atrial pressure, except for hypovolemic states, when respiratory variation decreases.

A

B

Figs 10.32A and B: Subcostal long axis of the abdominal aorta (Abd Ao), color Doppler study. Examination of the abdominal aorta is an obligatory part of the transthoracic echocardiogram (TTE). It allows detection of the atherosclerotic plaques and aneurysms of the abdominal aorta. A normal aorta (A) has smooth contours and a normal size; its walls look similar to those of the inferior vena cava (IVC), and systolic pulsation is clearly seen as demonstrated by pulsed wave (PW) Doppler (B).

Suprasternal Views The suprasternal window allows interrogation of the transverse and descending aortic arch (Figs 10.33A and B). The patient should lay flat without a pillow and with the chin up, and the probe should be placed into the suprasternal notch initially pointed at 2 o’clock. Superficial to the arch is a space that represents the brachiocephalic vein and deep to the arch is the circular right pulmonary artery seen as it crosses under the arch. If the brachiocephalic diameter approaches that of half the aortic arch, elevated venous pressure is suspected. If the right pulmonary artery approaches the size of the

arch, chronically elevated pulmonary pressure or elevated pulmonary flow is suspected. The great vessels can be seen occasionally as they leave the arch. Distal to the right pulmonary artery is the superior wall of the LA, the contractions of which can be sampled on M-mode. These contractions provide a unique timing mechanism for atrial arrhythmias.26 In very well-resolved images, the body of the LA with the pulmonary veins can be seen in the far field with perpendicular angulation (see Fig. 10.33B). When successful, this view is known as the crab view because the pulmonary veins resemble crab claws radiating from the body of the atrium. The distal aortic arch (thoracic

Chapter 10: The Standard Transthoracic Examination: A Different Perspective

A

185

B

Figs 10.33A and B: Suprasternal view of the long-axis of the aortic arch. The wall of the aorta is smooth, and normal systolic pulsation of the aorta can be appreciated on video. Several branches of the aorta are clearly seen here. The brachiocephalic vein, closest to the transducer, is occasionally mistaken for aortic dissection. Increased resolution of echocardiography allows visualization of structures, which previously were rarely seen—it is important not to mistake them for abnormalities. The right pulmonary artery can be seen under the aortic arch. Its lower wall is pulsating with contractions of the left atrium. This view is the only one, where an M-mode interrogation of left atrial contraction can be recorded; sometimes it is used in electrophysiology. Pulmonary veins may also be seen in this view, with some angulation. A prime example is shown in figure B after rotating the probe 90°; in this individual, all four pulmonary veins were visualized. (AO: Aorta; Desc Ao: Descending aorta; LA: Left atrium; LUPV: Left upper pulmonary vein; PA: Pulmonary artery; RPA: Right pulmonary artery; RUPV: Right upper pulmonary vein). See accompanying Movie clip.

A

B

Figs 10.34A and B: Suprasternal long-axis view of the aortic arch; pulsed wave (PW) Doppler interrogation of flow in the descending aorta (A). A normal flow pattern with laminar systolic profile and brief retrograde flow in diastole is seen. Retrograde (toward the transducer) flow occupying all diastole is a sign of significant aortic insufficiency; biphasic flow may indicate patent ductus arteriosus or galenic aneurysm; high-velocity antegrade systolic flow continuing into diastole occurs with the coarctation of aorta. Continuous wave (CW) Doppler (B) is important to perform in the descending aorta. Bidirectional flow may be seen if the CW Doppler line catches a branch vessel as occurs here.

descending aorta) allows Doppler interrogation. Normally, the forward flow signal is distinct with little reverse aortic flow in diastole (Figs 10.34A and B). However, in aortic regurgitation, a diastolic signal of reverse flow appears and its VTI is useful for quantitating the severity of regurgitation.27

To the right of the ascending aortic arch, the superior vena cava can be sampled by 2D, color, and pulsed wave Doppler (Figs 10.35A and B). As a central vein, systolic forward flow accentuated during inspiration and dominant to diastolic flow is the normal pattern.

186

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 10.35A and B: Superior vena cava (SVC) view. Color (A) and pulsed wave (PW) Doppler (B, arrows) are important for SVC interrogation as it provides additive information regarding filling pressures and hemodynamics in pericardial diseases. See accompanying Movie clip.

CONCLUSION We have reviewed in detail the features of the standard echocardiographic examination in this chapter. The reader should take note that only by reading a multitude of studies does one come to appreciate better the variation of normality between different patients; therefore, no textbook guide can replace an adequate reading experience alongside knowledgeable echocardiographers. Finally, it is important to note that unlike many other imaging modalities, the echocardiographic examination should be interpreted as it is being performed, so that additional images from alternate views or added color and spectral Doppler can help inform the diagnosis.

REFERENCES 1. Hansen WH, Gilman G, Finnesgard SJ, et al. The transition from an analog to a digital echocardiography laboratory: the Mayo experience. J Am Soc Echocardiogr. 2004;17(11): 1214–24. 2. Van Dantzig JM, Delemarre BJ, Koster RW, et al. Pathogenesis of mitral regurgitation in acute myocardial infarction: importance of changes in left ventricular shape and regional function. Am Heart J. 1996;131(5):865–71. 3. Silverman NH, Lewis AB, Heymann MA, et al. Echocardiographic assessment of ductus arteriosus shunt in premature infants. Circulation. 1974;50(4):821–5. 4. Waller BF. The old-age heart: normal aging changes which can produce or mimic cardiac disease. Clin Cardiol. 1988; 11(8):513–7.

5. Massie BM, Schiller NB, Ratshin RA, et al. Mitral-septal separation: new echocardiographic index of left ventricular function. Am J Cardiol. 1977;39(7):1008–16. 6. Child JS, Krivokapich J, Perloff JK. Effect of left ventricular size on mitral E point to ventricular septal separation in assessment of cardiac performance. Am Heart J. 1981;101 (6):797–805. 7. Himelman RB, Lee E, Schiller NB. Septal bounce, vena cava plethora, and pericardial adhesion: informative twodimensional echocardiographic signs in the diagnosis of pericardial constriction. J Am Soc Echocardiogr. 1988;1(5): 333–40. 8. Teerlink J, Newman TB, Schiller NB, et al. Aortic sclerosis as well as aortic stenosis, is a significant predictor of mortality. Circulation (suppl). 1997;96(8):4208 (abstract). 9. Aazami MH, Salehi M. The Arantius nodule: a “stressdecreasing effect.” J Heart Valve Dis. 2005;14(4):565–6. 10. Barbier P, Solomon S, Schiller NB, et al. Determinants of forward pulmonary vein flow: an open pericardium pig model. J Am Coll Cardiol. 2000;35(7):1947–59. 11. Barbier P, Solomon SB, Schiller NB, et al. Left atrial relaxation and left ventricular systolic function determine left atrial reservoir function. Circulation. 1999;100(4): 427–36. 12. Rossvoll O, Hatle LK. Pulmonary venous flow velocities recorded by transthoracic Doppler ultrasound: relation to left ventricular diastolic pressures. J Am Coll Cardiol. 1993;21(7):1687–96. 13. Goldman JH, Schiller NB, Lim DC, et al. Usefulness of stroke distance by echocardiography as a surrogate marker of cardiac output that is independent of gender and size in a normal population. Am J Cardiol. 2001;87(4): 499–502, A8.

Chapter 10: The Standard Transthoracic Examination: A Different Perspective

14. Ristow B, Ahmed S, Wang L, et al. Pulmonary regurgitation end-diastolic gradient is a Doppler marker of cardiac status: data from the Heart and Soul Study. J Am Soc Echocardiogr. 2005;18(9):885–91. 15. Silverman NH, Schiller NB. Apex echocardiography: a twodimensional technique for evaluating congenital heart disease. Circulation. 1978;57(3):503–11. 16. Simonson JS, Schiller NB. Descent of the base of the left ventricle: an echocardiographic index of left ventricular function. J Am Soc Echocardiogr. 1989;2(1):25–35. 17. Guron CW, Hartford M, Rosengren A, et al. Usefulness of atrial size inequality as an indicator of abnormal left ventricular filling. Am J Cardiol. 2005;95(12):1448–52. 18. Kusumoto FM, Muhiudeen IA, Kuecherer HF, et al. Response of the interatrial septum to transatrial pressure gradients and its potential for predicting pulmonary capillary wedge pressure: an intraoperative study using transesophageal echocardiography in patients during mechanical ventilation. J Am Coll Cardiol. 1993;21(3): 721–8. 19. Ports TA, Silverman NH, Schiller NB. Two-dimensional echocardiographic assessment of Ebstein’s anomaly. Circulation. 1978;58(2):336–43. 20. Yoshida K, Yoshikawa J, Shakudo M, et al. Color Doppler evaluation of valvular regurgitation in normal subjects. Circulation. 1988;78(4):840–7.

187

21. Kuecherer HF, Kusumoto F, Muhiudeen IA, et al. Pulmonary venous flow patterns by transesophageal pulsed Doppler echocardiography: relation to parameters of left ventricular systolic and diastolic function. Am Heart J. 1991;122(6):1683–93. 22. Kuecherer HF, Muhiudeen IA, Kusumoto FM, et al. Estimation of mean left atrial pressure from transesophageal pulsed Doppler echocardiography of pulmonary venous flow. Circulation. 1990;82(4):1127–39. 23. Isaaz K, Munoz del Romeral L, Lee E, et al. Quantitation of the motion of the cardiac base in normal subjects by Doppler echocardiography. J Am Soc Echocardiogr. 1993;6 (2):166–76. 24. Nagueh SF, Middleton KJ, Kopelen HA, et al. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30 (6):1527–33. 25. Lester SJ, Ryan EW, Schiller NB, et al. Best method in clinical practice and in research studies to determine left atrial size. Am J Cardiol. 1999;84(7):829–32. 26. Wang Y, Zatzkis M, Schiller N. Noninvasive measurement of interatrial conduction time and atrial contraction time. J Cardiovasc Ultrasonograph. 1984;3:235–8. 27. Touche T. Pulsed wave Doppler flow reversal in the descending aorta and the severity of aortic regurgitation. Circulation. 1985;72:823.

CHAPTER 11 Nonstandard Echocardiographic Examination Navin C Nanda, Aylin Sungur, Kunal Bhagatwala, Nidhi M Karia, Tuğba Kemaloğlu Öz

Snapshot  Right Parasternal Examina on Planes  Right and Le Supraclavicular Examina on  Le Parasternal and Apical Planes for Examina on of

 Examina on of Le Atrial Appendage  Examina on from the Back  Abdominal Examina on

  Coronary Arteries

INTRODUCTION In addition to standard echocardiographic planes described in the previous chapter, there are many so-called nonstandard echocardiographic examination windows and planes that have been found useful in clinical practice. Standard planes have also been utilized with or without modification to find structures not routinely detected during echocardiographic examination. These are described below.

RIGHT PARASTERNAL EXAMINATION PLANES The patient is placed in the right lateral decubitus position in an attempt to slightly displace the lung to the right, and the transducer is positioned in the second to fourth right intercostal space very close to the sternum. Somewhat superior angulation is used to view the aortic root and ascending aorta, and this has been found useful in assessing aortic aneurysms as well as estimating the severity of aortic valve stenosis by color Doppler-directed continuous-wave Doppler interrogation or using a “standalone” Doppler probe. Inferior angulation facilitates

examination of the superior vena cava as it enters the right atrium. The crista terminalis, a segment of the right coronary artery and the right atrial appendage, may also be viewed using this approach. This window is also useful to view the entire extent of the atrial septum, and both sinus venosus and secundum atrial septal defects are easily identified in this view by color Doppler because the flow signals are parallel to the ultrasonic beam. Because of this, accurate estimation of flow velocities through the defect can be obtained leading to more reliable estimation of shunt flow. Thrombi and other masses in the superior vena cava can be well evaluated. The inferior vena cava and the coronary sinus together with their valves and tributaries have also been visualized in this view. Pulmonary veins may also be observed entering the left atrium. In some patients, it has been possible to view the aortic arch and proximal descending aorta together with the surrounding structures utilizing this window. Examination using this approach is easier when the right heart or the ascending aorta is dilated as this results in further rightward displacement of the right lung producing a larger window. The two-dimensional study can be supplemented by live/real time, three-dimensional echocardiography,

Chapter 11: Nonstandard Echocardiographic Examination

which may provide significant incremental information, and thus a more comprehensive assessment of various, normal anatomic structures and abnormal findings identified by this examination approach. Figures 11.1 to 11.24 and Movie clips 11.1 to 11.24 show normal and abnormal findings obtained from the right parasternal approach using two-dimensional and live/real time, threedimensional echocardiography.1–5

RIGHT AND LEFT SUPRACLAVICULAR EXAMINATION This is performed by placing the transducer above the right and left clavicles. The superior vena cava further upstream from its junction with the right atrium is

189

easily visualized using the right supraclavicular examination approach. Both the left and right innominate veins that join to form the superior vena cava may also be delineated as well as a venous valve often present at the junction with the superior vena cava. Standard textbooks of anatomy do not mention this venous valve, but it is frequently noted echocardiographically and has sometimes been mistaken for a dissection flap in the aorta or an aortic branch. The left supraclavicular window is also useful to examine the left innominate vein and the adjoining arterial vessels. This view is also useful to detect a left-sided superior vena cava. Catheters, pacemaker wires, thrombi, and other mass lesions present in these veins are readily visualized

Fig. 11.1: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). The left arrowhead shows the Eustachian valve, and the right arrowhead points to crista terminalis. IVC, inferior vena cava; (LA: Left atrium; RAA: Right atrial appendage; RUPV: Right upper pulmonary vein; SVC: Superior vena cava; TV: Tricuspid valve) (Movie clips 11.1A and B).

A

B

Figs 11.2A and B: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). (A) The arrowhead shows the right marginal vein draining into the coronary sinus (CS); (B) The left arrowhead points to the Thebesian valve at the entrance of the CS into the right atrium (RA), and the right arrowhead shows the right marginal vein. (LV: Left ventricle; RA: Right atrium; TV: Tricuspid valve) (Movie clip 11.2).

190

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 11.3: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). The right arrowhead points to the right marginal vein, and left arrowhead shows the interventricular vein, both of which drain into the coronary sinus (CS). (RA: Right atrium; TV: Tricuspid valve) (Movie clip 11.3).

Fig. 11.4: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). Shows flow signals (red) moving from the superior vena cava (SVC) and inferior vena cava (IVC) into the right atrium. In Movie clip 11.4, flow in the coronary sinus (CS) is also seen. (LA: Left atrium; RAA: Right atrial appendage; TV: Tricuspid valve).

Fig. 11.5: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). The arrowhead points to right coronary artery in the right atrioventricular junction. (LA: Left atrium; LV: Left ventricle; MV: Mitral valve; RAA: Right atrial appendage; RV: Right ventricle) (Movie clip 11.5).

Fig. 11.6: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP) showing flow signals (red) moving from the right lower pulmonary vein (RLPV) to the left atrium. (LV: Left ventricle; MV: Mitral valve; RAA: Right atrial appendage; RUPV: Right upper pulmonary vein; RV: Right ventricle) (Movie clip 11.6).

and evaluated. Figures 11.25 to 11.33 and Movie clips 11.25 to 11.33 demonstrate normal and abnormal findings imaged from the right and left supraclavicular approaches using two-dimensional and live/real time, three-dimensional echocardiography.1–3

LEFT PARASTERNAL AND APICAL PLANES FOR EXAMINATION OF CORONARY ARTERIES Even though the orifices and proximal portions of both left and right coronary arteries can be evaluated using

Chapter 11: Nonstandard Echocardiographic Examination

A

191

B

Figs 11.7A and B: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). (A) shows an image of the ascending aorta (AO) using this window and (B) shows the superior vena cava (SVC) and coronary sinus (CS) entering the right atrium. Movie clip 11.7 shows the angulation of the transducer to acquire these images using RP. (LA: Left atrium; LV: Left ventricle; RAA: Right atrial appendage; RPA: Right pulmonary artery; TV: Tricuspid valve).

A

B

C

Figs 11.8A to C: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). (A) The arrowhead shows flow signals (blue) in the left main coronary artery between the aorta and the main pulmonary artery (PA); (B) The arrow points to flow signals obtained from the ascending aorta (AA) using pulsed wave Doppler; (C) The arrow points to flow signals obtained from the descending thoracic aorta (DA) using pulsed wave Doppler. (ACH: Aortic arch; AV: Aortic valve; LA: Left atrium; LPA: Left pulmonary artery) (Movie clip 11.8).

192

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 11.9: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP) showing the main pulmonary artery (MPA) and the left pulmonary artery (LPA) located below the aortic arch (ACH). (AV: Aortic valve; DA: Descending thoracic aorta; LA: Left atrium) (Movie clip 11.9).

A

B

C

D

Figs 11.10A to D

Chapter 11: Nonstandard Echocardiographic Examination

E

G

193

F Figs 11.10A to G: Two-dimensional transthoracic echocardiography. (A to C) Right parasternal approach (RP). (A) Color Doppler examination shows flow signals in the pulmonary artery and descending thoracic aorta (DA); (B) The arrowhead points to a Doppler sample volume in the main pulmonary artery and the arrow shows flow signals obtained by pulsed Doppler interrogation; (C) The arrowhead points to a Doppler sample volume in the left atrium (LA), and the arrow shows flow signals obtained by pulsed Doppler interrogation; (D to G) Suprasternal approach (SS) images obtained from a different patient for comparison; (D and E) shows the aortic arch and its branches using B-mode; (D) and color Doppler examination (E); (F) shows flow signals in the DA; (G) The arrow points to flow signals acquired from the DA using pulsed wave Doppler interrogation. (AA: Ascending aorta; IA: Innominate artery; LA: Left atrium; LCC: Left common carotid artery; LIV: Left innominate vein; LPA: Left pulmonary artery; LSA: Left subclavian artery; PA: Pulmonary artery; PV: Pulmonary valve) (Movie clips 11.10A and D to F).

Fig. 11.11: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP) showing the main pulmonary artery (MPA) bifurcating into the left (LPA) and right (RPA) branches. (AO: Aorta; PV: Pulmonary valve) (Movie clip 11.11).

194

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 11.12: Two-dimensional transthoracic echocardiography. Parasternal long-axis view. (A) The upper arrowhead points to a ventricular septal aneurysm (actually formed by extension of the septal leaflet of the tricuspid valve) and the lower to an anatomical defect in the interventricular septum. In Movie clip 11.12B, the upper arrowhead points to the aneurysm and the lower to the defect in the interventricular septum. Movie clip 11.12C shows the close relationship of the septal tricuspid leaflet (left arrowhead) to the aneurysm (right arrowhead). (AO: Aorta; LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle) (Movie clips 11.12A to C).

A

Fig. 11.13: Two-dimensional transthoracic echocardiography. Right ventricular inflow view. The upper arrow points to the Doppler cursor line passing through the tricuspid valve (TV) regurgitation jet (arrowhead in Movie clip 11.13) and the lower shows a low peak velocity of 2.3 m/s obtained using continuous-wave Doppler. This indicates the absence of significant pulmonary hypertension. (LV: Left ventricle; RA: Right atrium; RV: Right ventricle) (Movie clip 11.13).

B

Figs 11.14A and B: Two-dimensional transthoracic echocardiography. Apical four-chamber view. Color Doppler examination. (A) The upper arrowhead shows the aneurysm, and the lower arrowhead points to flow signals moving into the right ventricle (RV) through a small defect in the aneurysm; (B) The upper arrow points to a Doppler cursor line passing through the defect, and the lower arrow shows a high peak velocity of 4.01 m/s obtained using continuous-wave Doppler. This high velocity also suggests the absence of significant pulmonary hypertension. The arrowhead points to the aneurysm. In Movie clip 11.14B, the upper arrowhead points to the aneurysm and the lower to the septal leaflet of the tricuspid valve. (LA: Left atrium; LV: Left ventricle; MV: Mitral valve; RA: Right atrium) (Movie clips 11.14A and B).

Chapter 11: Nonstandard Echocardiographic Examination

A

C

Fig. 11.16: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). Color Doppler examination shows a second secundum atrial septal defect (left arrowhead) close to the first one (right arrowhead) seen in Figure 11.15. (LA: Left atrium; RA: Right atrium; TV: Tricuspid valve) (Movie clip 11.16).

195

B Figs 11.15A to C: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). Color Doppler examination. (A) The arrowhead shows flow signals moving from the left atrium (LA) into the right atrium (RA) through a secundum atrial septal defect located close to the opening of the superior vena cava (SVC; Movie clip 11.15A). The parallel orientation of the shunt signals with the Doppler beam resulting from horizontal viewing of the atrial septum in this examination plane facilitates not only the detection of the defect high up in the atrial septum but also an accurate measurement of the shunt velocities and shunt volume; (B) The arrowhead points to the Doppler sample volume placement in the shunt flow signals, and the arrow points to the velocity waveforms obtained by pulsed Doppler interrogation; (C) Color M-mode examination demonstrating atrial septal defect flow signals (arrow). For comparison, Movie clip 11.15B is obtained from the subcostal approach and shows no definitive evidence of an atrial septal defect. This is most likely related to the nonhorizontal orientation of the interatrial septum (IAS) in this view. (IVC: Inferior vena cava; LV: Left ventricle; RV: Right ventricle; TV: Tricuspid valve).

Fig. 11.17: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). Color Doppler examination shows normal flow signals moving from the inferior vena cava (IVC) and superior vena cava (SVC) into the right atrium. (RV: Right ventricle; TV: Tricuspid valve) (Movie clip 11.17).

196

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 11.18: Two-dimensional transthoracic echocardiography. Right parasternal approach (RP). Fig. 11.18 and Movie clip 11.18A show an aneurysmal ascending aorta (AA) measuring 5.03 cm using this window. The arrowhead points to an area of calcification; (AV: Aortic valve) (Movie clips 11.18A and B). Movie clip 11.18B shows Color Doppler flow signals in the AA.

A

B

C

D

Figs 11.19A to D

Chapter 11: Nonstandard Echocardiographic Examination

E

F

G

H

I

J

Figs 11.19E to J

197

198

Section 2: Echocardiography/Ultrasound Examination and Training

K

L

M

N

O

P

Figs 11.19K to P

Chapter 11: Nonstandard Echocardiographic Examination

Q

199

R

Figs 11.19A to R: Live/real time, three-dimensional right parasternal transthoracic echocardiographic examination of atrial septum and superior and inferior vena cava. (A) The atrial septum (*), the entrance of superior vena cava (SVC) into the right atrium, the base of the right atrial appendage (RAA), tricuspid valve (TV), and left atrium (LA) are shown; (B) The previous image has been tilted to view the atrial septum (*) en face and to more clearly demonstrate the entrance of both the right upper (RUPV) and the right lower (RLPV) pulmonary veins into the LA; (C) The entrance of coronary sinus (CS) into the right atrium is shown. A longer segment of SVC is demonstrated; (D) The arrowhead points to the right coronary artery located in the right atrioventricular groove; (E) The arrowhead points to crista terminalis; (F) SVC viewed in the short axis; (G) RA, RV, and TV viewed from top; (H) Mitral valve (MV), left ventricle (LV), and RUVP are brought into view by further cropping; (I) Another view demonstrating SVC in the short axis, long segment of RUPV, LA appendage (LAA), MV, LV, and ascending aorta (AA); (J to M) Arrowheads demonstrate Eustachian valve at the entrance of the inferior vena cava (IVC) into RA in long-axis; (J, K) and short-axis; (L, M) views. The aortic valve (AV) is also imaged in (K); (N) shows the relationship of AV to RA and LA; (O) Color Doppler examination showing flow signals moving into RA through a secundum atrial septal (AS) defect in a different patient; (P and Q) The arrowheads (arrow in Movie clip 11.19P and Q) point to a large thrombus lodged in RA adjacent to the atrial septum (*) in another patient; (R) A large area of non-coaptation (N) is shown during tricuspid valve closure in systole in a patient with an infected tricuspid valve and torrential tricuspid regurgitation. The anterior leaflet (A) was predominantly involved and appears echogenic. (P: Posterior or inferior tricuspid leaflet; PE: Pericardial effusion; RA: Right atrium; RV: Right ventricle; S: Septal tricuspid leaflet; VS: Ventricular septum) (Movie clips 11.19 Parts 1 and 2). Source: Reproduced with permission from reference 3.

A Figs 11.20A and B

B

200

Section 2: Echocardiography/Ultrasound Examination and Training

C

D

E

F

G

H

Figs 11.20C to H

Chapter 11: Nonstandard Echocardiographic Examination

I

K

A Figs 11.21A and B

201

J

Figs 11.20A to K: Live/real time, three-dimensional right parasternal transthoracic echocardiographic examination of ascending aorta and right atrial appendage (RAA). (A and B) Normal ascending aorta (AA). The arrowhead in (B) points to the left main coronary artery; (C) Enlarged AA; (D to H) RAA and its relationship to the superior vena cava (SVC) are demonstrated. The arrowhead in (E) points to contrast signals in RAA following an intravenous bubble study. A small portion of AA is imaged between RAA and SVC. Color Doppler examination (F) shows flow signals in SVC and RAA. The arrowhead in (G) points to the right coronary artery. RAA is viewed from the top in (H); (I) The relationship of RAA to both AA and pulmonary valve (PV) is shown; (J) RAA viewed from the back; (K) shows the relationship of RAA to SVC, AA, and PA. AV, aortic valve; (LA: Left atrium; PA: Pulmonary artery; PE: Pericardial effusion; RPA: Right pulmonary artery) (Movie clips 11.20 Parts 1 and 2). Source: Reproduced with permission from reference 3.

B

202

Section 2: Echocardiography/Ultrasound Examination and Training

C

D

E

F

G

Figs 11.21A to G: Live/real time, three-dimensional right parasternal transthoracic echocardiographic examination of the pulmonary valve, the main pulmonary artery, the pulmonary artery branches, and the left atrium. (A to D) shows the pulmonary valve (PV), the main PA, the proximal RPA, the left pulmonary artery (LPA) branches, and the LA appendage (LAA); (E to G) PA viewed in the short-axis adjacent to AA, MV, LV, LA, and LAA. The descending thoracic aorta (DA) is also imaged (Movie clip 11.21). Source: Reproduced with permission from reference 3.

Chapter 11: Nonstandard Echocardiographic Examination

A

203

B

C

Figs 11.22A to C: Right parasternal approach (RPA). (A) Twodimensional transthoracic echocardiography. The coronary sinus is seen entering the right atrium (RA). The Thebesian valve is not detected; (B and C) Live/real time, three-dimensional echocardiography; (B) Coronary sinus and Thebesian valve. The arrow points to a prominent Thebesian valve; (C) The short-axis view demonstrates all three leaflets of the tricuspid valve (TV) and both leaflets of the mitral valve. (AL: Anterior leaflet; AML: Anterior mitral leaflet; IAS: Interatrial septum; PL: Posterior leaflet; PML: Posterior mitral leaflet; SL: Septal leaflet) (Movie clip 11.22A to C).

A

B

Figs 11.23A and B: Live/real time, three-dimensional transthoracic echocardiographic assessment of thrombus in the innominate veins and superior vena cava utilizing the right parasternal approaches. (A) The arrowhead shows a large thrombus protruding into the right atrium (RA) from the superior vena cava (SVC); (B) The thrombus in the SVC viewed in the short axis. (CT: Crista terminalis). Movie clips 11.23A and B. The thrombus is viewed in the RA in short axis in Movie clip 11.23B (from RA) Source: Reproduced with permission from reference 4.

204

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

E

Figs 11.24A to E: Live/real time, three-dimensional transthoracic echocardiographic visualization of the valve of foramen ovale. Right parasternal approach. (A) The arrowhead points to the atrial septum; (B and C) En face view of the atrial septum from the left atrial (LA) side shows the valve of foramen of ovale (arrowhead) in the open (B) and closed; (C) positions. In the closed position, it completely covers the foramen ovale; (D) The arrowhead points to a mobile flap of tissue at the junction of the superior vena cava (SVC) and the right atrium (RA) representing a remnant of right-sided sinus venosus valve; (E) The arrowhead shows the Eustachian valve (Movie clip 11.24). (AS: Atrial septum; IVC: Inferior vena cava). Source: Reproduced with permission from reference 5.

the aortic short-axis view, examination of other segments of the coronary arteries require the use of nonstandard planes. Keeping the transducer position in-between

those used for standard parasternal and apical views and angling it inferiorly such that the left ventricular cavity practically disappears may bring into view a long segment

Chapter 11: Nonstandard Echocardiographic Examination

A

B

C

D

205

Figs 11.25A to D: Two-dimensional transthoracic echocardiography. Right supraclavicular approach (RSC). (A) shows the left innominate vein (LIV) draining into the superior vena cava (SVC). The arrowhead points to a mildly thickened venous valve at the junction of LIV and SVC; (B) Color Doppler examination shows flow signals (red) in the innominate artery (IA) and a venous valve (arrowhead); (C) The arrow shows flow signals obtained from the IA using pulsed wave Doppler interrogation; (D) The arrowhead points to a mildly thickened venous valve (Movie clip 11.25).

Fig. 11.26: Two-dimensional transthoracic echocardiography. Left supraclavicular approach (LSC). The arrowhead points to a Doppler sample volume placed in the left common carotid artery (LCC), and the arrow shows flow signals obtained by pulsed Doppler interrogation (Movie clip 11.26).

206

A

Section 2: Echocardiography/Ultrasound Examination and Training

B

Figs 11.27A and B: Two-dimensional transthoracic echocardiography. Left supraclavicular approach (LSC). (A) The upper arrowhead shows a catheter, and the lower arrowhead points to a venous valve in the left innominate vein (LIV); (B) The arrowhead shows the venous valve in the LIV (Movie clips 11.27A and B).

A

C

B

Figs 11.28A to C: Two-dimensional transthoracic echocardiography. Right supraclavicular approach (RSC). (A) shows the left innominate vein (LIV) draining into the superior vena cava (SVC); (B) Color Doppler examination shows flow signals (blue) in the SVC; (C) The arrow points to flow signals obtained from the SVC using pulsed wave Doppler (Movie clips 11.28A and B).

Chapter 11: Nonstandard Echocardiographic Examination

A

207

B

Figs 11.29A and B: Two-dimensional transthoracic echocardiography. Left supraclavicular approach (LSC). (A) The arrow points to flow signals obtained from the left subclavian artery (LSA); (B) The arrow points to flow signals acquired from the left innominate vein (LIV) using pulsed wave Doppler.

A

B

Figs 11.30A and B: Two-dimensional transthoracic echocardiography. The right supraclavicular (RSC) approach. (A) Color Doppler examination shows flow signals (blue) in the superior vena cava (SVC) and the pulmonary artery (PA); (B) The transducer was angled to image the ascending aorta (AO) and the innominate artery (IA) from this approach. (LIV: Left innominate vein) (Movie clips 11.30A and B).

of the mid-left anterior descending coronary artery. This can be evaluated for the presence of atherosclerotic plaques and lumen stenosis in B-mode as well as using color Doppler and pulsed Doppler interrogation. Coronary artery flow reserve can be estimated by giving intravenously dipyridamole or adenosine during pulsed Doppler interrogation. An increase in peak velocity of at least four times the baseline value indicates good flow reserve and absence of significant stenosis in the relevant coronary territory whereas a lower value portends insufficient flow reserve and significant obstructive

disease. Apical and para-apical views have been used to identify and assess flow reserve in visualized segments of circumflex and posterior descending coronary arteries. Occasionally, intramyocardial coronary vessels have also been detected using the parasternal approach especially in the presence of external compression, which results in a significant increase in their flow velocity. Figures 11.34 and 11.38 and Movie clips 11.34 and 11.38 depict normal and abnormal findings acquired using two-dimensional and live/real time, three-dimensional echocardiography.6–8

208

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

E

F

Figs 11.31A to F

Chapter 11: Nonstandard Echocardiographic Examination

209

G

Figs 11.31A to G: Left-sided superior vena cava. Two-dimensional transthoracic echocardiography. (A) Parasternal long-axis view shows a dilated coronary sinus (CS); (B to D) Left supraclavicular (LSC) examination shows the left-sided superior vena cava (SVC) (L) superior to the aortic arch and the descending thoracic aorta. The arrow (in B) points to a venous valve in L; (E) Pulsed Doppler interrogation of L shows continuous flow throughout the cardiac cycle (arrow); (F) Right supraclavicular (RSC) examination. The right SVC is also present in this patient; (G) Pulsed Doppler interrogation of SVC shows continuous flow throughout the cardiac cycle. (ACH: Aortic arch; AO: Aorta; DA: Descending thoracic aorta; LA: Left atrium; LV: Left ventricle; PA: Pulmonary artery; RV: Right ventricle) (Movie clips 11.31A to D and 11.31F).

A

B

C

D

Figs 11.32A to D

210

Section 2: Echocardiography/Ultrasound Examination and Training

E

F

G

H

I

J

Figs 11.32A to J: Live/real time, three-dimensional supraclavicular transthoracic echocardiographic examination. (A) Foreshortened image demonstrates both right (RIV) and left (LIV) innominate veins joining to form the superior vena cava (SVC), which then enters into right atrium (RA). A venous valve (V) is seen at the entrance of the SVC. Another venous valve (V1) is imaged at the junction of the azygos vein (AZ) and the SVC. Inferior vena cava (IVC) is also shown entering the RA inferiorly; (B) Entrance of AZ into SVC from the posteroright aspect; (C) Another patient showing AZ entering the SVC from the left instead of from the usual posteriorright aspect. The arrowhead points to a venous valve in AZ; (D) Color Doppler examination shows flow signals in the SVC and AZ; (E) The arrowhead points to a venous valve at the junction of LIV and SVC; (F and G) The arrowhead points to a venous valve at the entrance of SVC. Note thickening of one of the leaflets of the venous valve; (H) The arrowhead points to a closed venous valve in LIV viewed from the top; (I) shows the LIV (with a venous valve, V), aortic arch (ACH), innominate artery (IA), left common carotid artery (LCA), left subclavian artery (LSA), and DA; (J) AA and ACH viewed from below. A venous valve is also imaged (Movie clip 11.32). Source: Reproduced with permission from reference 3.

Chapter 11: Nonstandard Echocardiographic Examination

A

B

C

D

E

F

Figs 11.33A to F

211

212

Section 2: Echocardiography/Ultrasound Examination and Training

G

H

I

J

Figs 11.33A to J: Live/real time, three-dimensional transthoracic echocardiographic assessment of thrombus in the innominate veins and superior vena cava (SVC) utilizing supraclavicular approaches. (A to C) Long-axis views. The arrowhead points to a large thrombus occupying the right innominate vein (RIV) and the SVC. The asterisk in (A) points to a mobile component of the thrombus. No thrombus is visualized in the left innominate vein (LIV) in (B); (D) No thrombus is noted in the inferior thyroid vein (ITV) and the RIV further upstream from the RIV–SVC junction. The arrow points to a venous valve in the ITV; (E to H) Short-axis views; (E) Short-axis view of SVC showing the thrombus surrounding the catheter (C). The arrow in (F) points to an area of lysis in the thrombus. The arrowhead in (G) points to the thrombus, which occupies about 50% of the SVC. The short-axis section was taken near SVC entrance into right atrium (RA); (H) No thrombus is visualized in the azygos vein (AZ) and LIV. V is a venous valve at the junction of innominate veins and SVC. V1 is a venous valve at the junction of AZ and SVC; (I) The arrowhead points to a portion of the thrombus extending to involve the LIV; (J) No thrombus is visualized in LIV, RIV, and SVC. (ACH: Aortic arch; LIJ: Left internal jugular vein; LSV: Left subclavian vein; R: Reverberation from the catheter). Movie clips 11.33A Parts 1 and 2, 11.33E to I.

EXAMINATION OF LEFT ATRIAL APPENDAGE Although most books do not describe the technique to examine the left atrial appendage, this structure can be easily detected in most of the patients using conventional planes. Aortic short-axis and mitral or left ventricularpulmonic planes can be utilized to find the appendage

with slight leftward and superior angulation. Minimal adjustment of the transducer is needed to examine it fully from the base to the tip. Apical views are also useful to find the appendage. One generally begins with the fourchamber view and from this position, rotation of the probe toward the five-chamber view or two-chamber view will bring the appendage into view. The appendage is enlarged and, therefore, more easily visualized in patients with

Chapter 11: Nonstandard Echocardiographic Examination

213

Fig. 11.34: Left main coronary artery. Two-dimensional transthoracic echocardiography. Parasternal short-axis view at the level of the aorta (AO) shows a small, left main coronary artery (arrow) with luminal irregularity due to nonobstructive atherosclerotic plaques. (LA: Left atrium; PV: Pulmonary valve) (Movie clip 11.34).

A

B Figs 11.35A and B

214

Section 2: Echocardiography/Ultrasound Examination and Training

C Figs 11.35A to C: (A) Transthoracic color Doppler echocardiography demonstrating coronary blood flow (left) and schematic representation (right) in the distal LAD; (B) Transthoracic color Doppler echocardiography demonstrating coronary blood flow (left) and schematic representation (right) in the PDA; (C) Transthoracic color Doppler echocardiography demonstrating coronary blood flow (left) and schematic representation (right) in the LCX. (LAD: Left anterior descending artery; LCX: Left circumflex artery; PDA: Posterior descending artery). Source: Reproduced with permission from reference 7.

A

B

Figs 11.36A and B: Live/real time, transthoracic echocardiography of coronary arteries of a 69-year-old female. (A) The pyramidal section has been cropped to show normal left main (LM) and proximal circumflex (CX) coronary arteries. The left anterior descending coronary artery is located in a different plane; (B) Another section in the same patient demonstrates a normal proximal right coronary artery (RCA). (AO: Aorta). Source: Reproduced with permission from reference 8.

atrial fibrillation and mitral stenosis, two conditions in which it is important to rule out a thrombus. In patients with good acoustic windows and absolute or relative contraindications for transesophageal echocardiography, two-dimensional echocardiography has been successfully used to assess the appendage for the presence of a clot. In these cases, live/real time, three-dimensional echocardiography can increase the confidence level in

ruling out a clot. This is because the whole of the left atrial appendage can be acquired in the three-dimensional dataset, which can then be cropped sequentially in a systematic manner. Thus, short-axis and long-axis sections of the appendage can be viewed to diagnose or rule out the presence of a clot. Individual lobes of the appendage may also be examined using this technique. We have also had patients with atrial fibrillation in whom a clot was

Chapter 11: Nonstandard Echocardiographic Examination

215

Fig. 11.37: Live/real time, three-dimensional transthoracic echocardiography of coronary arteries of a 26-year-old male. The arrowheads demonstrate the midportion of the left anterior descending coronary artery (LAD) located in the anterior interventricular groove. (LV: Left ventricle; RV: Right ventricle). Source: Reproduced with permission from reference 8.

A

B

C

D

Figs 11.38A to D

216

Section 2: Echocardiography/Ultrasound Examination and Training

E

F

G

H

Figs 11.38A to H: Live/real time, three-dimensional transthoracic echocardiography of coronary arteries of a 30-year-old male, status postorthotopic cardiac transplantation. (A) The arrowhead points to severe stenosis at the origin of the first obtuse marginal branch of CX. Movie clip 11.38 shows the plaque producing the stenosis to be somewhat mobile indicating its soft consistency and probable propensity to rupture; (B) The image in (A) has been cropped and rotated to provide an en face view of the stenosis (arrowhead); (C) The arrowhead shows almost total stenosis of the proximal RCA; (D) The pyramidal section has been cropped to delineate a longer segment of CX, which shows no significant stenosis. M represents another marginal branch of CX with a normal lumen; (E) Three-dimensional color Doppler flow imaging shows flow signals in the visualized coronary arteries. Note that the baseline on the color Doppler bar has been shifted to provide an estimate of coronary flow velocities; (F) Three-dimensional color Doppler flow imaging demonstrates a segment of LAD adjacent to the ventricular septum (VS). This segment was not visualized by B-mode, threedimensional imaging; (G and H) The arrowheads point to multiple septal perforators imaged in the short-axis within the VS. Note also the presence of an intramural coronary artery branch (arrow) in the left ventricular posterior wall (PW) in (G). (AO: Aorta; D1: First diagonal branch of LAD; D2: Second diagonal branch of LAD; LM: Left main; RV: Right ventricle; RVOT: Right ventricular outflow tract). Source: Reproduced with permission from reference 8. (Movie clip 11.38).

diagnosed by transesophageal echocardiography and the patient placed on anticoagulant therapy for several weeks without any change in its size. Subsequently, combined two- and three-dimensional echocardiography showed the alleged clot to be a prominent pectinate muscle viewed in the short axis. No clot was found, and the patient underwent successful ablation. Figures 11.39 to 11.43 and Movie clips 11.39 to 11.43 demonstrate normal and abnormal findings acquired using two-dimensional and live/real time, three-dimensional echocardiography.1,9

EXAMINATION FROM THE BACK The presence of a large left or right pleural effusion opens up an acoustic window from the back, and the heart can be examined by placing the transducer in the posterior intercostal spaces. This is best accomplished by examining the patient in the sitting position. Four-chamber views of the heart are easily obtained when the effusion is large. A distinct advantage of this approach is assessment of a large segment of the descending thoracic aorta, which is

Chapter 11: Nonstandard Echocardiographic Examination

217

Fig. 11.39: Left atrial appendage (LAA). Two-dimensional transthoracic echocardiography. LAA is visualized using the apical fourchamber view and rotating the probe toward the five-chamber view. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle (Movie clip 11.39).

A

B

C

D

Figs 11.40A to D

218

Section 2: Echocardiography/Ultrasound Examination and Training

E

A

Figs 11.40A to E: Left ventricular (A) and aortic (B) short-axis views. The arrowheads show a clot in the left atrial appendage; (C and D) Live/real time, three-dimensional study showing the same clot (arrowheads). Cropping of the clot shows no echo lucency within it consistent with the absence of lysis. This is most likely because the clot is fresh and the natural anticoagulant mechanisms present in the blood; (E) have not yet had enough time to act on it. (LA: Left atrium; MPA: Main pulmonary artery; MV: Mitral valve) (Movie clip 11.40). Source: Reproduced with permission from reference 9.

B

Figs 11.41A and B: Live/real time, three-dimensional transthoracic echocardiography. (A) The left atrial appendage (LAA) is visualized using the apical view in a patient with mitral prosthesis; (B) Utilizing the multiplanar mode, several short-axis sections of the appendage are taken (Movie clip 11.41B Parts 1 and 2) and show no evidence of thrombus. This technique is useful to systematically and sequentially examine the appendage in a comprehensive manner and increase the confidence level in ruling out a clot. (LA: Left atrium; LV: Left ventricle; R: Reverberation; RA: Right atrium; RV: Right ventricle) (Movie clips 11.41A, B Parts 1 and 2).

difficult to visualize using standard transthoracic windows. This approach has also been used in patients with pleural effusion undergoing percutaneous interventions in the cardiac catheterization laboratory since, unlike the

anterior transthoracic approach, it does not cause any significant interference with the procedure. The main utility of this window is in making a confident diagnosis of right- or left-sided pleural effusion and distinguishing

Chapter 11: Nonstandard Echocardiographic Examination

A

219

B

Figs 11.42A and B: Live/real time, three-dimensional transthoracic echocardiography. (A) The arrow points to the left atrial appendage (LAA) viewed in the aortic short-axis view. Note that the tip (apex) of the appendage is narrow and elongated and is free of clot; (B) The arrows point to three lobes of the LAA. (AV: Aortic valve; LA: Left atrium; RA: Right atrium) (Movie clip 11.42). Source: Reproduced with permission from reference 9.

A

B

C

D

Figs 11.43A to D: (A) Two-dimensional transesophageal echocardiogram. The arrowhead points to an echo-dense mass within the left atrial appendage (LAA) consistent with a thrombus; (B to D) Three-dimensional transthoracic echocardiogram. Sequential cropping shows the echo- dense mass to be a prominent pectinate muscle seen in the short axis (top arrowhead) and not a thrombus in the same patient. A second, smaller pectinate muscle is also seen (bottom arrowhead). (AV: Aortic valve; LA: Left atrium; LUPV: Left upper pulmonary vein; LV: Left ventricle)(Movie clip 11.43). Source: Reproduced with permission from reference 9.

220

Section 2: Echocardiography/Ultrasound Examination and Training

Subcostal examination is a part of standard echocardiographic examination protocol. However, often scant attention is paid to examining the abdominal aorta. This is an important vessel that can be involved in aneurysm

formation or dissection that can go undetected clinically because often the patient may not present with any symptoms. Therefore, it is useful to routinely attempt to image the abdominal aorta in all patients undergoing echocardiography. Other abnormal findings such as gall stones, which can be a causative factor in patients presenting with chest pain, should also be reported. Figures 11.46 and 11.47 and Movie clips 11.46 and 11.47 depict normal and abnormal findings acquired using two-dimensional and live/real time, three-dimensional echocardiography.1,10

A

B

C

D

it from other large fluid collections such as ascites and coexisting pericardial effusion. Figures 11.44 and 11.45 and Movie clips 11.44 and 11.45 demonstrate normal and abnormal findings acquired using two-dimensional and live/real time, three-dimensional echocardiography.

ABDOMINAL EXAMINATION

Figs 11.44A to D

Chapter 11: Nonstandard Echocardiographic Examination

E

221

F

Figs 11.44A to F: Two-dimensional transthoracic echocardiographic examination from the back in a 77-year-old patient with lymphoma and bilateral pleural effusion. (A) Apical four-chamber view showing left pleural effusion (LPL) and pericardial effusion (PE); (B) Examination from left back (LB). The arrow points to a portion of the collapsed lung floating in LPL; (C) Examination of heart from LB. The arrow shows a part of the collapsed lung. Both the left (LV) and the right (RV) ventricles as well as the descending thoracic aorta (DA) are visualized through the pleural effusion; (D) Color Doppler examination showing flow signals (blue) in the DA imaged from LB. The arrow points to a portion of the collapsed lung; (E) The lower arrow points to flow signals in the DA (upper arrow) acquired using pulsed wave Doppler interrogation; (F) Examination from right back (RB). The arrow shows an area of increased echo density probably caused by bleeding into the right pleural effusion (RPL). (L: Liver; LA: Left atrium; RA: Right atrium; S: Spleen) (Movie clips 11.44A to D and 11.44F).

A

B

Figs 11.45A and B: Two-dimensional transthoracic echocardiography. Examination from the left back (LB). Large left pleural effusion. (A) All the four cardiac chambers are surrounded by pleural effusion (PLE); (B) Parasternal long-axis view in the same patient shows PLE anteriorly and posteriorly. (AO: Aorta; LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle) (Movie clips 11.45A and B).

222

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 11.46A to D: Two-dimensional subcostal echocardiography. (A) shows a long-axis view of the abdominal aorta (AB). It is enlarged measuring 3.95 cm and demonstrates a dissection flap with perfusing (PL) and nonperfusing lumens (NPL); (B and C) Short-axis view of the abdominal aorta using B-mode and color Doppler examination, respectively. The arrowhead points to an atherosclerotic plaque within the aorta. The NPL is clotted; (D) The upper arrow points to a Doppler cursor line passing through AB, and the lower arrow shows pulsatile flow signals obtained from the AB using pulsed wave Doppler (Movie clips 11.46A to C).

A Figs 11.47A and B

B

Chapter 11: Nonstandard Echocardiographic Examination

223

Figs 11.47A to C: Two-dimensional transthoracic echocardiography. Subcostal approach. (A) shows abdominal aorta (AB) in the short axis using B-mode (left panel) and color Doppler examination (right panel); (B) The arrowhead in the left panel points to an atherosclerotic plaque seen in the AB viewed in the long axis. The right panel shows flow signals in the AB using color Doppler examination; (C) The arrowhead points to a sample volume in the AB, and the arrow shows flow signals obtained using pulsed wave Doppler interrogation (Movie clips 11.47A and B).

C

REFERENCES 1. Cooper JW, Aggarwal KK, Fan P, et al. Echocardiographic examination technique: a new practical approach. In: Nanda NC, editor. Textbook of Color Doppler Echocardiography. 2nd ed. Philadelphia, PA: Lea & Febiger; 1989: 99–115. 2. Nanda NC, Hsiung MC, Miller AP, et al. editors. How to do a 3D echocardiogram: examination protocol and normal anatomy. In: Live/Real Time 3D Echocardiography. Oxford, England: Blackwell; 2010: 23–54. 3. Patel V, Nanda NC, Upendram S, et al. Live three-dimensional right parasternal and supraclavicular transthoracic echocardiographic examination. Echocardiography. 2005; 22(4):349–60. 4. Upendram S, Nanda NC, Vengala S, et al. Live threedimensional transthoracic echocardiographic assessment of thrombus in the innominate veins and superior vena cava utilizing right parasternal and supraclavicular approaches. Echocardiography. 2005;22(5):445–9. 5. Panwar SR, Perrien JL, Nanda NC, et al. Real time/threedimensional transthoracic echocardiographic visualization

6.

7.

8.

9.

10.

of the valve of foramen ovale. Echocardiography. 2007; 24(10):1105–7. Nanda NC, Hsiung MC, Miller AP, et al. (Eds). Ischemic heart disease. In: Live/Real Time 3D Echocardiography. Oxford, England: Blackwell; 2010: 128–36. Murata E, Hozumi T, Matsumura Y, et al. Coronary flow velocity reserve measurement in three major coronary arteries using transthoracic Doppler echocardiography. Echocardiography. 2006;23(4):279–86. Vengala S, Nanda NC, Agrawal G, et al. Live threedimensional transthoracic echocardiographic assessment of coronary arteries. Echocardiography. 2003;20(8):751–4. Karakus G, Kodali V, Inamdar V, et al. Comparative assessment of left atrial appendage by transesophageal and combined two- and three-dimensional transthoracic echocardiography. Echocardiography. 2008;25(8):918–24. Daly DD Jr, El-Shurafa H, Nanda NC, et al. Does the routine echocardiographic exam have a role in the detection and evaluation of cholelithiasis and gallbladder wall thickening? Echocardiography. 2012;29(8):991–6.

CHAPTER 12 Technique and Applications of Continuous Transthoracic Cardiac Imaging Premindra PAN Chandraratna, Dilbahar S Mohar, Peter Sidarous

Snapshot  Feasibility of ConƟnuous Cardiac Imaging

INTRODUCTION The use of echocardiography has become an indispensible adjunctive clinical tool in the practice of modern cardiovascular medicine, as it allows for noninvasive, highly accurate, and rapid assessment of cardiac structure and function. However, limitations remain as echocardiographic data reflects only cross-sectional information at a fixed point in time, in what is often a highly dynamic functional environment. Furthermore, accuracy and quality of image acquisition is greatly dependent on the technician skill level and thus, data may have great interobserver variability. Although, serial measurements can be done, this is laborious, and “round-the-clock” availability of sonographers is limited and often not feasible. Sudden and rapid changes in hemodynamic status mean finding the right operator and setting up the ultrasound machine; often times, this may lead to significant delay in some clinical situations. Further, handheld transducers are not conducive to continuous intraoperative monitoring.

FEASIBILITY OF CONTINUOUS CARDIAC IMAGING To circumvent the limitations of current handheld transducers, Chandraratna and colleagues have developed and

 LimitaƟons

described the feasibility of a low-profile hemispherical ultrasound transducer (CONTISCAN; Fig. 12.1), which can be attached to the chest wall using an adhesive ring.1,1a The 2.5-MHz hemispherical transducer (CONTISCAN) was mounted on an external housing to permit steering in 360°. The external housing was attached to the chest

Fig. 12.1: The CONTISCAN transducer attached to the chest wall of a patient to obtain a parasternal short-axis view. Source: Reproduced with permission from Ref. 1.

Chapter 12: Technique and Applications of Continuous Transthoracic Cardiac Imaging

225

wall using an adhesive ring. The transducer was placed in the third or fourth interspace at the left sternal border to permit imaging of the left ventricle (LV) in its short axis and attached to the chest wall. The transducer was then attached to an ultrasound machine. Ten normal subjects and 20 patients with previous myocardial infarction were studied. The following maneuvers were performed at the beginning of the study: 1. The patient was rotated from the supine position (0°) in 20° increments to the left lateral decubitus position (90°). The echocardiogram was displayed continuously and was recorded on videotape (parasternal short-axis view) at 0°, 20°, 40°, 60°, 80°, and 90° (Fig. 12.2/Movie clip 12.1). 2. The patient was returned to the supine position and an echocardiogram was obtained. The patient was then seated up 20°, 40°, 60°, 80°, and 90° by using the controls on the bed (Fig. 12.3). 3. The patient was then returned to the supine position and the echocardiogram was displayed continuously on the monitor.

The echocardiogram was recorded every 15 minutes for a period of 4 hours. All segments of the LV were visualized in the supine position and during lateral rotation (0–90°). Thus, body position did not substantially affect the image. All segments of the LV were visualized during sitting up (0– 90°), and all segments were visualized during the 4 hours of imaging. The patients were able to move around without distortion of the image. The CONTISCAN transducer permitted continuous imaging of LV wall motion. Body position did not affect interpretation of wall motion. No additional ultrasound gel was required. The use of the CONTISCAN transducer has been described in a variety of clinical scenarios: • Evaluation of acute coronary syndromes • Exercise echocardiography • Ambulatory echocardiography • Noninvasive hemodynamic monitoring • Monitoring of pericardiocentesis • Monitoring of balloon valvuloplasty • Monitoring of cannulation of the coronary sinus • Intraoperative monitoring (noncardiac surgery)

Fig. 12.2: Echocardiograms of the short axis of the left ventricle in the supine position (0°) and during lateral rotation from (0°–90°) in 20° increments. Source: Reproduced with permission from Ref. 1.

Fig. 12.3: Echocardiograms of the short axis of the left ventricle in the supine position (0°) and when the patient was seated up (0°–90°) in 20° increments. Source: Reproduced with permission from Ref. 1.

226

Section 2: Echocardiography/Ultrasound Examination and Training

Evaluation of Acute Coronary Syndromes Approximately 5 million patients present to the emergency room annually with chest pain and about 2 million patients are admitted with acute coronary syndromes (ACSs).2,3 The diagnosis of ST segment elevation ACS is made on the basis of typical anginal chest pain, electrocardiographic (ECG) changes, elevated serum enzymes, and the presence of wall motion abnormalities (WMAs) on the echocardiogram.4 However, in patients with non-ST segment elevation ACS, the ECG may not show acute changes suggestive of myocardial ischemia in a substantial proportion of these patients.5–7 The value of ECG changes is further diminished in subsets with baseline ECG abnormalities, and in patients with left ventricular hypertrophy, left bundle branch block, pre-excitation syndrome, and women.8 Furthermore, although serum troponins are sensitive and specific for acute myocardial infarction, serial measurements are required, as cardiac enzymes may only be elevated hours after initial presentation when myocardial necrosis has occurred.9 Additionally, a single echocardiogram performed on admission may be nondiagnostic in many patients with non-ST segment elevation ACS. An echocardiogram performed in a patient who is free of chest pain may not show regional WMAs (RWMAs). Therefore, in the setting of typical chest pain with indeterminate ECG findings and equivocal biomarkers, the detection of WMAs on the echocardiogram may be of diagnostic value. The efficacy of the CONTISCAN transducer in the evaluation of acute chest pain syndromes has been evaluated, as 70 patients with intermediate to high probability of coronary artery disease (CAD) who presented with typical anginal chest pain and no evidence of ST segment elevation on the ECG were studied.10 The transducer was placed at the left sternal border to image the left ventricular short-axis view and recorded on video tape at baseline, every 15 minutes and during and after episodes of chest pain. Two ECG leads were continuously monitored and during episodes of chest pain, 12 lead ECGs were performed. The presence of CAD was confirmed by coronary arteriography or nuclear or echocardiographic stress testing. Twenty-four patients had RWMAs on their initial echo, which were unchanged during the period of monitoring. All had evidence of CAD. Twenty-eight patients had transient RWMA. All had evidence of CAD. Eighteen patients had normal wall motion throughout the monitoring period, 14 of these had no evidence of CAD, and four had evidence of

CAD. These four patients did not have chest pain during monitoring. The sensitivity, specificity, and accuracy of echocardiographic monitoring for diagnosing non-ST elevation myocardial infarction was 88%, 100%, and 91% respectively. The sensitivity, specificity, and accuracy of the ECG for diagnosis of CAD were 31%, 100%, and 52%, respectively. Echocardiography was superior to ECG (P < 0.001). A representative example of a WMA is shown in Movie clip 12.2. This patient had a history of chest pain prior to admission; however, on admission to the emergency room, he had no anginal chest pain, no acute ECG changes, normal wall motion, and normal troponins. He developed typical anginal chest pain during monitoring. The ECG and troponins were normal. The echocardiogram showed anterolateral hypokinesis. The administration of nitroglycerin relieved chest pain and cardiac wall motion became normal. Half an hour later, he developed chest pain and akinesis of the anterolateral wall. There were no acute ECG changes and serum troponin done at the time was elevated (troponin negative on admission). Coronary angiography showed 90% stenosis of the left anterior descending artery, 50% stenosis of the circumflex and right coronary artery. This case illustrates dynamic left ventricular WMA in a patient with non-ST segment elevation ACS. Further, collective data indicated that continuous cardiac imaging is superior to ECG monitoring for the diagnosis of CAD in patients presenting with acute nonST segment elevation chest pain syndromes. Further, the use of the CONTISCAN transducer and associated techniques could be a useful adjunct to ECG monitoring for myocardial ischemia in the acute care setting. Because of increasingly limited resources and growing patient load, more accurate and efficient risk stratification modalities are needed to allocate appropriate resources. Continuous echocardiography performed using the CONTISCAN transducer is a useful adjunct in the evaluation of non-ST elevation myocardial infarction (NSTEMI) ACS. In addition to ease of availability, cost advantages, and low inherent risk due to its noninvasive nature, diagnostic accuracy of continuous echocardiography is superior to current and comparable models of continuous monitoring.

Exercise Echocardiography The use of stress echocardiography has progressed dramatically since Wann et al. first demonstrated the feasibility of exercise echocardiography in the diagnosis

Chapter 12: Technique and Applications of Continuous Transthoracic Cardiac Imaging

of CAD in a 1979 landmark article.11 Echocardiographic imaging using a handheld transducer in conjunction with treadmill exercise testing is now commonly used for the diagnosis of CAD. Historically, based on meta-analysis, the sensitivity and specificity of stress echocardiography in the detection of CAD have been reported to be approximately 80% to 90%.12,13 As a diagnostic method, stress echocardiography is superior to stress electrocardiography in detecting CAD.14,15 However, difficulties in acquiring images during exercise is a limitation of the technique.11 Also, during the time it takes for the patient to lie down for imaging, heart rate decreases and WMAs may resolve. Thus, the sensitivity of the test decreases. Because of limitations of handheld ultrasound transducers, the “hands-free” CONTISCAN low-profile ultrasound transducer may be of value in the detection of WMAs caused by CAD. The CONTISCAN transducer permits continuous imaging of cardiac structures and Doppler flow velocity profiles during treadmill exercise.16 This feasibility study was performed in 10 normal male subjects aged 28 to 36 years. The hands-free system was attached to the chest wall using an adhesive ring. Ultrasound gel was applied to the surface of the transducer prior to attachment. The transducer was placed in the third or fourth intercostal space at the left sternal border to permit imaging of the left ventricle in its short axis. The transducer was in a fixed position and not moved during exercise. The transducer was interfaced with a commercially available ultrasound machine, Hewlett

227

Packard SONOS 5500 (Andover, MA). The left ventricle was imaged at rest with the subjects standing. The subjects then performed treadmill exercise according to a standard Bruce protocol (Fig. 12.4). Exercise was discontinued when the target heart rate was reached or when the patient developed chest pain. The echocardiogram was continuously displayed on a monitor and recorded on videotape for a minute every 3 minutes. The results are summarized in Table 12.1. The resting heart rate was 87 ± 15/min and the blood pressure was 114 ± 11 mm Hg systolic and 79 ± 6 mm Hg diastolic. The peak heart rate was 176 ± 19/min and peak blood pressure was 131 ± 13 mm Hg systolic and 83 ± 5 mm Hg diastolic. Excellent delineation of all segments of the left ventricular short axis was seen at rest in all subjects (Figs 12.5A and B; Movie clip 12.3). Increase in left ventricular wall motion at peak exercise was noted in all subjects. Adjustment of the transducer was not required in any of the subjects. None of the subjects experienced any discomfort. With increased exercise, there was an increase in respiratory rate which intermittently interfered with imaging, due to lung artifact (Movie clip 12.4). To circumvent difficulty in interpretation of wall motion due to rapid breathing during exercise, slow playback was used to enable the detection of end-diastolic and end-systolic frames (Figs 12.6A and B). The video was analyzed and a single beat, devoid of lung artifact, was isolated, replicated three times, and played as a loop (Movie clip 12.5). The CONTISCAN transducer permitted hands-free continuous imaging of left ventricular wall motion during treadmill exercise. The two major limitations of exercise echocardiography, that is, the movement of the hand and transducer during exercise and respiratory interference due to lung artifact, were circumvented using techniques described earlier.

Ambulatory Echocardiography Stress echocardiography is a versatile diagnostic tool used in the detection of obstructive CAD.17 An ischemic stress Table 12.1: Heart Rate and Systolic and Diastolic Blood Pressure at Rest and Peak Exercise

Fig. 12.4: The CONTISCAN transducer attached to the chest wall while the patient is standing. Arrow points to the transducer. Source: Reproduced with permission from Ref. 16.

Rest

Peak Exercise

Heart rate

87 ± 15/min

176 ± 19/min

Systolic BP

114 ± 11 mm Hg

131 ± 13 mm Hg

Diastolic BP

79 ± 6 mm Hg

83 ± 5 mm Hg

Source: Reproduced with Permission from Ref. 16

228

Section 2: Echocardiography/Ultrasound Examination and Training

Rest

A

B

Figs 12.5A and B: Short-axis view of the left ventricle at rest. (A) End diastole; (B) End systole. Source: Reproduced with permission from Ref. 16.

Exercise

A

B

Figs 12.6A and B: Short-axis view of the left ventricle during peak exercise. (A) End diastole; (B) End systole. Source: Reproduced with permission from Ref. 16.

response depicted on echocardiography may include new or worsening RWMAs, drop in ejection fraction, and delayed contraction. Stress echocardiography offers decided benefits over traditional ECG stress testing in establishing likely territories of obstructive coronary vasculature. Regional wall motion changes generally precede the development of ST segment changes and chest pain. Echocardiographic changes are more useful in the diagnosis of CAD when there are baseline ECG abnormalities.18

The CONTISCAN transducer has been studied as an ambulatory echocardigraphic modality for the detection of transient WMAs due to myocardial ischemia induced by walking.19 Two groups were studied. Group 1 consisted of 10 males (mean age 34 years) who had no symptoms of angina. Group 2 consisted of eight selected patients (mean 61 years) with angina and angiographic evidence of CAD. The CONTISCAN external housing was attached to the chest wall using an adhesive patch. The transducer was

Chapter 12: Technique and Applications of Continuous Transthoracic Cardiac Imaging

229

Table 12.2: WMA on Ambulatory Echocardiography versus Coronary Angiography in Group 2 Patients

No. of Patients

WMA on Echo

Coronary Angiography

1

Anterior septum

LM 50%, LAD 85%, Cx 60%

2

Anterior septum + anteriolateral

LM 60%, LAD 70%, Cx 75%, RCA 80%

3

Anterior septum + anteriolateral

LAD 90%, Cx 50%, RCA 50%

4

Anterior septum + anteriolateral

LM 75%, LAD 85%, RCA 100%

5

Anterior septum + anteriolateral

LAD 100%, OM 75%

6

Anteriolateral + posteriolateral

LAD 70%, Cx 80%, RCA 95%

7

Anteriolateral + posteriolateral

LAD 80%, Cx 90%, RCA 75%

8

Posteriolateral

LAD 60%, OM 70%, RCA 80%

(Cx: Circumflex coronary artery; LAD: Left anterior descending coronary artery; OM: Obtuse marginal; RCA: Right coronary artery; WMAs: Wall motion abnormalities; LM: Left main coronary artery) Source: Reproduced with permission from Ref. 19

placed in the third or fourth intercostal space at the left sternal border to permit imaging of the left ventricle (LV) in its short axis and attached to the chest wall. The transducer was interfaced with an Acuson Cypress echocardiography system, which was placed on a mobile cart. To permit portability, the echocardiography system was powered by a capacitor (UPS device). The subjects were asked to walk along the corridor as fast as possible for 10 minutes or until the onset of symptoms while pushing the cart. The short axis of the LV was displayed on a monitor and recorded on optical disks. The heart rate, systolic blood pressure (SBP), and double product of Group 1 at rest were 77 ± 3 beats/ min, 119 ± 13 mm Hg, and 9,150 ± 868, respectively, and increased to 106 ± 8 beats/min, 129 ± 15 mm Hg, and 1,3793 ± 2,176 with walking. The baseline heart rate, SBP, and double product were 71 ± 12 beats/min, 130 ± 14 mm Hg, and 8,555 ± 1,928 in Group 2 and increased to 94 ± 14 beats/min, 135 ± 20 mm Hg, and 12,480 ± 3,830 with walking. In Group 1, all patients had normal wall motion at rest and during walking. Patients in Group 2 had normal wall motion at rest and new WMAs were noted during walking. Echocardiographic abnormalities correlated with the angiographic findings (Table 12.2). The WMAs resolved shortly after discontinuation of walking. Further, it is emphasized that in the current study we imaged only the LV short axis. Therefore, it is conceivable that WMAs in other segments may not have been detected. Movie clip 12.6 shows normal wall motion at rest and increased wall motion during walking. An example of WMAs appearing during walking is shown in Movie clip 12.7. Normal wall motion was noted at baseline. After 1 minute of walking, akinesis of the anterior

septum was noted. The patient was asymptomatic at the time. Thus, this represents silent ischemia. At 2 minutes, the patient was symptomatic and there was akinesis of the anterior septum and anterolateral wall with dilatation of the left ventricle. These changes were indicative of myocardial ischemia in the left anterior descending coronary artery (LAD) territory. The WMAs resolved shortly after discontinuation of walking. The coronary angiogram showed a 90% stenosis of the proximal LAD. The CONTISCAN transducer produced satisfactory images of the left ventricular short axis with good endocardial definition during walking. There was no deterioration of the image (compared to baseline) during walking. Further addition of ultrasound gel or adjustment of the transducer was not required. No local discomfort from the transducer was observed. Ambulatory echocardiography using the CONTISCAN transducer permitted the detection of transient WMAs in patients with CAD. This technique could be potentially useful in evaluating selected patients for myocardial ischemia.

Noninvasive Hemodynamic Monitoring Pulmonary artery (PA) catheterization is performed to assess hemodynamic status and tailor therapy. The possible adverse consequences of PA catheterization include ventricular arrhythmias, bleeding, local infection, infective endocarditis, and pneumothorax. Recent reports have indicated that patients undergoing PA catheterization have a higher mortality than patients with similar disease severity who do not have this procedure.20–23 These observations have raised concerns that PA catheterization

230

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 12.7: Spectral Doppler flow velocity signal of pulmonic regurgitation. Arrow points to end-diastolic velocity. Source: Reproduced with permission from Ref. 28.

Fig. 12.8: Relationship between pulmonary artery (PA) end-diastolic pressure (PAD) by Doppler ultrasound versus PA catheterization. Solid star refers to overlap of four values, open star depicts overlap of three values, and open circle overlap of two values. SEE: Standard error of the estimate. Source: Reproduced with permission from Ref. 28.

may increase patient morbidity and mortality. Therefore, a noninvasive method for obtaining hemodynamic data is desirable. Several studies have indicated that PA diastolic pressure (PADP) and cardiac output (CO) can be noninvasively estimated by Doppler ultrasound signals from the PA, from which CO and PADP can be derived.24–27 The feasibility for continuous recording of PA diastolic pressure and cardiac output using the CONTISCAN transducer has been demonstrated.28 Fifty patients in the coronary care unit who had PA catheters had Doppler ultrasound studies. The 2.5-MHz hemispherical transducer was placed at the left sternal border to permit imaging of the pulmonic valve and was attached to a commercial ultrasound machine. The PA was imaged and its diameter measured. The pulmonary flow velocity signal was recorded and the time velocity integral obtained. The cardiac output (CO) was calculated as: CO = time velocity integral of the PA systolic flow velocity signal × π diameter2 divided by 4 × heart rate. The pulmonary regurgitation signal was then recorded and the end-diastolic velocity of the regurgitant signal was measured (Fig. 12.7). Right atrial pressure was assessed from the jugular venous pressure or from the size and pulsatility of the inferior vena cava. The PADP was calculated as: PADP = 4 end-diastolic velocity of the regurgitant signal2 + right atrial pressure. The CO, PADP, and pulmonary wedge pressure were recorded from the PA catheter immediately after the ultrasound studies. Serial data were obtained every half hour or 1 hour up to a maximum of 5 hours. Adequate Doppler signals were obtained in 43 patients.

There was good correlation between the PA diastolic pressure (PADP) by Doppler versus PA catheter (r = 0.90, standard error of the estimate = 3.3 mm Hg; Fig. 12.8); PADP by Doppler versus PA wedge pressure (r = 0.88, standard error of the estimate = 3.7 mm Hg; Fig. 12.9); and CO by Doppler versus PA catheter (r = 0.92, standard error of the estimate = 0.7 L/min; Fig. 12.10). It is conceivable that hemodynamic data obtained by this transducer could be used in place of PA catheterization to tailor therapy of patients with congestive heart failure and other forms of hemodynamic instability. There are other potential indications for noninvasive hemodynamic monitoring. Patients with borderline indications for PA catheterization, such as those who have unexplained tachycardia or basal rales (Killip class 2), may have unsuspected significant elevations of left ventricular filling pressures which could be detected and treated using this transducer. Patients who have PA catheterization could potentially have early discontinuation of the catheter after 1 day and subsequent hemodynamic monitoring could be performed with the CONTISCAN transducer. This could permit early transfer out of the intensive care unit (with continuation of hemodynamic monitoring in the step-down unit) and result in substantial cost savings.

Monitoring of Pericardiocentesis Pericardiocentesis may be associated with serious sequelae, such as cardiac puncture and cardiac tamponade. Echocardiographic monitoring of pericardiocentesis by a handheld transducer has been demonstrated to be more

Chapter 12: Technique and Applications of Continuous Transthoracic Cardiac Imaging

Fig. 12.9: Relationship between pulmonary artery (PA) end-diastolic pressure (PAD) by Doppler ultrasound versus PA wedge pressure (PAW). Open star depicts overlap of three values, and open circle overlap of two values. (SEE: Standard error of the estimate). Source: Reproduced with permission from Ref. 28.

sensitive than electrocardiographic monitoring for detection of cardiac perforation by the exploring needle.29,30 This echocardiographic technique is particularly helpful when there is frank blood in the pericardial sac. The technique currently used for echocardiographic monitoring of pericardiocentesis requires the presence of an ultrasonographer, which adds to the expense and inconvenience of the procedure. With the use of the CONTISCAN transducer, a single operator can perform pericardiocentesis. This is particularly helpful during nights and weekends when a sonographer may not be present in the hospital. The CONTISCAN transducer has demonstrated feasibility and utility of continuous hands-free monitoring of pericardiocentesis.31 Nine patients with large pericardial effusions were studied. Prior to pericardiocentesis, the CONTISCAN transducer was placed at the cardiac apex to obtain an apical four-chamber view. The 2.5-MHz hemispherical transducer was attached to the apical chest wall using an adhesive patch (Fig. 12.11). Ultrasound gel was applied to the surface of the transducer prior to attachment. The transducer was interfaced with a commercially available ultrasound machine. Prior to pericardiocentesis, a pulsed Doppler sample volume was placed at the tips of the mitral leaflets to ascertain the presence of mitral flow velocity paradoxus. The echocardiogram of the apical four-chamber view was continuously recorded during the pericardiocentesis. The needle was advanced from a subcostal position until fluid was withdrawn. Fifty milliliters of fluid was aspirated and sent for cytology, culture, and so on. Five milliliters of

231

Fig. 12.10: Relationship between cardiac output (CO) by Doppler ultrasound versus pulmonary artery (PA) catheterization. (SEE: Standard error of the estimate). Source: Reproduced with permission from Ref. 28.

Fig. 12.11: CONTISCAN transducer attached to the chest wall of a subject to obtain an apical four-chamber view. Source: Reproduced with permission from Ref. 31.

agitated saline was injected through the pericardiocentesis needle. A cloud of echoes indicated needle position. The Doppler mitral inflow velocity signal was recorded after completion of pericardiocentesis. Successful pericardiocentesis was performed in eight of nine patients. Saline injection through the pericardiocentesis needle produced a contrast effect in the pericardial sac indicating proper needle position. Little or no pericardial fluid was noted at the end of the pericardiocentesis. Mitral flow velocity paradoxus was noted in five patients. The mitral flow velocity paradoxus normalized after pericardiocentesis in four patients.

232

Section 2: Echocardiography/Ultrasound Examination and Training

Complications associated with pericardiocentesis were noted in two patients. In the first patient, saline injection produced a contrast effect in the left ventricle indicating left ventricular puncture (Figs 12.12 to 12.14). The needle was gradually withdrawn until a contrast effect was noted in the pericardial sac, indicating proper needle position (Fig. 12.15). A total of 1,100 mL was removed without complications. The second patient had an initially successful pericardiocentesis with a contrast effect in the pericardial sac and a clear aspirate. Shortly after that a blood-stained aspirate was noted, and

granular echoes suggestive of pericardial clot appeared in the pericardial sac. The patient’s heart rate increased and the blood pressure decreased by 10 mm Hg. Because further aspiration of fluid was not possible, the patient was referred for surgical evacuation of pericardial fluid. Intrapericardial clot was noted and evacuated at surgery. However, no active bleeding site was noted. The patient made an uneventful recovery. The CONTISCAN transducer provided excellent definition of the pericardial sac and no extra ultrasound gel was required in these patients. No adjustment of the

Fig. 12.12: Apical four-chamber view depicting a large pericardial effusion (PE). Note multiple linear echoes within the pericardial sac and that the distribution of fluid is small over some areas of the right ventricle. Source: Reproduced with permission from Ref. 31.

Fig. 12.13: Ultrasound image that illustrates the pericardiocentesis needle (arrow) within the left ventricle. Source: Reproduced with permission from Ref. 31.

Fig. 12.14: Image obtained after agitated saline injection through the pericardiocentesis needle illustrates a contrast effect in the left ventricle (LV). Source: Reproduced with permission from Ref. 31.

Fig. 12.15: Image obtained after repositioning of the needle reveals a contrast effect in the pericardial sac (C). Source: Reproduced with permission from Ref. 31.

Chapter 12: Technique and Applications of Continuous Transthoracic Cardiac Imaging

233

transducer was required in any of the patients. None of the patients complained of discomfort at the site or attachment of the transducer. Continuous hands-free transthoracic echocardiographic monitoring may be particularly valuable in situations where rapid reaccumulation of fluid after pericardiocentesis may occur. Further, this technique should reduce the cost and inconvenience of echocardiographic guidance of pericardiocentesis using handheld transducers.

Monitoring of Balloon Valvuloplasty Transseptal cardiac catheterization has been used for percutaneous transvenous mitral commissurotomy,32–34 as well as radiofrequency catheter ablation of cardiac arrhythmias.35,36 Perforation of the aorta, atria, and left ventricle are some of the rare but potentially serious complications of transseptal cardiac catheterization.37,38 Various modalities have been proposed to assist in the transseptal puncture. Two-dimensional echocardiography, transesophageal echocardiography (TEE), and intracardiac echocardiography all have been studied.39–42 These modalities can potentially help reduce the complications of the procedure but have their own limitations. For example, TEE adds additional discomfort and stress to the patient. The usefulness of intracardiac echocardiography is limited by its absence of three-dimensional capabilities, and therefore, fluoroscopy for the manipulation of the catheter/needle and transseptal puncture is needed. In addition, due to limited depth penetration of the 10 MHz transducer, the entire septum cannot be visualized in some patients.42 Space limitation in a catheterization lab and the need to preserve a sterile field make the use of transthoracic echocardiography during transseptal catheterization difficult. In addition, placement of the transducer on the patient’s chest wall poses a radiation hazard to the echocardiographer. Vahdat et al. have described the feasibility of monitoring transseptal cardiac catheterization by continuous hands-free echocardiography using the CONTISCAN transducer.43 This permits visualization of the needle and ensures that the needle traverses through the interatrial septum at the level of the fossa ovalis. Moreover, they demonstrated that using this method, one can potentially avoid many limitations of other modalities used in assisting transseptal puncture. They discussed a case report in which a 38-year-old Hispanic woman with severe mitral stenosis and congestive heart failure was admitted for percutaneous mitral commissurotomy. The 2.5 MHz transducer (CONTISCAN)

Fig. 12.16: Apical four-chamber view prior to insertion of the transseptal needle. (RA: Right atrium). Source: Reproduced with permission from Ref. 43.

was placed at the cardiac apex to permit imaging of the apical four-chamber view (Fig. 12.16). The fossa ovalis was clearly visualized. Right- and left-sided cardiac catheterization were performed. During the procedure, the needle appeared as a linear echogenic structure in the right atrium (Figs 12.16 and 12.17). Under guidance of echocardiography and fluoroscopy, the needle was advanced from the right atrium into the left atrium by puncturing the atrial septum (Fig. 12.18). Mitral valve flow velocity profile was obtained. The mean mitral valve gradient was 30 mm Hg by Doppler echocardiography (Fig. 12.19) and 28 mm Hg by cardiac catheterization. Double-balloon catheter commissurotomy (CBC) was performed. The mean mitral gradient after CBC was 5.1 mm Hg by Doppler echocardiography (Fig. 12.20) and 4 mm Hg by catheterization. There was no evidence of mitral regurgitation by color flow imaging (Fig. 12.21).

Monitoring of Cannulation of the Coronary Sinus Heart failure may progress in some patients despite the use of multiple pharmacologic agents. Alternative therapies such as heart transplantation and implantation of a left ventricular assist device may be required in these patients. More recently, cardiac resynchronization therapy

234

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 12.17: Four-chamber view illustrating transseptal needle in right atrium (arrow). Source: Reproduced with permission from Ref. 43.

Fig. 12.18: Image depicting transseptal needle (arrow) across atrial septum. Source: Reproduced with permission from Ref. 43.

Fig. 12.19: Doppler ultrasound recording of mitral flow velocity profile prior to CBC. The mean mitral gradient is 30 mm Hg. (CBC: Catheter balloon commissurotomy). Source: Reproduced with permission from Ref. 43.

Fig. 12.20: Doppler ultrasound recording of mitral flow velocity profile after CBC. The mitral gradient is 5.1 mm Hg. (CBC: Catheter balloon commissurotomy). Source: Reproduced with permission from Ref. 43.

with biventricular pacing has been shown to be beneficial in improving heart failure in patients with prolonged QRS duration (≥ 120 ms) and low ejection fraction (≤ 35%).44 Biventricular pacing requires the placement of pacing leads in the right and left heart. Techniques for right atrial and ventricular lead placement are well established. Pacing of the left heart requires a left ventricular lead,

which is placed in a distal cardiac vein by way of the coronary sinus (CS) through a guiding catheter. CS cannulation is achieved rapidly in some patients using standard fluoroscopic guidance; however, in other patients, cannulation of the CS may take prolonged periods of time and in some patients may be unachievable. Large, multicenter clinical trials studying biventricular

Chapter 12: Technique and Applications of Continuous Transthoracic Cardiac Imaging

235

Fig. 12.21: Color flow imaging post-CBC illustrates absence of mitral regurgitation. (CBC: Catheter balloon commissurotomy). Source: Reproduced with permission from Ref. 43.

Fig. 12.22: Coronary sinus prior to guide wire insertion. Arrow points to CS ostium. (CS: Coronary sinus; LV: Left ventricle; RA: right atrium). Source: Reproduced with permission from Ref. 51.

pacing for the treatment of heart failure have reported procedure time up to a few hours in a few cases and nearly 10% procedure failure rates due to inability to cannulate the CS.44,45 The CS is easily imaged by echocardiography from the apical view.46 However, ultrasound imaging is not routinely used during the cardiac resynchronization therapy procedure to identify the CS.47 Previous studies have used different techniques, other than fluoroscopy, such as transesophageal echocardiography, to achieve CS cannulation.48–50 Currently, fluoroscopy is used to cannulate the CS for the placement of pacemaker lead into ventricles. However, neither CS ostium nor body of the CS is imaged with fluoroscopy. The use of the CONTISCAN transducer for CS cannulation for biventricular lead placement during resynchronization therapy of patients with congestive heart failure has been demonstrated.51 When placed in the apical position, the ultrasound transducer does not interfere with fluoroscopy and provides an adjuvant imaging modality for CS cannulation during biventricular pacemaker implantation. The transducer was positioned medial to the cardiac apex and tilted slightly posterior to permit imaging of the coronary sinus and its ostium in the four-chamber view. The external housing was then secured to the chest wall

using an adhesive patch. The transducer was connected to a commercially available ultrasound machine. The time from the appearance of the wire in the right atrium to cannulation of the CS was noted. If successfully cannulated, the rest of the procedure was continued using standard technique. If it was unsuccessful after 10 minutes, fluoroscopy was used to attempt to enter the coronary sinus. The guide wire was placed in the right atrium through the left subclavian vein under fluoroscopic guidance. The CS was cannulated with ultrasound guidance. Figure 12.22 illustrates the CS and its ostium prior to cannulation. Figure 12.23 shows the guide wire in the CS. An introducer was then advanced over the guide wire which was then removed (Fig. 12.24). The feasibility study was done in 11 patients with ejection fractions ≤ 35% and QRS intervals > 120 milliseconds. CS ostium and body were imaged in all patients. Cannulation was successfully achieved in nine patients with a mean cannulation time of 1 minute 16 seconds. In two patients, poor image quality precluded adequate visualization of CS. Fluoroscopy was not used for cannulation. The cannulation time ranged from 0.18 to 6.27 minutes with a mean of 1.16 ± 2.37 seconds. Results are summarized in Table 12.3.

236

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 12.23: Guide wire in the coronary sinus. Arrow points to the guide wire. (CS: Coronary sinus; LV: Left ventricle; RA: Right atrium). Source: Reproduced with permission from Ref. 51.

Table 12.3: Subject’s Cannulation Time

Age (y)

Gender

Cannulation Time (min:s)

83

M

0:18

72

M

0:20

77

M

0:55

75

M

1:10

71

F

1:16

87

M

2:51

48

M

4:45

78

M

5:48

76

F

6:27

Fig. 12.24: Introducer in the coronary sinus. Arrow points to the introducer. Source: Reproduced with permission from Ref. 51.

right atrium causing displacement of the CS ostium. Bashir et al. demonstrated CS cannulation, combining transesophageal echocardiography and fluoroscopy. The mean duration was 9.3 minutes. The main limitation was the need for general anesthesia.49 In addition to facilitating CS cannulation, complications such as CS perforation and pericardial effusion may be detectable by the CONTISCAN transducer. Evidence also suggests that maximum benefit of cardiac resynchronization therapy depends on the pacing site.52 Use of CONTISCAN transducer may increase the success rate with significantly less cannulation time while reducing radiation exposure.

Source: Reproduced with permission from Ref. 51

Zhong et al. compared coronary sinus cannulation time using a standard handheld transducer versus X-ray. Mean cannulation times were 5.8 ± 5.7 and 5.9 ± 3.3 minutes, respectively, without statistically significant difference. Risk of contamination of the sterile field and potential exposure of the sonographer to radiation are limitations of this technique. Their study population consisted of patients undergoing intracardiac electrophysiologic study or radiofrequency catheter ablation.47 Usually, these patients have normal right atrial size. Difficulty in cannulation is encountered in the setting of enlarged

Intraoperative Monitoring of Noncardiac Surgery Patients who undergo noncardiac surgery may have associated CAD. These patients may develop perioperative myocardial ischemia caused by changes in heart rate, blood pressure, and contractility. The onset of myocardial ischemia may be associated with typical electrocardiographic changes. However, ECG changes may not be present in all patients with myocardial ischemia. These patients may develop regional left ventricular WMAs suggestive of ischemia. The detection of RWMAs using a

Chapter 12: Technique and Applications of Continuous Transthoracic Cardiac Imaging

handheld transducer is impractical. However, RWMAs may be detected on images obtained using the CONTISCAN transducer. These dynamic changes may be useful in assessing both the presence and extent of myocardial ischemia. Improvement in wall motion associated with medical therapy may be detectable with the CONTISCAN transducer. Preliminary data indicate both the feasibility and the usefulness of perioperative monitoring using the CONTISCAN transducer.28 Monitoring of intraoperative left ventricular wall motion using the CONTISCAN transducer may be performed without invasion of the sterile field during intra-abdominal surgery.

LIMITATIONS Some limitations of handheld transducers apply to the CONTISCAN transducer. Satisfactory imaging may not be possible in obese patients and in those with severe emphysema. Imaging may be intermittent in those with marked dyspnea. Additionally, inherent to most methods of echocardiographic assessment of LV wall motion, evaluation is subjective and experience dependent. We wish to emphasize that in the current study we imaged only the LV short axis. Therefore, it is conceivable that WMAs in other segments may not have been detected. Additionally, it should be noted that if continuous echocardiography using the CONTISCAN transducer is utilized, multiple ultrasound units would be required in order to monitor study subjects concurrently. However, small inexpensive ultrasound machines are available and would allow monitoring of several patients concurrently. This would be the case for a moderate-sized coronary care unit.

REFERENCES 1. Chandraratna PA, Vijayasekaran S, Brar R, et al. Feasibility of continuous transthoracic cardiac imaging using a novel ultrasound transducer. Echocardiography. 2001;18(8): 651–5. 1a. Chandraratna PAN, Stern RA. Ultrasound transducer denice for continuous imaging of the heart and other body parts. US patent #5,598,845, February 4, 1997. 2. Puleo PR, Meyer D, Wathen C, et al. Use of a rapid assay of subforms of creatine kinase-MB to diagnose or rule out acute myocardial infarction. N Engl J Med. 1994;331(9): 561–6. 3. Go AS, Mozaffarian D, Roger VL, et al. American Heart Association Statistics Committee and stroke statistics subcommittee. Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6-e245.

237

4. The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial infarction redefined—a consensus document of the joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J. 2000;21:1502–13; J Am Coll Cardiol. 2000;36: 959–69. 5. ACC/AHA Guidelines for the management of patients with unstable angina and non-ST segment elevation myocardial infarction executive summary and recommendations: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation. 2000;102(10):1193–209. 6. Kontos MC, Arrowood JA, Paulsen WH, et al. Early echocardiography can predict cardiac events in emergency department patients with chest pain. Ann Emerg Med. 1998;31(5):550–7. 7. Sabia P, Abbott RD, Afrookteh A, et al. Importance of two-dimensional echocardiographic assessment of left ventricular systolic function in patients presenting to the emergency room with cardiac-related symptoms. Circulation. 1991;84(4):1615–24. 8. Cheitlin MD, Alpert JS, Armstrong WF, et al. ACC/AHA guidelines for the clinical application of echocardiography: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Clinical Application of Echocardiography). Developed in collaboration with the American Society of Echocardiography. J Am Coll Cardiol. 1997;29(4):862–79. 9. Newby LK, Christenson RH, Ohman EM, et al. Value of serial troponin T measures for early and late risk stratification in patients with acute coronary syndromes. The GUSTO-IIa Investigators. Circulation. 1998;98(18):1853–9. 10. Chandraratna PA, Mohar DS, Sidarous PF, et al. Evaluation of non-ST segment elevation acute chest pain syndromes with a novel low-profile continuous imaging ultrasound transducer. Echocardiography. 2012;29(8):895–9. 11. Wann LS, Faris JV, Childress RH, et al. Exercise crosssectional echocardiography in ischemic heart disease. Circulation. 1979;60(6):1300–8. 12. O’Keefe JH Jr, Barnhart CS, Bateman TM. Comparison of stress echocardiography and stress myocardial perfusion scintigraphy for diagnosing coronary artery disease and assessing its severity. Am J Cardiol. 1995;75(11):25D–34D. 13. Fleischmann KE, Hunink MG, Kuntz KM, et al. Exercise echocardiography or exercise SPECT imaging? A metaanalysis of diagnostic test performance. JAMA. 1998;280 (10):913–20. 14. Schartl M, Beckmann S, Bocksch W. [Stress echocardiography—an evaluation of current status]. Z Kardiol. 1994; 83(8):531–47. 15. Southard J, Baker L, Schaefer S. In search of the falsenegative exercise treadmill testing evidence-based use of exercise echocardiography. Clin Cardiol. 2008;31(1):35–40. 16. Chandraratna PA, Gajanayaka R, Makkena SM, et al. “Handsfree” continuous echocardiography during treadmill exercise using a novel ultrasound transducer. Echocardiography. 2010;27(5):563–6.

238

Section 2: Echocardiography/Ultrasound Examination and Training

17. Cheitlin MD, Alpert JS, Armstrong WF, et al. ACC/AHA Guidelines for the Clinical Application of Echocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography). Developed in collaboration with the American Society of Echocardiography. Circulation. 1997;95(6):1686–744. 18. Marwick TH, Anderson T, Williams MJ, et al. Exercise echocardiography is an accurate and cost-efficient technique for detection of coronary artery disease in women. J Am Coll Cardiol. 1995;26(2):335–41. 19. Chandraratna PA, Mohar DS, Sidarous PF, et al. Detection of wall motion abnormalities during ambulatory echocardiography using a novel ultrasound transducer. Echocardiography. 2012;29(5):509–12. 20. Gore JM, Goldberg RJ, Spodick DH, et al. A communitywide assessment of the use of pulmonary artery catheters in patients with acute myocardial infarction. Chest. 1987; 92(4):721–7. 21. Connors AF Jr, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. JAMA. 1996;276(11): 889–97. 22. Zion MM, Balkin J, Rosenmann D, et al. Use of pulmonary artery catheters in patients with acute myocardial infarction. Analysis of experience in 5,841 patients in the SPRINT Registry. SPRINT Study Group. Chest. 1990;98(6):1331–5. 23. Guyatt G. A randomized control trial of right-heart catheterization in critically ill patients. Ontario Intensive Care Study Group. J Intensive Care Med. 1991;6(2):91–5. 24. Masuyama T, Kodama K, Kitabatake A, et al. Continuouswave Doppler echocardiographic detection of pulmonary regurgitation and its application to noninvasive estimation of pulmonary artery pressure. Circulation. 1986;74(3): 484–92. 25. Lee RT, Lord CP, Plappert T, et al. Prospective Doppler echocardiographic evaluation of pulmonary artery diastolic pressure in the medical intensive care unit. Am J Cardiol. 1989;64(19):1366–70. 26. Chandraratna PA, Nanna M, McKay C, et al. Determination of cardiac output by transcutaneous continuous-wave ultrasonic Doppler computer. Am J Cardiol. 1984;53(1): 234–7. 27. Nishimura RA, Callahan MJ, Schaff HV, et al. Noninvasive measurement of cardiac output by continuous-wave Doppler echocardiography: initial experience and review of the literature. Mayo Clin Proc. 1984;59(7):484–9. 28. Chandraratna PA, Brar R, Vijayasekaran S, et al. Continuous recording of pulmonary artery diastolic pressure and cardiac output using a novel ultrasound transducer. J Am Soc Echocardiogr. 2002;15(11):1381–6. 29. Chabdraratna PA, First J, Langevin E, et al. Echocardiographic contrast studies during pericardiocentesis. Ann Intern Med. 1977;87(2):199–200. 30. Chandraratna PA, Reid CL, Nimalasuriya A, et al. Application of 2-dimensional contrast studies during pericardiocentesis. Am J Cardiol. 1983;52(8):1120–2.

31. Chandraratna PA, Vijayasekaran S, Brar P, et al. “Hands-free” continuous transthoracic monitoring of pericardiocentesis using a novel ultrasound transducer. Echocardiography. 2003;20(6):491–4. 32. Inoue K, Owaki T, Nakamura T, et al. Clinical application of transvenous mitral commissurotomy by a new balloon catheter. J Thorac Cardiovasc Surg. 1984;87(3):394–402. 33. Zaibag MA, Kasab SA, Ribeiro PA, et al. Percutaneous double balloon mitral valvulotomy for rheumatic mitral valve stenosis. Lancet. 1986;1:757–61. 34. Palacios I, Block PC, Brandi S, et al. Percutaneous balloon valvotomy for patients with severe mitral stenosis. Circulation. 1987;75(4):778–84. 35. De Ponti R, Casari A, Salerno JA, et al. Radiofrequency transcatheter ablation of left-sided atrioventricular accessory pathways: Role of the transseptal approach. G Ital Cardiol 1992:22:1255–64. 36. De Ponti R, Zardini M, Storti C, et al. Trans-septal catheterization for radiofrequency catheter ablation of cardiac arrhythmias. Results and safety of a simplified method. Eur Heart J. 1998;19(6):943–50. 37. Lindeneg O, Hansen AT. Complications in transseptal left heart catheterization. Acta Med Scand. 1966;180(4):395–9. 38. Adrouny ZA, Sutherland DW, Griswold HE, Ritzmann LW. Complications with transseptal left heart catheterization. Am Heart J. 1963;65:327–33. 39. Kronzon I, Glassman E, Cohen M, et al. Use of twodimensional echocardiography during transseptal cardiac catheterization. J Am Coll Cardiol. 1984;4(2):425–8. 40. Ballal RS, Mahan EF 3rd, Nanda NC, et al. Utility of transesophageal echocardiography in interatrial septal puncture during percutaneous mitral balloon commissurotomy. Am J Cardiol. 1990;66(2):230–2. 41. Bidoggia H, Maciel JP, Alvarez JA. Transseptal left heart catheterization: usefulness of the intracavitary electrocardiogram in the localization of the fossa ovalis. Cathet Cardiovasc Diagn. 1991;24(3):221–5. 42. Hung JS, Fu M, Yeh KH, et al. Usefulness of intracardiac echocardiography in transseptal puncture during percutaneous transvenous mitral commissurotomy. Am J Cardiol. 1993;72(11):853–4. 43. Vahdat A, Vijayasekaran S, Durairaj A, et al. Continuous ultrasonic monitoring of balloon valvuloplasty. Echocardiography. 2002;19(4):325–8. 44. Abraham WT, Fisher WG, Smith AL, et al. MIRACLE Study Group. Multicenter InSync Randomized Clinical Evaluation. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002;346(24):1845–53. 45. Gras D, Mabo P, Tang T, et al. Multisite pacing as a supplemental treatment of congestive heart failure: preliminary results of the Medtronic Inc. InSync Study. Pacing Clin Electrophysiol. 1998;21(11 Pt 2):2249–55. 46. Weyman AE. Left ventricular inflow tract II: the left atrium, pulmonary veins and coronary sinus. In: Principles and Practice of Echocardiography, 2nd edition Philadelphia, PA: Lea and Febiger; 1994: 471–97.

Chapter 12: Technique and Applications of Continuous Transthoracic Cardiac Imaging

47. Zhong JQ, Dorian P, Zhang W, et al. Using transthoracic two-dimensional echocardiography to guide the placement of coronary sinus catheters: a randomized study. Echocardiography. 2006;23(2):93–6. 48. Kautzner J, Riedlbauchová L, Cihák R, et al. Technical aspects of implantation of LV lead for cardiac resynchronization therapy in chronic heart failure. Pacing Clin Electrophysiol. 2004;27(6 Pt 1):783–90. 49. Bashir JG, Frank G, Tyers O, et al. Combined use of transesophageal ECHO and fluoroscopy for the placement of left ventricular pacing leads via the coronary sinus. Pacing Clin Electrophysiol. 2003;26(10):1951–4.

239

50. Vogt J, Schwarz T, Gras D, et al. The use of telescoping guide catheters for coronary sinus cannulation and subselecting tributaries in left ventricular lead placement. J Interv Card Electrophysiol. 2007;19(1):61–8. 51. Chandraratna PA, Kosar E, Gajanayaka R, et al. Use of a low profile ultrasound transducer for coronary sinus cannulation: a pilot study. J Clin Ultrasound. 2010;38(8): 426–9. 52. Auricchio A, Klein H, Tockman B, et al. Transvenous biventricular pacing for heart failure: can the obstacles be overcome? Am J Cardiol. 1999;83(5B):136D–42D.

CHAPTER 13 The Basics of Performing Three-Dimensional Echocardiography Steven Bleich, Navin C Nanda, Satish K Parashar, H K Chopra, Rakesh Gupta

Snapshot  3D Technology  3D ExaminaƟon Protocol  LeŌ Parasternal Approach  Apical Approach  Subcostal Approach

 Suprasternal Approach  Supraclavicular Approach  Right Parasternal Approach  Color Doppler Imaging  Advantages/Disadvantages of 3D Echocardiography

INTRODUCTION Three-dimensional (3D) echocardiography is an important imaging tool that is gaining popularity amongst cardiologists because of its ability to better understand relevant cardiac anatomy and function. With the creation of the full matrix array transducer, 3D echocardiography can capture more real-life images of the heart compared to traditional two-dimensional imaging. This technology provides a real time 3D pyramidal data set that can be cropped and viewed from infinite angles. The advancement of 3D echocardiography has already made a significant clinical impact in diagnosing and treating patients with cardiovascular disease, but with continued improvement in technology and further education of the capabilities of 3D imaging, the potential for even greater impact is promising.

3D TECHNOLOGY Current 3D matrix-array transducers are comprised of around 3,000 piezoelectric components with varying operating frequencies (2–7 MHz) based on the

Fig. 13.1: The scanning beam performs azimuth steering along the Y-axis in a phased array manner and produces two-dimensional (2D) sector images. The 2D sector image performs elevation steering along the Z-axis and finally produces a pyramidal threedimensional (3D) data set. Courtesy: Philips Medical Systems, Bothell, Washington. Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604. Movie clip 13.1.

echocardiographic approach (Figs 13.1 to 13.3).1 A laser is used to divide the piezoelectric crystal into equal parts

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

241

Fig. 13.2: Left shows 30° elevation steering along the Z-axis and right shows 60° azimuth steering along the Y-axis. Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604.

Fig. 13.3: In order to generate a “full volume” pyramidal data set, four adjacent 15° images generated by elevation steering along the Z-axis are combined to produce 60° images on the left, and the right shows the image with 60° azimuth steering along the Y-axis. Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604.

that ultimately form the matrix.2 The system utilizes connections between multiple digital channels and mini-circuit boards to develop immediate 3D volumerendered, color-Doppler, and harmonic functions. 3D echocardiography uses an ultrasound beam to create twodimensional (2D) images and then incorporates the Z-axis to generate a 3D pyramidal data set that is scanned along each axis (X, Y, Z) in a perpendicular fashion. 3D data sets can be obtained in two ways: real time/ live 3D echocardiography and electrocardiographically (ECG) triggered.1 These two methods are distinguished by the number of heartbeats over which data is acquired. Real time/live 3D echocardiography analyzes data in a single heart beat while ECG triggered analyzes data over successive heart beats which is combined to create a single data set. Live/real time echocardiography can be described as a “narrow-angled display” or a “wide-angled display” depending on the imaging angle along the Y- and Z-axes.2 A wide-angled display, also called “pyramidal imaging,” involves the combination of four narrow angle scans that depicts a larger area of the heart in a more realistic fashion without having to adjust the transducer.2 Cropping is responsible for 3D echocardiography’s ability to create real life anatomic depictions of the heart. The location of the “viewing perspective” within the specific area of interest allows the operator to maneuver the images in all directions so that relevant structures (both internal and external) can be viewed from various view

points.1,3 For example when viewing the interventricular septum, the free walls of the left and right ventricles can be removed virtually, so that the septum can be viewed from both the right and left ventricular aspects.1 Cropping can be done at the time images and data are obtained or any time afterward by the operator. The use of cropping provides a major advantage to 3D echocardiography compared to the 2D echocardiography.

3D EXAMINATION PROTOCOL 3D echocardiography essentially utilizes the same anatomic views that are used in 2D echocardiography; however, the added dimension provides a more realistic depiction of the cardiac anatomy (Figs 13.4 to 13.10). A major advantage of 3D over 2D examination in clinical practice is en face visualization of various cardiac structures. 3D echocardiography is rarely done alone and is usually performed as an adjunct to 2D examination to provide incremental information or confirm 2D findings. The presence of a standard protocol allows readers to visualize images in a specific sequence that can aid in the clinical evaluation of a patient. There are two existing 3D transthoracic echocardiographic (TTE) protocols in clinical practice: focused exam and complete exam.3 A focused exam first relies on 2D TTE to identify structures of interest and then 3D TTE is used to perform

242

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 13.4A to C: Some of the standard two-dimensional echocardiographic imaging planes. (A) Parasternal long-axis plane; (B) parasternal short-axis plane, and (C) apical four-chamber plane. Note that the planes are described in relation to the left ventricle of the heart rather than to the anatomic orientation of the patient. Source: Reproduced with permission from Nanda NC, Gramiak R. Clinical Echocardiography. St. Louis: C.V. Mosby; 1978:371, 393, 408.

Fig. 13.5: Transducer positions for live three-dimensional echocardiography standard examination used to acquire a full-volume data set of the heart. Source: Reproduced with permission from Nanda et al. Echocardiography 2004;21:763–8.

Fig. 13.6: Cropping planes used for three-dimensional echocardiography. The long-axis of the heart is at an angle to the body axis. The planes of the heart are in reference to the heart itself and not the body axis. Source: Reproduced with permission from Nanda et al. Echocardiography. 2004;21:763–8.

a more comprehensive evaluation of details such as valve morphology and area or ventricular size, shape, and function. On the other hand, a complete exam includes a thorough assessment of all cardiac anatomy with 3D TTE, without prior imaging by 2D TTE. It is important to understand that the echocardiographic views are named in relation to the left ventricle assuming the patient is standing up and facing forward.4 The standard and nonstandard views of 2D echocardiography include left

parasternal, apical, subcostal, suprasternal, right/left supraclavicular, and right parasternal approaches. Once the pyramidal data set is captured, 3D echocardiography has the capability to crop the images in various planes from six different cardiac perspectives (above, below, left, right, posteroanterior and anteroposterior). Although some experts suggest that the apex should be positioned at the bottom of the echocardiographic window before cropping takes place, the “apex-down” theory has not

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

243

Fig. 13.7: The use of anatomic planes to describe live threedimensional echocardiographic images results in six different cardiac perspectives for any cardiac structure. These may be described using two descriptive terms, the plane and the viewing perspective. Source: Reproduced with permission from Nanda et al. Echocardiography. 2004;21:763–8.

Fig. 13.8: Sagittal (long-axis or longitudinal) section—viewed from left side or right side—as used in live three-dimensional echocardiography. Source: Reproduced with permission from Nanda et al. Echocardiography. 2004;21:763–8.

Fig. 13.9: Oblique coronal (frontal) section—viewed from above and below—as used in live three-dimensional echocardiography. Source: Reproduced with permission from Nanda et al. Echocardiography. 2004;21:763–8.

Fig. 13.10: Transverse (short-axis) section—viewed from base or apex—as used in live three-dimensional echocardiography. Source: Reproduced with permission from Nanda et al. Echocardiography. 2004;21:763–8.

been widely accepted for left ventricular imaging.1 Others prefer that the apex be located at the top of the viewing window and with right-sided structures appearing on the left side of the screen.1 The most commonly used cropping planes are sagittal, coronal, and transverse.1,3–5 The sagittal (longitudinal) plane dissects the heart into left and right sides similar to the long-axis view. The coronal (frontal)

plane separates the heart into anterior and posterior parts analogous to the apical four-chamber view. Finally, the transverse plane partitions the heart into superior and inferior segments comparable to the short-axis view. 3D echocardiography uses the basic planes offered by 2D echocardiography, but in addition allows the observer to view the heart from any desired angle. These capabilities

244

Section 2: Echocardiography/Ultrasound Examination and Training

offer observers significantly more detail regarding the structure and function of the heart and can play a significant role in the clinical evaluation of patients.

LEFT PARASTERNAL APPROACH The left parasternal approach is well known to those familiar with 2D echocardiography and offers significant information regarding the structure and function of both the right and left cardiac chambers and the corresponding valves (Figs 13.11 to 13.21). Specifically, the left atrium, left ventricle, left ventricular outflow tract, right ventricle, mitral valve, and aortic valve are clearly visualized using the parasternal long-axis approach. Short-axis views examine the aortic root, atrial septum, tricuspid valve, and pulmonary valve. The atrioventricular valves can be viewed en face from both the ventricular and atrial aspects and the semilunar valves from the great vessel and ventricular outflow sides. One advantage of this approach in 3D TTE is better understanding of the “echo-free space” that is located posterior to the proximal ascending aorta.6 This echo-free space usually contains structures such as the superior vena cava (SVC) most commonly, or the right pulmonary artery (RPA); however, visualization of this space can also be used to detect significant cardiac pathology including aortic dissection/intimal hematoma, aortic pseudoaneurysm, sinus of Valsalva aneurysm, or an abscess.6 Visualization of the SVC is very important in patients with central venous catheters or pacing electrodes and can help in detecting the presence of a thrombus. Using the left parasternal approach, the transducer should be angled superior and to the right to capture the proximal ascending aorta and then directed posteriorly to visualize the SVC.6

APICAL APPROACH The apical approach can capture two, three, four, or even five chambers of the heart and is well known for its ability to visualize the entire left ventricle (Figs 13.22 and 13.23). In a patient with an ideal acoustic window, all apical views including apical two-, three-, and five-chamber views as well as short-axis views of the left ventricle at any desired level can be examined from a single full-volume apical four-chamber data set by suitable cropping. By visualizing the left ventricle, volumetric data (end-diastolic and endsystolic volumes) can be precisely measured and used in the calculation of left ventricular ejection fraction. Studies

of 3D echocardiography have shown greater accuracy and reproducibility with regard to measurements of the left ventricle compared to 2D echocardiography using this approach.7 Another unique function of 3D echocardiography using the apical approach is the simultaneous visualization of all four cardiac valves by cropping from the base or the apex.4

SUBCOSTAL APPROACH The subcostal approach is routinely used but takes on special importance in patients with poor echocardiographic windows obtained from the parasternal and apical views (Figs 13.24A to H). This view can identify the inferior vena cava (IVC) which is relevant in evaluating a patient’s volume status as well as cardiac tamponade in the setting of a large pericardial effusion. The subcostal approach can also provide important information regarding measurements of the right-sided heart chambers and valves which can be useful in the assessment of pulmonary hypertension. It is also a useful view to visualize the abdominal aorta and its relationship to the inferior vena cava. Liver and other abdominal structures can also be assessed in this view.

SUPRASTERNAL APPROACH The suprasternal approach is performed by placing the transducer in the suprasternal notch (Figs 13.25A to C). The suprasternal approach is best known for its visualization of the ascending aorta, the aortic arch and its arising arteries, the pulmonary arteries, central venous structures, and the proximal descending aorta.

SUPRACLAVICULAR APPROACH In the supraclavicular approach, the transducer is placed in the right and then the left supraclavicular fossa next to the sternocleidomastoid muscle (Figs 13.26A to J).7 The supraclavicular approach is helpful in visualizing the entire SVC and its tributaries (innominate veins, azygos vein), as well as the junction of the IVC and right atrium. This view can also capture the ascending aorta, aortic arch and its arising vessels, and the proximal descending thoracic aorta, which helps to supplement the images obtained via the suprasternal approach. Left supraclavicular examination is also useful for detecting a left-sided SVC.

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

A

245

B

Figs 13.11A and B: Live three-dimensional (3D) echocardiographic images of a long-axis view of the normal left heart. Left shows a long-axis view of the left heart. Left ventricle (LV), left atrium (LA), right ventricle (RV), and aorta (AO) are displayed clearly. During systole, the mitral orifice (MVO) is closed. On the right is the same live 3D image in diastole with the mitral orifice open. Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604.

A

B

C

D

Figs 13.12A to D

246

Section 2: Echocardiography/Ultrasound Examination and Training

E

F

G

H

Figs 13.12A to I: Live/real time three-dimensional transthoracic echocardiography. Parasternal examination. (A to G) Multiple sections showing various anatomic structures obtained by cropping a single parasternal long-axis data set. The arrow in (C) points to the tricuspid valve (TV). The arrow in (D) shows the left main coronary artery; (H and I) Cropping of another parasternal data set from the same patient shows a long segment of the left anterior descending coronary artery (arrow) in B-mode (H) and with color Doppler (I). Short-axis views of this artery are also visualized in the accompanying Movie clip 13.12. (AO: Aorta; LA: Left atrium; LV: Left ventricle; MV: Mitral valve; PA: Pulmonary artery; PV: Pulmonary valve; RA: Right atrium; RV: Right ventricle). Source: Reproduced with permission from Nanda NC, Hsiung MC, Miller AP, et al. Live/Real Time 3D Echocardiography. Chichester, West Sussex: Wiley, Blackwell; 2010.

I

RIGHT PARASTERNAL APPROACH The right parasternal approach is especially useful in conditions which move the right lung away from the sternum including a pericardial effusion, right heart

enlargement, or ascending aorta dilatation (Figs 13.27 to 13.29). 3D echocardiography performed in the right parasternal approach can identify structures such as the right atrial appendage and tricuspid valve leaflets both of which can be difficult to visualize using 2D imaging.8

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

A

B

C

D

E

F

Figs 13.13A to F

247

248

Section 2: Echocardiography/Ultrasound Examination and Training

G

H

Figs 13.13A to H: Two- and live/real time three-dimensional transthoracic echocardiographic identification of the superior vena cava and right pulmonary artery behind the aorta imaged in parasternal long-axis view. Bounded echo-free space behind the aorta imaged in parasternal long-axis view. (A to C) Two-dimensional transthoracic echocardiographic (2D TTE) bubble study. Intravenous injection of agitated normal saline shows contrast echoes first appearing in the bounded echo-free space (arrowhead in B) and then in the right ventricle (RV, arrow in C). This suggests that the echo-free space represents the superior vena cava (SVC). Movie clip shows biplane imaging with bubble study; (D to H) Real time three-dimensional echocardiographic (3D TTE) bubble study. Intravenous injection of agitated normal saline shows contrast echoes appearing first in the bounded echo-free space (arrow in E) and then sequentially moving into the right atrium (RA, arrow in F) and RV (arrow in G and H). This suggests that the bounded space is the SVC. The 3D TTE image was tilted to demonstrate the progression of contrast echoes into the RA and RV. (AO: Aorta, LA: Left atrium; LV: Left ventricle. RA: Right atrium; RV: Right ventricle) Movie clips 13.13A to H. Source: Reproduced with permission from Burri MV, et al. Superior vena cava, right pulmonary artery or both: real time two- and threedimensional transthoracic contrast echocardiographic identification of the echo free space posterior to the ascending aorta. Echocardiography. 2007;24:875–82.

The best images can be obtained by placing the patient in the right lateral decubitus position with maneuvering of the transducer between the second and fifth right intercostal spaces near the sternum. This approach can visualize the entrance of the SVC into the right atrium and has practical clinical application in diagnosing or excluding a sinus venosus atrial septal defect. Entrance of the pulmonary veins into the left atrium and of the IVC and coronary sinus into the right atrium can also be visualized using this examination window.8 The right parasternal approach is valuable in the assessment of atrial switch procedures (Senning or Mustard) in a patient with transposition of the great arteries. This view can also clearly depict the diversion of blood from the right atrium to the pulmonary arteries (Fontan procedure) in patients with tricuspid atresia. Both of these findings are commendable as many of the classic echocardiographic views are unsuccessful in adequately visualizing abnormal cardiac anatomy. Furthermore, 3D TTE in this view can visualize the entire atrial septum en face which not only diagnoses a secundum atrial septal defect, but also helps in evaluating the appropriate treatment options. Even coronary artery

anatomy can be viewed in 3D TTE from the right parasternal approach. The right coronary artery in the atrioventricular groove and the origin and proximal portion of the left main coronary artery as it branches from the ascending aorta can often be seen from this view.

COLOR DOPPLER IMAGING It is important to recognize that each echocardiographic approach offers a unique view that may identify useful information not obtained from other views (Figs 13.30A to D).9 In addition to performing B-mode 3D examination, 3D color Doppler studies in various examination windows should also be considered in selected patients, especially those with stenotic, regurgitant, or shunt lesions detected or suspected on 2D echocardiography. 3D technology is useful in viewing the vena contracta of both stenotic and regurgitant jets. Unlike 2D TTE, the exact shape and size of the vena contracta regurgitant jet can be accurately assessed. The volume of regurgitant flow is calculated by multiplying the planimetered area of the vena contracta with the velocity time integral of the regurgitation

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

249

A

B

C

Figs 13.14A to C: Two- and live/real time three-dimensional (3D) transthoracic echocardiographic identification of the superior vena cava and right pulmonary artery behind the aorta imaged in parasternal long-axis view. Bounded echo-free space behind the aorta imaged in parasternal long-axis view. Live three-dimensional transthoracic echocardiography. (A to C) Tilting of the fullvolume 3D data set shows the bounded echo-free space (arrowhead) to be continuous with the RA. This is consistent with SVC. (AO: Aorta; IVC: Inferior vena cava; LA: Left atrium; LV: Left ventricle; RV: Right ventricle; TV: Tricuspid valve) Movie clip 13.14. Source: Reproduced with permission from Burri MV, et al. Superior vena cava, right pulmonary artery or both: real time two- and threedimensional transthoracic contrast echocardiographic identification of the echo free space posterior to the ascending aorta. Echocardiography. 2007;24:875–82.

A

B

Figs 13.15A and B

250

Section 2: Echocardiography/Ultrasound Examination and Training

C

D

Figs 13.15A to D: Two- (2D) and live/real time three-dimensional (3D) transthoracic echocardiographic (TTE) identification of the superior vena cava and right pulmonary artery behind the aorta imaged in parasternal long-axis view. Bounded echo-free space behind the aorta imaged in parasternal long-axis view. 2D TTE and 3D TTE. (A to C) Arrow points to the central line in the bounded echo-free space imaged behind the AO by 2D TTE in (A) and (B), and by 3D TTE in (C). The asterisk in (A) points to the dissection flap in the descending thoracic aorta (DA); (D) Chest X-ray (posteroanterior view) shows the tip of the central line (asterisk) located at the SVC–RA junction. The above findings indicate that the bounded echo-free space is the SVC. (AO: Aorta; LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle PE: Pericardial effusion). Movie clips 13.15A to C. Source: Reproduced with permission from Burri MV, et al. Superior vena cava, right pulmonary artery or both: real time two- and threedimensional transthoracic contrast echocardiographic identification of the echo free space posterior to the ascending aorta. Echocardiography. 2007;24:875–82.

A

B

C

D

Figs 13.16A to D

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

E

251

Figs 13.16A to E: Two- (2D) and live/real time three-dimensional transthoracic echocardiographic (TTE) identification of the superior vena cava (SVC) and right pulmonary artery behind the aorta imaged in parasternal long-axis view. Two bounded echo-free spaces behind the aorta imaged in parasternal long-axis view in a patient with primary pulmonary hypertension. 2D TTE bubble study. (A to E) Intravenous injection of agitated normal saline resulted in the appearance of contrast echoes initially in the superior space (#1 in B) and then in the more inferior space (#2 in C). The superior space therefore represents the SVC. The inferior space is the right pulmonary artery and its continuity with the main pulmonary artery (PA) is clearly shown (D and E). (AO: Aorta; LA: Left atrium; LPA: Left pulmonary artery; LV: Left ventricle; PV: Pulmonary valve; RPA: Right pulmonary artery; RV: Right ventricle. Movie clips 13.16A to E. Source: Reproduced with permission from Burri MV, et al. Superior vena cava, right pulmonary artery or both: real time two- and threedimensional transthoracic contrast echocardiographic identification of the echo free space posterior to the ascending aorta. Echocardiography. 2007;24:875–82.

A

B

C

Figs 13.17A to C: Two- (2D) and live/real time three-dimensional transthoracic echocardiographic (TTE) identification of the superior vena cava (SVC) and right pulmonary artery behind the aorta imaged in parasternal long-axis view. Bounded echo-free space behind the aorta imaged in parasternal long-axis view in a patient with systemic hypertension and no obvious pulmonary hypertension. 2D TTE bubble study. (A to C) Intravenous injection of agitated normal saline resulted in contrast echoes first appearing in the RV (arrow in B) and then in the bounded echo-free space (arrowhead in C). This suggests that the bounded echo-free space represents a pulmonary artery and not the SVC. (AO: Aorta; LA: Left atrium; LV: Left Ventricle; RA: Right atrium) Movie clip 13.17. Source: Reproduced with permission from Burri MV, et al. Superior vena cava, right pulmonary artery or both: real time two- and three-dimensional transthoracic contrast echocardiographic identification of the echo free space posterior to the ascending aorta. Echocardiography. 2007;24:875–82.

252

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 13.18A to D: Live three-dimensional (3D) echocardiography in mitral stenosis. (A) shows a live 3D image from the long-axis view of the left heart. The left atrium (LA) is enlarged and, in systole, the mitral orifice is closed with good coaptation between anterior and posterior leaflets; (B) shows the same live 3D image in diastole with restricted opening of the mitral orifice (arrow); (C) View from left ventricle to left atrium with the mitral valve closed in systole (arrow); (D) Shows the same image in diastole. The mitral orifice is an elliptical small opening (arrow). (LV: Left ventricle; RV: Right ventricle). Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604.

A Figs 13.19A and B

B

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

C

253

D

Figs 13.19A to D: Live three-dimensional echocardiography using narrow angle display in a patient with a ventricular septal defect. (A to D) Images are obtained from frontal, posterior, inferior, or superior direction and the defect is visualized (arrows) clearly. (LA: Left atrium; LV: Left ventricle; RV: Right ventricle). Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604.

A

B

C

Figs 13.20A to C: These are the wide-angle pyramidal display images (60° × 60°). The echo of the chest wall on top of the threedimensional was removed and the wide-angle square images of intracardiac structure are shown clearly. A ventricular septal defect was visualized (arrows). The tubular defect from left ventricle into right ventricle is seen in Figures A to C. Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604.

254

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 13.21A and B: Live/real time three-dimensional transthoracic echocardiography images of a patient with interventricular septal defect which was repaired with a patch (arrow). The left shows a long-axis view of the left heart viewed from the superior aspect. The echo of the chest wall was removed and the patch appears separating the right (RV) and left (LV) ventricles. The right shows a long-axis view of the left heart viewed from the inferior aspect. Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604.

A

B

C

D

signals obtained by continuous wave Doppler. Because of the slice-like nature of 2D echocardiography planes, it is not possible to reliably view the vena contracta en face and sometimes inaccurate assumptions are made regarding its shape when calculating the regurgitant volume. Commonly the vena contracta is considered ellipsoid in shape, however when calculating the area from two orthogonal dimensions by 2D TTE it is assumed to be circular. However, it has been shown by 3D echocardiography and other techniques that the vena

Figs 13.22A to D: Live/real time three-dimensional (3D) transthoracic echocardiography. Apical examination. (A) Apical fourchamber view and endocardial margin of the left ventricle; (B) Twochamber view and endocardial margin of the left ventricle; (C) Short-axis view of the ventricles and their endocardial margin; (D) Reconstructed 3D volume of the left ventricle. Source: Reproduced with permission from Wang et al. Echocardiography. 2003;20:593–604. Other apical views such as apical fivechamber, apical two-chamber, and apical three-chamber views can be obtained by suitable cropping of the apical four-chamber data set (Movie clip 13.22, Part 1). Short-axis views of the left ventricle at various levels such as apex, papillary muscles, and mitral valve can also be obtained from the same data set. Movie clip 13.22, Parts 1 and 2. Movie clips reproduced with permission from Nanda NC, Hsiung MC, Miller AP, Hage FG. Live/Real Time 3D Echocardiography. Oxford, UK: Wiley-Blackwell; 2010:38, Fig. 3.22.

contracta is most often irregular and does not conform to any geometric shape and, therefore, the calculation of regurgitant volume by 2D TTE cannot be accurate. Even the proximal flow acceleration (PISA) has been found to be nonhemispheric by 3D echocardiography in most patients further confirming the inaccuracies of 2D methods in quantifying the severity of valvular regurgitation. Because of the ease with which the regurgitation jet vena contracta can be reliably evaluated by 3D echocardiography, we do not find it necessary to use the relatively more complicated

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

A

255

B

C Figs 13.23A to C: Live/real time three-dimensional (3D) transthoracic echocardiography. Apical examination. (A) Cropping of the apical three-dimensional data set permits viewing of all four cardiac valves simultaneously. This is not possible using standard two-dimensional echocardiography; (B) Anatomic schematic showing the relationship of the four cardiac valves. Note the striking resemblance of the live 3D echo image to actual anatomy; (C) Another live 3D echo view from the same patient, showing the relationship of three cardiac valves. (AV: Aortic valve; MV: Mitral valve; PV: Pulmonary valve; TV: Tricuspid valve). Movie clip 13.23, Part 1, shows cropping of the apical data set from both ventricular and atrial aspects to view all four cardiac valves. Oblique cropping was also used to view the ventricular septum (VS) en face from the right side. The asterisk points to a few trabeculations in the left ventricular cavity resulting from the cropping plane cutting through the apical portion of the VS. A pacing lead is also noted in the right atrium (RA) and right ventricle (RV). Oblique cropping was also used from the left side to view the LV more comprehensively. (AO: Aortic valve and aorta; MV: Mitral valve; PV: Pulmonary valve; TV: Tricuspid valve). Movie clip 13.23, Part 2, shows an apical data set that has been cropped to view the attachment (arrow) of the anterolateral papillary muscle in the left ventricle (LV). A small papillary muscle is also visualized in the right ventricle (RV). Short-axis cropping using the same data set views both anterolateral and posteromedial papillary muscles (arrows). (LA: Left atrium; RA: Right atrium). Movie clip 13.23, Part 3, shows cropping of the right heart to display the entrance of the coronary sinus (CS) into the right atrium (RA). The anterior (A) and septal (S) leaflet of the tricuspid valve are well seen. (LA: Left atrium; RV: Right ventricle). Movie clips 13.23, Parts 1 to 3. Movie clips reproduced with permission from Nanda NC, Hsiung MC, Miller AP, Hage FG. Live/Real Time 3D Echocardiography. Oxford, UK: Wiley-Blackwell; 2010:39, Fig. 3.23. Source: (A and C) Reproduced with permission from Philips Medical Systems, Bothell, WA; Source: (B) Reproduced with permission from a modified figure with permission of Williams & Wilkins, Baltimore, MD, from a modified Figure from H. Gray, Anatomy of the Human Body. 30th ed. In: Clemente CD, editor. 1985:632.

3D PISA approach for quantitatively assessing the severity of regurgitation. Intracardiac shunts can also be visualized by 3D color Doppler en face at their origin which helps in assessing the anatomic shape and size of the shunt vena

contracta. This can then be used to calculate shunt volume by multiplying the vena contracta area by the velocity time integral of the Doppler shunt signals in a manner similar to calculation of valvular regurgitant volume.

256

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

E

F

Figs 13.24A to F

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

G

257

H

Figs 13.24A to H: Live/real time three-dimensional transthoracic echocardiography. Subcostal examination. Demonstrates several anatomic structures in B-mode and with color Doppler obtained from cropping of subcostally acquired three-dimensional data sets. The arrow in C points to tricuspid subvalvular apparatus. The arrow in G denotes the right ventricular apex. (AS: Interatrial septum; AV: Aortic valve; LA: Left atrium; LPA: Left pulmonary artery; LV: Left ventricle; PA: Pulmonary artery; PV: Pulmonary valve; RPA: Right pulmonary artery; RV: Right ventricle). Source: Reproduced with permission from Nanda NC, Hsiung MC, Miller AP, et al. Live/Real Time 3D Echocardiography. Chichester, West Sussex: Wiley, Blackwell; 2010.

A

C

B

Figs 13.25A to C: Live three-dimensional suprasternal echocardiographic examination. (A and B) Demonstrates a long segment of innominate artery (IA); (C) Arrowhead points to a venous valve in left innominate vein (LIV); Left carotid artery (LCA), left subclavian artery (LSA), and descending thoracic aorta (DA) are shown. AA, ascending aorta. Source: Reproduced with permission from Patel et al. Echocardiography. 2005;22:349–60.

258

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

E

F

Figs 13.26A to F

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

G

H

I

J

259

Figs 13.26A to J: Live three-dimensional supraclavicular transthoracic echocardiographic examination. (A) Foreshortened image demonstrates both right (RIV) and left (LIV) innominate veins joining to form the SVC, which then enters into RA. A venous valve (V) is seen at the entrance of SVC. Another venous valve (V1) is imaged at the junction of azygos vein (AZ) and SVC. IVC is also shown entering RA inferiorly; (B) Entrance of AZ into SVC from the postero-right aspect; (C) Another patient showing AZ entering the SVC from the left instead of from the usual posterior-right aspect. Arrowhead points to a venous valve in AZ; (D) Color Doppler examination shows flow signals in the SVC and AZ; (E) Arrowhead points to a venous valve at the junction of LIV with SVC; (F and G) Arrowhead points to a venous valve at the entrance of SVC. Note thickening of one of the leaflets of the venous valve; (H) Arrowhead points to a closed venous valve in LIV viewed from top; (I) Shows LIV (with a venous valve, V), aortic arch (ACH), innominate artery (IA), left common carotid artery (LCA), left subclavian artery (LSA), and DA; (J) AA and ACH viewed from below. A venous valve is also imaged. Source: Reproduced with permission from Patel et al. Echocardiography. 2005;22:349–60. Movie clip 13.26.

A Figs 13.27A and B

B

260

Section 2: Echocardiography/Ultrasound Examination and Training

C

D

E

F

G

H

Figs 13.27C to H

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

I

J

K

L

M

N

Figs 13.27I to N

261

262

Section 2: Echocardiography/Ultrasound Examination and Training

O

P

Q

R

Figs 13.27A to R: Live three-dimensional right parasternal transthoracic echocardiographic examination of atrial septum and superior and inferior vena cavae. (A) The atrial septum (*), the entrance of superior vena cava (SVC) into the right atrium, the base of the right atrial appendage (RAA), tricuspid valve (TV), and left atrium (LA) are shown. RV: Right ventricle; (B) The previous image has been tilted to view the atrial septum (*) en face and to more clearly demonstrate the entrance of both right upper (RUPV) and right lower (RLPV) pulmonary veins into LA; (C) The entrance of coronary sinus (CS) into the right atrium is shown. A longer segment of SVC is demonstrated; (D) The arrowhead points to the right coronary artery located in the right atrioventricular groove; (E) The arrowhead points to crista terminalis. (RA: Right atrium; (F) SVC viewed in short axis; (G) RA, RV, and TV viewed from top; (H) Mitral valve (MV), left ventricle (LV), and RUVP are brought into view by further cropping; (I) Another view demonstrating SVC in short axis, long segment of RUPV, LA appendage (LAA), MV, LV, and ascending aorta (AA). PE: Pericardial effusion; (J to M) Arrowheads demonstrate Eustachian valve at the entrance of inferior vena cava (IVC) into RA in long-axis; (J and K) and short-axis; (L and M) views. Aortic valve (AV) is also imaged in K; (N) Shows relationship of AV to the RA and LA; (O) Color Doppler examination showing flow signals moving into RA through a secundum atrial septal (AS) defect in a different patient; (P and Q) Arrowheads (arrow in the Movie clip 13.27P and Q) point to a large thrombus lodged in RA adjacent to atrial septum (*) in another patient; (R) A large area of noncoaptation (N) is shown during tricuspid valve closure in systole in a patient with an infected tricuspid valve and torrential tricuspid regurgitation. The anterior leaflet (A) was predominantly involved and appears echogenic. (P: Posterior or inferior tricuspid leaflet; S: Septal tricuspid leaflet, VS: Ventricular septum. Source: Reproduced with permission from Patel et al. Echocardiography. 2005;22:349–60. Movie clips 13.27A and B, P and Q.

ADVANTAGES/DISADVANTAGES OF 3D ECHOCARDIOGRAPHY Since the quality of 3D images is generally inferior to those obtained by 2D echocardiography, it is very important to

obtain the best quality 2D images for 3D acquisition in any given examination plane. In a more recent innovation, the same transducer can be used for both 2D and 3D TTE, which makes it very convenient to acquire images in 3D as soon as an optimal quality 2D examination plane is

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

A

B

C

D

E

F

Figs 13.28A to F

263

264

Section 2: Echocardiography/Ultrasound Examination and Training

G

H

I

J

K

Figs 13.28A to K: Live three-dimensional right parasternal transthoracic echocardiographic examination of ascending aorta and right atrial appendage (RAA). (A and B) Normal ascending aorta (AA). Arrowhead in B points to left main coronary artery; (C) Enlarged AA; (D to H) RAA and its relationship to superior vena cava (SVC) are demonstrated. Arrowhead in E points to contrast signals in RAA following an intravenous bubble study. A small portion of AA is imaged between RAA and SVC. Color Doppler examination; (F) shows flow signals in SVC and RAA. Arrowhead in G points to the right coronary artery. RPA: Right pulmonary artery RAA is viewed from top in H; (I) Relationship of RAA to both AA and pulmonary valve (PV) is shown. (PA: Main pulmonary artery); (J) RAA viewed from the back; (K) Shows relationship of RAA to SVC, AA, and PA. Source: Reproduced with permission from Patel et al. Echocardiography. 2005;22:349–60. Movie clips 13.28, Parts 1 and 2.

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

A

B

C

D

E

F

Figs 13.29A to F

265

266

G

Section 2: Echocardiography/Ultrasound Examination and Training

Figs 13.29A to G: Live three-dimensional right parasternal transthoracic echocardiographic examination of pulmonary valve, main pulmonary artery, pulmonary artery branches, and left atrium. (A to D) Shows pulmonary valve (PV), main pulmonary artery (PA), proximal right pulmonary artery (RPA), left pulmonary artery (LPA) branches, and left atrial appendage (LAA); (E to G) PA viewed in short axis adjacent to atrial appendage (AA), mitral valve (MV), left ventricle (LV), left atrium (LA), and LAA. Descending thoracic aorta (DA) is also imaged. Source: Reproduced with permission from Patel et al. Echocardiography. 2005;22:349–60. Movie clip 13.29.

A

B

C

D

Figs 13.30A to D: Live three-dimensional (3D) transthoracic echocardiographic assessment of tricuspid valve regurgitation. (A) Shows optimal visualization of the tricuspid valve (TV) regurgitation jet and the vena contracta (arrowhead) acquired using the apical fourchamber view. This was done by posteroanterior cropping of 3D data set; (B) Next, the data set was cropped from top to the level of the vena contracta; (C and D) It was then tilted en face and the previously cropped posteroanterior tissue data added back. Subsequently, the maximum size of the banana-shaped TV regurgitation vena contracta was planimetered. (AS: Atrial septum; RA: Right atrium; RV: Right ventricle; VS: Ventricular septum). Source: Reproduced with permission from Velayudhan DE, Brown TM, Nanda NC, et al. Quantification of tricuspid regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area. Echocardiography. 2006;23:793–800. Movie clip 13.30.

Chapter 13: The Basics of Performing Three-Dimensional Echocardiography

obtained. Transient breath holding also helps to avoid stitch artifacts facilitating acquisition of optimal quality 3D images resulting in more accurate assessment of normal and abnormal findings. Generally speaking, acquisition of 2D images in a 3D format is relatively easy to learn but appropriate cropping of the 3D data sets is more difficult to master and has a significant learning curve. A major mental “block” is not adequately “thinking” in three dimensions and this results from a mindset honed by years of viewing and interpreting thin, slice-like 2D echocardiographic sections of the heart. For example, we are familiar with viewing the aortic valve in a 2D short-axis plane as three moving lines, which has no resemblance to its anatomic appearance when viewed by a surgeon or a pathologist. When the aortic valve is examined by 3D TTE, the en face view with depiction of individual leaflet surfaces more closely resembles the aortic valve seen anatomically. Also, a 2D echocardiographic assessment of a wall motion abnormality is done by looking at only a few thin sections of the heart, most often not obtaining the images in a proper sequential manner, making it difficult to accurately gauge the extent and severity. This problem is obviated by 3D echocardiography in which the whole left ventricle can be potentially captured in the 3D data set. This unique technology provides sequential and systematic cropping at any desired angulation resulting in more comprehensive and accurate evaluation of wall motion abnormalities. Furthermore, the data set can be stored permanently in a computer or DVD and is available for cropping by the same or different observer at any desired time. Currently, 3D TTE is not used as a stand alone technique but as an adjunct to 2D TTE in many clinical situations which are described in other chapters in this book. Depending on the findings encountered during a 2D TTE examination, a decision can be made whether the patient will benefit from a follow-up 3D study. Most often this does not involve a full 3D TTE study but only a focused examination, as described earlier, either to confirm or exclude a suspected abnormality found on 2D TTE or to provide additional information such as more reliable quantification of valvar regurgitation severity.

267

CONCLUSION 3D echocardiography has a great potential but in order for it to be used as an independent stand alone technique that replaces 2D echocardiography, its quality needs to improve considerably as well as incorporate pulsed wave and continuous wave Doppler technology. Current research is underway devoted to maximizing the usefulness of 3D echocardiography in clinical medicine to obtain information not obtainable by 2D echocardiography.

REFERENCES 1. Lang RM, Badano LP, Tsang W, et al.; American Society of Echocardiography; European Association of Echocardiography. EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. Eur Heart J Cardiovasc Imaging. 2012;13(1):1–46. 2. Wang XF, Deng YB, Nanda NC, et al. Live three-dimensional echocardiography: imaging principles and clinical application. Echocardiography. 2003;20(7):593–604. 3. Hung J, Lang R, Flachskampf F, et al.; ASE. 3D echocardiography: a review of the current status and future directions. J Am Soc Echocardiogr. 2007;20(3):213–33. 4. Nanda NC, Hsiung MC, Miller AP, et al. Live/Real Time 3D Echocardiography. Chichester, West Sussex: WileyBlackwell; 2010. 5. Nanda NC, Kisslo J, Lang R, et al. Examination protocol for three-dimensional echocardiography. Echocardiography. 2004;21(8):763–8. 6. Burri MV, Mahan EF 3rd, Nanda NC, et al. Superior vena cava, right pulmonary artery or both: real time two- and threedimensional transthoracic contrast echocardiographic identification of the echo-free space posterior to the ascending aorta. Echocardiography. 2007;24(8):875–82. 7. Yamani H, Cai Q, Ahmad M. Three-dimensional echocardiography in evaluation of left ventricular indices. Echocardiography. 2012;29(1):66–75. 8. Patel V, Nanda NC, Upendram S, et al. Live three-dimensional right parasternal and supraclavicular transthoracic echocardiographic examination. Echocardiography. 2005; 22(4):349–60. 9. Velayudhan DE, Brown TM, Nanda NC, et al. Quantification of tricuspid regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area. Echocardiography. 2006;23(9):793–800.

CHAPTER 14 How to do Three-Dimensional Transthoracic Echocardiography Examination Fabrice Larrazet, Colette Veyrat

Snapshot  History  Methods for Data AcquisiƟon  LeŌ Ventricular Assessment  Reproducibility  Regional LV FuncƟon  AorƟc RegurgitaƟon

HISTORY Three-dimensional (3D) ultrasonic systems for imaging the human heart were launched in the 1970s.1 Reliable measurements of intracardiac volumes and cardiac masses were obtained 15 years later and could be compared with magnetic resonance imaging (MRI).2–4 Data acquisition was, however, limited due to time-consuming sequential acquisition of multiple-triggered twodimensional (2D) image planes from 10 to 60 heart cycles using transesophageal rotational, transthoracic rotational, or transthoracic freehand approaches. These approaches were limited by long acquisition and analysis time in combination with poor image quality. Improvements in the size of matrix array probes and matrix array technology allowed real time 3D imaging with instantaneous online volume-rendered reconstruction. Improvements in the computing power of modern ultrasound equipment have significantly increased both spatial and temporal resolution of second-generation real time 3D systems in the mid-2000s.5 Fully sampled matrix-array transducers provide excellent real time imaging of the beating heart. These matrixes are composed of 3,000 piezoelectric

 AorƟc Annulus  Mitral Stenosis  Mitral RegurgitaƟon  Tricuspid Valve Disease  Pulmonic Valve Disease  Advances in Pediatric and Fetal Cardiac Pathologies

elements with operating frequencies ranging from 2 MHz to 4 MHz with harmonic capabilities. The most recent generation of transducers acquire both 2D and 3D echocardiographic (E) studies. We will present the methods for 3D data acquisition and then focus on each cardiac structure. As suggested by Marwick, the first step for the application of 3D echocardiography (3DE) to everyday practice is the development of normal ranges.6 We suggest following the recent recommendations for image acquisition and display using 3DE published by the American Society of Echocardiography and the European Association of Echocardiography.7 Studies issued from research on animals are voluntarily excluded from this chapter for ethical reasons. The references mainly list the studies with the most recent generation of transducers.

METHODS FOR DATA ACQUISITION Multiplane Mode 3DE probes usually allow biplane and triplane modes of acquisitions, which may be useful for mitral stenosis quantification, geometric volume acquisition, and to

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

269

rapidly check whether the entire left ventricle (LV) is visualized or not before switching to the real 3D mode. The first image is typically a reference view of a particular structure, while the second image or “lateral plane” represents a plane rotated from the reference plane. Multiplane imaging in the elevation plane is also available. Color flow Doppler imaging can also be superimposed onto the 2D images.

Real Time 3DE Real time (RT) 3D mode or live 3DE refers to the acquisition of multiple pyramidal data sets per second in a single beat. This mode overcomes the limitations imposed by rhythm disturbances often present in clinical practice (atrial fibrillation, premature heart beat) and/or respiratory motion. Live 3DE is particularly useful during bicycle stress echocardiography. It is however limited by temporal and spatial resolution. The size of the sector is usually insufficient to visualize the entire LV or right ventricle (RV) with a good image quality (i.e. with >12 frames/s). However, it permits accurate diagnoses of valvular disease or endocardial regional motion.

Fig. 14.1: A cropped image of the pulmonary trunk (PT) in systole from the subcostal view from the right ventricular outflow tract (RVOT) in a 70-year-old patient (three-dimensional probe, vivid 9, GE).

the region of interest excessively will result in a further detrimental decrease of the spatial and temporal resolution relative to RT-3DE.

Image Display

Multiple-Beat 3DE Imaging

3DE Color Flow Doppler Imaging

Electrocardiographically triggered multiple-beat 3DE provides images achieved through acquisitions of sequential volumes of data over two to seven cardiac cycles. These narrow volumes are stitched together to create a single volume. This mode of acquisition provides images of higher temporal resolution but with artifacts created by cardiac rhythm irregularities and/or respiratory motion. Apnea is often necessary over two cardiac cycle data acquisition mode. The full-volume mode has the largest acquisition sector possible, which is ideal when imaging specific structures such as the mitral valve or aortic root. This mode also has optimal spatial resolution, which permits detailed diagnosis of complex pathologies. As well, it has high temporal resolution (>30 Hz). Similar to the real time 3D and the focused wide sector—“Zoom” modalities—the gated full volume can also be rotated to orient structures such as valves in unique en face views. Furthermore, the full-volume data set can be cropped or multiplane transected to remove tissue planes in order to identify components of valvular structures within the volume or to visualize 2D cross-sectional x, y, and orthogonal planes using off-line analysis software. The Zoom mode permits a focused, wide sector view of cardiac structures. It must be noted that enlarging

3DE color flow Doppler imaging can be achieved in every mode but preferentially with full-volume acquisition. Color scale must be adjusted before switching to the 3D mode. It is very helpful to visualize the extension of eccentric regurgitation and to localize the origin of regurgitations.

Cropping The concept of cropping is inherent to 3DE. In contrast to cross-sectional modalities, 3DE requires that the “viewing perspective” be in the chamber that is in immediate continuity with the region of interest (Fig. 14.1). For example, to view the atrioventricular junctions “en face,” the operator must crop off the base and the apex of the heart so that the operator may visualize the junctions looking up from below or looking down from above. Similarly, to view the ventricular septum en face, the echocardiographer must crop off the free walls of both ventricles to view the RV aspect of the septum from right to left or the LV aspect of the septum from left to right. The paradigm for the echocardiographer, therefore, is to change from the crosssectional approach to that of the anatomist or surgeon, who can only view intracardiac structures after exposing them, by cropping the walls of the different chambers. 3D

270

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 14.2: 2D cutting planes from a volumetric three-dimensional data set obtained from an apical view (see arrow) in a patient with hypertrophic cardiomyopathy (nine short-axis and three long-axis images). The apex is in the upper left short-axis image.

cropping can be performed before, during, or after data acquisition. Cropping performed before acquisition has the advantage of providing better temporal and spatial resolution, while also providing immediate availability of the cropped image. However, if a cropped image is stored, that image may not be amenable to “uncropping” later. In contrast, if a wide data set is acquired and cropped after acquisition, it provides the advantage of retaining more diagnostic information, but at the expense of loss of spatial and temporal resolution.

Tomographic Slices It is possible to select unique 2D cutting planes (which may be difficult or virtually impossible to obtain with 2D transducer manipulation from standard windows) from a volumetric 3D data set and to display the corresponding 2D tomographic images in a cine loop format. The crosssectional planes of the heart allow accurate measurements of chamber dimensions and valve or septal defect areas as well as improved evaluation of the morphology and function of different structures with more objectivity and less operator dependency but with a lower resolution than that obtained with 2D probes in short-axis views (Fig. 14.2). The simultaneous orthogonal 2D slice mode provides multiple visualization of the same segment within a single cardiac cycle, which can be useful for ventricular function analysis as well as for wall motion assessment during stress echocardiography.8

Fig. 14.3: Semiautomated volumetric analysis and volume curves in a patient with hypertensive cardiopathy. The low outflow (2 L/min) is due to an underestimation of cardiac volumes. This apical view does not show the ventricle in its longer axis. The inferobasal boundary (three-chamber view, bottom left) is not well detected. (LV: Left ventricle)

LEFT VENTRICULAR ASSESSMENT Image Acquisition Methods Left ventricle imaging is acquired from the apical view. The operator should verify that the entire LV is imaged with its external boundaries to measure LV mass and wall motion. There are two methods to reach this goal. The first one is to begin the study in a triplanar mode ensuring a good definition of the myocardium. The second one is to begin the study in a multislice mode (12 slices) and adjust the view in order to visualize the entire LV. Adjustment of the lower and upper slice levels is often necessary. Frame rate should allow automatic LV ejection fraction (LVEF) measurements (> 12 frames/s). Multiple-beat 3DE imaging is often necessary to measure LVEF. A semiautomated volumetric analysis gives accurate and reproducible assessment of LVEF and volume curves (Fig. 14.3).9 Adjustment of optimal LV position is performed and landmarks used to initiate edge detection are positioned at the mitral annulus or the middle part of the virtual mitral annulus line in the fourchamber view and LV apex. Accuracy of edge detection depends on initial image quality. Manual corrections are often necessary but should be limited. This method allows measurements of LV volumes, ejection fraction, cardiac output, and LV mass if external borders are well defined. The operator must choose the view with the longest LV cavity to avoid underestimation of the volume and outflow that is to be shown in Figure 14.3, for example. Some apparatus provide assessment of segmental motion with a 16- or 17-segment model.

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

LV Volume and Systolic Function Assessment 3DE makes no assumptions about the shape of the LV and therefore, the calculation should be more accurate than LVEF determination by 2DE area–length method or the truncated ellipsoid method. There is accumulating evidence that the 3DE method may be advantageous in this respect. Recent comparative studies were performed with radionuclide angiography and MRI.10,11 Unlike reconstruction methods, RT-3DE can acquire volumetric 3D data usually within a single heartbeat, obviating the limitation of cardiac arrhythmia or breath hold that may impair image quality. It may also avoid cumbersome offline manipulation and allow routine integration of 3DE into everyday clinical practice. Twenty-five subjects with various cardiac pathologies were studied by RT-3DE and MRI for the assessment of LV volume by Schmidt et al. Left ventricular end-diastolic volume (LVEDV) and Left ventricular end-systolic volume (LVESV) were determined by a manual tracing technique. There was a strong correlation between volume measurements by MRI and RT-3DE (r = 0.91). LVEDV by MRI was significantly greater than that obtained by RT-3DE (182 ± 76 vs 149 ± 66 mL), which was in part explained by a significantly lower heart rate during MRI study than with RT-3DE.12 Lee et al. also validated RT-3DE against MRI for LV volume assessment. No significant differences were found between RT-3DE and MRI. It was noted that measuring volume with RT-3DE in larger cardiac chambers might be less reliable and less repeatable. This was in part attributed to a smaller transducer sector angle, which in some cases may not be able to encompass the entire LV. Importantly, RT-3DE was significantly less time-consuming for data acquisition compared to 2DE and MRI (3 ± 1, 20 ± 4, and 56 ± 10 minutes, respectively).13 Jenkins et al. found that RT-3DE could reduce the variation of sequential LV volume measurements.14 The majority of the patients had wall motion abnormalities. A semiautomated border detection software was used with manual adjustments as needed with 2D views. The correlation for 3DE was superior for both LVEDV and LVESV compared to 2DE. RT3DE had lower test–retest variation and high interobserver reproducibility. This may be important in the setting when patients require serial tests.10 The feasibility of 3DE semiautomated LV endocardial surface detection was also demonstrated in other studies.15 In 2DE, geometric assumptions made when trying to assess volume and function may not be accurate

271

in patients with wall motion abnormalities. Arai et al. conducted a study that sought to evaluate the accuracy of RT-3DE to assess LV volume and LVEF in patients with wall motion abnormalities against quantitative gated singlephoton emission computed tomography (QGSPECT) as a reference. Twenty-five patients with a history of myocardial infarction and wall motion abnormality were enrolled. The apical approach was used to obtain full-volume data sets and the endocardial borders were traced manually. RT-3DE was found to correlate better with QGSPECT in measuring LVEDV, LVESV and LVEF as compared to 2DE.16 Contrast RT-3DE allows an accurate assessment of LVEF compared to LVEF measured by single-photon emission computed tomography (SPECT) and shows low variability between observers.17

3DE Assessment of LV Regional Function RT-3DE instantaneously captures the entire LV and the ventricle can be viewed in any arbitrary plane. It is suitable for simultaneous analysis of regional wall motion in all segments. Corsi et al. used RT-3DE dynamic volumetric information to study global and regional LV function with semiautomated detection of LV endocardial surface. They first tested LV chamber volumes at three levels (basal, mid, and apical) and regional wall motion-time curves against cardiac MRI values.18 There was good agreement between RT-3DE and MRI values in global and partial LV volumes and regional wall motion. However, there were marked differences at different levels of the LV. There were lower rates of agreement at the apical level compared with mid and basal ventricular levels. Peak systolic wall motion from both modalities had modest correlation; this was driven by the variance of volumes at the apical level. Patients with dilated cardiomyopathy (DCM) were found to have increased regional volumes compared with normal subjects. Data also suggested a less synchronous contractile pattern for patients with cardiomyopathy. Their data showed that regional wall motion detection by RT-3DE was feasible.18 One of the limitations of this study was that the MRI reference values were obtained from stacked, short-axis values of the ventricle. This method is not optimal because apical endocardial definition may be inaccurate due to partial volume artifacts and LV systolic shortening may not be taken into account. Nesser et al. used a novel software package to analyze both radial long-axis MRI images and RT-3DE data sets based on LV segmental changes throughout the cardiac cycle, and regional EF was calculated from both MRI and

272

Section 2: Echocardiography/Ultrasound Examination and Training

RT-3DE modalities. This allowed for direct comparisons between both techniques without errors attributed to differences in analysis. Thirty-one patients were studied. Pyramidal scan data sets in the apical windows were obtained. They first demonstrated intertechnique agreement in wall motion assessment between RT-3DE and MRI. There was a trend toward lower correlation with MRI in the distal segments. By using semiautomated wall motion interpretation in a 16-segment model, patients with normal wall motion had similar averaged regional EF by MRI and RT-3DE (65% vs 62%, respectively). However, there were significant differences on a regional level. RT-3DE values were lower in the basal anterior, lateral and posterior segments, the mid-lateral and posterior segments, and the apical posterolateral segment. The MRI values were lower in the mid-anteroseptal and apical anterior segments. In patients with regional wall motion abnormalities, 206 of 256 (80%) segments were noted to be abnormal by MRI images. RT-3DE automated classification software detected 215 of 256 (84%) segments as abnormal in these patients. RT-3DE data were as accurate as MRI interpreted by the semiautomated interpretation software.19 Jenkins and Marwick evaluated LV regional wall motion change over time with serial 3DE and MRI in 30 patients with previous myocardial infarction at baseline and at 1 year during follow-up. Full-volume images over four cardiac cycles were obtained from an apical window with 3D offline measurement using semiautomated border detection software. Baseline end-diastolic andsystolic measurements were underestimated by 3DE when compared with the MRI landmark method (EDV 173 ± 43 vs 197 ± 57 mL, r = 0.76, P < 0.01; ESV 90 ± 38 vs 104 ± 54 mL, r = 0.87, P < 0.01). The EDV and ESV were reduced at 1-year follow-up by both techniques with no significant change in LVEF (P = NS). Of the regional volumes measured, at baseline, there was correlation between average regional EDV (r = 0.37, 13.04 ± 6 vs 8.21 ± 4 mL, P < 0.01) and ESV (r = 0.57, 6.89 ± 4 vs 4.37 ± 2 mL, P < 0.01) by both methods. However, MRI landmark method measurements were greater. At follow-up, similar correlations and differences between regional EDV were seen, but regional ESV was found better. The results were similar whether the myocardial segments were divided into basal, mid, and apical regions or if they were divided by the coronary territories. Discrepancies in the regional volumes found in this study were attributed in part to different software analysis algorithms for regional wall motion analysis by 3DE and MRI. Poor endocardial border

definition was also considered as a potential source of discrepancy.20 Advances in 3DE technology along with further sophistication of 3DE software analysis packages may help to improve accuracy and reliability.

Normal Values Chahal et al. defined age-, sex-, and ethnicity-specific reference values for 3DE LV volumes and LVEF in a large cohort of white European and Asian Indian subjects.21 Transthoracic 3DE imaging is recommended for the routine evaluation of LV volumes and function. However, there remains a lack of population-based reference values for 3DE LV volumes and LVEF, hindering adoption of this technique into routine clinical practice. They identified subjects from the London Life Sciences Prospective Population (LOLIPOP) study who were free of clinical cardiovascular disease, hypertension, and type 2 diabetes. All subjects underwent transthoracic 2D and 3DE for quantification of LV end-systolic volume index, LV end-diastolic volume index and LVEF. 3DE image quality was satisfactory in 978 subjects (89%) for the purposes of LV volumetric analysis. Indexed 3DE LV volumes were significantly smaller in female subjects compared with males and in Indian Asians compared with white European. Upper limit of normal (mean ± 2 SD) reference values for the LV end-systolic volume index and LV end-diastolic volume index for the four ethnicitysex subgroups were, respectively, as follows: European white men, 29 mL/m2 and 67 mL/m2; Indian Asian men, 26 mL/m2 and 59 mL/m2; European white women, 24 mL/m2 and 58 mL/m2; Indian Asian women, 23 mL/m2 and 55 mL/m2, respectively. Compared with 3DE studies, 2D echocardiography underestimated the LV end-systolic volume index and LV end-diastolic volume index by an average of 2.0 mL/m2 and 4.7 mL/m2, respectively. LVEF was similar among all four groups and between 2D and 3D techniques, with a lower cutoff of 52% for the whole cohort. They conclude that these reference values should facilitate the standardization of the technique and encourage its adoption for the routine assessment of LV volumes and LVEF in the clinical echocardiography laboratory. This study supports the application of ethnicity-specific reference values for indexed LV volumes.

REPRODUCIBILITY A recent study identified the best echocardiographic method for sequential quantification of LVEF and volumes

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

Fig. 14.4: Three-dimensional echocardiography of the left ventricle (LV) in a patient with hypertrophic cardiomyopathy.

in patients undergoing cancer chemotherapy.22 They selected patients in whom stable function in the face of chemotherapy for breast cancer was defined by stability of global longitudinal strain (GLS) at up to five time points (baseline, 3, 6, 9 and 12 months). In this way, changes in EF were considered to reflect temporal variability of measurements rather than cardiotoxicity. A comprehensive echocardiogram consisting of 2D and 3D acquisitions with and without contrast administration was performed at each time point. Stable LV function was defined as normal GLS (≤ –16.0%) at each examination. The EF and volumes were measured with 2D-biplane Simpson’s method, 2D triplane, and 3DE by two investigators blinded to any clinical data. Inter-, intra-, and test–retest variability were assessed in a subgroup. Among 56 patients (all females, 54 ± 13 years of age), noncontrast 3D EF, end-diastolic volume, and end-systolic volume had significantly lower temporal variability than all other methods. Contrast only decreased the temporal variability of LV end-diastolic volume measurements by the 2D biplane method. Their data suggested that a temporal variability in EF of 0.06 might occur with noncontrast 3DE due to physiological differences and measurement variability, whereas this might be > 0.10 with 2D methods. Overall, 3DE also had the best intra- and interobserver as well as test–retest variability. The authors concluded that noncontrast 3DE was the most reproducible technique for LVEF and LV volume measurements over 1 year of follow-up.

LV Mass The 3DE is able to directly identify the LV epicardial and endocardial boundaries and measure the mass

273

of LV myocardium (Figs 14.2 and 14.4).23 Mor-Avi et al. used RT-3DE data sets as a tool to guide selecting nonforeshortened apical two- and four-chamber views. The LV mass was calculated by the use of biplane method of disks. The RT-3D data resulted in significantly larger LV long-axis dimensions, and measurements of LV mass better correlated with MRI (r = 0.90) than 2D (r = 0.79). The 2D technique underestimated LV mass (bias 39%), whereas RT-3D measurements showed only minimal bias (3%). In addition, the RT-3D technique reduced interobserver variability (37–7%) and intraobserver variability (19–8%).24 The same group subsequently investigated LV mass determination with a new RT-3DE volumetric method by using direct endocardial and epicardial surface detection that would not involve subjective image plane selection. The study showed that LV mass obtained directly from RT-3DE data was more accurate than that from RT-3DE-guided 2D methods. The direct RT-3DE measurements were also found to have tighter limits of agreement with MRI.25 Despite the promising results found in this study, the interobserver variability of RT-3DE LV mass was 12.5% that was relatively high compared to other imaging modalities. This was attributed to suboptimal epicardial visualization and elements of subjectivity in terms of selecting initialization points and poor visualization of basal segments.26 van den Bosch et al. conducted an interesting study that compared RT-3DE LV mass in patients with congenital heart disease (CHD). Twenty patients with CHD (including tetralogy of Fallot, pulmonary stenosis, transposition of great arteries, congenital aortic stenosis and Ebstein’s anomaly) underwent M-mode echocardiography, MRI and RT-3DE. Full-volume RT-3DE scans were obtained. Two- and four-chamber views with the largest long axis were selected and epicardial and endocardial borders were manually traced. There was a significant difference between RT-3DE and MRI LV mass calculations (135 ± 52 vs 154 ± 55, P < 0.01). However, this difference appears to have been driven by poor-quality 3DE data sets. When good to moderate RT-3DE images were compared with MRI, there was no significant difference (144 ± 59 [MRI], 143 ± 58 [RT-3DE]). A poor correlation was found between M-mode LV mass measurements compared to both RT-3DE and MRI.27 In addition to LV mass, it is evident that 3DE is also feasible, accurate and reproducible for LV volume and EF assessment in this population. This study is important in that an abnormally shaped LV was studied by RT-3DE. In such scenarios, it is difficult to make

274

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 14.5: Tomographic systolic short-axis views from the apex (upper left) to the base (bottom right) during bicycle stress echo (132 bpm). Anterior region is at the top, inferior region at the bottom, septum on the left, and lateral wall on the right side of each view. (Movie clip 14.5).

Fig. 14.7: Tomographic views during a bicycle stress test (180 bpm). (LV: Left ventricle) (Movie clip 14.7).

geometric assumptions, and this is an arena in which 3DE is advantageous over 2D and 1D echocardiography. The easiness and relative speed of data acquisition as compared to MRI makes RT-3DE an attractive alternative.

3D Stress Echocardiography Because LV volumes often decrease during stress echo, real time 3D mode can be applied in echogenic patients at rest as well as at peak stress, and image quality can be optimized with contrast agents for nonechogenic patients. Image quality is often excellent on apex section and midportion but not on basal segments even with high heart rate values (Figs 14.5 to 14.7).

Fig. 14.6: Tomographic views of the left ventricle (LV) in diastole during a bicycle stress test (135 bpm).

Using 3DE for stress testing may circumvent the limiting issues of 2DE stress testing and become a more efficient noninvasive stress modality.28,29 In 3DE stress testing, the images are obtained from single volumetric acquisition without having to change transducer position. It reduces the recording time and delay from peak stress, thus enhancing the detection rate of transient ischemia. Furthermore, foreshortening is avoided by way of fullvolume scanning, which incorporates the entire LV. Alignment and cropping data sets enable visualization of the true apex. Cropping full-volume data sets could provide enhanced and comprehensive interpretation of wall motion so that regional wall motion abnormalities are not missed. A number of studies have applied RT-3DE during dobutamine stress echocardiography (DSE) for the assessment of ischemia.30–33 Ahmad et al. were the first to compare 3D DSE with 2D DSE to test the feasibility and efficacy of ischemia detection. RT-3DE and 2DE images were obtained in 253 patients within 30 seconds of each other at baseline and then at peak stress. They found good agreement between the two techniques in detecting baseline and peak stress wall motion abnormalities (84% and 88.9%, respectively). Stress RT-3DE was superior compared to its 2D counterpart for detection of ischemia at peak stress (92.7% vs 84.6%, P < 0.05, respectively). Importantly, scanning time was significantly less for 3D DSE compared to 2D DSE (27.4 ± 10.7 seconds vs 62.4 ± 20.1 seconds, respectively, P < 0.0001). Finally, stress RT3DE was more sensitive in CAD detection compared to 2D DSE in patients who underwent coronary angiography (87.9% vs 79.3%, respectively).34 Similarly, Matsumura et al.

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

demonstrated that RT-3D DSE had comparable sensitivity (86% vs 86%), specificity (80% vs 83%), and accuracy (82% vs 84%) as compared to 2D DSE for the detection of CAD but was much more rapid (29 ± 4 vs 68 ± 6 seconds, P < 0.0001).35 RT-3D is highly feasible and shows a high concordance with standard 2D stress echo during dipyridamole stress echocardiography imaging. 2D images take a longer time to acquire and RT-3D is more time-consuming to analyze.35 One of the current limitations of RT-3DE is the relatively poor image quality, which could result in poor visualization of subtle wall motion abnormalities. Additional challenges include limited temporal resolution, spatial resolution, range of transducers, and heterogeneity of the chamber quantification algorithms, and so on. Pulerwitz et al. and Nemes et al. showed that performing contrast during RT-3D DSE is feasible to improve image quality.36,37 Ultrasound contrast significantly increased the proportion of segments adequately visualized during rest (from 91% to 98%, P = 0.001) and peak dobutamine infusion (from 87% to 99%, P = 0.001). Contrast generated higher concordance between observers (96.9% at rest and 98.2% at peak stress) whereas noncontrast studies had much lower agreement (84.4% at rest and 79.9% at peak stress). RT-3D stress testing shortens the stress protocol without compromising the accuracy for the diagnosis of CAD, which favors a potentially widespread use in routine clinical practice. 3DE has made a transition from being a research tool to a clinically applicable imaging modality. The clinical value of 3DE in LV assessment is being increasingly appreciated. Future improvement of 3DE resolution should pave the way for this technique to emerge as the new standard for routine assessment of LV mass, volume and function.

3D Speckle-Tracking Applications Six acquisitions of different parasternal and apical LV views are still required to obtain all strain components in all LV segments with 2D methods. With developments in ultrasound transducer technology and both hardware and software computing, systems capable of acquiring real time volumetric LV data are now widely available.38 These 3D approaches can measure all strain components in all LV segments from a single acquisition. Furthermore, they are angle independent, do not suffer from strain estimation errors associated with out-of-plane motion, and may in theory allow more precise calculations of LV twist and assessment of shear strain components. However, tracking in 3D indeed raises some challenges. The increased field of

275

Fig. 14.8: Bull’s-eye plots. Three-dimensional speckle tracking of a hypertrophic left ventricle (LV) with normal ejection fraction. Global strain is low (– 12%). Data from two segments were not available because the entire structure was not well visualized.

view of volumetric images comes at the cost of both spatial and temporal resolution of the data set. In other words, the current volumetric data sets show a coarser speckle pattern and a higher speckle decorrelation between subsequent volumes. The latter effect becomes even more pronounced in data sets acquired at high heart rates (e.g. during stress echocardiography). Moreover, because of the amount of data available in volumetric data sets, the computational load is also higher compared with 2D data sets. These aspects pose a challenging environment for myocardial motion and deformation imaging. A 3D LV surface can be built, which is subdivided into several segments (ranging from 16 to 18 depending on the segment model). These segments are usually color coded for visual inspection. After tracking the LV surface, deformation is estimated and presented in different ways, with strain curves for different segments, using bull’s-eye plots (Fig. 14.8), or by showing the deformed surface.

Methods of Validation The most common 3D STE approach is based on block matching. A speckle pattern within a region of interest is identified in one frame and tracked within a search region of the successive frame. After comparing this block with all possible matching regions within this search region (dotted blocks), the position of the best matching block compared with the original block determines tissue motion. By repeating this process for multiple regionof-interest blocks, motion between two successive frames for the whole myocardium may be estimated.

276

Section 2: Echocardiography/Ultrasound Examination and Training

The validation of any strain imaging method and its implementation into clinical routine can be regarded as a four-step process, beginning with a validation on simulated models. In the next step, the method is usually validated using in vitro and in vivo experiments. Finally, its implementation in clinical practice can begin. In every step, deformation measurements are compared against a reference measurement (i.e. a ground truth). With every stage, ultrasound images become more realistic (i.e. containing more image artifacts and having an increased level of noise), while obtaining a ground truth deformation measurement becomes more complicated.

Clinical Validations and Applications Global LV Function Several recent publications indicate that 3D speckletracking echocardiography (STE) is a trustworthy technique for the evaluation of global LV function.39–41 Interestingly, global CS extracted by 3D STE seemed to be 10% higher (i.e. more negative) in comparison with tagged MRI. 3DE with speckle tracking can be useful for the analysis of LV dyssynchrony.

REGIONAL LV FUNCTION It still remains unclear whether 3D STE regional strain values are as reliable as those obtained by Dopper tissue imaging (DTI) or 2D ST. In the clinical setting, delayed enhancement MRI is commonly used as a gold standard to locate and quantify the extent of myocardial scar. As such, measured segmental strain values can be compared against those segments identified as being scar tissue. It is important to note that this is not a direct comparison of two techniques as strain is a parameter of myocardial function, whereas delayed enhancement MRI characterizes the ventricle morphologically. To date, delayed enhancement MRI has been used as a reference method by only one 3D STE study, in which Hayat et al. found significantly decreased segmental LS, CS and RS values obtained by both 3D block matching and 2D ST in the segments identified as transmural myocardial scar.40 Occasionally, strain values are compared with the wall motion scores estimated by eyeballing. However, the meaningfulness of such comparisons is questionable as wall motion scoring is known to be rather subjective and to require considerable expertise of the observer.

Contractile Reserve Assessment of contractile reserve using 3D global circumferential strain (GCS) has also the potential to predict cardiovascular events in patients with DCM and may thus have clinical implications for the management of such patients.42 Sixty-five patients with DCM with a mean ejection fraction of 34 ± 8% (all 50 mm2 (sensitivity = 92% and specificity = 87%) for severe aortic regurgitation. Fang et al. found that aortographic or surgical grading of aortic regurgitation correlated better with 3D TTE VCA (r = 0.95) than with 2D TTE vena contracta width (VCW). 3D TTE VCA also demonstrated excellent distinction between angiographic grades, whereas 2DE VCW had more overlap between aortographic grades. Whether the regurgitant jet was central or eccentric did not affect VCA grading. They proposed 3DE VCA of < 0.2 cm2, 0.2 to 0.4 cm2, 0.4 to 0.6 cm2, and >0.6 cm2 for angiographic Grade I, II, III, and IV aortic regurgitation, respectively.60 The proximal isovelocity surface area (PISA) geometry can be variable depending on the shape of the regurgitant orifice. Using RT-3DE color Doppler technique, the PISA can be directly visualized and measured without geometric assumptions. In an in vitro model of aortic regurgitation, PISA-derived aortic regurgitant volumes obtained by 2D and 3D methods were compared with actual volumes measured by an ultrasonic flow meter. Correlation with the reference value was stronger for 3D PISA method. For the 3D PISA method, correlations between effective regurgitant orifice area (EROA) and the actual area were similar for both circular and noncircular orifices. However, there was no significant correlation between actual area and 2D-calculated EROA for noncircular (triangles and arc) orifices. 3D PISA yielded a more pronounced improvement compared with 2D in noncircular orifices.61 However, it should be noted that the 2D or 3D Doppler flow map does not reflect the true isovelocity shells, especially at the periphery where there is significant flow angle alignment problem. 3D will correct the measu-

rement errors related to the shape but will not correct underestimation caused by Doppler dependency at the periphery of the isovelocity shells. A recent review described the assessment of the aortic valve by echocardiography and also the roles that multidetector CT (MDCT) and cardiac magnetic resonance have to play as complimentary imaging modalities. It also described how to resolve apparent discrepancies in grading aortic stenosis and discussed the management of apparently moderate stenosis associated with cardiac symptoms or LV dysfunction.62

AORTIC ANNULUS The strengths of echocardiography are its wide availability and extensive validation. Furthermore, its portability makes it natural for real time guidance of procedures. However, it is quite well established that echocardiographic visualization of the aortic valve from the transthoracic approach is difficult to guarantee. Because of the relatively low spatial resolution, 3DE is not ideal for visualization of the coronary arteries, in particular, the location of the origin of the left main artery, which is extremely important during pre-Transcatheter aortic valve replacement (TAVR) evaluation to prevent the prosthesis from affecting coronary circulation.63

Mitral Valve Assessment Mitral valves and prosthesis are preferentially analyzed from apical views (Figs 14.17 to 14.21). RT-3D TTE is often feasible for structure analysis either from the ventricular or the atrial aspect. Multiple-beat 3DE is necessary for the visualization of the origin of regurgitations and for VCA and EROA measurements.

MITRAL STENOSIS The assessment of mitral valve commissures, leaflets, and subvalvular apparatus morphology by 3DE is more accurate than 2DE (Fig. 14.22). Surgical and en face views from either the left atrium or LV can be easily obtained by 3DE. The position and degree of leaflet fusion and thickening, as well as the pliability of the mitral subvalvular apparatus, can be completely visualized on 3DE. RT3DE showed superior interobserver and intraobserver variability of echocardiographic Wilkins score based on valve flexibility, thickening, and calcification, a significant predictor for the success of percutaneous valvuloplasty in rheumatic mitral stenosis.64,65 3DE enables unique

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

281

Fig. 14.17: Mitral valve (arrows showing the anterior valve leaflet on the top and the posterior valve leaflet on the bottom) from the left ventricle. (Movie clips 14.17 and 14.17A).

Fig. 14.18: Mitral valve fibrosis with moderate stenosis (apical approach, view from the ventricle). (LA: Left atrium; LV: Left ventricle).

Fig. 14.19: Mitral bioprosthesis in diastole (apical approach, view from the ventricle). (LA: Left atrium; LV: Left ventricle).

Fig. 14.20: Mitral bioprosthesis in systole (apical approach, view from the left ventricle). (LA: Left atrium; LV: Left ventricle; MP: Mitral prosthesis).

Fig. 14.21: Mechanical mitral valve prosthesis in diastole with open leaflets (en face view). (LA: Left atrium).

Fig. 14.22: View from the left ventricle (LV) of mitral stenosis and commissural fusion (apical approach). (LA: Left atrium).

282

Section 2: Echocardiography/Ultrasound Examination and Training

MITRAL REGURGITATION

Fig. 14.23: Posterior mitral valve prolapse and ruptured chordae tendinae (apical approach, view from the left atrium). The posterior leaflet is visualized at the bottom. (LA: Left atrium; LV: Left ventricle). (Movie clips 14.23 and 14.23A).

orientation of the mitral valve. The valve is visualized in a long-axis view and a cursor is steered to perpendicularly intersect the leaflet tips and to provide a short-axis view. It is much easier and faster to define the image plane with the smallest orifice area. This allows a more accurate direct planimetry of mitral valve area (MVA). Errors due to transducer malpositioning can be obviated. The utility of RT-3DE in the assessment of mitral stenosis has been established by multiple studies.66–69 Sugeng et al. compared 3DE planimetry and 2D TTE/Doppler methods with the invasive Gorlin formula.70 They found that MVA estimated by 3DE planimetry had the best agreement with the invasively determined MVA (r = 0.98, average difference of 0.06 cm2). Kasliwal et al. reported a high degree of agreement between MVA obtained by 3DE with the true mitral orifice measured directly at surgery, whereas 2DE planimetry tended to overestimate the MV orifice area. 3DE planimetry modified the clinical classification of severity by 2D method in 46% of patients. In patients with moderate to severe stenosis by 3DE, 50% were clinically underestimated by 2DE (average difference 0.2 ± 0.1 cm2). 3D guidance significantly reduced intraobserver and interobserver variability.68 Accuracy of RT-3DE planimetry may be even superior to the invasive Gorlin’s method, when the median value obtained from three classical noninvasive methods (2D planimetry, pressure half-time, and PISA) were used as the reference. Therefore, RT-3DE planimetry has been proposed as the new gold standard for MVA quantification.71

3DE provides additional information in understanding the mechanism of MR.72,73 Mitral valve pathologies such as prolapse, flail leaflets, or perforation are better delineated by 3DE, which leads to better surgical planning (repair vs replacement).74 The exact scallops involved and the extent of prolapse can be better visualized and quantified with 3DE. 3D TEE is superior to 3D TTE. Atrial view derived from 3D TTE can evidence the extent of valve prolapse (Fig. 14.23). Pepi et al. showed that 3D techniques were feasible in a relatively short time (3D TTE 7 ± 4 minutes; 3D TEE 8 ± 3 min), with good (3D TTE 55%; 3D TEE 35%) and optimal (3D TTE 21%; 3D TEE 45%) imaging quality in the majority of cases.74 3D TEE allowed more accurate identification (95.6% accuracy) of all MV lesions in comparison with other techniques. 3D TTE and 2D TEE had similar accuracies (90% and 87%, respectively), whereas the accuracy of 2D TTE (77%) was significantly lower. The concordance between 3D TTE and surgery in locating prolapsing mitral valve scallops was 87% and 93% for the anterior and posterior leaflets, respectively, compared to 76% and 75%, respectively, for 2D TEE. The incremental value was seen in assessing the commissures and the anterior leaflet but not the posterior leaflet. 3DE analysis of the mitral annulus geometry and its motion improves the understanding of the mechanisms of functional MR.75 The deformation of the mitral valve was asymmetric in ischemic cardiomyopathy whereas it was symmetrical in dilated cardiomyopathy. This differentiation should lead to better surgical strategies. The 2DE PISA method is based on the assumption that the mitral valve flow convergence zone is hemispheric. It does not account for the impact of orifice shape and leaflet angle on the geometry.76 In a study by Yosefy et al., only 1 in 50 patients with MR had a hemispheric flow convergence contour by RT-3D, with the remaining being hemielliptic.77 Applying a hemiellipsoid formula, instead of a hemispheric model, reduced the underestimation from 49% to 26%.78 The geometry of PISA is dependent on the disorder of the mitral valve. 3D color Doppler images showed an elongated and curved PISA in functional MR, whereas the geometry was rounder in mitral valve prolapse. PISA’s flattened shape correlates with a more severe degree of underestimation of EROA. The PISA method underestimated the EROA by 24% in functional MR, but not in mitral valve prolapse. 3DE is particularly useful in patients who have eccentric

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

283

Fig. 14.24: Direct measurement of the mitral vena contracta (VC) and regurgitant orifice (0.58 cm2). (LA: Left atrium; LV: Left ventricle).

Fig. 14.25: Tricuspid anterior, inferior (posterior), and septal leaflets (apical approach, view from the left ventricle). (RA: Right atrium; RV: Right ventricle). (Movie clip 14.25).

jets. 3D color Doppler reveals the origin, direction and spatial orientation of complex jet geometry, allowing direct assessment of its shape and regurgitant volume quantitation.78,79 De Simone et al. demonstrated that 3D TEE jet volumes quantified by tracing the jet in a rotational manner, unlike 2D jet area, significantly correlated with angiography and 2D volumetric regurgitation assessment in patients with eccentric jets.80,81 Shiota et al. showed in an in vitro MR model that noncircular regurgitant orifice with eccentric wall-hugging jets forms a flattened and elongated flow convergence zone which is easily underestimated by 2DE. A more suitable 3DE hemielliptical model resulted in a better estimation of actual flow rates with less underestimation.82 Another promising 3D approach to assess MR severity is to directly measure the anatomic regurgitant orifice to overcome the limitations of the PISA method (Fig. 14.24). The regurgitant orifice can be seen en face from a left atrial perspective. By systematic and sequential cropping of the 3D data set, a plane is placed at the gap between the leaflets to trace an orifice area. Iwakura et al. reported that regurgitant orifice area on 3D TTE color Doppler was almost identical to that obtained by quantitative echocardiography regardless of the shape of the regurgitant orifice.83 Khanna et al. demonstrated that VCA from RT-3D TTE, but not VCW or calculated VCA by 2D TTE, closely correlated with angiographic grading with very little overlap, with VCA < 0.2 cm2 for mild MR and > 0.4 cm2 for severe MR.84 In an in vitro pulsatile circulatory loop model with various shapes (circle, slit and arc) and sizes to model MR, 3D manual tracing of equidistant radial planes and 3D-VCA had good correlation with actual

regurgitant volumes and orifice area.85 In a clinical study of 61 patients, 3D-VCA correlated with Doppler-derived EROA; the relationship was stronger than for 2D-VCW. The advantage of 3D-VCA over 2D-VCW was more pronounced in eccentric jets and in moderate or severe MR.85

TRICUSPID VALVE DISEASE Compared with mitral and aortic valves, the assessment of tricuspid valve is not as feasible and accurate with 3DE. Tricuspid valve is geometrically more variable due to the unique configuration of tricuspid leaflets and annulus. A major advantage of 3D TTE over 2D TTE is the capability of obtaining a short-axis plane of the tricuspid valve allowing simultaneous visualization of all three leaflets and their attachment to the annulus (Fig. 14.25). In order to improve the visualization of the tricuspid leaflets, the gain should be increased more than for mitral valve analysis.86 RT3DE supplements 2D TTE and 2D TEE with detailed morphology of the valve including size and thickness of leaflets, annulus shape and size, myocardial walls and their anatomic relationships.87 RT-3D TTE has demonstrated substantial incremental value in the assessment of various tricuspid valve pathologies in identifying the mechanism of TR like infective endocarditis, congenital disease, like Ebstein anomaly or atrioventricular septal defects, rheumatic fever, carcinoid syndrome, endomyocardial fibrosis, myxomatous degeneration of the TV leading to prolapse, penetrating and nonpenetrating trauma, and iatrogenic damages during cardiac surgery, biopsies, pace maker leads, and catheter placement for chemotherapy in right heart chambers (Fig. 14.26).88 Loss of tricuspid valve

284

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 14.26: Catheter (arrow) for chemotherapy visible through the tricuspid valve (view from the right ventricle). (RA: Right atrium; RV: Right ventricle).

Fig. 14.28: Pulmonary valve from the outflow tract in diastole (subcostal view). (RVOT: Right ventricle outflow tract).

leaflet tissue, defects in leaflets, and size of noncoaptation can be delineated.90 The exact sites of leaflet prolapse and chordae rupture is well visualized by 3D TTE.88 These can be accurately depicted from the right atrial surgical view to help in the surgical planning. 2DE assessment of TR severity has been challenging due to the complex geometry of the tricuspid valve. RT-3D TTE color demonstrated the feasibility of obtaining VCA of the TR jet by systematic and sequential cropping of the RT-3DE color Doppler data set with imaging planes exactly parallel to the tricuspid valve orifice. These Doppler measurements of VCA can be used for quantitative assessment of TR. Velayudhan et al. found a reasonable relationship between VCA measured by RT-3DE with

Fig. 14.27: Pulmonary valve from the outflow tract in diastole (parasternal view). (RVOT: Right ventricle outflow tract).

that measured by 2DE/Doppler ratio of regurgitant jet area/right atrial area but there was a poor correlation with VCW by 2DE. This is particularly true in patients with eccentric jets where 2D TTE measurements of VCW can be underestimated.89 The presence of eccentric jets does not affect the accuracy of the 3D TTE measurement of VCA. They proposed VCA 0.5 cm2 for mild and 0.75 cm2 for severe TR. Manually traced 3D TR volumes and regurgitant/atrial volume ratios provide a new method of assessing the severity of TR.90 Short-axis imaging of the tricuspid valve orifice is rarely feasible by 2DE. Using RT3DE, the orifice of tricuspid valve can be clearly visualized and planimetered, allowing accurate assessment of orifice area in patients with tricuspid stenosis or carcinoid disease.91,92

PULMONIC VALVE DISEASE Direct evaluation of pulmonic valve and planimetry of 3D VCA can be performed from the parasternal and subcostal views (Figs 14.27 to 14.29). However, 3DE has a slow frame rate, which can result in the largest PR jet falling between frames. Sometimes a modified apical view offers the possibility to visualize the pulmonic valve. 3DE may play an incremental role for the preoperative assessment of patients with carcinoid heart disease. RT-3D TTE provides an en face view of pulmonary valve from the RV outflow perspective, which is not obtainable by routine 2DE. Additional information such as thickened and retracted PV annulus and leaflets can be clearly visualized.93,94

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

Fig. 14.29: Pulmonary valve from the outflow tract in systole (subcostal view). (RVOT: Right ventricle outflow tract).

ADVANCES IN PEDIATRIC AND FETAL CARDIAC PATHOLOGIES The recent development of specific 3D pediatric probes allows imaging of pediatric hearts with high temporal and spatial resolution. Lesions are often anatomically complex, and 3DE allows increased appreciation of complex spatial relationships and can thereby be valuable in understanding functional anatomy and planning interventions. Assessment of pediatric myocardial function can be difficult, with highly variable ventricular morphology. Assessment of RV function and function of the single ventricle are current challenges in CHD. The introduction of myocardial tissue Doppler velocities and deformation imaging (strain and strain-rate quantification) facilitates the quantification of myocardial function independent of underlying morphology. These techniques offer new insights into the mechanics of CHD.95 Automated RT3D TTE techniques for measuring volumetric flow (VF) in children are also available. With two orthogonal sections of valve flow, a hemispheric Gaussian control surface is placed at the level of the orifice; the region of interest is selected by tracing cross-sectional contours of color Doppler signals during diastolic or systolic phase depending on the valve and flow rate curves. VF for MV is derived from area under the flow rate curve. Compared with stroke volume by RT-3DE, the correlation with VF was excellent for MV (r = 0.91), good for AV (r = 0.89) and PV (r = 0.89), but poor for TV (r = 0.20) by RT-3DE in 19 healthy children (age = 11.5 ± 3.5 years). There were good agreements for AV (bias = 0.9 ± 5.0 mL), PV (bias = –0.4 ± 5.7 mL), and MV (bias = 4.1 ± 4.7 mL), and marked

285

underestimation for TV (bias = –24.4 ± 14.6 mL).96 En face reconstruction of VSD on RV septal surface using RT-3DE gives irreplaceable noninvasive information concerning this pathology.97 The gains, compress, and smoothening are adjusted to render an en face view of the RV surface of the interventricular septum. Subxiphoid long-axis view with color Doppler interrogation can show the ventricular septal defects. When the interventricular septum is serially sliced on subxiphoid short-axis views, basal slices can demonstrate perimembranous defects in relation to the tricuspid and aortic valves, mid-cavity slices can demonstrate mid-muscular defects, and apical slices can show apical muscular defects. In 3D ultrasound, volumetric data are acquired from a single window using a few seconds scanning, which are subsequently used for reconstruction of multiple views in any plane. This reduces the overall scanning time and operator and window dependence, in addition to improving the assessment of cardiac anatomy. Planes that are not accessible in 2D scanning, such as the interventricular septum or coronal plane, can be reconstructed. Volume-rendered or surface-shaded images give an illusion of depth, which might be useful in the detection of complex anomalies, such as those involving the conotruncal septum. Alternatively, the images can be displayed as three or four simultaneous multiplanar reformatted projections with the ability to move through the volumes. 3D quantitative measurements are more accurate and reproducible than 2D techniques. Acquisition of temporal information with cardiac gating enables display of these images as cine loops in multiple planes [four-dimensional (4D) imaging], which is useful in the evaluation of cardiac motion, cardiac function, valvular function, volumes and cardiac output. 3D imaging of regurgitant and stenotic jets is possible when 3D ultrasound is combined with color or power Doppler imaging. 3D color flow angiography can reveal complex cardiovascular anatomy, anomalous vessels, and small septal defects.98 Hongmei et al. recently evaluated the role of 4D ultrasound with B-flow imaging and spatiotemporal image correlation (STIC) in the evaluation of 31 normal fetuses and 28 fetuses with CHD (6 with double-outlet RV, 5 with complete transposition of great arteries, 8 with tetralogy of Fallot, 3 with right aortic arch, 2 with persistent left superior vena cava, 3 with truncus arteriosus communis, and 1 with interruption of aortic arch) at gestation ages ranging from 18 to 39 weeks using transabdominal 4D B-flow sonography. In all but two normal fetuses, all extracardiac vessels such as the aorta, pulmonary artery, ductus arteriosus, inferior vena cava,

286

Section 2: Echocardiography/Ultrasound Examination and Training

and ductus venosus could be detected on reconstructed images. In seven normal cases, a 4D image was recorded to allow simultaneous visualization of all four pulmonary veins. In the 28 fetuses with cardiac anomalies, 4D sonography with B-flow imaging and STIC detected the “digital casts” of the outflow tracts, great arteries, and veins draining into the heart.99

CONCLUSION So far, 3DE superiority over 2D imaging cannot be disputed and is already supported by a relevant and documented literature, even if series on wider population samples are further needed. Above all, the newness of 3D data opens new fields of research. Two preliminary issues are however raised, specifically dedicated to new 3D users. First, as a general consideration, prior to the work on these new perspectives, a new task is mandatory: we have to complement our anatomic knowledge, which differs from 2D information we were used to. Most of the anatomic descriptions we were formatted with since decades have to be updated, both for the already 2D imaged structures we are familiar with, due to their sometimes unexpected connections we discover when we crop off planes, but overall for those structures which were ignored or incompletely imaged. New users and students will grow easily familiar with this new imaging modality in the same way as 2D facilitated our understanding of cardiac anatomy vs 1D visualization. One of 3D imaging’s strength lies in its synthetic representation of moving and live structures, which even surgeons do not often completely master. As a first step of the second issue, we have to solve a practical question for today: can we perform TTE with the sole 3DE transducer or should we still use 2D matrix transducers? Imbedded 2D imaging in 3D transducers does not actually offer as good images as 2D probes do. 3D probes are bigger than 2D probes and their use can be more uncomfortable for the patient. Mitral planimetry with tomographic slices is feasible but with poorer definitions than with 2D probes. Endocardial borders during stress echo and/or vegetations are better visualized with 2D matrix probes. Actually, stress echo can be performed with 3DE in echogenic patients only. Baseline echoes should be performed with both 2D and 3D probes and sometimes with the continuous wave 2 MHz probe. Much of the second issue concerns the technological progress which should accompany our efforts to renew our echocardiographic knowledge. One of the limitations

of the current 3D systems is the lower frame rate yielding limited spatial and temporal resolution. Therefore, thinner structures such as valve leaflets are not imaged well. Improving the acquisition rate will provide higher resolution imaging, potentially enabling new perspectives for qualitative and quantitative assessment of valvular structures. Ongoing advances in microprocessor technology will provide the tools necessary to reduce matrix array transducer size, enhance resolution and will decrease the time required for acquisition, reconstruction, and data processing. It is not unrealistic to expect that echocardiography will be carried out using a single probe with excellent resolution in one single apical sequence with or without color imaging depending on the presence or absence of disturbed flow. Automatization of volume, valve surface and regurgitant surface measurements will further shorten the examination time. Finally, our exciting goal is the renewal of our pathophysiological insight through this 3D imaging of cardiac structures and function which should pave the way toward new research in cardiology.

REFERENCES 1. Dekker DL, Piziali RL, Dong E Jr. A system for ultrasonically imaging the human heart in three dimensions. Comput Biomed Res. 1974;7(6):544–53. 2. Sheikh K, Smith SW, von Ramm O, et al. Real-time, threedimensional echocardiography: feasibility and initial use. Echocardiography. 1991;8(1):119–25. 3. King DL, Harrison MR, King DL Jr, et al. Improved reproducibility of left atrial and left ventricular measurements by guided three-dimensional echocardiography. J Am Coll Cardiol. 1992;20:1238–45. 4. Gopal AS, Schnellbaecher MJ, Shen Z, et al. Freehand three-dimensional echocardiography for determination of left ventricular volume and mass in patients with abnormal ventricles: comparison with magnetic resonance imaging. J Am Soc Echocardiogr. 1997;10(8):853–61. 5. Sugeng L, Weinert L, Thiele K, Lang RM. Real-time threedimensional echocardiography using a novel matrix array transducer. Echocardiography. 2003;20(7):623–35. 6. Marwick TH. Application of 3D echocardiography to everyday practice: development of normal ranges is step 1. JACC Cardiovasc Imaging. 2012;5(12):1198–200. 7. Lang RM, Badano LP, Tsang W, et al.; American Society of Echocardiography; European Association of Echocadiography. EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. J Am Soc Echocardiogr. 2012;25(1):3–46. 8. Yoshitani H, Takeuchi M, Mor-Avi V, et al. Comparative diagnostic accuracy of multiplane and multislice three-

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

9. 10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

dimensional dobutamine stress echocardiography in the diagnosis of coronary artery disease. J Am Soc Echocardiogr. 2009;22(5):437–42. Monaghan MJ. Role of real time 3D echocardiography in evaluating the left ventricle. Heart. 2006;92(1):131–6. Pouleur AC, le Polain de Waroux JB, Pasquet A, et al. Assessment of left ventricular mass and volumes by threedimensional echocardiography in patients with or without wall motion abnormalities: comparison against cine magnetic resonance imaging. Heart. 2008;94(8):1050–7. Müller H, Frangos C, Fleury E, et al. Measurement of left ventricular ejection fraction by real time 3D echocardiography in patients with severe systolic dysfunction: comparison with radionuclide angiography. Echocardiography. 2010;27(1):58–63. Schmidt MA, Ohazama CJ, Agyeman KO, et al. Real-time three-dimensional echocardiography for measurement of left ventricular volumes. Am J Cardiol. 1999;84(12):1434–9. Lee D, Fuisz AR, Fan PH, Hsu TL, et al. Real-time 3-dimensional echocardiographic evaluation of left ventricular volume: correlation with magnetic resonance imaging—a validation study. J Am Soc Echocardiogr. 2001;14(10):1001–9. Jenkins C, Bricknell K, Hanekom L, et al. Reproducibility and accuracy of echocardiographic measurements of left ventricular parameters using real-time three-dimensional echocardiography. J Am Coll Cardiol. 2004;44(4):878–86. Caiani EG, Corsi C, Zamorano J, et al. Improved semiautomated quantification of left ventricular volumes and ejection fraction using 3-dimensional echocardiography with a full matrix-array transducer: comparison with magnetic resonance imaging. J Am Soc Echocardiogr. 2005; 18(8):779–88. Arai K, Hozumi T, Matsumura Y, et al. Accuracy of measurement of left ventricular volume and ejection fraction by new real-time three-dimensional echocardiography in patients with wall motion abnormalities secondary to myocardial infarction. Am J Cardiol. 2004; 94(5):552–8. Cosyns B, Haberman D, Droogmans S, et al. Comparison of contrast enhanced three-dimensional echocardiography with MIBI gated SPECT for the evaluation of left ventricular function. Cardiovasc Ultrasound. 2009;7:27. Corsi C, Lang RM, Veronesi F, et al. Volumetric quantification of global and regional left ventricular function from real-time three-dimensional echocardiographic images. Circulation. 2005;112(8):1161–70. Jaochim Nesser H, Sugeng L, Corsi C, et al. Volumetric analysis of regional left ventricular function with realtime three-dimensional echocardiography: validation by magnetic resonance and clinical utility testing. Heart. 2007;93(5):572–8. Jenkins C, Marwick TH. Baseline and follow-up assessment of regional left ventricular volume using 3-Dimensional echocardiography: comparison with cardiac magnetic resonance. Cardiovasc Ultrasound. 2009;7:55.

287

21. Chahal NS, Lim TK, Jain P, et al. Population-based reference values for 3D echocardiographic LV volumes and ejection fraction. JACC Cardiovasc Imaging. 2012;5(12):1191–7. 22. Thavendiranathan P, Grant AD, Negishi T, et al. Reproducibility of echocardiographic techniques for sequential assessment of left ventricular ejection fraction and volumes: application to patients undergoing cancer chemotherapy. J Am Coll Cardiol. 2012;17. pii: S0735-1097 (12)05286-2. 23. Yamani H, Cai Q, Ahmad M. Three-dimensional echocardiography in evaluation of left ventricular indices. Echocardiography. 2012;29(1):66–75. 24. Mor-Avi V, Sugeng L, Weinert L, et al. Fast measurement of left ventricular mass with real-time three-dimensional echocardiography: comparison with magnetic resonance imaging. Circulation. 2004;110(13):1814–8. 25. Caiani EG, Corsi C, Sugeng L, et al. Improved quantification of left ventricular mass based on endocardial and epicardial surface detection with real time three dimensional echocardiography. Heart. 2006;92(2):213–9. 26. van den Bosch AE, Robbers-Visser D, Krenning BJ, et al. Comparison of real-time three-dimensional echocardiography to magnetic resonance imaging for assessment of left ventricular mass. Am J Cardiol. 2006;97(1):113–7. 27. van den Bosch AE, Robbers-Visser D, Krenning BJ, et al. Real-time transthoracic three-dimensional echocardiographic assessment of left ventricular volume and ejection fraction in congenital heart disease. J Am Soc Echocardiogr. 2006;19(1):1–6. 28. Takeuchi M, Lang RM. Three-dimensional stress testing: volumetric acquisitions. Cardiol Clin. 2007;25(2):267–72. 29. Yang HS, Pellikka PA, McCully RB, et al. Role of biplane and biplane echocardiographically guided 3-dimensional echocardiography during dobutamine stress echocardiography. J Am Soc Echocardiogr. 2006;19 (9):1136–43. 30. Aggeli C, Giannopoulos G, Misovoulos P, et al. Real-time three-dimensional dobutamine stress echocardiography for coronary artery disease diagnosis: validation with coronary angiography. Heart. 2007;93(6):672–5. 31. Nemes A, Geleijnse ML, Krenning BJ, et al. Usefulness of ultrasound contrast agent to improve image quality during real-time three-dimensional stress echocardiography. Am J Cardiol. 2007;99(2):275–8. 32. Nemes A, Geleijnse ML, Vletter WB, et al. Role of parasternal data acquisition during contrast enhanced real-time three-dimensional echocardiography. Echocardiography. 2007;24(10):1081–5. 33. Geleijnse ML, Nemes A, Vletter WB. Response to: “Contrastenhanced real-time 3-dimensional dobutamine stress echocardiography”. J Am Soc Echocardiogr. 2006;19(8):1076. 34. Ahmad M, Xie T, McCulloch M, et al. Real-time threedimensional dobutamine stress echocardiography in assessment stress echocardiography in assessment of ischemia: comparison with two-dimensional dobutamine stress echocardiography. J Am Coll Cardiol. 2001; 37(5):1303–9.

288

Section 2: Echocardiography/Ultrasound Examination and Training

35. Matsumura Y, Hozumi T, Arai K, et al. Non-invasive assessment of myocardial ischaemia using new real-time three-dimensional dobutamine stress echocardiography: comparison with conventional two-dimensional methods. Eur Heart J. 2005;26(16):1625–32. 36. Pulerwitz T, Hirata K, Abe Y, et al. Feasibility of using a realtime 3-dimensional technique for contrast dobutamine stress echocardiography. J Am Soc Echocardiogr. 2006;19 (5):540–5. 37. Nemes A, Leung KY, van Burken G, et al. Side-by-side viewing of anatomically aligned left ventricular segments in three-dimensional stress echocardiography. Echocardiography. 2009;26(2):189–95. 38. Jasaityte R, Heyde B, D’hooge J. Current state of threedimensional myocardial strain estimation using echocardiography. J Am Soc Echocardiogr. 2013;26(1):15–28. 39. Reant P, Barbot L, Touche C, et al. Evaluation of global left ventricular systolic function using three-dimensional echocardiography speckle-tracking strain parameters. J Am Soc Echocardiogr. 2012;25(1):68–79. 40. Hayat D, Kloeckner M, Nahum J, et al. Comparison of real-time three-dimensional speckle tracking to magnetic resonance imaging in patients with coronary heart disease. Am J Cardiol. 2012;109(2):180–6. 41. Keijn SA, Brouwer WP, Aly MF, et al. Comparison between three-dimensional speckle-tracking echocardiography and cardiac magnetic resonance imaging for quantification of left ventricular volumes and function. Eur Heart J Cardiovasc Imaging. 2012;13:834–9. 42. Matsumoto K, Tanaka H, Kaneko A, et al. Contractile reserve assessed by three-dimensional global circumferential strain as a predictor of cardiovascular events in patients with idiopathic dilated cardiomyopathy. J Am Soc Echocardiogr. 2012;25(12):1299–308. 43. Lilli A, Baratto MT, Meglio JD, et al. Left ventricular rotation and twist assessed by four-dimensional speckle tracking echocardiography in healthy subjects and pathological remodeling: a single center experience. Echocardiography. 2012; Nov 21: doi: 10.1111/echo.12026. 44. Kumar V, Nanda NC. Is it time to move on from twodimensional transesophageal to three-dimensional transthoracic echocardiography for assessment of left atrial appendage? Review of existing literature. Echocardiography. 2012;29(1):112–16. 45. Sugeng L, Mor-Avi V, Weinert L, et al. Multimodality comparison of quantitative volumetric analysis of the right ventricle. JACC Cardiovasc Imaging. 2010;3(1):10–18. 46. Tamborini G, Marsan NA, Gripari P, et al. Reference values for right ventricular volumes and ejection fraction with real-time three-dimensional echocardiography: evaluation in a large series of normal subjects. J Am Soc Echocardiogr. 2010;23(2):109–15. 47. Gopal AS, Chukwu EO, Iwuchukwu CJ, et al. Normal values of right ventricular size and function by real-time 3-dimensional echocardiography: comparison with cardiac magnetic resonance imaging. J Am Soc Echocardiogr. 2007;20(5):445–5.

48. Cai Q, Ahmad M. Three-dimensional echocardiography in valvular heart disease. Echocardiography. 2012;29(1): 88–97. 49. Kasprzak JD, Nosir YF, Dall’Agata A, et al. Quantification of the aortic valve area in three-dimensional echocardiographic data sets: analysis of orifice overestimation resulting from suboptimal cut-plane selection. Am Heart J. 1998;135(6 Pt 1):995–1003. 50. Handke M, Schäfer DM, Heinrichs G, et al. Quantitative assessment of aortic stenosis by three-dimensional anyplane and three-dimensional volume-rendered echocardiography. Echocardiography. 2002;19(1):45–53. 51. Handke M, Jahnke C, Heinrichs G, et al. New threedimensional echocardiographic system using digital radiofrequency data—visualization and quantitative analysis of aortic valve dynamics with high resolution: methods, feasibility, and initial clinical experience. Circulation. 2003;107(23):2876–9. 52. Vengala S, Nanda NC, Dod HS, et al. Images in geriatric cardiology. Usefulness of live three-dimensional transthoracic echocardiography in aortic valve stenosis evaluation. Am J Geriatr Cardiol. 2004;13(5):279–84. 53. Menzel T, Mohr-Kahaly S, Kölsch B, et al. Quantitative assessment of aortic stenosis by three-dimensional echocardiography. J Am Soc Echocardiogr. 1997;10(3): 215–23. 54. Blot-Souletie N, Hébrard A, Acar P, et al. Comparison of accuracy of aortic valve area assessment in aortic stenosis by real time three-dimensional echocardiography in biplane mode versus two-dimensional transthoracic and transesophageal echocardiography. Echocardiography. 2007;24(10):1065–72. 55. Poh KK, Levine RA, Solis J, et al. Assessing aortic valve area in aortic stenosis by continuity equation: a novel approach using real-time three-dimensional echocardiography. Eur Heart J. 2008;29(20):2526–35. 56. Alunni G, Giorgi M, Sartori C, et al. Real time triplane echocardiography in aortic valve stenosis: validation, reliability, and feasibility of a new method for valve area quantification. Echocardiography. 2010;27(6):644–50. 57. Gutiérrez-Chico JL, Zamorano JL, Prieto-Moriche E, et al. Real-time three-dimensional echocardiography in aortic stenosis: a novel, simple, and reliable method to improve accuracy in area calculation. Eur Heart J. 2008;29(10): 1296–306. 58. Fang L, Hsiung MC, Miller AP, et al. Assessment of aortic regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area: usefulness and validation. Echocardiography. 2005;22(9): 775–81. 59. Chin CH, Chen CH, Lo HS. The correlation between three-dimensional vena contracta area and aortic regurgitation index in patients with aortic regurgitation. Echocardiography. 2010;27(2):161–6. 60. Fang L, Hsiung MC, Miller AP, et al. Assessment of aortic regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area: usefulness and validation. Echocardiography. 2005;22(9): 775–81.

Chapter 14: How to do Three-Dimensional Transthoracic Echocardiography Examination

61. Pirat B, Little SH, Igo SR, et al. Direct measurement of proximal isovelocity surface area by real-time threedimensional color Doppler for quantitation of aortic regurgitant volume: an in vitro validation. J Am Soc Echocardiogr. 2009;22(3):306–13. 62. Rajani R, Hancock J, Chambers JB. The art of assessing aortic stenosis. Heart. 2012;98(Suppl 4):iv14–iv22. 63. Mor-Avi V, Patel AR. Aortic annulus measurements: should we use multislice computed tomography, 3D echocardiography or MRI? Expert Rev Cardiovasc Ther. 2013;11(1):1–3. 64. Wilkins GT, Weyman AE, Abascal VM, et al. Percutaneous balloon dilatation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilatation. Br Heart J 1988;60(4):299–308. 65. Zamorano J, Cordeiro P, Sugeng L, et al. Real-time threedimensional echocardiography for rheumatic mitral valve stenosis evaluation: an accurate and novel approach. J Am Coll Cardiol. 2004;43(11):2091–6. 66. Binder TM, Rosenhek R, Porenta G, et al. Improved assessment of mitral valve stenosis by volumetric real-time three-dimensional echocardiography. J Am Coll Cardiol. 2000;36(4):1355–61. 67. Xie MX, Wang XF, Cheng TO, et al. Comparison of accuracy of mitral valve area in mitral stenosis by real-time, threedimensional echocardiography versus two-dimensional echocardiography versus Doppler pressure half-time. Am J Cardiol. 2005;95(12):1496–9. 68. Sebag IA, Morgan JG, Handschumacher MD, et al. Usefulness of three-dimensionally guided assessment of mitral stenosis using matrix-array ultrasound. Am J Cardiol. 2005;96(8):1151–6. 69. Singh V, Nanda NC, Agrawal G, et al. Live threedimensional echocardiographic assessment of mitral stenosis. Echocardiography. 2003;20(8):743–50. 70. Sugeng L, Weinert L, Lammertin G, et al. Accuracy of mitral valve area measurements using transthoracic rapid freehand 3-dimensional scanning: comparison with noninvasive and invasive methods. J Am Soc Echocardiogr. 2003;16(12):1292–300. 71. Perez de Isla L, Casanova C, Almeria C, et al. Which method should be the reference method to evaluate the severity of rheumatic mitral stenosis? Gorlin’s method versus 3D-echo. Eur J Echocardiogr. 2007;8:470–3. 72. Valocik G, Kamp O, Visser CA. Three-dimensional echocardiography in mitral valve disease. Eur J Echocardiogr. 2005;6(6):443–54. 73. Patel V, Hsiung MC, Nanda NC, et al. Usefulness of live/real time three-dimensional transthoracic echocardiography in the identification of individual segment/scallop prolapse of the mitral valve. Echocardiography. 2006;23(6):513–18. 74. Pepi M, Tamborini G, Maltagliati A, et al. Head-to-head comparison of two- and three-dimensional transthoracic and transesophageal echocardiography in the localization of mitral valve prolapse. J Am Coll Cardiol. 2006;48(12): 2524–30.

289

75. Kwan J, Shiota T, Agler DA, et al.; Real-time three-dimensional echocardiography study. Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: realtime three-dimensional echocardiography study. Circulation. 2003;107(8):1135–40. 76. Kahlert P, Plicht B, Schenk IM, et al. Direct assessment of size and shape of noncircular vena contracta area in functional versus organic mitral regurgitation using realtime three-dimensional echocardiography. J Am Soc Echocardiogr. 2008;21(8):912–21. 77. Yosefy C, Levine RA, Solis J, et al. Proximal flow convergence region as assessed by real-time 3-dimensional echocardiography: challenging the hemispheric assumption. J Am Soc Echocardiogr. 2007;20(4):389–96. 78. Matsumura Y, Fukuda S, Tran H, et al. Geometry of the proximal isovelocity surface area in mitral regurgitation by 3-dimensional color Doppler echocardiography: difference between functional mitral regurgitation and prolapse regurgitation. Am Heart J. 2008;155(2):231–8. 79. Matsumura Y, Saracino G, Sugioka K, et al. Determination of regurgitant orifice area with the use of a new threedimensional flow convergence geometric assumption in functional mitral regurgitation. J Am Soc Echocardiogr. 2008;21(11):1251–6. 80. De Simone R, Glombitza G, Vahl CF, et al. Three-dimensional color Doppler: a new approach for quantitative assessment of mitral regurgitant jets. J Am Soc Echocardiogr. 1999;12(3):173–85. 81. De Simone R, Glombitza G, Vahl CF, et al. Threedimensional color Doppler: a clinical study in patients with mitral regurgitation. J Am Coll Cardiol. 1999;33(6):1646–54. 82. Shiota T, Sinclair B, Ishii M, et al. Three-dimensional reconstruction of color Doppler flow convergence regions and regurgitant jets: an in vitro quantitative study. J Am Coll Cardiol. 1996;27(6):1511–18. 83. Iwakura K, Ito H, Kawano S, et al. Comparison of orifice area by transthoracic three-dimensional Doppler echocardiography versus proximal isovelocity surface area (PISA) method for assessment of mitral regurgitation. Am J Cardiol. 2006;97(11):1630–7. 84. Khanna D, Vengala S, Miller AP, et al. Quantification of mitral regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area. Echocardiography. 2004;21(8):737–43. 85. Little SH, Pirat B, Kumar R, et al. Three-dimensional color Doppler echocardiography for direct measurement of vena contracta area in mitral regurgitation: in vitro validation and clinical experience. JACC Cardiovasc Imaging. 2008;1 (6):695–704. 86. Badano LP, Agricola E, Perez de Isla L, et al. Evaluation of the tricuspid valve morphology and function by transthoracic real-time three-dimensional echocardiography. Eur J Echocardiogr. 2009;10(4):477–84. 87. Pothineni KR, Duncan K, Yelamanchili P, et al. Live/real time three-dimensional transthoracic echocardiographic assessment of tricuspid valve pathology: incremental value

290

88.

89.

90.

91.

92.

93.

Section 2: Echocardiography/Ultrasound Examination and Training

over the two-dimensional technique. Echocardiography. 2007;24(5):541–52. Looi JL, Lee AP, Wong RH, et al. 3D echocardiography for traumatic tricuspid regurgitation. JACC Cardiovasc Imaging. 2012;5(12):1285–7. Velayudhan DE, Brown TM, Nanda NC, et al. Quantification of tricuspid regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area. Echocardiography. 2006;23(9):793–800. Sugeng L, Weinert L, Lang RM. Real-time 3-dimensional color Doppler flow of mitral and tricuspid regurgitation: feasibility and initial quantitative comparison with 2-dimensional methods. J Am Soc Echocardiogr. 2007;20(9):1050–7. Faletra F, La Marchesina U, Bragato R, et al. Three dimensional transthoracic echocardiography images of tricuspid stenosis. Heart. 2005;91(4):499. Anwar AM, Geleijnse ML, Soliman OI, et al. Evaluation of rheumatic tricuspid valve stenosis by real-time threedimensional echocardiography. Heart. 2007;93(3):363–4. Lee KJ, Connolly HM, Pellikka PA. Carcinoid pulmonary valvulopathy evaluated by real-time 3-dimensional transthoracic echocardiography. J Am Soc Echocardiogr. 2008;21(4):407.e1–407.e2.

94. Kelly NF, Platts DG, Burstow DJ. Feasibility of pulmonary valve imaging using three-dimensional transthoracic echocardiography. J Am Soc Echocardiogr. 2010;23(10): 1076–80. 95. Bharucha T, Mertens L. Recent advances in pediatric echocardiography. Expert Rev Cardiovasc Ther. 2013;11(1): 31–47. 96. Lu X, Nadvoretskiy V, Klas B, et al. Measurement of volumetric flow by real-time 3-dimensional Doppler echocardiography in children. J Am Soc Echocardiogr. 2007;20(8):915–20. 97. Sivakumar K, Singhi A, Pavithran S. En face reconstruction of VSD on RV septal surface using real-time 3D echocardiography. JACC Cardiovasc Imaging. 2012;5(11): 1176–80. 98. Rajiah P, Mak C, Dubinksy TJ, Dighe M. Ultrasound of fetal cardiac anomalies. AJR Am J Roentgenol. 2011;197(4): W747–60. 99. Hongmei W, Ying Z, Ailu C, et al. Novel application of four-dimensional sonography with B-flow imaging and spatiotemporal image correlation in the assessment of fetal congenital heart defects. Echocardiography. 2012;29(5):614–19.

CHAPTER 15 Point-of-Care Diagnosis with Ultrasound Stethoscopy JRTC Roelandt

Snapshot ¾¾ Battery-Powered Ultrasound Imagers ¾¾ The Traditional Physical Examination ¾¾ The New Physical Examination ¾¾ Acute Care Environment

INTRODUCTION Echocardiography is now the first diagnostic imaging test ordered when cardiac disease is suspected and most often when a definitive diagnosis is made. Progress in microtechnology has led to the constr­ uction of small battery-powered ultrasound imaging devices which are referred to by various names: small personal ultrasound imager, handheld ultrasound, handcarried ultrasound, ultrasound cardioscope, and ultra­ sound stethoscope. Since stethoscope stands for “seeing the heart” (stethos: chest; skopein: see), the term ultrasound stethoscope seems most correct. The standard aural “stethoscope” should be more appropriately termed “stethophone” (phone: sound). Recently, pocket-sized imaging devices have become available and are now gradually becoming an essential part of the physical examination at the point-of-care. However, it must be emphasized that these small imagers are not designed to supplant the range of diagnostic functions available on the “high-end” systems and they should also not be confused with the full-featured portable desktop systems. They are developed to be used at the point-of-care to increase the yield of physical examination, not only in

¾¾ Screening ¾¾ Preparticipation Screening of Athletes ¾¾ Imaging in Remote Areas and Developing Countries ¾¾ Training Requirements

cardiology but also in other disciplines including internal and emergency medicine, vascular medicine, obstetrics/ gynecology, surgery, pediatrics, and the like.

BATTERY-POWERED ULTRASOUND IMAGERS The idea of a small battery-powered ultrasound system for bedside imaging is not new and was already built at the Thoraxcentre of the Erasmus MC, Rotterdam, in 1978 (MinivisorTM)1,2 (Fig. 15.1). It was marketed by Organon Teknika (Oss, The Netherlands) with limited success. In the late 1990s and on the incentive of the US Army, Sonosite Inc. (Bothell, WA) started a program developing small battery-powered ultrasound imagers for diagnosing severe trauma in the front line. They soon introduced the SonoheartTM system, and over the years, several devices with many modalities and measurement functions have become commercially available for application in many disciplines. Another early system (OptigoTM) was a development of Agilent Technologies (Andover, MA) and marketed by Philips Medical Systems (Eindhoven, The Netherlands).

292

Section 2:  Echocardiography/Ultrasound Examination and Training

A

B

C Fig. 15.1: The MinivisorTM, a handheld, battery-powered ultrasound imager was developed at the Thoraxcentre in 1978 for augmenting the yield of the physical examination at the bedside.

Figs 15.2A to C: The SonoHeart (A) and Optigo (B) are batterypowered, handheld ultrasound imagers. The V-ScanTM is the latest generation and is pocket-sized (C). These systems allow combined two-dimensional and color Doppler flow imaging at the point-of-care.

The latest generation of handheld ultrasound imagers was introduced in 2010 and is pocket-sized (V-Scan, GE Vingmed Ultrasound AS, Horten, Norway) and weighs approximately 400 g (Fig. 15.2). It makes use of a broadband, phased-array transducer and provides high-resolution, two-dimensional imaging combined with color Doppler flow imaging. An electronic caliper allows dimensional measurements. Data are stored on microcards and can be downloaded to any computer for documentation and offline analysis.

method as their primary method in clinical diagnosis. Consequently, it appears that there is less need for their skills in traditional physical examination, particularly auscultation, to match those of the master teachers of medicine’s “golden era.”3–8 Some bemoan this loss of reliance on patient examination skills and the increasing dependence on sophisticated imaging technologies However, there are several important justifications for this evolution: • In the hectic modern medical world, there is less time to perform a thorough traditional physical examination. • Direct imaging identifies an abnormality more accu­ rately than an indirect examination with inspection, palpation, and auscultation. • Echo/Doppler examination always provides more qualitative and even quantitative information than inspection, palpation, and auscultation. • Many common cardiac conditions such as pericardial effusion, early ventricular dysfunction, cardiomy­ opathy, silent valvular disease, and mass lesions may not be detected by a traditional physical examination, even if performed by an experienced clinician. Most of these conditions are readily detected by an echo/ Doppler examination.8–10 • Preclinical disease and unsuspected abnormalities are regularly detected by a simple echo/Doppler examination. Earlier diagnosis improves management and outcome.11 In a considerable number of patients, preclinical cardiac disease can be detected by imaging in combination with other tests (e.g. biomarkers).

THE TRADITIONAL PHYSICAL EXAMINATION Physical examination was introduced into medical practice in the time of pharaohs 4,000 years ago. It included history taking, inspection, palpation, and direct auscultation. For thousands of years, medical theory and practice did not change, and apart from paying some attention to the quality of the pulse, most doctors did not examine their patients. Early in the 19th century, Laennec (1781–1826) revolu­ tionized the physical examination with the introduction of the “stethoscope,” the first technological aid in diagnostic medicine. Although not accepted by many clinicians at the time, history shows that the introduction of the stethoscope and a century later X-ray imaging and electrocardiography were major milestones in diagnostic medicine. Echo/Doppler was the next major breakthrough in the 1950s, and modern cardiologists now rely on this imaging

Chapter 15:  Point-of-Care Diagnosis with Ultrasound Stethoscopy

A

B

Figs 15.3A and B: This 35-year-old woman, known with systemic lupus erythematosus, developed complaints of shortness of breath. The referral diagnosis was pericarditis. The point-of-care examination with the OptigoTM imager showed aortic regurgitation (A, arrow) and mitral regurgitation (B, arrowhead).

Fig. 15.5: Apical four-chamber view showing a large unexpected pericardial effusion (V-scan, arrow). (LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle).

• The frequency of cardiovascular misdiagnosis in unselected patients who die in the hospital has halved over the past 20 years and paralleled increasing use of echo/Doppler examinations.12

THE NEW PHYSICAL EXAMINATION Clinical Applications of the Ultrasound Stethoscope The patient interview and the physical examination remain the cornerstone of the initial evaluation of a patient with

A

293

B

Figs 15.4A and B: This patient was referred to the outpatient clinic for evaluation of a heart murmur. V-scan examination showed an unexpected dilated aorta (AO) and aortic regurgitation (B, arrow). (LA: Left atrium; LV: Left ventricle; RV: Right ventricle).

suspected cardiovascular disease. However, the limitations of a physical examination to detect specific cardiac condi­ tions and its inaccuracy are well documented.13–17 Clearly, extending our physical senses by “seeing the heart” during the initial physical examination provides information far beyond the traditional inspection, palp­ ation, and auscultation. Pocket-sized ultrasound imagers are used just like the conventional stethoscope at the point-of-care anywhere and at any time in office practice, consultation rounds, in new health-care settings, and in remote and difficult accessible areas3 (Figs 15.3 to 15.5). They augment both the diagnostic yield and accuracy of the physical examination and allow to detect unan­ ticipated preclinical disease even after limited training.10,18-23 Unsuspected significant pathologies are found in approxi­mately 20% of patients. Other advantages are better physician–patient inter­ action, shortening the physical examination, and to deter­ mine if more elaborate tests are needed.13 It has been shown that the incorporation of ultrasound stethoscopy into the physical examination during cardiac consultation rounds in noncardiac departments provides information that results in hospital cost savings and earlier efficient management.24,25

Follow-up Echocardiography Standard echocardiography with “high-end” systems is complex and requires considerable training and exper­ ience and is relatively expensive.

294

Section 2:  Echocardiography/Ultrasound Examination and Training

Many specific clinical questions can be quickly answered by a brief limited examination. Furthermore, the follow-up of many cardiac conditions requires only a fraction of the many modalities of a “high-end” system (most often the ejection fraction is ordered for follow-up testing of the effect of interventions). However, the danger of missing an abnormality by addressing a single specific question should be recognized. Left ventricular hypertrophy is a potent independent marker of cardiovascular risk in patients with arterial hypertension, a common condition in the general population. Physical examination and electrocardiography do not reliably detect this pathology in these patients whereas it is readily detected by echocardiography.26 Early detection will initiate therapy and improve outcome. Standard echocardiography is not considered costeffective for this application. Therefore, the World Health Organization–International Society of Hypertension (WHO-ISH) does not recommend its use in all hypertensive patients. However, there is a close agreement between ultrasound stethoscopy and standard echocardiography for the detection of left ventricular hypertrophy (93% for left ventricular mass/body surface area and 90% for left ventricular mass/height).27 Therefore, a focused ultra­ sound stethoscope examination could provide a cheap, quick means for assessing hypertensive patients even those with borderline blood pressure and, hence, a low probability of left ventricular hypertrophy. Ultrasound stethoscopy can be used for patient follow-up and therapy effect assessment by quickly measuring cardiac dimensions and left ventricular function.10,20,25,28 Other specific follow-up questions are, for example, the resolution of a pericardial effusion after pericardiocentesis.

ACUTE CARE ENVIRONMENT The ultrasound stethoscope can assist in the initial evaluation and rapid diagnosis of life-threatening condi­ tions in the emergency room, intensive care unit, neonatal intensive care, or other situations where quick decisions are essential and standard echocardiography or other imaging methods are not rapidly available.29–34 There is a close agreement between the ultrasound stethoscope and standard echocardiography for the detection of left ventricular wall motion abnormalities.25 Therefore, it allows to rapidly screen out wall motion abnormalities in patients with acute chest pain and a nondiagnostic electrocardiogram. Right ventricular involvement in acute myocardial infarction and the

mechanical complications of a myocardial infarction are readily diag­nosed in the coronary care unit. The demonstration of right ventricular dilatation and paradoxical septal motion significantly raises the possibility of acute pulmonary embolism. Even though the absence of these findings does not exclude pulmonary embolus, a prompt ultrasound examination may also identify conditions that clinically mimic it. Emergent tamp­ onade, a dilated heart, or valvular pathology (e.g. calcific aortic stenosis with a low output state) are immediately recognized. Moreover, prolonged futile resuscitation attempts can be prevented by the rapid identification of ventricular standstill and electromechanical dissociation. Guiding emergency pericardiocentesis, central line placement, monitoring wall dynamics, and the effects of acute inter­ ventions, such as fluid challenges and inotropic drug infusions by estimating cavity dimensions, are other applications. The loss of inferior vena cava narrowing during inspiration is a reliable and sensitive marker of elevated central venous pressure and right heart failure, while persistent inferior vena cava collapse indicates hypovolemia and low filling pressure. American Medics are now using battery-powered ultrasound imagers based on iPAQ technology. In urban trauma centers and during helicopter transports, immediate echocardiography considerably shortens the time to diagnosis of penetrating cardiac and abdominal injuries, greatly improving survival.35,36 Ultrasound stetho­ scopes are also used in neonatal clinics for the continuous evaluation of critically ill neonates.39

SCREENING The ultrasound stethoscope has been proven useful for the screening and identification of cardiac disorders either in the general population or in selected patient groups at risk for specific conditions.37

Abdominal Aortic Aneurysm Patients at risk of abdominal aortic aneurysm (i.e. male gender, smokers, over 65 years of age, hypertension, and a past or family history of coronary artery disease) should be screened and undergo prophylactic repair if aortic diameter exceeds 55 mm. Acute rupture has a perio­ perative mortality rate of 50%, while it is only 1–2% for elective repair. The Multicenter Aneurysm Screen Study (MASS) showed that a population-based screening program for abdominal aortic aneurysm was beneficial in men 65–74 years of age.38

Chapter 15:  Point-of-Care Diagnosis with Ultrasound Stethoscopy

The physical examination alone may not detect a moderately enlarged aneurysm, especially in obese patients. Since it has been shown that the abdominal aortic diameter can be measured equally well with small ultrasound imagers as with standard equipment, they can be used in a cost-effective way for their detection by only adding a few extra minutes to the routine physical examination.39–41

Left Ventricular Dysfunction Ischemic left ventricular dysfunction is currently the main cause of congestive heart failure and is associated with high morbidity, mortality, and health-care costs. Both left ventricular dysfunction and heart failure are becoming more and more prevalent as the population ages. The clinical diagnosis of heart failure can be difficult and general practitioners may fail to diagnose it in up to 25–30% of cases.42,43 Early left ventricular dysfunction in asymptomatic patients is impossible to detect clinically.44–46 Standard echocardiography is the screening method of choice for the early detection of left ventricular dysfunction but it is not cost-effective if there is a low probability of the condition. Brain natriuretic peptide (BNP), however, is a sensitive biomarker for increased intracardiac pressure of any cause. In the future BNP, in combination with ultrasound stethoscopy, should provide a cost-effective screening tool for both left ventricular dysfunction and heart failure. Studies have indicated that ultrasound stethoscopes compare well with standard echocardiography for the diagnosis of left ventricular dysfunction (agreement in 75–93%) and is even better if combined with the physical examination.10,25,28,47 However, precise estimates of ejection fraction (i.e. < 40% vs 40–54% vs 55–70%) cannot be made with the same confidence using the ultrasound stetho­ scope as with a standard echocardiograph—discordance rates between the two techniques is around 10%.25 Whatever type of imaging ultrasound machine is used, it must be remembered that occasionally even experienced echocardiographers may misclassify borderline estimates of left ventricular function and ejection fraction. This limitation obviously applies to all types of operatordependent imaging modalities.

Mitral Valve Prolapse The diagnosis of mitral valve prolapse may be difficult by auscultation. Echocardiography most often allows to accurately confirm or exclude this disorder by imaging

295

a single parasternal long-axis view.48 Ultrasound stetho­ scopy has proven a quick, cheap, and reliable method of detecting this abnormality and is, therefore, suitable for screening in experienced hands.

PREPARTICIPATION SCREENING OF ATHLETES Potentially dangerous cardiac conditions can be identified in otherwise asymptomatic individuals in preparticipation screening programs for athletes. Hypertrophic cardio­ myopathy, a dilated ascending aorta (Marfan’s disease) and valvular abnormalities (bicuspid valve, mitral valve prolapse) are the most common disorders and are reliably detected by experienced examiners. In a limited echocardiographic screening program, valvular abnormalities requiring endocarditis prophylaxis were found by echocardiography in 10.4% of the screened athletes.49 Notwithstanding the high rate of detected abnormalities in this study, it must be remembered that screening for cardiac disorders in young athletes and asymptomatic individuals carries the risk of a false-positive diagnosis. Screening should therefore be performed by well-trained and experienced clinicians and should always be followed by a complete examination before a definitive diagnosis/advice is made.

IMAGING IN REMOTE AREAS AND DEVELOPING COUNTRIES The use of imaging technologies in remote areas and developing countries is limited because of lack of portability, electrical power, trained personnel, technical support, and expense.50,51 Remotely downloaded images can now be transmitted via smart phone (mobile-tomobile) with dedicated medical imaging software.52 Small ultrasound devices will provide a practical alternative when health-care resources are limited and there is little or no access to other forms of diagnostic imaging technology. Training in ultrasound imaging should be offered to all doctors who intend to work in such settings.

TRAINING REQUIREMENTS The increasing availability of the ultrasound stethoscope raises several important questions. The limited number of functions and the size of these devices do not mean that less training is required for using a standard echocardi­ ography machine. A lot will depend on how and by whom

296

Section 2:  Echocardiography/Ultrasound Examination and Training

these devices will be used in the future. Appropriate training is mandatory for their effective use as an integral part of the physical examination which ultimately will be performed by all clinicians including general practitioners.53 The American Society of Echocardiography and the European Association of Echocardiography published guidelines for the use of ultrasound stethoscopes and recommended Level 1 training as an absolute minimum.54,55 However, to use the machines independently, Level 2 training is strongly recommended (i.e. 150 personally performed studies and 300 interpreted studies). However, the level of competence required might vary depending on the application and clinical scenarios under consideration. For instance, rapid screening and identification of acute problems in a critical care environment is different from answering referral questions in an outpatient clinic and a screening program. In a study at Duke University, it was shown that students could be trained in a short period of time to detect significant pathology.56 Limited training can also suffice if the examination is for a focused purpose (e.g. screening). The American College of Emergency Physicians has taken a pragmatic approach and has provided guidelines for emergency room physicians to perform and interpret basic ultrasound studies in emergency situations.57 If ultrasound stethoscopes are only used as part of the physical examination, then every clinician need not be trained in every aspect of echo/ Doppler assessment, and the level of training could be confined to the identification of cardiac conditions and emergency problems. Training programs for the integrated use of an ultra­ sound stethoscope should be incorporated in the core curriculum of medical schools in the same way as use of the standard aural stethoscope.58 Echocardiography is an ideal means of teaching cardiac anatomy and function. After 6 hours of training (i.e. ultrasound theory, handson practice, and demon­ stration of major pathology), 25 preclinical medical students improved their correct identification of cardiac structures from 4% to 91%, and 23 of the 25 students recognized over 90% of 25 major cardiac abnormalities (e.g. a dilated heart, wall motion abnormalities, ventricular hypertrophy, valve disease, pericardial effusion, etc.).59 Teaching ultrasound imaging provides an effective bridge between theory and practice. It encourages the integration and application of knowledge of several basic disciplines including physics, anatomy, pathology, and pathophysiology.59 This interdisciplinary approach forces students to rearrange knowledge and information from different disciplines and prepares them to deal with complex medical problems.

FUTURE DIRECTIONS The natural evolution of technology is for it to become simpler and easier to use and then become widely disseminated, often being applied to uses it was not originally intended for. The small pocket-sized ultrasound systems have followed this pattern by getting smaller, cheaper, and simpler to use. Although these devices will not replace the high-end systems, they will become an integral part of the physical examination at the pointof-care and be available to physicians of all specialties. Training in their use will become an important issue and should focus on the identification of normal findings as well as the common clinically important or life-threatening disorders. If use of both the traditional aural and ultrasound stethoscope are taught together at medical school, the next generation of physicians will be capable of using both devices as an extension to physical examination. Advances in pattern recognition software and telecommunications will further enable the provision of interpretation support from experienced laboratories or nearby intensive care units.60

REFERENCES 1. Roelandt J, Cate FJ Ten, Hugenholtz PG, et al. The ultrasonic stethoscope: a miniature hand-held device for real time cardiac imaging. Circulation. 1978;58:II-75. 2. Roelandt J, Bom K, Hugenholtz PG. The ultrasound cardioscope: a hand-held scanner for real-time cardiac imaging. J Clin Ultrasound. 1980;8(3):221–5. 3. Roldan CA, Shively BK, Crawford MH. Value of the cardiovascular physical examination for detecting valvular heart disease in asymptomatic subjects. Am J Cardiol. 1996;77(15):1327–31. 4. Mangione S, Nieman LZ. Cardiac auscultatory skills of internal medicine and family practice trainees. A comparison of diagnostic proficiency. JAMA. 1997;278(9): 717–22. 5. Lok CE, Morgan CD, Ranganathan N. The accuracy and interobserver agreement in detecting the “gallop sounds” by cardiac auscultation. Chest. 1998;114(5):1283–8. 6. Attenhofer Jost CH, Turina J, Mayer K, et al. Echocardi­ ography in the evaluation of systolic murmurs of unknown cause. Am J Med. 2000;108(8):614–20. 7. Roelandt JR. Ultrasound stethoscopy. Eur J Intern Med. 2004;15(6):337–47. 8. Popp RL. The physical examination of the future: echocar­ diography as part of the assessment. ACC Current Rev. 1998;7:79–81. 9. Roelandt JR. Ultrasound stethoscopy. Eur J Intern Med. 2004;15(6):337–47. 10. Vourvouri EC, Poldermans D, De Sutter J, et al. Experience with an ultrasound stethoscope. J Am Soc Echocardiogr. 2002;15(1):80–5.

Chapter 15:  Point-of-Care Diagnosis with Ultrasound Stethoscopy

11. Bossone E, DiGiovine B, Watts S, et al. Range and prevalence of cardiac abnormalities in patients hospitalized in a medical ICU. Chest. 2002;122(4):1370–6. 12. Sonderegger-Iseli K, Burger S, Muntwyler J, et al. Diagnostic errors in three medical eras: a necropsy study. Lancet. 2000;355(9220):2027–31. 13. Wray NP, Friedland JA. Detection and correction of house staff error in physical diagnosis. JAMA. 1983;249(8):1035–7. 14. Kinney EL. Causes of false-negative auscultation of regurgitant lesions: a Doppler echocardiographic study of 294 patients. J Gen Intern Med. 1988;3(5):429–34. 15. Gadsboll N, Hoilund-Carlsen PF, Nielsen GG, et al. Symptoms and signs of heart failure in patients with myocardial infarction: reproducibility and relationship to chest X-ray, radionuclide ventriculography and right heart catheterization. Eur Heart J. 1989;10(11):1017–28. 16. Chakko S, Woska D, Martinez H, et al. Clinical, radiographic, and hemodynamic correlations in chronic congestive heart failure: conflicting results may lead to inappropriate care. Am J Med. 1991;90(3):353–9. 17. Butman SM, Ewy GA, Standen JR, et al. Bedside cardio­ vascular examination in patients with severe chronic heart failure: importance of rest or inducible jugular venous distension. J Am Coll Cardiol. 1993;22(4):968–74. 18. Rugolotto M, Hu BS, Liang DH, et al. Rapid assessment of cardiac anatomy and function with a new hand-carried ultrasound device (OptiGo): a comparison with standard echocardiography. Eur J Echocardiogr. 2001;2(4):262–9. 19. Spencer KT, Anderson AS, Bhargava A, et al. Physicianperformed point-of-care echocardiography using a laptop platform compared with physical examination in the cardiovascular patient. J Am Coll Cardiol. 2001;37(8): 2013–18. 20. Rugolotto M, Hu BS, Liang DH, et al. Rapid assessment of cardiac anatomy and function with a new hand-carried ultrasound device (OptiGo): a comparison with standard echocardiography. Eur J Echocardiogr. 2001;2(4):262–9. 21. Vourvouri EC, Poldermans D, Deckers JW, et al. Evaluation of a hand carried cardiac ultrasound device in an outpatient cardiology clinic. Heart. 2005;91(2):171–6. 22. DeCara JM, Lang RM, Spencer KT. The hand-carried echocardiographic device as an aid to the physical examination. Echocardiography. 2003;20(5):477–85. 23. Prinz C, Voigt JU. Diagnostic accuracy of a hand-held ultrasound scanner in routine patients referred for echocardiography. J Am Soc Echocardiogr. 2011;24(2): 111–16. 24. Gorcsan J. Utility of hand-carried ultrasound for consultative cardiology. Echocardiography. 2003;20(5):463–9. 25. Bruce CJ, Montgomery SC, Bailey KR, et al. Utility of handcarried ultrasound devices used by cardiologists with and without significant echocar­diographic experience in the cardiology inpatient and outpatient settings. Am J Cardiol. 2002;90(11):1273–5. 26. Sheps SG, Frohlich ED. Limited echocardiography for hypertensive left ventricular hypertrophy. Hypertension. 1997;29(2):560–3.

297

27. Vourvouri EC, Poldermans D, Schinkel AF, et al. Left ventricular hypertrophy screening using a hand-held ultrasound device. Eur Heart J. 2002;23(19):1516–21. 28. Kimura BJ, Amundson SA, Willis CL, et al. Usefulness of a hand-held ultrasound device for bedside examination of left ventricular function. Am J Cardiol. 2002;90(9):1038–9. 29. Rugolotto M, Chang CP, Hu B, et al. Clinical use of cardiac ultrasound performed with a hand-carried device in patients admitted for acute cardiac care. Am J Cardiol. 2002;90(9):1040–2. 30. Testuz A, Müller H, Keller PF, et al. Diagnostic accuracy of pocket-size handheld echocardiographs used by cardiologists in the acute care setting. Eur Heart J Cardiovasc Imaging. 2013;14(1):38–42. 31. Goodkin GM, Spevack DM, Tunick PA, et al. How useful is hand-carried bedside echocardiography in critically ill patients? J Am Coll Cardiol. 2001;37(8):2019–22. 32. Croft LB, Stanizzi M, Harish S, et al. Impact of frontline limited, focused and expedited echocardiography in the adult emergency department using a compact echo machine. Circulation. 2001;104:II-335. 33. Kimura BJ, Bocchicchio M, Willis CL, et al. Screening cardiac ultrasonographic examination in patients with suspected cardiac disease in the emergency department. Am Heart J. 2001;142(2):324–30. 34. Burdjalov V, Srinivasan P, Baumgart S, et al. Handheld, portable ultrasound in the neonatal intensive care nursery: a new, inexpensive tool for the rapid diagnosis of common neonatal problems. J Perinatol. 2002;22(6):478–83. 35. Price DD, Wilson SR, Murphy TG. Trauma ultrasound feasibility during helicopter transport. Air Med J. 2000; 19(4):144–6. 36. Kirkpatrick AW, Simons RK, Brown R, et al. The hand-held FAST: experience with hand-held trauma sonography in a level-I urban trauma center. Injury. 2002;33(4):303–8. 37. Galasko GI, Lahiri A, Senior R. Portable echocardiography: an innovative tool in screening for cardiac abnormalities in the community. Eur J Echocardiogr. 2003;4(2):119–27. 38. Ashton HA, Buxton MJ, Day NE, et al.; Multicentre Aneurysm Screening Study Group. The Multicentre Aneurysm Screening Study (MASS) into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial. Lancet. 2002;360(9345):1531–9. 39. Vourvouri EC, Poldermans D, Schinkel AF, et al. Abdominal aortic aneurysm screening using a hand-held ultrasound device. “A pilot study”. Eur J Vasc Endovasc Surg. 2001;22(4):352–4. 40. Bruce CJ, Spittell PC, Montgomery SC, et al. Personal ultrasound imager: abdominal aortic aneurysm screening. J Am Soc Echocardiogr. 2000;13(7):674–9. 41. Dijos M, Pucheux Y, Lafitte M, et al. Fast track echo of abdominal aortic aneurysm using a real pocket-ultrasound device at bedside. Echocardiography. 2012;29(3):285–90. 42. Remes J, Miettinen H, Reunanen A, et al. Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J. 1991;12(3):315–21.

298

Section 2:  Echocardiography/Ultrasound Examination and Training

43. Hobbs FDR. Unmet need for diagnosis of heart failure: the view from primary care. Heart. 2002;88(Suppl II):ii9–11. 44. Stevenson LW, Perloff JK. The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA. 1989;261(6):884–8. 45. Sackett DL. The rational clinical examination. A primer on the precision and accuracy of the clinical examination. JAMA. 1992;267(19):2638–44. 46. Badgett RG, Lucey CR, Mulrow CD. Can the clinical examination diagnose left-sided heart failure in adults? JAMA. 1997;277(21):1712–19. 47. Lemola K, Yamada E, Jagasia D, et al. A hand-carried personal ultrasound device for rapid evaluation of left ventricular function: use after limited echo training. Echocardiography. 2003;20(4):309–12. 48. Kimura BJ, Scott R, Willis CL, DeMaria AN. Accuracy and cost-effectiveness of single-view echocardiographic screening for suspected mitral valve prolapse. Am J Med. 2000;108(4):331–3. 49. Weidenbener EJ, Krauss MD, Waller BF, et al. Incorporation of screening echocardiography in the preparticipation exam. Clin J Sport Med. 1995;5(2):86–9. 50. Istensen H. Developing countries. Diagnostic imaging and laboratory technology. WHO, Switzerland. Ultrasound Med Biol. 2000;26(Suppl 1):159–61. 51. Mindel S. Role of imager in developing world. Lancet. 1997;350(9075):426–429. 52. Choi BG, Mukherjee M, Dala P, et al. Interpretation of remotely downloaded pocket-size cardiac ultrasound images on a web-enabled smartphone: validation against workstation evaluation. J Am Soc Echocardiogr. 2011; 24(12):1325–30.

53. Prinz C, Dohrmann J, van Buuren F, et al. The importance of training in echocardiography: a validation study using pocket echocardiography. J Cardiovasc Med (Hagerstown). 2012;13(11):700–7. 54. Seward JB, Douglas PS, Erbel R, et al. Hand-carried cardiac ultrasound (HCU) device: recommendations regarding new technology. A report from the Echocardiography Task Force on New Technology of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 2002;15(4):369–73. 55. Sicari R, Galderisi M, Voigt JU, et al. The use of pocketsize imaging devices: a position statement of the European Association of Echocardiography. Eur J Echocardiogr. 2011; 12(2):85–7. 56. Alexander JH, Peterson PD, Chen AY, et al. Feasibility of point of care echo by noncardiologist physicians to assess left ventricular function, pericardial effusion, mitral regurgitation and aortic valve thickening. Circulation. 2001;104(Suppl 11):334. 57. American College of Emergency Physicians, ACEP Emer­ gency Ultrasound Guidelines, 2001. 58. Wittich CM, Montgomery SC, Neben MA, et al. Teaching cardiovascular anatomy to medical students by using a handheld ultrasound device. JAMA. 2002;288(9):1062–3. 59. Brunner M, Moeslinger T, Spieckermann PG. Echocar­ diography for teaching cardiac physiology in practical student courses. Am J Physiol. 1995;268(6 Pt 3):S2–9. 60. Sable C. Digital echocardiography and telemedicine appli­ cations in pediatric cardiology. Pediatr Cardiol. 2002; 23(3):358–69.

CHAPTER 16 Spectral Doppler of the Hepatic Veins Bahaa M Fadel, Bader Almahdi, Mohammad Al-Admawi, Giovanni Di Salvo

Snapshot  Imaging of the Hepa c Veins  Physiological and Other Factors that Affect Hepa c

Venous Flow  Doppler Pa ern of the Hepa c Veins Versus the

Superior Vena Cava

INTRODUCTION Interrogation of flow in the central veins is highly useful for the evaluation of right heart hemodynamics.1,2 As such, Doppler examination of blood flow in the hepatic veins (HVs) has become an integral part of any routine echocardiographic examination.3,4 Data derived from the HV Doppler provide useful information regarding a wide spectrum of physiological and pathological processes that affect right heart function. Systematic analysis of the direction, regularity, velocity of the waveforms, and their phasic response to respiration allows one to distinguish normal from abnormal Doppler patterns and carries important diagnostic and prognostic implications. Optimal visualization of the HVs, adequate recording of blood flow, and proper interpretation of the Doppler signal are important requirements for a comprehensive evaluation.

IMAGING OF THE HEPATIC VEINS Invasive measurement of flow velocities in the vena cava has long been replaced by noninvasive recording.1,2,5 Interrogation of superior vena cava (SVC) flow as a marker of right ventricle (RV) filling is routinely performed; however, Doppler recording of the HVs arose as a surrogate

 Transthoracic Echocardiography  Transesophageal Echocardiography  Technical Considera ons  Hepa c Venous Flow in Disease States  Limita ons, Technical Pi alls and Ar facts

to the inferior vena cava (IVC) for several reasons. The IVC is not well visualized from the parasternal and apical windows making a Doppler signal difficult to obtain. It is best visualized from the subcostal window.4 From this approach, there is a wide angle of interrogation and poor alignment of the Doppler beam with IVC flow. Additionally, the IVC changes significantly in size with respiration. It normally decreases by >50% in diameter during inspiration and its lumen may completely collapse, thus rendering the recording of flow technically challenging.6 Since flow in the HVs reflects IVC flow and shows good alignment with the ultrasound beam, the HVs together with the SVC became the standard structures used for the assessment of systemic venous filling of the right heart.4

Anatomy of the Hepatic Veins The HVs drain blood from the liver, an organ that possesses a dual blood supply from the hepatic artery and portal vein. They drain posteriorly into the retrohepatic IVC, approximately 2–3 cm caudal to its junction with the right atrium (RA). The HVs are the largest visceral tributaries of the IVC.4 The anatomical position of the HVs is used to demarcate the various lobes and segments of the liver.7

300

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 16.1A and B: (A) Schematic drawing of the transverse section of a liver. The left hepatic vein (LHV), middle hepatic vein (MHV), and right hepatic vein (RHV) are shown draining posteriorly into the inferior vena cava (IVC). The three imaging windows of the HVs include the subcostal,1 mid-clavicular,2 and mid-axillary;3 (B) Transthoracic echocardiogram with image obtained from the subcostal window. The three hepatic veins are noted draining into the IVC. The veins are dilated due to elevation in right atrial pressure. Source: Modified from Scheinfeld MH, Bilali A, Koenigsberg M. Understanding the spectral Doppler waveform of the hepatic veins in health and disease. Radiographics. 2009;29:2081–98.

The right HV drains the right lobe whereas the middle and left HVs drain the left lobe of the liver and join to form a single vein before entering the IVC in most individuals (Figs 16.1A and B).8 Normal HVs measure 5 to 11 mm in diameter near their entrance into the IVC.9

Physiology of Hepatic Venous Flow The flow profile in the HVs resembles the pressure waveforms in the RA. Similar to the pulmonary veins (PVs), blood flow in the HVs is pulsatile and the changes in velocity reflect changes in RA pressure (Fig. 16.2).1–3,10 The Eustachian valve, located at the entrance of the IVC into the RA, does not restrict flow even when well developed. Thus, flow in the HVs reflects RA filling throughout the cardiac cycle and RV filling during diastole. Similar to the IVC and SVC, normal flow in the HVs is primarily influenced by right heart hemodynamics and respiration.3,10 It is altered in disease states that affect filling of the right heart and/or alter respiratory or hepatic function. Disorders of the right heart often result in restriction to filling either independently of the respiratory cycle or conditional on a particular phase of respiration. Normal flow in the HVs is phasic and predominantly antegrade.3,4 Spectral Doppler interrogation reveals three or four distinct waveforms: (a) a large antegrade wave (negative velocity) during systole (S wave); (b) a small

retrograde wave (positive velocity) in late systole (V wave) that may or may not be visible above the baseline; (c) an antegrade wave in early-mid diastole (D wave); and (d) a retrograde wave in late diastole following atrial contraction (A wave) (Fig. 16.3). The systolic wave occurs in response to the fall in RA pressure caused by the increase in RA volume. The volume increase results from atrial relaxation and from the systolic displacement of the tricuspid annulus toward the apex that correspond to the “x” (atrial relaxation) and x′ descents (annular displacement) on RA pressure recording, respectively (Fig. 16.4). The two components of the S wave are occasionally visualized on the HV Doppler signal. The S wave is followed by a retrograde V wave that occurs in late systole toward the end of the electrocardiographic T wave. It results from the continued filling and rise in RA pressure before TV opening and temporally correlates with the “v” wave on pressure recording. The Doppler V wave is transitional and the least predictable of the waveforms. Its visualization depends on its peak velocity, timing, and heart rate. Thus, the V wave may not be visible above the zero line (Figs 16.4 and 16.5). The V wave is normally followed by an antegrade diastolic (D) wave with a lower peak velocity than the S wave. The D wave corresponds to the y descent on RA pressure recording and often follows the T wave on the electrocardiogram (ECG) tracing. It results from the fall

Chapter 16: Spectral Doppler of the Hepatic Veins

301

Fig. 16.3: Normal spectral Doppler of the middle hepatic vein. The four phasic components that represent the normal waveforms are noted. The systolic (S) is larger than the diastolic (D) waveform as is the atrial reversal (A) as compared to the late systolic (V) wave. The color Doppler signal that corresponds to the S, D, and A waveforms is noted. The brighter color of the S wave indicates a higher velocity than the D wave.

Fig. 16.2: Schematic drawing of hepatic venous Doppler with simultaneous hemodynamic events in the right heart. (RV: Right ventricle; RA: Right atrium; TVC: Tricuspid valve closure; TVO: Tricuspid valve opening).

in RA pressure that follows TV opening and the emptying of the RA into the RV. Finally, a small retrograde A wave is noted in late diastole and follows the electrocardiographic P wave. It is caused by atrial contraction with rise in RA pressure that exceeds IVC pressure, leading to flow reversal in the HVs. Rarely a small retrograde C wave can be identified following the A wave. It results from the transient rise in RA pressure that accompanies bulging of the tricuspid annulus into the RA during the isovolumic contraction period.

Fig. 16.4: Normal hepatic vein Doppler showing the two components of the systolic flow. The first component, indicated by an arrow, corresponds to flow during right atrial relaxation. The second component, indicated by an arrowhead, corresponds to flow related to the descent of the tricuspid annulus during ventricular systole. The effect of the V wave on flow is noted between the S and D waves; however, no independent V wave is noted above the baseline.

Similar to events in the left heart, the HV D wave corresponds temporally to the tricuspid inflow E wave whereas the HV A reversal corresponds to the tricuspid inflow A wave (Fig. 16.2). The peak of the S and D waves

302

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 16.5: Normal hepatic vein Doppler showing the transient nature of the V wave. On the first cardiac cycle, the V wave is visible above the baseline. The second cycle shows an increase in forward flow (S and D velocities) indicative of the onset of inspiration. Here the V wave, indicated by an arrow, occurs at a higher systolic velocity and thus is not visible above the baseline.

Fig. 16.6: Various waveforms of the hepatic vein Doppler with the relevant measurements. Source: Modified from Scheinfeld MH, Bilali A, Koenigsberg M. Understanding the spectral Doppler waveform of the hepatic veins in health and disease. Radiographics. 2009;29:2081–98.

is temporally related to the nadir of the x and y descents, respectively (Fig. 16.2). The morphology of the flow pattern may vary among different HVs.11 The left and middle HVs tend to demonstrate more pulsatile flow than the right HV likely due to their drainage closer to the heart. Common HV Doppler measurements include peak velocity of the S, D, and A waves, A wave duration, and peak S/D velocity ratio (Fig. 16.6).10 Due to respiratory variability, the average peak velocities are assessed during inspiration, expiration, and apnea. The systolic fraction, a ratio of the S to the sum of the S and D time velocity integral (TVI) is rarely measured in clinical practice and is inferred by the peak S/D velocity ratio. The effect of respiration on the pattern of flow, particularly flow reversals, and its timing during inspiration or expiration should be noted. For the assessment of right heart hemodynamics, the HV Doppler should constitute one part of an integrated assessment that includes the following parameters: 1. Pulsed wave (PW) Doppler of tricuspid valve inflow. 2. Color Doppler for the presence and degree of tricuspid regurgitation (TR). 3. M-mode and two-dimensional (2D) assessment of the IVC size and collapsibility as an index of mean RA pressure. 4. Continuous wave (CW) Doppler of the TR signal for assessment of pulmonary artery (PA) pressure. 5. PW Doppler of the pulmonary regurgitation, RV outflow tract, and SVC flow.

6. M-mode measurement of tricuspid annular plane systolic excursion (TAPSE). 7. Tissue Doppler of the TV annulus and RV free wall. 8. Assessment of RA size. 9. Assessment of RV size and systolic function.

PHYSIOLOGICAL AND OTHER FACTORS THAT AFFECT HEPATIC VENOUS FLOW Respiration Flow in the HVs is dependent on right heart hemodynamics and on the respiratory cycle.3 Interpretation of the Doppler signal should take into account the various phases of respiration (i.e. inspiration, expiration, and apnea).10,12,13 The effect of respiration on flow is more prominent in the HVs than the PVs with phasic changes in the shape, direction, and velocity of the waveforms. Inspiration is associated with a normal decline in intrathoracic pressure by 5 to 7 mm Hg. This pressure drop is transmitted to the intrathoracic structures including RA, SVC, and IVC resulting in an increase in blood return from the vena cava to the right heart.14 The HV Doppler shows an augmented forward flow manifested by an increase in the peak velocity and TVI of the S and D waves (Fig. 16.7).3 With inspiration causing a volume load to the right heart, the normally compliant RV can accommodate the increase in preload without abnormal increase in filling pressures.3

Chapter 16: Spectral Doppler of the Hepatic Veins

Fig. 16.7: Effect of respiration on hepatic venous flow. The hepatic vein Doppler is recorded at a 25 mm/s speed with simultaneous respiratory recording. At this speed, one can often assess the effect of more than one respiratory cycle on flow. With inspiration, forward flow velocities increase as compared to apnea. The normal late diastolic reversal is most prominent in early expiration and is indicated by arrows.

Thus, no significant flow reversals are noted in the HVs. With the onset of expiration, the intrathoracic pressure rapidly increases and becomes less negative leading to opposite effects on HV flow. As compared to apnea, the S and D waveforms demonstrate a decrease in peak velocity and TVI. An increase in flow reversals particularly in early expiration is noted.3,10 Often, the S/D ratio decreases with inspiration and increases with expiration due to more pronounced changes in diastolic flow.3,12 Under normal conditions, the percentage increase in flow averages 20% from expiration to inspiration.15 Since no relationship exists between the cardiac and respiratory cycles, the effect of respiration on flow velocities and direction varies from one respiratory cycle to another. The magnitude of the effect of respiration depends on its depth and the intrathoracic pressures that are generated during inspiration and expiration. Analysis of the flow signal over several respiratory cycles is useful. It might be helpful to select cardiac cycles that begin immediately after the onset of inspiration and expiration for analysis. A simultaneous respiratory recording can prove valuable in identifying the various respiratory phases, particularly the onset of inspiration and expiration. It may help in the interpretation of the pattern of flow (Fig. 16.7).3,10,14 However, the use of a respiratory recording is not always required since one can often determine the phase of respiration by carefully observing the pattern of change in forward flow velocities over several respiratory cycles. When disease states such as constrictive pericarditis or

303

restrictive cardiomyopathy are suspected, a simultaneous respiratory recording during HV and TV Doppler acquisition is strongly recommended.16 Recording of the Doppler signal at a slow speed (25 mm/s) allows one to better analyze the pattern of changes in waveform direction and velocity over more than one respiratory cycle and assess the extent and timing of the flow reversals. A comprehensive evaluation of right heart hemodynamics should include separate evaluation of the filling pressure and the filling pattern. Assessment of the RA pressure is obtained via analysis of the IVC and HV diameters, the collapsibility of the IVC with inspiration, and to a lesser extent by analysis of the HV S/D ratio (see below).17 Assessment of the filling pattern provides information on RV compliance and is primarily accomplished via evaluation of the HV and TV inflow Doppler and the response of various waveforms to respiration. If the RV is compliant, the normal inspiratory increase in filling is not associated with an increase in filling pressures and no exaggerated reversals are noted in the HVs during inspiration. Conversely, a noncompliant RV demonstrates an abnormal increase in pressure in response to the inspiratory increase in filling, leading to flow reversals in the HVs (see section on RV diastolic dysfunction).10,18 A normal filling pattern may coexist with normal or elevated mean RA pressure. Similarly, an abnormal filling pattern may coexist with normal or elevated mean RA pressure.

Other Factors Age and gender have minor effect on the HV Doppler. With aging there is a gradual increase in peak A velocity, likely due to reduction in RV compliance, similar to findings in the PV Doppler.15,19 Females tend to have lower peak diastolic and atrial reversal velocities with a greater percentage of systolic forward flow.15 Exercise results in an increase in the velocity of all waveforms with no change in waveform morphology.20 Fasting or fatty meals do not significantly alter the HV flow pattern.20,21 During pregnancy, the HV Doppler shows reduction in pulsatility with dampening of the waveforms. A monophasic flow profile can be encountered in the late stages of pregnancy, and the HV flow may remain abnormal beyond 8 weeks postpartum.22,23 Thus, caution should be exercised when diagnosing abnormal HV Doppler during pregnancy and in the early postpartum period. Mechanical ventilation with the use of positive end-expiratory pressure reduces forward flow velocities but does not result in increased reversals.21 The Valsalva maneuver may cause a monophasic HV signal.12

304

Section 2: Echocardiography/Ultrasound Examination and Training

more able to change its diameter within the mediastinum, making it more compliant than the HVs. An increase in the SVC diameter with inspiration explains the lack of increase and sometimes the paradoxical decrease in forward flow velocity despite an increase in blood flow.3 Some disorders including TR and constrictive pericarditis may manifest dissimilar or discordant flow patterns in the HVs and SVC. Analysis of the flow pattern in both veins is required for a comprehensive assessment of right heart filling.

TRANSTHORACIC ECHOCARDIOGRAPHY Fig. 16.8: Normal spectral Doppler of the superior vena cava. The various waveforms are indicated. This often shows a lower velocity of the A and V waves and less respiratory reversals than the hepatic vein Doppler.

DOPPLER PATTERN OF THE HEPATIC VEINS VERSUS THE SUPERIOR VENA CAVA Flow in the intrathoracic SVC is recorded from the supraclavicular area with the sample volume placed at a 5- to 7-cm depth.3,10 The SVC shows a similar flow profile to the HVs since it is under the influence of the same hemodynamic forces (Fig. 16.8). However, the flow pattern is not identical in both veins. Normally the HVs demonstrate a more prominent A wave reversal.3 Additionally, the V wave reversal that is commonly encountered in the HV Doppler is less often noted in the SVC (Fig. 16.2).3 The HV and SVC Doppler show similar S/D ratio; however, the SVC often demonstrates higher forward flow velocities.24 With inspiration, forward flow increases more in the HVs than in the SVC.3 The peak of the S and D velocities occurs simultaneously in both veins. One explanation for the discrepancy in the flow pattern between the HVs and SVC is the pressure difference between the intra-abdominal and intrathoracic cavities. The intraabdominal location of the HVs may lead to blunting of the respiratory changes in intrathoracic pressure to which the SVC is exposed. Additionally, the confinement of the HVs within the liver parenchyma and capsule alters their compliance, allowing for better recording of flow reversals.3 Since the SVC is not anatomically confined, it is

The HV Doppler can be recorded in the majority of subjects by transthoracic echocardiography (TTE). The subcostal window often provides the best approach for imaging the HVs.4 From a subcostal four-chamber view, medial angulation of the transducer allows visualization of the long-axis view of the IVC. Counterclockwise rotation often brings into view the left and middle HVs (see Fig. 16.1). Slight medial and lateral angulation of the transducer may be required to improve alignment with the long axis of one of the veins. Often, the middle HV offers a better alignment of flow with the Doppler beam (see Fig. 16.1).25 Occasionally, the subcostal window does not allow optimal visualization of the HVs due to body habitus, chest deformity, lung disease, mechanical ventilation, or following surgery.10 Alternative imaging windows can be attempted. In one approach, with the subject in a supine position and the index mark pointed to the left shoulder, the transducer is moved from the subxyphoid area along the rib margin to the right mid-clavicular area to visualize the HVs (Fig. 16.9). In another approach, the subject is placed in a left decubitus position. With the index mark pointed toward the feet, the transducer is moved at the same level from the subxyphoid area to the right midaxillary area. From the mid-clavicular window, flow in the middle HV is best aligned with the Doppler beam whereas the mid-axillary window provides better alignment with the right HV.26 In the absence of congenital malformations or obstruction to flow, the identification of dilated HVs (diameter > 11 mm) indicates an elevation in mean RA pressure (see Fig. 16.1).27 Many disorders that affect the right heart lead to high filling pressures and dilatation of the HVs, thus technically facilitating the recording of a good quality HV signal.

Chapter 16: Spectral Doppler of the Hepatic Veins

Fig. 16.9: Color Doppler of the middle hepatic vein (MHV) and right hepatic vein (RHV) from the mid-clavicular window.

TRANSESOPHAGEAL ECHOCARDIOGRAPHY Transesophageal echocardiography (TEE) allows optimal visualization of the HVs and recording of an adequate flow signal;28–31 however, it is rarely required for imaging of the HVs since these are often well imaged from the transthoracic window. TEE is mostly useful as an adjunct to color Doppler for the assessment of the degree of TR preoperatively. Following cardiopulmonary bypass (CPB) and TV repair, the HV Doppler often demonstrates systolic flow reversal in the absence of TR (see section on Cardiopulmonary bypass). The reversal limits the value of the post-CPB assessment of TR by HV Doppler in the operating room (see section on Tricuspid regurgitation).

TECHNICAL CONSIDERATIONS Training and experience are required for optimal visualization and recording of the HV Doppler. Color flow mapping is helpful to guide the PW Doppler examination by demonstrating blood flow. It allows to distinguish the HVs from biliary ducts that show no flow signal and to better visualize veins that are not well seen on 2D imaging (Fig. 16.10). A 2-mm PW sample volume is placed 1 to 2 cm into the HV, proximal to its junction with the IVC.32 The velocity filter is adjusted to optimize the quality of the spectral display and to allow visualization of low-velocity waveforms.33–35 In case a satisfactory recording cannot

305

Fig. 16.10: Hepatic veins versus biliary ducts. The middle and right hepatic veins demonstrate flow on color Doppler, indicated by arrows. A biliary duct does not demonstrate flow, indicated by an arrowhead.

be obtained, another HV can be attempted from the same transducer location or from an alternative imaging window as described above.26 Data should be derived from recording of several respiratory cycles. The requirements for optimal recording and interpretation of the HV Doppler are summarized in Table 16.1.

HEPATIC VENOUS FLOW IN DISEASE STATES Several disease states lead to characteristic abnormalities in the HV flow pattern. Understanding the physiological parameters that underlie each waveform and the pathological factors that affect the velocity profile, conducting a systematic evaluation of the Doppler signal, and assessing the response to respiration are all essential requirements for correct data interpretation. Disorders of the right heart may coexist. The resulting abnormal hemodynamics may amplify or cancel out their individual effect on the HV Doppler. For example, atrial fibrillation and reduction in RV systolic function independently cause reduction in the forward systolic velocity. Their combined presence causes severe blunting or reversal of the S wave. Conversely, pulmonary hypertension (PHTN) causes blunting or loss of the D wave whereas severe TR often results in reversal of the S wave. Their combined presence, not a rare occurrence, often leads to reappearance of the D wave (see below).

306

Section 2: Echocardiography/Ultrasound Examination and Training

Table 16.1: Requirements for Optimal Recording and Interpretation of the Hepatic Venous Doppler

Transducer location in the subcostal area Visualize the long-axis view of the inferior vena cava Optimize two-dimensional (2D) image quality Identify the left or middle hepatic veins and visualize flow within the vein using color Doppler If hepatic veins are not well visualized, consider the mid-clavicular or mid-axillary window Ensure alignment of Doppler signal with flow Ensure optimal pulsed wave Doppler settings: • Sample volume size: 2 mm • Sample volume location: 1–2 cm inside the vein proximal to IVC • Gain settings • Filter settings • Recording speed of 25 mm/s to assess respiratory variability • Recording speed of 50–100 mm/s to assess waveform morphology and measure hepatic vein A wave duration Obtain tricuspid inflow Doppler at same recording speed for comparison Good echocardiogram tracing showing P wave and QRS complex Know the underlying rhythm Know the PR interval Be aware of pitfalls and artifacts Interpretation should take into account additional findings on 2D, color, spectral, and tissue Doppler imaging

Abnormal Respiratory Changes in Intrathoracic Pressures The effect of respiration on the HV Doppler depends on the depth of breathing, that is, on the level of inspiratory and expiratory pressures that are generated within the thoracic cavity. Individuals with increased respiratory effort or airway obstruction typically demonstrate large swings in intrathoracic pressure. They generate more negative pressure during inspiration than normal subjects and less negative pressure (or even positive pressure) during expiration.36 Disorders that manifest this phenomenon include chronic obstructive lung disease (COPD), respiratory distress, and postoperative states. The HV Doppler often demonstrates a marked increase in forward flow velocity during inspiration with possible exaggerated expiratory reversals. An uncoupling between the HV flow and right heart hemodynamics may occur with inspiration. Instead, the flow pattern becomes governed by the drop in intrathoracic pressure irrespective of the phase of the cardiac cycle. Typically, the HV Doppler shows a high velocity and continuous wave from the onset of systole to the onset of atrial contraction. The loss of distinct systolic and diastolic waves implies a dissociation of flow from the cardiac cycle and dependence on the

respiratory cycle. However, the contribution of the right heart dynamics is not completely abolished since the effect of atrial contraction is intermittently visible on the forward flow (Fig. 16.11A). Significant respiratory variability in flow is noted across the MV, TV, and SVC with increase in forward flow velocity during inspiration (Figs 16.11A and B).37

Rhythm and Conduction Disorders Arrhythmias or frequent ectopic beats pose a challenge to the interpretation of the HV Doppler.

Sinus Bradycardia and Tachycardia At a slow heart rate (< 60 bpm), the HV Doppler may demonstrate flow reversal in mid-diastole (Fig. 16.12).3 This reversal corresponds to the H wave described in jugular venous pulse tracings during bradycardia.38 Sinus tachycardia affects mainly the forward D and A reversal waves. An increase in heart rate leads to shortening of the diastolic filling period with the atrial contraction occurring during the rapid filling phase. This causes significant reduction or obliteration of the smaller A wave and decrease in the peak velocity of the D wave (Fig. 16.13). The S wave velocity may increase due to the lack of flow reversal during atrial contraction.

Chapter 16: Spectral Doppler of the Hepatic Veins

A

307

B

Figs 16.11A and B: Chronic obstructive lung disease. (A) The hepatic vein Doppler shows a marked increase in forward flow velocity with inspiration, indicated by arrows. There is a loss of distinct waveforms during inspiration implying a dissociation of flow from the cardiac cycle and a dependence on the respiratory cycle; (B) Doppler of the superior vena cava shows similar findings. The arrow shows inadvertent recording of flow from the ascending aorta.

Fig. 16.12: Sinus bradycardia. The hepatic vein Doppler shows normal mid-diastolic flow reversal, indicated by arrows, noted between the forward D wave and the A wave. This flow is due to the slow heart rate of 56 bpm.

Fig. 16.13: Sinus tachycardia. At a heart rate of 112 bpm, there is shortening of diastole with atrial contraction occurring during the rapid filling phase. This pattern results in obliteration of the A wave reversal and decrease in the peak velocity of the D wave on the hepatic vein Doppler.

Short PR Interval

(Fig. 16.14). The Doppler pattern mimics the abnormal elevation in right ventricular end-diastolic pressure (RVEDP) (see section on RVEDP). The short PR interval affects the HV Doppler to a lesser degree than the PV Doppler. This difference is due to the fact that the TV normally closes later than the mitral valve. Thus, the PR interval has to be very short to result in changes in the HVs. A prominent A wave reversal in the PV is not necessarily associated with a similar finding in the HV. However, if this finding is identified in the HV, it should be present as well in the PV.

A short PR interval < 120 milliseconds may affect the HV Doppler. The shorter the PR interval, the more likely one would identify changes. With a short atrioventricular (AV) delay, the abrupt rise in RV pressure in early systole causes premature termination of flow across the TV. This translates into a TV A wave that has a short duration. Since RA pressure has not decreased yet, backflow occurs into the vena cava and HVs. The HV Doppler demonstrates a prominent A wave that lasts beyond the TV A wave

308

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 16.14: Short PR interval of 115 milliseconds in a 44-yearold female. The hepatic vein (HV) Doppler shows a large A wave reversal with a high flow velocity (45–50 cm/s) and an average duration of 210 milliseconds. The A reversal ends 110 milliseconds later than the tricuspid (TV) A wave. This finding is caused by the short PR interval and is not due to an elevation in right ventricular end-diastolic pressure.

Fig. 16.15: Prolonged PR interval of 260 milliseconds in a 55-yearold male. The hepatic vein Doppler shows an A wave that occurs following the D wave. The atrial relaxation wave that follows, indicated by an arrow, begins and peaks before the onset of systole and is widely separated from the systolic wave. There is a “triple forward wave” pattern to the flow signal.

When the heart rate is relatively slow, atrial contraction may still occur after the D wave has ended and neither wave is affected. The atrial relaxation wave is evident before the onset of the following systole, giving a “triple forward wave” pattern to the HV signal (Fig. 16.15). The S wave thus results from the sole contribution of the TV annular descent and shows a reduced velocity since it starts at the zero line rather than at the higher velocity generated by the atrial relaxation wave.

Atrioventricular Dissociation Fig. 16.16: Atrioventricular dissociation. The hepatic vein Doppler shows intermittent “cannon A waves,” indicated by arrows, which result from atrial contraction during ventricular systole.

Prolonged PR Interval Findings on the HV Doppler depend on the degree of the AV delay and heart rate. Similar to tachycardia, a long PR interval causes the atrial contraction to occur before the rapid filling phase has ended. If atrial contraction occurs simultaneously with the D wave, it causes attenuation of the latter and reduction or absence of an A wave reversal.

AV dissociation often results from asynchronous ventricular pacing or complete heart block. The absence of AV synchrony leads to beat-to-beat variability in the HV Doppler. The flow pattern is dependent on the temporal relationship between atrial systole (P wave) and ventricular systole (QRS complex). The HV A wave and atrial relaxation wave are inscribed irrespective of the phase of the cardiac cycle. When atrial contraction occurs during ventricular systole and against a closed TV, the rise in RA pressure results in large “cannon wave” reversals (Fig. 16.16).39,40 When atrial contraction occurs early in diastole, the A wave becomes superimposed on the D wave resulting in reduction in D wave velocity and no clear A wave.

Chapter 16: Spectral Doppler of the Hepatic Veins

309

Fig. 16.17: Premature ventricular beat. The hepatic vein Doppler demonstrates a large reversal (cannon A wave), indicated by an arrow, when atrial contraction occurs during ventricular systole induced by the premature beat.

Fig. 16.18: Atrial fibrillation. The hepatic vein Doppler shows a dominant D wave with a small S wave on every beat. The late diastolic reversals, indicated by arrows, occur intermittently and do not represent an A wave.

Premature ventricular contractions may cause large reversals if simultaneous atrial contraction or retrograde conduction occurs (Fig. 16.17).

Disorders that cause abnormalities in RV diastolic function and reduction in chamber compliance initially lead to an increase in RVEDP. The pressure rise in end diastole within the RV exceeds RA pressure before the latter has begun to decline. This phenomenon causes an abrupt closure of the TV and shortening of the tricuspid A wave duration. Since blood flow can no longer proceed forward across the TV, it backflows into the HVs for a longer duration than across the TV. The most reliable parameter of elevated RVEDP is a prominent A wave reversal in the HVs that consistently exceeds in duration the abbreviated A wave across the TV (Fig. 16.19).27 This finding should be present on consecutive beats irrespective of the phase of the respiratory cycle. An increase in the velocity of the HV A reversal is often present and shows little respiratory variability (Fig. 16.20). Before a diagnosis of elevated RVEDP is made, one must ensure that the PR interval is not abnormally shortened (see section on Short PR interval). The elevation in RVEDP coexists with either normal or elevated mean RA pressure. Most patients with elevated RVEDP demonstrate an HV signal with normal S/D ratio (S > D) and no exaggerated inspiratory reversals as long as RV compliance remains normal. Even in the presence of elevated mean RA pressure, the HV Doppler often continues to demonstrate a systolic dominant pattern. A decrease in the systolic filling fraction with reversal of the normal S/D ratio (S/D < 1) occurs when elevation of RA pressure coexists with reduction in RV compliance

Atrial Fibrillation The loss of atrial contraction leads to the absence of a retrograde A wave. The loss of atrial relaxation, in turn, results in a decrease in the peak S velocity and an S < D configuration (Fig. 16.18).10,41 The S wave may even disappear.41,42 The coexistence of TR and/or decrease in RV systolic function further reduce the amplitude of the S wave and often lead to systolic flow reversal.

Assessment of Right Ventricular End-Diastolic Pressure Comparison of flow characteristics in the HVs and across the TV at atrial contraction provides insight into the level of the RVEDP. This comparison is similar to the one between the PV and MV flow for the assessment of left ventricular (LV) end-diastolic pressure (see the chapter on Pulmonary vein Doppler). Following RA contraction in normal individuals, the net volume of blood flow is larger forward (toward the RV) than backward (toward the HVs). The duration of the A wave is normally similar in the HVs and across the TV at the same phase of respiration (Fig. 16.19).

310

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 16.19: Relationship between right atrial (RA) and right ventricular end-diastolic pressure (RVEDP), tricuspid valve (TV), and hepatic vein (HV) Doppler. (A): Normal RVEDP. The TV and HV Doppler show similar A wave duration due to timely TV closure (TVC). (B): Elevated RVEDP. RA contraction leads to rapid rise in RVEDP that exceeds RA pressure and results in early TVC. This causes shortening of the TV A wave duration. Since RA pressure remains elevated at TVC, blood backflows into the HV for a longer duration than across the TV resulting in a longer HV A wave duration with a higher velocity.

(see section on RV diastolic dysfunction). Similarly, an S/D ratio < 1 does not necessarily imply elevation in mean RA pressure despite such report.43 Reversal of the ratio occurs with several conditions including atrial fibrillation, reduction in RV longitudinal function, and following CPB in the setting of normal RA pressure (see below). As mentioned above, the HV Doppler provides more data regarding the filling pattern than the filling pressure of the right heart.

Tricuspid Valve Disease Tricuspid Regurgitation Changes in HV flow in the setting of TR mirror the changes in PV flow in mitral regurgitation. The HV Doppler provides a semiquantitative assessment of the severity of TR. It complements findings on color Doppler imaging and helps discriminate between hemodynamically significant and nonsignificant degree of TR.44 A normal HV flow pattern strongly argues against the presence of severe TR.

Fig. 16.20: Elevated right ventricular end-diastolic pressure (RVEDP) in a 31-year-old male with severe pulmonary valve stenosis. The tricuspid valve (TV) Doppler shows an A wave duration of 125 milliseconds. There is a prominent mid-diastolic flow reversal, indicated by an arrow, suggestive of elevated RV diastolic pressure. The hepatic vein (HV) Doppler demonstrates a large A wave with high peak velocity and significantly longer duration (230 milliseconds) than the TV A wave suggestive of elevated RVEDP. The PR interval on the echocardiogram (ECG) is not shortened.

Mild TR does not affect the HV Doppler.32 Worsening of TR leads to progressive decrease in the peak systolic velocity and the systolic filling fraction (Fig. 16.21). In severe TR, the normal antegrade S wave is often replaced by a prominent retrograde wave or systolic reversal (SR) (Fig. 16.22).32,44 The SR is noted in approximately two third of patients with severe TR.32,45 It reflects the transmission of the RV pressure into the RA and corresponds to the abnormally large v wave noted on RA pressure recording in late systole. In general, the more severe the TR, the larger the v wave becomes and the lower the S velocity.41 The S/D ratio inversely correlates with RA pressure.41 Occasionally the SR begins before systole due to merging of the A wave with the reversed S and V waves to form a single large retrograde wave. Frequently an increase in the D velocity is noted since all forward flow and right heart filling occur in diastole. The SR can often be identified by color Doppler imaging of the HVs. On physical examination, the SR is manifested by the presence of a pulsatile liver. Patients with moderate TR and some patients with severe TR may demonstrate blunting of the S wave with an S < D pattern (Fig. 16.21).41,45 Blunting of the S wave and SR should not be used as the only markers to quantify the degree of TR since other variables affect the S wave velocity and direction. These variables include RA pressure and

Chapter 16: Spectral Doppler of the Hepatic Veins

Fig. 16.21: Moderate tricuspid regurgitation (TR) in a patient with sinus rhythm and normal right ventricular function. The hepatic vein (HV) Doppler shows blunting of the systolic velocity with an S/D ratio < 1. This pattern can be observed with more severe TR and with other conditions such as atrial fibrillation, prior cardiopulmonary bypass, and reduced RV systolic function. With such a flow pattern, the HV Doppler should not be used as the sole parameter for grading TR.

compliance, RV systolic function, PA pressure, and the underlying rhythm.10 A large and compliant RA may not demonstrate a prominent v wave in the setting of severe TR, and the HV Doppler will show a reduced S wave velocity rather than flow reversal.10,32,45 Conversely, a noncompliant RA may demonstrate SR in the absence of severe TR.10 Thus, severe TR can be present without SR and the latter may result from pathologies other than severe TR. Conditions that cause or contribute to SR in the absence of TR include a reduced RV systolic function (particularly longitudinal motion), CPB, and atrial fibrillation.41,46 Whereas these entities often cause blunting of the S wave, they may lead to SR when combined or when RV longitudinal function is severely reduced. Timing of the peak SR may help distinguish its etiology. Severe TR typically causes a late peaking SR coincident with the v wave on the RA pressure tracing (Fig. 16.22).41 Reduction in RV systolic function typically results in an early peaking SR. In patients with TR, normal sinus rhythm, preserved RV systolic function, and no prior CPB, a late peaking SR suggests severe TR. If TR is associated with any of the other conditions, an early peaking SR does not necessarily imply severe regurgitation. In case some of these conditions coexist, the SR becomes more prominent and may not follow a characteristic pattern. For example, the association of severe TR with atrial fibrillation results in a more prominent SR than during

311

Fig. 16.22: Severe tricuspid regurgitation (TR). The forward S wave on the hepatic vein Doppler is replaced by a prominent systolic reversal (SR) of flow with a late peaking reversal (indicated by an arrow) noted on every beat. This pattern is highly suggestive of significant TR.

sinus rhythm. The presence of severe TR following CPB or in association with reduced RV function leads to worse SR than each condition alone, and the SR may not demonstrate a characteristic late systolic peak (Figs 16.23A to C). When severe TR is present, the SVC Doppler often demonstrates a less abnormal flow pattern than the HV Doppler. Blunting of the S wave in the SVC is more common than SR. Patients with large SR in the HVs often demonstrate no SR in the SVC (Fig. 16.24). In a similar fashion to TR, a Gerbode defect with a large LV to RA shunt may cause SR on the HV Doppler.

Tricuspid Stenosis When a significant obstruction to the RV inflow is present, the HV Doppler shows attenuation of the forward S and D velocities. Similar to the PV Doppler in mitral stenosis, the most characteristic finding is a prolongation of the D wave pressure halftime that reflects the slow pressure decay across the TV. The duration of the pressure halftime is often similar for the HV D and TV E waves. A prominent atrial reversal can be present in the setting of normal RA function and sinus rhythm (Fig. 16.25).

Pulmonary Hypertension Abnormalities in central venous flow are common in patients with significant PHTN.47,48 The HV Doppler is often abnormal when moderate or severe PHTN exists.49 The pattern of the Doppler signal depends on several factors including heart rate, rhythm, RV systolic function, and degree of TR.

312

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 16.23A to C: Severe tricuspid regurgitation (TR) with reduced right ventricular function. Transesophageal echocardiogram with color Doppler (still frames). (A) A hepatic vein (HV) shows flow reversal during systole; (B) The same HV shows forward flow during diastole; (C) Spectral Doppler of the HV shows prominent holosystolic reversal (SR); however, the latter is not late peaking.

Fig. 16.24: Severe tricuspid regurgitation associated with atrial Fig. 16.25: Tricuspid stenosis. The hepatic vein Doppler shows low fibrillation. The hepatic vein (HV) Doppler shows prominent systolic S and D velocities with prolongation of the D wave deceleration reversal (SR) with every beat, indicated by arrows. Spectral Dop- time (indicated by an arrow). A prominent A wave is also noted. pler of the superior vena cava (SVC) shows the loss of systolic flow on most beats; however, no SR is noted.

Chapter 16: Spectral Doppler of the Hepatic Veins

313

Fig. 16.26: Severe pulmonary hypertension (PHTN). The hepatic vein Doppler shows a prominent A wave with no respiratory variability suggestive of elevated right ventricular end-diastolic pressure. There is a forward S wave; however, no D wave can be identified. This pattern is highly suggestive of PHTN.

Fig. 16.27: Severe pulmonary hypertension (PHTN) associated with significant tricuspid regurgitation. The hepatic vein Doppler shows a prominent A wave as compared to the forward waves. The S wave is absent with occasional systolic reversal (arrow) and the D wave has re-emerged despite the presence of severe PHTN. The forward waves indicated by arrowheads are related to atrial relaxation rather than tricuspid annular descent.

The main finding in significant PHTN is a prominent A wave reversal, indicative of elevated RVEDP due to RV hypertrophy (Fig. 16.26) (see section on RVEDP).27,49 The A wave velocity often shows minimal variability with respiration. Blunting or absence of the D wave is often noted in severe PHTN. This finding results from the delay in TV opening due to impairment in myocardial relaxation.10 The D wave can be blunted at slow heart rate and absent or reversed at a faster rate and during expiration (Fig. 16.26). When PHTN is associated with severe TR, the features of TR predominate. The S wave is attenuated or SR is present causing the D wave to re-emerge since most or all forward flow now occurs in diastole (Fig. 16.27). Still, the onset of the D wave is delayed due to delay in TV opening. The combination of PTHN and RV systolic dysfunction or atrial fibrillation also leads to blunting of the S wave or to frank SR with re-emergence of the D wave.

The effect of various conditions on the S wave velocity is incremental. As such, atrial fibrillation, reduction of RV systolic function, and TR all independently cause blunting or reversal of the S wave. Coexistence of these conditions often leads to the absence of the S wave or to more prominent reversals than each condition alone (Fig. 16.30).

Right Ventricular Systolic Dysfunction A reduction in RV systolic function, particularly the longitudinal motion, results in a decrease of the S velocity and increase in the D velocity (Figs 16.28A and B). Progressive worsening of RV function leads to more blunting of the S wave. When severe RV dysfunction is present, an early peaking SR ensues in the absence of significant TR (Fig. 16.29).46

Right Ventricular Diastolic Dysfunction Abnormal relaxation is often the first manifestation of RV myocardial involvement in many disease states.10 Due to slowing in myocardial relaxation, the fall in RV pressure during the isovolumic relaxation time (IVRT) leads to a delay in RA–RV pressure crossover and, thus, in TV opening with prolongation of the right-sided IVRT. The TV Doppler demonstrates a decrease in peak E velocity together with a prolongation of the deceleration time (DT) and an increase in A wave velocity and duration.50 The HV Doppler shows reduction in the peak velocity of the D wave (Fig. 16.31) and the latter can be absent when severe impairment in RV relaxation exists.10,27 Similar findings on the TV and HV Doppler occur in the setting of hypovolemia and reduced preload. With progression of the myocardial disease, impaired relaxation becomes associated with a reduction in RV chamber compliance.18 The latter is initially manifested by an increase in RVEDP (see section on Assessment

314

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 16.28A and B: Right ventricular systolic dysfunction. (A) The hepatic vein (HV) Doppler shows a reduced S velocity with an S/D ratio < 1. Note the normal increase in forward flow during inspiration and the early expiratory reversals indicated by arrows; (B) The same patient with the HV Doppler obtained during apnea. Note the flat profile with lack of respiratory variability in flow velocities.

Fig. 16.29: Severe right ventricular systolic dysfunction. The hepatic vein Doppler shows systolic flow reversal (SR) with early peaking signal (arrow). This pattern contrasts with the late peaking SR of severe tricuspid regurgitation.

Fig. 16.30: Right ventricular systolic dysfunction with atrial fibrillation. The combination of these conditions often leads to systolic reversal (SR) on the hepatic vein Doppler.

of RVEDP). With more reduction in RV compliance, a restrictive filling pattern develops.18,51 This pattern is characterized by an abrupt and premature cessation of RV filling in mid–late diastole. Elevation in mean filling pressures is often noted with dilatation of the IVC and poor inspiratory collapse. Similar to changes across the mitral valve, the TV Doppler demonstrates increased E velocity with reduced respiratory variability, a shortened DT (< 160 milliseconds) and reduced A wave velocity and duration.18 Mid- or late diastolic TR can also occur. In the HVs, the restrictive filling leads to a gradual decrease in the S wave

and a progressive increase in the D wave with reversal of the S/D ratio (S/D < 1).18,51 Abbreviation in systolic and diastolic flow in the HVs is noted. In advanced disease, the S wave is absent and all forward flow occurs in diastole.18 The occurrence and magnitude of the diastolic dominant pattern depends on several factors including RA pressure and contractility, RV systolic function, degree of TR, and the presence of atrial fibrillation.10 With a restrictive physiology, the RV is unable to accommodate the increase in venous return that normally occurs during inspiration. This leads to an inspiratory

Chapter 16: Spectral Doppler of the Hepatic Veins

Fig. 16.31: Impaired right ventricular relaxation pattern. The tricuspid valve (TV) Doppler shows an E/A ratio < 1. The hepatic vein (HV) Doppler shows intermittent absence of the D wave.

increase in filling pressures and flow reversals in the central veins (Fig. 16.32). During inspiration, the TV Doppler shows an increase in E wave velocity with abrupt decrease in DT and shortening of the A wave duration. The latter may even disappear or reverse. The HV Doppler shows inspiratory decrease or loss of the S velocity with prominent systolic, early, and late diastolic flow reversals.10,18,51 Additionally, the short DT of the D wave shortens further during inspiration. Findings on the TV and HV Doppler during inspiration are sensitive indicators to the presence of restriction to RV filling.18 Whenever a restrictive physiology is suspected, a simultaneous respiratory recording allows for better interpretation of the Doppler findings. Patients with RV myocardial infarction may manifest a pattern of impaired relaxation or restrictive physiology depending on the degree of myocardial involvement.

Myocardial and Pericardial Diseases Restrictive Cardiomyopathy This entity is characterized by infiltration and/or fibrosis of the myocardium leading to reduction in RV chamber compliance and increase in stiffness.18,51 Restrictive cardiomyopathy should be distinguished from restrictive filling or physiology. The former describes an intrinsic and progressive myocardial disease that evolves through stages of abnormal RV filling pattern from impaired relaxation to restrictive filling (Fig. 16.32) (see section on RV diastolic dysfunction). A restrictive physiology is a hemodynamic

315

Fig. 16.32: Restrictive right ventricular filling pattern in a patient with restrictive cardiomyopathy due to cardiac amyloidosis. The tricuspid valve (TV) Doppler demonstrates an increase in peak E velocity during inspiration with shortening of the deceleration time. The hepatic vein (HV) Doppler shows abbreviation of the S and D wave duration and low velocity with exaggerated inspiratory reversals.

abnormality that results from a decrease in RV compliance and impairment in filling and is associated with elevation in filling pressures regardless of the underlying cardiac disease. Many patients with restrictive cardiomyopathy are diagnosed at a late stage when a restrictive filling pattern already exists. Restrictive cardiomyopathy shares many hemodynamic features with constrictive pericarditis. The infiltrative form of the disease, most commonly cardiac amyloidosis, is relatively easy to distinguish from constrictive pericarditis on the basis of 2D, spectral, tissue Doppler, and strain echocardiographic findings.52 The noninfiltrative form characterized by myocardial fibrosis is more difficult to distinguish. The HV Doppler is highly useful for this purpose. Whereas both entities are characterized by impairment in diastolic filling, the presence of exaggerated inspiratory reversals suggests that the hemodynamic derangement resides in the myocardium (restrictive cardiomyopathy) whereas exaggerated expiratory reversals suggest that the derangement resides in the pericardium (constrictive pericarditis).16,18

Constrictive Pericarditis The echocardiographic diagnosis of constrictive pericarditis is based on the constellation of 2D and Doppler findings. Characteristic Doppler patterns are mostly

316

Section 2: Echocardiography/Ultrasound Examination and Training

related to the respiratory variation in central venous flow as a result of the dissociation between intrathoracic and intracardiac pressures and the exaggerated LV–RV interdependence.16,53–55 With inspiration, the decrease in LV filling leads to a leftward ventricular septal shift that allows augmented and unimpeded RV filling. As a result, an increase in forward flow occurs in the HVs and across the TV. During expiration, the increase in LV filling leads to a decrease in RV filling due to rightward ventricular septal shift. A significant decrease in tricuspid flow velocity and increase in diastolic HV flow reversals develop.16,53 Comparison of left-sided Doppler parameters across the PV and MV with right-sided parameters across the HV and TV is essential to identify opposite changes in flow velocities. During apnea or inspiration, most patients with constrictive pericarditis demonstrate a higher systolic than diastolic velocity in the HVs. In severe constriction or coexistence of atrial fibrillation, a dominant diastolic velocity often develops. Abrupt termination of the systolic and diastolic waveforms is evident due to abbreviated filling and leads to a “W” pattern mainly on inspiration.56 The S and D waveforms show reduced velocity (< 60 cm/s) due to a low flow state.14 A characteristic finding on HV Doppler is the exaggerated diastolic flow reversal that occurs with expiration.16,53 The first beat of expiration often demonstrates the most prominent reversal (Fig. 16.33).16 A simultaneous respiratory recording is thus useful to identify the onset of expiration. In patients with severe constriction, inspiratory flow reversal can be present; however, it tends to worsen with the onset of expiration. Exaggerated expiratory reversals are not specific for constriction and may occur in other conditions associated with forced or strong expiration such as COPD, following CPB, RV infarction, and acute pulmonary embolism.14,37 The latter two conditions can be distinguished from constriction by echocardiography and other imaging modalities. The diagnosis of COPD is more difficult and findings on the TV and SVC Doppler are useful to distinguish it from constrictive pericarditis. Both constriction and COPD demonstrate a significant decrease in peak TV E velocity with expiration. In constrictive pericarditis, the most prominent reduction in TV E velocity occurs on the first beat of expiration (Fig. 16.33).14,37 It corresponds in timing to the exaggerated diastolic reversals in the HVs that are most marked on the first beat of expiration. In COPD, the reduction in TV E velocity and the HV reversals are most prominent later during expiration.

Fig. 16.33: Constrictive pericarditis. The hepatic vein (HV) Doppler shows reduced forward flow (S and D waves) with higher systolic than diastolic velocity during inspiration. There is abbreviation of diastolic filling with exaggerated diastolic reversals, most prominent on the first beat of expiration. The tricuspid valve (TV) Doppler demonstrates a marked decrease in flow velocity on the first beat of expiration.

In patients with COPD, a greater decrease in intrathoracic pressure occurs during inspiration leading to significant increase in flow toward the RA. This phenomenon is mostly evident on the SVC Doppler that demonstrates significant variability in flow with respiration. In constrictive pericarditis, no significant respiratory changes in flow are noted in the SVC and the difference in peak systolic velocity does not exceed 20 cm/s between inspiration and expiration.14,37 Patients with constrictive pericarditis may demonstrate a discordant effect of respiration on the flow pattern in the HVs and SVC. The HV Doppler is highly useful in suspected constriction when the value of left heart parameters, such as MV and tissue Doppler, is compromised by coexisting MV prosthesis or underlying myocardial infarction.14 However, the value of the HV Doppler in suspected constriction is lost if hemodynamically significant TR coexists.14 In patients with suspected constrictive pericarditis, a slow recording speed of the HV Doppler at 25 mm/s should be obtained to assess the respiratory variability in flow. The filter setting and velocity scale should be kept low to allow recording of low-velocity waveforms. The presence of atrial fibrillation poses a challenge to the diagnosis of constrictive pericarditis. The flow profile becomes additionally dependent on the R–R interval, thus

Chapter 16: Spectral Doppler of the Hepatic Veins

317

Fig. 16.34: Constrictive pericarditis with atrial fibrillation. The hepatic vein (HV) Doppler shows a dominant diastolic velocity due to atrial fibrillation. Despite the variability in the R–R interval, exaggerated expiratory reversals (indicated by arrows) are evident. The tricuspid valve (TV) Doppler shows significant reduction in flow velocity on the first beat of expiration.

Fig. 16.35: Cardiac tamponade. The hepatic vein Doppler shows significant reduction and cessation of forward diastolic flow (indicated by a star) with prominent diastolic reversals during expiration (indicated by arrows).

introducing another variable and thus making the Doppler signal more difficult to interpret (Fig. 16.34). Regularizing the heart rate with temporary ventricular pacing removes the cardiac cycle-dependent component and allows one to evaluate the respiratory variability in flow.14 Patients with combined constrictive pericarditis and restrictive cardiomyopathy typically demonstrate exaggerated reversals during both inspiration and expiration.14

The hemodynamic abnormalities that occur in cardiac tamponade resemble those in constrictive pericarditis.57,58 The main difference is a failure of early diastolic filling in tamponade. Due to the elevation and equalization of diastolic pressures between the RA, RV, and pericardial cavity, the RV fills in early diastole via exchange of blood with the RA; however, minimal or no blood flow enters the heart from the vena cava. Thus, early diastolic flow is markedly reduced or ceases leading to significant decrease or loss of the HV D velocity together with prominent expiratory diastolic reversals (Fig. 16.35).58,59 Blunting of the D wave corresponds to the attenuation of the y descent on the RA pressure recording.57

dominance of the flow profile (Fig. 16.36A).28,30,46,61,62 This pattern results from a significant reduction in systolic and mild increase in diastolic flow velocity.46,61 The mechanisms underlying this phenomenon include a reduction in tricuspid annular motion despite preserved RV ejection fraction and possibly alteration in RA relaxation and compliance.5,30,41 Occasionally, the S velocity is undetectable and SR may develop. When present, the reversal is often early systolic; however, late SR may also occur in the absence of TR.46,61 The SR is more pronounced with coexisting TR and/or atrial fibrillation. Exaggerated expiratory reversals are often noted, usually in early diastole. However, there is no abbreviation in diastolic filling contrary to patients with constrictive pericarditis or restrictive cardiomyopathy. The switch from a normal systolic to an abnormal diastolic dominance of HV flow is noted immediately after weaning from CPB and prior to chest closure.30 This finding is most pronounced early after surgery. The HV Doppler improves slowly over several months to years;46 however, the flow signal may never return to its preoperative pattern (Fig. 16.36B). The changes in HV Doppler that occur following CPB are not observed in the PVs.

Cardiopulmonary Bypass

Congenital Heart Disease

Cardiopulmonary bypass is used during most cardiac surgeries and leads to significant alterations in central venous flow.5,41,60 Following CPB, the HV Doppler shows diastolic

Patients with Ebstein’s anomaly show findings on HV Doppler that depend on the severity of TR and the degree of RV systolic and diastolic dysfunction.

Cardiac Tamponade

318

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 16.36A and B: Aortic valve replacement with cardiopulmonary bypass in a 24-year-old male. (A) Preoperative hepatic vein (HV) Doppler shows a normal systolic dominant pattern (S > D); (B) One year postoperatively, the HV Doppler continues to demonstrate an abnormal diastolic dominant pattern (S < D) with prominent late systolic V waves.

common and of low velocity (Fig. 16.37). The dependency of flow on inspiration is independent of the level of pressure in the RA.63

Liver Disease

Fig. 16.37: Fontan circulation. Hepatic vein Doppler in a 14-yearold male 7 years following the Fontan operation. Note the dependency of flow on inspiration. The first inspiration results in more forward flow than the second shallower inspiration (arrows). No flow reversals are noted. Between inspirations, only minimal forward flow is recorded.

Following the Fontan procedure, changes in the HV Doppler reflect the dissociation between the subdiaphragmatic venous flow and the ventricular pumping chamber that is no longer present. If a direct RA–PA connection is used, the HV flow often remains phasic and dependent on the cardiac cycle due to the influence of RA contraction and relaxation. With the use of a conduit, a low-velocity forward flow is noted that is dependent on the respiratory cycle. Forward flow increases with inspiration and decreases or ceases during expiration. Flow reversals are un-

Liver disease typically leads to uncoupling between right heart filling and HV flow. This results from a decrease in HV compliance that is normally determined by the surrounding liver tissue. The intrahepatic deposition of fat, fibrosis, or tumor leads to stiffening of the liver parenchyma that adversely affects venous compliance. Thus, the HV flow would no longer reflect right heart hemodynamics and instead demonstrates a flat profile with reduced phasicity that is determined by the severity of the underlying liver pathology.64–66 In the presence of combined right heart and liver disease, the HV Doppler may no longer demonstrate the characteristic findings of the cardiac disorder. Abnormalities in HV Doppler have been described in various conditions including liver cirrhosis, fatty infiltration of the liver, metastasis, liver transplantation, and tense ascites among others. Typically there is dampening of the waveforms with decrease in velocity and loss of flow reversals. A flat monophasic or biphasic pattern often develops (Fig. 16.38).64–66 Occasionally, a difference in the flow pattern between HVs reflects a focal liver pathology.25 Obesity is commonly associated with fatty infiltration of the liver. Up to a half of obese individuals demonstrate a loss of the normal triphasic or quadriphasic HV flow

Chapter 16: Spectral Doppler of the Hepatic Veins

319

Fig. 16.38: Chronic liver disease with cirrhosis. The hepatic vein Doppler shows a typical monophasic flow with marked dampening of the waveforms.

Fig. 16.39: Obesity. The hepatic vein Doppler demonstrates diminished oscillations with loss of flow reversals and a biphasic pattern showing forward S and D waves. Note the effect of atrial contraction on flow, indicated by arrows.

pattern. Instead, diminished oscillations with dampening of the waveforms occur. Most commonly a biphasic pattern showing only forward S and D waves is noted with decrease or loss of flow reversal (Fig. 16.39). Occasionally, a monophasic flow pattern occurs with no distinguishable waveforms.66 An inverse relationship exists between the phasicity of the HV flow and the degree of steatosis in the liver.67 In Budd-Chiari syndrome, HV obstruction leads to the absence of flow in the main HVs with evidence of intrahepatic venous collaterals on color Doppler.67 HV stenosis leads to a turbulent flow on color Doppler originating from the direction of one of the veins. CW Doppler demonstrates abnormally high waveform velocities or a monophasic flow with effacement of individual waveforms.66,68 Transjugular intrahepatic portosystemic shunt (TIPS) consists of a stent that connects a portal vein to an HV and is used for the treatment of portal hypertension associated with gastrointestinal bleeding. The spectral Doppler usually shows high velocity (1–2 m/s) and continuous flow within the stent with reduced pulsatility.69 Stent occlusion results in a lack of flow inside the stent.

however, HV flow is not necessarily easier to record, particularly in normal subjects. This is mainly due to the anatomical limitations imposed by the small caliber of the HVs in subjects with normal or low RA pressure.15 Patients with right heart disease often demonstrate dilatation of the HVs due to the elevation in RA pressure. This facilitates recording of HV flow and decreases the wall motion artifacts on the Doppler signal. In case the HV Doppler cannot be obtained, Doppler of the SVC provides valuable information on RV filling and is easily recordable in the majority of individuals.3,15 Since the HV and SVC Doppler may provide different information in some disease states, they should be considered as complementary rather than a substitute for one another. While recording the spectral Doppler, a correct location of the sample volume within the HV is essential. Placing the sample volume at the orifice of the HV often results in increased flow velocity and changes in the morphology of the waveforms. A wide angle of interrogation often leads to blunting of individual waveforms. Movement of the diaphragm and liver with normal breathing may cause the HV to move horizontally across the image display. This places the sample volume outside the HV during a part of the respiratory cycle and causes intermittent vanishing of the spectral Doppler image (Fig 16.40). Repositioning the transducer or interrogating a different HV may prove useful. Increasing the size of the sample volume to 3 to 4 mm can be attempted; however, this may increase wall motion artifacts.70 Occasionally recording

LIMITATIONS, TECHNICAL PITFALLS AND ARTIFACTS The HVs are easier to visualize than the PVs and are imaged at a lower depth of interrogation (7 cm vs ≥ 14 cm);

320

Section 2: Echocardiography/Ultrasound Examination and Training

has to be obtained during apnea; however, this deprives one from the assessment of the effect of respiration on flow (see Fig. 16.28B). If recording is performed during apnea, this should be done following expiration and the subject should be instructed not to inadvertently perform a Valsalva maneuver during breath-hold. There is a lesser chance of misrecording of flow from adjacent vascular structures in the HVs than the PVs. When sampling from the right midclavicular and midaxillary windows, one should not confuse flow in the HVs with flow in the portal vein or hepatic artery (Fig.16.41A). Distinguishing flow between the HV portal vein and hepatic artery is relatively simple. Whereas flow in the HV is phasic and predominantly below the baseline, the Fig. 16.40: Vanishing of the spectral Doppler image. Movement of the hepatic vein with respiration intermittently places the sample portal vein shows a monophasic and low-velocity flow volume outside the vein and results in the inability to interrogate above the baseline (Fig. 16.41B). This can be distinguished flow (indicated by an arrow). from abnormal monophasic HV flow by its direction.

A

B

C

Figs 16.41A to C: Pitfalls originating from inadvertent recording of hepatic venous flow. (A) Color Doppler from the mid-clavicular window showing the portal vein (PV), right hepatic vein (HV), and inferior vena cava (IVC); (B) Doppler recording of the portal vein shows a monophasic and low-velocity flow above the baseline; (C) Doppler recording of the hepatic artery shows a pulsatile flow during systole and low-velocity flow throughout diastole above the baseline.

Chapter 16: Spectral Doppler of the Hepatic Veins

In some disease states such as severe TR, portal vein flow may show pulsatility.71 Flow in the hepatic artery is pulsatile during systole with low-velocity flow throughout diastole above the baseline (Fig. 16.41C).35 The systolic pulsations should not be confused with systolic flow reversals in the HVs. By 2D imaging, the biliary ducts can occasionally be confused with the HVs; however, they do not demonstrate flow on color or spectral Doppler (Fig. 16.10). Assessment of the effect of respiration on the HV signal allows one to distinguish among disease states and to assess RV diastolic function. It is easiest to interpret the influence of respiration in subjects with a slow respiratory rate and relatively fast heart rate. Likewise, it is difficult to interpret the effect of respiration in subjects with rapid respiratory rate and a slow heart rate. When using simultaneous respiratory recording, a number of pitfalls should be kept in mind. The diastolic flow reversals that normally occur in early expiration can be recorded as if they occur at peak inspiration. This is due to the inherent time delay between the onset of a respiratory event such as expiration and its actual recording. There is a learning curve to the use of respiratory recording and interpretation of the Doppler velocities in relation to the various phases of respiration.53 The subject should be instructed in the technique of normal breathing. Erratic, labored, or irregular breathing, particularly in hospitalized patients, adds difficulty to the interpretation of the Doppler signal. The major challenge to the use of HV Doppler in clinical practice is often not technical and is not related to signal acquisition. It is rather the correct interpretation of the flow pattern and its integration with other right-sided parameters to provide an optimal assessment of right heart filling.

CONCLUSION The HV Doppler provides a window to the assessment of right heart function. Careful evaluation of the various components of the flow signal and the response to respiration allow the identification and analysis of several physiological and pathological processes. It provides important information regarding RV systolic and diastolic function, RV filling pattern and pressures, the severity of TR, the diagnosis and differentiation of constrictive pericarditis and restrictive cardiomyopathy, the presence

321

Fig. 16.42: Schematic drawing of various hepatic vein Doppler patterns. A differential diagnosis for each pattern is included; however, the effect of respiration on the flow signal is not shown. (TAPSE: Tricuspid annular plane systolic excursion; TR: Tricupid regurgitation; RV: Right ventricle; MI: Myocardial infarction; RVEDP: Right ventricular end-diastolic pressure).

of PHTN, and cardiac tamponade. Additionally, it provides useful information regarding cardiac rhythm, particularly the presence of AV dissociation. A differential diagnosis for the most common abnormal HV flow patterns is listed in Figure 16.42.

ACKNOWLEDGMENTS The authors would like to acknowledge the professionalism, dedication to duty, high quality performance, and hard work of the sonographers and staff of the Echocardiography Laboratory at the King Faisal Specialist Hospital and Research Center. Writing this chapter would not have been possible without their commitment and support.

322

Section 2: Echocardiography/Ultrasound Examination and Training

REFERENCES 1. Wexler L, Bergel DH, Gabe IT, et al. Velocity of blood flow in normal human venae cavae. Circ Res. 1968;23(3): 349–59. 2. Gabe IT, Gault JH, Ross J Jr, et al. Measurement of instantaneous blood flow velocity and pressure in conscious man with a catheter-tip velocity probe. Circulation. 1969; 40(5):603–14. 3. Appleton CP, Hatle LK, Popp RL. Superior vena cava and hepatic vein Doppler echocardiography in healthy adults. J Am Coll Cardiol. 1987;10(5):1032–9. 4. Reynolds T, Appleton CP. Doppler flow velocity patterns of the superior vena cava, inferior vena cava, hepatic vein, coronary sinus, and atrial septal defect: a guide for the echocardiographer. J Am Soc Echocardiogr. 1991;4(5): 503–12. 5. Sivaciyan V, Ranganathan N. Transcutaneous Doppler jugular venous flow velocity recording. Circulation. 1978; 57(5):930–9. 6. Moreno FL, Hagan AD, Holmen JR, et al. Evaluation of size and dynamics of the inferior vena cava as an index of rightsided cardiac function. Am J Cardiol. 1984;53(4):579–85. 7. Cosgrove DO, Arger PH, Coleman BG. Ultrasonic anatomy of hepatic veins. J Clin Ultrasound. 1987;15(4):231–5. 8. Skandalakis JE, Skandalakis LJ, Skandalakis PN, et al. Hepatic surgical anatomy. Surg Clin North Am. 2004;84(2): 413–35, viii. 9. Triulzi M, Gillam L, Gentile F, et al. Normal adult crosssectional echocardiographic values: linear dimensions and chamber areas. Echocardiography. 1984;1;403–26. 10. Nishimura RA, Abel MD, Hatle LK, et al. Assessment of diastolic function of the heart: background and current applications of Doppler echocardiography. Part II. Clinical studies. Mayo Clin Proc. 1989;64(2):181–204. 11. Jequier S, Jequier JC, Hanquinet S, et al. Doppler waveform of hepatic veins in healthy children. AJR Am J Roentgenol. 2000;175(1):85–90. 12. Abu-Yousef MM. Normal and respiratory variations of the hepatic and portal venous duplex Doppler waveforms with simultaneous electrocardiographic correlation. J Ultrasound Med. 1992;11(6):263–8. 13. Altinkaya N, Koc Z, Ulusan S, et al. Effects of respiratory manoeuvres on hepatic vein Doppler waveform and flow velocities in a healthy population. Eur J Radiol. 2011;79 (1):60–3. 14. Oh JK, Seward JB, Tajik AJ. Pericardial disease. In: Oh JK, Seward JB, Tajik AJ (Eds). The Echo Manual. Philadelphia, PA: Lippincott Raven; 1999:181–94. 15. Klein AL, Leung DY, Murray RD, et al. Effects of age and physiologic variables on right ventricular filling dynamics in normal subjects. Am J Cardiol. 1999;84(4):440–8.

16. Hatle LK, Appleton CP, Popp RL. Differentiation of constrictive pericarditis and restrictive cardiomyopathy by Doppler echocardiography. Circulation. 1989;79(2): 357–70. 17. Simonson JS, Schiller NB. Sonospirometry: a new method for noninvasive estimation of mean right atrial pressure based on two-dimensional echographic measurements of the inferior vena cava during measured inspiration. J Am Coll Cardiol. 1988;11(3):557–64. 18. Appleton CP, Hatle LK, Popp RL. Demonstration of restrictive ventricular physiology by Doppler echocardiography. J Am Coll Cardiol. 1988;11(4):757–68. 19. Sebban C, Job D, Caen JL, et al. Ventricular compliance and ageing. Biomedicine. 1975; 22(1):56–61. 20. Teichgräber UK, Gebel M, Benter T, et al. Effect of respiration, exercise, and food intake on hepatic vein circulation. J Ultrasound Med. 1997;16(8):549–54. 21. Coulden RA, Lomas DJ, Farman P, et al. Doppler ultrasound of the hepatic veins: normal appearances. Clin Radiol. 1992;45(4):223–7. 22. Roobottom CA, Hunter JD, Weston MJ, et al. Hepatic venous Doppler waveforms: changes in pregnancy. J Clin Ultrasound. 1995;23(8):477–82. 23. Pekindil G, Varol FG, Yüce MA, et al. Evaluation of hepatic venous pulsatility and portal venous velocity with Doppler ultrasonography during the puerperium. Eur J Radiol. 1999;29(3):266–9. 24. Maeda T, Matsuzaki M, Shiomi K, et al. Characteristics of blood flow velocity patterns of central systemic veins in healthy adults assessed by Doppler echocardiography. Jpn Circ J. 1991;55(6):535–42. 25. Scheinfeld MH, Bilali A, Koenigsberg M. Understanding the spectral Doppler waveform of the hepatic veins in health and disease. Radiographics. 2009;29(7):2081–98. 26. Reynolds T, Szymanski K, Langenfeld K, et al. Visualization of the hepatic veins: new approaches for the echocardiographer. J Am Soc Echocardiogr. 1991;4(2):93–6. 27. Weyman AE. Right ventricular inflow tract. In: Principles and Practice of Echocardiography. 2nd edn. Philadelphia, PA: Lea & Febiger; 1994:824–62. 28. Pinto FJ, Wranne B, St Goar FG, et al. Hepatic venous flow assessed by transesophageal echocardiography. J Am Coll Cardiol. 1991;17(7):1493–8. 29. Nomura T, Lebowitz L, Koide Y, et al. Evaluation of hepatic venous flow using transesophageal echocardiography in coronary artery bypass surgery: an index of right ventricular function. J Cardiothorac Vasc Anesth. 1995;9(1): 9–17. 30. Gårdebäck M, Settergren G, Brodin LA. Hepatic blood flow and right ventricular function during cardiac surgery assessed by transesophageal echocardiography. J Cardiothorac Vasc Anesth. 1996;10(3):318–22.

Chapter 16: Spectral Doppler of the Hepatic Veins

31. Meierhenric R, Gauss A, Georgieff M, et al. Use of multiplane transoesophageal echocardiography in visualization of the main hepatic veins and acquisition of Doppler sonography curves. Comparison with the transabdominal approach. Br J Anaesth. 2001;87(5):711–17. 32. Pennestrí F, Loperfido F, Salvatori MP, et al. Assessment of tricuspid regurgitation by pulsed Doppler ultrasonography of the hepatic veins. Am J Cardiol. 1984;54(3):363–8. 33. Kruskal JB, Newman PA, Sammons LG, et al. Optimizing Doppler and color flow US: application to hepatic sonography. Radiographics. 2004;24(3):657–75. 34. Kim MJ, Kim KW, Kim SY, et al. Technical essentials of hepatic Doppler sonography. Curr Probl Diagn Radiol. 2009;38(2):53–60. 35. Wood MM, Romine LE, Lee YK, et al. Spectral Doppler signature waveforms in ultrasonography: a review of normal and abnormal waveforms. Ultrasound Q. 2010;26(2): 83–99. 36. Blaustein AS, Risser TA, Weiss JW, et al. Mechanisms of pulsus paradoxus during resistive respiratory loading and asthma. J Am Coll Cardiol. 1986;8(3):529–36. 37. Boonyaratavej S, Oh JK, Tajik AJ, et al. Comparison of mitral inflow and superior vena cava Doppler velocities in chronic obstructive pulmonary disease and constrictive pericarditis. J Am Coll Cardiol. 1998;32(7):2043–8. 38. Tavel ME. The jugular pulse tracing: its clinical application. In: Tavel ME (Ed). Clinical Phonocardiography and External Pulse Recording. 2nd edn. Chicago: Year Book Medical Publishers; 1978:50–3. 39. de Zuttere D, Galey A, Jolly G, et al. Diagnosis of pacemaker syndrome by suprahepatic vein pulsed Doppler echocardiography. Eur J Echocardiogr. 2011;12(3):E25. 40. Shaikh AY, Meyer TE, Robotis DA, et al. Systolic pulmonary and hepatic vein flow reversal due to pacemaker-induced retrograde ventriculoatrial conduction. Echocardiography. 2013;30(3):E61–3. 41. Sakai K, Nakamura K, Satomi G, et al. Evaluation of tricuspid regurgitation by blood flow pattern in the hepatic vein using pulsed Doppler technique. Am Heart J. 1984;108(3 Pt 1):516–23. 42. Sakoda S, Mitsunami K, Kinoshita M. [Evaluation of hepatic venous flow patterns using a pulsed Doppler technique]. J Cardiol. 1990;20(1):193–208. 43. Nagueh SF, Kopelen HA, Zoghbi WA. Relation of mean right atrial pressure to echocardiographic and Doppler parameters of right atrial and right ventricular function. Circulation. 1996;93(6):1160–9. 44. Shapira Y, Porter A, Wurzel M, et al. Evaluation of tricuspid regurgitation severity: echocardiographic and clinical correlation. J Am Soc Echocardiogr. 1998;11(6):652–9. 45. Abu-Yousef MM. Duplex Doppler sonography of the hepatic vein in tricuspid regurgitation. AJR Am J Roentgenol. 1991;156(1):79–83.

323

46. Wranne B, Pinto FJ, Hammarström E, et al. Abnormal right heart filling after cardiac surgery: time course and mechanisms. Br Heart J. 1991;66(6):435–42. 47. Ranganathan N, Sivaciyan V. Abnormalities in jugular venous flow velocity in pulmonary hypertension. Am J Cardiol. 1989;63(11):719–24. 48. Matsuyama W, Ohkubo R, Michizono K, et al. Usefulness of transcutaneous Doppler jugular venous echo to predict pulmonary hypertension in COPD patients. Eur Respir J. 2001;17(6):1128–31. 49. Zhang-An, Himura Y, Kumada T, et al. The characteristics of hepatic venous flow velocity pattern in patients with pulmonary hypertension by pulsed Doppler echocardiography. Jpn Circ J. 1992;56:317–24. 50. Marangoni S, Scalvini S, Schena M, et al. Right ventricular diastolic function in chronic obstructive lung disease. Eur Respir J. 1992;5(4):438–43. 51. Klein AL, Tajik AJ. Doppler assessment of diastolic function in cardiac amyloidosis. Echocardiography. 1991;8(2): 233–51. 52. Dal-Bianco JP, Sengupta PP, Mookadam F, et al. Role of echocardiography in the diagnosis of constrictive pericarditis. J Am Soc Echocardiogr. 2009;22(1):24–33;quiz 103. 53. Oh JK, Hatle LK, Seward JB, et al. Diagnostic role of Doppler echocardiography in constrictive pericarditis. J Am Coll Cardiol. 1994;23(1):154–62. 54. Hurrell DG, Nishimura RA, Higano ST, et al. Value of dynamic respiratory changes in left and right ventricular pressures for the diagnosis of constrictive pericarditis. Circulation. 1996;93(11):2007–13. 55. Talreja DR, Nishimura RA, Oh JK, et al. Constrictive pericarditis in the modern era: novel criteria for diagnosis in the cardiac catheterization laboratory. J Am Coll Cardiol. 2008;51(3):315–19. 56. von Bibra H, Schober K, Jenni R, et al. Diagnosis of constrictive pericarditis by pulsed Doppler echocardiography of the hepatic vein. Am J Cardiol. 1989;63(7):483–8. 57. Shabetai R, Fowler NO, Guntheroth WG. The hemodynamics of cardiac tamponade and constrictive pericarditis. Am J Cardiol. 1970;26(5):480–9. 58. Appleton CP, Hatle LK, Popp RL. Cardiac tamponade and pericardial effusion: respiratory variation in transvalvular flow velocities studied by Doppler echocardiography. J Am Coll Cardiol. 1988;11(5):1020–30. 59. Burstow DJ, Oh JK, Bailey KR, et al. Cardiac tamponade: characteristic Doppler observations. Mayo Clin Proc. 1989; 64(3):312–24. 60. Ranganathan N, Sivaciyan V, Pryszlak M, et al. Changes in jugular venous flow velocity after coronary artery bypass grafting. Am J Cardiol. 1989;63(11):725–9. 61. Pinto FJ, Wranne B, St Goar FG, et al. Systemic venous flow during cardiac surgery examined by intraoperative transesophageal echocardiography. Am J Cardiol. 1992; 69(4):387–93.

324

Section 2: Echocardiography/Ultrasound Examination and Training

62. Mishra M, Swaminathan M, Malhotra R, et al. Evaluation of Right Ventricular Function During CABG: Transesophageal Echocardiographic Assessment of Hepatic Venous Flow Versus Conventional Right Ventricular Performance Indices. Echocardiography. 1998;15(1):51–8. 63. Hsia TY, Khambadkone S, Redington AN, et al. Effects of respiration and gravity on infradiaphragmatic venous flow in normal and Fontan patients. Circulation. 2000;102(Suppl 3): III148–53. 64. Bolondi L, Li Bassi S, Gaiani S, et al. Liver cirrhosis: changes of Doppler waveform of hepatic veins. Radiology. 1991;178(2):513–16. 65. von Herbay A, Frieling T, Häussinger D. Association between duplex Doppler sonographic flow pattern in right hepatic vein and various liver diseases. J Clin Ultrasound. 2001;29(1):25–30. 66. Desser TS, Sze DY, Jeffrey RB. Imaging and intervention in the hepatic veins. AJR Am J Roentgenol. 2003;180(6):1583–91.

67. Karabulut N, Kazil S, Yagci B, et al. Doppler waveform of the hepatic veins in an obese population. Eur Radiol. 2004;14(12):2268–72. 68. Grant EG, Schiller VL, Millener P, et al. Color Doppler imaging of the hepatic vasculature. AJR Am J Roentgenol. 1992;159(5):943–50. 69. Kanterman RY, Darcy MD, Middleton WD, et al. Doppler sonography findings associated with transjugular intrahepatic portosystemic shunt malfunction. AJR Am J Roentgenol. 1997;168(2):467–72. 70. Appleton CP, Jensen JL, Hatle LK, et al. Doppler evaluation of left and right ventricular diastolic function: a technical guide for obtaining optimal flow velocity recordings. J Am Soc Echocardiogr. 1997;10(3): 271–92. 71. Görg C, Riera-Knorrenschild J, Dietrich J. Pictorial review: Colour Doppler ultrasound flow patterns in the portal venous system. Br J Radiol. 2002;75(899):919–29.

CHAPTER 17 Spectral Doppler of the Pulmonary Veins Bahaa M Fadel, Bader Almahdi, Mohammad Al-Admawi, Giovanni Di Salvo

Snapshot  Historical Perspec ve  Imaging of the Pulmonary Veins  Physiological Factors that Affect Pulmonary

 Pulmonary Venous Flow in Disease States  Limita ons and Technical Pi alls  Ar facts

Venous Flow

INTRODUCTION Evaluation of pulmonary vein (PV) flow by spectral Doppler imaging is an essential component of any transthoracic echocardiography (TTE) study. Proper recording and interpretation of the PV Doppler signal provide valuable information to physicians regarding a wide variety of physiological and pathological processes.

HISTORICAL PERSPECTIVE Pulmonary vein flow has been recorded invasively since the 1970s and its pulsatile pattern was found to be related to left atrial (LA) pressure.1,2 Noninvasive recording of PV flow by pulsed wave Doppler TTE was first reported in the 1980s;3,4 however, the atrial reversal component was not initially identified.3 Transesophageal echocardiography (TEE) allowed one to obtain a high-quality signal in virtually all patients.5 Abnormal and at times characteristic PV flow profile has been noted in many disease states including conduction disturbances, rhythm disorders, diastolic left ventricular (LV) dysfunction, mitral valve (MV) stenosis and regurgitation, pericardial and myocardial diseases, PV stenosis, and congenital anomalies.6,7

IMAGING OF THE PULMONARY VEINS Anatomy of the Pulmonary Veins There are four PVs including the right and left upper and lower veins with frequent anatomical variations.8,9 The right veins run posterior to the right atrium (RA) and superior vena cava (SVC) to connect medially to the superior and posterior aspects of the LA wall near the interatrial septum. The left veins run anterior to the descending aorta and connect laterally to the same portions of the LA wall.8 The ostia of the upper veins are directed anteriorly whereas those of the lower veins are directed posteriorly.9

Physiology of Pulmonary Venous Flow The PVs are thin walled, collapsible, and highly compliant structures that allow to maintain a constant LV stroke volume despite beat-to-beat changes in right ventricular (RV) stroke volume.2 Pressure recording in the extraparenchymal PVs resembles LA pressure, and the PV flow signal is a mirror image of the pressure waveforms in the LA.2,10 The flow profile in the PVs is determined by the pressure gradient between the PV and the LA and

326

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 17.1A and B: (A) Simultaneous recording of pulmonary venous flow, pulmonary venous (PV) pressure, and left atrial (LA) pressure; (B) Schematic drawing of the pressure gradient between the pulmonary vein and left atrium that determines the velocity and morphology of individual components of the pulmonary venous flow. Source: Reproduced with permission from Appleton CP. Hemodynamic determinants of Doppler pulmonary venous flow velocity components: new insights from studies in lightly sedated normal dogs. J Am Coll Cardiol. 1997; 30:1562-74.

shows a biphasic forward flow with systolic and diastolic components.2,10 The PV-LA pressure gradient is influenced by several physiological and pathological factors that affect various components of the PV flow.7,10 Under normal conditions, four PV flow components can be identified: forward flow in early systole [pulmonary vein first systolic wave (PV-S1)], forward flow in mid–late systole [pulmonary vein second systolic wave (PV-S2)], forward flow in early–mid-diastole [pulmonary vein diastolic wave (PV-D)], and flow reversal in late diastole [pulmonary vein atrial reversal wave (PV-AR)] (Figs 17.1A and B).10–12 With the onset of systole, the PV and LA fill with blood as a result of LA relaxation and fall in pressure, which causes a “suction effect” leading to the S1 wave. Later in systole, the propagation of the RV systolic pulse pressure wave across the lungs reaches the PV, causing a “pushing effect” on blood flow. This, together with the descent of the MV plane that further increases LA compliance, leads to the S2 wave. Throughout this systolic phase, the LA functions as a reservoir. With the onset of diastole and MV opening, the LA empties and its function changes to a conduit. The LA pressure decreases more than the pressure in the PV, thus, resulting in the PV-D waveform. At end diastole, the LA functions as a pump and atrial contraction causes LA pressure to increase above PV pressure. This leads to flow reversal in the PV and results in the PV-AR waveform.3,10,13 PV-D corresponds temporally to the transmitral E wave whereas PV-AR corresponds to the transmitral A wave (Fig. 17.2). The maximal PV-LA gradient and peak D

velocity occur at the lowest LA pressure. The peak S and D velocities temporally correlate with the nadir of the x and y descents, respectively.10,14 The PV–LA pressure gradient and, thus, the velocity and contour of the various PV flow components are influenced by physiologic events that are summarized in Figure 17.3. PV-S1 is determined by left-sided events that relate to the efficiency of LA relaxation, itself dependent on LA contractility.10,13 PV-S2 is mainly determined by right-sided events, that is, the RV stroke volume, but also by LA compliance, partly determined by LV longitudinal function and increase in LA dimensions during systole.10,13 The PV-D is determined by the state of LV relaxation and compliance and its velocity is influenced by the same factors that affect early transmitral filling (E wave).15 Finally, PV-AR is influenced by LA contractility and LV stiffness.10,13 The timing of PV-S2 and PV-D are relatively fixed in the cardiac cycle because of their relation to RV systole and LV relaxation. However, PV-AR and PV-S1 are variable depending on the PR interval, cardiac rhythm, and their relation to LV systole.10 Common measurements of the PV Doppler include peak velocities of PV-S, PV-D, and PV-AR and the PV-AR duration (Fig. 17.3). The systolic fraction, a ratio of PV-S to the sum of PV-S and PV-D velocity time integrals, is rarely measured in clinical practice. It is inferred by the peak S/D velocity ratio. The PV Doppler should be interpreted in conjunction with the transmitral Doppler and should

Chapter 17: Spectral Doppler of the Pulmonary Veins

327

can at times prove difficult due to higher depths of interrogation and to anatomic variations.9,10,17 The apical four-chamber view often provides the best imaging window for Doppler interrogation of the PVs. In this view, the right upper pulmonary vein (RUPV) is visualized (Figs 17.4A and B).11 The right lower pulmonary vein (RLPV) can be imaged with a slight posterior tilt; however, it is more difficult to visualize. The left upper pulmonary vein (LUPV) can be seen in the apical four-chamber (Fig. 17.4C) and parasternal short-axis views whereas the left lower pulmonary vein (LLPV) can be visualized in the parasternal short-axis view (Fig. 17.4D).18 Of all PVs, the RUPV is the easiest and best to interrogate because of linearity of the Doppler signal with blood flow. With current equipments, an interpretable PV Doppler signal can be obtained in approximately 90% of adults.17,19 Recording of a measurable PV-AR has a lower success rate than recording of the PV-S and PV-D waveforms.17 The S1 and S2 components of the PV signal cannot be discriminated by TTE in 70%–85% of subjects.17,20,21

Transesophageal Echocardiography

Fig. 17.2: Schematic drawing of pulmonary venous flow with simultaneous hemodynamic events in the left heart. (LV: Left ventricle; LA: Left atrium; AR: Atrial reversal; MVC: Mitral valve closure; MVO: Mitral valve opening).

constitute part of an integrated assessment including other Doppler flow signals and two-dimensional (2D) imaging.

Transthoracic Echocardiography In the pediatric population, recording of PV flow is feasible in almost all subjects and a high-quality signal is often obtained.16 The suprasternal window provides visualization of all four PVs; however, this is not feasible in most adults. Pulsed wave recording of the PV in adults

TEE provides improved visualization of the PVs and allows a higher quality Doppler signal than TTE. This is due to the proximity of the transducer to the PVs (2–4 cm distance) and to near-parallel interrogation of flow.12,22 Unlike TTE, TEE allows identification of separate S1 and S2 components in 70% of individuals.12 Whereas the upper PVs are identified in almost all patients from the midesophageal window, the lower PVs can be imaged in 75% of individuals.5 The right PVs are best visualized at a 60°–80° angle in an off-axis view of the aortic valve with clockwise rotation of the transducer shaft to the patient’s right. The left PVs are visualized at 110° angle in an off-axis longitudinal view of the aortic valve with counterclockwise rotation of the shaft to the patient’s left.5

Technical Considerations Training and experience are required for optimal recording of the PV Doppler.17,23 From an apical four-chamber transducer position, color flow imaging is used to identify flow in the RUPV. To maximize frame rate, the 2D and color sectors are kept as narrow as possible. In case the RUPV ostium is difficult to visualize, slight transducer rotation toward the apical three-chamber view can be helpful. If flow is not seen well, the velocity scale can be reduced to improve visualization of the color signal. A 2–3 mm sample

328

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 17.3: Influence of different physiological and pathological parameters on the various waveforms of the pulmonary venous flow. Common measurements of PV Doppler include peak S, D, and AR velocities, AR duration, and peak S/D velocity ratio. (RV: Right ventricle; LA: Left atrium; LV: Left ventricle; LVEDP: Left ventricular end-diastolic pressure; AV: Atrioventricular; AR: Atrial reversal).

A

B

C

D

Figs 17.4A to D: Imaging of various pulmonary veins by transthoracic echocardiography. (A and B) The right upper pulmonary vein imaged in the apical four-chamber view with still frames in systole (arrow) and early diastole (arrow). Flow is more turbulent in diastole indicating a higher PV-D than PV-S, a normal finding in this young patient; (C) The left upper pulmonary vein imaged in the apical fourchamber view (arrow); (D) The left lower pulmonary vein imaged in the parasternal short-axis view just below the level of the aortic valve (arrow).

Chapter 17: Spectral Doppler of the Pulmonary Veins

329

Table 17.1: Requirements for Optimal Recording and Interpretation of the Pulmonary Venous Doppler

Transducer location in apical four-chamber view Optimize two-dimensional (2D) image quality Identify the right upper pulmonary vein orifice and visualize flow within the vein using color Doppler Ensure alignment of Doppler signal with flow Ensure optimal pulse wave Doppler settings: Sample volume size: 2–3 mm Sample volume location: 1–2 cm inside the vein Gain settings Relatively low filter settings Recording speed of 25–50 mm/s to assess waveform morphology and respiratory variability Recording speed of 100 mm/s to measure PV-AR duration Obtain transmitral Doppler at same recording speeds for comparison Good echocardiogram tracing showing P wave and QRS complex Know the underlying rhythm Know the PR interval Be aware of pitfalls: mistaking superior vena cava or descending aortic signal for a pulmonary venous signal Be aware of artifacts Know the age of the patient Interpretation should take into account additional findings on 2D, color, spectral, and tissue Doppler imaging

volume is then placed 1–2 cm into the PV. The velocity filter should initially be set at low level and adjustments made depending on the quality of the spectral display. Interrogation of the LUPV can be attempted in case a satisfactory recording from the RUPV cannot be obtained; however, flow is often not linear with the Doppler signal. Additional imaging windows including the parasternal short axis, suprasternal notch, and subcostal window can be attempted. Data should be derived from recording of several cycles due to the respiratory variability in waveform pattern. Few patients demonstrate excessive cardiac motion with respiration that displaces the sample volume outside the PV and recording may have to be obtained during apnea. The requirements for optimal recording and interpretation of the PV Doppler are summarized in Table 17.1.

PHYSIOLOGICAL FACTORS THAT AFFECT PULMONARY VENOUS FLOW Respiration The PV flow profile changes minimally during quiet respiration in normal individuals. Peak velocities and time velocity integrals slightly decrease with inspiration and increase with expiration.11 Respiration affects

PV-AR duration as well, which increases during expiration. PV-AR can vary by as much as 50 milliseconds during the respiratory cycle. This may have significant implications if unaccounted for when assessing left ventricular end-diastolic pressure (LVEDP) (see below).10,15,24 Obese patients and those with chronic lung disease or respiratory distress can show significant respiratory variability in flow.25

Age The PV flow varies with the state of LV myocardial relaxation, a parameter that is affected by age.21,26 Normal adolescents and young adults have rapid LV relaxation with excellent elastic recoil and suction properties. This results in rapid LV filling in early diastole with only minor contribution to filling during atrial contraction. The transmitral Doppler shows a prominent E wave with a relatively short deceleration time (DT), a short isovolumic relaxation time (IVRT), and a small A wave. The PV Doppler shows diastolic predominance to filling with S/D ratio < 1 and a small PV-AR that ends simultaneously with or earlier than the transmitral A wave (Fig. 17.5).20 With aging, LV relaxation slows with gradual loss of elastic recoil. This results in progressive delay in MV opening, decrease in LV filling in early diastole, and

330

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 17.5: Normal pulmonary venous Doppler in a 24-year-old female with no structural heart disease. The transmitral (MV) Doppler shows a high E/A ratio with an E wave deceleration time of 170 milliseconds, A wave duration of 110 milliseconds, and isovolumic relaxation time of 72 milliseconds. The pulmonary venous (PV) Doppler shows a higher diastolic (D) than systolic (S) velocity with a small atrial reversal (AR) that has similar duration to the MV A wave.

Fig. 17.6: Normal pulmonary venous Doppler in a 55-year-old female with no structural heart disease. The transmitral (MV) Doppler shows similar peak E and A velocities with an E wave deceleration time of 200 milliseconds, A wave duration of 140 milliseconds, and isovolumic relaxation time of 85 milliseconds. The pulmonary venous (PV) Doppler shows a slightly higher systolic (S) than diastolic (D) velocity with a small atrial reversal (AR) that is slightly shorter in duration (130 milliseconds) than the MV A wave.

Fig. 17.7: Normal pulmonary venous Doppler in a 75-year-old male with no structural heart disease. The transmitral (MV) Doppler shows evidence of impaired left ventricular relaxation with an E/A ratio < 1 and prolonged E wave deceleration time (240 milliseconds), A wave duration (150 milliseconds), and isovolumic relaxation time (110 milliseconds). Pulmonary venous (PV) Doppler shows a higher S/D ratio, prolonged PV-D deceleration time (arrow) at 280 milliseconds, and atrial reversal (AR) duration of 140 milliseconds. Note the systolic flow reversal (arrowhead) that represents an artifact originating from the adjacent descending thoracic aorta.

increase in filling at atrial contraction.20,27 Normal middleaged individuals in their fifties show near equalization of the transmitral E and A wave velocities with equal or slightly more prominent PV-S than PV-D (Fig. 17.6). In patients > 65–70 years of age, MV Doppler shows a smaller E than A wave with prolonged E wave DT and IVRT. The PV Doppler

shows progressive increase in PV-S wave with decrease in PV-D (S >> D) and increase in PV-AR (Fig. 17.7).

Loading Conditions A reduction in preload leads to a decrease in PV-AR duration and velocity and decrease in PV-D velocity. The

Chapter 17: Spectral Doppler of the Pulmonary Veins

331

Fig. 17.8: Short PR interval of 120 milliseconds in a 32-year-old female with no structural heart disease. The transmitral (MV) Doppler shows a shortened A wave duration of 90 milliseconds. The pulmonary venous (PV) Doppler shows a large A wave reversal (AR) with high velocity (50 cm/s) and a duration of 130 milliseconds that ends 40 milliseconds later than the transmitral A wave. This finding is caused by the short PR interval, not by elevation in left ventricular end-diastolic pressure.

Fig. 17.9: Prolonged PR interval of 250 milliseconds in a 45-yearold male. The pulmonary venous (PV) Doppler shows an atrial reversal (AR) wave that occurs toward the end of the diastolic (D) wave. The atrial relaxation (S1) wave that follows begins and peaks before systole and the S1–S2 peaks are widely separated. There is a “double diastolic peak” pattern (arrows) to the PV signal.

latter reflects the reduction in the MV-E waveform and prolongation of DT.15 An increase in preload by volume loading causes an increase in peak PV-S and PV-AR velocity and duration.10,15

Prolonged PR Interval

PULMONARY VENOUS FLOW IN DISEASE STATES Conduction Disorders Short PR Interval A PR interval ≤ 120–130 milliseconds affects the PV Doppler. The shorter the PR interval, the more likely one would identify changes. Due to a short atrioventricular (AV) delay, the abrupt rise in LV pressure during systole causes premature termination of transmitral flow. This results in cutoff and shortening of the transmitral A wave. Since LA pressure has not decreased at the time of MV closure, backflow into the PV persists resulting in a prominent PV-AR duration and amplitude (Fig. 17.8).20 A short PR interval mimics elevation of the LVEDP (see below); however, PV-AR has often a longer duration in the latter. Thus, before a diagnosis of elevated LVEDP is made, one must ensure that the PR interval is not shortened. Patients with intra-atrial conduction delay show similar findings to those with short PR interval.20

An abnormally long PR interval (first degree AV block) produces an effect similar to tachycardia (see below). Atrial contraction occurs before the rapid filling phase has ended, thus, shortening the diastolic filling period. This causes some attenuation of the PV-D velocity and reduction or absence of a PV-AR waveform. The atrial relaxation wave (PV-S1) that follows often begins before the QRS complex and gives a “double diastolic peak” pattern to the PV signal. The systolic waveform becomes clearly biphasic with wide separation between the peaks of S1 and S2 (Fig. 17.9).28 The transmitral Doppler shows superimposed E and A waves.

Atrioventricular Dissociation Normally atrial contraction occurs after the rapid filling phase has ended and sufficiently before ventricular systole has begun. This ensures optimal diastolic LV filling and avoidance of premature termination of transmitral flow. In patients with AV dissociation, the loss of AV synchrony leads to beat-to-beat variability in PV flow with the pattern being dependent on the temporal relationship between the P wave (atrial systole) and the QRS complex (ventricular systole). Thus, PV-AR and PV-S1 follow atrial contraction and relaxation irrespective of the phase of the

332

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 17.10: Atrioventricular dissociation. The pulmonary venous Doppler shows intermittent “cannon A waves” that result from atrial contraction occurring during ventricular systole. When atrial contraction occurs in early diastole, the resulting waveform becomes superimposed on the diastolic velocity (D), resulting in a poorly defined reversal wave (arrow).

Fig. 17.11: Premature ventricular beat. The pulmonary venous Doppler demonstrates a large reversal (cannon A wave) (arrow) when atrial contraction occurs during ventricular systole induced by a premature beat.

Premature ventricular contractions may lead to large reversals if simultaneous atrial contraction or VA conduction occurs (Fig. 17.11).

Rate and Rhythm Disorders Rate and rhythm disorders are commonly encountered in clinical practice and influence PV flow pattern. Recognition of the changes on PV Doppler is essential to avoid misinterpretation and incorrect diagnosis.

Sinus Tachycardia and Bradycardia Fig. 17.12: Sinus tachycardia in a 29-year-old female with no structural heart disease. At a heart rate of 115 beats/min, atrial contraction occurs before the rapid filling phase (D) has ended and is totally obliterated.

cardiac cycle.10 When atrial contraction occurs early in diastole, PV-AR becomes superimposed on PV-D resulting in reduction in peak PV-D velocity and no clear PV-AR wave. When atrial contraction occurs during ventricular systole and against a closed MV, the rise in LA pressure results in large “cannon wave” reversals (Fig. 17.10).3,4,29,30 AV dissociation is most often encountered in patients with complete heart block or asynchronous ventricular pacing (see below).

A rapid heart rate affects primarily PV-AR and PV-S1.10 Due to shortened diastolic filling period, atrial contraction occurs before the rapid filling phase has ended. Depending on the timing of atrial contraction and the PV-D velocity at which it occurs, PV-AR is either significantly reduced or totally obliterated (Fig. 17.12). Occasionally, when no reversal is noted, the atrial contraction wave may cause indentation of the descending portion of the PV-D waveform. PV-S1 may also increase due to lack of flow reversal during PV-AR.10 At slow heart rate, diastasis is noted between PV-D and PV-AR due to equilibration of PV and LA pressures. The PV-AR is often quite visible (Fig. 17.13).

Chapter 17: Spectral Doppler of the Pulmonary Veins

Fig. 17.13: Sinus bradycardia in a 17-year-old male with no structural heart disease. At a heart rate of 52 beats/min, there is a period of diastasis (arrow) between the rapid filling phase (D) and atrial contraction (AR). The S1 and S2 waves are well visualized. The predominance of the diastolic (D) velocity is normal at this age.

333

Fig. 17.14: Atrial fibrillation. The pulmonary venous Doppler shows a dominant diastolic (D) waveform with a small S2, no atrial contraction (AR) or relaxation (S1) waveforms. Instead of the retrograde AR, antegrade flow is noted in late diastole (arrow), likely due to impaired left ventricular relaxation.

With LA filling occurring predominantly during diastole, the PV Doppler shows an S < D pattern (Fig. 17.14).33 This mimics the pattern seen in older patients in sinus rhythm with elevated LA pressure. A misdiagnosis of elevated filling pressures can thus be made if atrial fibrillation is not recognized. In patients with atrial fibrillation and LV systolic dysfunction, the S2 velocity is further reduced or absent. Following conversion to sinus rhythm, the resulting atrial stunning is associated with low velocity of all waveforms, particularly PV-AR and PV-S1. At 10 days postcardioversion, a significant increase in all velocities is usually noted.34

Fig. 17.15: Atrial flutter. The transmitral (MV) Doppler shows the changes in flow velocity (arrows) induced by the rapid sequence of atrial contraction and relaxation. The pulmonary venous (PV) Doppler shows indentations on the contour of the diastolic (D) velocity (arrows).

Atrial Fibrillation The PV-AR and PV-S1 waveforms are generated by LA contraction and relaxation, respectively. Atrial fibrillation leads to the loss of effective atrial contraction and relaxation and both waveforms are often absent (Fig. 17.14).4 Thus, the PV systolic component results from the sole contribution of S2. Since S2 normally arises before S1 has returned to baseline velocity, peak S2 decreases due to lower velocity at which it starts.10,15,31 Early systolic flow reversal can also be observed.32,33

Atrial Flutter Atrial flutter can lead to various flow patterns on the PV Doppler. The most characteristic is an abrupt change in the contour of the waveforms particularly PV-D, which reflects changes in pressure due to the rapid sequence of atrial contraction and relaxation. Similar findings are often noted on the transmitral Doppler (Fig. 17.15).

Junctional Rhythm In patients with junctional rhythm and retrograde conduction, atrial contraction occurs during ventricular systole resulting in significant pressure increase in the LA. Large flow reversals (cannon waves) are noted in the PV with every beat during systole (Fig. 17.16).

334

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 17.16: Junctional rhythm. Due to retrograde conduction to the atria, the pulmonary venous (PV) Doppler shows large systolic reversals (SRs) resulting from atrial contraction against a closed mitral valve.

Paced Rhythm Patients with dual chamber pacing and normal AV delay show no significant abnormalities on the PV Doppler. An abnormally prolonged or shortened AV delay results in similar findings to a long and short PR interval, respectively. Asynchronous pacing occurs when sinus rhythm is associated with venticular (VVI mode) pacing. PV Doppler shows similar findings to AV dissociation (Fig. 17.10).29,30 Patients with VVI pacing and VA conduction have similar findings to the junctional rhythm (Fig. 17.16).

Assessment of Left-Sided Filling Pressures Assessment of Left Ventricular End-Diastolic Pressure Comparison of flow characteristics at atrial contraction across the MV and in the PV provides insight into the LVEDP.24 Following LA contraction in normal individuals, the volume of blood flow is larger forward (toward the LV) than backward (toward the PV). With a simultaneous onset of flow across the MV and PV, the transmitral A wave and PV-AR begin concurrently and the duration of flow is either similar or slightly longer across the MV. Thus, individuals with a compliant LV and normal LVEDP have a PV-AR duration that is similar to or shorter than the transmitral A wave.20

Fig. 17.17: Relationship between left atrial and left ventricular end-diastolic pressures, transmitral and pulmonary venous Doppler. (A) Normal left ventricular end-diastolic pressure (LVEDP). The transmitral (MV) and pulmonary venous (PV) Doppler show similar A wave duration due to timely closure of the MV; (B) Elevated LVEDP. Left atrial (LA) contraction leads to rapid rise in LVEDP that exceeds LA pressure and results in early MV closure. This causes reduction in LA stroke volume and shortening of the transmitral A wave duration. Since LA pressure remains elevated at MV closure, blood backflows into the PV for a longer duration than across the MV resulting in a longer atrial reversal (AR) wave duration; (C) Severely elevated LVEDP. The transmitral A wave is even shorter due to faster rise in LV diastolic pressure and earlier MV closure. At this stage, mean LA pressure is often elevated.

Disorders that lead to abnormalities in LV diastolic properties and compliance initially cause an increase in LVEDP. The latter is an earlier marker of abnormal hemodynamics than the increase in mean LA pressure.20 Atrial contraction results in a pressure rise within the LV in end diastole that exceeds LA pressure before the latter has begun to decline. This causes an abrupt closure of the MV and shortening of the transmitral A wave duration. Since LA pressure has not decreased yet, however, blood flow can no longer proceed forward across the MV; it backflows into the low-resistance PV circuit and for a longer duration than across the MV (Fig. 17.17).24,35 The most reliable sign of elevated LVEDP (>18 mm Hg) is a wide difference in duration between PV-AR and transmitral A wave. A PV-AR duration exceeding by >30 milliseconds the transmitral A wave duration indicates an elevated LVEDP with a good sensitivity (82%) and high specificity (92%) (Fig. 17.18).19,36,37 This parameter is useful in patients with preserved and impaired LV systolic function.

Chapter 17: Spectral Doppler of the Pulmonary Veins

335

Fig. 17.18: Left ventricular end-diastolic pressure (LVEDP) versus the difference in A wave duration between pulmonary venous and mitral flow. The horizontal line at 15 mm Hg indicates an arbitrary upper limit of normal for the LVEDP. Source: Modified from Rossvoll O, Hatle LK. Pulmonary venous flow velocities recorded by transthoracic Doppler ultrasound: relation to left ventricular diastolic pressures. J Am Coll Cardiol. 1993;21:1687–96.

Fig. 17.19: Elevated left atrial (LA) and left ventricular end-diastolic pressure in a 50-year-old male with aortic stenosis and left ventricular hypertrophy. The transmitral (MV) Doppler shows a restrictive filling pattern with elevated E/A ratio, shortened deceleration time (90 milliseconds) and shortened A wave duration (110 milliseconds) suggestive of elevated mean LA pressure. The pulmonary venous (PV) Doppler demonstrates an atrial reversal (AR) wave with longer duration (170 milliseconds) than the MV A wave. The dashed lines show the end of the MV A wave that occurs well before the end of the PV-AR wave.

A precise timing for the onset of PV-AR may prove difficult to determine by TTE and an accurate measurement of PV-AR duration can be challenging. Since one is mostly interested in timing the end of flow, a simpler approach is to compare the ends of the transmitral A wave and PVAR using the electrocardiogram (ECG) as a reference. APV-AR that ends > 30 milliseconds after the transmitral A wave identifies patients with high LVEDP (Fig. 17.19).20 To increase specificity and account for the changes in PV-AR duration with respiration, this finding should be present on consecutive beats.10 A less-powerful indicator of elevated LVEDP is an increased PV-AR velocity (> 35 cm/s). However, since LA mechanical dysfunction may accompany LV systolic and diastolic dysfunction, PV-AR velocity can be normal despite an elevated LVEDP. The difference in duration between PV-AR and transmitral A wave cannot be used during atrial fibrillation due to loss of atrial contraction.

Doppler, likely due to less influence by heart rate and blood pressure.14 As mean LA pressure rises above normal, the PV systolic fraction decreases with decrease in S velocity and increase in D velocity.20 In older patients or those with heart disease, a S/D ratio < 1 suggests a larger v than a wave and elevation in mean LA pressure. Two abnormal diastolic filling patterns can be identified: impaired relaxation and restrictive physiology.

Assessment of Mean Left Atrial Pressure Used in combination with other parameters, PV Doppler significantly aids in the assessment of left atrial pressure. Doppler variables in the PV have a stronger correlation with mean LA pressure than those in the transmitral

Impaired Myocardial Relaxation Pattern Abnormal LV relaxation is often the first manifestation of myocardial involvement in many disease states. Due to slow myocardial relaxation, the fall in LV pressure during the isovolumic relaxation phase is slow, leading to a delay in LA-LV pressure crossover and MV opening. This results in prolongation of the IVRT, decrease in transmitral peak E velocity, prolongation of the DT and increase in LA stroke volume. Since changes in PV-D mirror those in MV-E, this leads to a decrease in PV-D velocity with compensatory increase in PV-S and normal PV-AR duration. Whereas the transmitral E/A ratio decreases, the PV S/D ratio increases.20 At this stage, LVEDP and mean LA pressure remain normal. With further progression of disease, LVEDP increases while an impaired relaxation pattern

336

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 17.20: Elevated left atrial (LA) pressure and left ventricular end-diastolic pressure (LVEDP) by transesophageal echocardiography in a 71-year-old male with normal left ventricular systolic function. Transmitral (MV) Doppler shows a shortened A wave duration (80 milliseconds). Pulmonary venous (PV) Doppler demonstrates an atrial reversal (AR) with significantly longer duration (160 milliseconds) suggestive of elevated LVEDP. Additionally, the S/D ratio is < 1 with shortened deceleration time (DT) of the PV-D (160 milliseconds), high E/A ratio, and shortened MV-E DT (160 milliseconds) suggestive of elevated mean LA pressure.

persists. This is manifested by an increase in PV-AR duration with opposite changes in the transmitral A wave (see Assessment of LVEDP).

a rapid rise in LV pressure (Fig. 17.20). The PV-AR can be prolonged due to elevation in LVEDP. In tachycardic patients, the PV-AR is superimposed on the diastolic velocity and may not be visualized. Stretching of the LA may also lead to atrial mechanical failure and PV-AR can be small or absent despite significantly elevated LVEDP (Figs 17.21A and B). The S/D ratio exhibits a nonlinear and inverse relation to LA pressure. However, the S2 velocity is also affected by LV contractility and stroke volume. In patients with reduced left ventricular ejection fraction (LVEF) and/ or low cardiac output, an S/D < 1 is a marker of elevated filling pressures.39 In those with normal LVEF, the S/D ratio is not a sensitive marker of elevated filling pressures due to a preserved systolic mitral annular motion that opposes blunting of S2.40 Thus, an S/D ratio > 1 does not exclude elevated filling pressures in individuals with preserved LVEF. As LA pressure increases, the deceleration of PV-D becomes shorter, similar to the transmitral E wave.41 In patients with diseased hearts, a PV-D DT < 175 milliseconds correlates with elevation in LA pressure during sinus rhythm and atrial fibrillation (Figs 17.21 and 17.22).42 A good PV Doppler signal is required to measure the DT by TTE.

Mitral Valve Disease

Pseudonormal Filling Pattern

Mitral Regurgitation

This is a transitional stage where abnormal relaxation coexists with modest elevation in LA pressure.38 The transmitral inflow resembles a normal filling pattern. The PV Doppler often shows evidence of elevated LVEDP with progressive increase in peak PV-D and decrease in PV-S. The S/D ratio varies depending on several parameters.

The main abnormality in hemodynamically significant mitral regurgitation (MR) is the development of a prominent v wave in the LA. Since this is a mid–late systolic event, the S2 component of the PV Doppler is initially and mostly affected. As the MR volume increases, pressure recordings demonstrate a gradual increase in the amplitude of the v wave and v–y descent with a gradual decrease in the a wave and a–x descent. This translates into a decrease and, ultimately, reversal of the S wave with increase in D wave velocity (Figs 17.23A to D).43–46 In patients with mild MR, no significant changes in PV Doppler are expected. With increasing degrees of MR, there is progressive decrease in PV-S2 and increase in PV-D velocity. Hemodynamically significant MR often results in a blunted PV-S2 (S < D) or, more characteristically, reversal of PV-S2 with S1 being either forward or absent (Fig. 17.24). Pansystolic flow reversal may also develop with inversion of S1 and S2 and further increase in PV-D (Fig. 17.25).44,45 A simplified scheme for grading MR would

Restrictive Filling Pattern This marks the most advanced stage of diastolic dysfunction. The main hemodynamic alterations are a reduction in LV compliance and marked elevation in LA pressure. Abnormal relaxation coexists; however, it is masked by the elevation in filling pressures. Transmitral Doppler shows a short IVRT, high E velocity, shortened DT, and markedly reduced A wave velocity and duration. The PV Doppler reveals a small PV-S due to elevated LA pressure and reduced LA compliance. The PV-D is large, reflecting the transmitral E wave, with short DT due to

Chapter 17: Spectral Doppler of the Pulmonary Veins

A

337

B

Figs 17.21A and B: Elevated left atrial pressure with loss of atrial mechanical function in a 69-year-old male with ischemic cardiomyopathy and severely reduced left ventricular systolic function. (A) Baseline pulmonary venous Doppler shows a large atrial reversal (duration 180 milliseconds) suggestive of elevated left ventricular end-diastolic pressure (LVEDP). The S1 wave is preserved reflecting good atrial relaxation. The S2 wave is markedly reduced with dominant diastolic (D) wave that has a shortened deceleration time (DT = 180 milliseconds) suggestive of elevated left atrial pressure; (B) Six months later, the patient presented with decompensated heart failure. The D wave amplitude has increased with further shortening of the DT (100 milliseconds) indicating an increase in left-sided filling pressures. However, the AR wave has decreased in duration (110 milliseconds) and amplitude. This finding does not reflect a decrease in LVEDP but a decrease in atrial mechanical function despite a normal sinus rhythm. The S1 velocity has also markedly decreased, reflecting poor atrial relaxation as a result of reduced atrial contraction.

Fig. 17.22: Atrial fibrillation with elevated left ventricular filling pressures in a 50-year-old male with dilated cardiomyopathy and severely reduced left ventricular systolic function. Note the absence of atrial contraction (AR) and relaxation (S1) waves. The S2 wave is markedly reduced with dominant diastolic (D) flow that shows very shortened deceleration time (130 milliseconds) suggestive of elevated filling pressures. Antegrade flow in mid-diastole (arrows) likely indicates underlying impaired left ventricular relaxation.

suggest a normal PV flow pattern in mild MR, blunting of PV-S2 in moderate MR, and PV-S reversal in severe MR. However, several factors influence the amplitude of PV-S to render this qualitative grading of MR inaccurate.7 Even

Fig. 17.23: Relationship between left atrial pressure and pulmonary venous (PV) Doppler in mitral regurgitation (MR). With increasing severity of MR, the v wave and y descent increase and the a wave and x descent decrease in amplitude. This results in progressive decrease of the S wave and increase in the D wave on the PV Doppler. Note that severe MR can be associated with modest (B) or severe blunting (C) of the S wave, mid-late systolic (C), or holosystolic flow reversal (D). In the setting of MR, blunting of the S wave (B) does not necessarily imply moderate or severe MR. Source: Modified from Klein AL, Stewart WJ, Bartlett J, et al. Effects of mitral regurgitation on pulmonary venous flow and left atrial pressure: an intraoperative transesophageal echocardiographic study. J Am Coll Cardiol. 1992;20:1345–52.

338

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 17.24: Severe mitral regurgitation in a patient with atrial fibrillation. Pulmonary venous Doppler shows late systolic flow reversal (arrow).

Fig. 17.25: Severe mitral regurgitation in a patient with atrial fibrillation and underlying paced ventricular rhythm. Pulmonary venous Doppler shows holosystolic flow reversal (arrow).

though changes in PV-S and PV-D velocities correlate with the height of the v wave, a large v wave is neither sensitive nor specific for severe MR.47,48 A number of technical and physiological parameters influence the PV flow pattern in severe MR. These include LA compliance, LA pressure, LV systolic function, direction of the MR jet, coexistence of mitral stenosis (MS), AV conduction abnormalities, and rhythm disturbances, particularly atrial fibrillation. Despite significant MR, a compliant LA may not demonstrate a prominent v wave, and the PV Doppler will not show significant blunting or reversal of PV-S or a large PV-D.47 Conversely, in patients with a poorly compliant LA and elevated LA pressure and/or atrial fibrillation, blunting of the systolic velocity occurs with a lesser degree of MR.7,49 Severe MR is often accompanied by a blunted PV-AR waveform. An increase in PV-AR duration or amplitude indicates an elevated LVEDP and implies the presence of LV systolic dysfunction. The flow pattern may vary between different PVs depending on the direction and eccentricity of the MR jet, among other factors.50,51 Discordant flow between the LUPV and RUPV can be observed in approximately one quarter of patients with MR and in one third of patients with severe MR. The RUPV shows more common systolic reversals than the LUPV.52 Wall impinging and highly eccentric jets may selectively direct flow into one of the PVs. Thus, Doppler interrogation of more than one PV is essential. Furthermore, eccentric and wall-impinging MR jets may lead to differences in flow patterns within the same PV. Flow reversal can be noted on the side of the vein where the eccentric MR jet enters with the opposite side showing forward flow (Figs 17.26A to C).

The PV Doppler should not be used as the sole parameter for grading MR. Nevertheless, a completely normal flow pattern is unlikely in patients with severe MR whereas the presence of PV-S2 or pansystolic reversals in more than one PV is highly suggestive of the diagnosis.7 At least one-third of patients with severe MR do not show systolic reversal in the PVs, and thus, its absence should not exclude the diagnosis.50 In patients with MR and blunting of S2, several parameters can be responsible for the systolic wave attenuation and caution must be exercised not to use this as a marker of the degree of MR.

Mitral Stenosis Findings on PV Doppler depend on the severity of MS, the underlying rhythm, and associated abnormalities.53,54 Often, the PV Doppler demonstrates characteristic findings in hemodynamically significant MS. All PV waveforms including S, D, and AR are usually attenuated.55 A characteristic finding is the prolongation of the PV-D pressure halftime that reflects the slow pressure decay across the MV (Fig. 17.27).53–55 This correlates with the pressure halftime of the transmitral E wave and inversely with MV area.53 Some patients with severe MS and sinus rhythm demonstrate a lower S than D velocity. This is even more exaggerated in patients with MS and atrial fibrillation.55 With progression of MS, the contribution of atrial contraction to LV filling gradually decreases.56 An inverse relationship exists between the severity of MS, mean LA pressure, and PV-AR.57 In severe MS and high LA pressure, AR becomes significantly reduced in amplitude and duration.

Chapter 17: Spectral Doppler of the Pulmonary Veins

A

C

339

B

Figs 17.26A to C: Severe mitral regurgitation with an eccentric jet. Transesophageal echocardiogram with color Doppler (still frames) of the left upper pulmonary vein during systole. One side of the vein (1) shows flow reversal whereas the other side (2) shows forward flow. Spectral Doppler at point 1 shows mid–late systolic flow reversal (arrow) following S1 (B). At point 2, the S2 waveform is antegrade (C).

Following successful balloon valvuloplasty, all flow velocities increase as a result of improved LA emptying with PV-S increasing proportionately more than PV-D and PV-AR.58 Following MV replacement, the peak D velocity increases whereas the S velocity does not change significantly.55

Myocardial and Pericardial Diseases Restrictive Cardiomyopathy

Fig. 17.27: Severe mitral stenosis with valve area of 1.0 cm2. The transmitral (MV) Doppler shows peak and mean gradients of 21 and 13 mm Hg, respectively, at a heart rate of 64 beats/min and prolonged pressure halftime at 216 milliseconds. The pulmonary venous (PV) Doppler shows reduction in the velocities of all waveforms including the systolic (S), diastolic (D), and atrial reversal (AR) waves. Characteristically, the pressure halftime of the diastolic velocity is markedly prolonged at 226 milliseconds.

The most common disorders are infiltrative diseases, particularly cardiac amyloidosis and the idiopathic form. The main hemodynamic abnormality is an increase in LV chamber stiffness. This leads to a restrictive LV filling with elevation in LA pressure. The PV Doppler is characterized by the following: (a) severe blunting of systolic flow; (b) significant increase in peak PV-D with rapid DT and minimal respiratory variability; (c) increased PV-AR duration due to elevated LVEDP.59,60 However, the latter is reduced in the setting of atrial mechanical failure (Fig. 17.28).

340

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 17.29: Constrictive pericarditis. Pulmonary venous Doppler with respiratory monitoring. Marked respiratory variation in flow is noted with significant decrease in peak S and particularly D velocities from expiration to inspiration. (Exp: Expiration; Insp: Inspiration).

Fig. 17.28: Restrictive cardiomyopathy in a 69-year-old male due to cardiac amyloidosis with marked increase in left ventricular wall thickness. The transmitral (MV) Doppler shows a restrictive pattern characterized by high peak E wave velocity, large E/A ratio, and a rapid deceleration time (150 milliseconds), all suggestive of significant elevation in left-sided filling pressures. On pulmonary venous (PV) Doppler, the S2 velocity has disappeared and a dominant D velocity is present with rapid deceleration time (140 milliseconds).

Constrictive Pericarditis Characteristic hemodynamic disturbances occur in patients with constrictive pericarditis.61 These include: (a) dissociation between the intrathoracic (pulmonary capillary and PV) and intracavitary (LA and LV) pressures; (b) exaggerated ventricular interdependence. Abnormalities noted in PV flow relate to the dynamic changes that occur with respiration.62–64 Inspiration results in a significant decrease in PV-D velocity and TVI and, to a lesser extent, a decrease in PV-S. During expiration, opposite changes occur. The respiratory changes are most markedly on the first inspiratory and expiratory beats (Fig. 17.29). The inspiratory decrease and expiratory increase in PV-D velocity parallel the same changes noted in the transmitral E wave; however, the percentage change is often more pronounced in the PV.60 Normal individuals show respiratory variability in MV-E velocity by an average

of 4% (often < 15%) and in PV-D velocity by an average of 7%.26,62 In constrictive pericarditis, peak MV-E velocity often decreases by >15%–25% and PV-D velocity by >40% with inspiration (Fig. 17.29). In one study, the combination of a PV S/D ratio >0.65 during inspiration and respiratory variation in PV-D velocity by >40% classified 86% of patients with constrictive pericarditis.60

Special Scenarios Lack of respiratory variability in constrictive pericarditis: Up to 12% of patients with constrictive pericarditis do not show significant respiratory variability in MV flow.65 Some of these patients continue to show variability in PV flow. Possible causes for this phenomenon include: (a) very shallow breathing: here respiratory variability can be unmasked by having the patient take deeper breaths during Doppler recording; (b) markedly elevated LA pressure: in this situation, the MV opens at a steep portion of the pressure–volume curve. The normal decline in intrathoracic pressure by 5–7 mm Hg during inspiration may not cause significant decrease in LA pressure.66 Therefore, no significant respiratory variability in MV-E and PV-D velocities are detected. Preload reduction and lowering LA pressure by sitting or standing, head-up tilt, or diuresis may unmask the respiratory changes in flow;67 and (c) combined constrictive-restrictive process (see below). Abnormal respiratory variability in the absence of constrictive pericarditis: Many individuals with significant respiratory variability in MV and PV flow velocities do not

Chapter 17: Spectral Doppler of the Pulmonary Veins

341

constriction. Additionally, comparison of similar R–R cycle lengths may show significant variation in peak PV-D velocity that has to be attributed to the effect of respiration (Fig. 17.30).

Fig. 17.30: Constrictive pericarditis with atrial fibrillation. At similar R–R cycle length, the first expiratory beat (arrow) of the pulmonary venous Doppler shows significant increase in peak diastolic velocity as compared to the inspiratory beat (arrowhead). With a similar duration of diastole, the difference in flow velocity is due to the effect of respiration. (Exp: expiration; Insp: inspiration).

have constrictive pericarditis. This may occur in acute cardiac dilatation (pulmonary embolism or RV infarction) or more commonly in patients with increased respiratory effort, such as chronic obstructive lung disease and obesity. In the last two entities, SVC Doppler shows a significant increase in peak systolic velocity by >20 cm/s with inspiration whereas no significant respiratory changes are noted in constrictive pericarditis.68 Additionally, changes in flow velocity are more gradual occurring later in the respiratory cycle rather than on the first inspiratory or expiratory beat.69 Atrial fibrillation: This is noted in up to 25% of patients with constrictive pericarditis and poses a challenge to the interpretation of the PV Doppler.65 Here MV and PV flow velocities are influenced not only by respiration, but also by the R–R cycle length. The respiratory changes noted across the PV are more pronounced (average change 35%) than those across the MV in atrial fibrillation (average change 15%).65 Constrictive pericarditis should be suspected if a paradoxical decrease (rather than increase) in peak PV-D velocity occurs following a long cycle length at the onset of inspiration.65 Likewise, paradoxical increase in peak PV-D velocity that occurs following a short cycle length at the onset of expiration is also suggestive.65 Patients with atrial fibrillation and normal pericardium usually show respiratory variability in peak PV-D velocity by 1.6 m/s indicates a functionally significant obstruction. When severe

The presence of a large atrial septal defect (ASD) with leftto-right shunt results in uncoupling between PV flow and left heart filling. This is due to the shunting of blood into the more compliant right heart. Thus, the effect of left heart dynamics on PV flow is diminished. PV Doppler usually demonstrates the loss of distinct systolic and diastolic waveforms. Instead, a single continuous wave is noted from onset of systole to the onset of atrial contraction (Fig. 17.32). Additionally, the PV-AR is reduced. These abnormalities return to normal immediately following ASD closure.78

LIMITATIONS AND TECHNICAL PITFALLS The major challenge to the use of PV Doppler is the difficulty in obtaining a signal that is adequate for interpretation. The PV-AR waveform is often more difficult to record than the forward PV-S and PV-D waves due to its lower velocity and timing.17,19 The position of the sample

Chapter 17: Spectral Doppler of the Pulmonary Veins

volume where an optimal PV-AR signal is obtained could be different from where PV-S and PV-D velocities are best recorded.17 Several conditions including obesity, chronic lung disease, shadowing from mitral calcifications, reverberations from prosthetic valves, and mechanical ventilation increase the difficulty in obtaining an optimal PV Doppler signal. In patients with severely dilated LA and/ or LV, a signal can be difficult to record due to the far-field sector, and the PVs may no longer be well visualized by TTE due to the distorted anatomy. Off-axis views and the use of a higher intercostal window may help alleviate this problem. Common pitfalls in recording a PV signal include improper sample volume size, sample volume location, and filter setting of the pulsed wave Doppler.23 A sample volume of 2–3 mm provides the best quality spectral display. A smaller sample volume (1 mm) results in a weak Doppler signal and excessive wall motion artifacts. A large sample volume (≥5 mm) leads to a dense spectral display and indistinct waveforms that are difficult to resolve.23 If the signal intensity is weak or the Doppler envelope is incomplete, increasing the sample volume to 4–5 mm and/or increasing the gain setting may prove helpful. Care must be taken to place the sample volume 1–2 cm inside the PV and not within the LA cavity or at the PV ostium (Table 17.1).22,23 The latter positions result in spectral broadening, distortion of the waveforms, and often underestimation of the PV-AR velocity.23 It is also advisable to record the PV Doppler signal using anatomical guidance by color Doppler. An attempt to place the sample volume in the RUPV on a frozen image may inadvertently result in recording flow from the adjacent SVC draining across the interatrial septum into the RA (Fig. 17.33A).23 One may also inadvertently place the sample volume outside the vein and record flow from the adjacent descending thoracic aorta.23 Here, the normal systolic aortic flow below the zero baseline velocity can be misdiagnosed as systolic flow reversal in the PV (Fig. 17.7 and 17.33B). Similarly, attempt at sampling the left-sided veins in the apical window may inadvertently record descending thoracic aortic flow above the zero baseline that mimics the systolic antegrade flow in the PV (Fig. 17.33C). Optimal filter setting is essential since a high filter leads to attenuation of weak and low-velocity signals such as the AR waveform. A low-filter setting leads to excessive noise and difficulty in the identification of individual waveforms.

343

TEE bypasses most of the difficulties described above.5 It allows the interrogation of flow from various PVs and provides a high signal quality in the majority of patients. Often the LUPV provides a better Doppler quality, a more common biphasic systolic signal, and a higher waveform velocity than other PVs.12,22 Placing the sample volume at a depth of 1 to 2 cm within the vein is optimal since a deeper or shallower location results in deterioration of the Doppler signal.12,22

ARTIFACTS Low-velocity wall motion artifacts are often present during PV Doppler recording by TTE. These artifacts occur most often during rapid changes in atrial volume and result from the spatial motion of the PV during atrial contraction, atrial relaxation, and the rapid filling phase.23 The most common and problematic artifact is the one occurring during atrial contraction in late diastole, simultaneously with the AR wave. This artifact is most often present when the PV is not dilated and a forceful atrial contraction is present resulting in a large atrial stroke volume with a pattern of impaired relaxation on the transmitral Doppler.23 Because of its timing, it can be easily mistaken for the AR or may completely mask it. This artifact usually starts before the PV-AR, is shorter in duration, and has a darker spectral signal than PV-S and PV-D (Fig. 17.34A).23 Since PV-AR starts simultaneously with the transmitral A wave and has the same signal intensity as PV-S and PV-D, the artifact can be recognized. The two other artifacts that are simultaneous with PV-S1 and PV-S2 pose less difficulty to the interpretation of the PV signal. Another late diastolic artifact that occurs simultaneously with PV-AR results from range ambiguity and originates from the LV outflow tract.23 This typically results in a dark signal mimicking a large AR waveform with unexpectedly high velocity (> 50 cm/s) (Fig. 17.34B). It is often accompanied by a systolic artifact in the same direction. Similarly, an aortic regurgitation signal originating from the LV outflow tract can obscure the PV-D waveform (Fig. 17.34C). An artifact can also be observed if the patient is talking or wheezing during PV Doppler recording. This type of artifact is often noted on both sides of the baseline and may obscure various waveforms depending on the phase of respiration (Fig. 17.34D). Whereas artifacts are difficult to eliminate completely, steps can be taken to alleviate their impact. Changing transducer location, usually to a higher intercostal space, slight angulation of the transducer, increasing the size of

344

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 17.33A to C: Pitfalls originating from inadvertent recording of pulmonary venous flow in the four-chamber view. (A) Inadvertent recording of flow from the superior vena cava adjacent to the right upper pulmonary vein. Note the systolic (S) and diastolic (D) velocities that resemble pulmonary venous flow. The absence of atrial reversal wave should raise this possibility; (B) Inadvertent recording of flow from the descending thoracic aorta adjacent to the right upper pulmonary vein. The systolic flow in the aorta (arrow) can be mistaken for systolic flow reversal in the pulmonary vein, implying a false diagnosis of severe mitral regurgitation. (C) Inadvertent recording of flow from the descending thoracic aorta adjacent to the left lower pulmonary vein. Note the systolic forward flow (arrow); however, no diastolic flow is noted.

A

B

Figs 17.34A and B

Chapter 17: Spectral Doppler of the Pulmonary Veins

C

345

D

Figs 17.34A to D: Artifacts on the pulmonary venous Doppler. (A) Late diastolic artifact. This type of artifact (arrowhead) often starts before the atrial reversal (AR) wave, is shorter in duration, and has a darker spectral profile. It should not be mistaken for the AR wave; (B) Late diastolic and systolic artifacts. Here the late diastolic artifact (arrow) obscures the atrial reversal wave. The systolic artifact (arrowhead) often accompanies the late diastolic artifact and should not be mistaken for late systolic flow reversal due to mitral regurgitation; (C) Artifact originating from the aortic regurgitation signal and obscuring the diastolic flow (arrow) in the right upper pulmonary vein; (D) Artifact related to wheezing. This may obscure any waveform (arrows) depending on the phase of respiration.

Doppler parameters, it provides important information regarding a wide variety of cardiac diseases, particularly in the initial assessment and follow-up of LV filling pressures, MR, myocardial and pericardial diseases, and PV stenosis among other conditions. A differential diagnosis for the most common abnormal PV flow patterns is listed in Figure 17.35.

ACKNOWLEDGMENTS

Fig. 17.35: Differential diagnosis for various waveform patterns of the pulmonary venous Doppler.

the sample volume to 4–5 mm, and advancing the sample volume farther into the PV may help improve signal quality and decrease artifacts.23 As a last resort, imaging the PV from a different window or interrogating another PV may be required.

CONCLUSION Doppler of the PV should be performed routinely as part of a complete and comprehensive echocardiographic study. Used in combination with other 2D, spectral, and tissue

The authors would like to acknowledge the professionalism, dedication to duty, high quality performance, and hard work of the sonographers and staff of the Echocardiography Laboratory at the King Faisal Specialist Hospital and Research Center. Writing this chapter would not have been possible without their commitment and support.

REFERENCES 1. Skagseth E. Pulmonary vein flow pattern in man during thoracotomy. Scand J Thorac Cardiovasc Surg. 1976;10(1): 36–42. 2. Rajagopalan B, Friend JA, Stallard T, Lee GD. Blood flow in pulmonary veins: I. Studies in dog and man. Cardiovasc Res. 1979;13(12):667–76. 3. Keren G, Sherez J, Megidish R, Levitt B, Laniado S. Pulmonary venous flow pattern—its relationship to cardiac dynamics. A pulsed Doppler echocardiographic study. Circulation. 1985;71(6):1105–12.

346

Section 2: Echocardiography/Ultrasound Examination and Training

4. Keren G, Bier A, Sherez J, et al. Atrial contraction is an important determinant of pulmonary venous flow. J Am Coll Cardiol. 1986;7(3):693–5. 5. Seward JB, Khandheria BK, Oh JK, et al. Transesophageal echocardiography: technique, anatomic correlations, implementation, and clinical applications. Mayo Clin Proc. 1988;63(7):649–80. 6. Klein AL, Tajik AJ. Doppler assessment of pulmonary venous flow in healthy subjects and in patients with heart disease. J Am Soc Echocardiogr. 1991;4(4):379–92. 7. Tabata T, Thomas JD, Klein AL. Pulmonary venous flow by Doppler echocardiography: revisited 12 years later. J Am Coll Cardiol. 2003;41(8):1243–50. 8. Edwards WD. Applied anatomy of the heart. In: Brandenburg RO, Fuster V, Giuliani ER, McGoon DC. eds. Cardiology: Fundamentals and Practice. Chicago, IL: Year Book Medical Publishers; 1987:58. 9. van der Voort PH, van den Bosch H, Post JC, Meijer A. Determination of the spatial orientation and shape of pulmonary vein ostia by contrast-enhanced magnetic resonance angiography. Europace. 2006;8(1):1–6. 10. Appleton CP. Hemodynamic determinants of Doppler pulmonary venous flow velocity components: new insights from studies in lightly sedated normal dogs. J Am Coll Cardiol. 1997;30(6):1562–74. 11. Smallhorn JF, Freedom RM, Olley PM. Pulsed Doppler echocardiographic assessment of extraparenchymal pulmonary vein flow. J Am Coll Cardiol. 1987;9(3):573–9. 12. Castello R, Pearson AC, Lenzen P, et al. Evaluation of pulmonary venous flow by transesophageal echocardiography in subjects with a normal heart: comparison with transthoracic echocardiography. J Am Coll Cardiol. 1991;18(1):65–71. 13. Smiseth OA, Thompson CR, Lohavanichbutr K, et al. The pulmonary venous systolic flow pulse—its origin and relationship to left atrial pressure. J Am Coll Cardiol. 1999;34(3):802–9. 14. Kuecherer HF, Muhiudeen IA, Kusumoto FM, et al. Estimation of mean left atrial pressure from transesophageal pulsed Doppler echocardiography of pulmonary venous flow. Circulation. 1990;82(4):1127–39. 15. Nishimura RA, Abel MD, Hatle LK, et al. Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography. Effect of different loading conditions. Circulation. 1990;81(5):1488–97. 16. Smallhorn JF, Freedom RM. Pulsed Doppler echocardiography in the preoperative evaluation of total anomalous pulmonary venous connection. J Am Coll Cardiol. 1986;8(6):1413–20. 17. Jensen JL, Williams FE, Beilby BJ, et al. Feasibility of obtaining pulmonary venous flow velocity in cardiac patients using transthoracic pulsed wave Doppler technique. J Am Soc Echocardiogr. 1997;10(1):60–6. 18. Huang X, Huang Y, Huang T, et al. Individual pulmonary vein imaging by transthoracic echocardiography: an

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

inadequate traditional interpretation. Eur J Echocardiogr. 2008;9(5):655–60. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study. Circulation. 2000;102(15):1788–94. Oh JK, Appleton CP, Hatle LK, et al. The noninvasive assessment of left ventricular diastolic function with twodimensional and Doppler echocardiography. J Am Soc Echocardiogr. 1997;10(3):246–70. Gentile F, Mantero A, Lippolis A, et al. Pulmonary venous flow velocity patterns in 143 normal subjects aged 20 to 80 years old. An echo 2D colour Doppler cooperative study. Eur Heart J. 1997;18(1):148–64. Masuyama T, Nagano R, Nariyama K, et al. Transthoracic Doppler echocardiographic measurements of pulmonary venous flow velocity patterns: comparison with transesophageal measurements. J Am Soc Echocardiogr. 1995;8(1): 61–9. Appleton CP, Jensen JL, Hatle LK, et al. Doppler evaluation of left and right ventricular diastolic function: a technical guide for obtaining optimal flow velocity recordings. J Am Soc Echocardiogr. 1997;10(3):271–92. Rossvoll O, Hatle LK. Pulmonary venous flow velocities recorded by transthoracic Doppler ultrasound: relation to left ventricular diastolic pressures. J Am Coll Cardiol. 1993;21(7):1687–96. Hoit B, Sahn DJ, Shabetai R. Doppler-detected paradoxus of mitral and tricuspid valve flows in chronic lung disease. J Am Coll Cardiol. 1986;8(3):706–9. Klein AL, Burstow DJ, Tajik AJ, et al. Effects of age on left ventricular dimensions and filling dynamics in 117 normal persons. Mayo Clin Proc. 1994;69(3):212–24. Miyatake K, Okamoto M, Kinoshita N, et al. Augmentation of atrial contribution to left ventricular inflow with aging as assessed by intracardiac Doppler flowmetry. Am J Cardiol. 1984;53(4):586–9. Douchet MP, Quiring E, Vi-Fane R, et al. Optimizing the hemodynamic performance of the DDD pacemaker: impact of the atrioventricular delay on the pulmonary venous flow pattern. Pacing Clin Electrophysiol. 1998;21(11 Pt 2):2261–8. Tabata T, Grimm RA, Bauer FJ, et al. Giant flow reversal in pulmonary venous flow as a possible mechanism for asynchronous pacing-induced heart failure. J Am Soc Echocardiogr. 2005;18(7):722–8. Stierle U, Krüger D, Mitusch R, et al. Adverse pacemaker hemodynamics evaluated by pulmonary venous flow monitoring. Pacing Clin Electrophysiol. 1995;18(11): 2028–34. Bartzokis T, Lee R, Yeoh TK, et al. Transesophageal echoDoppler echocardiographic assessment of pulmonary venous flow patterns. J Am Soc Echocardiogr. 1991;4(5): 457–64.

Chapter 17: Spectral Doppler of the Pulmonary Veins

32. Oki T, Iuchi A, Tabata T, et al. Transesophageal pulsed doppler echocardiographic study of systolic flow velocity patterns of the pulmonary vein in patients with atrial fibrillation. Echocardiography. 1998;15(2):147–56. 33. Chao TH, Tsai LM, Tsai WC, et al. Effect of atrial fibrillation on pulmonary venous flow patterns assessed by Doppler transesophageal echocardiography. Chest. 2000;117(6): 1546–50. 34. Iuchi A, Oki T, Fukuda N, et al. Changes in transmitral and pulmonary venous flow velocity patterns after cardioversion of atrial fibrillation. Am Heart J. 1996;131(2):270–5. 35. Matsuda Y, Toma Y, Matsuzaki M, et al. Change of left atrial systolic pressure waveform in relation to left ventricular end-diastolic pressure. Circulation. 1990;82(5):1659–67. 36. Yamamoto K, Nishimura RA, Burnett JC Jr, et al. Assessment of left ventricular end-diastolic pressure by Doppler echocardiography: contribution of duration of pulmonary venous versus mitral flow velocity curves at atrial contraction. J Am Soc Echocardiogr. 1997;10(1):52–9. 37. Brunner-La Rocca HP, Rickli H, Attenhofer Jost CH, et al. Left ventricular end-diastolic pressure can be estimated by either changes in transmitral inflow pattern during valsalva maneuver or analysis of pulmonary venous flow. J Am Soc Echocardiogr. 2000;13(6):599–607. 38. Poerner TC, Goebel B, Unglaub P, et al. Detection of a pseudonormal mitral inflow pattern: an echocardiographic and tissue Doppler study. Echocardiography. 2003;20(4): 345–56. 39. Castello R, Vaughn M, Dressler FA, et al. Relation between pulmonary venous flow and pulmonary wedge pressure: influence of cardiac output. Am Heart J. 1995;130(1): 127–34. 40. Yamamoto K, Nishimura RA, Chaliki HP, et al. Determination of left ventricular filling pressure by Doppler echocardiography in patients with coronary artery disease: critical role of left ventricular systolic function. J Am Coll Cardiol. 1997;30(7):1819–26. 41. Hunderi JO, Thompson CR, Smiseth OA. Deceleration time of systolic pulmonary venous flow: a new clinical marker of left atrial pressure and compliance. J Appl Physiol. 2006;100(2):685–9. 42. Kinnaird TD, Thompson CR, Munt BI. The deceleration [correction of declaration] time of pulmonary venous diastolic flow is more accurate than the pulmonary artery occlusion pressure in predicting left atrial pressure. J Am Coll Cardiol. 2001;37(8):2025–30. 43. Castello R, Pearson AC, Lenzen P, et al. Effect of mitral regurgitation on pulmonary venous velocities derived from transesophageal echocardiography color-guided pulsed Doppler imaging. J Am Coll Cardiol. 1991;17(7):1499–506. 44. Klein AL, Obarski TP, Stewart WJ, et al. Transesophageal Doppler echocardiography of pulmonary venous flow: a new marker of mitral regurgitation severity. J Am Coll Cardiol. 1991;18(2):518–26. 45. Klein AL, Stewart WJ, Bartlett J, et al. Effects of mitral regurgitation on pulmonary venous flow and left atrial pressure: an intraoperative transesophageal echocardiographic study. J Am Coll Cardiol. 1992;20(6): 1345–52.

347

46. Kamp O, Huitink H, van Eenige MJ, et al. Value of pulmonary venous flow characteristics in the assessment of severity of native mitral valve regurgitation: an angiographic correlated study. J Am Soc Echocardiogr. 1992;5(3):239–46. 47. Fuchs RM, Heuser RR, Yin FC, et al. Limitations of pulmonary wedge V waves in diagnosing mitral regurgitation. Am J Cardiol. 1982;49(4):849–54. 48. Pichard AD, Diaz R, Marchant E, et al. Large V waves in the pulmonary capillary wedge pressure tracing without mitral regurgitation: the influence of the pressure/ volume relationship on the V wave size. Clin Cardiol. 1983;6(11):534–41. 49. Passafini A, Shiota T, Depp M, et al. Factors influencing pulmonary venous flow velocity patterns in mitral regurgitation: an in vitro study. J Am Coll Cardiol. 1995;26(5):1333–9. 50. Mark JB, Ahmed SU, Kluger R, et al. Influence of jet direction on pulmonary vein flow patterns in severe mitral regurgitation. Anesth Analg. 1995;80(3):486–91. 51. Klein AL, Savage RM, Kahan F, et al. Experimental and numerically modeled effects of altered loading conditions on pulmonary venous flow and left atrial pressure in patients with mitral regurgitation. J Am Soc Echocardiogr. 1997;10(1):41–51. 52. Klein AL, Bailey AS, Cohen GI, et al. Importance of sampling both pulmonary veins in grading mitral regurgitation by transesophageal echocardiography. J Am Soc Echocardiogr. 1993;6(2):115–23. 53. Klein AL, Bailey AS, Cohen GI, et al. Effects of mitral stenosis on pulmonary venous flow as measured by Doppler transesophageal echocardiography. Am J Cardiol. 1993;72(1):66–72. 54. Tabata T, Oki T, Fukuda N, et al. Transesophageal pulsed Doppler echocardiographic study of pulmonary venous flow in mitral stenosis. Cardiology. 1996;87(2):112–18. 55. Kranidis AI, Kostopoulos KG, Filippatos GB, et al. Doppler echocardiographic study of pulmonary venous flow in mitral stenosis and early after mitral valve replacement. J Heart Valve Dis. 1994;3(4):425–31. 56. Oki T, Iuchi A, Tabata T, et al. Left atrial contribution to left ventricular filling in patients with mitral stenosis: combined analysis of transmitral and pulmonary venous flow velocities. Echocardiography. 1998;15(1):43–50. 57. Stojnic BB, Radjen GS, Perisic NJ, et al. Pulmonary venous flow pattern studied by transoesophageal pulsed Doppler echocardiography in mitral stenosis in sinus rhythm: effect of atrial systole. Eur Heart J. 1993;14(12):1597–601. 58. Tatani SB, Campos O, Moises VA, et al. Impact of effective valvotomy in mitral stenosis on pulmonary venous flow pattern. Echocardiography. 2006;23(7):531–5. 59. Abdalla I, Murray RD, Lee JC, et al. Duration of pulmonary venous atrial reversal flow velocity and mitral inflow a wave: new measure of severity of cardiac amyloidosis. J Am Soc Echocardiogr. 1998;11(12):1125–33. 60. Klein AL, Cohen GI, Pietrolungo JF, et al. Differentiation of constrictive pericarditis from restrictive cardiomyopathy by Doppler transesophageal echocardiographic measurements of respiratory variations in pulmonary venous flow. J Am Coll Cardiol. 1993;22(7):1935–43.

348

Section 2: Echocardiography/Ultrasound Examination and Training

61. Shabetai R, Fowler NO, Guntheroth WG. The hemodynamics of cardiac tamponade and constrictive pericarditis. Am J Cardiol. 1970;26(5):480–9. 62. Hatle LK, Appleton CP, Popp RL. Differentiation of constrictive pericarditis and restrictive cardiomyopathy by Doppler echocardiography. Circulation. 1989;79(2):357–70. 63. Oh JK, Hatle LK, Seward JB, et al. Diagnostic role of Doppler echocardiography in constrictive pericarditis. J Am Coll Cardiol. 1994;23(1):154–62. 64. Hurrell DG, Nishimura RA, Higano ST, et al. Value of dynamic respiratory changes in left and right ventricular pressures for the diagnosis of constrictive pericarditis. Circulation. 1996;93(11):2007–13. 65. Tabata T, Kabbani SS, Murray RD, et al. Difference in the respiratory variation between pulmonary venous and mitral inflow Doppler velocities in patients with constrictive pericarditis with and without atrial fibrillation. J Am Coll Cardiol. 2001;37(7):1936–42. 66. Oh JK, Seward JB, Tajik AJ. Pericardial disease. In: Oh JK, Seward JB, Tajik AJ. eds. The Echo Manual. Philadelphia, PA: Lippincott Raven; 1999:181–94. 67. Oh JK, Tajik AJ, Appleton CP, et al. Preload reduction to unmask the characteristic Doppler features of constrictive pericarditis. A new observation. Circulation. 1997;95(4): 796–9. 68. Boonyaratavej S, Oh JK, Tajik AJ, et al. Comparison of mitral inflow and superior vena cava Doppler velocities in chronic obstructive pulmonary disease and constrictive pericarditis. J Am Coll Cardiol. 1998;32(7):2043–8. 69. Dal-Bianco JP, Sengupta PP, Mookadam F, et al. Role of echocardiography in the diagnosis of constrictive pericarditis. J Am Soc Echocardiogr. 2009;22(1):24–33; quiz 103.

70. Abdalla IA, Murray RD, Lee JC, et al. Does rapid volume loading during transesophageal echocardiography differentiate constrictive pericarditis from restrictive cardiomyopathy? Echocardiography. 2002; 19(2):125–34. 71. Sun JP, Abdalla IA, Yang XS, et al. Respiratory variation of mitral and pulmonary venous Doppler flow velocities in constrictive pericarditis before and after pericardiectomy. J Am Soc Echocardiogr. 2001;14(11):1119–26. 72. Appleton CP, Hatle LK, Popp RL. Cardiac tamponade and pericardial effusion: respiratory variation in transvalvular flow velocities studied by Doppler echocardiography. J Am Coll Cardiol. 1988;11(5):1020–30. 73. Burstow DJ, Oh JK, Bailey KR, et al. Cardiac tamponade: characteristic Doppler observations. Mayo Clin Proc. 1989;64(3):312–24. 74. Robbins IM, Colvin EV, Doyle TP, et al. Pulmonary vein stenosis after catheter ablation of atrial fibrillation. Circulation. 1998;98(17):1769–75. 75. Sohn RH, Schiller NB. Left upper pulmonary vein stenosis 2 months after radiofrequency catheter ablation of atrial fibrillation. Circulation. 2000;101(13):E154–5. 76. Smallhorn JF, Pauperio H, Benson L, et al. Pulsed Doppler assessment of pulmonary vein obstruction. Am Heart J. 1985;110(2):483–6. 77. Stavrakis S, Madden GW, Stoner JA, et al. Transesophageal echocardiography for the diagnosis of pulmonary vein stenosis after catheter ablation of atrial fibrillation: a systematic review. Echocardiography. 2010;27(9):1141–6. 78. Saric M, Applebaum RM, Phoon CK, et al. Pulmonary venous flow in large, uncomplicated atrial septal defect. J Am Soc Echocardiogr. 2001;14(5):386–90.

349

CHAPTER 18 Tissue Doppler Imaging Hisham Dokainish

Snapshot  Technical ConsideraƟons  Development of Tissue Doppler Imaging

INTRODUCTION Tissue Doppler (TD) imaging is a Doppler echocardiographic technique that directly measures myocardial velocities. Systolic TD measurements assess left and right ventricular (RV) myocardial contractile function. Diastolic TD velocities measure myocardial relaxation, and in combination with conventional Doppler measurements, ratios (early transmitral Doppler velocity/TD early diastolic mitral annular velocity, E/e′) have been developed to estimate left ventricular (LV) filling pressures. TD values and derived ratios have been demonstrated to be valuable in the diagnosis of myocardial disease, LV filling pressures, assessment of LV and left atrial function in patients with atrial fibrillation, LV dyssynchrony, RV function, and the prognosis of patients with cardiac disease. This chapter focuses on the current clinical uses of TD imaging in the assessment of patients with known or suspected cardiac disease.

TECHNICAL CONSIDERATIONS The Doppler principle states that the frequency of a reflected sound wave will be altered by the velocity of a moving object with which it comes in contact. In conventional Doppler imaging, wall filters are employed to eliminate high-amplitude, low-frequency signals reflected from myocardium in favor of low-amplitude,

 Current Clinical Uses of TD Imaging

high-frequency signals reflected from moving red blood cells. In TD imaging, wall filters are bypassed in order to specifically measure myocardial velocities. Thus, the typical velocities of the human myocardium range from 0 cm/s to 20 cm/s, and Doppler gain settings must be increased to adequately visualize TD waveforms.1 In spectral TD imaging, a 2–3 mm sample volume is placed along the myocardial wall (typically 1 cm above the mitral or tricuspid annuli), and pulsed Doppler is activated, obtaining peak myocardial velocities. In color TD imaging, autocorrelation techniques are utilized to measure mean myocardial velocities.1 The numerical values obtained by color TD imaging are roughly one-half of the values obtained by spectral TD imaging.2 In clinical TD applications, three main waveforms are visualized per cardiac cycle: the peak systolic wave (s′), early diastolic wave (e′), and end-diastolic wave produced by atrial contraction (a′). Two important time intervals are also seen: isovolumic relaxation (IVR) and contraction (IVC) (Fig. 18.1), which can be used in the calculation of myocardial performance indices. Although TD myocardial velocities decrease with age, a normal 50-year-old adult has LV and RV spectral TD values of generally ≥10 cm/s, and color TD values of generally ≥6 cm/s for s′, e′, and a′.3,4 Figures 18.2A and B depict LV spectral TD velocities in a normal patient and in a patient with cardiac disease, and Figures 18.3A and B display these respective velocities

350

Section 2: Echocardiography/Ultrasound Examination and Training

using spectral TD imaging of the RV. Figures 18.4A and B depict mean myocardial TD velocities using color Doppler TD imaging in a normal heart, and in a patient with chronic hypertensive heart disease. Figure 18.5 shows RV mean myocardial TD velocities using color Doppler TD imaging in normal heart. In addition, TD data can be used to determine regional myocardial strain, but a detailed

discussion of strain is beyond the scope of this chapter, and TD strain has been largely supplanted by speckle tracking strain measures, which are not angle-dependent and can be measured in multiple vectors.

DEVELOPMENT OF TISSUE DOPPLER IMAGING Tissue Doppler imaging of the heart was first described in 1989. Isaaz et al. demonstrated that low myocardial velocities at the posterior mitral annulus correlated with abnormal posterior wall motion on LV angiography.5 The use of TD myocardial imaging, both spectral and color TD, to indicate the presence of cardiac disease, was expanded in work by Sutherland et al.6 Regional variation of myocardial velocity gradients was demonstrated to be of value in the assessment of segmental LV wall motion.7,8 TD systolic mitral annular velocities were also shown to correlate with global LV myocardial function as assessed by radionuclide ventriculography.9

CURRENT CLINICAL USES OF TD IMAGING Fig. 18.1: Spectral tissue Doppler imaging in a patient with cardiac disease. This 67-year-old man with chronic hypertension had a left ventricular ejection fraction of 64%. Note that both the s′ and e′ velocities are ~5 cm/s, indicating depressed myocardial velocities (normal 10 cm/s). (a′: late diastolic tissue Doppler (TD) myocardial velocity; e′: early diastolic TD myocardial velocity; IVC: Isovolumic contraction TD myocardial velocity; IVR: Isovolumic relaxation TD myocardial velocity; s′: systolic TD myocardial velocity).

Given that e′ is a relatively preload-independent estimation of LV relaxation in patients with cardiac disease, studies have employed e′ to quantitatively assess early (subclinical) manifestations of cardiac disease. Nagueh et al. demonstrated that s′ and e′ values were reduced in

A

B

TD in the Detection of Myocardial Disease

Figs 18.2A and B: Left ventricular tissue Doppler velocities in a normal patient and a patient with cardiac disease. In the normal myocardium (A), the tissue Doppler velocities are 10 cm/s, whereas in myocardial disease (B), the velocities are ~ 5 cm/s. (a′: late diastolic tissue Doppler (TD) myocardial velocity; e′: early diastolic TD myocardial velocity; IVC: Isovolumic contraction TD myocardial velocity; IVR: Isovolumic relaxation TD myocardial velocity; s′: systolic TD myocardial velocity).

Chapter 18: Tissue Doppler Imaging

A

351

B

Figs 18.3A and B: Right ventricular tissue Doppler velocities in a normal patient and a patient with cardiac disease. In the normal myocardium (A), the tissue Doppler velocities are 10 cm/s, whereas in myocardial disease (B), the velocities are ~5 cm/s. (a′: late diastolic tissue Doppler (TD) myocardial velocity; e′: early diastolic TD myocardial velocity; IVC: Isovolumic contraction TD myocardial velocity; IVR, Isovolumic relaxation TD myocardial velocity; s′: systolic TD myocardial velocity).

A

B

Figs 18.4A and B: Color tissue Doppler left ventricular myocardial velocities in the normal patient and the patient with cardiac disease. In the normal myocardium (A), the tissue Doppler (TD) velocities are 6 to 7 cm/s, whereas in myocardial disease (B), the velocities are 2 to 5 cm/s. It is important to note that, as stated in the text, color TD imaging measures mean myocardial velocities, which are 30% to 50% lower than the peak myocardial velocities measured by pulsed spectral TD imaging. Also note the significant intraventricular dyssynchrony—the velocities from the septal wall in yellow occur at a different time than the velocities from the lateral wall in green—in Fig. B in the cardiac disease patient compared to lack of dyssynchrony in the normal patients in Fig. A. (a′: late diastolic TD myocardial velocity; e′: early diastolic TD myocardial velocity; IVC: Isovolumic contraction TD myocardial velocity; IVR: Isovolumic relaxation TD myocardial velocity; s′: systolic TD myocardial velocity).

patients who had genetic mutations of hypertrophic cardiomyopathy (HCM), whether or not the patients manifested left ventricular hypertrophy (LVH).10 Thus, TD velocities were able to detect patients with HCM mutations, in the absence of clinically apparent disease. It was

subsequently demonstrated that patients with subclinical disease and reduced TD velocities went on to develop significant hypertrophy and clinical HCM.11 However, more recent data have challenged the stand-alone use of TD imaging in the identification of HCM mutation

352

Section 2: Echocardiography/Ultrasound Examination and Training

there is a gradient of normal or supranormal TD velocities in athletic hearts, mildly to moderately depressed in hypertensive patients, and severely depressed in HCM patients all of whom have normal LVEF.19

TD Imaging in the Assessment of Diastolic Function and Estimation of LV Filling Pressures

Fig. 18.5: Color tissue Doppler right ventricular myocardial velocities in the normal patient. In the normal myocardium, the tissue Doppler (TD) velocities are 6 to 7 cm/s, which are lower than the pulsed spectral (peak) TD velocities in the RV as seen in Figure 18.3A. (a′: late diastolic TD myocardial velocity; e′: early diastolic TD myocardial velocity; IVC: Isovolumic contraction TD myocardial velocity; IVR: Isovolumic relaxation TD myocardial velocity; s′: systolic TD myocardial velocity).

carriers.12 Similarly, others have shown that in patients with genetic mutations for Fabry disease and LVH have lower TD myocardial velocities than patients with Fabry mutations and no LVH.13 Both mutation groups had lower velocities than characteristic-matched controls. Similarly, it has been demonstrated that values of s′ (< 8.7 cm/s) were highly sensitive, but modestly specific, for the detection of heart transplant rejection diagnosed by cardiac biopsy.14 TD imaging of the LV has also been shown to be useful in patients undergoing chemotherapy, as TD-derived s′ and strain rate become significantly depressed before changes in LV ejection fraction (EF) are seen.15 The presence of depressed e′ velocities (indicating impaired myocardial relaxation) has also been valuable in distinguishing restrictive cardiomyopathy from constriction, the former being a myocardial disease with depressed TD velocities, the latter a process extrinsic to the myocardium with normal TD velocities.16,17 TD velocities have also been used to indicate the presence of cardiac amyloidosis, which has very depressed TD velocities yet often preserved LVEF,18 and in distinguishing pathologic hypertrophy (hypertension and hypertrophic cardiomyopathy—HCM) from athletic hearts, in which

Tissue Doppler imaging, and specifically early diastolic TD relaxation velocity (e′)—and derived ratios such as E/e′— have proven to be of great value in the echocardiographic assessment of LV diastolic function. Sohn et al.20 demonstrated that e′ correlated with τ (an invasive index of LV relaxation), and Nagueh et al.21 demonstrated that the peak pulsed Doppler early inflow velocity (E) divided by e′ resulted in a ratio (E/e′), which correlated well with pulmonary capillary wedge pressure (PCWP), an invasive estimate of LV filling pressures. In general, an E/e′ ≤ 8 cm/s indicated normal LV filling pressures, an E/e′ ≥ 15 indicated elevated filling pressures, and an E/e′ of 9–14 was a gray zone, requiring additional Doppler information from mitral inflow (deceleration time) pulmonary venous flow, and two-dimensional echocardiographic information such as left atrial (LA) size. Ommen et al. corroborated this work, demonstrating the utility of E/e′ estimating mean LV diastolic pressures.22 The E/e′ ratio has since been demonstrated to be useful in estimating LV filling pressures in hypertrophic cardiomyopathy,23 sinus tachycardia,24 atrial fibrillation,25 and postcardiac transplantation.26 Although in patients with cardiac disease, e′ is relatively preload independent, there had been little information on whether this holds true in patients without myocardial disease. It has been shown that, in healthy volunteers, e′ varies with alterations in preload, thus implying that E/e′ is less reliable in patients without cardiac disease.27 In patients with preserved LVEF [ejection fraction (EF) ≥ 50%], TD has been employed to demonstrate that such patients may not only have diastolic abnormalities, but also abnormalities in systolic function. It has been shown that there is a continuum of increasing TD velocities, with patients with systolic heart failure being the lowest, followed by diastolic heart failure, then by diastolic dysfunction without heart failure.28 All three groups had depressed s′ when compared to healthy controls.

Chapter 18: Tissue Doppler Imaging

Given that LVEF may be preserved, in the presence of cardiac disease, it is important to determine whether the E/e′ ratio can be employed to estimate LV filling pressures in patients with preserved EF yet with cardiac disease. In patients with EF ≥ 50%, the lateral mitral annulus can be used to estimate pulmonary capillary wedge pressure (PCWP) using E/e′; furthermore, in patients with regional wall motion abnormalities, the average of the septal and lateral mitral annuli can be utilized in E/e′ to accurately estimate LV filling pressure.29 It has also been shown that, using invasive hemodynamics as the reference standard, E/e′ is more accurate and reproducible than B-type natriuretic peptide (BNP, a protein released from the myocytes in response to pressure or volume overload) in estimating LV filling pressures in patients admitted to intensive care.30 The time interval from onset of early diastolic mitral annular relaxation (e′) to the onset of early diastolic filling by pulsed Doppler (E) correlated well with invasively measured . Patients with myocardial disease had a delayed e′–E time interval; when combined in an equation incorporating LV end-systolic pressure and IVRT, e′–E accurately predicted PCWP.31 Another unclear scenario is the effect of significant mitral regurgitation (MR) on e′ and the E/e′ ratio in estimating LV filling pressures. It has been shown that in patients with secondary MR (due to LV disease), E/e′ accurately predicted PCWP; however, in patients with primary MR (due to a primary mitral valve abnormality), E/e′ was not reliably predictive of PCWP.32 It is noteworthy that, while the clear majority of TD studies using invasive measurements of LV filling pressures as the reference standard have demonstrated reasonable correlations of E/e′ to LV filling pressure, one group has shown weak correlations of E/e′ to PCWP in 106 patients with decompensated and advanced systolic heart failure.33 Figures 18.7A to D and 18.8A to D show how pulsed and color tissue Doppler imaging, respectively, can be used in the assessment of LV diastolic function and estimation of filling pressures.

TD Imaging in Patients with Atrial Fibrillation Tissue Doppler imaging has also been used to determine the myocardial substrate for the development of atrial fibrillation (AF), either by demonstrating LV diastolic

353

abnormalities that can lead to atrial stretch and AF or by applying TD imaging directly to the atrial tissue to demonstrate decreased velocities or deformation in the atria themselves. Following electrical cardioversion, patients with recurrence of AF within 2 weeks had higher E/e′ ratios than patients who did not have early AF recurrence, highlighting the association of LV diastolic dysfunction, its impact on the LA, and propensity to AF.34 TD imaging can also be applied to LA tissue itself, and has been shown to be useful in demonstrating depressed atrial function (atrial s′ wave) and interatrial dyssynchrony by the use of TD-determined atrial time intervals.35 Atrial TD imaging has also been shown to predict the propensity to develop AF (in patients without a history of AF) as patients who developed AF had lower atrial TD velocities than those who did not go on to develop AF.36

TD Imaging for LV Dyssynchrony Given that TD imaging has high temporal resolution, it can be employed to time myocardial activation after the onset of the QRS complex, or in response to pacing. In this regard, color TD tracking can be used to identify the myocardial site with the most delayed activation after the onset of the widened QRS complex.37 The pace-making electrode is thus placed in this area to provide the best sequential myocardial resynchronization, resulting in the best decreases in LV volumes and increases in LVEF. It has also been shown that TD imaging could be used to demonstrate a significant increase in systolic contraction velocities after biventricular pacing, and that the degree of myocardial delay as demonstrated by tissue tracking (a derivative of TD imaging) predicted response to biventricular pacing.38 Yu et al. demonstrated that an index employing the time from QRS onset to the peak systolic myocardial velocity in a given segment provided an index of dyssynchrony, useful in the prediction of response to resynchronization therapy by biventricular pacing.39 However, more recent data has cast doubt on the robustness of TD parameters for the accurate assessment of LV dyssynchrony in the clinical setting, mainly owing to multiple measurements needed and significant interobserver variabilities that may preclude widespread clinical application and reproducibility.40,41 Figures 18.6A and B illustrate the use of TD (tissue synchronization) imaging to resynchronize LV activation after biventricular pacemaker implantation.

354

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 18.6A and B: Tissue Doppler imaging for ventricular resynchronization: ventricular dyssynchrony before and after biventricular pacemaker insertion. (A) The time from the QRS complex to the peak tissue Doppler systolic velocity at the lateral wall is indicated by the dashed arrow, and the time from QRS to peak tissue Doppler velocity at the septal wall is displayed by the solid arrow. The time to peak velocity is markedly longer at the septal wall owing to delayed septal activation from the left bundle branch block (0.51 seconds) than at the lateral wall (0.18 seconds). Therefore, there is marked intraventricular dyssynchrony owing to the left bundle branch block and myocardial disease; (B) The time from the QRS complex to the peak tissue Doppler systolic velocity at the lateral wall is indicated by the dashed arrow, and the time from QRS to peak tissue Doppler velocity at the septal wall is displayed by the solid arrow. Note that the time to peak velocity is nearly equal at the septal wall (0.34 seconds) and the lateral wall (0.33 seconds) after biventricular pacemaker insertion. Therefore, there is now intraventricular synchrony since the septal and lateral are being nearly simultaneously activated by the pacemaker wires.

TD Assessment of Right Ventricular Function Tissue Doppler imaging has also been studied for the detection of RV dysfunction in patients with cardiac disease. It has been shown that s′, e′, and a′ taken from the lateral tricuspid annulus are lower in patients with first inferior myocardial infarction (MI) with RV infarction (as assessed by ST elevation in lead V4R) than in patients with inferior MI but without RV infarction.42 Furthermore, depressed s′ velocities at the tricuspid annulus (reflecting RV myocardial impairment) not only correlate with the presence of RV infarction, but also predict cardiac readmission and death in patients with first acute inferior MI.43 Similarly, it has been shown that RV dysfunction evidenced by a depressed s′ at the tricuspid annulus predicts prognosis in patients with LV cardiomyopathy.44,45 RV myocardial performance index, calculated using TD velocities and intervals (as seen in Fig. 18.1), has been shown to correlate well with RV ejection fraction (RVEF) and RV fractional area change in patients with pulmonary hypertension.46 Depressed RV myocardial TD velocities— by sampling the RV free wall just apically to the tricuspid annulus—have also been shown to detect RV dysfunction

in dilated cardiomyopathy,47 cor pulmonale,48 and hypertrophic cardiomyopathy.49 Figures 18.9A to D show how tissue Doppler imaging can be used in the assessment of RV function.

TD Imaging and Prognosis There has been great interest in the ability of TD imaging, by detecting and quantitating the degree of myocardial disease, to provide important prognostic information. In patients with acute myocardial infarction, it has been shown that e′ and E/e′ were univariate predictors of death or hospital readmission.50 Furthermore, s′, e′, and a′ added incremental prognostic information to 2D variables (LVEF, LV mass, and LA dimension) in predicting cardiac death in patients with cardiac disease.51 Redfield et al. have demonstrated, in a population-based study that included TD imaging, that patients with increasing degrees of diastolic dysfunction have increasingly worse outcome.52 It has also been demonstrated that E/e′ is a strong multivariate predictor of patient outcome when assessed early after acute myocardial infarction.53 E/e′ also predicted cardiac death or rehospitalization in patients hospitalized with congestive heart failure, and added incremental prognostic value to conventional echocardiographic

Chapter 18: Tissue Doppler Imaging

A

B

C

D

355

Figs 18.7A to D: Pulsed tissue Doppler imaging for the assessment of left ventricular (LV) diastolic function. (A) An apical four-chamber view with enlarged left atrium (LA); (B) Septal tissue Doppler (TD) early diastolic velocity (e′) is 4 cm/s; (C) Demonstrates early transmitral diastolic velocity (E) of 80 cm/s, and; (D) A tricuspid regurgitation peak velocity of 40 mm Hg, which when added to the right atrial pressure estimate of 10 mm Hg, gives a pulmonary artery systolic pressure of 50 mm Hg. Therefore, E/e′ = 20, with enlarged LA and pulmonary hypertension indicating impaired LV relaxation with elevated LV filling pressures and mild to moderate pulmonary hypertension.

predictors, and BNP, in predicting patient outcome.54 Another TD ratio that has been employed to assess LV diastolic function (e′/a′) has been shown, along with LVEDP, to be a predictor of cardiac events in 173 patients with dilated cardiomyopathy and LVEF < 45%.55 In a population-based study of 1,036 healthy volunteers, s′ and e′ were shown to be powerful and independent predictors of death in volunteers with normal ejection fraction.56 In a study of 49 patients with severe systolic heart failure awaiting cardiac transplantation, it has been shown that DT and E/e′ were predictors of cardiac death or transplantation, but that E/e′ was the only independent predictor of outcome when adjusted for invasively measured LA

pressure.57 Therefore, there are substantial data demonstrating the robustness of TD LV and RV velocities in determining the prognosis of patients with cardiac disease.

SUMMARY Tissue Doppler imaging, a Doppler technique that directly measures myocardial velocities, has developed into an important and user-friendly measure that can be incorporated into the echocardiographic assessment of patients with known or suspected cardiac disease. TD variables (s′, e′ and a′) are being used to diagnose subclinical disease in patients with known genetic mutations for cardiac diseases such as HCM, and to detect

356

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 18.8A to D: Color tissue Doppler imaging for the assessment of left ventricular (LV) diastolic function. (A) An apical fourchamber view with color tissue Doppler (TD) imaging activated; (B) Septal tissue Doppler (TD) early diastolic velocity (e′) = 5 cm/s; (C) Demonstrates early transmitral diastolic velocity (E) = 97 cm/s, and; (D) Lateral e′ = 4 cm/s. Therefore, E/e′ septal= 19.7, and E/e′ lateral = 24.25, indicating impaired LV relaxation with elevated LV filling pressures.

A Figs 18.9A and B

B

Chapter 18: Tissue Doppler Imaging

C

357

D

Figs 18.9A to D: Tissue Doppler imaging in the assessment of right ventricular function. A 47-year-old woman presented to the hospital with increasing exercise intolerance. She had mitral valve replacement with a St. Jude’s prosthesis 8 years prior for rheumatic mitral stenosis. On examination, blood pressure was 110/74 mm Hg, and heart rate was 67 and irregularly irregular. Jugular venous pressure was elevated, and heart sounds revealed a crisp, mechanical S1 and a prominent S2. Lungs were clear and chest X-ray revealed no evidence of pulmonary edema. Echo Doppler examination revealed a left ventricular ejection fraction of 40% with a normally functioning mechanical mitral valve with a mean mitral gradient of 4.1 mm Hg. There was biatrial enlargement, and the right ventricle (RV) was mildly dilated with normal systolic function (A). Tissue Doppler interrogation of the tricuspid annulus revealed a markedly depressed systolic velocity (Sa = 4.7 cm/s), and a depressed diastolic velocity of 6 cm/s (B; note the single diastolic wave, as the patient was in atrial fibrillation). The tricuspid regurgitation velocity was 3.4 m/s, resulting in an RV–RA pressure gradient of 46 mm Hg (C). The RA pressure was estimated at 10 mm Hg using the inferior vena cava diameter (2.5 cm) and response to respiration (D), resulting in a pulmonary artery systolic pressure estimate of 56 mm Hg. Thus, this case demonstrates significant RV impairment as demonstrated by depressed tricuspid annular tissue Doppler velocities, despite a normal RV ejection fraction by two-dimensional echocardiography, in a patient with a mechanical mitral valve and pulmonary hypertension.

subclinical, chemotherapy-associated cardiomyopathy. TD-derived ratios (E/e′) are being commonly used to estimate LV filling pressures in a widening group of patients and are important predictors of outcome in patients with cardiac disease. TD imaging is also of value in the assessment of patients with, or prone to AF, and in the optimization of intervals and sites of pacing in patients with heart failure and intraventricular delay. TD has been applied to the RV to detect both clinical and subclinical dysfunction, and there is a significant body of literature on the use of TD variables as important prognosticators of outcome in patients with cardiac disease. TD imaging now plays an integral role in the daily echocardiographic assessment of patients.

REFERENCES 1. Sutherland GR, Bijnens B, McDicken WN. Tissue Doppler Echocardiography: Historical Perspective and Technological Considerations. Echocardiography. 1999;16 (5):445–53.

2. McCulloch M, Zoghbi WA, Davis R, et al. Color tissue Doppler myocardial velocities consistently underestimate spectral tissue Doppler velocities. JASE. 2004;7(5) Suppl. 3. Alam M, Wardell J, Andersson E, et al. Characteristics of mitral and tricuspid annular velocities determined by pulsed wave Doppler tissue imaging in healthy subjects. J Am Soc Echocardiogr. 1999;12(8):618–28. 4. Nikitin NP, Witte KK, Thackray SD, et al. Longitudinal ventricular function: normal values of atrioventricular annular and myocardial velocities measured with quantitative two-dimensional color Doppler tissue imaging. J Am Soc Echocardiogr. 2003;16(9):906–21. 5. Isaaz K, Thompson A, Ethevenot G, et al. Doppler echocardiographic measurement of low velocity motion of the left ventricular posterior wall. Am J Cardiol. 1989;64(1): 66–75. 6. Sutherland GR, Stewart MJ, Groundstroem KW, et al. Color Doppler myocardial imaging: a new technique for the assessment of myocardial function. J Am Soc Echocardiogr. 1994;7(5):441–58. 7. Uematsu M, Miyatake K, Tanaka N, et al. Myocardial velocity gradient as a new indicator of regional left ventricular contraction: detection by a two-dimensional tissue Doppler imaging technique. J Am Coll Cardiol. 1995; 26(1):217–23.

358

Section 2: Echocardiography/Ultrasound Examination and Training

8. Gorcsan J 3rd, Gulati VK, Mandarino WA, et al. Color-coded measures of myocardial velocity throughout the cardiac cycle by tissue Doppler imaging to quantify regional left ventricular function. Am Heart J. 1996;131(6):1203–13. 9. Gulati VK, Katz WE, Follansbee WP, et al. Mitral annular descent velocity by tissue Doppler echocardiography as an index of global left ventricular function. Am J Cardiol. 1996;77(11):979–84. 10. Nagueh SF, Bachinski LL, Meyer D, et al. Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy. Circulation. 2001;104(2):128–30. 11. Nagueh SF, McFalls J, Meyer D, et al. Tissue Doppler imaging predicts the development of hypertrophic cardiomyopathy in subjects with subclinical disease. Circulation. 2003;108(4):395–8. 12. Gandjbakhch E, Gackowski A, Tezenas du Montcel S, et al. Early identification of mutation carriers in familial hypertrophic cardiomyopathy by combined echocardiography and tissue Doppler imaging. Eur Heart J. 2010;31(13): 1599–607. 13. Pieroni M, Chimenti C, Ricci R, et al. Early detection of Fabry cardiomyopathy by tissue Doppler imaging. Circulation. 2003;107(15):1978–84. 14. Stengel SM, Allemann Y, Zimmerli M, et al. Doppler tissue imaging for assessing left ventricular diastolic dysfunction in heart transplant rejection. Heart. 2001;86(4):432–7. 15. Jassal DS, Han SY, Hans C, et al. Utility of tissue Doppler and strain rate imaging in the early detection of trastuzumab and anthracycline mediated cardiomyopathy. J Am Soc Echocardiogr. 2009;22(4):418–24. 16. Garcia MJ, Rodriguez L, Ares M, et al. Differentiation of constrictive pericarditis from restrictive cardiomyopathy: assessment of left ventricular diastolic velocities in longitudinal axis by Doppler tissue imaging. J Am Coll Cardiol. 1996;27(1):108–14. 17. Ha JW, Ommen SR, Tajik AJ, et al. Differentiation of constrictive pericarditis from restrictive cardiomyopathy using mitral annular velocity by tissue Doppler echocardiography. Am J Cardiol. 2004;94(3):316–19. 18. Koyama J, Ray-Sequin PA, Davidoff R, et al. Usefulness of pulsed tissue Doppler imaging for evaluating systolic and diastolic left ventricular function in patients with AL (primary) amyloidosis. Am J Cardiol. 2002;89(9):1067–71. 19. Palka P, Lange A, Fleming AD, et al. Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension. J Am Coll Cardiol. 1997;30(3):760–8. 20. Sohn DW, Chai IH, Lee DJ, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997;30(2):474–80. 21. Nagueh SF, Middleton KJ, Kopelen HA, et al. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997; 30(6):1527–33.

22. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study. Circulation. 2000;102(15):1788–94. 23. Nagueh SF, Lakkis NM, Middleton KJ, et al. Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation. 1999;99(2): 254–61. 24. Nagueh SF, Mikati I, Kopelen HA, et al. Doppler estimation of left ventricular filling pressure in sinus tachycardia. A new application of tissue doppler imaging. Circulation. 1998;98(16):1644–50. 25. Sohn DW, Song JM, Zo JH, et al. Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation. J Am Soc Echocardiogr. 1999;12(11):927–31. 26. Sundereswaran L, Nagueh SF, Vardan S, et al. Estimation of left and right ventricular filling pressures after heart transplantation by tissue Doppler imaging. Am J Cardiol. 1998;82(3):352–7. 27. Firstenberg MS, Levine BD, Garcia MJ, et al. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers. J Am Coll Cardiol. 2000;36(5):1664–9. 28. Yu CM, Lin H, Yang H, et al. Progression of systolic abnormalities in patients with “isolated” diastolic heart failure and diastolic dysfunction. Circulation. 2002;105(10): 1195–201. 29. Rivas-Gotz C, Manolios M, Thohan V, et al. Impact of left ventricular ejection fraction on estimation of left ventricular filling pressures using tissue Doppler and flow propagation velocity. Am J Cardiol. 2003;91(6):780–4. 30. Dokainish H, Zoghbi WA, Lakkis NM, et al. Optimal noninvasive assessment of left ventricular filling pressures: a comparison of tissue Doppler echocardiography and B-type natriuretic peptide in patients with pulmonary artery catheters. Circulation. 2004;109(20):2432–9. 31. Rivas-Gotz C, Khoury DS, Manolios M, et al. Time interval between onset of mitral inflow and onset of early diastolic velocity by tissue Doppler: a novel index of left ventricular relaxation: experimental studies and clinical application. J Am Coll Cardiol. 2003; 42(8):1463–70. 32. Bruch C, Stypmann J, Gradaus R, et al. Usefulness of tissue Doppler imaging for estimation of filling pressures in patients with primary or secondary pure mitral regurgitation. Am J Cardiol. 2004;93(3):324–8. 33. Mullens W, Borowski AG, Curtin RJ, et al. Tissue Doppler imaging in the estimation of intracardiac filling pressure in decompensated patients with advanced systolic heart failure. Circulation. 2009;119(1):62–70. 34. Caputo M, Urselli R, Capati E, et al. Usefulness of left ventricular diastolic dysfunction assessed by pulsed tissue Doppler imaging as a predictor of atrial fibrillation recurrence after successful electrical cardioversion. Am J Cardiol. 2011;108(5):698–704. 35. Sakabe K, Fukuda N, Fukuda Y, et al. Interatrial dyssynchrony on tissue Doppler imaging predicts progression to chronic atrial fibrillation in patients with non-valvular paroxysmal atrial fibrillation. Heart. 2009;95(12):988–93.

Chapter 18: Tissue Doppler Imaging

36. De Vos CB, Weijs B, Crijns HJ, et al. Atrial tissue Doppler imaging for prediction of new-onset atrial fibrillation. Heart. 2009;95(10):835–40. 37. Ansalone G, Giannantoni P, Ricci R, et al. Doppler myocardial imaging to evaluate the effectiveness of pacing sites in patients receiving biventricular pacing. J Am Coll Cardiol. 2002;39(3):489–99. 38. Søgaard P, Egeblad H, Kim WY, et al. Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol. 2002; 40(4):723–30. 39. Yu CM, Zhang Q, Fung JW, et al. A novel tool to assess systolic asynchrony and identify responders of cardiac resynchronization therapy by tissue synchronization imaging. J Am Coll Cardiol. 2005;45(5):677–84. 40. Kleijn SA, van Dijk J, de Cock CC, et al. Assessment of intraventricular mechanical dyssynchrony and prediction of response to cardiac resynchronization therapy: comparison between tissue Doppler imaging and real-time threedimensional echocardiography. J Am Soc Echocardiogr. 2009;22(9):1047–54. 41. Chung ES, Leon AR, Tavazzi L, et al. Results of the Predictors of Response to CRT (PROSPECT) trial. Circulation. 2008; 117(20):2608–16. 42. Alam M, Wardell J, Andersson E, et al. Right ventricular function in patients with first inferior myocardial infarction: assessment by tricuspid annular motion and tricuspid annular velocity. Am Heart J. 2000; 139(4):710–15. 43. Dokainish H, Abbey H, Gin K, et al. Usefulness of tissue Doppler imaging in the diagnosis and prognosis of acute right ventricular infarction with inferior wall acute left ventricular infarction. Am J Cardiol. 2005;95(9):1039–42. 44. Meluzín J, Spinarová L, Dusek L, et al. Prognostic importance of the right ventricular function assessed by Doppler tissue imaging. Eur J Echocardiogr. 2003;4(4):262–71. 45. Dokainish H, Sengupta R, Patel R, et al. Usefulness of right ventricular tissue Doppler imaging to predict outcome in left ventricular heart failure independent of left ventricular diastolic function. Am J Cardiol. 2007;99(7): 961–5. 46. Zimbarra Cabrita I, Ruisanchez C, Dawson D, et al. Right ventricular function in patients with pulmonary hypertension; the value of myocardial performance index measured by tissue Doppler imaging. Eur J Echocardiogr. 2010;11(8):719–24. 47. Meluzín J, Spinarová L, Bakala J, et al. Pulsed Doppler tissue imaging of the velocity of tricuspid annular systolic motion;

48.

49.

50.

51.

52.

53.

54.

55.

56.

57.

359

a new, rapid, and non-invasive method of evaluating right ventricular systolic function. Eur Heart J. 2001;22(4): 340–8. Moustapha A, Lim M, Saikia S, et al. Interrogation of the tricuspid annulus by Doppler tissue imaging in patients with chronic pulmonary hypertension: implications for the assessment of right-ventricular systolic and diastolic function. Cardiology. 2001;95(2):101–4. Severino S, Caso P, Cicala S, et al. Involvement of right ventricle in left ventricular hypertrophic cardiomyopathy: analysis by pulsed Doppler tissue imaging. Eur J Echocardiogr. 2000;1(4):281–8. Møller JE, Søndergaard E, Poulsen SH, et al. Color M-mode and pulsed wave tissue Doppler echocardiography: powerful predictors of cardiac events after first myocardial infarction. J Am Soc Echocardiogr. 2001;14(8):757–63. Wang M, Yip GW, Wang AY, et al. Peak early diastolic mitral annulus velocity by tissue Doppler imaging adds independent and incremental prognostic value. J Am Coll Cardiol. 2003;41(5):820–6. Redfield MM, Jacobsen SJ, Burnett JC Jr, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289(2):194–202. Hillis GS, Møller JE, Pellikka PA, et al. Noninvasive estimation of left ventricular filling pressure by E/e′ is a powerful predictor of survival after acute myocardial infarction. J Am Coll Cardiol. 2004;43(3):360–7. Dokainish H, Zoghbi WA, Lakkis NM, et al. Incremental predictive power of B-type natriuretic peptide and tissue Doppler echocardiography in the prognosis of patients with congestive heart failure. J Am Coll Cardiol. 2005;45 (8):1223–6. Lee CH, Hsieh MJ, Chu CM, et al. Prognostic significance of diastolic dysfunction by tissue Doppler imaging in patients with chronic heart failure. Am J Med Sci. 2009;337(6): 415–20. Mogelvang R, Sogaard P, Pedersen SA, et al. Cardiac dysfunction assessed by echocardiographic tissue Doppler imaging is an independent predictor of mortality in the general population. Circulation. 2009;119(20):2679–85. Rossi D, Pinna GD, La Rovere MT, et al. Prognostic significance of tissue-Doppler imaging in chronic heart failure patients on transplant waiting list: a comparative study with right heart catheterization. Eur J Echocardiogr. 2011;12(2):112–19.

CHAPTER 19 Speckle Tracking Echocardiography: Clinical Usefulness Shyam Padmanabhan, Siddharth Singh, Navin C Nanda

Snapshot  Cardiac Muscular Anatomy, Cardiac Mechanics  What is Strain?  Two-Dimensional Speckle Tracking

Echocardiography (2D STE)  Image AcquisiƟon and Processing

INTRODUCTION Traditionally, the assessment of left ventricular (LV) function has been made from an overall visual impression of LV thickening noted on multiple views on two-dimensional (2D) echocardiograms. Objective measurements such as fractional shortening on M-mode imaging and calculation of the ejection fraction (EF) based on the modified Simpson’s rule, although useful, often provide only a global estimation of LV function and are subject to interobserver and intraobserver variability. Operator experience also influences the visual assessment of LV function.1 Strain imaging, also called myocardial deformation imaging, is a technique developed in an attempt to standardize regional assessment of LV mechanics. The extent and the rate of deformation of a myocardial segment during the systolic and diastolic phases of the cardiac cycle was measured as changes in velocity of the respective myocardial segment along the axis of interrogation and was called tissue velocity imaging (TVI) or Doppler tissue imaging (TDI). Initially introduced in an effort to objectively quantify regional LV function, the application of TDI in clinical and research cardiology and cardiovascular imaging has grown exponentially.2 However, it does have limitations that stem from its basis as a Doppler technique. TDI measurements are highly dependent on the angle of

 Clinical ApplicaƟon of 2D STE  Three-Dimensional Speckle Tracking

Echocardiography (3D STE)  Clinical ApplicaƟons of 3D STE  LimitaƟons of Speckle Tracking Echocardiography

insonation and are highly limited by tethering: an akinetic segment may have normal velocities as it is dragged by a contracting segment.3 With growth in ultrasound technology, it has become possible to track speckles produced by interactions of ultrasound waves with the myocardium. Scatter echoes are produced as a result of reflection of ultrasound waves by myocardial fibers that are smaller than the wavelength of sound. They characteristically have lower amplitude than specular echoes and provide visualization of “grainy” myocardium between the epicardium and the endocardium in grayscale. Scatter echoes are also called speckles. Speckle tracking echocardiography (STE) filters out random noise produced by interaction of sounds waves with tissues, keeps the temporally stable speckles with their unique image pattern, and then tracks blocks of speckles from frame to frame using block matching. Speckle tracking is angle independent and overcomes some of the shortcomings of TDI (Table 19.1).

CARDIAC MUSCULAR ANATOMY, CARDIAC MECHANICS The pattern of myocardial fiber distribution and the sequence of events during ventricular contraction and

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

361

Table 19.1: Comparison of Tissue Doppler Imaging with Speckle Tracking for Evaluation of Strain

Tissue Doppler Imaging

Speckle Tracking

Dependent on angle of insonation

Angle independent

Can measure deformation only along one axis (axis of the transducer)

Can measure longitudinal, radial, and circumferential strain. Can also measure left ventricular twist mechanics

Movement assessed in relation to transducer

Movements assessed in relation to adjacent speckles

Higher frame rates and hence good temporal resolution

Lower frame rates and poor temporal resolution. Hence limited utility in tachycardic patients and in those with nonsinus rhythms

Limited spatial resolution

Better spatial resolution

Measures regional strain only

Both regional and global strain can be computed

Measures tissue velocity, strain is derived

Strain and strain rate can be measured directly

Influenced by translational motion

Less influenced by translational motion

Image quality less important

Relies on good image quality

Less reproducibility

Greater concordance among observers

Source: Adapted from Biswas M et al. Two- and three-dimensional speckle tracking echocardiography: clinical applications and future directions. Echocardiography. 2013;30(1):88–105.

A

B

Figs 19.1A and B: Schematic model and dissected heart model showing myocardial fiber arrangements. (A) depicts the apical and basal loops. The apical loop consists of an outer ascending segment (AS) with oblique counterclockwise fiber orientation and an inner descending segment (DS) with fibers oriented in an oblique clockwise direction. The basal loop covers the upper two-thirds of the apical loop and its fibers are oriented in a circumferential or transverse direction. It can be considered to have two segments: right (RS) and left (LS); (B) depicts the way the circumferential fibers of the basal loop wrap around the ascending and descending segments. Source: Reproduced from Buckberg G, Hoffman JI, Nanda NC, et al. Ventricular torsion and untwisting: further insights into mechanics and timing interdependence: a viewpoint. Echocardiography. 2011;28:782–804, with permission from Wiley-Blackwell). Movie clip 19.1B (courtesy of Gerald Buckberg, MD) shows how the heart can be considered as a long piece of muscle, which wraps on itself in a helical, figure of 8 orientation.

relaxation have been much debated. The helical model of myocardial fiber layout described by Torrent Guasp et al. describes the myocardium as a single band of muscular tissue that stretches from the pulmonary artery to the aorta, making two loops around a central axis—the double loop helical structure.4 This intricate arrangement of myocardial fibers results in complex LV mechanics during the cardiac cycle (Figs 19.1A and B). During the

systolic phase, longitudinal motion with the apex moving toward the base is associated with inward movement of the ventricular walls and differential rotation of the apex and the base. The opposite events are seen in diastole. While in systole the base rotates clockwise, the apex rotates counterclockwise. Untwisting occurs in diastole with opposite movements of the apex (clockwise) and base (counterclockwise).5

362

Section 2: Echocardiography/Ultrasound Examination and Training

Table 19.2: Different Types of Strain

Strain Type

Parameter Represented

Longitudinal strain (negative value)

Decrease in the longitudinal length of the ventricle during systole

Radial strain (positive value)

Thickening of myocardium during systole due to inward movement of LV measured in short axis

Transverse strain (positive value)

Thickening of myocardium during systole due to inward movement of LV measured in apical

Circumferential strain (negative value)

Change in length measured circumferentially around the perimeter of the ventricle

Rotational strain (clockwise: negative value, counterclockwise: positive value)

Rotational movement of myocardium along the long axis of ventricle

Twist and untwist

Difference in rotation between apex and base. During systole referred to as twist and during diastole referred to as untwist

(LV: Left ventricle). Source: Adapted from Biswas M, et al. Two- and three-dimensional speckle tracking echocardiography: clinical applications and future directions. Echocardiography. 2013;30(1):88–105.

WHAT IS STRAIN? Strain is a measure of myocardial deformation. It is dimensionless and is represented as a percentage or ratio. Strain (ε) is calculated by subtracting the resting myocardial fiber length (Lo) from that at the end of systole (L) and dividing it by the resting length (Lo) at end diastole. ε = (L – Lo)/Lo Shortening of the fiber during systole results in a negative value for strain, while lengthening results in a positive value for strain. The strain rate (ε′) is the myocardial deformation rate. It is expressed as seconds–1. It is less dependent on LV load variations than strain.6 However, because the strain rate signal is noisier and less reproducible, most clinical studies still use strain measurements. LV contraction involves myocardial motion along three-dimensional (3D; x, y, and z) co-ordinates and results in a variety of strain parameters that can be derived for each myocardial segment. Interestingly by virtue of moving in 3D space, each myocardial segment can be described as having strain in three planes (x, y, and z) and six shear stresses. However for practical purposes, linear strains are widely used for research purposes. Radial or transverse strain refers to thickening of the wall of the LV during systole. Since wall thickness normally increases, the measured strain is a positive value. It is typically measured in parasternal short-axis basal and

apical views. Prior studies based on Doppler strain echocardiography found normal volunteers to have radial strain >44.5%.7 Longitudinal strain represents shortening of the LV from base to apex during systole and is usually measured in any of the long-axis views. It follows that it has a negative value. Longitudinal strain increases from base (–15%) to apex (–20%). Lower limit of –18.5% may be appropriate for global longitudinal strain in normal volunteers.8 Circumferential strain is measured using kernels placed along the circumference of the myocardium in parasternal short-axis views and has a negative value. In normal volunteers, it increases from base through apex (–28% to –33% to –35% from base to mid to apex). Different types of strain are shown in Table 19.2 and Figures 19.2 to 19.6. Normal values for strain in normal adults are shown in Table 19.3. Parameters of rotational strain that take into account rotation of the heart have also been described. With LV contraction, the cardiac apex and the base move in counterclockwise and clockwise directions, respectively, when viewed from the apex. Conventionally, clockwise rotations carry a negative value and counterclockwise rotations are assigned a positive value. Twist represents the mathematical difference in the rotation of the apex and base during these phases: Twist = Apex – (–Base) In normal controls, apical rotation is 6° and basal rotation is –6°, producing a twist of 12°.

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

363

Fig. 19.2: Radial strain. Shows radial thickening of the myocardium during systole. In the end-diastolic frame on the left, the myocardial thickness is 1.6 cm and increases to 2.3 cm in end systole as depicted on the right; hence, the radial strain will be +43.7% (Movie clip 19.2) (Figure and movie clip courtesy of Toshiba Medical Systems Europe BV).

Fig. 19.3: Transversal strain. The calculations are similar to radial strain, except that the measurements are done using apical views.

Fig. 19.4: Longitudinal strain. Shows shortening of ventricular length during systole. The figure on the left denotes end diastole and the one on the right depicts end systole. Note the downward descent of the mitral annulus toward the apex in systole. There is a reduction in length by 2 cm, which is a 25% decrease. As there is a decrease in the longitudinal length, it will be denoted by a negative (–) sign; hence the longitudinal strain will be –25% (Movie clip 19.4). (Figure and movie clip courtesy of Siemens Ultrasound).

Fig. 19.5: Circumferential strain. This refers to the change in the circumference of each segment as denoted by the dotted yellow line in the figure. There is a 25% reduction in the circumferential length in end-systole from the baseline end-diastole; hence the circumferential strain will be –25% (Movie clip 19.5) (Figure and movie clip courtesy of Toshiba Medical Systems Europe BV).

When twist is normalized to the length of the LV cavity (vertical distance between apex and base), it is referred to as torsion (degrees/cm). Previously LV twisting could only be measured using magnetic resonance imaging (MRI).

However, STE has allowed measurement of LV twisting (Fig. 19.7), and measurements have been validated against MRI.9 Normal rotation and torsion values are shown in Table 19.4.

364

Section 2: Echocardiography/Ultrasound Examination and Training

Table 19.3: Mean Percentage Strain Values by Left Ventricular Region in Normal Adults

Longitudinal strain

Apical septal 21 ± 4

Circumferential strain Anterior 24 ± 6 Radial strain

Mid septal 19 ± 4

Basal septal 17 ± 4

Lateral 22 ± 7 Posterior 21 ± 7

Apical lateral 21 ± 7

Mid lateral 19 ± 6

Basal lateral 19 ± 6

Inferior 22 ± 6

Septal 24 ± 6

Anteroseptal 26 ± 11

Anterior 39 ± 16 Lateral 37 ± 8 Posterior 37 ±1 7 Inferior 37 ± 17 Septal 37 ± 19 Anteroseptal 39 ± 15

Source: Reproduced with permission from Hurlburt HM, Aurigemma GP, Hill JC. Direct ultrasound measurement of longitudinal, circumferential, and radial strain using 2-dimensional strain imaging in normal adults. Echocardiography. 2007;24:723–31.

Table 19.4: Normal Rotation and Torsion in Young Adults

Peak apical rotation (°)

10.1 ± 1.9

Peak apical rotation rate (°/s)

61.6 ± 25.3

Peak basal rotation (°)

4.9 ± 2.0

Peak basal rotation rate (°/s)

44.2 ± 17.8

Source: Reproduced with permission from Takahashi K, Al Naami G, Thompson R. Normal rotational, torsion and untwisting data in children, adolescents and young adults. J Am Soc Echocardiogr. 2010;23:286–93.

Fig. 19.6: Different patterns of strain obtained by two-dimensional speckle tracking echocardiography are schematically depicted. (Courtesy of Dr Shemy Carasso, Rambam Healthcare Campus and Israel Institute of Technology, Haifa, Israel).

Growing attention has also been recently given to the role of untwisting in diastolic LV filling mechanics. Untwisting velocity is thought to be an important initial manifestation of active relaxation. It seems to be less dependent on load compared to other diastolic parameters.10 The regional strains for different segments of the myocardium can further be combined to generate global myocardial strain. While it is commonplace to calculate

Fig. 19.7: Depicts the differential rotational movements of left ventricular apex and the base. In the normal individual, the apex rotates more than the base. By convention, counterclockwise motion is assigned a positive (+) sign and clockwise motion a negative (–) sign. In the above example, the apex rotates 20° in counterclockwise direction from end diastole (point A) to end systole (point B); hence the rotation of the apex will be +20°. As the base rotates at the same time 10° clockwise from point C to D, the rotation of the base will be –10°. “Twist” is calculated as the algebraic difference in the rotation of the apex and base; in other words, how far apart a point in the apex and base move from each other. In the above example, the twist will be apex rotation (20°) minus base rotation (–10°), that is, 20 – (–10) = +30°. Twist can be calculated for any point in the myocardium compared to a reference basal point. “Torsion” is a way of adjusting for the distance of a point of interest from the reference point in the base, as it is expected that the twist will be higher for the segments farther away from the base. Torsion = twist/the distance from the base or distance between any two points that are evaluated. In the above example, the torsion, calculated between apex and base, would be 30/8 = 3.75°/cm. As would be expected, the middle portion of the left ventricle would not show any rotation. This is illustrated in the accompanying Movie clip 19.7 (Part 2). Movie clip 19.7 (Part 1) shows clockwise rotation of the left ventricular base during systole, followed by counterclockwise rotation in diastole (Figure and movie clip courtesy of Toshiba Medical Systems Europe BV).

regional and global strain for the LV, it can also be derived for structures such as the right ventricle (RV), left and right atria, although these are not adequately validated.

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

Other types of strain not routinely in use in echocardiographic assessment are Lagrangian strain, natural strain, and shear strain.11 Decrease in peak strain usually indicates segmental dysfunction. Analysis of time to peak strain (measured from the beginning of the QRS complex or end diastole to the end of systole) in various segments can be used to measure ventricular dyssynchrony. Segmental variation in time to peak strain may represent regional dyssynchrony and can be used to predict response and assist in cardiac resynchronization therapy (CRT). Occasionally, peak strain occurs after closure of the aortic valve. This postsystolic contraction may be representative of myocardial ischemia. These concepts are described in more detail later in the text.

TWO-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY (2D STE) The interaction of the ultrasound beam with the myocardium results in grayscale digital images formed

365

by small dots also known as speckles. With the help of postprocessing computer algorithms, groups of speckles form a specific pattern (kernel) on the myocardium and can be tracked throughout the cardiac cycle (Fig. 19.8). Analysis of the temporal and sequential relationship of these speckles within a user-defined area can yield velocity vectors (Fig. 19.9) and strain data. Also, several such areas can be simultaneously studied allowing a comparative analysis of regional myocardial motion. The information obtained can also be used to generate a graph depicting the change in myofiber length over the duration of the cardiac cycle. The speckle tracking software uses different algorithms that are both vendor dependent and vendor independent.12 Velocity vector imaging, analogous to 2D STE, also tracks the speckles using 2D echocardiography, but utilizes additional physiological information to more robustly track the speckle kernels (Fig. 19.9).13 Examples showing measurement of strain using velocity vector imaging are shown in Figures 19.10 and 19.11. TDI and STE are different in many aspects (Table 19.1). STE requires that high-quality 2D or 3D images be

Fig. 19.8: Speckle tracking imaging. Left ventricular short-axis view showing frame-by-frame tracking of a large group of pixels (denoted by a circle). Courtesy: Toshiba Medical Systems Europe BV.

Fig. 19.9: Velocity vector imaging. Apical four-chamber view: the direction of the arrows indicates the direction of the movement of the left ventricular myocardium, and the length of the arrows indicates the velocity of such movement. This is also shown in Movie clip 19.3 (Part 1). Movie clips 19.3 (Part 2) and 19.2 (Part 3) show velocity vectors obtained separately from the left ventricular endocardium and epicardium. [Figure 19.9 and Movie clip 19.9, Part 1, reproduced from Buckberg G, Hoffman JI, Nanda NC, et al. Ventricular torsion and untwisting: further insights into mechanics and timing interdependence: a viewpoint. Echocardiography. 2011;28:782–804, with permission from Wiley-Blackwell. Movie clips 19.9 (Parts 2 and 3), courtesy of Siemens Ultrasound].

366

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 19.10: Shows radial and circumferential strain (A) and longitudinal strain rate; (B) from different segments using velocity vector imaging. The left panel also depicts global peak strain and maximum wall delay (courtesy of Siemens Ultrasound).

Fig. 19.11: Shows longitudinal strain rate from different segments using velocity vector imaging. The negative peak systolic strain rate is highlighted. (Ac: Aortic valve closure; Ao: Aortic valve opening; Mc: Mitral valve closure; Mo: Mitral valve opening). (courtesy of Siemens Ultrasound).

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

produced at high frame rates (60–110 Hz) with high spatial resolution. STE is independent of angle of insonation and mostly unaffected by translational motion and tethering in contrast to TDI. STE has been validated in several studies using sonomicrometric studies, hemodynamic studies, TDI, and tagged MRI. Reproducibility of the data with STE was noted to be better than TDI.14

IMAGE ACQUISITION AND PROCESSING To permit assessment of strain values by speckle tracking, gated images during end expiratory breathhold of good quality without foreshortening are needed. Optimal frame rate is about 60 to 110 frames/s. Lower frame rates hinder temporal resolution and lead to poor tracking of the endocardial border. Higher frame rates are not optimal as well, as speckles may not change enough from frame to frame. Apical four-chamber, two-chamber, and three-chamber views are used to estimate LV and RV longitudinal and transversal strains and strain rates by 2D STE. Parasternal short-axis views are used to estimate radial and circumferential strains and rotation, twist and torsion. For timing of cardiac events, mitral inflow and LV outflow velocities are recorded using pulsed Doppler echocardiography, and the aortic and mitral valve closure times are obtained from this. Images can be analyzed either offline or on cart using software available from various vendors. Region of interest and endocardial border are traced manually. Automatic edge detection is available to trace epicardium, but the wall thickness and trace can be adjusted. The way segments are divided varies between vendors; but all vendors use a 16- to 18-segment model. Some softwares enable users to reject segments that have not tracked optimally from the analysis.

CLINICAL APPLICATION OF 2D STE Although there is extensive literature on the clinical applications of STE, it is yet to be used in routine clinical decision making and remains largely a research tool providing insights into pathophysiological mechanisms in cardiovascular diseases. STE may have a clinically meaningful role in detecting subclinical cardiac involvement in various disorders where estimation of left ventricular ejection fraction (LVEF) and chamber size by 2D or 3D echo yields normal results. By early detection of cardiac involvement, therapeutic strategies to prevent additional myocardial damage could be instituted, and this may improve outcomes.

367

Potential clinical applications are discussed below (summarized in Table 19.5).

Coronary Artery Disease (CAD) Since CAD affects both regional and global function of the LV, STE demonstrates subtle variations in both regional and global strain before obvious visual manifestations appear in the form of wall motion abnormalities. Moreover, ischemic wall motion abnormalities are often associated with passive wall motion, and it may be difficult to distinguish active contraction from passive motion or “tethering” by visual examination or TDI. Use of STE has expanded the ability of echocardiography to detect and objectively quantify patterns of ischemia. Although longitudinal, radial, and circumferential strains may all be affected in the ischemic cascade, longitudinal strain is one of the earliest to be affected due to the subendocardial location of the longitudinal fibers. Reduction in longitudinal peak systolic strain as detected by STE was present before a visual decrement in LV function was observed in patients with severe CAD.15 When there is associated LV dysfunction, peak strain may be diminished. An interesting phenomenon that is being increasingly studied with the help of STE is postsystolic contraction (PSC). This is defined as myocardial contraction occurring after the closure of the aortic valve. Although occasionally seen in normal hearts, it has been shown to be a sensitive indicator of myocardial ischemia.16 Several mechanisms have been proposed to explain this phenomenon including passive recoil or stretching of dyskinetic segments and active contraction of hypokinetic and akinetic segments.17 Claus et al. described inhomogeneity in the passive thickening of neighboring myocardial segments due to elastic interaction as the etiological mechanism for PSC.18 Altered myocardial fatty acid metabolism due to ischemia has also been implicated in the mechanism of PSC.19 PSC is mainly seen in acute ischemia and myocardial stunning and is thought to be proportional to the severity of ischemia (Fig. 19.12). 2D STE has also been used to improve the sensitivity of dobutamine stress echocardiography in detecting regional wall motion abnormalities in patients with inducible ischemia.6,20 Using longitudinal strain with dobutamine stress echocardiography may also have a role in predicting viable segments.21 Early work has also shown that in ischemic cardiomyopathy, areas of scarring on contrastenhanced MRI have lower longitudinal strain values than normal areas (–10.4 ± 5.2% compared with 0.6 ± 4.9% in segments with transmural scarring; p < 0.01).22

368

Section 2: Echocardiography/Ultrasound Examination and Training

Table 19.5: Clinical Conditions where Two-Dimensional Speckle Tracking is Useful

1.

Myocardial ischemia

Reduction in strain by 2D STE more objective and accurate than the traditional visual method of assessing WMA Longitudinal, radial, and circumferential strain reduced in ischemic areas in coronary artery disease Postsystolic thickening (deformation), detected by radial strain correlates with the severity of ischemia

2.

Myocardial infarction

2D STE successful in differentiating transmural from subendocardial infarction by showing lower circumferential strain in the former Reduced subendocardial LV twist also noted in patients with ST-segment elevated myocardial infarction Decreased LV torsion and segmental longitudinal strain predicts progressive LV dilatation after myocardial infarction

3.

Myocardial viability

Strain measurements by 2D STE more objective and accurate than visual WMA for assessment of myocardial viability during low-dose dobutamine stress echocardiography. 2D STE differentiates active contraction from passive motion due to tethering

4.

Heart failure with normal LVEF

Reduced and delayed LV untwisting—at rest and exercise

5.

Cardiac resynchronization therapy (CRT)

Combining longitudinal strain from TDI velocity with 2D STE radial strain may help in predicting response to CRT Longitudinal strain delay index (calculated from the difference between peak and endsystolic strain) of >25% predicts response to CRT (sensitivity 95%, specificity 83%) Speckle Tracking and Resynchronization (STAR) study showed that radial and transversal strain were better than longitudinal and circumferential strain in predicting LVEF response and long-term survival after CRT Lack of dyssynchrony before CRT by 2D STE radial strain associated with death or hospitalization for heart failure

6.

Stress cardiomyopathy

Impaired longitudinal strain noted particularly in apical and midventricular segments

7.

Restrictive cardiomyopathy

Impaired longitudinal deformation and twist mechanics are noted

8.

Constrictive pericarditis

Impaired LV circumferential deformation and torsion

9.

Detection of rejection and coronary stenosis in heart transplant patients

Sudden reduction of ≥15% in global radial strain associated with acute rejection. Decrease in strain and strain rate at rest and with dobutamine stress echo also useful to detect significant coronary stenosis

10. Early detection of chemotherapyinduced cardiotoxicity

Reduction in radial strain may occur before reduction in LVEF and associated with histologic changes

11. Detection of subclinical diseases/early myocardial involvement

Reduction in strain may occur before changes in LVEF in systemic hypertension, diabetes mellitus, systemic sclerosis, amyloidosis, Duchenne’s muscular dystrophy, and Kawasaki syndrome

12. Valvular heart disease

Decreased radial, circumferential, and longitudinal strain in patients with severe aortic stenosis and normal LVEF. Long-term follow-up after valve replacement showed significant improvement with no change in EF Reduced preoperative 2D STE longitudinal strain in the ventricular septum (apical four-chamber view) predicts a postoperative LVEF decrease of ≥10% in patients with chronic severe mitral regurgitation

13. Congenital heart disease

Atrial septal defect—basal clockwise rotation during systole is reduced Tetralogy of Fallot—right ventricular global longitudinal strain and strain rate is decreased significantly

(2D: Two-dimensional; EF: Ejection fraction; LV: Left ventricle; LVEF: Left ventricular ejection fraction; TDI: Tissue Doppler imaging; STE: Speckle tracking echocardiography; WMA: Wall motion abnormalities). Source: Reproduced with permission from Biswas M, et al. Two- and three-dimensional speckle tracking echocardiography: clinical applications and future directions. Echocardiography. 2013;30(1):88–105.

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

Fig. 19.12: An example of the display of information by a commercial software. The graph on the right side of the figure displays longitudinal strain values from a single cardiac cycle. Different myocardial segments are denoted by different colors of the curves. The dotted vertical green line indicates end-systole. As normal longitudinal strain is denoted by a negative sign, normal longitudinal strain curves would be plotted below the baseline with negative values and they would peak in end systole. However, in this example, some curves are abnormal. For instance, the light green curve (yellow arrowhead) representing the midinferolateral segment (MIL) of the left ventricle is located above the baseline indicative of wall thinning during systole. The peak strain value can be read from the graph and in this case is abnormal at around +6%. Also, the purple curve (green arrowhead) representing the basal inferoseptal segment peaks way beyond end systole and during diastole indicating postsystolic thickening. This finding is frequently associated with myocardial ischemia. All the values and curves shown in the illustration were obtained using 3D echocardiography (Movie clip 19.12).

Cardiac Resynchronization Therapy for Heart Failure (HF) Ventricular dyssynchrony is a well-known cause and result of LV dysfunction. CRT is a Class I recommendation for Stage III and ambulatory Stage IV patients with advanced heart failure, LVEF ≤ 35%, and QRS duration >120 milliseconds on optimal medical therapy. Unfortunately, 30% to 50% patients who get CRT fail to respond with improvement in symptoms. In the multicenter PROSPECT trial, none of 12 conventional and tissue Doppler-based echocardiographic indices of dyssynchrony was shown to be a reliable predictor of the response to CRT. This led to tempered enthusiasm about using echo-derived indices to guide decision making about CRT placement and positioning of LV lead.

369

In the last few years, emerging literature has suggested that indices derived from speckle tracking may have a role in predicting response to CRT.23 Various parameters of strain analysis including longitudinal, radial, circumferential, and rotational strain have been used to outline the LV activation sequence and make an objective assessment of LV dyssynchrony in patients with heart failure and consequently achieve an optimal LV lead positioning during CRT for HF (Figs 19.13 and 19.14).24,25 Becker et al. demonstrated greater improvement in LV function and LV remodeling when circumferential strain analysis was used for optimal lead positioning in CRT.26 STE has been used to predict the response to CRT in a variety of studies.27 In the first prospective study using speckle tracking for CRT use (Speckle Tracking and Resynchronization—STAR), Tanaka et al. showed that response to CRT was more strongly related to radial and transverse strain rather than longitudinal and circumferential strain.28 Ongoing studies will serve to establish or refute utility of STE in guiding decision making about CRT.

Cardiomyopathies Excellent correlation between global longitudinal strain and LVEF29 has been noted in several studies. Moreover, strain analysis also permits recognition of subclinical regional or global myocardial dysfunction in patients with preserved LVEF. For example, studies have shown that radial and longitudinal strain are both impaired in patients with concentric LVH and hypertension. However, circumferential strain and LV torsion are well preserved. This compensation allows LVEF to remain in the normal range,30 in the initial stages of hypertensive cardiomyopathy. STE may also permit early detection of subclinical cardiac involvement in diseases like diabetes mellitus, Duchenne’s muscular dystrophy, systemic sclerosis, and Kawasaki syndrome.31–34 STE has also provided insights into the pathophysiological mechanisms underlying myocardial dysfunction in disorders such as Takotsubo’s cardiomyopathy (stressinduced cardiomyopathy). Burri et al. from our institution showed that not only radial systolic dysfunction, but also systolic and diastolic longitudinal dysfunction are seen particularly in the apical and midventricular segments of patients with Takotsubo’s cardiomyopathy, which was largely reversible.35 Lower longitudinal strain values have also been found in patients with cardiac amyloidosis. It has also been

370

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 19.13A and B: Schematic showing dyssynchronous left ventricular contraction depicted by radial strain. Note the time difference between peak strain of the posterior wall and ventricular septum denoted by the yellow arrow. The peak strain or contraction of the posterior wall is much delayed in comparison with the septum (A). The goal of resynchronization therapy is to get the peak strains (contractions) as close as possible to each other as depicted in (B). (ES: End-systole).

A

B

Figs 19.14A and B: (A) Normal individual. Left: color-coded, two-dimensional speckle tracking echocardiographic radial strain in a normal individual. Top left: homogeneous color coding during systole without segments of delayed contraction (6 segments, counterclockwise: ant. sept, anteroseptal; ant, anterior; lat, lateral; post, posterior; inf, inferior; sept, septal). Bottom left: color-coded map representing strain as relative wall thickening of individual segments in red colors of different brightness related to the cycle time period and demonstrating peak strain in end-systole without delay between each of the segments; arrow = peak strain, segments represented by colored lines. Right: corresponding radial strain curves are lined up during the cycle indicating no evidence of dyssynchrony; (B) Dilated cardiomyopathy. Left: color-coded speckle tracking echocardiography representing delayed contraction posteriorly. Right: corresponding segmental radial strain curves. The time delay between the ventricular septum (red curves) and the lateral wall (green curve) is 340 milliseconds, representing distinct dyssynchrony. (AVC: Aortic valve closure). Source: Reproduced from Nesser HJ, Winter S. Speckle tracking in the evaluation of left ventricular dyssynchrony. Echocardiography. 2009;26;324–36, with permission from Wiley-Blackwell.

suggested that lower longitudinal strain values may help identify patients with subclinical cardiac amyloidosis (using biopsy as the gold standard).31 LV mechanics in patients with constrictive pericarditis have demonstrated normal longitudinal LV strain with abnormal rotational mechanics due to tethering of the

myocardium by the pericardium. This was in contrast to preserved LV twisting with abnormal longitudinal strain in patients with restrictive cardiomyopathy.36 2D STE may also be able to distinguish between the various types of cardiac hypertrophy, both physiological and pathological (hypertrophic cardiomyopathy, athlete’s

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

371

Table 19.6: Differentiation of Athlete’s Heart from Hypertrophic Cardiomyopathy Using Speckle Tracking

Athlete’s Heart

Hypertrophic Cardiomyopathy

Normal longitudinal and other types of strain

Decreased longitudinal strain

Increased LV EDV

Decreased LV EDV

Decreases after deconditioning for 3 months

No change with deconditioning

Increased LV twist

Delayed LV untwisting

Increased early LA strain rate

Reduced LA strain and strain rate

No postsystolic thickening

Postsystolic thickening present

(EDV: End-diastolic volume; LA: Left atrium; LV: Left ventricle). Source: Reproduced with permission from Biswas M, et al. Two- and three-dimensional speckle tracking echocardiography: clinical applications and future directions. Echocardiography. 2013;30(1):88–105.

heart, and hypertensive heart disease; Table 19.6).37 In the case of athlete’s heart, longitudinal, radial, and circumferential strain are normal, with increased LV twist and increased LA strain. In hypertrophic cardiomyopathy, there is decreased longitudinal strain and delayed LV untwisting and reduced LA strain and strain rate.14,37–41 Moreover, investigators using TDI strain have also shown that longitudinal strain in midseptum in patients with hypertrophic cardiomyopathy is significantly lower than in apical and basal segments, and in many patients it may be positive (termed paradoxical systolic expansion).42 This latter finding has not been verified using strain with speckle tracking. Regional peak longitudinal speckle tracking strain may be able to distinguish fibrotic from nonfibrotic myocardium in patients with hypertrophic cardiomyopathy and normal LV myocardium in healthy controls.43 STE may also have a role in early detection of cardiac involvement in relatives of patients with hypertrophic cardiomyopathy. Subtle abnormalities in diastolic function are present in genotype+, phenotype– relatives of patients with hypertrophic cardiomyopathy. Although results from speckle tracking studies to detect myocardial involvement have shown increased peak late diastolic annular velocities in genotype+ phenotype– carriers, overlap among carriers and controls does not permit determination of cutoffs to permit distinction of affected individuals based on strain parameters at present.44

Cardiac Transplantation STE has also been used to evaluate allograft function in transplant recipients and for the assessment of rejection. Myocardial deformation imaging has been used for early detection of chronic allograft vasculopathy both by TDI45 and by the application of 2D STE in combination

with dobutamine stress echocardiography (positive and negative predictive values 90–95% and 91–97%, respectively).46 While endomyocardial biopsy still remains the gold-standard for diagnosis of allograft rejection, preliminary research has evaluated the role of STE as a reliable noninvasive diagnostic modality to identity rejection. Abnormal twist mechanics as evidenced by a 25% decrease in LV torsion from baseline was able to diagnose allograft rejection (ISHLT Grade 2) with a sensitivity of 73.7%, specificity of 95.1% and a positive predictive value of 92.9%.47

Valvular Heart Diseases Strain analysis using 2D STE has also been useful in the evaluation of myocardial function in patients with valvular heart diseases. It is possible to identify subtle LV dysfunction as seen by diminished longitudinal, radial, and circumferential strain in patients with severe aortic stenosis long before a visible decrease in LVEF. Surgical correction of aortic stenosis has also resulted in the improvement of all the three strain variables.48 In patients with chronic severe mitral regurgitation, 2D STE was able to predict a postoperative drop of LVEF of 10% when longitudinal strain rate assessed at the level of the midventricular septum was less than 0.8 s–1 (sensitivity, 60%; specificity, 96.5%).49

Chemotherapy Cardiotoxicity An area where strain imaging has shown tremendous potential is in the early detection of cardiotoxicity of targeted chemotherapy agents. Ho et al. showed that breast cancer survivors who had received Traztuzumab showed lower global longitudinal strain values than controls (18.1 ± 2.2% vs 19.6 ± 1.8%; p = 0.0001).50 LVEFs between the two groups were similar. At present, the feasibility of using strain with STE to follow patients receiving

372

Section 2: Echocardiography/Ultrasound Examination and Training

potentially cardiotoxic chemotherapies remains to be seen. Cut offs for strain values to detect clinically meaningful reduction in myocardial systolic function also need to be determined.

Congenital Heart Disease and Right Ventricular Function Global and regional RV function can also be evaluated in patients with pulmonary arterial hypertension (PAH). This may assume importance especially as most current methods to measure RV function using 2D echocardiography are at best qualitative. Peak systolic strain and strain rate of the RV basal wall can be used to reliably assess RV function in patients with PAH. STE in these patients is less affected by myocardial tethering, translation, and cardiac rotation and hence offers an advantage over TDI.51 STE has also provided broader insights into the pathophysiological mechanisms of congenital heart diseases and response to therapy. Dong et al. demonstrated that in patients with secundum atrial septal defect, while LV apical torsional deformation was preserved, there was significant decrease in basal LV systolic twist and time to peak twist.52 This was attributed to heterogenous basal rotation. They also demonstrated that following transcatheter closure, there was considerable improvement in systolic LV twist, while diastolic untwisting was unchanged.53 STE has also been used to objectively assess global RV function in patients with tetralogy of Fallot.54

Role of Rotational Dynamics Twist decreases to about half the normal, that is, around 6°, in patients with hypertrophic cardiomyopathy (nonapical variants). In these patients, the midventricle rotates clockwise instead of counterclockwise.55 Twist is even lower in patients with dilated cardiomyopathy (Fig. 19.15) and advanced heart failure. Twist increases markedly in patients with diastolic dysfunction from hypertension and apical variant of hypertrophic cardiomyopathy.56,57 It is hypothesized that the increase in twist (or rotational strain-torsion) is a compensatory mechanism to preserve cardiac index in these conditions. Interesting literature sheds light on the link between untwisting rate and diastolic function. Notomi et al. showed that peak untwisting rate was significantly related to tau and peak intraventricular pressure gradient in animal studies. Other investigators have shown that

Fig. 19.15: Two-dimensional apical and basal left ventricular (LV) rotation and twist curves versus time, from (A) a healthy control; (B) a patient with dilated cardiomyopathy (DCM) without LV dyssynchrony, and; (C) a patient with DCM with LV dyssynchrony. In the two patients with DCM, apical and basal rotations and LV twist in turn were decreased. In addition, in the patient with DCM with LV dyssynchrony, apical and basal rotations were temporally discoordinate and away from aortic valve closure (AVC). As a result, peak LV twist and LV twist at AVC were severely diminished. (ECG: Electrocardiogram). Source: Reprinted from Sade LE, Demir O, Atar I, et al. Effect of mechanical dyssynchrony and cardiac resynchronization therapy on left ventricular rotational mechanics. Am J Cardiol. 2008;101:1163–9, 2008, with permission from Elsevier).

reduced and delayed untwisting correlates with diastolic dysfunction seen in STEMI patients and in heart failure patients at rest and with exercise.58–62

THREE- DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY (3D STE) 3D STE images are acquired by postprocessing software algorithms similar to those for 2D STE. In the case of 3D STE, since a larger pyramidal volume of the heart is imaged as opposed to a thin slice in 2D STE, the speckle is tracked with better spatial resolution providing more reliable strain data (Figs 19.16A and B). Also newer 3D echocardiography machines are able to obtain the full pyramidal volume in a single beat in comparison, which permits analysis of most segments simultaneously and saves time. More accurate assessment of the ventricular geometry and dimensions are feasible as the user is now able to identify the longest diameter in two long-axis images perpendicular to each other allowing accurate assessment of ventricular segments.63,64 Compared to 2D STE, 3D STE provides better temporal and spatial resolution.

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

A

373

B

Figs 19.16A and B: Advantage of three-dimensional speckle tracking echocardiography over the two-dimensional (2D) technique. (A) As 2D echocardiography represents only a thin slice through the cardiac structures, it is easy for the speckle particle to move out of the scanning plane as the heart moves, making it difficult or impossible to track the same speckle during the cardiac cycle; (B) On the other hand, with the three-dimensional (3D) technique, a much larger pyramidal-shaped section is obtained, making it more difficult for the speckle particle to move out of the 3D data set (courtesy of Toshiba Medical Systems Europe BV).

Studies with 3D STE in normal subjects have shown slightly lower longitudinal strain and slightly higher circumferential strain values than those seen with 2D STE.8 Other strain measurements that have been described with 3D STE include transversal strain, 3D strain, and area strain (Figs 19.17A to C). Transversal strain is measured in a direction perpendicular to the applied load. Simplistically speaking, it is similar to radial strain in apical long-axis views. 3D strain tracks speckles in three dimensions and is theoretically superior to other kinds of strain measurements as it is independent of geometric assumptions. Area strain is obtained in 3D STE by combined assessment of longitudinal and circumferential strain (Fig. 19.18). Since longitudinal and circumferential strain are both negative, area strain also has a negative value.65 Normal values for area strain in adults are shown in Table 19.7. 3D STE has been used in several clinical scenarios. In a study comparing both 2D and 3D STE with MRI, all 3D strain parameters were noted to be lower in patients with transmural infarcts in comparison to patients with nontransmural infarcts and controls. Also, while all 3D strain parameters correlated with LV function, only longitudinal and area strain correlated with infarct size.66 In another study done by Abate et al. a segmental 3D longitudinal strain >11.1% was reliably able to predict functional recovery of the LV after myocardial infarction (sensitivity 92% and specificity 91%).67

CLINICAL APPLICATIONS OF 3D STE 3D STE may have its most important role in the determination of dyssynchrony in patients being evaluated for CRT. Pyramidal data sets generated with 3D echo permit division of the entire LV into 16 segments. Time– strain curves, polar maps, and 3D maps can be generated. Maximum opposing wall delay by 3D STE significantly correlates with 2D STE measures. The main advantage of 3D STE over 2D STE is more precise mechanical activation mapping, which shows the site of latest ventricular activation with more accuracy. Tanaka et al. used time to peak maximal radial strain on 3D STE to identify sites of delayed LV activation. By representing them on colorcoded bull’s eye plots containing the 16 segments of the LV, they proposed that this would help in identifying optimal lead positioning for CRT.68 Kleijn et al. using the systolic dyssynchrony index (SDI) for 16 LV segments calculated with the help of 3D STE, were able to predict response to CRT in eligible heart failure patients with a sensitivity and specificity of 93% and 75%, respectively.69 Baccouche et al. utilized variations in the LV twist mechanics to distinguish patients with cardiac amyloidosis from hypertrophic cardiomyopathy. Patients with cardiac amyloidosis had significantly diminished basal rotational strain with increased apical rotation contrary to patients with hypertrophic cardiomyopathy who retained the physiological pattern of increased

374

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C Figs 19.17A to C: Three-dimensional (3D) strain imaging based on speckle tracking in a healthy volunteer. (A) First step is to image either an apical four- or five-chamber view (labeled A). The system then automatically calculates and presents an orthogonal plane (labeled B) and three short-axis planes labeled C1, C2, and C3 taken at apical, mid-ventricular, and basal levels, respectively; (B) Threedimensional circumferential strain imaging, based on speckle tracking in a healthy volunteer. Left panel: after determination of three endocardial points including the apex, the inner and outer borders of LV myocardium are plotted automatically, but these can be corrected manually. Based on changes in speckle location in the 3D data set, left ventricular end diastolic (EDV) and end systolic (ESV) volumes and ejection fraction (EF) are calculated by the computer and shown as numerical data on the screen. Right panel: circumferential strain curves are lined up indicating no evidence of dyssynchrony; (C) Three-dimensional circumferential strain imaging based on speckle tracking in a healthy volunteer. Dynamic polar map. Left panel: lack of colorization represents end diastole. Right panel: homogenous color coding in red, representing synchronous contraction of basal, midventricular, and apical segments: ant-sept, anteroseptal; ant, anterior; lat, lateral; post, posterior; inf, inferior; sept, septal. Source: Reproduced from Nesser HJ, Winter S. Speckle tracking in the evaluation of left ventricular dyssynchrony. Echocardiography. 2009;26;324–36, with permission from Wiley-Blackwell.

basal radial strain in comparison to apical radial strain (sensitivity 83%).70 They also utilized 3D STE to assess and monitor clinical improvement in patients with Takotsubo’s cardiomyopathy.71 Other applications include evaluating LV function in patients following transcatheter aortic valve replacements72 and assessment of RV function before and after atrial septal defect closure with 3D volumetry and myocardial strain analysis as predictors of unfavorable outcomes.73

Potential clinical applications of 3D STE are shown in Table 19.8.

LIMITATIONS OF SPECKLE TRACKING ECHOCARDIOGRAPHY 2D STE as mentioned above has tremendous clinical and research applications. However, its routine application in day-to-day clinical practice has been limited due to several

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

Fig. 19.18: Area strain by three-dimensional speckle tracking echocardiography from different left ventricular endocardial segments. The values are negative and the different colored curves from various segments are plotted below the baseline. This is because area strain is a combination of circumferential and longitudinal strain, both of which result in shortening and are denoted by negative values. Note that the peak circumferential strain is delayed and also reduced in some segments (around –16 to –19%) as compared with others (–26 to –37%); Movie clip 19.18. (Figure and Movie clip courtesy of Toshiba Medical Systems Europe BV). Movie clips for Figures 19.1B, 19.3 (Parts 1, 2, and 3), 19.2, 19.4, 19.5, 19.7 (Parts 1 and 2), 19.9, and 19.18. Movie clip 19.19 Two-dimensional intraventricular flow analysis from an apical long-axis view with a small amount of echo contrast agent (Definity), imaged with harmonic frequencies that have been tracked over time using echo-specific particle imaging velocity software. Direction and relative speed of the contrast agent is displayed as vectors. The resulting patterns represent blood motion in two dimensions in the left ventricle. This differs from color Doppler assessment, which is only one-dimensional. This kinetic circular motion of blood in the ventricle is referred to as vorticity (movie clip courtesy of Siemens Ultrasound, Mountain View, CA). Movie clip 19.20 Three-dimensional left ventricular simulated flow assessment from computerized tomography of the heart. Flow direction and speed are derived from mathematical algorithms and blood tissue boundary conditions. Flow patterns are displayed with a smoke-like appearance. (courtesy of Siemens Corporate Research, Princeton, NJ). Table 19.7: Normal Parameters for Area Strain in Adults

LV basal segment (%)

–38.42 ± 7.58

LV middle segment (%)

–38.74 ± 6.34

LV apical segment (%)

–43.18 ± 12.81

(LV: Left ventricle). Source: Reproduced with permission from Perez de Isla L, Millan M, Lennie V, et al. Area strain: normal values for a new parameter in healthy people. Rev Esp Cardiol. 2011;64:1194–7.

375

shortcomings. Interobserver and Intraobserver variability in strain assessment results in lack of reproducibility and nonuniform strain values.74 Another major limitation of 2D STE is the lack of standardization. Variable vendor packages use variable software algorithms resulting in heterogenous strain values. This has also led to confusion in determining the actual normal values for strain.75,76 Since the user defines the area on the myocardium representative of the segment being studied, the actual location where the region of interest is placed may vary from study to study resulting in heterogeneity. Although standardization seems to be an issue, the clinical relevance of heterogeneity of strain values due to vendor variability and imaging techniques remains to be established. While it does seem that such standardization will improve clinical acceptance of this imaging modality, the feasibility of such standardization and its necessity remains debatable.77,78 Moreover, strain analysis is not accurate in the presence of nonsinus rhythms. The automatic endocardial border tracking function of software presumes uniformity in the myocardial wall thickness, which is not the case with all patients. Since the user defines a small area of interest within a particular myocardial segment, intrasegmental variability in motion is neglected, which limits the diagnostic utility of STE in early stages of myocardial diseases such as arrhythmogenic RV dysplasia, where significant regional abnormalities are seen. Excellent image acquisition is mandatory for satisfactory temporal and spatial correlation of speckles in STE. Moreover, with 3D STE, it is important that the endocardium be well visualized so that it can be tracked. Oblique short-axis views due to faulty transducer positioning falsely alter the strain values and can introduce errors into the study. Other imaging artifacts such as lateral wall dropout and rib artifacts can also ruin the quality of the study.

CONCLUSION Myocardial deformation imaging or strain imaging allows objective evaluation of myocardial mechanical function. Both 2D STE and 3D STE overcome several shortcomings of TDI and demonstrate enormous potential for clinical use. At present they are firmly established as valuable research tools and show tremendous promise for broader

376

Section 2: Echocardiography/Ultrasound Examination and Training

Table 19.8: Clinical Conditions where Three-Dimensional Speckle Tracking is Useful

1.

Ischemic LV dysfunction

3D STE longitudinal and area strains correlated with infarct size and scar extent evaluated by magnetic resonance imaging

2.

Acute myocardial infarction

Global 3D longitudinal strain superior to other echo findings in predicting LV function improvement following acute myocardial infarction

3.

LV wall motion abnormalities (WMA)

3D STE superior to 2D STE for assessing LV WMA. 3D area strain accurate and reproducible in detecting LV WMA as evaluated by experienced echocardiographers

4.

Early LV systolic dysfunction

3D global area strain identified early LV systolic dysfunction in patients with risk factors for heart failure

5.

LV volume assessment

LV volume assessment more accurate and more reproducible by 3D STE as compared with 2D STE using cardiac magnetic resonance as a reference

6.

Left ventricular dyssynchrony

Systolic dyssynchrony index of 9.8%, 93% sensitive, and 75% specific in predicting response to CRT (meta-analysis of 73 studies)

7.

LV noncompaction

3D STE confirmed 2D STE findings that LV twist is nearly absent with both apex and base moving in the same direction (clockwise) in systole

8.

Differentiation of hypertrophic cardiomyopathy (HCM) from cardiac amyloidosis

3D LV basal radial strain more reduced in amyloidosis (7.5 ± 19.7%) than HCM (22.3 ± 22.7%, p < 0.0001); radial strain increased from base to apex in amyloidosis, but decreased in HCM (normal but reduced pattern)

9.

Stress (Takotsubo) cardiomyopathy

3D STE provided rapid detection and follow-up of LV WMA

3D STE assessment of strain is superior to 2D STE in LV lead positioning

10. Cardiac sarcoidosis

Global radial strain significantly lower in sarcoidosis (18.5 ± 8.4%) than dilated cardiomyopathy (28.5 ± 8.3%, p < 0.01). Global radial strain ≤ 21.1%, 70% sensitive, and 88% specific in differentiating sarcoidosis from dilated cardiomyopathy

11. Sickle cell disease

3D STE detected LV diastolic dysfunction

12. Hypertension

3D STE global strain reduced in untreated early hypertensives compared with controls

13. Transcatheter aortic valve replacement

3D STE similar to 2D STE in showing increased LV global longitudinal strain and twist following TAVR (especially when pre-TAVR LVEF was decreased), but faster image acquisition and data analysis

14. Atrial septal defect

3D right ventricular ejection fraction and apical strain more sensitive predictors of unfavorable outcome than 2D Doppler indexes

(3D: Three-dimensional; LV: Left ventricle; STE: Speckle tracking echocardiography; LVEF: Left ventricular ejection fraction; TAVR: Transcatheter aortic valve replacement; 2D: Two-diamensional; CRT: Cardiac resynchronization therapy). Source: Reproduced with permission from Biswas M, et al. Two- and three-dimensional speckle tracking echocardiography: clinical applications and future directions. Echocardiography. 2013;30(1):88–105.

use in areas of ischemic heart disease, cardiomyopathies, assessment of cardiac dyssynchrony, and guidance for LV lead placement and assessment of diastolic function.

REFERENCES 1. Picano E, Lattanzi F, Orlandini A, et al. Stress echocardiography and the human factor: the importance of being expert. J Am Coll Cardiol. 1991;17(3):666–9. 2. Citro R, Bossone E, Kuersten B, et al. Tissue Doppler and strain imaging: anything left in the echo-lab? Cardiovasc Ultrasound. 2008;6:54.

3. Storaa C, Aberg P, Lind B, et al. Effect of angular error on tissue Doppler velocities and strain. Echocardiography. 2003;20(7):581–7. 4. Torrent-Guasp F, Buckberg GD, Clemente C, et al. The structure and function of the helical heart and its buttress wrapping. I. The normal macroscopic structure of the heart. Semin Thorac Cardiovasc Surg. 2001;13(4): 301–19. 5. Buckberg G, Hoffman JI, Nanda NC, et al. Ventricular torsion and untwisting: further insights into mechanics and timing interdependence: a viewpoint. Echocardiography. 2011;28(7):782–804.

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

6. Marwick TH. Measurement of strain and strain rate by echocardiography: ready for prime time? J Am Coll Cardiol. 2006;47(7):1313–27. 7. Mor-Avi V, Lang RM, Badano LP, et al. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr. 2011;24(3):277–313. 8. Saito K, Okura H, Watanabe N, et al. Comprehensive evaluation of left ventricular strain using speckle tracking echocardiography in normal adults: comparison of threedimensional and two-dimensional approaches. J Am Soc Echocardiogr. 2009;22(9):1025–30. 9. Notomi Y, Lysyansky P, Setser RM, et al. Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking imaging. J Am Coll Cardiol. 2005;45(12):2034–41. 10. Esch BT, Warburton DE. Left ventricular torsion and recoil: implications for exercise performance and cardiovascular disease. J Appl Physiol. 2009;106(2):362–9. 11. D’hooge J, Heimdal A, Jamal F, et al. Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations. Eur J Echocardiogr. 2000;1(3):154–70. 12. Risum N, Ali S, Olsen NT, et al. Variability of global left ventricular deformation analysis using vendor dependent and independent two-dimensional speckle-tracking software in adults. J Am Soc Echocardiogr. 2012;25(11):1195–203. 13. Vannan MA, Pedrizzetti G, Li P, et al. Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging: description and initial clinical application of a novel method using high-frame rate B-mode echocardiographic images. Echocardiography. 2005;22(10):826–30. 14. Dandel M, Hetzer R. Echocardiographic strain and strain rate imaging–clinical applications. Int J Cardiol. 2009;132 (1):11–24. 15. Choi JO, Cho SW, Song YB, et al. Longitudinal 2D strain at rest predicts the presence of left main and three vessel coronary artery disease in patients without regional wall motion abnormality. Eur J Echocardiogr. 2009;10(5): 695–701. 16. Voigt JU, Lindenmeier G, Exner B, et al. Incidence and characteristics of segmental postsystolic longitudinal shortening in normal, acutely ischemic, and scarred myocardium. J Am Soc Echocardiogr. 2003;16(5):415–23. 17. Skulstad H, Edvardsen T, Urheim S, et al. Postsystolic shortening in ischemic myocardium: active contraction or passive recoil? Circulation. 2002;106(6):718–24. 18. Claus P, Weidemann F, Dommke C, et al. Mechanisms of postsystolic thickening in ischemic myocardium: mathematical modelling and comparison with experimental ischemic substrates. Ultrasound Med Biol. 2007;33(12): 1963–70. 19. Asanuma T, Uranishi A, Masuda K, et al. Assessment of myocardial ischemic memory using persistence of postsystolic thickening after recovery from ischemia. JACC Cardiovasc Imaging. 2009;2(11):1253–61.

377

20. Bjork Ingul C, Rozis E, Slordahl SA, et al. Incremental value of strain rate imaging to wall motion analysis for prediction of outcome in patients undergoing dobutamine stress echocardiography. Circulation. 2007;115(10):1252–9. 21. Hanekom L, Jenkins C, Jeffries L, et al. Incremental value of strain rate analysis as an adjunct to wall-motion scoring for assessment of myocardial viability by dobutamine echocardiography: a follow-up study after revascularization. Circulation. 2005;112(25):3892–900. 22. Roes SD, Mollema SA, Lamb HJ, et al. Validation of echocardiographic two-dimensional speckle tracking longitudinal strain imaging for viability assessment in patients with chronic ischemic left ventricular dysfunction and comparison with contrast-enhanced magnetic resonance imaging. Am J Cardiol. 2009;104(3):312–17. 23. Hunt SA, Abraham WT, Chin MH, et al. Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):e391–479. 24. Becker M, Franke A, Breithardt OA, et al. Impact of left ventricular lead position on the efficacy of cardiac resynchronisation therapy: a two-dimensional strain echocardiography study. Heart. 2007;93(10):1197–203. 25. Ypenburg C, van Bommel RJ, Delgado V, et al. Optimal left ventricular lead position predicts reverse remodeling and survival after cardiac resynchronization therapy. J Am Coll Cardiol. 2008;52(17):1402–9. 26. Becker M, Kramann R, Franke A, et al. Impact of left ventricular lead position in cardiac resynchronization therapy on left ventricular remodelling. A circumferential strain analysis based on 2D echocardiography. Eur Heart J. 2007;28(10):1211–20. 27. Gorcsan J 3rd, Tanabe M, Bleeker GB, et al. Combined longitudinal and radial dyssynchrony predicts ventricular response after resynchronization therapy. J Am Coll Cardiol. 2007;50(15):1476–83. 28. Tanaka H, Nesser HJ, Buck T, et al. Dyssynchrony by speckle-tracking echocardiography and response to cardiac resynchronization therapy: results of the Speckle Tracking and Resynchronization (STAR) study. Eur Heart J. 2010;31(14):1690–700. 29. Brown J, Jenkins C, Marwick TH. Use of myocardial strain to assess global left ventricular function: a comparison with cardiac magnetic resonance and 3-dimensional echocardiography. Am Heart J. 2009;157(1):102 e1–5. 30. Wang J, Khoury DS, Yue Y, et al. Preserved left ventricular twist and circumferential deformation, but depressed longitudinal and radial deformation in patients with diastolic heart failure. Eur Heart J. 2008;29(10):1283–9. 31. Bellavia D, Abraham TP, Pellikka PA, et al. Detection of left ventricular systolic dysfunction in cardiac amyloidosis with strain rate echocardiography. J Am Soc Echocardiogr. 2007;20(10):1194–202.

378

Section 2: Echocardiography/Ultrasound Examination and Training

32. Galderisi M, de Simone G, Innelli P, et al. Impaired inotropic response in type 2 diabetes mellitus: a strain rate imaging study. Am J Hypertens. 2007;20(5):548–55. 33. D’Andrea A, Stisi S, Caso P, et al. Associations between left ventricular myocardial involvement and endothelial dysfunction in systemic sclerosis: noninvasive assessment in asymptomatic patients. Echocardiography. 2007;24(6): 587–97. 34. Mori K, Hayabuchi Y, Inoue M, et al. Myocardial strain imaging for early detection of cardiac involvement in patients with Duchenne’s progressive muscular dystrophy. Echocardiography. 2007;24(6):598–608. 35. Burri MV, Nanda NC, Lloyd SG, et al. Assessment of systolic and diastolic left ventricular and left atrial function using vector velocity imaging in Takotsubo cardiomyopathy. Echocardiography. 2008;25(10):1138–44. 36. Sengupta PP, Krishnamoorthy VK, Abhayaratna WP, et al. Disparate patterns of left ventricular mechanics differentiate constrictive pericarditis from restrictive cardiomyopathy. JACC Cardiovasc Imaging. 2008;1(1):29–38. 37. Richand V, Lafitte S, Reant P, et al. An ultrasound speckle tracking (two-dimensional strain) analysis of myocardial deformation in professional soccer players compared with healthy subjects and hypertrophic cardiomyopathy. Am J Cardiol. 2007;100(1):128–32. 38. Butz T, van Buuren F, Mellwig KP, et al. Two-dimensional strain analysis of the global and regional myocardial function for the differentiation of pathologic and physiologic left ventricular hypertrophy: a study in athletes and in patients with hypertrophic cardiomyopathy. Int J Cardiovasc Imaging. 2011;27(1):91–100. 39. Galderisi M, Lomoriello VS, Santoro A, et al. Differences of myocardial systolic deformation and correlates of diastolic function in competitive rowers and young hypertensives: a speckle-tracking echocardiography study. J Am Soc Echocardiogr. 2010;23(11):1190–8. 40. D’Ascenzi F, Cameli M, Zacà V, et al. Supernormal diastolic function and role of left atrial myocardial deformation analysis by 2D speckle tracking echocardiography in elite soccer players. Echocardiography. 2011;28(3):320–6. 41. Serri K, Reant P, Lafitte M, et al. Global and regional myocardial function quantification by two-dimensional strain: application in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2006;47(6):1175–81. 42. Yang H, Sun JP, Lever HM, et al. Use of strain imaging in detecting segmental dysfunction in patients with hypertrophic cardiomyopathy. J Am Soc Echocardiogr. 2003; 16(3):233–9. 43. Yajima R, Kataoka A, Takahashi A, et al. Distinguishing focal fibrotic lesions and non-fibrotic lesions in hypertrophic cardiomyopathy by assessment of regional myocardial strain using two-dimensional speckle tracking echocardiography: comparison with multislice CT. Int J Cardiol. 2012;158(3):423–32.

44. Kauer F, van Dalen BM, Michels M, et al. Diastolic abnormalities in normal phenotype hypertrophic cardiomyopathy gene carriers: a study using speckle tracking echocardiography. Echocardiography. 2013;30(5):558–63. 45. Dandel M, Wellnhofer E, Hummel M, et al. Early detection of left ventricular dysfunction related to transplant coronary artery disease. J Heart Lung Transplant. 2003;22(12): 1353–64. 46. Dandel M, Knosalla C, Lehmkuhl H, et al. Non-Doppler two-dimensional strain imaging-clinical applications. J Am Soc Echocardiogr. 2007;20(8):1019. 47. Sato T, et al. Utility of left ventricular systolic torsion derived from two-dimensional speckle-tracking echocardiography in monitoring acute cellular rejection in heart transplant recipients. J Heart Lung Transplant. 2011;30(5):536–43. 48. Delgado V, Tops LF, van Bommel RJ, et al. Strain analysis in patients with severe aortic stenosis and preserved left ventricular ejection fraction undergoing surgical valve replacement. Eur Heart J. 2009;30(24):3037–47. 49. de Isla LP, de Agustin A, Rodrigo JL, et al. Chronic mitral regurgitation: a pilot study to assess preoperative left ventricular contractile function using speckle-tracking echocardiography. J Am Soc Echocardiogr. 2009;22(7):831–8. 50. Ho E, Brown A, Barrett P, et al. Subclinical anthracyclineand trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors: a speckle tracking echocardiographic study. Heart. 2010;96 (9):701–7. 51. Pirat B, McCulloch ML, Zoghbi WA. Evaluation of global and regional right ventricular systolic function in patients with pulmonary hypertension using a novel speckle tracking method. Am J Cardiol. 2006;98(5):699–704. 52. Dong L, Zhang F, Shu X, et al. Left ventricular torsion in patients with secundum atrial septal defect. Circ J. 2009; 73(7):1308–14. 53. Dong L, Zhang F, Shu X, et al. Left ventricular torsional deformation in patients undergoing transcatheter closure of secundum atrial septal defect. Int J Cardiovasc Imaging. 2009;25(5):479–86. 54. Li Y, Xie M, Wang X, et al. Evaluation of right ventricular global longitudinal function in patients with tetralogy of fallot by two-dimensional ultrasound speckle tracking imaging. J Huazhong Univ Sci Technol Med Sci. 2010; 30(1):126–31. 55. Carasso S, Yang H, Woo A, et al. Systolic myocardial mechanics in hypertrophic cardiomyopathy: novel concepts and implications for clinical status. J Am Soc Echocardiogr. 2008;21(6):675–83. 56. Wang J, Buergler JM, Veerasamy K, et al. Delayed untwisting: the mechanistic link between dynamic obstruction and exercise tolerance in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2009;54(14):1326–34. 57. Santoro A, Caputo M, Antonelli G, et al. Left ventricular twisting as determinant of diastolic function: a speckle tracking study in patients with cardiac hypertrophy. Echocardiography. 2011;28(8):892–8.

Chapter 19: Speckle Tracking Echocardiography: Clinical Usefulness

58. Notomi Y, Martin-Miklovic MG, Oryszak SJ, et al. Enhanced ventricular untwisting during exercise: a mechanistic manifestation of elastic recoil described by Doppler tissue imaging. Circulation. 2006;113(21):2524–33. 59. Notomi Y, Popovic ZB, Yamada H, et al. Ventricular untwisting: a temporal link between left ventricular relaxation and suction. Am J Physiol Heart Circ Physiol. 2008;294(1):H505–13. 60. Notomi Y, Thomas JD. Presto untwisting and legato filling. JACC Cardiovasc Imaging. 2009;2(6):717–19. 61. Tan YT, Wenzelburger F, Lee E, et al. The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion. J Am Coll Cardiol. 2009; 54(1):36–46. 62. Bertini M, Delgado V, Nucifora G, et al. Left ventricular rotational mechanics in patients with coronary artery disease: differences in subendocardial and subepicardial layers. Heart. 2010;96(21):1737–43. 63. Urbano-Moral JA, Patel AR, Maron MS, et al. Threedimensional speckle-tracking echocardiography: methodological aspects and clinical potential. Echocardiography. 2012;29(8):997–1010. 64. Ammar KA, Paterick TE, Khandheria BK, et al. Myocardial mechanics: understanding and applying three-dimensional speckle tracking echocardiography in clinical practice. Echocardiography. 2012;29(7):861–72. 65. Perez de Isla L, et al. Area strain: normal values for a new parameter in healthy people. Rev Esp Cardiol. 2011;64 (12):1194–7. 66. Hayat D, Kloeckner M, Nahum J, et al. Comparison of real-time three-dimensional speckle tracking to magnetic resonance imaging in patients with coronary heart disease. Am J Cardiol. 2012;109(2):180–6. 67. Abate E, Hoogslag GE, Antoni ML, et al. Value of threedimensional speckle-tracking longitudinal strain for predicting improvement of left ventricular function after acute myocardial infarction. Am J Cardiol. 2012;110(7):961–7. 68. Tanaka H, Hara H, Saba S, et al. Usefulness of three-dimensional speckle tracking strain to quantify dyssynchrony and the site of latest mechanical activation. Am J Cardiol. 2010;105(2):235–42.

379

69. Kleijn SA, Aly MF, Knol DL, et al. A meta-analysis of left ventricular dyssynchrony assessment and prediction of response to cardiac resynchronization therapy by threedimensional echocardiography. Eur Heart J Cardiovasc Imaging. 2012;13(9):763–75. 70. Baccouche H, Maunz M, Beck T, et al. Differentiating cardiac amyloidosis and hypertrophic cardiomyopathy by use of three-dimensional speckle tracking echocardiography. Echocardiography. 2012;29(6):668–77. 71. Baccouche H, Maunz M, Beck T, et al. Echocardiographic assessment and monitoring of the clinical course in a patient with Tako-Tsubo cardiomyopathy by a novel 3D-speckle-tracking-strain analysis. Eur J Echocardiogr. 2009;10(5):729–31. 72. Schueler R, Sinning JM, Momcilovic D, et al. Threedimensional speckle-tracking analysis of left ventricular function after transcatheter aortic valve implantation. J Am Soc Echocardiogr. 2012;25(8):827–34.e1. 73. Vitarelli A, Sardella G, Roma AD, et al. Assessment of right ventricular function by three-dimensional echocardiography and myocardial strain imaging in adult atrial septal defect before and after percutaneous closure. Int J Cardiovasc Imaging. 2012;28(8):1905–16. 74. Kleijn SA, Aly MF, Terwee CB, et al. Reliability of left ventricular volumes and function measurements using threedimensional speckle tracking echocardiography. Eur Heart J Cardiovasc Imaging. 2012;13(2):159–68. 75. Marwick TH, Leano RL, Brown J, et al. Myocardial strain measurement with 2-dimensional speckle-tracking echocardiography: definition of normal range. JACC Cardiovasc Imaging. 2009;2(1):80–4. 76. Gayat E, Ahmad H, Weinert L, et al. Reproducibility and inter-vendor variability of left ventricular deformation measurements by three-dimensional speckle-tracking echocardiography. J Am Soc Echocardiogr. 2011;24(8): 878–85. 77. Nelson MR, Hurst RT, Raslan SF, et al. Echocardiographic measures of myocardial deformation by speckle-tracking technologies: the need for standardization? J Am Soc Echocardiogr. 2012;25(11):1189–94. 78. Marwick TH. Will standardization make strain a standard measurement? J Am Soc Echocardiogr. 2012;25(11): 1204–6.

CHAPTER 20 Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM Michael J Campbell, David A Parra, Daniel Forsha, Piers Barker, Jonathan H Soslow

Snapshot  ApplicaƟon of Velocity Vector Imaging by Age and

Disease Group  Dyssynchrony, Velocity Vector Imaging Analysis

INTRODUCTION The ideal method to assess cardiac contractility would provide an accurate, reproducible, noninvasive, and loadindependent method to quantify global and segmental myocardial function. While load independence has been impossible to achieve so far, more advanced imaging techniques have allowed for improved quantification of global and segmental function. Velocity Vector ImagingTM (Syngo VVI, Siemens, Erlangen, Germany) and TomTec Cardiac Performance Analysis (TomTec, Unterschleissheim, Germany) are types of speckle tracking echocardiography (STE) that use similar algorithms to track the endocardial and epicardial borders. Velocity Vector Imaging (VVI) and Cardiac Performance Analysis (CPA) allow for the accurate evaluation of systolic and diastolic global and segmental function. These software packages can assess myocardial function in multiple planes, better approximating the intricate contraction pattern that results from the complex three-dimensional (3D) anatomy of the heart.

Cardiac Anatomy The subtleties of myocardial architecture and motion have been oversimplified by the two-dimensional nature of the

 Reproducibility and CorrelaƟon between Vendors  Future DirecƟons

different imaging techniques. Traditional angiography in the catheterization lab and B-mode echocardiography display cardiac function as a shortening or planar decrease in volume, in contrast to the rotational motion visualized by surgeons. This simplified understanding of cardiac mechanics is also disjointed from our understanding of myocardial architecture that has evolved over the past century.1 Myocardial fibers are arranged in a three-dimensional helical pattern that courses from endocardium to epicardium in various muscle bands for both the right and left ventricles.1–3 In addition to the longitudinal and radial contraction patterns measured by most imaging modalities, the organized contraction of these fibers produce a distinct “wringing” or “twisting” motion of the heart. This includes active contributions to isovolumetric contraction, ejection and isovolumetric relaxation periods, all of which have exciting implications for potential treatment of both systolic and diastolic disease states.1 Taken one step further, the helical motion of the heart produces three-dimensional flow, leading to theorized preserved kinetic energy in diastole and optimally organized flow in systole.3 Various techniques have been tried to measure these geometric and rotational movements. These have included implanting radio-opaque markers at the time of

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

381

Fig. 20.1: Three-dimensional left ventricular ejection fraction (LVEF) in transplant patient with chronic rejection and abnormal LVEF (TomTec, Unterschleissheim, Germany).

Fig. 20.2: Three-dimensional right ventricular ejection fraction (RVEF) in pediatric patient with tetralogy of Fallot, RV dilation, and mildly depressed RVEF (TomTec, Unterschleissheim, Germany).

surgery, to be visualized later by angiography,1 implanting of sonomicrometric beads in animal models, myocardial tagging by magnetic resonance imaging (MRI), and interrogation of the myocardium with various forms of B-mode imaging and spectral Doppler.3 VVI represents one of these latter techniques. VVI has the ability to quantify global and segmental longitudinal and radial contraction; it can also quantify circumferential contraction and perform complex three-dimensinal strain analysis, giving it the ability to better resolve the complex rotational and geometric motion of the heart.

significant bias and variability were seen in both the 3D and 2D measurements.4 In addition, this volumetric measure is heavily dependent upon loading conditions and it is based on geometric assumptions that fail frequently in abnormal left ventricles. More importantly, LVEF has limitations in predicting important outcomes such as death and progressive heart failure.5,6 There are multiple other measures of left ventricular systolic function (mitral annular plane systolic excursion, fractional shortening, etc.), but all have significant limitations as measures of global systolic function. Global right ventricular systolic function has been an even more difficult puzzle to solve. Because the complex right ventricle anatomy makes reproducible quantification of RV function difficult, subjective visual assessment has become the most common method to evaluate RV function;7 however, this subjective assessment leads to issues with both accuracy and reproducibility. As with the LV, CMR right ventricular ejection fraction (RVEF) is the noninvasive gold standard for RV functional assessment. RV fractional area change (FAC) using the four-chamber apical view has not correlated well with CMR RVEF.8 RV volumes and ejection fraction measured using 3D RV imaging correlate strongly (r > 0.9) with CMR and demonstrate adequate reproducibility (Fig. 20.2).9,10 However, high quality 3D image acquisition of all RV walls from a single echo window is difficult in some patients. Other investigators found that echo 3D RVEF underestimated volumes and correlated in the moderate to poor range with CMR RVEF (r = 0.42).11 Alternate measures, including tricuspid annular plane systolic

Traditional Echocardiographic Limitations in Assessing Ventricular Systolic Function Global ventricular systolic function has been assessed using numerous modalities. Global strain is gaining acceptance as a reproducible measure of global function. However, the gold standard and most frequently used measure for global left ventricular systolic function is left ventricular ejection fraction (LVEF). LVEF can be estimated visually, measured using calculations based on 2D images (Simpson’s rule, area-length method, etc.), or measured directly using 3D images. As long as it is calculated using the same method, LVEF can easily be used to compare function between patients or to follow function longitudinally in the same patient. LVEF by cardiac MRI (CMR) is considered the gold standard, and LVEF by 3D echocardiography (Fig. 20.1) correlates better with CMR LVEF than 2D echocardiography, although

382

Section 2: Echocardiography/Ultrasound Examination and Training

excursion (TAPSE), fractional area change (FAC), and RV S′ using tissue Doppler have all been found to correlate moderately with CMR RVEF in different studies.11,12 The correlation between TAPSE and CMR RVEF was found to be weak in the adult tetralogy of Fallot (TOF) population, likely because of anatomical distortion of an already complex 3D structure.13 None of these alternate measures are truly a global assessment of the complex right ventricle as they are calculated from a single view. The difficulties in measuring global RV systolic function are multifactorial and include the anterior position of the RV, different septal and free wall thicknesses, and different loading conditions than in the left ventricle. However, the main issue is likely the complicated and asymmetric RV geometry and mechanics. Regional function has traditionally been assessed predominantly in the left ventricle using echocardiography and is typically assessed visually. Regional assessment can help identify wall motion defects associated with myocardial infarction, dyssynchrony and postsurgical scar. Visual assessment is complicated by the complexity of ventricular motion in multiple planes. In addition, tethering of a hypocontractile segment to a normal neighboring segment can create the appearance of normal function in the abnormal segment. A previous study compared visual assessment by echo to pathology and demonstrated sensitivities of 90% and 70% for detecting transmural and nontransmural infarcts, respectively.14 However, one third of all segments diagnosed as abnormal visually were normal by pathology and there was significant variability among different observers. In addition, the lack of a quantitative analysis technique renders comparisons between patients, or longitudinally in the same patient, difficult. Overall, there are limitations to all current global and regional echocardiographic functional assessments.

Introduction to Strain and Velocity Vector ImagingTM The concept of myocardial strain was first described by Mirsky and Parmley.15 In practice, the measurement of myocardial gradient velocities using tissue Doppler imaging (TDI) was one of the earliest measurements of myocardial strain and a precursor to VVI.16 In order to better assess regional myocardial thickening, the strain rate, or the rate of change of the length of myocardial fibers, can be derived from tissue velocities; myocardial strain, or the change in myocardial fiber length, can be calculated by taking the integral of the strain rate.17 Although TDI provides the ability to assess regional myocardial

velocities, strain, and strain rate, it has multiple limitations. Strain rate measurement by TDI can be prone to noise and studies have demonstrated high interobserver and intraobserver variability; in addition, TDI imaging is dependent on angle of insonation.18,19 This angle dependence necessitates the assessment of only certain strain values in certain imaging planes.17 Speckle tracking echocardiography (STE) was developed as an alternative method of calculating strain and strain rate; because it is relatively angle-independent, strain and strain rate can be calculated in multiple directions and segments from each imaging plane. STE represents a mathematical analysis of the returning ultrasound signal created by the backscatter and reflection of the myocardium. At each acoustic interface, the ultrasound signal may be transmitted, reflected, or scattered depending on the angle of incidence of the beam and the properties of the interface.20 Each scattered signal may then be transmitted, reflected or further scattered, again depending on beam incidence and acoustic interfaces. This complex interaction of multiple reflectors ultimately creates the “gray-scale” image of the myocardium displayed on the ultrasound machine, with the “speckles” of the image grossly representing the multiple reflectors. Again, it is an oversimplification to assume that these “speckles” represent true anatomical microsegments of myocardium, and that these speckles only move in two-dimensional X and Y planes (rather than the three-dimensional X, Y, and Z planes) and are, therefore, uniquely tracked by any speckle tracking algorithm. Rather, STE is possible because the “speckles” have defined periodicity to their reflection and movement, which can be resolved with appropriate mathematical modeling.21 Velocity vector imaging analyzes these reflected “speckles” in conjunction with user-defined points of reference to define myocardial motion. For longitudinal analysis, the user defines the atrioventricular (AV) valve annulus, the ventricular apex, and the endocardial border. The VVI algorithm then determines both the speed a “speckle” moves along this line, based on comparing the position of a speckle from one frame to the next, and the direction based on the reference coordinates of the AV valve annulus, apex, and endocardium. This analysis produces a velocity vector that represents both myocardial speed and direction. The algorithm works in a similar way for circumferential and radial analyses, with the differences being the cavity center and endocardium as points of reference for circumferential motion, and the additional tracking of a user-defined epicardial border

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

for radial motion. From this calculation, many different measurements can be derived, including displacement, velocity, strain, strain rate, rotation, rotation rate, and even twist and torsion when integrated into a 3D model of the left ventricle. Examples of all of these analyses on a

383

normal pediatric heart are shown in Figures 20.3 to 20.12 and Movie clips 20.1 to 20.3. It is even possible to extend this analysis to any structure or segment, such as the left atrium, or even the aorta or pulmonary artery in crosssection.

Fig. 20.3: Global analysis overview using cardiac performance analysis in the short axis (top left). Left ventricular volume (orange line, lower left) and its first derivative (dA/dt, blue line, lower left). Parametric map of radial strain (top right) and circumferential strain (bottom right).

A Figs 20.4A and B

B

384

Section 2: Echocardiography/Ultrasound Examination and Training

C

D

E

F

Figs 20.4A to F: Rotation rate (A), rotation (B), circumferential strain (C), and circumferential strain rate (D) along with values of global and segmental circumferential strain (E) are shown. Taken from the short axis (F) of a healthy adolescent using cardiac performance analysis (TomTec, Unterschleissheim, Germany).

Fig. 20.5: Rotation rate of the left ventricular apex (apical of papillary muscles) in a healthy adolescent male. VVI (Siemens, Erlangen, Germany).

Fig. 20.6: Rotation of the left ventricular apex (apical of papillary muscles) in a healthy adolescent male. VVI (Siemens, Erlangen, Germany).

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

Fig. 20.7: Rotation rate of the left ventricular base in a healthy adolescent male. VVI (Siemens, Erlangen, Germany).

Fig. 20.9: Left ventricular endocardial circumferential strain at level of papillary muscles in a healthy adolescent male. VVI (Siemens, Erlangen, Germany).

Velocity vector imaging primarily examines the blood–endocardial interface, rather than the full thickness myocardium analyzed by other algorithms. The superiority of one algorithm over another remains controversial, with benefits and weaknesses intrinsic to each technique. Arguably, if the purpose of the cardiac system is to move blood into and out of the heart in the most efficient way possible, then the mechanics of the blood–heart interface (i.e. endocardium) is the most important to understand.1 However, this ignores the contributions of the other layers of the myocardium. A whole thickness algorithm overcomes this limitation, but potentially at the expense of summating multiple layers that may be contracting and moving in different directions at different times.

385

Fig. 20.8: Rotation of the left ventricular base in a healthy adolescent male. VVI (Siemens, Erlangen, Germany).

This chapter will discuss the physics, research and clinical uses, advantages, limitations, and possible future directions of VVI and CPA analysis. When necessary, any gaps in the literature will be filled in with studies using other software analysis packages such as EchoPAC (GE Healthcare, Milwaukee, USA) and QLAB (Philips, Best, The Netherlands), but the chapter will focus on the study and application of VVI and CPA. Although there are software packages that allow both VVI and CPA to be applied to CMR images, for simplicity, any time we refer to echocardiographic analysis, we will use the terms VVI and CPA. If referring to CMR analysis, we will use CMR VVI (Siemens, Erlangen, Germany) or feature tracking (TomTec, Unterschleissheim, Germany). There is currently no standardization in the literature, so this chapter will report “better” longitudinal and circumferential strain as an “increase” in strain because it is more intuitive and the majority of publications report it in this manner; however, it should be noted that improved longitudinal and circumferential strain is represented by a more negative number (see below) and “worse” or “decreased” longitudinal strain by a more positive number.

Physics of Strain Strain is the change in length, or deformation, of an object normalized to its original length. There are two basic types of strain: (a) normal strain and (b) shear strain. In normal strain, loading conditions lead to stress that cause a change in length, or deformation. If you divide this deformation by the original length, the result is normal strain. Shear strain, on the other hand, deals with changes in the angle between

386

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

E

F

Figs 20.10A to F: Radial velocity (A), displacement (B), strain (C), and strain rate (D) along with values of global and segmental radial strain (E) are shown. Taken from the short axis (F) of a healthy adolescent using Cardiac performance analysis (CPA) (TomTec, Unterschleissheim, Germany).

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

A

B

C

D

E

F

387

Figs 20.11A to F: Longitudinal velocity (A), displacement (B), strain (C), and strain rate (D) along with values of global and segmental longitudinal strain (E) are shown. Taken from the short axis (F) of a healthy adolescent using cardiac performance analysis (TomTec, Unterschleissheim, Germany).

388

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

E

F

Figs 20.12A to F: Longitudinal velocity (A), displacement (B), strain (C), and strain rate (D) along with values of global and segmental longitudinal strain (E) are shown. Taken from the long axis (F) of a healthy adolescent using cardiac performance analysis (TomTec, Unterschleissheim, Germany).

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

Figs 20.13A to E: Diagram representing strain calculation. Threedimensional rendering of a left ventricle (A) with a short-axis and long-axis slice in diastole (B and D) and systole (C and E). Circumferential strain represents the change in length of line C divided by the original length; radial strain represents the change in length R divided by the original length; longitudinal strain represents the change in length L divided by the original length. There are six possible shear strains (only circumferential–radial and radial– circumferential are demonstrated in this diagram). Shear strain is calculated by taking the tangent of the angle that represents the change in circumferential in the radial direction (CR) and the change in radial in the circumferential direction (RC).

two line segments. Whereas normal strain deals with linear deformation, such as contraction of the ventricle in the long axis, shear strain is related to a distortion of the tissue and would be more analogous to differential contraction of the epicardium and endocardium. Strain is considered positive when it is associated with elongation and negative when associated with contraction. Because strain is a length divided by another length (change in length divided by original length) it is a unitless measure and, by convention in cardiac imaging, is expressed as a percentage. In a complex system, such as myocardial contraction, the deformation occurs in multiple directions at once. In order to simplify myocardial strain, it is broken down into three types of normal strain and six types of shear strain.22 The types of normal strain are longitudinal, circumferential, and radial (Figs 20.13A to E). Longitudinal strain represents strain along the long axis of the heart, or apex to base, while circumferential strain represents the contraction of myocardium in the short-axis dimension in a rotational motion. Because the lengths shorten during contraction, both longitudinal and circumferential strains

389

are negative. Radial strain, on the other hand, represents myocardial thickening. It can be measured in the short axis (radial) or long axis (transverse) of the heart and, because the myocardium thickens with contraction, is a positive number. Unlike longitudinal, circumferential, and radial strain, shear strain is the angle change between two line segments and results from loading conditions that lead to shear stress (Figs 20.13A to E). The six types of shear strain are circumferential–radial, radial–circumferential, longitudinal–radial, radial–longitudinal, circumferential– longitudinal and longitudinal–circumferential shear strain. Twist and torsion are methods of describing shear strain in the circumferential–longitudinal direction. Although it can be calculated using VVI, shear strain is not as well studied as normal strain and will not be a focus of this chapter. It is important to note that none of these types of strain are true representations of myocardial strain as deformation occurs in multiple directions simultaneously; the strains are separated into various dimensions purely for simplification. Three-dimensional strain is the ideal method to measure strain, but the measurement and interpretation of 3D strain is limited by current technology (discussed further in the section “Future Directions”). There are two basic methods of calculating strain: (a) Eulerian (or natural) and (b) LaGrangian. Eulerian methods measure strain by placing a mesh and watching movement of the body or fluid behind the mesh—the mesh does not move with this method. Measurement of movement is based on spatial position. On the other hand, LaGrangian strain is measured by placing the mesh on the material of interest, and these points move with the material being studied. In fluid mechanics, the difference between these two methods is relatively simple to understand. The Eulerian method would be equivalent to placing a number of fixed buoys in a bay and measuring the flow of water around those buoys. LaGrangian, on the other hand, is equivalent to placing free-floating sensors in the water and allowing those sensors to move with the water. In terms of myocardial strain, LaGrangian strain requires knowledge of the original length while Eulerian strain measures instantaneous strain (calculating strain using the integral of the myocardial velocity is a technique that derives the Eulerian, or natural strain). The default type of strain reported by CPA is LaGrangian strain; however, Eulerian strain can be derived from LaGrangian strain. Harmonic phase (HARP) CMR and TDI both report Eulerian strain, although HARP also reports LaGrangian strain values derived from Eulerian strain.

390

Section 2: Echocardiography/Ultrasound Examination and Training

APPLICATION OF VELOCITY VECTOR IMAGING BY AGE AND DISEASE GROUP Fetal The assessment of fetal cardiac function is a constant challenge to clinicians and researchers, even while fetal echocardiography continues to expand as a clinical tool to detect and manage heart disease in utero. Fetal cardiovascular physiology is uniquely different from the “transitional” circulation of the newborn, and dramatically different from the “mature” circulation of the older infant and adult. During fetal life, both the right and left ventricles eject into the systemic circulation and are, therefore, exposed to equal afterload conditions, albeit a low afterload state due to the low placental resistance. The fetal right ventricle also functions at a state of increased preload, due to the connection of the ductus venosus to the systemic venous circulation, while the left ventricle functions at a state of decreased preload, receiving only the venous return from the pulmonary veins (10–25% of cardiac output depending on gestational age)23 and the right to left flow across the fossa ovalis. These unique loading conditions can be altered by many different pathological states, such as premature ductal restriction, twin–twin transfusion syndrome, placental disease (e.g. pre-eclampsia), fetal arrhythmias, or congenital heart disease (CHD), which may place the fetus at high risk of developing fetal congestive heart failure (CHF; i.e. hydrops fetalis). Technically, it has been difficult to apply traditional methods of measuring fetal cardiac function such as shortening fraction, ejection fraction, and myocardial performance index due to the high fetal heart rates, small fetal cardiac volumes, and variable maternal–fetal acoustic windows. Achieving an appropriate angle of insonation is always challenging due to the variable position of the fetus in the uterus, making angle dependent measurements such as M-mode or TDI-derived indices more challenging. Velocity vector imaging to quantify fetal myocardial velocities, strain, and strain rate has been applied as a method to resolve some of the difficulties associated with M-mode, 2D, and Doppler measurements (Movie clips 20.4 and 20.5). The acquisition of a standard oblique transverse/apical four-chamber view of the fetal heart permits the measurement of longitudinal indices for both the right and left ventricles. As an angle-independent tool, the problem of fetal lie is also overcome, and the ability to apply this tool across multiple vendor ultrasound systems has permitted its use in several clinical studies.

In the first study applying VVI to fetal hearts, Younoszai et al. noted a high degree of success in acquiring adequate images for analysis (89%) across a wide range of second and third trimester fetal ages (18–39 weeks). Fetal left and right ventricular strain and strain rate remained constant during gestation, while longitudinal velocities increased with gestational age, suggesting an adaptation to maintain stroke volume in the face of somatic growth.24 This stability of fetal strain and strain rate across gestational age, accompanied by an increase in myocardial velocities, was confirmed in 2009 and 2010 in series examining only the fetal left ventricle25 and only the fetal right ventricle.26 Fetal circumferential strain has also been recently reported from VVI data analysis, with reasonable feasibility (64% success rate for the left ventricle) in a retrospective series, and the interesting observation that circumferential strain may be a compensatory mechanism to follow in fetal patients with left ventricular outflow tract obstruction.27 In a 2009-study examining both normal and abnormal fetal hearts across a similar range of gestational age, Barker et al. demonstrated a similarly high success rate in adequate software tracking for analysis, and no differences in regional versus global longitudinal strain, (GLS) and strain rate in fetuses with normal cardiac anatomy. When velocity analysis was included, only apical velocities were regionally decreased compared to other segments. Global longitudinal strain and strain rate were similar to published adult studies. For fetuses with acquired heart disease (arrhythmia, twin–twin transfusion syndrome) and CHD, strain and strain rate measurements were more variable, suggesting that strain changes with the loading conditions associated with each diagnosis, although the limited number of fetal patients with specific diagnoses prevented more detailed analysis.28 Subsequent studies have used VVI to investigate fetal cardiac function in various disease states. These studies have especially focused on fetuses with single ventricle physiology and have had mixed results. In two studies examining fetuses with hypoplastic left heart syndrome (HLHS), right ventricular longitudinal strain was noted to be decreased compared to normal fetal right ventricular strain,29,30 while a broader study comparing single left and right ventricles with right and left ventricles in a normal biventricular arrangement detected no difference,31 suggesting that there is functional compensation of the fetal heart for the different loading conditions. These conflicting results highlight the limitations of small sample sizes in relatively uncommon diseases, and mandate further investigation before strain and strain rate imaging can be uniformly applied in the fetal population.

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

One additional significant limitation in the application of VVI to fetal imaging has been the difference between acquired versus stored frame rate. The current standard in Digital Imaging and Communication (DICOM) is a stored frame rate of 30 Hz, although the maximum achievable frame rate during a fetal echocardiogram may be much higher (approximately 100 Hz). When this compression is applied in the setting of the relatively fast fetal heart rate (120–160 beats/minute), only 11 to 15 frames may be available for analysis,24 of which only half may represent ventricular systole. This deficit in temporal resolution stands in marked contrast to the much greater temporal resolution of TDI or current M-mode techniques (approximately 200–300 Hz),32 and creates the potential for missed detection of peak events and limited ability to discern differences between patients. This issue was studied and reported in detail by Matsui et al. comparing high frame rate versus low frame rate acquisitions in fetuses,33 as well as differences between natural strain (calculated automatically by VVI) and LaGrangian strain (calculated from the raw geometric data). As might be expected, there was greater software tracking success with higher frame rate acquisitions, and greater detail available in the velocity curves compared to low frame rate acquisitions. More concerning was the development of greater variability in natural strain values compared to LaGrangian strain values at higher frame rates, suggesting that natural strain values may be a less reliable measurement, and that strain decreased with gestational age, in contrast to prior studies.33 In summary, speckle tracking tools such as VVI hold potential promise as a tool to quantify fetal cardiac function due to the independence of angle of insonation. However, additional prospective studies with high frame rate acquisition and storage in both normal and disease states need to be performed before this tool can be reliably applied in a clinical environment.

Congenital Heart Disease The assessment of congenital heart disease (CHD) by echocardiography focuses not only on the description of detailed anatomical morphology of each individual lesion or the features of the various surgical repairs or palliative operations, but also is intended to evaluate hemodynamic data, particularly ventricular function. Unfortunately, the assessment of ventricular function in this group of individuals may be quite difficult. The use of standard and relatively basic measurements such as fractional

391

shortening or ejection fraction can be inappropriate for the assessment of the left ventricle due to the altered hemodynamics affected by intracardiac shunting, preload, afterload, or presence of surgical materials. The assessment of function of the right ventricle is notoriously more challenging due to its shape, and is also affected by the same factors noted above. This becomes even more complicated in the setting of single ventricle physiology or palliative surgeries that leave the morphological right ventricle functioning as a systemic ventricle. Velocity vector imaging is a method of speckle tracking that can quantify multidirectional components of ventricular deformation and assess regional and global function. Normal values for velocities, strain, and displacement of the right ventricle in children have been published,34 and these parameters will help in the determination of both therapeutic and surgical options for children with congenital heart defects. In CHD, this new technique has been recently applied with great interest as noted in a large number of studies evaluating ventricular function. The recent applications of VVI for selected congenital cardiac disease states will be reviewed.

Tetralogy of Fallot Tetralogy of Fallot (TOF) is the most common cyanotic heart defect at birth with an incidence of 3.9 per 10,000 live births.35 In the current era, surgical repair occurs early in life with excellent long-term survival. However, complications associated with the repair are not inconsequential and can lead to significant morbidity later in life. The assessment of tissue velocities, strain, and strain rate has been evaluated in this group of patients after surgical repair. It is well described that longitudinal tissue velocities, strain, and strain rate are decreased in patients after TOF repair, even in patients who are asymptomatic.36 The abnormalities of regional wall motion may be further affected by the type of operation (transannular patch reconstruction of the right ventricular outflow tract compared with a valve sparing repair). In addition to wall motion abnormalities, the risk of malignant arrhythmias and sudden death increases after surgical correction of TOF. These findings have been linked not only to the right ventricle, but also to abnormalities in regional wall motion of the left ventricle both in adults and in children.36–38 Fernandes et al. studied left ventricular (LV) strain in children and adolescents after TOF repair with residual pulmonary regurgitation and right ventricular dilatation, and demonstrated that

392

Section 2: Echocardiography/Ultrasound Examination and Training

LV regional and circumferential strain were significantly reduced compared to controls.39 Interestingly, it was found that radial strain was affected more than circumferential and longitudinal strain, suggesting that the segments affected can be localized at the circumferential midwall and subepicardial fiber level. Recently, Alghamdi et al. reviewed the strain patterns of the right ventricle in the areas unaffected by a transannular patch and determined that longitudinal strain correlates best with predicted maximal oxygen consumption during exercise stress testing.40 Velocity vector imaging has been also used to assess regional wall motion in repaired TOF patients who have undergone surgical or transcatheter pulmonary valve replacement.41,42 These studies have shown that, despite the fact that strain and strain rate are dependent on loading conditions, they correlate with the shortening of the myocyte prior to intervention.43 The replacement of the pulmonary valve in these patients increases the deformation of the right ventricle, particularly in the short term.

Systemic Right Ventricle The assessment of ventricular function of the systemic right ventricle has become an extremely challenging task. The classic congenital heart defects where the morphological right ventricle supports the systemic circulation include D transposition of the great arteries (DTGA) after atrial switch operation (Senning or Mustard) and congenitally corrected transposition of the great arteries (ccTGA). In these conditions, the right ventricle commonly develops contractile dysfunction as a result of exposure to chronic pressure overload and often volume overload from AV valve insufficiency; clinically, these patients show symptoms of heart failure.44–46 As a consequence, the early detection of myocardial dysfunction is essential, and a reliable method to do so objectively is crucial. Strain and strain rate have been studied in both of these subgroups to evaluate myocardial deformation parameters of the systemic right ventricle with good reproducibility and can be used as a method to detect both systolic and diastolic abnormalities. In patients with DTGA after atrial switch operation, Kalogeropoulos et al. measured global peak strain, systolic strain rate, and early diastolic strain rate and compared these to controls.47 All measurements of systemic ventricular performance were impaired in DTGA compared to controls, and the reproducibility of these measurements

was superior compared to the calculated RV ejection fraction in these patients. A larger study in 2012, with 64 adults with DTGA who underwent atrial switch operation, demonstrated reduced longitudinal global strain of the systemic right ventricle that predicted clinical events such as atrial and ventricular arrhythmias, and heart failure.48 In another study of 129 patients, of which 87 had an atrial switch and 42 had ccTGA, longitudinal systolic strain was again noted to be significantly reduced in the systemic right ventricle, and this decrease was attributed to subpulmonary ventricular function and ventriculoventricular interactions.49 In patients with ccTGA, Grewal et al. demonstrated abnormal subaortic RV myocardial deformation patterns.50 Longitudinal strain and strain rate of the free and septal walls of the systemic RV resemble that of a normal systemic LV and are reduced compared with a normal subpulmonic right ventricle. This suggests some adaptation of the RV to systemic pressures; however, the circumferential RV free wall shortening remained decreased when compared to a normal left ventricle, suggesting that the RV fails to fully adapt to systemic pressures. These findings have been reproduced and suggest that VVI is a useful echocardiographic tool to assess subclinical myocardial dysfunction in this group of patients.51

Single Ventricle The term “single ventricle” applies to patients with CHD who have hypoplasia of the right or left ventricle resulting in the opposite ventricle providing both pulmonary and systemic blood flow. These patients often undergo a series of operations (palliations) to redirect pulmonary blood flow directly to the lungs so that the single ventricle provides only systemic blood flow. The single ventricle has unique functional demands. This is especially apparent in patients with a single morphological right ventricle.52 These patients often have ventricular dysfunction, both regionally and globally. This can progress to severe ventricular dysfunction leading to congestive heart failure, arrhythmias, cardiac transplant, or death. VVI could allow for the identification of early markers of regional and global ventricular dysfunction. In the future, this could lead to improved therapies such as: changes in surgical timing or techniques, development and assessment of new medical therapies, and creation of multisite ventricular pacing strategies. There is previous limited experience performing multisite ventricular pacing in postoperative

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

single ventricle patients.53,54 These studies evaluated response to pacing with hemodynamic parameters and 3D echocardiography. The authors noted an improvement in ventricular synchrony, blood pressure, and cardiac index in addition to a shortened QRS duration. These results increased interest in imaging modalities to assess dyssynchrony as well as regional and global cardiac function in these patients. Single ventricle patients with a morphological left ventricle and those with a morphological right ventricle are thought to be distinct patient populations.52 The myocardial structure of the morphological right and left ventricles are thought to be unique and have different adaptive properties. Several studies have performed STE or VVI to evaluate patients with a single morphological left ventricle.55–58 These studies found reduced longitudinal55,57 and circumferential55,56 strain and strain rates. Marked dyssynchrony has been noted in the single left ventricle population.56,57,59 Patients with single morphological right ventricles are particularly intriguing as these patients are felt to be at a greater risk for ventricular failure because the morphological right ventricle is not meant to be a systemic ventricle.52 Because STE and VVI were developed for assessment of morphological left ventricles, the adaptation of this technology to morphological right ventricles requires special consideration. Multiple studies have evaluated STE and VVI in patients with a single morphological right ventricle.58,60–67 These studies have found reduced longitudinal,61 circumferential,66 and radial strain.66 Dyssynchrony has also been noted.60,61,65,67 Studies by Friedberg et al. and Motonaga et al. have used VVI in this patient population and have noted mechanical dyssynchrony in the presence of normal electrical activation.60,67 Hypoplastic left heart syndrome (HLHS) is one of the most complex congenital heart defects. The defect is characterized by the presence of a single functioning right ventricle that provides both pulmonary and systemic output, the latter dependent on the patency of a ductus arteriosus. Variations to this defect are related to the morphology of the aortic and mitral valves, which can both be either atretic, or stenotic, and thus giving four anatomical subtypes: mitral atresia (MA) and aortic atresia (AA), mitral stenosis and AA, MA and aortic stenosis (AS), and MA and AS; all with varying degrees of aortic arch hypoplasia. Over the years, advancement in operative techniques and medical management prevent what 25 years ago would have been considered a uniformly lethal

393

diagnosis. With the staged palliative surgical approach described by Norwood in 1980, survival is possible.68 This surgical strategy includes three operations during early childhood: the Norwood operation in the first 2 weeks of life (with either a modified Blalock–Taussig shunt (BTS) or a Sano shunt which involves a right ventricle to pulmonary artery conduit), followed by a stage II cavopulmonary connection (Glenn or hemiFontan) typically between 4 to 6 months, and the stage III or Fontan operation performed at 18 to 36 months of age. The right ventricle in HLHS is susceptible to failure.69 Ventricular dysfunction will lead to increased morbidity and mortality, requiring further intervention or ultimately heart transplantation.70 Velocity Vector Imaging in this group of patients prior to and after all stages of surgical palliation has demonstrated significant mechanical dyssynchrony of the right ventricle compared to controls.71 The assessment of right ventricular function and deformation by VVI is shining new light on the mechanics of myocardial contractility, particularly after the different surgical approaches for stage I palliation. Global longitudinal strain in the postoperative Norwood patients with BTS is lower compared to preoperative values, and these changes are seen before abnormalities in parameters of global function, such as RV fractional area of change, are detected.64 In the subgroup of HLHS patients who have undergone a Norwood with Sano shunt, the effects on regional contractility as a result of the right ventriculotomy have been investigated successfully with VVI.66 Menon et al. demonstrated significantly reduced myocardial deformation at the ventriculotomy site before and after stage II, suggesting that persistent, irreversible scarring and fibrosis occur in this area. This group followed these VVI findings and compared them to histopathological changes from patients at either heart transplant or autopsy, and noted decreased velocity, strain, and strain rate in the area of ventriculotomy compared to the contralateral segments in patients with a Sano shunt; no regional hypokinesia was seen in the group with a BTS.72 Khoo et al. demonstrated good correlation between circumferential strain and strain rate measured by STE and RVEF by CMR.65 Measurements of strain in this study were reproducible, suggesting that it can be used as a tool for the monitoring of function in HLHS. Differences in outcomes after the Fontan operation have also been analyzed by two-dimensional speckle tracking. Petko et al. compared the subgroup of mitral and aortic atresia with other anatomical subtypes.73 Those with

394

Section 2: Echocardiography/Ultrasound Examination and Training

mitral and aortic atresia have small or no left ventricular cavity and, therefore, less ventricular septum, which in the other types is more prominent and often fibrotic and less contractile. In this region, strain and strain rate were compromised; however, global strain and strain rate were not different between these groups.73 Zaidi et al. performed STE in adult patients with single ventricles and compared the data to multiple biomarker levels. The authors discovered that there was correlation between regional strain rates and procollagen I C-terminal peptide (PCIP), cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and creatinine.74 This introduces the possibility of correlating biomarkers to early changes in myocardial function. The use and study of VVI and STE in single ventricle patients is in its infancy but holds great promise. There are a great number of issues requiring further study including the ideal method to evaluate a morphological right ventricle by STE and whether to use pattern recognition or absolute parameters for assessment. With further study, the use of VVI in single ventricle patients will likely become more clinically useful and widespread.

Acquired Heart Disease Cardiomyopathy The assessment of myocardial systolic and diastolic function is extremely important in all types of cardiomyopathy. VVI provides a reproducible method to assess the systolic and diastolic function of both the left and right ventricles. In addition, VVI analysis has the potential to identify subclinical dysfunction, which could be vital for the identification of patients at risk of cardiomyopathy; this population includes patients with a family history of cardiomyopathy but normal standard echocardiographic measures of function, patients with a risk of developing cardiomyopathy but normal systolic function [i.e. Duchenne muscular dystrophy (DMD) and anthracycline exposure], and patients with myocardial hypertrophy and a diagnosis of either athlete’s heart or hypertrophic cardiomyopathy (HCM). Dilated Cardiomyopathy: The hallmarks of dilated cardiomyopathy (DCM) are left ventricular dysfunction and dilatation. These findings are often accompanied by myocyte necrosis and myocardial fibrosis. Early TDI studies in patients with amyloidosis suggested that strain and strain rate are more sensitive in detecting systolic

dysfunction than standard echocardiographic measures;75 it stands to reason that VVI will provide similar diagnostic sensitivity. Patients with idiopathic DCM have abnormal strain when compared to controls, with significantly lower peak systolic longitudinal strain and early diastolic longitudinal strain in all segments; DCM patients also have delayed time to peak myocardial velocities, strain, and strain rate.76 Radial and circumferential strain in patients with DCM are also abnormal and studies have demonstrated that global circumferential strain (GCS) is predictive of mortality, although it may not add incremental predictive value to standard echocardiographic measures.77,78 Global longitudinal strain, on the other hand, shows better sensitivity for prediction of adverse events (death, transplantation, or heart failure admission) in adults with CHF and adds incremental value to prediction based on standard echocardiographic measures.78 Strain values correlate well with 3D EF, but correlation is weaker with markers of diastolic dysfunction such as E′, E-wave deceleration, and E/E′.78–80 However, atrial strain can approximate diastolic function, and Meluzin et al. demonstrated correlation between atrial strain and filling pressure by cath; in a separate study, left atrial lateral wall systolic strain and LA volume predicted peak oxygen consumption during exercise testing in patients with both DCM and ischemic cardiomyopathy.81,82 Caution must be used in interpreting atrial strain, as it depends not only on atrial function but also pulmonary and ventricular function.83 Peak atrial longitudinal strain (corresponding to left atrial reservoir function) correlates highly with global longitudinal ventricular strain, probably because the filling of the left atrium during the reservoir phase is based almost entirely on left ventricular contraction.84 Atrial strain requires further study and its correct interpretation demands an understanding of all three phases of left atrial function (reservoir, conduit and active contraction) and the relationship between atrial and ventricular function. RV function in DCM is also important due to the elevated pulmonary artery pressures associated with left atrial hypertension. As with atrial strain, right ventricular strain has been shown to correlate with exercise capacity in patients with idiopathic DCM.85 Even with the advances in genetic testing, genetic mutations are found in only 30% of patients with idiopathic DCM.86 That leaves a large number of patients with DCM who do not have an identifiable mutation. This becomes more problematic when screening relatives of patients with

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

genotype-negative DCM. Family members with normal systolic function by echocardiography may not necessarily be disease-free. Advanced imaging methods such as strain have the potential to identify subclinical disease in patients that may necessitate more frequent screening or earlier medical therapy, although this potential use of strain has not been proven to date and needs further exploration. Anthracycline exposure can lead to acute or chronic cardiotoxicity; the development of chronic heart failure is dose-dependent, with as many as many as 50–60% of patients developing heart failure after higher doses.87 Delayed toxicity has significant implications for children exposed to anthracyclines early in life. Studies have demonstrated lower strain, strain rate, peak torsion, and apical untwisting in patients exposed to anthracyclines when compared with controls, and decreased strain when compared to baseline values in patients receiving anthracycline.88–92 While a weak correlation between decreasing strain values and decreasing LVEF has been reported, enthusiasm is significantly diminished by the minimal change in both strain and LVEF, the clinical significance of which is unclear.89 Studies thus far have been small and of limited utility as the longitudinal relationship between abnormal strain and future cardiomyopathy has not been elucidated; however, the possibility of VVI identifying patients with subclinical myocardial abnormalities who may benefit from early therapy is appealing. Hypertrophic Cardiomyopathy: It is classically thought of as asymmetric ventricular hypertrophy; it is often associated with left ventricular outflow tract obstruction, systolic anterior motion of the mitral valve, and mitral regurgitation. While the most common form is asymmetric hypertrophy of the ventricular septum, asymmetric hypertrophy of the midventricle, apex, and posteroseptal and lateral walls as well as concentric hypertrophy have all been described.93 Histological examination usually demonstrates myocardial disarray. Over the past 20 years, genetic evaluation has led to discovery of more than 1,400 mutations in over 11 genes; currently, genetic testing has a yield of approximately 50% in the proband.94 However, the new era of genetic testing has led to multiple dilemmas: (1) many probands have negative genetic testing, (2) many families have mutations of unknown significance, and (3) family members who are genotype positive can be phenotype negative. Genetic testing has created a diagnostic gap that has the potential to be filled by advanced echocardiographic techniques such as strain.

395

In addition, strain may be useful in distinguishing patients with HCM from those with athlete’s heart. Multiple studies have demonstrated decreased global longitudinal strain and increased global circumferential strain in patients with HCM.95,96 Segmental analysis suggests that these abnormalities are related to extent of hypertrophy.97 While the changes in GLS appear to be uniform across platforms, some studies suggest decreased GCS in HCM patients; these differences may depend largely on differences in strain algorithms as discussed in the reproducibility section.98,99 Strain also has significant potential to help with tissue characterization in HCM. Abecasis et al. report a case of apical HCM, which can be difficult to diagnose by echocardiography, where VVI analysis helped in finalizing the diagnosis.100 Multiple studies have demonstrated the ability of STE to distinguish between HCM and secondary causes of myocardial hypertrophy.98,101 Going forward, these techniques may prove beneficial in distinguishing between patients with athlete’s heart and HCM, as well as in the evaluation of patients with a family history of HCM. Restrictive Cardiomyopathy: Distinguishing between restrictive cardiomyopathy (RCM) and constrictive pericarditis (CP) or other causes of restrictive physiology can be difficult; while symptoms in patients with CP can resolve after pericardial stripping, especially if performed early in the process, patients with RCM require cardiac transplantation.102 Early studies suggest that patients with RCM have preserved circumferential strain and twist but significantly decreased longitudinal strain while patients with CP have abnormal apical circumferential strain and twist, and preserved longitudinal strain.103 VVI may provide an additional noninvasive measure to help distinguish between these two disease processes. Arrhythmogenic Right Ventricular Dysplasia (ARVD): It is a heritable cardiomyopathy caused by fibrofatty infiltration of the RV that leads to RV dilatation, RV dysfunction, and arrhythmia.104 The first indication of disease is often sudden cardiac death in young, asymptomatic individuals. Findings by ECG, echocardiogram, and CMR can be subtle and guidelines for ARVD diagnosis have been published to address this, with the most recent revision in 2010.105 Because the diagnosis can be difficult and those with positive genetic testing can have variable penetrance, VVI has potential to aid in diagnosis and risk stratification. In addition, RV dysfunction is often segmental, lending itself to diagnosis with STE.104

396

Section 2: Echocardiography/Ultrasound Examination and Training

Cardiac performance analysis has demonstrated lower resting global and segmental RV strain values in ARVD versus control, although significant overlap limited the diagnostic utility.106 The addition of exercise testing to strain analysis improved ARVD detection, with global change of both RV and LV longitudinal strain having the best sensitivity and specificity for diagnosis.106 Although these patients had a clear diagnosis of ARVD and abnormal RV function, studies have demonstrated abnormal peak segmental strain and abnormal mechanical dispersion in asymptomatic genetic carriers as compared to controls.107,108 In terms of risk stratification, multivariate logistic regression suggests that mechanical dispersion predicts those at risk of arrhythmia.107 Left Ventricular Noncompaction (LVNC): It is characterized by thick left ventricular myocardium with multiple crypts and areas of compacted and noncompacted muscle. During cardiac development, the left ventricle undergoes a process of myocardial compaction; failure of this process to occur can lead to LVNC. Patients with echocardiographic features of LVNC can be asymptomatic or can suffer from significant heart failure, arrhythmia, thromboembolic events and sudden death.109 However, diagnosis can be difficult as features of LVNC overlap with other forms of cardiomyopathy and normal controls.110 Studies have demonstrated a unique strain and strain rate pattern in LVNC as compared to DCM, with higher values of both strain and strain rate in the basal segments in LVNC, whereas DCM patients had diffusely decreased values and different patterns of twist.111,112 Children with LVNC have abnormal strain and strain rate as compared to controls, as do adult patients with LVNC and normal cardiac function.113,114 Evaluation of strain and strain rate in LVNC is in its infancy, particularly when using VVI, and further studies are necessary. Cardiomyopathy in Neuromuscular Disorders: Although there is phenotypic and genotypic overlap between classical forms of dilated, restrictive, and HCM and those associated with neuromuscular disorders, the onset, progression, and pathological features deviate enough that they should be discussed in a separate section.115 Multiple neuromuscular disorders are associated with cardiac effects, either cardiomyopathy or arrhythmias. These include, but are not limited to, Duchenne and Becker muscular dystrophy, limb-girdle muscular dystrophy, fascioscapulohumeral muscular dystrophy, Emery–Dreifuss muscular dystrophy, and myotonic dystrophy. Because of skeletal muscle

effects, these patients are often diagnosed prior to cardiac manifestations; therefore, identification of subclinical myocardial disease and initiation of early treatment is felt to be the future of cardiac management in these disorders. Because of limited echocardiographic windows in these patients, abnormal strain in muscular dystrophy has primarily been evaluated using CMR tissue tagging.116,117 CMR strain evaluation has been promising in patients with Duchenne muscular dystrophy (DMD), who have abnormal circumferential strain that progresses with age and begins before manifest systolic dysfunction.117 Comparison of circumferential strain by echo VVI and tissue tagging in patients with DMD demonstrated poor correlation between segmental circumferential strain by VVI and CMR (r = 0.27) and concluded that VVI is an inadequate method of strain quantification in DMD patients.118 This poor correlation may be partially related to poor echocardiographic windows as more than half of their study population was 15 years or older. Evaluation of DMD circumferential strain in patients less than 8 years of age demonstrated small but statistically significant decreases in global and segmental circumferential strain as compared to controls; however, the higher baseline heart rates in DMD subjects combined with low frame rates may have contributed to this small difference in strain.119 At this point, no other types of muscular dystrophy have been evaluated with either VVI or CPA by echocardiography, although CMR VVI and feature tracking have been applied to cine MRI images in various muscular disorders.120,121 Strain and strain rate imaging using VVI has the potential to identify patients with subclinical dysfunction prior to manifest systolic dysfunction (Fig. 20.14), although further research is required and results in older patients may be limited by poor imaging windows.

Coronary Heart Disease The noninvasive assessment of coronary artery disease (CAD) is an important and controversial field. Identifying patients with CAD who are likely to respond from reperfusion interventions is critical. This involves differentiating normal, infarcted, and salvageable/stunned myocardium. There are a number of imaging modalities such as radionuclide myocardial perfusion/metabolic imaging, CMR, and echocardiography, which have been used in this role. The use of echocardiography in the assessment of CAD has historically involved visual assessment of ventricular wall motion, with or without pharmacological stress.

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

Fig. 20.14: Global and segmental longitudinal strain in a patient with Duchenne muscular dystrophy (DMD) and mild left ventricular dilatation but normal cardiac function by standard echocardiographic measures. The global longitudinal strain is abnormal (-15.6%) as is the segmental longitudinal strain. CPA (TomTec, Unterschleissheim, Germany). Of note, because of anatomical imaging, the labels for septal and free wall strain in the figure are reversed.

With the advent of echocardiographic myocardial deformation analysis, new avenues for the assessment of CAD have been discovered. It is known that, following acute coronary artery occlusion, affected areas of myocardium have decreased systolic shortening or passive movement compared to unaffected myocardium.122,123 This passive movement, compared to areas of active movement, is the foundation of visual wall motion assessment. Myocardial deformation imaging has the potential to measure and quantify these differences in wall motion. Doppler strain analysis (TDI) was first used to assess myocardial deformation in CAD. In 1998, Derumeaux et al. performed TDI analysis in a canine model of left anterior descending coronary artery occlusion and noted decreased velocities and systolic shortening.124 Since then, multiple studies in humans have demonstrated that, when compared to normal myocardium, infarcted myocardium has abnormal strain as measured by TDI.125–127 TDI strain imaging can also be used to differentiate between transmural and nontransmural infarctions.123,124,128,129 TDI strain analysis during dobutamine stress echocardiography can be used to identify ischemic myocardium130,131 and areas of myocardium that are salvageable/stunned and may be improved by coronary artery intervention.132–134

397

Hanekom et al. found that TDI strain could identify areas of myocardium that were salvageable, but TDI strain performed no better than visual wall motion assessment. However, combining TDI strain and visual wall motion assessment improved the sensitivity and specificity of salvageable myocardium.132 Doppler strain analysis is useful to assess patients with CAD, but does have the limitation of angle dependence. The development of STE has provided a relatively angleindependent modality for the assessment of regional myocardial function in patients with CAD. Roes et al. performed STE and CMR in patients with chronic ischemic disease and compared STE strain values to areas of abnormal delayed enhancement on CMR. They found good correlation between areas of infarction on CMR and global left ventricular strain by STE. A global strain of -4.5% discriminated between segments of myocardium with and without infarction.135 Butz et al. performed STE imaging and delayed enhancement CMR in patients following myocardial infarction and found that the areas corresponding to infarction on CMR had decreased velocities, strain, and strain rate as compared to noninfarcted areas.136 Global longitudinal strain by STE is a better predictor of infarction than LVEF,137 and in patients with left main or three vessel CAD, peak longitudinal strain could identify abnormalities even in patients without visual regional wall motion abnormalities.138 Aarsaether et al. performed a study in a porcine model of myocardial infarction and compared STE analysis to 2,3,5-triphenyltetrazolium chloride (TTC) staining of myocardial infarction. They found that there was correlation between all strain parameters and extent of infarction, with longitudinal strain performing the best.139 STE can be used to predict whether an area of infarction is transmural or not and thereby provide important prognostic information.140 STE combined with dobutamine stress echocardiography identified areas of ischemia in a porcine model of ischemia.141 Bansal et al. used STE with and without dobutamine stress in patients with a history of CAD and left ventricular dysfunction who were undergoing reperfusion. They found that longitudinal and circumferential strain and strain rate at rest and with dobutamine stress could identify areas of myocardium that would recover function. Radial strain and strain rate at rest, but not with dobutamine stress, were predictive; however, the authors found that strain TDI performed better than STE in the same analysis.133

398

Section 2: Echocardiography/Ultrasound Examination and Training

The role of STE in the assessment of CAD is evolving. Bansal et al. found no improvement over visual wall motion analysis or TDI strain in the identification of salvageable myocardium when compared head to head.133 Currently, CMR and radionuclide myocardial perfusion/ metabolic imaging are more commonly used modalities; however, these studies have limitation and cost concerns. Continued advancements in the use of VVI in CAD are needed to improve its clinical utility.

Kawasaki Disease Kawasaki disease (KD) is an acute, self-limited inflammatory vasculitis of unknown etiology.142 The acute phase is characterized by inflammation of small arteries, including coronary arteries. This can result in coronary artery dilation and aneurysms that can predispose to thrombus formation and subsequent embolization and infarction. The acute phase can also result in myocarditis. The standard treatment of KD is intravenous immunoglobulin (IVIG). The convalescent phase of KD in patients with coronary artery involvement can result in resolution of coronary artery dilation or the development of coronary artery stenosis, which predisposes to ischemia and infarction. The possibility of CAD and myocarditis in KD makes this a patient population who may benefit from assessment with strain analysis. Yu et al. performed 2D speckle tracking imaging (longitudinal, circumferential and radial) of the left ventricle in controls and in patients during the acute and convalescent phases of KD. This study found that longitudinal strain at the basal and midventricular level was decreased in the acute phase of disease. This correlated with an increased left ventricular mass index and decreased albumin level but did not correlate with coronary artery size. The authors concluded that this was secondary to vascular leakage and myocardial edema, and not CAD.143 Ge et al. performed myocardial strain and strain rate imaging with VVI in patients with KD in the acute phase (prior to treatment), convalescent phase (following treatment), and in controls. They found that, compared to controls, patients with acute KD had decreased longitudinal strain rate in nine myocardial segments. After treatment, these areas improved but remained decreased compared to controls. Radial strain rate was decreased in eight myocardial segments in the acute phase of KD compared to controls but improved and normalized in

the convalescent phase. Circumferential peak systolic velocities also decreased in the acute phase and improved following treatment.144 These few studies illustrate the possible applications of strain analysis in patients with KD. Further investigation is needed in this patient population to better characterize strain patterns and response to treatment.

Velocity Vector Imaging in Diabetes The development of left ventricular dysfunction is a common complication in patients with diabetes and can be associated with hypertension and/or CADs, but can also be independent of these factors. VVI analysis of strain and strain rate has been used to assess early left ventricular involvement in this population;145 Fang et al. have described how longitudinal and radial myocardial function are diminished in patients with normal ejection fraction, suggesting that myocyte death and dysfunction is initially focused on the subendocardium. Interestingly, increased radial function seems to compensate for this dysfunction, possibly due to the development of hypertrophy in the midwall or by redistribution of blood flow to different layers of the myocardium. Ceyhan et al. demonstrated an association between impaired LV longitudinal systolic and diastolic function and glucose metabolism in prediabetic patients.145,146 Although more study is necessary, VVI has the potential to help monitor diabetic patients for signs of early LV dysfunction.

Velocity Vector Imaging in Myocarditis Acute myocarditis may present with variable symptoms, and its diagnosis, particularly with normal left ventricular function, can be challenging. Inflammatory involvement of the myocardium has been recognized in up to 12% of cases in an autopsy series of sudden death, suggesting that unrecognized myocarditis is potentially lethal.147 A study of left ventricular strain, strain rate, and twist deformation in children and young adults with myocarditis by the group in Edmonton demonstrated impaired systolic and diastolic patterns in patients with normal LV ejection fraction. Five different variables of strain and twist were identified as independent predictors of myocarditis confirmed by CMR. These predictors included: fourchamber longitudinal strain, basal circumferential early diastolic strain rate, peak twist rate, earlier time to peak twist, and lateral annular e′ velocity. Finding any two of these variables had a 93% sensitivity, 91% specificity,

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

399

and 82% positive predictive value for a CMR diagnosis of myocarditis.148 These findings are similar to those recently reported by Hsiao et al. in a similar group of adults.149 In this group, longitudinal and circumferential strain and strain rate predicted major clinical events in patients with either decreased or normal LVEF.

Amyloid Disease Amyloidosis is a disease that results from the deposition of amyloid proteins in various organs such as the heart, liver, kidneys, or peripheral nerves. The heart is affected by primary amyloidosis, a light-chain immunoglobulin, although hereditary and senile systemic amyloidosis has also been described.150 Amyloid penetrates the myocardial interstitium as nodular deposits and branching filaments interlacing between myocytes. Sun et al. demonstrated that in patients with amyloidosis, global myocardial deformation (torsion) is lower when compared to patients with HCM, hypertrophy from hypertension, and healthy controls; they also demonstrated that longitudinal strain differentiated amyloid from the other groups, with some overlap.98 Cappelli et al. demonstrated that RV longitudinal strain is a predictor of prognosis;151 RV involvement occurs later than left ventricular deposition but, when it occurs, it dramatically worsens the clinical status. In this group of patients, STE has been used to assess rotational mechanics of the left ventricle. Studies have shown that there is decreased twisting and untwisting motion even before cardiac involvement, suggesting impaired relaxation of the left ventricle and making this finding a possible marker of subclinical cardiac involvement.152

Pulmonary Hypertension Pulmonary artery hypertension (PAH) is the result of progressive pulmonary vascular remodeling that leads to increased right-sided cardiac pressures and further right heart failure and death.153 The assessment of right ventricular strain and strain rate is a novel approach to estimate function in this geometrically complex chamber. Haeck et al. recently recognized that longitudinal peak systolic strain in this group of patients is associated with mortality.154 In a study of 45 patients with PAH, longitudinal strain of the RV free wall was lower than that of controls and was overall strongly related to RV function, making it possible to follow the progression of disease and response to therapy serially in patients with PAH.155

Fig. 20.15: Global and segmental longitudinal strain in patient status post heart transplant with chronic rejection. Global longitudinal strain is abnormal (-12.4%); segmental longitudinal strain is especially decreased in the mid portion of the lateral wall (-5.3%) and the apical, mid, and basal septum (-12.8%, -12.2%, and -10.6%, respectively). These areas of abnormal strain correspond to wall motion abnormalities and provide an objective measure of segmental function. CPA (TomTec, Unterschleissheim, Germany). Of note, because of anatomical imaging, the labels for septal and free wall strain in the figure are reversed.

Heart Transplantation Detection of subclinical rejection in heart transplant recipients is quite difficult; many protocols require frequent screening cardiac catheterizations with endomyocardial biopsies. Recognition of coronary artery vasculopathy in patients with older grafts can also be challenging and often requires invasive techniques such as intravascular ultrasound. VVI provides global and segmental functional assessment in transplant patients (Fig. 20.15) and may allow for more sensitive detection of subclinical dysfunction. Studies have demonstrated that global longitudinal strain and strain rate are abnormal in pediatric and adult heart transplant patients without rejection as compared with controls, while circumferential strain and strain rate are preserved.156,157 Strain and strain rate may have the ability to distinguish between transplant patients with and without rejection, and strain has been used to detect rejection in the setting of standard echocardiographic measures that are normal or near normal.158,159 In addition, global longitudinal strain analyzed with STE early after transplantation may be predictive of a 1-year mortality.160 More studies are necessary, but additional methods for

400

Section 2: Echocardiography/Ultrasound Examination and Training

noninvasive monitoring would have significant implications in heart transplantation and could decrease the frequency of endomyocardial biopsies.

Exercise The response of the cardiac system to stress, most typically exercise, represents an important area for the application of VVI. This investigation is challenged by many of the same issues facing fetal echocardiography, namely higher heart rates, greater cardiac translation due to body movement, and limited acoustic windows during exercise due to lung interference. Exercise imaging is also limited by the need to obtain adequate images (usually with the subject in a supine position) antagonized by the typical subject position while exercising (upright), and the typically qualitative means of assessing changes in cardiac function with exercise. For these reasons, VVI holds promise for quantification of regional and global changes during exercise, and has been the subject of limited investigation. Velocity vector imaging and speckle tracking echocardigraphy have been shown to be feasible with both pharmacological (dobutamine) and exercise (treadmill, supine cycle ergometry, and hand grip) stress testing.161–164 These investigations have examined subjects without heart disease, subjects with heart disease,165 and athletes of varying degrees performing different types of exercise at baseline. Information obtained from STE has been compared to TDI measurements with good correlation. In particular, STE has been useful for quantifying right ventricular function, with high tracking success161 and demonstrated increasing strain rate (SR) and velocities but not strain or displacement. Compared to CMR, right ventricular strain correlates well with EF, while RV SR correlates best with VO2.12 Right ventricular parameters have also been noted to be decreased in patients with pulmonary hypertension, repaired TOF, and ARVD, and noted to correlate with exercise performance;164,166,167 interestingly, this correlation was not found with exercise in patients with ccTGA and systemic RVs.50 In athletes performing endurance, strength, or mixed training, right ventricular strain has been noted to be decreased at rest and increased with exercise compared to control subjects.168 These measurements have even been applied to athletic horses169 with documented decreased strain but increased SR at exercise. The ability of STE to calculate strain parameters as well as radial and rotational motion has been applied to analyze epicardial and endocardial apical function in

elite cyclists,170–172 and have provided insights into atrial mechanics during exercise to shift left ventricular filling into an earlier phase of diastole.173,174 Measurement of shear strain has been feasible,171 providing insights into the cardiac adaptation to exercise in cyclists and potential explanations for the functional changes seen in AS.171 While this diverse experience with STE opens multiple possibilities for additional investigation, further work is necessary to standardize imaging protocols, similar to exercise protocols, and determine optimal frame rates for exercise VVI to become more clinically useful.

DYSSYNCHRONY, VELOCITY VECTOR IMAGING ANALYSIS The discovery that cardiac resynchronization therapy (CRT) can lead to reverse remodeling and improved ventricular function in some patients with cardiomyopathy has led to many patients receiving biventricular pacing systems. Using standard ECG and LVEF criteria as the indication for CRT, many patients respond, although specificity is poor. There are currently a wide array of strain measures, mostly analyzing time to peak strain, that are being studied to better target those patients that will respond to CRT. Many of these measures have not improved our ability to predict CRT response over standard criteria, although investigation is ongoing.175 A novel strain methodology using regional pattern analysis to identify opposing wall patterns consistent with underlying electrical activation delays using GE acquisition and EchoPAC analysis has shown promise, but has not been validated in a large trial nor using VVI.176 Until these analyses have been more completely validated between vendors, care must be taken to remain vendor-consistent within a study (see Reproducibility section below). This section will focus on studies using VVI analysis.

Velocity Vector Imaging Analysis to Predict Cardiac Resynchronization Therapy Response in Adults with Cardiomyopathy By tracking motion of the myocardium over time, strain analysis has the capability to reveal many features of ventricular mechanics. However, given the huge number of adult patients fulfilling standard criteria for CRT, the potential utility of strain analysis to diagnose mechanical dyssynchrony and better predict CRT response generates

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

the greatest excitement. The VALIANT study confirmed that post-myocardial infarction subjects with mechanical dyssynchrony by time to peak analysis had a higher rate of death and heart failure than those without dyssynchrony.177 Early reports using VVI analysis to evaluate mechanical dyssynchrony showed promise for identifying those most likely to respond to CRT.178,179 The largest studies using VVI strain analysis were in the analyses of the MADIT subjects.180,181 This trial enrolled patients with decreased ventricular function (LVEF ≤ 30%) and prolonged QRS duration (≥130 ms) who only had mild to moderate symptoms of heart failure and randomized to implantable cardioverter defibrillator (ICD) only versus ICD plus CRT. The dyssynchrony index measuring standard deviation of the time to peak strain was an independent predictor of CRT response and larger decreases in the standard deviation post-CRT were associated with a decreased number of primary events (death or heart failure). Another study analyzed nonischemic cardiomyopathy patients with LVEF < 40%.182 More than half of these patients had mechanical dyssynchrony using time to peak indices despite an average QRS duration of 98 ms in the study population before CRT. Only 12% remained dyssynchronous post CRT. A novel methodology was reported using VVI strain analysis on intracardiac echo images obtained during coronary sinus (CS) lead placement. CRT response rate increased to 82% in the VVI analysis population compared to 63% in the population where CS positioning was not adjusted based on strain analysis (P = 0.03).183 Overall, these studies suggest that VVI strain analysis using time to peak assessment may be able to improve the predictive pre-test characteristics to identify CRT responders, although a significant nonresponse rate remains. Furthermore, improvement in dyssynchrony indices after CRT can decrease death or heart failure, and VVI to aide CS lead positioning may improve response rates. Many questions remain concerning reproducibility, correlation to non-VVI strain platforms, optimal strain dimension (radial, longitudinal, circumferential, or transverse), and optimal dyssynchrony index. Further studies, including application of regional pattern analysis, examining VVI strain analyses are currently underway.

Velocity Vector Imaging Analysis to Evaluate Dyssynchrony in Pediatric and Congenital Heart Disease Mechanical dyssynchrony in pediatric and congenital heart disease (CHD) populations have also been evaluated

401

using VVI strain analysis. Prior to frequent use of VVI or speckle tracking strain echocardiography, multiple trials had demonstrated that CRT can benefit a majority of patients with CHD and diminished LV systolic function in the setting of mechanical dyssynchrony or prolonged QRS duration.184–188 These studies included subgroup analysis on systemic LV and systemic RV patients as well as single ventricle patients. While there were significant variations in CRT response rate (22–76%) by ventricular morphology and study, most had CRT response rates similar to those seen in normal anatomy adults using standard CRT criteria (discussed above). However, these trials did not include a standardized method of diagnosis of mechanical dyssynchrony, nor did most use a strain echo technique. Small studies using VVI strain have evaluated mechanical dyssynchrony in CHD populations, but none have CRT outcome data. Children with HLHS, most post-Fontan, had RV mechanical dyssynchrony.71 This was measured with standard deviation of the time to RV peak strain and was elevated compared to normal age-matched children. VVI strain analysis has also been used to demonstrate adverse LV mechanics and dyssynchrony in adults with TOF status postsurgical repair189 and LV dyssynchrony in children with idiopathic cardiomyopathy.190 These studies suggest that mechanical dyssynchrony is not a rare problem in CHD and pediatric populations. Strain analysis, including VVI platforms, can provide a wealth of information on either LV or RV ventricular mechanics in these populations that frequently suffer from ventricular dysfunction and heart failure (Fig. 20.16). This analysis tool may also prove useful in understanding of the elusive concept of ventricular interdependence when biventricular strain analyses are performed. Future research is also necessary to better evaluate the prognosis of different CHD populations with dyssynchrony and find the optimal strain index to predict CRT response.

REPRODUCIBILITY AND CORRELATION BETWEEN VENDORS When interpreting strain analysis, it is important to note that values are not necessarily identical across platforms. This problem of poor reproducibility and correlation is complex and likely secondary to multiple variables, including: (1) different vendor carts used for acquisition of data, (2) different vendor software used for analysis, and (3) different methods of calculation of global strain values after segmental strain has been calculated. In effect, different software packages provide different

402

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 20.16: Two-dimensional strain analysis using Velocity Vector Imaging software on an infant with an unbalanced atrioventricular septal defect post Norwood procedure with acute development of a right bundle branch block (RBBB). The left ventricular (LV) and right ventricular (RV) walls were tracked on the pre- and postRBBB four-chamber apical view. The pre-RBBB strain curves demonstrate low-normal to mildly diminished global peak systolic strain and a relatively synchronous contraction pattern. The postRBBB curves show severely diminished global peak systolic strain and a pattern of dyssynchrony consistent with early LV free wall contraction and late RV free wall contraction due to the underlying activation delay. VVI (Siemens, Erlangen, Germany).

results because they are measuring different things. Until addressed, these differences across vendors make the creation of normal values for clinical interpretation of strain difficult. The consensus statement by ASE and ESE in 2008 noted the following, A significant limitation of the current implementation of 2D STE is the differences among vendors, driven by the fact that STE analysis is performed on data stored in a proprietary scan line (polar) format, which cannot be analyzed by other vendors’ software. There are some implementations that operate on images stored in a raster (Cartesian) Digital Imaging and Communications in Medicine format, but there is only limited experience to date cross-comparing different vendors’ images. This issue needs further investigation before STE can become a mainstream methodology. There is currently a joint effort between the American Society of Echocardiography (ASE), European Association of Echocardiography (EAE), and the industry to address this issue.

The call for more comparisons across platforms has led to some validation studies, although more are necessary. These studies are made difficult by the number of software platforms and the frequent updates to these platforms that make previous comparisons obsolete.

The fact that many software packages are only able to analyze raw data in certain formats has made these comparisons more difficult—for example, a comparison of GE EchoPac strain with Philips QLab strain would necessitate obtaining images on the same patients with GE and Philips carts. Clearly, there will be variability in both the timing of image acquisition, with possible changes in the patient’s hemodynamic state, and the location of image acquisition, as identical imaging planes are difficult to achieve. This study design would lead to increased variability that is not necessarily related to the analysis packages themselves. These limitations are overcome when comparing either VVI or CPA to other software packages because of the flexibility in type of images that can be analyzed; both VVI and CPA can analyze native data or DICOM images, allowing analysis to be performed on identical images and direct comparisons to be made. This section will discuss some of the comparisons that have been published so far with a focus on VVI and CPA. In an early comparison of VVI with EchoPac and tagged harmonic phase (HARP) analysis of CMR images (Diagnosoft version 1.02; Diagnosoft, Inc, Baltimore, MD), VVI and EchoPac correlated with HARP for global longitudinal strain, although EchoPac had a slightly better correlation.191 VVI did not correlate with HARP circumferential strain, while EchoPac did. Neither method of speckle tracking correlated with radial strain by CMR. In general, EchoPac was superior to VVI when compared to the gold standard, tissue tagging, but this study was performed in 2008 prior to updates in all three software packages, making the usefulness of the comparison to current versions less clear. In a more recent study, Koopman et al. initially imaged patients with either a GE Vivid 7 or Philips IE33, then analyzed the data using EchoPac, QLab, and Software Package for Echocardiographic Quantification Leuven (SPEQLE; University of Leuven, Leuven, Belgium), a TDI analysis package, in children.192 They found that longitudinal strain was the most reproducible, followed by circumferential strain; the assessment of radial strain correlated poorly across platforms and had the worst inter- and intraobserver variability. A similar study by Koopman compared CPA analysis with analysis from QLabs and EchoPac.193 The images obtained on the IE33 were analyzed with QLabs and CPA, while the images obtained by the VIVID-7 were analyzed with EchoPac and CPA. They found relatively good correlation between vendor-specific software and CPA when evaluating global longitudinal and circumferential strain; however,

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

the software demonstrated increased variability when evaluating radial strain and when performing segmental strain, and a systematic bias when comparing images obtained on a Philips IE33 to those obtained on a GE VIVID-7. The researchers also evaluated the difference between strain values from VIVID-7 stored at the default DICOM frame rate of 30 fps and images stored as native data; in this analysis, the native data had slightly higher strain values (more negative) for global longitudinal strain and circumferential strain, and significantly higher values (more positive) for radial strain; these increased values are likely secondary to higher frame rates that allow for more accurate determination of peak strain. A similar study was performed in healthy adults comparing EchoPac and VVI at acquisition frame rates and after conversion to DICOM images (30 fps); this study also found good agreement between EchoPac and VVI assessment of global longitudinal strain and poor agreement for global circumferential and radial strain.194 The agreement between the two software packages was better when acquisition frame rates were used for VVI analysis in a subset of patients. Interestingly, time to peak values were relatively comparable across all three types of strain between VVI and EchoPac; this also held true for segmental analysis of time to peak. The authors felt this was likely because the peak values depended on the particular algorithm used, while time to peak depends on the timing of contraction by electrocardiography; while the absolute peak values seem to vary significantly across platforms, the timing of the peak strain appears to be relatively constant. The comparison of radial time to peak strain in adults using EchoPAC analysis at acquisition frame rates and VVI analysis on DICOM images has also been performed.195 Variability between platforms depended largely on the amount of dyssynchrony present. The strain curves with more significant dyssynchrony demonstrated high variability between platforms while those in subjects with synchronous or only mildly dyssynchronous contraction patterns were similar. In patients with significant dyssynchrony, the early contracting walls often have their contraction terminated early by the late contracting walls. These short, low amplitude early peaks may be missed or their peak timing altered when analyzed using lower frame rate images or DICOM images with spatial averaging as compared to acquisition frame rate analysis in EchoPAC. When the dyssynchrony index was dichotomized to present or not present, there was close agreement between platforms and both predicted CRT response similarly.

403

The study by Biaggi194 assessed healthy adults without dyssynchrony, which may explain their good time to peak correlation between platforms and strain dimensions. Another recent analysis was performed by Risum et al. and compared images from the same patients performed on IE33 native data, IE33 DICOM data (30 fps), and GE native and DICOM data; strain analysis was performed using CPA for all images and EchoPac for GE uncompressed data.196 Using acquisition frame rates, there was good reproducibility of global longitudinal strain across all platforms and software packages, moderate circumferential strain reproducibility with increased variability, and poor radial strain reproducibility (measured in both short axis and apical images). A breakdown of comparisons at different frame rates again demonstrated good reproducibility between CPA, EchoPac and QLabs for global longitudinal strain, no matter which frame rates were analyzed, although the strain values were slightly higher with acquisition frame rates when compared with DICOM (30 fps) images. Comparison across frame rates seemed to have a larger effect on circumferential strain, as the agreement remained high but the increased variance led to nonsignificant results; agreement of radial strain across frame rates remained poor (Figs 20.17A and B). Interestingly, the data from Risum suggests that, for global longitudinal strain analysis, frame rates are less important than expected. This suggests that global longitudinal data analyzed retrospectively from DICOM images is accurate. The analysis of circumferential and radial strain at lower frame rates is less reproducible. Although the effect of faster heart rates in children has not specifically been assessed, one would assume that DICOM image analysis is suboptimal at higher heart rates and should be performed with caution. All three of these studies were limited by small sample sizes (n = 33 and 49 in Koopman studies, n = 30 in Risum study). In addition, the authors used EchoPac as the gold standard, which biases data toward EchoPac. Another difficulty in comparing speckle tracking software from different vendors relates to the underlying algorithms. VVI and CPA both analyze endocardial and epicardial strain while other packages measure combinations of endocardial and epicardial strain or averages of the strain for the entire thickness of traced myocardium. When calculating global strain, CPA calculates the average of the individual peak strains, which does not take into account temporal variations in peak strain, while other packages calculate an average peak

404

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 20.17A and B: Intraobserver and interobserver reproducibility. This figure from Risum et al. demonstrates the coefficients of variation for longitudinal, circumferential, radial and transverse strain. Images labeled GE were obtained on a GE Vivid 9 and images labeled PH were obtained on a Philips IE33. Analysis of images obtained on a GE Vivid 9 was performed using EchoPAC (VSSGE60), cardiac performance analysis (CPA) at the acquisition frame rate (VIS-GE60), or CPA at compressed frame rates (VIS-GE30). Additional analysis in the same patients of images obtained on a Philips IE33 was performed using CPA at the acquisition frame rate (VIS-PH60) or CPA at the compressed frame rate (VIS-PH30). Source: Reproduced with permission from Risum, et al. JASE; 2012.

strain curve and report the peak strain of that curve. In addition, some packages measure LaGrangian strain while others measure Eulerian strain. Until standardization occurs, strain measurements will always differ across software packages. For example, Nelson et al. demonstrated poor correlation between CPA and EchoInsight (EchoInsight version 1.5.0, Epsilon, Ann Arbor, MI) using “out of the box settings”; correlation improved significantly with adjustment of analysis settings (adjustments included changing EchoInsight to measure the mean of the peak strain of all segments as opposed to the peak of the mean curve, setting EchoInsight to evaluate endocardial strain instead of a combination of endocardial and epicardial strain, and setting EchoInsight to measure LaGrangian strain instead of natural strain).197 The advantage of the study by Nelson is that both software packages were vendor-independent and analyzed the same images with the same frame rates. Other authors have also suggested that the primary difference between software packages is related to what the algorithm is measuring (i.e. endocardial strain, as in VVI and CPA, versus an average of the entire thickness of the myocardium, as in EchoPac).194,198 As suggested by Biaggi, this may be because there is a “gradient” with much higher circumferential and radial strain values on the endocardial surface while longitudinal strain values are more constant throughout the entire thickness of the myocardium.

Standardization of strain measurement is necessary in order for strain to move beyond research and into routine use in the clinical realm. Deciding how to standardize may be complicated and the best algorithm may vary depending on the strain value measured. Because longitudinal fibers are concentrated in the subendocardium and subepicardium,199 it may be preferable to use an algorithm that only focuses endocardial or epicardial strain, such as VVI, when evaluating longitudinal strain. Conversely, an algorithm that averages the strain throughout the thickness of the myocardium or focuses on the midportion may be better for circumferential strain. Further comparisons of strain measurements across platforms are necessary to eventually determine the best method of standardization.

FUTURE DIRECTIONS Three-Dimensional STE Three-dimensional STE is an exciting new area in myocardial function analysis (Fig. 20.18). 2D STE has inherent limitations, including: (1) assumption that speckles remain in the 2D plane and can be tracked throughout the cardiac cycle and (2) foreshortening of views of the heart that affect quantification of cardiac motion.200 3D STE is an angle-independent imaging method that can track speckles throughout the imaging volume. 3D volumes are created using ECG gating to

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

405

Fig. 20.18: Example of three-dimensional (3D) strain analyzed on a transplant patient with chronic rejection and wall motion abnormalities using CPA. Three-dimensional, longitudinal, circumferential and radial strain can be analyzed using a 3D dataset. CPA (TomTec, Unterschleissheim, Germany).

acquire multiple smaller volumes throughout subsequent cardiac cycles.201 Studies have revealed that 3D STE images can be acquired in much less time than 2D STE;202,203 3D STE also allows for better visualization of a larger number of segments.203 In head-to-head comparison with 2D STE, 3D STE had decreased longitudinal strain and increased circumferential strain.202 Comparison of 3D STE and 2D STE volumetric measurements to CMR volumes revealed that 3D STE volumes had better correlation to CMR volumes.204 3D STE global longitudinal strain agreed with conventional measures of ventricular function such as ejection fraction and Doppler-derived cardiac output.205 Although these early studies on 3D STE are promising, there are notable limitations. 3D STE, like most imaging modalities, is dependent on good image quality. In addition, it has low spatial resolution that can limit endocardial border detection.200,201 Low temporal resolution can make it difficult to accurately measure strain rate and the timing of peak strain values and, while 3D STE is good at assessing global strain, it is not as robust at detecting regional differences in strain.201 Another limitation of 3D STE is that different vendors use different algorithms to create and analyze the 3D data. This makes it difficult to validate and to compare the different software.200 The use of 3D STE in the clinical setting is still in an early phase with further studies needed to determine the utility of 3D STE strain and volume data in clinical care.

MRI Tagging Versus MRI Velocity Vector Imaging CMR offers advantages over echocardiography in that it can provide excellent images in many patients who do not have ideal echocardiographic windows. This allows for the creation of an image with an excellent endocardial–blood pool interface that can be used to visualize and quantify regional myocardial dysfunction. Myocardial tagging has been the gold standard for evaluation of regional myocardial performance in CMR. This method involves superimposing lines or grids on the myocardium and following the subsequent deformation of these lines through the cardiac cycle on a cine CMR image.206–210 This is usually performed before the administration of contrast and requires unique imaging sequences that use radiofrequency prepulses to apply lines and grids.206 Image acquisition is performed using a prospectively gated cine image, either single shot steady state free precession (SSFP) or gradient echo (GRE). Postprocessing is then performed using an automated HARP analysis.206,209,210 Comparison to STE has revealed similar values for regional myocardial performance.206,211,212 However, the postprocessing using HARP can be time consuming. Myocardial tagging also requires specific imaging sequences that are not a part of the standard CMR examination. In addition, T1-related fading effects can reduce accuracy of some measurements, primarily those of diastolic function.206

406

Section 2: Echocardiography/Ultrasound Examination and Training

Feature tracking and CMR VVI represent additional modalities for assessing regional myocardial performance by CMR. An advantage of feature tracking is that standard cine MRI images can be used without the need for a specific prepulse or imaging sequence. The DICOM data can be loaded into feature tracking software (TomTec). Epicardial and endocardial borders are defined in a single cardiac phase and are followed throughout the cardiac cycle. Longitudinal, circumferential and radial velocity, displacement, strain, and strain rate can be obtained.213 Feature tracking uses a hierarchical algorithm to generate values of regional myocardial performance.213 Several studies have found that regional myocardial performance data obtained by feature tracking compare well with myocardial tagging.213–216 Maret et al. have demonstrated that feature tracking can identify areas of abnormal myocardium affected by scar.215 Initial studies comparing feature tracking to myocardial tagging have revealed similar indices of regional myocardial function and these are obtained in much less time. However, feature tracking does have some potential drawbacks. As opposed to myocardial tagging, the midmyocardial segments are not tracked using feature tracking. It is yet to be determined if this is a significant difference. Also, the hierarchical algorithm used in feature tracking has not been released to the public. Further analysis into the methodologies of feature tracking, through collaboration with industry, is needed to lead to more robust validation. Finally, further studies are needed comparing these modalities in different disease states.

Twist The base of the left ventricle rotates in a clockwise direction while the apex rotates in a counterclockwise direction, leading to a twisting or wringing of the left ventricle during contraction.217 Diastolic filling is characterized by a similar untwisting. LV twist is calculated by taking the difference in rotation between different segments, usually the apex and base. Because VVI and CPA can analyze cardiac rotation, both programs can be used to evaluate LV twist. LV twist analyzed with VVI is significantly decreased in patients with DCM when compared with controls and correlates with LVEF; untwisting is also significantly decreased in DCM, suggesting diastolic dysfunction.218,219 Mitral annular displacement and 3D strain can also be measured with speckle tracking and hold future promise for LV functional analysis.220,221

There is some debate whether absolute twist is abnormal in patients with HCM,99,222 but most studies report different patterns of twist in patients with HCM as compared to controls. Patients with HCM have identical LV rotation at the base and apex, clockwise and counterclockwise, respectively; however, the rotation at the midventricle is reversed and remains clockwise, leading to very little twist between the base and midportion of the ventricle.96,97 Untwist is also abnormal and is prolonged in patients with HCM, suggesting a deficit in diastolic filling that correlates with peak VO2 by exercise testing in some studies.99,223 Although measurement of LV twist is in the early stages, it shows promise as a better representation of the complex three-dimensional motion of the LV.

CONCLUSION Velocity vector imaging represents an important tool in the ongoing effort to better measure the threedimensional nature of cardiac motion, detect pathology, and assess response to treatment. Like other speckletracking algorithms, and all forms of cardiac imaging in general, it has both the strength of apparent simplicity and the weakness of analyzing only a piece of the more complex myocardial architecture. It has the capability of generating a tremendous amount of data from each image, but how this data can best be used for clinical decisionmaking remains to be determined. For strain in particular, consensus is needed on whether LaGrangian or Eulerian strain is the most robust measurement. Velocity vector imaging also has the capability to be applied to non– speckle-based images, such as CMR datasets. This may become especially important for analysis of ventricular torsion, which compares the rotation of different segments of the ventricle across a defined longitudinal distance (Movie clip 20.7). As the use of VVI and other forms of torsional analysis increases, it is important to sound a cautionary note: electrical–mechanical coupling in the human heart operates on a millisecond to millisecond basis, with a mere 60 milliseconds separating a normal QRS duration from profound bundle branch block. For standard imaging storage rates of 30 Hz, this represents less than two full frames of imaging data (33 ms/frame). Crucial segments of the cardiac cycle, such as isovolumetric contraction and relaxation, take place in even shorter time periods, which currently require the extremely fine temporal resolution of spectral Doppler or M-mode for detection. For VVI to reach

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

its full potential, every effort must be made to maximize the frame rates of both the acquired and stored images, so that the appropriate events are not misinterpreted. Ultimately, if the strengths of VVI can be merged with temporal resolution in the sub-10 millisecond range, then the potential for complete imaging of all the complex myocardial mechanics may be possible.

REFERENCES 1. Buckberg G, Hoffman JI, Mahajan A, Saleh S, Coghlan C. Cardiac mechanics revisited: the relationship of cardiac architecture to ventricular function. Circulation. 2008;118 (24):2571–87. 2. Torrent-Guasp F, Ballester M, Buckberg GD, et al. Spatial orientation of the ventricular muscle band: physiologic contribution and surgical implications. J Thorac Cardiovasc Surg. 2001;122(2):389–92. 3. Sengupta PP, Krishnamoorthy VK, Korinek J, et al. Left ventricular form and function revisited: applied translational science to cardiovascular ultrasound imaging. J Am Soc Echocardiogr. 2007;20(5):539–51. 4. Dorosz JL, Lezotte DC, Weitzenkamp DA, et al. Performance of 3-dimensional echocardiography in measuring left ventricular volumes and ejection fraction: a systematic review and meta-analysis. J Am Coll Cardiol. 2012;59(20): 1799–808. 5. Fogel MA. Use of ejection fraction (or lack thereof ), morbidity/mortality and heart failure drug trials: a review. Int J Cardiol. 2002;84(2-3):119–32. 6. Santangeli P, Dello Russo A, Casella M, et al. Left ventricular ejection fraction for the risk stratification of sudden cardiac death: friend or foe? Intern Med J. 2011;41(1a):55–60. 7. Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685–713; quiz 786. 8. Ling LF, Obuchowski NA, Rodriguez L, et al. Accuracy and interobserver concordance of echocardiographic assessment of right ventricular size and systolic function: a quality control exercise. J Am Soc Echocardiogr. 2012;25(7): 709–13. 9. Morikawa T, Murata M, Okuda S, et al. Quantitative analysis of right ventricular function in patients with pulmonary hypertension using three-dimensional echocardiography and a two-dimensional summation method compared to magnetic resonance imaging. Am J Cardiol. 2011;107(3):484–9. 10. Niemann PS, Pinho L, Balbach T, et al. Anatomically oriented right ventricular volume measurements with dynamic three-dimensional echocardiography validated by 3-Tesla magnetic resonance imaging. J Am Coll Cardiol. 2007;50(17):1668–76.

407

11. Kjaergaard J, Petersen CL, Kjaer A, et al. Evaluation of right ventricular volume and function by 2D and 3D echocardiography compared to MRI. Eur J Echocardiogr. 2006;7(6):430–8. 12. Leong DP, Grover S, Molaee P, et al. Nonvolumetric echocardiographic indices of right ventricular systolic function: validation with cardiovascular magnetic resonance and relationship with functional capacity. Echocardiography. 2012;29(4):455–63. 13. Morcos P, Vick GW 3rd, Sahn DJ, et al. Correlation of right ventricular ejection fraction and tricuspid annular plane systolic excursion in tetralogy of Fallot by magnetic resonance imaging. Int J Cardiovasc Imaging. 2009;25(3): 263–70. 14. Beppu S, Park YD, Yoshikawa J, et al. Two-dimensional echocardiography in diagnosing the region of myocardial infarction: a comparative study by several independent examiners. J Cardiogr. 1985;15(1):31–42. 15. Mirsky I, Parmley WW. Assessment of passive elastic stiffness for isolated heart muscle and the intact heart. Circ Res. 1973;33(2):233–43. 16. Uematsu M, Miyatake K, Tanaka N, et al. Myocardial velocity gradient as a new indicator of regional left ventricular contraction: detection by a two-dimensional tissue Doppler imaging technique. J Am Coll Cardiol. 1995;26(1):217–23. 17. Heimdal A, Støylen A, Torp H, et al. Real-time strain rate imaging of the left ventricle by ultrasound. J Am Soc Echocardiogr. 1998;11(11):1013–19. 18. Pislaru C, Abraham TP, Belohlavek M. Strain and strain rate echocardiography. Curr Opin Cardiol. 2002;17(5):443–54. 19. Castro PL, Greenberg NL, Drinko J, et al. Potential pitfalls of strain rate imaging: angle dependency. Biomed Sci Instrum. 2000;36:197–202. 20. Edelman SK. Understanding Ultrasound Physics: Fundamentals and Exam Review. 2nd edition. Houston, TX: ESP; 1994. 21. Valckx FM, Thijssen JM. Characterization of echographic image texture by cooccurrence matrix parameters. Ultrasound Med Biol. 1997;23(4):559–71. 22. D’hooge J, Heimdal A, Jamal F, et al. Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations. Eur J Echocardiogr. 2000; 1(3):154–70. 23. Kiserud T. Physiology of the fetal circulation. Semin Fetal Neonatal Med. 2005;10(6):493–503. 24. Younoszai AK, Saudek DE, Emery SP, et al. Evaluation of myocardial mechanics in the fetus by velocity vector imaging. J Am Soc Echocardiogr. 2008;21(5):470–4. 25. Peng QH, Zhou QC, Zeng S, et al. Evaluation of regional left ventricular longitudinal function in 151 normal fetuses using velocity vector imaging. Prenat Diagn. 2009; 29(12):1149–55. 26. Pu DR, Zhou QC, Zhang M, et al. Assessment of regional right ventricular longitudinal functions in fetus using velocity vector imaging technology. Prenat Diagn. 2010; 30(11):1057–63.

408

Section 2: Echocardiography/Ultrasound Examination and Training

27. Ishii T, McElhinney DB, Harrild DM, et al. Circumferential and longitudinal ventricular strain in the normal human fetus. J Am Soc Echocardiogr. 2012;25(1):105–11. 28. Barker PC, Houle H, Li JS, et al. Global longitudinal cardiac strain and strain rate for assessment of fetal cardiac function: novel experience with velocity vector imaging. Echocardiography. 2009;26(1):28–36. 29. Miller TA, Puchalski MD, Weng C, et al. Regional and global myocardial deformation of the fetal right ventricle in hypoplastic left heart syndrome. Prenat Diagn. 2012; 32(10):949–53. 30. Brooks PA, Khoo NS, Mackie AS, et al. Right ventricular function in fetal hypoplastic left heart syndrome. J Am Soc Echocardiogr. 2012;25(10):1068–74. 31. Truong UT, Sun HY, Tacy TA. Myocardial deformation in the fetal single ventricle. J Am Soc Echocardiogr. 2013; 26(1):57–63. 32. Weidemann F, Kowalski M, D’hooge J, et al. Doppler myocardial imaging. A new tool to assess regional inhomogeneity in cardiac function. Basic Res Cardiol. 2001;96(6): 595–605. 33. Matsui H, Germanakis I, Kulinskaya E, et al. Temporal and spatial performance of vector velocity imaging in the human fetal heart. Ultrasound Obstet Gynecol. 2011;37(2):150–7. 34. Kutty S, Deatsman SL, Nugent ML, et al. Assessment of regional right ventricular velocities, strain, and displacement in normal children using velocity vector imaging. Echocardiography. 2008;25(3):294–307. 35. Improved national prevalence estimates for 18 selected major birth defects–United States, 1999–2001. MMWR Morb Mortal Wkly Rep. 2006;54(51):1301–5. 36. Weidemann F, Eyskens B, Mertens L, et al. Quantification of regional right and left ventricular function by ultrasonic strain rate and strain indexes after surgical repair of tetralogy of Fallot. Am J Cardiol. 2002;90(2):133–8. 37. Abd El Rahman MY, Hui W, Yigitbasi M, et al. Detection of left ventricular asynchrony in patients with right bundle branch block after repair of tetralogy of Fallot using tissue-Doppler imaging-derived strain. J Am Coll Cardiol. 2005;45(6):915–21. 38. Kempny A, Diller GP, Orwat S, et al. Right ventricularleft ventricular interaction in adults with Tetralogy of Fallot: a combined cardiac magnetic resonance and echocardiographic speckle tracking study. Int J Cardiol. 2012;154(3):259–64. 39. Fernandes FP, Manlhiot C, Roche SL, et al. Impaired left ventricular myocardial mechanics and their relation to pulmonary regurgitation, right ventricular enlargement and exercise capacity in asymptomatic children after repair of tetralogy of Fallot. J Am Soc Echocardiogr. 2012;25(5): 494–503. 40. Alghamdi MH, Mertens L, Lee W, et al. Longitudinal right ventricular function is a better predictor of right ventricular contribution to exercise performance than global or outflow tract ejection fraction in tetralogy of Fallot: a combined echocardiography and magnetic resonance study. Eur Heart J Cardiovasc Imaging. 2013;14(3):235–9.

41. Knirsch W, Dodge-Khatami A, Kadner A, et al. Assessment of myocardial function in pediatric patients with operated tetralogy of Fallot: preliminary results with 2D strain echocardiography. Pediatr Cardiol. 2008;29(4):718–25. 42. Moiduddin N, Asoh K, Slorach C, et al. Effect of transcatheter pulmonary valve implantation on shortterm right ventricular function as determined by twodimensional speckle tracking strain and strain rate imaging. Am J Cardiol. 2009;104(6):862–7. 43. Weidemann F, Eyskens B, Jamal F, et al. Quantification of regional left and right ventricular radial and longitudinal function in healthy children using ultrasound-based strain rate and strain imaging. J Am Soc Echocardiogr. 2002;15 (1):20–8. 44. Graham TP Jr, Bernard YD, Mellen BG, et al. Long-term outcome in congenitally corrected transposition of the great arteries: a multi-institutional study. J Am Coll Cardiol. 2000;36(1):255–61. 45. Piran S, Veldtman G, Siu S, et al. Heart failure and ventricular dysfunction in patients with single or systemic right ventricles. Circulation. 2002;105(10):1189–94. 46. Roos-Hesselink JW, Meijboom FJ, Spitaels SE, et al. Decline in ventricular function and clinical condition after Mustard repair for transposition of the great arteries (a prospective study of 22-29 years). Eur Heart J. 2004;25(14):1264–70. 47. Kalogeropoulos AP, Georgiopoulou VV, Giamouzis G, et al. Myocardial deformation imaging of the systemic right ventricle by two-dimensional strain echocardiography in patients with d-transposition of the great arteries. Hellenic J Cardiol. 2009;50(4):275–82. 48. Kalogeropoulos AP, Deka A, Border W, et al. Right ventricular function with standard and speckle-tracking echocardiography and clinical events in adults with D-transposition of the great arteries post atrial switch. J Am Soc Echocardiogr. 2012;25(3):304–12. 49. Diller GP, Radojevic J, Kempny A, et al. Systemic right ventricular longitudinal strain is reduced in adults with transposition of the great arteries, relates to subpulmonary ventricular function, and predicts adverse clinical outcome. Am Heart J. 2012;163(5):859–66. 50. Grewal J, Crean A, Garceau P, et al. Subaortic right ventricular characteristics and relationship to exercise capacity in congenitally corrected transposition of the great arteries. J Am Soc Echocardiogr. 2012;25(11):1215–21. 51. Becker M, Hümpel C, Ocklenburg C, et al. The right ventricular response to high afterload: comparison between healthy persons and patients with transposition of the great arteries: a 2D strain study. Echocardiography. 2010; 27(10):1256–62. 52. Mahle WT, Coon PD, Wernovsky G, et al. Quantitative echocardiographic assessment of the performance of the functionally single right ventricle after the Fontan operation. Cardiol Young. 2001;11(4):399–406. 53. Zimmerman FJ, Starr JP, Koenig PR, et al. Acute hemodynamic benefit of multisite ventricular pacing after congenital heart surgery. Ann Thorac Surg. 2003;75(6):1775–80.

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

54. Bacha EA, Zimmerman FJ, Mor-Avi V, et al. Ventricular resynchronization by multisite pacing improves myocardial performance in the postoperative single-ventricle patient. Ann Thorac Surg. 2004;78(5):1678–83. 55. Singh GK, Cupps B, Pasque M, et al. Accuracy and reproducibility of strain by speckle tracking in pediatric subjects with normal heart and single ventricular physiology: a two-dimensional speckle-tracking echocardiography and magnetic resonance imaging correlative study. J Am Soc Echocardiogr. 2010;23(11):1143–52. 56. Truong UT, Li X, Broberg CS, et al. Significance of mechanical alterations in single ventricle patients on twisting and circumferential strain as determined by analysis of strain from gradient cine magnetic resonance imaging sequences. Am J Cardiol. 2010;105(10):1465–9. 57. Moiduddin N, Texter KM, Zaidi AN, et al. Two-dimensional speckle strain and dyssynchrony in single left ventricles vs. normal left ventricles. Congenit Heart Dis. 2010;5(6): 579–86. 58. Petko C, Hansen JH, Scheewe J, et al. Comparison of longitudinal myocardial deformation and dyssynchrony in children with left and right ventricular morphology after the Fontan operation using two-dimensional speckle tracking. Congenit Heart Dis. 2012; 7(1):16–23. 59. Ho PK, Lai CT, Wong SJ, et al. Three-dimensional mechanical dyssynchrony and myocardial deformation of the left ventricle in patients with tricuspid atresia after Fontan procedure. J Am Soc Echocardiogr. 2012;25(4):393–400. 60. Friedberg MK, Silverman NH, Dubin AM, et al. Right ventricular mechanical dyssynchrony in children with hypoplastic left heart syndrome. J Am Soc Echocardiogr. 2007;20(9):1073–9. 61. Moiduddin N, Texter KM, Zaidi AN, et al. Two-dimensional speckle strain and dyssynchrony in single right ventricles versus normal right ventricles. J Am Soc Echocardiogr. 2010;23(6):673–9. 62. Petko C, Hoffmann U, Möller P, et al. Assessment of ventricular function and dyssynchrony before and after stage 2 palliation of hypoplastic left heart syndrome using two-dimensional speckle tracking. Pediatr Cardiol. 2010;31(7):1037–42. 63. Petko C, Möller P, Hoffmann U, et al. Comprehensive evaluation of right ventricular function in children with different anatomical subtypes of hypoplastic left heart syndrome after Fontan surgery. Int J Cardiol. 2011;150 (1):45–9. 64. Petko C, Uebing A, Furck A, et al. Changes of right ventricular function and longitudinal deformation in children with hypoplastic left heart syndrome before and after the Norwood operation. J Am Soc Echocardiogr. 2011;24(11):1226–32. 65. Khoo NS, Smallhorn JF, Kaneko S, et al. Novel insights into RV adaptation and function in hypoplastic left heart syndrome between the first 2 stages of surgical palliation. JACC Cardiovasc Imaging. 2011;4(2):128–37.

409

66. Menon SC, Minich LL, Casper TC, et al. Regional myocardial dysfunction following Norwood with right ventricle to pulmonary artery conduit in patients with hypoplastic left heart syndrome. J Am Soc Echocardiogr. 2011;24(8):826–33. 67. Motonaga KS, Miyake CY, Punn R, et al. Insights into dyssynchrony in hypoplastic left heart syndrome. Heart Rhythm. 2012;9(12):2010–5. 68. Norwood WI, Kirklin JK, Sanders SP. Hypoplastic left heart syndrome: experience with palliative surgery. Am J Cardiol. 1980;45(1):87–91. 69. Altmann K, Printz BF, Solowiejczky DE, et al. Twodimensional echocardiographic assessment of right ventricular function as a predictor of outcome in hypoplastic left heart syndrome. Am J Cardiol. 2000;86(9):964–8. 70. Mitchell ME, Ittenbach RF, Gaynor JW, et al. Intermediate outcomes after the Fontan procedure in the current era. J Thorac Cardiovasc Surg. 2006;131(1):172–80. 71. Friedberg MK, Silverman NH, Dubin AM, et al. Right ventricular mechanical dyssynchrony in children with hypoplastic left heart syndrome. J Am Soc Echocardiogr. 2007;20(9):1073–9. 72. Menon SC, Erickson LK, McFadden M, et al. Effect of ventriculotomy on right-ventricular remodeling in hypoplastic left heart syndrome: a histopathological and echocardiography correlation study. Pediatr Cardiol. 2013; 34(2): 354–63. 73. Petko C, Voges I, Schlangen J, et al. Comparison of right ventricular deformation and dyssynchrony in patients with different subtypes of hypoplastic left heart syndrome after Fontan surgery using two-dimensional speckle tracking. Cardiol Young. 2011;21(6):677–83. 74. Zaidi AN, White L, Holt R, et al. Correlation of serum biomarkers in adults with single ventricles with strain and strain rate using 2D speckle tracking. Congenit Heart Dis. 2013;8(3):255–65. 75. Al-Zahrani GB, Bellavia D, Pellikka PA, et al. Doppler myocardial imaging compared to standard two-dimensional and Doppler echocardiography for assessment of diastolic function in patients with systemic amyloidosis. J Am Soc Echocardiogr. 2009;22(3):290–8. 76. Zeng S, Zhou QC, Peng QH, et al. Assessment of regional myocardial function in patients with dilated cardiomyopathy by velocity vector imaging. Echocardiography. 2009; 26(2):163–70. 77. Cho GY, Marwick TH, Kim HS, et al. Global 2-dimensional strain as a new prognosticator in patients with heart failure. J Am Coll Cardiol. 2009; 54(7):618–24. 78. Motoki H, Borowski AG, Shrestha K, et al. Incremental prognostic value of assessing left ventricular myocardial mechanics in patients with chronic systolic heart failure. J Am Coll Cardiol. 2012;60(20):2074–81. 79. Abduch MC, Salgo I, Tsang W, et al. Myocardial deformation by speckle tracking in severe dilated cardiomyopathy. Arq Bras Cardiol. 2012;99(3):834–43.

410

Section 2: Echocardiography/Ultrasound Examination and Training

80. Tanaka H, Tanabe M, Simon MA, et al. Left ventricular mechanical dyssynchrony in acute onset cardiomyopathy: association of its resolution with improvements in ventricular function. JACC Cardiovasc Imaging. 2011;4 (5):445–56. 81. Meluzin J, Spinarova L, Hude P, et al. Estimation of left ventricular filling pressures by speckle tracking echocardiography in patients with idiopathic dilated cardiomyopathy. Eur J Echocardiogr. 2011;12(1):11–8. 82. D’Andrea A, Caso P, Romano S, et al. Association between left atrial myocardial function and exercise capacity in patients with either idiopathic or ischemic dilated cardiomyopathy: a two-dimensional speckle strain study. Int J Cardiol. 2009;132(3):354–63. 83. Appleton CP, Kovács SJ. The role of left atrial function in diastolic heart failure. Circ Cardiovasc Imaging. 2009; 2(1):6–9. 84. Ersbøll M, Andersen MJ, Valeur N, et al. The prognostic value of left atrial peak reservoir strain in acute myocardial infarction is dependent on left ventricular longitudinal function and left atrial size. Circ Cardiovasc Imaging. 2013;6(1):26–33. 85. Salerno G, D’Andrea A, Bossone E, et al. Association between right ventricular two-dimensional strain and exercise capacity in patients with either idiopathic or ischemic dilated cardiomyopathy. J Cardiovasc Med (Hagerstown). 2011;12(9):625–34. 86. Fatkin D; members of the CSANZ Cardiac Genetic Diseases Council Writing Group. Guidelines for the diagnosis and management of familial dilated cardiomyopathy. Heart Lung Circ. 2011;20(11):691–3. 87. Carvalho FS, Burgeiro A, Garcia R, et al. Doxorubicininduced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy. Med Res Rev; 2013 Mar 11 [Epub ahead of print]. 88. Park JH, Kim YH, Hyun MC, et al. Cardiac functional evaluation using vector velocity imaging after chemotherapy including anthracyclines in children with cancer. Korean Circ J. 2009;39(9):352–8. 89. Poterucha JT, Kutty S, Lindquist RK, et al. Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction. J Am Soc Echocardiogr. 2012;25(7):733–40. 90. Cheung YF, Li SN, Chan GC, et al. Left ventricular twisting and untwisting motion in childhood cancer survivors. Echocardiography. 2011;28(7):738–45. 91. Cheung YF, Hong WJ, Chan GC, et al. Left ventricular myocardial deformation and mechanical dyssynchrony in children with normal ventricular shortening fraction after anthracycline therapy. Heart. 2010;96(14):1137–41. 92. Ho E, Brown A, Barrett P, et al. Subclinical anthracyclineand trastuzumab-induced cardiotoxicity in the longterm follow-up of asymptomatic breast cancer survivors: a speckle tracking echocardiographic study. Heart. 2010;96(9):701–7. 93. Wigle ED, Sasson Z, Henderson MA, et al. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis. 1985;28(1): 1–83.

94. Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Am Coll Cardiol. 2012;60(8):705–15. 95. Gruner C, Verocai F, Carasso S, et al. Systolic myocardial mechanics in patients with Anderson-Fabry disease with and without left ventricular hypertrophy and in comparison to nonobstructive hypertrophic cardiomyopathy. Echocardiography. 2012;29(7):810–7. 96. Carasso S, Yang H, Woo A, et al. Systolic myocardial mechanics in hypertrophic cardiomyopathy: novel concepts and implications for clinical status. J Am Soc Echocardiogr. 2008;21(6):675–83. 97. Yang H, Carasso S, Woo A, et al. Hypertrophy pattern and regional myocardial mechanics are related in septal and apical hypertrophic cardiomyopathy. J Am Soc Echocardiogr. 2010;23(10):1081–9. 98. Sun JP, Stewart WJ, Yang XS, et al. Differentiation of hypertrophic cardiomyopathy and cardiac amyloidosis from other causes of ventricular wall thickening by two-dimensional strain imaging echocardiography. Am J Cardiol. 2009;103(3):411–5. 99. Abozguia K, Nallur-Shivu G, Phan TT, et al. Left ventricular strain and untwist in hypertrophic cardiomyopathy: relation to exercise capacity. Am Heart J. 2010;159(5):825–32. 100. Abecasis J, Dourado R, Arroja I, et al. Utility of tissue characterization in apical hypertrophic cardiomyopathy diagnosis. Eur J Echocardiogr. 2009;10 (2):325–8. 101. Richand V, Lafitte S, Reant P, et al. An ultrasound speckle tracking (two-dimensional strain) analysis of myocardial deformation in professional soccer players compared with healthy subjects and hypertrophic cardiomyopathy. Am J Cardiol. 2007;100(1):128–32. 102. Mookadam F, Jiamsripong P, Raslan SF, et al. Constrictive pericarditis and restrictive cardiomyopathy in the modern era. Future Cardiol. 2011;7(4):471–83. 103. Sengupta PP, Krishnamoorthy VK, Abhayaratna WP, et al. Disparate patterns of left ventricular mechanics differentiate constrictive pericarditis from restrictive cardiomyopathy. JACC Cardiovasc Imaging. 2008;1(1):29–38. 104. McKenna WJ, Thiene G, Nava A, et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br Heart J. 1994;71(3):215–18. 105. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/ dysplasia: proposed modification of the task force criteria. Circulation. 2010;121(13):1533–41. 106. Vitarelli A, Cortes Morichetti M, Capotosto L, et al. Utility of strain echocardiography at rest and after stress testing in arrhythmogenic right ventricular dysplasia. Am J Cardiol. 2013;111(9):1344–50. 107. Sarvari SI, Haugaa KH, Anfinsen OG, et al. Right ventricular mechanical dispersion is related to malignant arrhythmias: a study of patients with arrhythmogenic right ventricular cardiomyopathy and subclinical right ventricular dysfunction. Eur Heart J. 2011;32(9):1089–96.

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

108. Teske AJ, Cox MG, Te Riele AS, et al. Early detection of regional functional abnormalities in asymptomatic ARVD/C gene carriers. J Am Soc Echocardiogr. 2012;25(9): 997–1006. 109. Bhatia NL, Tajik AJ, Wilansky S, et al. Isolated noncompaction of the left ventricular myocardium in adults: a systematic overview. J Card Fail. 2011;17(9):771–8. 110. Paterick TE, Tajik AJ. Left ventricular noncompaction: a diagnostically challenging cardiomyopathy. Circ J. 2012; 76(7):1556–62. 111. Niemann M, Liu D, Hu K, et al. Echocardiographic quantification of regional deformation helps to distinguish isolated left ventricular non-compaction from dilated cardiomyopathy. Eur J Heart Fail. 2012;14(2):155–61. 112. van Dalen BM, Caliskan K, Soliman OI, et al. Left ventricular solid body rotation in non-compaction cardiomyopathy: a potential new objective and quantitative functional diagnostic criterion? Eur J Heart Fail. 2008;10(11): 1088–93. 113. Koh C, Hong WJ, Wong SJ, et al. Systolic-diastolic coupling of myocardial deformation of the left ventricle in children with left ventricular noncompaction. Heart Vessels. 2010; 25(6):493–9. 114. Bellavia D, Michelena HI, Martinez M, et al. Speckle myocardial imaging modalities for early detection of myocardial impairment in isolated left ventricular noncompaction. Heart. 2010;96(6):440–7. 115. Kostareva A, Sejersen T, Sjoberg G. Genetic spectrum of cardiomyopathies with neuromuscular phenotype. Front Biosci (Schol Ed). 2013;5:325–40. 116. Smith GC, Kinali M, Prasad SK, et al. Primary myocardial dysfunction in autosomal dominant EDMD. A tissue doppler and cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2006;8(5):723–30. 117. Hor KN, Wansapura J, Markham LW, et al. Circumferential strain analysis identifies strata of cardiomyopathy in Duchenne muscular dystrophy: a cardiac magnetic resonance tagging study. J Am Coll Cardiol. 2009;53(14): 1204–10. 118. Bilchick KC, Salerno M, Plitt D, et al. Prevalence and distribution of regional scar in dysfunctional myocardial segments in Duchenne muscular dystrophy. J Cardiovasc Magn Reson. 2011;13:20. 119. Ryan TD, Taylor MD, Mazur W, et al. Abnormal circumferential strain is present in young duchenne muscular dystrophy patients. Pediatr Cardiol. 2013;34(5): 1159–65. 120. Rosales XQ, Moser SJ, Tran T, et al. Cardiovascular magnetic resonance of cardiomyopathy in limb girdle muscular dystrophy 2B and 2I. J Cardiovasc Magn Reson. 2011;13:39. 121. Hor KN, Gottliebson WM, Carson C, et al. Comparison of magnetic resonance feature tracking for strain calculation with harmonic phase imaging analysis. JACC Cardiovasc Imaging. 2010;3(2):144–51. 122. Guth BD, Schulz R, Heusch G. Time course and mechanisms of contractile dysfunction during acute myocardial ischemia. Circulation. 1993;87(5 Suppl): IV35–42.

411

123. Weidemann F, Wacker C, Rauch A, et al. Sequential changes of myocardial function during acute myocardial infarction, in the early and chronic phase after coronary intervention described by ultrasonic strain rate imaging. J Am Soc Echocardiogr. 2006;19(7):839–47. 124. Derumeaux G, Ovize M, Loufoua J, et al. Doppler tissue imaging quantitates regional wall motion during myocardial ischemia and reperfusion. Circulation. 1998;97(19):1970–7. 125. Voigt JU, Arnold MF, Karlsson M, et al. Assessment of regional longitudinal myocardial strain rate derived from doppler myocardial imaging indexes in normal and infarcted myocardium. J Am Soc Echocardiogr. 2000;13(6):588–98. 126. Skulstad H, Edvardsen T, Urheim S, et al. Postsystolic shortening in ischemic myocardium: active contraction or passive recoil? Circulation. 2002;106(6):718–24. 127. Edvardsen T, Urheim S, Skulstad H, et al. Quantification of left ventricular systolic function by tissue Doppler echocardiography: added value of measuring pre- and postejection velocities in ischemic myocardium. Circulation. 2002;105(17):2071–7. 128. Lim P, Pasquet A, Gerber B, et al. Is postsystolic shortening a marker of viability in chronic left ventricular ischemic dysfunction? Comparison with late enhancement contrast magnetic resonance imaging. J Am Soc Echocardiogr. 2008;21(5):452–7. 129. Zhang Y, Chan AK, Yu CM, et al. Strain rate imaging differentiates transmural from non-transmural myocardial infarction: a validation study using delayed-enhancement magnetic resonance imaging. J Am Coll Cardiol. 2005; 46(5):864–71. 130. Voigt JU, Exner B, Schmiedehausen K, et al. Strain-rate imaging during dobutamine stress echocardiography provides objective evidence of inducible ischemia. Circulation. 2003;107(16):2120–6. 131. Skulstad H, Urheim S, Edvardsen T, et al. Grading of myocardial dysfunction by tissue Doppler echocardiography: a comparison between velocity, displacement, and strain imaging in acute ischemia. J Am Coll Cardiol. 2006;47(8):1672–82. 132. Hanekom L, Jenkins C, Jeffries L, et al. Incremental value of strain rate analysis as an adjunct to wall-motion scoring for assessment of myocardial viability by dobutamine echocardiography: a follow-up study after revascularization. Circulation. 2005;112(25):3892–900. 133. Bansal M, Jeffriess L, Leano R, et al. Assessment of myocardial viability at dobutamine echocardiography by deformation analysis using tissue velocity and speckletracking. JACC Cardiovasc Imaging. 2010;3(2):121–31. 134. Lyseggen E, Skulstad H, Helle-Valle T, et al. Myocardial strain analysis in acute coronary occlusion: a tool to assess myocardial viability and reperfusion. Circulation. 2005;112(25):3901–10. 135. Roes SD, Mollema SA, Lamb HJ, et al. Validation of echocardiographic two-dimensional speckle tracking longitudinal strain imaging for viability assessment in patients with chronic ischemic left ventricular dysfunction and comparison with contrast-enhanced magnetic resonance imaging. Am J Cardiol. 2009;104(3):312–7.

412

Section 2: Echocardiography/Ultrasound Examination and Training

136. Butz T, Lang CN, van Bracht M, et al. Segment-orientated analysis of two-dimensional strain and strain rate as assessed by velocity vector imaging in patients with acute myocardial infarction. Int J Med Sci. 2011;8(2):106–13. 137. Sjoli B, Orn S, Grenne B, et al. Comparison of left ventricular ejection fraction and left ventricular global strain as determinants of infarct size in patients with acute myocardial infarction. J Am Soc Echocardiogr. 2009; 22(11):1232–8. 138. Choi JO, Cho SW, Song YB, et al. Longitudinal 2D strain at rest predicts the presence of left main and three vessel coronary artery disease in patients without regional wall motion abnormality. Eur J Echocardiogr. 2009;10(5): 695–701. 139. Aarsaether E, Rösner A, Straumbotn E, et al. Peak longitudinal strain most accurately reflects myocardial segmental viability following acute myocardial infarction: an experimental study in open-chest pigs. Cardiovasc Ultrasound. 2012;10:23. 140. Becker M, Hoffmann R, Kühl HP, et al. Analysis of myocardial deformation based on ultrasonic pixel tracking to determine transmurality in chronic myocardial infarction. Eur Heart J. 2006;27(21):2560–6. 141. Reant P, Labrousse L, Lafitte S, et al. Experimental validation of circumferential, longitudinal, and radial 2-dimensional strain during dobutamine stress echocardiography in ischemic conditions. J Am Coll Cardiol. 2008;51(2):149–57. 142. Newburger JW, Takahashi M, Gerber MA, et al. Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease; Council on Cardiovascular Disease in the Young; American Heart Association; American Academy of Pediatrics. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110(17):2747–71. 143. Yu JJ, Choi HS, Kim YB, et al. Analyses of left ventricular myocardial deformation by speckle-tracking imaging during the acute phase of Kawasaki disease. Pediatr Cardiol. 2010;31(6):807–12. 144. Ge D, Yang XY, Wang RL, et al. Assessment of regional left ventricular systolic function by VSI in children with Kawasaki disease. Zhongguo Dang Dai Er Ke Za Zhi. 2010;12(4):248–51. 145. Fang ZY, Leano R, Marwick TH. Relationship between longitudinal and radial contractility in subclinical diabetic heart disease. Clin Sci. 2004;106(1):53–60. 146. Ceyhan K, Kadi H, Koç F, et al. Longitudinal left ventricular function in normotensive prediabetics: a tissue Doppler and strain/strain rate echocardiography study. J Am Soc Echocardiogr. 2012; 25(3):349–56. 147. Fabre A, Sheppard MN. Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death. Heart. 2006;92(3):316–20. 148. Khoo NS, Smallhorn JF, Atallah J, et al. Altered left ventricular tissue velocities, deformation and twist in children and young adults with acute myocarditis and normal ejection fraction. J Am Soc Echocardiogr. 2012;25(3):294–303.

149. Hsiao JF, Koshino Y, Bonnichsen CR, et al. Speckle tracking echocardiography in acute myocarditis. Int J Cardiovasc Imaging. 2013;29(2):275–84. 150. Tsang W, Lang RM. Echocardiographic evaluation of cardiac amyloid. Curr Cardiol Rep. 2010;12(3):272–6. 151. Cappelli F, Porciani MC, Bergesio F, et al. Right ventricular function in AL amyloidosis: characteristics and prognostic implication. Eur Heart J Cardiovasc Imaging. 2012;13(5):416–22. 152. Porciani MC, Cappelli F, Perfetto F, et al. Rotational mechanics of the left ventricle in AL amyloidosis. Echocardiography. 2010;27(9):1061–8. 153. McLaughlin VV, Presberg KW, Doyle RL, et al. American College of Chest Physicians. Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126(1 Suppl):78S–92S. 154. Haeck ML, Scherptong RW, Marsan NA, et al. Prognostic value of right ventricular longitudinal peak systolic strain in patients with pulmonary hypertension. Circ Cardiovasc Imaging. 2012;5(5):628–36. 155. Fukuda Y, Tanaka H, Sugiyama D, et al. Utility of right ventricular free wall speckle-tracking strain for evaluation of right ventricular performance in patients with pulmonary hypertension. J Am Soc Echocardiogr. 2011;24(10): 1101–8. 156. Saleh HK, Villarraga HR, Kane GC, et al. Normal left ventricular mechanical function and synchrony values by speckle-tracking echocardiography in the transplanted heart with normal ejection fraction. J Heart Lung Transplant. 2011;30(6):652–8. 157. Kailin JA, Miyamoto SD, Younoszai AK, et al. Longitudinal myocardial deformation is selectively decreased after pediatric cardiac transplantation: a comparison of children 1 year after transplantation with normal subjects using velocity vector imaging. Pediatr Cardiol. 2012;33(5):749–56. 158. Kato TS, Oda N, Hashimura K, et al. Strain rate imaging would predict sub-clinical acute rejection in heart transplant recipients. Eur J Cardiothorac Surg. 2010;37(5):1104–10. 159. Lisi M, Cameli M, Tacchini D, et al. Two-dimensional speckle tracking echocardiography of acute cardiac transplant rejection following pregnancy. J Clin Ultrasound. 2012;40(7):451–4. 160. Sarvari SI, Gjesdal O, Gude E, et al. Early postoperative left ventricular function by echocardiographic strain is a predictor of 1-year mortality in heart transplant recipients. J Am Soc Echocardiogr. 2012;25(9):1007–14. 161. Yang HS, Mookadam F, Warsame TA, et al. Evaluation of right ventricular global and regional function during stress echocardiography using novel velocity vector imaging. Eur J Echocardiogr. 2010;11(2):157–64. 162. Stefani L, Pedrizzetti G, De Luca A, et al. Real-time evaluation of longitudinal peak systolic strain (speckle tracking measurement) in left and right ventricles of athletes. Cardiovasc Ultrasound. 2009;7:17. 163. Ryo K, Tanaka H, Kaneko A, et al. Efficacy of longitudinal speckle tracking strain in conjunction with isometric handgrip stress test for detection of ischemic myocardial segments. Echocardiography. 2012;29(4):411–8.

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

164. Vitarelli A, Cortes Morichetti M, Capotosto L, et al. Utility of strain echocardiography at rest and after stress testing in arrhythmogenic right ventricular dysplasia. Am J Cardiol. 2013;111(9):1344–50. 165. Donal E, Thebault C, O’Connor K, et al. Impact of aortic stenosis on longitudinal myocardial deformation during exercise. Eur J Echocardiogr. 2011;12(3):235–41. 166. Fukuda Y, Tanaka H, Sugiyama D, et al. Utility of right ventricular free wall speckle-tracking strain for evaluation of right ventricular performance in patients with pulmonary hypertension. J Am Soc Echocardiogr. 2011;24(10):1101–8. 167. Alghamdi MH, Mertens L, Lee W, et al. Longitudinal right ventricular function is a better predictor of right ventricular contribution to exercise performance than global or outflow tract ejection fraction in tetralogy of Fallot: a combined echocardiography and magnetic resonance study. Eur Heart J Cardiovasc Imaging. 2013;14(3):235–9. 168. Vitarelli A, Capotosto L, Placanica G, et al. Comprehensive assessment of biventricular function and aortic stiffness in athletes with different forms of training by threedimensional echocardiography and strain imaging. Eur Heart J Cardiovasc Imaging; 2013 Jan 8 [Epub ahead of print]. 169. Schefer KD, Bitschnau C, Weishaupt MA, et al. Quantitative analysis of stress echocardiograms in healthy horses with 2-dimensional (2D) echocardiography, anatomical M-mode, tissue Doppler imaging, and 2D speckle tracking. J Vet Intern Med. 2010;24(4):918–31. 170. De Luca A, Stefani L, Pedrizzetti G, et al. The effect of exercise training on left ventricular function in young elite athletes. Cardiovasc Ultrasound. 2011;9:27. 171. Nottin S, Doucende G, Schuster-Beck I, et al. Alteration in left ventricular normal and shear strains evaluated by 2D-strain echocardiography in the athlete’s heart. J Physiol (Lond). 2008;586(Pt 19):4721–33. 172. Nottin S, Ménétrier A, Rupp T, et al. Role of left ventricular untwisting in diastolic dysfunction after long duration exercise. Eur J Appl Physiol. 2012;112(2):525–33. 173. D’Ascenzi F, Cameli M, Zacà V, et al. Supernormal diastolic function and role of left atrial myocardial deformation analysis by 2D speckle tracking echocardiography in elite soccer players. Echocardiography. 2011;28(3):320–6. 174. Kim DG, Lee KJ, Lee S, et al. Feasibility of two-dimensional global longitudinal strain and strain rate imaging for the assessment of left atrial function: a study in subjects with a low probability of cardiovascular disease and normal exercise capacity. Echocardiography. 2009;26(10):1179–87. 175. Chung ES, Leon AR, Tavazzi L, et al. Results of the Predictors of Response to CRT (PROSPECT) trial. Circulation. 2008; 117(20):2608–16. 176. Risum N, Jons C, Olsen NT, et al. Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy: rationale, initial results, and advantages. Am Heart J. 2012;163(4):697–704. 177. Shin SH, Hung CL, Uno H, et al. Valsartan in Acute Myocardial Infarction Trial (VALIANT) Investigators. Mechanical dyssynchrony after myocardial infarction in patients with left ventricular dysfunction, heart failure, or both. Circulation. 2010;121(9):1096–103.

413

178. Vannan MA, Pedrizzetti G, Li P, et al. Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging: description and initial clinical application of a novel method using high-frame rate B-mode echocardiographic images. Echocardiography. 2005;22(10):826–30. 179. Cannesson M, Tanabe M, Suffoletto MS, et al. Velocity vector imaging to quantify ventricular dyssynchrony and predict response to cardiac resynchronization therapy. Am J Cardiol. 2006;98(7):949–53. 180. Pouleur AC, Knappe D, Shah AM, et al. MADIT-CRT Investigators. Relationship between improvement in left ventricular dyssynchrony and contractile function and clinical outcome with cardiac resynchronization therapy: the MADIT-CRT trial. Eur Heart J. 2011;32(14):1720–9. 181. Knappe D, Pouleur AC, Shah AM, et al. Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy Investigators. Dyssynchrony, contractile function, and response to cardiac resynchronization therapy. Circ Heart Fail. 2011;4(4):433–40. 182. Tanaka H, Tanabe M, Simon MA, et al. Left ventricular mechanical dyssynchrony in acute onset cardiomyopathy: association of its resolution with improvements in ventricular function. JACC Cardiovasc Imaging. 2011;4(5): 445–56. 183. Bai R, Di Biase L, Mohanty P, et al. Positioning of left ventricular pacing lead guided by intracardiac echocardiography with vector velocity imaging during cardiac resynchronization therapy procedure. J Cardiovasc Electrophysiol. 2011;22(9):1034–41. 184. Janousek J, Tomek V, Chaloupecký VA, et al. Cardiac resynchronization therapy: a novel adjunct to the treatment and prevention of systemic right ventricular failure. J Am Coll Cardiol. 2004;44(9):1927–31. 185. Janousek J, Gebauer RA, Abdul-Khaliq H, et al. Working Group for Cardiac Dysrhythmias and Electrophysiology of the Association for European Paediatric Cardiology. Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates. Heart. 2009;95(14):1165–71. 186. Dubin AM, Janousek J, Rhee E, et al. Resynchronization therapy in pediatric and congenital heart disease patients: an international multicenter study. J Am Coll Cardiol. 2005;46(12):2277–83. 187. Strieper M, Karpawich P, Frias P, et al. Initial experience with cardiac resynchronization therapy for ventricular dysfunction in young patients with surgically operated congenital heart disease. Am J Cardiol. 2004;94(10):1352–4. 188. Cecchin F, Frangini PA, Brown DW, et al. Cardiac resynchronization therapy (and multisite pacing) in pediatrics and congenital heart disease: five years experience in a single institution. J Cardiovasc Electrophysiol. 2009;20(1): 58–65. 189. Tzemos N, Harris L, Carasso S, et al. Adverse left ventricular mechanics in adults with repaired tetralogy of Fallot. Am J Cardiol. 2009;103(3):420–5.

414

Section 2: Echocardiography/Ultrasound Examination and Training

190. Friedberg MK, Silverman NH, Dubin AM, et al. Mechanical dyssynchrony in children with systolic dysfunction secondary to cardiomyopathy: a Doppler tissue and vector velocity imaging study. J Am Soc Echocardiogr. 2007;20(6): 756–63. 191. Bansal M, Cho GY, Chan J, et al. Feasibility and accuracy of different techniques of two-dimensional speckle based strain and validation with harmonic phase magnetic resonance imaging. J Am Soc Echocardiogr. 2008;21(12): 1318–25. 192. Koopman LP, Slorach C, Hui W, et al. Comparison between different speckle tracking and color tissue Doppler techniques to measure global and regional myocardial deformation in children. J Am Soc Echocardiogr. 2010; 23(9):919–28. 193. Koopman LP, Slorach C, Manlhiot C, et al. Assessment of myocardial deformation in children using Digital Imaging and Communications in Medicine (DICOM) data and vendor independent speckle tracking software. J Am Soc Echocardiogr. 2011;24(1):37–44. 194. Biaggi P, Carasso S, Garceau P, et al. Comparison of two different speckle tracking software systems: does the method matter? Echocardiography. 2011;28(5):539–47. 195. Tanaka H, Hara H, Saba S, et al. Prediction of response to cardiac resynchronization therapy by speckle tracking echocardiography using different software approaches. J Am Soc Echocardiogr. 2009;22(6):677–84. 196. Risum N, Ali S, Olsen NT, et al. Variability of global left ventricular deformation analysis using vendor dependent and independent two-dimensional speckle-tracking software in adults. J Am Soc Echocardiogr. 2012;25(11): 1195–203. 197. Nelson MR, Hurst RT, Raslan SF, et al. Echocardiographic measures of myocardial deformation by speckle-tracking technologies: the need for standardization? J Am Soc Echocardiogr. 2012;25(11):1189–94. 198. Marwick TH. Will standardization make strain a standard measurement? J Am Soc Echocardiogr. 2012;25(11):1204–6. 199. Henein MY, Gibson DG. Long axis function in disease. Heart. 1999;81(3):229–31. 200. Mor-Avi V, Lang RM, Badano LP, et al. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr. 2011;24(3):277–313. 201. Jasaityte R, Heyde B, D’hooge J. Current state of three-dimensional myocardial strain estimation using echocardiography. J Am Soc Echocardiogr. 2013;26(1): 15–28. 202. Saito K, Okura H, Watanabe N, et al. Comprehensive evaluation of left ventricular strain using speckle tracking echocardiography in normal adults: comparison of threedimensional and two-dimensional approaches. J Am Soc Echocardiogr. 2009;22(9):1025–30.

203. Perez de Isla L, Balcones DV, Fernandez-Golfin C, et al. Three-dimensional-wall motion tracking: a new and faster tool for myocardial strain assessment: comparison with two-dimensional-wall motion tracking. J Am Soc Echocardiogr. 2009;22(4):325–30. 204. Nesser HJ, Mor-Avi V, Gorissen W, et al. Quantification of left ventricular volumes using three-dimensional echocardiographic speckle tracking: comparison with MRI. Eur Heart J. 2009;30(13):1565–73. 205. Reant P, Barbot L, Touche C, et al. Evaluation of global left ventricular systolic function using three-dimensional echocardiography speckle-tracking strain parameters. J Am Soc Echocardiogr. 2012;25(1):68–79. 206. Jeung MY, Germain P, Croisille P, et al. Myocardial tagging with MR imaging: overview of normal and pathologic findings. Radiographics. 2012; 32(5):1381–98. 207. Zerhouni EA, Parish DM, Rogers WJ, et al. Human heart: tagging with MR imaging–a method for noninvasive assessment of myocardial motion. Radiology. 1988;169(1):59–63. 208. Axel L, Dougherty L. MR imaging of motion with spatial modulation of magnetization. Radiology. 1989;171(3): 841–5. 209. Osman NF, Kerwin WS, McVeigh ER, et al. Cardiac motion tracking using CINE harmonic phase (HARP) magnetic resonance imaging. Magn Reson Med. 1999;42 (6):1048–60. 210. Osman NF, Prince JL. Visualizing myocardial function using HARP MRI. Phys Med Biol. 2000;45(6):1665–82. 211. Cho GY, Chan J, Leano R, et al. Comparison of twodimensional speckle and tissue velocity based strain and validation with harmonic phase magnetic resonance imaging. Am J Cardiol. 2006;97(11):1661–6. 212. Amundsen BH, Crosby J, Steen PA, et al. Regional myocardial long-axis strain and strain rate measured by different tissue Doppler and speckle tracking echocardiography methods: a comparison with tagged magnetic resonance imaging. Eur J Echocardiogr. 2009;10(2):229–37. 213. Hor KN, Gottliebson WM, Carson C, et al. Comparison of magnetic resonance feature tracking for strain calculation with harmonic phase imaging analysis. JACC Cardiovasc Imaging. 2010;3(2):144–51. 214. Hor KN, Baumann R, Pedrizzetti G, et al. Magnetic resonance derived myocardial strain assessment using feature tracking. J Vis Exp. 2011;48:2356. 215. Maret E, Todt T, Brudin L, et al. Functional measurements based on feature tracking of cine magnetic resonance images identify left ventricular segments with myocardial scar. Cardiovasc Ultrasound. 2009;7:53. 216. Li P, Meng H, Liu SZ, et al. Quantification of left ventricular mechanics using vector-velocity imaging, a novel feature tracking algorithm, applied to echocardiography and cardiac magnetic resonance imaging. Chin Med J. 2012; 125(15):2719–27. 217. Sengupta PP, Khandheria BK, Narula J. Twist and untwist mechanics of the left ventricle. Heart Fail Clin. 2008;4(3):315–24.

Chapter 20: Echocardiographic Assessment of Global and Segmental Function Using Velocity Vector ImagingTM

218. Liu X, Li Z. Assessment of cardiac twist in dilated cardiomyopathy using velocity vector imaging. Echocardiography. 2010;27(4):400–5. 219. Liu XW, Li ZA. Assessment of cardiac twist in dilated cardiomyopathy using echocardiography velocity vector imaging. Zhonghua Yi Xue Za Zhi. 2009;89(27): 1892–6. 220. Suzuki K, Akashi YJ, Mizukoshi K, et al. Relationship between left ventricular ejection fraction and mitral annular displacement derived by speckle tracking echocardiography in patients with different heart diseases. J Cardiol. 2012;60(1):55–60.

415

221. Matsumoto K, Tanaka H, Kaneko A, et al. Contractile reserve assessed by three-dimensional global circumferential strain as a predictor of cardiovascular events in patients with idiopathic dilated cardiomyopathy. J Am Soc Echocardiogr. 2012;25(12):1299–308. 222. Kazui T, Niinuma H, Yamasaki M, et al. Septal myectomy and myotomy attenuate left ventricular hyper-contractility in a child with hypertrophic obstructive cardiomyopathy. Ann Thorac Cardiovasc Surg. 2012;18(2):162–5. 223. Carasso S, Yang H, Woo A, et al. Diastolic myocardial mechanics in hypertrophic cardiomyopathy. J Am Soc Echocardiogr. 2010;23(2):164–71.

CHAPTER 21 Contrast Echocardiography Jatinder Singh Pabla, Benoy Nalin Shah, Roxy Senior

Snapshot  What is Ultrasound Contrast?  How Does Ultrasound Contrast Work?  IndicaƟons for the Use of Ultrasound Contrast  Why Should I Use Ultrasound Contrast Agents?

INTRODUCTION Contrast echocardiography is a widely used, well-tolerated, noninvasive technique employing ultrasound contrast agents in order to improve image quality. Despite the introduction of tissue harmonic imaging (THI), echocardiography fails to yield diagnostic images in up to one-third of patients,1 the main impediments being high acoustic impedance of the patient’s chest wall because of obesity and lung disease. This results in poor delineation of the left ventricular endocardial borders preventing accurate assessment of left ventricle (LV) structure, volumes, ejection fraction and regional systolic thickening. Nondiagnostic echocardiographic studies necessitate referral for other noninvasive techniques, which in turn increases cost.2 Contrast echocardiography exploits the ultrasonic properties of microbubbles, acoustically active gas filled microspheres, which remain within the intravascular space and allow the simultaneous assessment of global and regional myocardial structure, function and perfusion. A wealth of published data attests to the clinical utility of ultrasound contrast agents for accurate

 PracƟcal Tips  Safety of Ultrasound Contrast Agents  Saline Contrast Echocardiography

measurement of chamber volumes, ejection fraction and identification of structural abnormalities, as well as assessment of myocardial perfusion during rest and stress echocardiography (SE), a technique known as myocardial contrast echocardiography (MCE). This chapter explains the basic physical principles of ultrasound contrast agents, reviews the clinical indications for and evidence supporting their use and provides practical tips for optimizing images during contrast echocardiography.

WHAT IS ULTRASOUND CONTRAST? The Structure of Contrast Microbubbles Red blood cells (RBCs) are poor reflectors of ultrasound during conventional echocardiography because of a small difference in acoustic impedance between them and the surrounding plasma. Only with aggregation of RBCs, as seen in low flow states, do they become echogenic. Ultrasound contrast agents (UCAs) increase the ultrasound backscatter intensity even with normal blood flow.3 These microbubble contrast agents behave

Chapter 21: Contrast Echocardiography

417

the smallest blood vessels in the body, the pulmonary capillaries, in order to reach the left heart. The shells are flexible in order to facilitate transit across the pulmonary capillary beds. The phospholipid shells are also negatively charged, which prevents them from aggregating and occluding the microvasculature. All the commercially available contrast agents contain a fluorocarbon gas of higher density and lower solubility compared with air which diffuses out of the shell slowly, thereby prolonging their duration of action. These gases are biologically inert and are exhaled via the lungs, whereas the shells undergo hepatic metabolism.

Commercially Available Contrast Agents Fig. 21.1: An illustration of the structure of second generation ultrasound contrast agents. The outer shell consists of albumin or phospholipids and contains an inner fluorocarbon gas of high density and low solubility.

similar to RBCs. When injected intravenously, they remain entirely within the vascular compartment (unless there is active bleeding). They do not cross the endothelium into the cell interstitium and should not be confused with iodine-based contrast used in computed tomography (CT) and X-ray angiography or the gadolinium-based contrast agents used in cardiac magnetic resonance (CMR) imaging. Manufactured UCAs consist of microbubbles encapsulating an acoustically active, high molecular-weight gas within an outer shell (Fig. 21.1). They have distinct ultrasound characteristics compared with surrounding tissue and enhance the ultrasound signal, allowing clearer LV endocardial border detection, improved structural and functional assessment of the LV, and assessment of myocardial perfusion. The first generation of UCAs consisted of an outer shell of denatured albumin encapsulating air. Although safe, these microbubbles were relatively large by today’s standards, their passage through the pulmonary capillaries was inconsistent and the air within the microbubbles dissipated quickly due to high solubility, resulting in a rapid deterioration of LV border enhancement. Thus, these agents had limited clinical use. Second generation UCAs consist of a thicker outer shell of albumin or phospholipids and an inner inert gas (nitrogen or fluorocarbon). The microbubbles are similar in size to RBCs and range from 1.1mm to 1.8 μm in diameter. They are small enough to flow through

The characteristics of the three currently available contrast agents are outlined in Table 21.1. Sonovue is the most widely used contrast agent in Europe (currently not approved in the United States), whereas Optison and Definity are most frequently used in the United States. Of note, Sonovue is currently contraindicated in patients with recent (< 7 days) acute coronary syndrome and New York Heart Association Class III to IV heart failure, although these restrictions do not apply to Optison or Definity.

Properties of the Ideal Contrast Agent The properties of the “ideal ultrasound contrast agent” are: • High echogenicity (strong reflector of ultrasound at the fundamental frequency of the ultrasound wave and at higher harmonics) • Linear relationship between concentration and signal intensity • Ability to cross the pulmonary capillary bed • High stability and persistence (ability to resist destruction at normal ultrasound power) • Ability for rapid destruction during delivery of pulsed high-intensity ultrasound and quick replenishment (of use during assessment of myocardial perfusion) • Minimal imaging artifacts • Safety.

HOW DOES ULTRASOUND CONTRAST WORK? Physics of Contrast Imaging Understanding the interaction between contrast agents and ultrasound is crucial if one wishes to learn contrast

418

Section 2: Echocardiography/Ultrasound Examination and Training

Table 21.1: Characteristics of Currently Available Contrast Agents Used in Echocardiography

Features

Sonovue

Optison

Definity

Gas Type

Sulphur Hexafluoride

Perfluoropropane

Octafluoropropane

Mean Diameter

2–8 μm

3.0–4.5 μm

1.1–2.5 μm

Shell

Phospholipid

Human albumin

Phospholipid

Manufacturer

Bracco Diagnostics

GE Healthcare

Lantheus Medical Imaging

The key difference between the way in which tissue and contrast respond to ultrasound is that with tissue, the incident (fundamental) frequency results in an equal and opposite vibration (i.e. a linear response), whereas microbubbles can expand to a greater degree than they can contract, resulting in unequal oscillation (i.e. a nonlinear response). This results in asymmetrical vibrations that produce harmonic frequencies (Fig. 21.2). Thus, the harmonic properties of microbubbles are a function of their nonlinear oscillation, which means that they reflect sound waves not only at the fundamental frequency (of the ultrasound source) but also at higher harmonic frequencies. Fig. 21.2: The response of microbubbles to increasing ultrasound intensity. (Top Row): At increasingly higher MIs, the intensity (I) of the reflected signal from the ultrasound contrast agent microbubbles increases, whereas the effective contrast duration (t) decreases. (Middle Row): At low MI, the microbubbles reflect the same frequency as the transmitted signal. When the MI rises, there is increasing compression and rarefaction of the microbubbles with eventual destruction. (Bottom Row): At a low MI, reflection of ultrasound occurs at the same fundamental frequency (f) and amplitude (A) as the transmitted signal (linear oscillation). At an intermediate MI, the microbubbles reflect ultrasound at the fundamental frequency and harmonics of this frequency (nonlinear oscillation), each with progressively lower amplitudes. At a high MI with microbubble destruction, a broad range of resonant frequencies are transmitted.

echocardiography from its basic principles. The frequency at which sound waves leave the transducer is known as the fundamental frequency. The ultrasound waves become distorted on passing through the body as they encounter tissues of differing composition and density. This changes the waveform and generates frequencies different from the fundamental frequency. These are harmonic frequencies, often shortened to harmonics, and this technique is sometimes referred to as THI. Harmonic frequencies include subharmonic, ultraharmonic, and multiples of the fundamental frequency. The strongest harmonic signals are multiples of the fundamental frequency.

Interaction between Ultrasound and Contrast Agents At any frequency, the magnitude of reflection of ultrasound energy is related to the size of the microbubble. The ultrasound scatter from microbubbles is proportional to the sixth power of the bubble’s radius, meaning that the largest bubble capable of traversing the pulmonary capillary bed without being destroyed will produce the best acoustic profile within the left heart. Therefore, the most desirable microbubble diameter is the largest that is still able to negotiate the pulmonary microcirculation. Microbubble contrast agents interact with ultrasound in three ways and this variation is dependent upon the mechanical index (MI). The MI is defined as the “peak rarefactional pressure (negative pressure) divided by the square root of the ultrasound frequency”; put simply, it is a measure of the power output from the ultrasound beam. Standard two-dimensional echocardiography is typically performed at an MI of 1.0–1.4. This MI would be too high for contrast imaging; however, the outer shells of the microspheres are destroyed by this strength of ultrasound waves, resulting in bubble implosion. Thus, a lower MI is required for contrast echocardiography.

Chapter 21: Contrast Echocardiography

A

419

B

Figs 21.3A and B: Microbubble response to a low mechanical index ultrasound signal. Compression and rarefaction of the microbubble shell occur at the same transmitted fundamental frequency and amplitude, resulting in linear oscillation.

A

B

Figs 21.4A and B: Microbubble response to an intermediate mechanical index ultrasound signal. The microspheres resonate in a nonlinear fashion and reflect ultrasound at both the fundamental frequency and harmonics of the fundamental frequency with lower amplitudes. Multiple harmonic generation results in an enhanced reflected signal.

There are three possible responses of microbubbles to ultrasound, dependent on the MI: 1. At low acoustic power (MI < 0.2), linear oscillation occurs, as the microbubbles undergo oscillation with compression and rarefaction that are equal in amplitude and thus no special contrast-enhanced signal is generated. Microbubbles act as strong scattering objects because of the difference in impedance between air and liquid, and the acoustic response is optimized at the resonant frequency of a microbubble (Figs 21.3A and B and Movie clip 21.1) 2. At intermediate acoustic power (MI between 0.2 and 0.5), nonlinear oscillation occurs (bubbles undergo rarefaction that is greater than compr-

ession). Ultrasound waves are created at harmonics of the delivered frequency. The harmonic response frequencies are different from that of the incident wave (fundamental frequency). These contrastenhanced ultrasound signals are microbubblespecific (Figs 21.4A and B and Movie clip 21.2). 3. At high acoustic power (MI > 0.5), microbubble destruction begins with subsequent transient emission of high intensity signals that are very rich in nonlinear components. Intermittent imaging becomes necessary to allow the capillaries to refill with further microbubbles. It should be noted that microbubble destruction occurs to some degree at all MIs, but is most prominent at higher MI imaging.

420

Section 2: Echocardiography/Ultrasound Examination and Training

•

Fig. 21.5: The various myocardial contrast echocardiography imaging modalities available at low and high mechanical indices. Source: Contrast Echo Tool Box (Senior et al, Recommended Reading 1)—with permission from the European Association of Cardiovascular Imaging (EACVI)

Contrast Modalities A number of contrast-specific imaging modalities, at low MI and high MI, are available for contrast imaging, as depicted in Figure 21.5.

Real Time Imaging—Low MI Real time imaging uses a MI low enough to generate little tissue signal while generating sufficient signal from microbubbles. This allows continuous imaging as the low MI avoids significant bubble destruction. Microbubbles can be intentionally cleared from the myocardium by a “flash” of high MI ultrasound pulses; contrast replenishment is then observed to allow qualitative and/or quantitative assessment of myocardial perfusion. • Pulse inversion: A pulse cancellation technique with alternate transmission of two identical pulses per image line but of opposing polarity. Tissues behave linearly at low MI, so the returning tissue signal is the same as the emitted (fundamental frequency), so they cancel each other. However, nonlinear microbubble oscillation ensures that this signal is not cancelled, and thus a pure contrast harmonic signal is obtained. The pulse inversion method is extremely sensitive to contrast, even at very low MI (< 0.1). • Power modulation: The ultrasound machine selectively detects backscatter signal from microbubbles while suppressing reflections from tissue. The transducer emits two pulses of identical shape along a scan line, the second pulse being half of the amplitude of the first. The smaller reflection (from second pulse) is doubled and subtracted from first reflection. Assuming linear oscillation of tissue at low MI, this subtraction

results in zero tissue signal. However, due to nonlinear oscillation of microbubbles, reflecting pulses from contrast differ in amplitude and shape. Thus, the subtraction still leaves a signal, purely from contrast rather than tissue, which is detected by the ultrasound machine. Coherent contrast imaging (CCI): The theoretical limitation of both pulse inversion and power modulation is that each scan line needs to be pulsed multiple times, which reduces frame rate and increases bubble destruction. CCI is a nonlinear technique that can cancel the fundamental frequency with a single pulse. It is a grey-scale rather than Doppler-based technique using transmit pulse shaping and single pulse cancellation technologies. Coherent imaging simply means that multiple beam-formers are used to construct an image, rather than the usual discrete scan lines that are phase-independent of each other. Thus, in a coherent dataset, both amplitude and phase information are present, so all acquired data is tied together (i.e. is coherent). Principal Advantages of Low MI Imaging:

• • •

Simultaneous assessment of function and perfusion possible Effective “automatic background subtraction” of tissue signal as low MI generates minimal tissue harmonics Minimal bubble destruction with lower MI  less contrast utilization Principal Disadvantage of Low MI Imaging:

•

Reduced oscillation of bubbles at low MI  reduced acoustic signal generated  less sensitive than high MI imaging.

Triggered/Intermittent Imaging—High MI Although there is an excellent tissue signal at a high MI because of strong harmonic signals, there is significant microbubbles destruction. This transiently produces a substantially greater detectable ultrasound signal than from the surrounding tissue; however, continued exposure results in on-going destruction of the contrast agent and is thus ineffective for imaging. This led to the development of intermittent or triggered imaging. In these high MI imaging techniques, microbubbles are intentionally destroyed by high power signals sent intermittently triggered to the electrocardiography (ECG; e.g. 1:4—every fourth cycle). The time between pulses allows replenishment of

Chapter 21: Contrast Echocardiography

421

Increased bubble destruction  more near field artifacts  risk of false perfusion defects.

microbubbles. With each destructive pulse, a highamplitude backscatter rich in harmonics is returned to the transducer, enabling static images of myocardial perfusion. By incrementally increasing the triggering intervals (continuous → 1:1 → 1:2 → 1:4 → 1:8 etc.), the rate of replenishment of the ultrasound beam over time can be assessed both qualitatively and quantitatively. • Power Doppler harmonic imaging (PDHI): Conventional (velocity) Doppler assesses the speed of motion of RBCs. However, the intensity of the Doppler signal reflects the number of scatterers (i.e. RBCs) within the ultrasound beam. The image display can be altered to show the amplitude or power of the Doppler signal rather than velocity—this is the basis of PDHI. It is a multipulse technique (sends ultrasound pulses along a single scan line and detects the changes between pulses). The greater the change between pulses, the greater the intensity of the PDHI display. A color is displayed if there has been a change between pulses, and the saturation of the color reflects the amplitude of the echo that has changed. • Ultraharmonics: When the MI is deliberately increased beyond the point of oscillation, microbubbles produce a very transient, high-amplitude signal before destruction. This is an ultraharmonic frequency produced only by microbubbles and not tissue. Tissues return a very low signal at ultraharmonic frequencies and so microbubbles are easily detected. • Power pulse inversion: This is the same principle as pulse inversion, but combines the nonlinear detection performance of pulse inversion with the motion discrimination of power Doppler. A sequence of more than two pulses of alternating phase is emitted. Echoes from successive pulses are then recombined to eliminate the effect of tissue motion. This allows suppression of moving tissue without needing to disrupt the bubbles and thus can be performed either as high MI or as real time low MI imaging.

•

Key Advantages of High MI Imaging:

Principles of Assessment of Myocardial Perfusion—Myocardial Contrast Echocardiography

•

Increased sensitivity to contrast (bubble destruction results in greatest amplitude backscatter).

Key Disadvantages of High MI Imaging • • • •

Lacks simultaneous assessment of function Requires reliable ECG triggering and image acquisition Can be time-consuming and is more technically challenging Increased bubble destruction  more contrast use increased cost

Contrast Administration UCAs are administered intravenously either by a bolus injection or continuous infusion. Each has advantages and disadvantages.

Bolus Injection A slow bolus injection of approximately 0.2 mL of contrast is followed by a 2-mL saline flush over 10 seconds. This results in a rapid increase in signal intensity until a plateau is reached and there is then a gradual decay in contrast concentration, the rate of which varies in each patient. There is a theoretical point at which there is a “steady-state” concentration of contrast, but this cannot be predicted because peak signal intensity is affected by numerous factors including, for example, cardiac output and the rate of injection of contrast. Bolus injections are acceptable for studies in which the aim is to improve endocardial border delineation (EBD), perform left ventricular opacification (LVO) or enhance Doppler signals. It is best avoided during perfusion studies; however, a continuous infusion is preferable to ensure a steady-state concentration of contrast within the myocardial capillaries.

Continuous Infusion An infusion provides a steady-state concentration of microbubbles and reduces the likelihood of artifacts. The contrast effect during the course of the study is consistent and the study is more reproducible. Because there is a steady state of contrast concentration, it allows the assessment of myocardial perfusion both qualitatively and by quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). Continuous infusions can also be used for EBD or LVO purposes but are mandatory for perfusion imaging.

A continuous intravenous infusion of UCA is administered until the myocardium is fully saturated and the signal intensity has reached a steady-state. At this point, the signal intensity reflects the capillary blood volume (CBV).4 Reduced signal intensity will thus reflect a reduction in CBV.

422

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 21.6: Linear illustration of the derivation of MBF from myocardial contrast echocardiography imaging. The peak ultrasound intensity (red arrow) following a steady-state infusion of contrast represents the myocardial blood volume (A). The rate at which contrast replenishment occurs (blue arrow) after bubble destruction (i.e. microbubble velocity) represents red blood cell velocity ( ). The product of A and represents MBF. (MBF: Myocardial blood flow).

Myocardial perfusion is defined as tissue blood flow at the capillary level. The two components of tissue blood flow are myocardial blood volume (MBV) and RBC velocity. As contrast microbubbles are RBC tracers, the product of peak microbubble intensity (representative of MBV) and their rate of appearance (representative of blood velocity) yields the MBF. The coronary microcirculation consists of myocardial blood vessels with a diameter of less than 300 μm and the capillaries contain 90% of the total MBV. At the end of systole, myocardial contraction results in larger intramyocardial vessels being emptied of blood and thus the majority of MBV is contained within the capillaries. Therefore, MBV is effectively the same as CBV. The intensity of the contrast signal, when the myocardium is fully saturated during a continuous infusion of contrast, therefore reflects the concentration of microbubbles within myocardial capillaries (CBV, denoted as A). Any alteration of signal in such a situation must, therefore, occur predominantly from a change in CBV.4–7 Once a steady-state concentration of contrast in the myocardium has been achieved, a high-intensity “flash” (a series of high MI ultrasound frames) is used to destroy the microbubbles and their rate of replenishment (microbubble velocity, denoted as ) is then observed by imaging either intermittently (during high-power imaging) or continuously (during low-power imaging) to observe

contrast intensity and microbubble velocity. The red cell velocity is directly and proportionately related to blood flow (i.e. a stenosis will limit blood flow and thus result in longer replenishment time).8 The product of microbubble velocity and capillary (or myocardial) blood volume (A × ) is thus MBF, illustrated in Fig. 21.6. This technique of assessing myocardial perfusion during echocardiography is known as myocardial contrast echocardiography (MCE). It can be performed at rest to yield the basal MBF, but if also performed after physiological or pharmacological stress, when maximal MBF is derived, then the CFR can be obtained as the ratio between maximal and basal CFR. Thus, quantitative rest and stress MCE permits the noninvasive determination of CFR. Specialist software, which allows calculation of A,  and their product A × , permits quantification of MBF during MCE by placing regions of interest in LV myocardial segments.7 This quantitative approach can be time-consuming in daily practice and so qualitative or semiquantitative MCE is sometimes used, as described in the following section. Myocardial contrast echocardiography protocols have evolved significantly over the years, but the most common technique performed at present involves imaging at rest and at stress using conventional apical four-chamber, two-chamber and three-chamber views. Once a steady state of microbubbles has been achieved (usually using a continuous intravenous UCA infusion), a high-intensity (high MI) pulse or “flash” of ultrasound is used to destroy the bubbles on screen. The replenishment of these bubbles in the myocardium is then studied either qualitatively or quantitatively.

Contrast Modality During MCE (Low vs High MI) Myocardial contrast echocardiography can be performed at high MI (> 0.5) or low MI (0.1–0.3). Each technique has advantages and disadvantages. High mechanical index: The advantage of using a high MI is the favorable sensitivity of this technique. The destruction of UCA with a high MI signal generates powerful harmonic signals at multiple frequencies. The imaging needs to be intermittent to allow contrast replenishment in the myocardium before further (high MI) imaging. With intermittent (triggered) imaging there in an interruption of ultrasound transmission once every few cycles (e.g. 1 in 2, 1 in 4, 1 in 8 depending on the time taken for complete replenishment). Therefore,

Chapter 21: Contrast Echocardiography

real time imaging is not possible using a high MI approach. In addition, there is a greater contrast requirement compared with a low MI technique. High MI imaging also generates strong harmonics from tissue and thus contrastspecific background subtraction imaging settings are required to suppress them. Low mechanical index: The two biggest advantages of low MI, real time imaging are that firstly, simultaneous assessment of both wall motion and perfusion are possible and secondly, because there is less bubble destruction at low MI, smaller volumes of contrast are usually used. The disadvantage is that, at low MI, the signal emanating from the bubbles is weaker than at high MI and so the sensitivity is slightly lower. Low MI imaging is less sensitive than when using a high MI because the reflected ultrasound signal is less strong. However, this also means that contrast-specific background subtraction imaging settings are not required. It is possible to assess perfusion independently from wall motion by using triggered imaging at end-systole with several resulting advantages. At end-systole, only UCA present in capillaries is imaged because the remaining microvasculature is compressed by myocardium, the regions of interest are more easily imaged as myocardium is at its thickest and the incidence of lateral artifacts is less.

Qualitative MCE A qualitative MCE assessment is a visual analysis of the acquired images. As with many imaging techniques, this method is, to a degree, dependent upon the expertise of the performing and interpreting cardiologist(s). However, there have been multiple studies demonstrating that this is a reliable and accurate method of assessment. The advantage of this technique is the immediate analysis of images as they are acquired. Artifacts can also be easily identified, which many automated software methods cannot distinguish from true perfusion defects. Red blood cells flow at a rate of around 1 mm/s. Since the elevation/depth of a conventional adult twodimensional transthoracic transducer (probe) is usually 5 mm, it takes approximately 5 seconds for the entire myocardium in a normal individual to refill with contrast following the complete destruction of contrast as described in the previous section. This equates to five cardiac cycles if the resting heart rate is 60 beats per minute. With a normal CFR, the resting MBF increases four to five times with maximal hyperemia. Thus the RBCs (and thus contrast) would now flow at 5 mm/s. Following contrast destruction, replenishment would now occur

423

within 1 second or 1 cardiac cycle if the heart rate remains the same. With vasodilator stress (e.g. dipyridamole), there is normally little change in the heart rate; so there should be complete myocardial contrast replenishment within 1 second. However, with exercise or dobutamine/atropine stress, where the heart rate has increased to 120 beats per minute or more, complete replenishment would take at least two cardiac cycles (i.e. 1 second). In the presence of a coronary stenosis, during hyperemia (stress), the perfusion/driving pressure in the capillary bed supplied by the diseased artery falls significantly and these capillaries close, known as derecruitment. Consequently, there is an absolute reduction in blood flow through the subtended myocardial segment(s) and this is detected by MCE as a filling or perfusion defect (Figs 21.7 & 21.8 and Movie clips 21.3 to 21.6).

Semiquantitative MCE This information can be applied to score the segments in a semiquantitative manner if desired. Each myocardial segment that is analyzed is scored in a similar way to the assessment of regional wall motion, for example: 0 = normal perfusion 1 = delayed or reduced perfusion 2 = no perfusion A global perfusion value called a Perfusion Score Index (PSI) can then be obtained, where the PSI equals the sum of all myocardial segment scores divided by the total number of scored segments. The PSI at rest subtracted from the PSI at stress gives the ischemic burden of myocardium. Contrast uptake is reduced in situations where the capillary blood flow is impaired (e.g. scar tissue or post stress in the presence of flow-limiting coronary artery disease [CAD]). This results in a greater PSI value than in normal myocardium, because a decrease in MBF will manifest as absent or delayed replenishment of contrast during destruction-replenishment imaging. At rest, a PSI greater than 1.5 is associated with a low probability of viable myocardium. An alternative semiquantitative method is used to manually trace zones with absent perfusion in all three apical views to obtain perfusion defect border lengths and areas (Figs 21.9A and B). The values from the three apical views are averaged to obtain the contrast defect length (CDL) and contrast defect area (CDA). Total endocardial lengths and LV wall area are obtained in a similar way. The CDL and CDA are then expressed as a percentage of the total endocardial length and LV wall area, respectively. CDL% = CDL/total endocardial length × 100 CDA% = CDA/total LV wall area × 100

424

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 21.7A to D: Resting myocardial contrast echocardiography. (A) Preflash image (apical 4-chamber view) showing homogenous contrast intensity in the septal and lateral walls; (B) Flash image where a high mechanical index ultrasound pulse results in microbubble destruction; (C) First frame immediately postbubble destruction. There is complete bubble destruction throughout the LV walls and apex except for the basal septal segment. The basal septal segment is still opacified by contrast, implying that the microbubbles were not destroyed and thus replenishment cannot be assessed in this segment. The remaining segments are black indicating complete microbubble destruction enabling replenishment to be assessed in those regions; (D) There is complete microbubble replenishment within 1 second following microbubble destruction, indicating normal perfusion. (LA: Left atrium; LV: Left ventricle). Source: Contrast Echo Tool Box (Senior et al, Recommended Reading 1)—with permission from the European Association of Cardiovascular Imaging (EACVI).

The indexed contrast defect length (CDL %) is representative of transmural perfusion defects. However, the indexed contrast area (CDA %) is representative of both transmural and subendocardial perfusion defects.

Quantitative MCE As described in the previous section, quantification of MCE images obtained at rest and at stress allows for the derivation of CBV, erythrocytes velocity and, therefore, MBF. The ratio of MBF at stress compared with MBF at rest

then yields the CFR. A number of scientific experiments performed in the 1990s revealed the following: • Once a steady-state of contrast has been achieved in the microcirculation (usually with contrast infusion), the peak signal intensity represents the capillary or MBV • The rate at which contrast replenishment occurs after bubble destruction (i.e. microbubble velocity) represents RBC velocity (because contrast agents are essentially RBC tracers)

Chapter 21: Contrast Echocardiography

A

B

C

D

425

Figs 21.8A to D: Stress myocardial contrast echocardiography. Images from the same patient as in Fig. 21.7, following dipyridamole stress. Figures A, B and C show preflash, flash and immediate postflash appearances; Figure D demonstrates a clear subendocardial perfusion defect (arrows) visible due to delayed replenishment of microbubbles, indicative of ischemia. This patient was found to have a severe proximal left anterior descending coronary stenosis on angiography. Source: Contrast Echo Tool Box (Senior et al, Recommended Reading 1)—with permission from the European Association of Cardiovascular Imaging (EACVI).

A

B

Figs 21.9A and B: Semiquantitative assessment of subendocardial perfusion defects. (A) Contrast defect length: the lateral wall defect seen in the apical four-chamber view is measured by contrast defect length or endocardial border length (green line) in reference to the total LV endocardial wall (blue line); (B) Contrast defect area: the same perfusion defect can be quantitated by contrast defect area (green contour) in reference to the total LV wall area (blue contour). (LV: Left ventricle; RV: Right ventricle).

426

Section 2: Echocardiography/Ultrasound Examination and Training

Improved Endocardial Border Delineation (EBD) for Assessment of LV Function

Fig. 21.10: Apical four-chamber images from a 60-year-old overweight man referred for echocardiography to investigate dyspnea. The top panel shows precontrast images at end-diastole and endsystole. The endocardial borders are not visible and thus it is not possible to determine LV volumes, ejection fraction or regional systolic thickening. The bottom panel shows images from the same patient following contrast administration. The endocardium and LV cavity are now clearly delineated following contrast, thus allowing accurate assessment of LV size, structure and function. (LV: Left ventricle; RV: Right ventricle).

•

•

If a graph is drawn plotting contrast video intensity (VI; y axis) against time (x axis), an exponential curve is obtained (see Fig. 21.6) Mathematical analysis reveals that the plateau represents the peak MBV (denoted as A) and the initial slope of the curve is the microbubble velocity (denoted as ). A ×  then gives MBF.

INDICATIONS FOR THE USE OF ULTRASOUND CONTRAST Contrast echocardiography has three broad indications: 1. Enhanced endocardial border delineation (EBD) for improved assessment of global and regional systolic function, LV volumes, and ejection fraction 2. Left ventricular opacification (LVO) for improved detection of structural abnormalities 3. Myocardial contrast echocardiography (MCE) for evaluation of myocardial perfusion Each of these can be performed during rest and SE, as described in the following section.

Use of ultrasound contrast is recommended during resting echocardiography for patients with suboptimal visualization of the LV (Fig. 21.10, and Movie clips 21.7 and 21.8), defined as two or more contiguous segments not seen, in order to allow accurate assessment of: • Global systolic function • Regional systolic function • Ejection fraction (quantitation by biplane Simpson’s method). Contrast is also recommended during SE studies, when two or more contiguous segments are suboptimally visualized, in order to: • Obtain diagnostic assessment of regional (segmental) wall thickening at rest and at stress • To reduce the proportion of nondiagnostic/inconclusive studies • To increase reader confidence in image interpretation.

Left Ventricular Opacification for Assessment of LV Structural Abnormalities Left ventricular opacification is performed using an intermediate MI (e.g. 0.2–0.3) since a higher MI will result in bubble destruction and a deterioration in image quality, especially in the near-field. A low MI setting produces little harmonic signal from the tissues, which may result in failure of detection of subtle abnormalities because the returned ultrasound signal may be too weak. Therefore, an intermediate MI is recommended because a stronger ultrasound signal is returned by nonlinear oscillation of the contrast microbubbles along with an improved tissue signal. The American Society of Echocardiography and European Association of Cardiovascular Imaging (formerly European Association of Echocardiography) have both issued consensus statements on the use of contrast echocardiography for LVO,9,10 stating that contrast should be used in patients requiring confirmation or exclusion of LV structural abnormalities, intracardiac masses, and to enhance Doppler signals.

Chapter 21: Contrast Echocardiography

A

427

B

Figs 21.11A and B: Apical four-chamber images before and after contrast administration in a patient with a myocardial infarction in the left anterior descending coronary artery territory. There is no definite apical abnormality visible in the unenhanced image. However, an apical thrombus is clearly visible following contrast administration (arrows). (LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle).

A

B

Figs 21.12A and B: Apical four-chamber views of a patient investigated for exertional chest pain. (A) In this unenhanced image, the endocardial definition is poor and no structural abnormality can be identified; (B) Following contrast administration, apical hypertrophy can clearly be seen and a diagnosis of apical hypertrophic cardiomyopathy was made. (LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle).

Tissue harmonic imaging produces weak ultrasound signals in the near field. Therefore, apical abnormalities may be difficult to visualize and diagnose. In addition, suboptimal image quality will result in failure of accurate diagnosis. Contrast echocardiography is a simple, quick, cheap and effective imaging modality for the diagnosis of numerous structural abnormalities,11–15 including the following: • Left ventricular thrombus (Figs 21.11A and B, and Movie clips 21.9 and 21.10) • Apical hypertrophic cardiomyopathy (Figs21.12A and B)

• •

Left ventricular noncompaction cardiomyopathy (Figs 21.13A to D and Movie clips 21.11 to 21.14) Unusual pathologies (e.g. myocardial abscesses or pseudoaneurysms—Figs 21.14A & B and Movie clips 21.15 and 21.16).

Myocardial Contrast Echocardiography for Assessment of Myocardial Perfusion Myocardial contrast echocardiography can be used during rest and SE to evaluate myocardial perfusion. This information can be used at rest to determine myocardial

428

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 21.13A to D: A 39-year-old female presented with palpitations. Figures A and B show unenhanced parasternal short axis and apical four-chamber images, respectively, whereas Figures C and D are similar views following contrast administration. Although there is no definite abnormality in the unenhanced images, the myocardium appears hyper-trabeculated. Following contrast, however, multiple deep trabeculations are clearly visible (arrows) in the inferior, posterior and lateral walls confirming a diagnosis of left ventricular noncompaction. (LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle).

viability and at peak stress to detect myocardial ischemia. Previous studies demonstrated that myocyte loss is associated with loss of the microvasculature16 and that contrast signal intensity correlated strongly with capillary density on biopsy samples obtained from corresponding segments.17 Therefore, MCE is able to detect presence or absence of viable myocardium by virtue of its ability to assess the integrity of the microcirculation (Fig. 21.15, and Movie clips 21.17 and 21.18). Regarding detection of ischemia, as perfusion defects manifest before wallthickening abnormalities during demand ischemia, perfusion imaging is considered more sensitive than wall motion assessment for detection of significant CAD. Perfusion defects noted at peak stress that are not present at rest are indicative of myocardial ischemia.

As MCE detects perfusion, it can also be used to assess the vascularity (or perfusion) of intracardiac masses. This is an echocardiographic form of tissue characterization and is useful for distinguishing thrombus (avascular) from tumor (usually vascular).18

WHY SHOULD I USE ULTRASOUND CONTRAST AGENTS? Assessment of LV Structure, Function, Volumes and Ejection Fraction The commercially available contrast agents have all been shown to improve endocardial border delineation.

Chapter 21: Contrast Echocardiography

A

429

B

Figs 21.14A and B: A 78-year-old lady with a 6-month history of increasing leg swelling and breathlessness underwent echocardiography. (A) A grossly abnormal appearance in the parasternal short-axis suggestive of a myocardial rupture was noted; (B) Contrast administration confirmed blood flow through the large defect (black arrow) but then contained by a small rim of myocardium (white arrows), thus confirming the extent of the rupture. (LV: Left ventricle; RV: Right ventricle).

Fig. 21.15: Use of resting myocardial contrast echocardiography to determine myocardial viability for predicting response to CRT. Top row images are from a patient with normal lateral wall perfusion and he did have a good response to CRT with reverse remodeling noted. The bottom images are from a patient with a clear lateral wall perfusion defect (arrows) indicative of scar tissue; the LV pacing lead should not be placed over the lateral wall in such a patient. (CRT: Cardiac resynchronization therapy; LV: Left ventricle).

Echocardiography without contrast underestimates LV volumes by up to 40% and LV ejection fraction by 3–6% when compared with CMR. Multiple studies involving hundreds of patients with suboptimal images on unenhanced echocardiography have demonstrated superior endocardial border delineation and left ventricular opacification postcontrast, thus providing diagn-

ostic images and a more accurate assessment of LV volumes and LV ejection fraction.19–22 These studies have included patients in the acute period following myocardial infarction and critically ill patients in the intensive care unit. Contrast echocardiography has been shown to be as accurate as CMR imaging in the assessment of LV volumes and LV ejection fraction.23 In another multicentre study, 56 patients had LV regional systolic function assessed using several imaging techniques. The best interobserver agreement was found with contrast echocardiography ( = 0.77), whereas it was significantly lower for ventriculography ( = 0.56) and CMR ( = 0.43). Accuracy to detect regional abnormalities, as defined by an expert panel, was also highest for contrast echocardiography.24 Contrast also improves interobserver variability even in patients with good baseline endocardial border definition.25 A prospective study involving 632 patients with suboptimal images demonstrated that after contrast administration, a statistically significant reduction in the percentage of uninterpretable studies from 11.7% to 0.3% was observed and technically difficult studies decreased from 86.7% to 9.8%. An LV thrombus was suspected in 35 patients and was definite in 3 patients before contrast. After contrast, only one patient had a suspected thrombus, and five additional patients with thrombus were identified. A significant impact of contrast on management was observed; additional diagnostic procedures were avoided in 32.8% of patients and drug management was altered in 10.4%, with a total impact (procedures avoided, change in

430

Section 2: Echocardiography/Ultrasound Examination and Training

drugs, or both) observed in 35.6% of patients. The impact of contrast increased with worsening quality of nonenhanced study, the highest being in intensive care units. A cost-benefit analysis showed a significant savings using contrast.26

number of nondiagnostic or inconclusive tests.32 A recent large follow-up study, in which more than 50% patients received contrast during SE, confirmed the feasibility and safety of using contrast during SE in acutely admitted patients.33

Contrast in SE

Myocardial Contrast Echocardiography

The European Association of Echocardiography statement on contrast echocardiography10 recommends the use of contrast in SE when two or more endocardial border contiguous segments of the left ventricle are not wellvisualized in order to: • Obtain diagnostic assessment of segmental wall motion and thickening at rest and stress • Increase the proportion of diagnostic studies • Increase reader confidence in interpretation. The cut-off of two or more segments was derived from the results of the OPTIMIZE study, a unique randomized controlled trial in which 101 patients referred for dobutamine echocardiography agreed to have the test twice within a 24-hour period—once with contrast and once without. The use of contrast improved the percentage of segments adequately visualized at baseline (from 72% to 95%) and more so at peak stress (67% to 96%). Interpretation of wall motion with high confidence also increased with contrast agent use from 36% to 74%. The study clearly showed that if 0 to 1 segments were suboptimally seen at rest, then the effect of contrast was minimal but, if two or more segments were suboptimally visualized, contrast dramatically improved the diagnostic accuracy and reader confidence with interpretation. Multiple other studies have also shown that contrast improves image quality during both exercise and pharmacological SE as a result of enhanced endocardial border delineation.27–31 Thus, there is improved visualization of regional wall-thickening abnormalities and global cavity size, leading to improved study quality and increased reader confidence. The use of contrast improves the sensitivity and specificity of SE studies where unenhanced images were suboptimal to an equivalent level to those with good image quality. Contrast can also be used safely in SE performed in acutely admitted patients. A randomized controlled trial of SE (30% patients received contrast) versus exercise electrocardiography (ex-ECG), in patients hospitalized with acute chest pain but negative troponin, demonstrated a reduced cost to diagnosis of CAD compared to ex-ECG even after including cost of contrast, because of reduced

Historical Papers in the Field of MCE The earliest work on MCE was performed in the early 1980s, although it was in the mid–late 1990s that several key studies were published that established the platform for growth of the technique. In 1998, a landmark study provided proof for the physiological basis of quantification of MCE by studying bubble and ultrasound interaction.7 MBF was studied in ex vivo and in vivo experimental models in 21 dogs and the authors demonstrated that the peak video intensity (A) reflected MBV; the slope of the curve obtained by plotting video intensity against pulsing interval was equal to the microbubble velocity () and their product (A × ) yields MBF. In 1999, a further study from the same group demonstrated, for the first time, that capillaries play a crucial role in regulation of coronary blood flow.8 A canine model of the coronary circulation with three compartments was created (arterial, capillary and venous). In a normal state, capillaries contributed just 25% of the total myocardial vascular resistance at rest but this rose to 75% during maximal hyperemia, despite total myocardial vascular resistance falling. In the presence of a noncritical stenosis, total myocardial vascular resistance increased during hyperemia predominantly because of increased capillary resistance. Thus, contrary to widely held beliefs at that time, capillaries were shown to participate in regulation of MBF.

Myocardial Contrast Echocardiography for Detection of CAD Numerous studies assessing the sensitivity and specificity of both qualitative and quantitative MCE to detect significant CAD, either alone or in comparison with other imaging modalities (e.g. single photon emission computed tomography [SPECT]), have been published. A meta-analysis of eight studies comparing the sensitivity and specificity of MCE versus SPECT or dobutamine SE to detect CAD has shown equivalence.34 An international, multicentre, phase 3 clinical trial assessed 662 patients and found MCE to be noninferior to SPECT.35 Another

Chapter 21: Contrast Echocardiography

study assessed adenosine MCE against adenosine CMR imaging in 65 patients with suspected CAD, and found the sensitivity and specificity of MCE comparable to CMR.36 A pooled aggregate of published studies (Table 21.2) reveals an average MCE sensitivity of 83% and specificity of 80% for the detection of CAD.

Myocardial Contrast Echocardiography for Detection of Myocardial Viability An intact microvasculature is required for myocardium to remain viable in dysfunctional LV segments.55 The density of the microvasculature is related to the intensity of contrast ultrasound signal and inversely related to the fibrotic scar collagen content.17 Myocardial contrast echocardiography can be used to assess viability in the acute phase following myocardial infarction or in patients with chronic coronary disease and chronic LV systolic dysfunction. In one study, MCE and CMR were performed in 42 patients 7–10 days after thrombolysis for ST segment elevation myocardial infarction. MCE was used to correlate perfusion with transmural extent of infarction (TEI) as defined by gadolinium-enhanced CMR. Contractile reserve was assessed with low-dose dobutamine 12 weeks following revascularization. Qualitative and quantitative MCE significantly inversely correlated with TEI and degree of contractile reserve. The study proved that MCE can reflect the transmurality of acute MI and, like CMR, predict the presence or absence of contractile reserve.56 A multicentre study of MCE in 100 patients with acute myocardial infarction demonstrated that microvascular integrity at MCE is the most important predictor of LV remodeling, as compared with persistent ST segment elevation and myocardial blush grade.57 The prognostic benefit of MCE in acute MI patients has also been shown in a study of 95 patients who underwent low-power MCE following acute MI. Over a follow-up period of 46 ± 16 months, the extent of residual myocardial viability by MCE independently predicted hard end-points of cardiac death and repeat MI.58 A contractile response to dobutamine requires a CFR as well as intact contractile proteins. Therefore, it may be less sensitive than MCE for the detection of hibernating myocardium which relies on CFR alone.59,60 Studies have shown that MCE has superior sensitivity and equal specificity in comparison to dobutamine SE, and equal sensitivity and superior specificity in comparison to SPECT, for the detection of hibernating myocardium.60,61 The mean sensitivity and specificity of resting MCE

431

for predicting myocardial viability is 85% and 70%, respectively, derived from 20 studies comprising a total of 736 patients.10

Myocardial Contrast Echocardiography for Derivation of the CFR As described in the previous section, MBF can be quantitated off-line using software in which the components of MBF (namely MBV [A] and microbubble velocity []) can be calculated. If MBF at rest and peak stress are measured, then the CFR is expressed as the ratio between maximal and basal (resting) MBF. Coronary flow reserve by MCE is closely correlated to CFR assessed by positron emission tomography.62 Coronary flow reserve assessed by MCE can assess the presence and severity of flow-limiting CAD63,64 and has also shown to be able to distinguish ischemic from nonischemic causes in patients presenting with acute heart failure65 and capable of predicting mortality in patients with heart failure.66

PRACTICAL TIPS Despite the advantages of contrast use in echocardiography, as with any imaging technique, there are potential problems that can arise and one must be aware of possible artifacts in order to avoid an incorrect diagnosis.

Attenuation Artifacts Because contrast agents reflect ultrasound in a very potent manner, a high concentration will significantly attenuate the penetration of ultrasound. The high concentration of contrast will result in almost complete absorption and reflection of ultrasound in the near field with little penetration of ultrasound deeper and beyond this. The image will show a bright near-field with only shadowing at greater depths, which appears as a false contrast defect in the basal segment(s) (Fig. 21.16 and Movie clip 21.19). This type of artifact is common during bolus injections of microbubble contrast. There are a number of strategies that can be employed to avoid this scenario but all result in a lower concentration of contrast in the LV as follows: • A lower bolus dose of contrast • A diluted concentration of contrast • A slower rate of injection of the bolus • A continuous infusion of contrast rather than bolus doses • Delaying image acquisition until the peak intensity of contrast effect has diminished.

432

Section 2: Echocardiography/Ultrasound Examination and Training

Table 21.2: The Accuracy of MCE for the Detection of CAD

Study

Number of Patients

CAD Present

MCE Sensitivity

MCE Specificity

Aggeli et al.37

532

413

92

61

38

132

85

81

77

Chiou et al.

39

Cwajg et al.

45

32

87

66

Elhendy et al.40

170

127

91

51

63

25

92

95

Heinle et al.

15

12

75

67

Jeetley et al.43

123

96

84

56

47

11

91

92

Korosoglou et al.

89

62

83

72

Lin et al.46

40

25

84

93

Malm et al.

43

33

77

72

Moir et al.30

90

48

93

65

44

44

96

93

35

22

41

Hayat et al.

42

44

Karavidas et al.

45

47

48

Olszowska et al. 49

Peltier et al.

85 (qualitative)

79 (qualitative)

97 (quantitative)

79 (quantitative)

Rocchi et al.50

12

12

89

100

Senior et al.51

55

43

86

88

52

Senior et al.

52

22

82

97

Shimoni et al.28

44

28

75

100

Tsutsui et al.53

16

13

64 (real time imaging)

92 (real time imaging)

41 (triggered imaging)

96 (triggered imaging)

81

67

83 (78–88)

80 (73–87)

54

Winter et al. TOTAL

36

35

1683

1345

MEAN (95% CI) (CAD: Coronary artery disease; MCE: Myocardial contrast echocardiography). Source: Adapted from Senior et al (Ref. 10).

Fig. 21.16: Attenuation defect seen in the basal lateral wall. The defect is continuous with the shadowing at the bottom of the image implying an attenuation defect rather than a dense perfusion defect. (LV: Left ventricle; RV: Right ventricle). Source: Contrast Echo Tool Box (Senior et al, Recommended Reading 1)—with permission from the European Association of Cardiovascular Imaging (EACVI).

Chapter 21: Contrast Echocardiography

A

433

B

Figs 21.17A and B: (A) Linear shadow (arrow) caused by ultrasound attenuation from the papillary muscle; (B) The same patient without appearance of the attenuation artifact after manipulation of the transducer to alter the scanning plane. (LV: Left ventricle). Source: Contrast Echo Tool Box (Senior et al, Recommended Reading 1)—with permission from the European Association of Cardiovascular Imaging (EACVI).

Attenuation defects are usually most apparent at the most distal part of the LV myocardium from the ultrasound transmitter. Thus, the basal lateral wall, basal inferior and basal inferoseptal segments are usually most affected and care must be taken to avoid mistaking such defects for the endocardial border when assessing for wall motion, ventricular volumes or for perfusion defects during MCE. This phenomenon can be more prominent when images are taken from the parasternal long axis view, where ultrasound must penetrate the right ventricle (RV) cavity and LV cavity in order to image the posterior myocardial wall. The focus position is the point where the MI is most concentrated. Thus, a focus at the near-field can result in a high near-field ultrasound signal as discussed earlier but with relative attenuation of signal at greater depths. Thus moving the focus to the basal segments can help reduce such artifacts when they occur. Artifact created by shadowing from the papillary muscles is also well-recognized and usually most apparent in the apical four-chamber view (Figs 21.17A and B). A linear shadow, created by ultrasound reflection at the interface of the proximal border of the papillary muscle and contrast, is directed from the papillary muscle toward the left atrium. Care should be taken to avoid mistaking this for the lateral endocardial border. Gentle alteration of the transducer angulation can often resolve this issue.

Swirling Excessive contrast microbubble destruction in the nearfield can result in a phenomenon called “swirling” in the apical part of the LV cavity. This may be due to a number of factors such as:

• • •

Excessively high MI Excessively high frame rate Low flow at the apex because of LV dysfunction (or aneurysm) • Insufficient contrast administered. This phenomenon results in apical artifacts and incomplete LV opacification, and endocardial border delineation (Figs 21.18A and B, and Movie clips 21.20 and 21.21). Adjusting the machine settings to lower the MI and frame rate, changing the focus toward the apex to increase image intensity, and increasing the volume of contrast agent will all help to correct this problem.

Blooming Blooming is a phenomenon where contrast signals appear to spread from the tissue of origin into neighboring structures (Fig. 21.19 and Movie clip 21.22). The signals may resemble those seen with myocardial perfusion. A lower rate of bolus injection, continuous contrast infusion or a delay in image acquisition will help to alleviate this problem.

Thoracic Cage Artifacts Apparent defects can occur when ribs or lung tissue prevent ultrasound penetration. This is often seen in the lateral wall, but may be seen elsewhere, and appears as a linear anechogenic area and may simulate perfusion defects (Fig. 21.20). However, these can be distinguished from true perfusion defects as the part of the image of interest will be lost in the entire field rather than contrast

434

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 21.18A and B: (A) A well-opacified left ventricle cavity with clear delineation of the endocardium; (B) Swirling and excessive contrast destruction due to a high mechanical index resulting in swirling, poor apical opacification and poor endocardial delineation of the apicolateral segment (arrow).

Fig. 21.19: In this apical four-chamber image, there appears to be contrast opacification in an extracardiac region adjacent to the apex (arrow) due to a blooming artifact. (LV: Left ventricle; RV: Right ventricle).

Fig. 21.20: Linear artifact seen in the apical two-chamber view due to ultrasound dropout from a rib. The artifact appears to be continuous with the extracardiac shadows and the myocardium cannot be distinguished clearly. (LV: Left ventricle).

defects seen within the myocardial wall itself. Adjusting the transducer position on the chest wall to adjust the position of the lateral wall in the sector plane or by asking the patient to temporarily halt respiration may help to alleviate this issue.

during stress, both in the acute setting and in those with stable symptoms.67–77 These studies have shown no difference in mortality or serious adverse events between those patients who received contrast versus those who did not, and this despite the contrast group often having a higher risk profile. Mortality rates compare favorably against other investigations (Table 21.3). Infrequent, mild and transient side effects have been reported for each of the approved second generation UCAs. The side effects include headache, weakness, fatigue, palpitations, nausea, dizziness, dry mouth, taste or smell perversion, dyspnea, chest pain, back pain, urticaria, pruritis, or rash.

SAFETY OF ULTRASOUND CONTRAST AGENTS Contrast echocardiography is safe. Ultrasound contrast agents have been administered to millions of patients worldwide with known or suspected CAD at rest and

Chapter 21: Contrast Echocardiography

Table 21.3: A Comparison of Mortality in Various Cardiac Investigations

Procedure

Mortality

Contrast Echo

1: 145,000 (Sonovue) 1: 500,000 (Definity)

Myocardial Scintigraphy

1: 10,000

Exercise Electrocardiography

1: 2,500

Coronary Arteriography

1,1000 72

Source: Adapted from Main et al.

A postmarketing approval surveillance of more than 1 million patients over a 5-year period demonstrated that serious allergic reactions are rare (1:10,000).4 These include angioedema, hypoxemia, cyanosis, hypotension, anaphylactoid and anaphylactic reactions. These reactions can occur due to acute immunoglobulin E (IgE)–mediated reactions or from complement activation. Anaphylactoid reactions related to complement activation are more typical for contrast agents with a phospholipid membrane. Complement-mediated reactions, in comparison to IgEmediated reactions, do not need prior exposure to the contrast agent; subsequent exposure usually results in milder or even an absence of adverse events and resolution may be spontaneous. Patients should be monitored closely for hypersensitivity reactions despite the rarity of serious adverse events. Physicians, nurses and echosonographers who use UCAs should be trained in the management of hypersensitivity reactions, including anaphylaxis. Resuscitation equipment should be easily accessible. Following the safety data available from multiple studies, the US Food and Drugs Administration removed previous warnings for the use of the contrast agents available in the United States, Optison and Luminity, in acute coronary syndromes and in patients at risk of developing pulmonary hypertension.78 The warnings on the use of Sonovue in acute coronary syndromes by the European Medicines Agency remain.79 However, it is hoped that this contraindication will be withdrawn in the future since all three contrast agents have a similar safety profile. Sonovue can be used 7 days post acute coronary syndrome. The current absolute contraindications for the use of contrast agents are: • Hypersensitivity to the constituents of the contrast agent • Known or suspected right-to-left intracardiac shunts.

435

SALINE CONTRAST ECHOCARDIOGRAPHY Ultrasound contrast, broadly speaking, can be considered in two categories: 1. Manufactured microbubbles designed to enter the left heart 2. Agitated saline microbubbles not designed to enter the left heart. The majority of this Chapter has focused upon manufactured UCAs, specifically designed to traverse the pulmonary capillaries and enter the left heart. However, microbubbles can also be produced by agitating saline (e.g. 8 mL) and a small amount of air (e.g. 1 mL) using two 10-mL syringes connected by a three-way tap. A small volume (e.g. 1 mL) of the patient’s blood can also be aspirated from the cannula and added to the saline mixture to stabilize the air microbubbles as plasma proteins partially encapsulate the air microbubble contrast. This agitation produces large microbubbles, widely variable in size, which are unstable and quickly dissolve in blood. However, as they are generally too large to enter the left heart, they have diagnostic use in the detection of intracardiac shunts, in particular of patent foramen ovale (PFO). Following rapid intravenous injection of the agitated saline contrast through a cannula sited in a large (e.g. antecubital fossa) vein, the right atrium and RV are intensely opacified. Because the microbubbles are large and thus generally filtered at the pulmonary capillary bed, the appearance of microbubbles in the left heart implies the presence of a pathological right-to-left shunt (Figs 21.21 & 21.22 and Movie clips 21.23 to 21.25). This can either be intracardiac (e.g. PFO or atrial septal defect) or extracardiac (e.g. pulmonary arteriovenous malformation). Microbubbles created using a gelatin-based solution instead of saline tend to be more stable with a longer duration of action and may occasionally be seen in the left heart although only after several cardiac cycles, whereas echo-contrast seen in the left heart because of a pathological right-to-left shunt are usually seen within one to three cardiac cycles. However, there is a rare chance of an allergic reaction with the use of gelatin. Air microbubble contrast is generally safe.80 A risk of less than 0.1% with no residual side effects or complications was noted in an American Society of Echocardiography survey. A variety of side effects which include neurological and respiratory symptoms have been reported and thus all precautions should be taken to prevent the intravenous injection of macroscopically visible air bubbles.

436

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 21.21A and B: Apical four-chamber view following injection of agitated saline-air contrast in a 45-year-old female who presented with an ischemic stroke. The interatrial septum is visibly bowing toward the LA (Figure A arrow) followed by the passage of contrast from the right atrium into the LA through a patent foramen ovale (Figure B arrow). (LA: Left atrium; LV: Left ventricle; RV: Right ventricle).

A

B

Figs 21.22A and B: Two-dimensional (A) and three-dimensional (B) transesophageal echocardiography images from the same patient as Figure 21.21. (A) Two-dimensional-TOE imaging in the bicaval view following injection of saline-air contrast showed passage of contrast from the right atrium into the left atrium (LA) through a patent foramen ovale and contrast is visible in the LA (arrow); (B) Three-dimensional TOE image showing the presence of a large number of contrast microbubbles in the LA (arrow). Three-dimensional imaging can be helpful for delineating the exact anatomy of the patent foramen ovale and determining suitability for device closure.

RECOMMENDED READING 1. European Association of Cardiovascular Imaging (EACVI). Contrast Echo Tool Box. Available at: http://www.escardio. org/communities/EACVI/education/echo-box/Pages/ welcome.aspx Accessed January 2013. 2. Mulvagh SL, Rakowski H, Vannan MA, et al. American Society of Echocardiography consensus statement on the clinical applications of ultrasonic contrast agents in echocardiography. J Amer Soc Echocardiogr. 2008;21(11): 1179–201. 3. Senior R, Becher H, Monaghan M, et al. Contrast echocardiography: evidence-based recommendations by

European Association of Echocardiography. Eur J Echocardiogr. 2009;10:194–212.

REFERENCES 1. Olszewski R, Timperley J, Szmigielski C, et al. The clinical applications of contrast echocardiography. Eur J Echocardiogr. 2007;8(3):S13–23. 2. Thanigaraj S, Nease RF Jr, Schechtman KB, et al. Use of contrast for image enhancement during stress echocardiography is cost-effective and reduces additional diagnostic testing. Am J Cardiol. 2001; 87(12):1430–2.

Chapter 21: Contrast Echocardiography

3. Lindner JR, Song J, Jayaweera AR, et al. Microvascular rheology of Definity microbubbles following intra-arterial and intravenous administration. J Am Soc Echocardiogr. 2002;15(5):396–403. 4. Kaul S, Jayaweera AR. Coronary and myocardial blood volumes: noninvasive tools to assess the coronary microcirculation? Circulation. 1997;96(3):719–24. 5. Wei K, Jayaweera AR, Firoozan S, et al. Basis for detection of stenosis using venous administration of microbubbles during myocardial contrast echocardiography: bolus or continuous infusion? J Am Coll Cardiol. 1998;32(1):252–60. 6. Linka AZ, Sklenar J, Wei K, et al. Assessment of transmural distribution of myocardial perfusion with contrast echocardiography. Circulation. 1998;98(18):1912–20. 7. Wei K, Jayaweera AR, Firoozan S, et al. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation. 1998;97(5):473–83. 8. Jayaweera AR, Wei K, Coggins M, et al. Role of capillaries in determining CBF reserve: new insights using myocardial contrast echocardiography. Am J Physiol. 1999;277(6 Pt 2): H2363–72. 9. Mulvagh SL, Rakowski H, Vannan MA, et al.; American Society of Echocardiography. American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography. J Am Soc Echocardiogr. 2008;21(11): 1179–201; quiz 1281. 10. Senior R, Becher H, Monaghan M, et al. Contrast echocardiography: evidence-based recommendations by European Association of Echocardiography. Eur J Echocardiogr. 2009;10(2):194–212. 11. Thanigaraj S, Schechtman KB, Pérez JE. Improved echocardiographic delineation of left ventricular thrombus with the use of intravenous second-generation contrast image enhancement. J Am Soc Echocardiogr. 1999;12(12):1022–6. 12. Soman P, Swinburn J, Callister M, et al. Apical hypertrophic cardiomyopathy: bedside diagnosis by intravenous contrast echocardiography. J Am Soc Echocardiogr. 2001;14(4): 311–13. 13. Koo BK, Choi D, Ha JW, et al. Isolated noncompaction of the ventricular myocardium: contrast echocardiographic findings and review of the literature. Echocardiography. 2002;19(2):153–6. 14. Walker N, Bhan A, Desai J, et al. Myocardial abscess: a rare complication of valvular endocarditis demonstrated by 3D contrast echocardiography. Eur J Echocardiogr. 2010;11(10):E37. 15. Moreno R, Zamorano JL, Almería C, et al. Usefulness of contrast agents in the diagnosis of left ventricular pseudoaneurysm after acute myocardial infarction. Eur J Echocardiogr. 2002;3(2):111–16. 16. Kloner RA, Rude RE, Carlson N, et al. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first? Circulation. 1980;62(5):945–52.

437

17. Shimoni S, Frangogiannis NG, Aggeli CJ, et al. Microvascular structural correlates of myocardial contrast echocardiography in patients with coronary artery disease and left ventricular dysfunction: implications for the assessment of myocardial hibernation. Circulation. 2002; 106(8):950–6. 18. Bhattacharyya S, Khattar R, Senior R. Characterisation of intra-cardiac masses by myocardial contrast echocardiography. Int J Cardiol. 2013;163(1):e11–13. 19. Hundley WG, Kizilbash AM, Afridi I, et al. Administration of an intravenous perfluorocarbon contrast agent improves echocardiographic determination of left ventricular volumes and ejection fraction: comparison with cine magnetic resonance imaging. J Am Coll Cardiol. 1998; 32(5):1426–32. 20. Reilly JP, Tunick PA, Timmermans RJ, et al. Contrast echocardiography clarifies uninterpretable wall motion in intensive care unit patients. J Am Coll Cardiol. 2000;35(2): 485–90. 21. Yu EH, Sloggett CE, Iwanochko RM, et al. Feasibility and accuracy of left ventricular volumes and ejection fraction determination by fundamental, tissue harmonic, and intravenous contrast imaging in difficult-to-image patients. J Am Soc Echocardiogr. 2000;13(3):216–24. 22. Malm S, Frigstad S, Sagberg E, et al. Accurate and reproducible measurement of left ventricular volume and ejection fraction by contrast echocardiography: a comparison with magnetic resonance imaging. J Am Coll Cardiol. 2004;44(5):1030–5. 23. Hoffmann R, von Bardeleben S, ten Cate F, et al. Assessment of systolic left ventricular function: a multi-centre comparison of cine ventriculography, cardiac magnetic resonance imaging, unenhanced and contrast-enhanced echocardiography. Eur Heart J. 2005;26(6):607–16. 24. Hoffmann R, von Bardeleben S, Kasprzak JD, et al. Analysis of regional left ventricular function by cineventriculography, cardiac magnetic resonance imaging, and unenhanced and contrast-enhanced echocardiography: a multicenter comparison of methods. J Am Coll Cardiol. 2006;47(1): 121–8. 25. Nayyar S, Magalski A, Khumri TM, et al. Contrast administration reduces interobserver variability in determination of left ventricular ejection fraction in patients with left ventricular dysfunction and good baseline endocardial border delineation. Am J Cardiol. 2006;98(8): 1110–14. 26. Kurt M, Shaikh KA, Peterson L, et al. Impact of contrast echocardiography on evaluation of ventricular function and clinical management in a large prospective cohort. J Am Coll Cardiol. 2009;53(9):802–10. 27. Dolan MS, Riad K, El-Shafei A, et al. Effect of intravenous contrast for left ventricular opacification and border definition on sensitivity and specificity of dobutamine stress echocardiography compared with coronary angiography in technically difficult patients. Am Heart J. 2001;142(5): 908–15. 28. Shimoni S, Zoghbi WA, Xie F, et al. Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography. J Am Coll Cardiol. 2001;37(3):741–7.

438

Section 2: Echocardiography/Ultrasound Examination and Training

29. Rainbird AJ, Mulvagh SL, Oh JK, et al. Contrast dobutamine stress echocardiography: clinical practice assessment in 300 consecutive patients. J Am Soc Echocardiogr. 2001;14(5): 378–85. 30. Moir S, Haluska BA, Jenkins C, et al. Incremental benefit of myocardial contrast to combined dipyridamole-exercise stress echocardiography for the assessment of coronary artery disease. Circulation. 2004; 110(9):1108–13. 31. Plana JC, Mikati IA, Dokainish H, et al. A randomized cross-over study for evaluation of the effect of image optimization with contrast on the diagnostic accuracy of dobutamine echocardiography in coronary artery disease The OPTIMIZE Trial. JACC Cardiovasc Imaging. 2008;1(2): 145–52. 32. Jeetley P, Burden L, Stoykova B, et al. Clinical and economic impact of stress echocardiography compared with exercise electrocardiography in patients with suspected acute coronary syndrome but negative troponin: a prospective randomized controlled study. Eur Heart J. 2007;28(2): 204–11. 33. Shah BN, Balaji G, Alhajiri A, et al. Incremental diagnostic and prognostic value of contemporary stress echocardiography in a chest pain unit: mortality and morbidity outcomes from a real-world setting. Circ Cardiovasc Imaging. 2013;6(2):202–9. 34. Dijkmans PA, Senior R, Becher H, et al. Myocardial contrast echocardiography evolving as a clinically feasible technique for accurate, rapid, and safe assessment of myocardial perfusion: the evidence so far. J Am Coll Cardiol. 2006;48(11):2168–77. 35. Senior R, Monaghan M, Main ML, et al.; RAMP-1 and RAMP-2 Investigators. Detection of coronary artery disease with perfusion stress echocardiography using a novel ultrasound imaging agent: two Phase 3 international trials in comparison with radionuclide perfusion imaging. Eur J Echocardiogr. 2009;10(1):26–35. 36. Arnold JR, Karamitsos TD, Pegg TJ, et al. Adenosine stress myocardial contrast echocardiography for the detection of coronary artery disease: a comparison with coronary angiography and cardiac magnetic resonance. JACC Cardiovasc Imaging. 2010;3(9):934–43. 37. Aggeli C, Giannopoulos G, Roussakis G, et al. Safety of myocardial flash-contrast echocardiography in combination with dobutamine stress testing for the detection of ischaemia in 5250 studies. Heart. 2008;94(12): 1571–7. 38. Chiou KR, Huang WC, Lin SL, et al. Real-time dobutamine stress myocardial contrast echocardiography for detecting coronary artery disease: correlating abnormal wall motion and disturbed perfusion. Can J Cardiol. 2004;20(12): 1237–43. 39. Cwajg J, Xie F, O’Leary E, et al. Detection of angiographically significant coronary artery disease with accelerated intermittent imaging after intravenous administration of ultrasound contrast material. Am Heart J. 2000;139(4): 675–83. 40. Elhendy A, O’Leary EL, Xie F, et al. Comparative accuracy of real-time myocardial contrast perfusion imaging and

41.

42.

43.

44.

45.

46.

47.

48.

49.

50.

51.

wall motion analysis during dobutamine stress echocardiography for the diagnosis of coronary artery disease. J Am Coll Cardiol. 2004;44(11):2185–91. Hayat SA, Dwivedi G, Jacobsen A, et al. Effects of left bundlebranch block on cardiac structure, function, perfusion, and perfusion reserve: implications for myocardial contrast echocardiography versus radionuclide perfusion imaging for the detection of coronary artery disease. Circulation. 2008;117(14):1832–41. Heinle SK, Noblin J, Goree-Best P, et al. Assessment of myocardial perfusion by harmonic power Doppler imaging at rest and during adenosine stress: comparison with (99m) Tc-sestamibi SPECT imaging. Circulation. 2000;102(1): 55–60. Jeetley P, Hickman M, Kamp O, et al. Myocardial contrast echocardiography for the detection of coronary artery stenosis: a prospective multicenter study in comparison with single-photon emission computed tomography. J Am Coll Cardiol. 2006;47(1):141–5. Karavidas AI, Matsakas EP, Lazaros GA, et al. Comparison of myocardial contrast echocardiography with SPECT in the evaluation of coronary artery disease in asymptomatic patients with LBBB. Int J Cardiol. 2006;112(3):334–40. Korosoglou G, Dubart AE, DaSilva KG Jr, et al. Real-time myocardial perfusion imaging for pharmacologic stress testing: added value to single photon emission computed tomography. Am Heart J. 2006;151(1):131–8. Lin SL, Chiou KR, Huang WC, et al. Detection of coronary artery disease using real-time myocardial contrast echocardiography: a comparison with dual-isotope resting thallium-201/stress technectium-99m sestamibi singlephoton emission computed tomography. Heart Vessels. 2006;21(4):226–35. Malm S, Frigstad S, Torp H, et al. Quantitative adenosine real-time myocardial contrast echocardiography for detection of angiographically significant coronary artery disease. J Am Soc Echocardiogr. 2006;19(4):365–72. Olszowska M, Kostkiewicz M, Tracz W, et al. Assessment of myocardial perfusion in patients with coronary artery disease. Comparison of myocardial contrast echocardiography and 99mTc MIBI single photon emission computed tomography. Int J Cardiol. 2003;90(1):49–55. Peltier M, Vancraeynest D, Pasquet A, et al. Assessment of the physiologic significance of coronary disease with dipyridamole real-time myocardial contrast echocardiography. Comparison with technetium-99m sestamibi singlephoton emission computed tomography and quantitative coronary angiography. J Am Coll Cardiol. 2004;43(2): 257–64. Rocchi G, Fallani F, Bracchetti G, et al. Non-invasive detection of coronary artery stenosis: a comparison among power-Doppler contrast echo, 99Tc-Sestamibi SPECT and echo wall-motion analysis. Coron Artery Dis. 2003; 14(3):239–45. Senior R, Lepper W, Pasquet A , et al. Myocardial perfusion assessment in patients with medium probability of coronary artery disease and no prior myocardial infarction:

Chapter 21: Contrast Echocardiography

52.

53.

54.

55.

56.

57.

58.

59.

60.

61.

62.

comparison of myocardial contrast echocardiography with 99mTc single-photon emission computed tomography. Am Heart J. 2004;147(6):1100–05. Senior R, Janardhanan R, Jeetley P, et al. Myocardial contrast echocardiography for distinguishing ischemic from nonischemic first-onset acute heart failure: insights into the mechanism of acute heart failure. Circulation. 2005;112(11):1587–93. Tsutsui JM, Xie F, McGrain AC, et al. Comparison of lowmechanical index pulse sequence schemes for detecting myocardial perfusion abnormalities during vasodilator stress echocardiography. Am J Cardiol. 2005;95(5):565–70. Winter R, Gudmundsson P, Willenheimer R. Real-time perfusion adenosine stress echocardiography in the coronary care unit: a feasible bedside tool for predicting coronary artery stenosis in patients with acute coronary syndrome. Eur J Echocardiogr. 2005;6(1):31–40. Ragosta M, Camarano G, Kaul S, et al. Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction. New insights using myocardial contrast echocardiography. Circulation. 1994;89(6):2562–9. Janardhanan R, Moon JC, Pennell DJ, et al. Myocardial contrast echocardiography accurately reflects transmurality of myocardial necrosis and predicts contractile reserve after acute myocardial infarction. Am Heart J. 2005;149(2): 355–62. Galiuto L, Garramone B, Scarà A, et al.; AMICI Investigators. The extent of microvascular damage during myocardial contrast echocardiography is superior to other known indexes of post-infarct reperfusion in predicting left ventricular remodeling: results of the multicenter AMICI study. J Am Coll Cardiol. 2008;51(5):552–9. Dwivedi G, Janardhanan R, Hayat SA, et al. Prognostic value of myocardial viability detected by myocardial contrast echocardiography early after acute myocardial infarction. J Am Coll Cardiol. 2007;50(4):327–34. Choi EY, Seo HS, Park S, et al. Prediction of transmural extent of infarction with contrast echocardiographically derived index of myocardial blood flow and myocardial blood volume fraction: comparison with contrast-enhanced magnetic resonance imaging. J Am Soc Echocardiogr. 2007; 49:131A. Hickman M, Chelliah R, Burden L, et al. Resting myocardial blood flow, coronary flow reserve, and contractile reserve in hibernating myocardium: implications for using resting myocardial contrast echocardiography vs. dobutamine echocardiography for the detection of hibernating myocardium. Eur J Echocardiogr. 2010;11(9):756–62. Shimoni S, Frangogiannis NG, Aggeli CJ, et al. Identification of hibernating myocardium with quantitative intravenous myocardial contrast echocardiography: comparison with dobutamine echocardiography and thallium-201 scintigraphy. Circulation. 2003;107(4):538–44. Vogel R, Indermühle A, Reinhardt J, et al. The quantification of absolute myocardial perfusion in humans by contrast echocardiography: algorithm and validation. J Am Coll Cardiol. 2005;45(5):754–62.

439

63. Moir S, Haluska BA, Jenkins C, et al. Myocardial blood volume and perfusion reserve responses to combined dipyridamole and exercise stress: a quantitative approach to contrast stress echocardiography. J Am Soc Echocardiogr. 2005;18(11):1187–93. 64. Janardhanan R, Senior R. Accuracy of dipyridamole myocardial contrast echocardiography for the detection of residual stenosis of the infarct-related artery and multivessel disease early after acute myocardial infarction. J Am Coll Cardiol. 2004;43(12):2247–52. 65. Senior R, Janardhanan R, Jeetley P, et al. Myocardial contrast echocardiography for distinguishing ischemic from nonischemic first-onset acute heart failure: insights into the mechanism of acute heart failure. Circulation. 2005;112(11):1587–93. 66. Anantharam B, Janardhanan R, Hayat S, et al. Coronary flow reserve assessed by myocardial contrast echocardiography predicts mortality in patients with heart failure. Eur J Echocardiogr. 2011;12(1):69–75. 67. Kusnetzky LL, Khalid A, Khumri TM, et al. Acute mortality in hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent: results in 18,671 consecutive studies. J Am Coll Cardiol. 2008;51(17):1704–6. 68. Timperley J, Mitchell AR, Thibault H, et al. Safety of contrast dobutamine stress echocardiography: a single center experience. J Am Soc Echocardiogr. 2005; 18(2):163–7. 69. Anantharam B, Chahal N, Chelliah R, et al. Safety of contrast in stress echocardiography in stable patients and in patients with suspected acute coronary syndrome but negative 12-hour troponin. Am J Cardiol. 2009;104(1): 14–18. 70. Tsutsui JM, Elhendy A , Xie F, et al. Safety of dobutamine stress real-time myocardial contrast echocardiography. J Am Coll Cardiol. 2005;45(8): 1235–42. 71. Aggeli C, Giannopoulos G, Roussakis G, et al. Safety of myocardial flash-contrast echocardiography in combination with dobutamine stress testing for the detection of ischaemia in 5250 studies. Heart. 2008;94(12): 571–7. 72. Main ML, Goldman JH, Grayburn PA. Thinking outside the “box”-the ultrasound contrast controversy. J Am Coll Cardiol. 2007;50(25):2434–7. 73. Wei K, Mulvagh SL, Carson L, et al. The safety of deFinity and Optison for ultrasound image enhancement: a retrospective analysis of 78,383 administered contrast doses. J Am Soc Echocardiogr. 2008;21(11):1202–6. 74. Dolan MS, Gala SS, Dodla S, et al. Safety and efficacy of commercially available ultrasound contrast agents for rest and stress echocardiography a multicenter experience. J Am Coll Cardiol. 2009;53(1):32–8. 75. Main ML, Ryan AC, Davis TE, et al. Acute mortality in hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent (multicenter registry results in 4,300,966 consecutive patients). Am J Cardiol. 2008;102(12): 1742–6. 76. Goldberg YH, Ginelli P, Siegel R, et al. Administration of perflutren contrast agents during transthoracic echocardiography is not associated with a significant increase in acute mortality risk. Cardiology. 2012;122(2): 119–25.

440

Section 2: Echocardiography/Ultrasound Examination and Training

77. Weiss RJ, Ahmad M, Villanueva F, et al.; CaRES Investigators. CaRES (Contrast Echocardiography Registry for Safety Surveillance): a prospective multicenter study to evaluate the safety of the ultrasound contrast agent definity in clinical practice. J Am Soc Echocardiogr. 2012;25(7):790–5. 78. US Food and Drug Administration. FDA: protecting and promoting your health. Available at: http://www.fda. gov/Drugs/DrugSafety/ostmarket Drug Safety Information for Patients and Providers/ucm125574.htm. Accessed January 2013.

79. European Medicines Agency. European public assessment report summary for the public: Sonovue. Available at: http://www.ema.europa .eu/docs/en_GB/document _ library/EPAR_-_Summary_for_the_public/human/000303/ WC500055374.pdf. Accessed January 2013. 80. Marriott K, Manins V, Forshaw A, et al. Detection of right-to-left atrial communication using agitated saline contrast imaging: experience with 1162 patients and recommendations for echocardiography. J Am Soc Echocardiogr. 2013;26(1):96–102.

CHAPTER 22 Myocardial Perfusion Echocardiography Angele A A Mattoso, Jeane M Tsutsui, Wilson Mathias Jr

Snapshot ¾¾ Acute Coronary Syndromes ¾¾ Assessment of Myocardial Viability

INTRODUCTION A specific class of contrast agents consisting of micro­ bubbles, along with new ultrasound imaging techniques allow the study of myocardial perfusion by contrast echo­ cardiography (CE). There are several types of commercially produced ultrasound contrast agents currently available. However, the microbubbles in these agents share common features that allow their use for analysis of myocardial perfusion by echocardiography. The microbubbles are structures that do not aggregate, are biologically inert and safe, remain entirely within the vascular space, mimic red blood cell rheology, respond nonlinearly to the ultrasound, and are eliminated from the body via the reticuloen­ dothelial system with the gas expelled by lungs.1 Contrast echoc­ardiography technology aims to detect the nonlinear echoes from the microbubbles present in the myocardium and suppress the linear echoes from myocardial tissue. Different techniques may be used to create specific images of microbubbles. These include methods that use high-power ultrasound (high mechanical index), such as power Doppler or ultraharmonics which utilize intermittent triggered imaging, or real time imaging that use low-power ultrasound (low mechanical index) with Doppler pulse inversion or pulse modulation.2–4 Intermittent triggered imaging allows visualization of myocardial perfusion, is very sensitive to microbubbles,

¾¾ Chronic Coronary Artery Disease

yields a high signal-to-noise ratio, and reduces artifact, but image acquisition is triggered to the electrocardiogram and acquired intermittently. Hence, wall motion information from the echocardiographic image cannot be obtained simultaneously with myocardial perfusion information. Real time imaging uses low energy ultrasound with a mechanical index of < 0.2 and a low frequency of ultrasonic pulses, around 25 pulses per second. This method is less sensitive to bubbles than high mechanical index imaging, but provides simultaneous information of wall motion and excellent left ventricular opacification. It is relatively easy to use, many artifacts can be avoided, and information of wall motion is obtained in real time along with the myocardial perfusion, making this technique particularly valuable for stress echocardiography. Myocardial perfusion can be evaluated both qualit­ atively and quantitatively. Qualitative analysis of myoc­ ardial perfusion is based on visual evaluation and a semiquantitative contrast score is generally used as follows: 1 = normal (clear homogeneous opacification, 2 = reduced (partial or heterogeneous opacification com­ pared with the normal region, “patchy pattern”), 3 = absent (no myocardial opacification). A contrast score index may be calculated by dividing the sum of the contrast scores for each segment by the number of visualized segments. Quantitative analysis is done in postprocessing using specific computer software, which allow the quantitation of

442

Section 2:  Echocardiography/Ultrasound Examination and Training

Fig. 22.1: Visualization of subsequent myocardial replenishment after microbubble destruction was achieved using a packet of high-intensity (mechanical index 1.5) pulses (flash). Software package automatically calculated the mean acoustic intensity of each region of interest and generated time–intensity curves depicting the different parameters of contrast echocardiography. (Vel: Velocity; Vol: Volume).

various parameters of microvascular flow. This is possible because there are similarities between the behavior of microbubbles and red blood cells, and quantification of myocardial blood flow (MBF) can be indirectly but accurately calculated. The technique for quantifying myocardial perfusion during CE was described and validated in a canine model in 1998.2 The method is based on continuous infusion of microbubbles (constant rate infusion and concentration) until a steady state (plateau) of microbubbles in the myocardium is achieved. This steady state of microbubbles is proportional to the volume of MBF. Then, purposeful destruction of the contrast agent in the myocardium is done by delivery of a burst of one to five pulses of highintensity ultrasound (high mechanical index). Such bursts are often referred to as flash artifacts. Imaging is then continued with a low energy of ultrasound that results in minimal destruction of microbubbles, allowing detection of refilling of microbubbles in the myocardium until a new steady state is reached. The measurement of the reappearance rate of microbubbles within the myocardium provides an estimation of mean myocardial microbubble velocity.

The replenishment of microbubbles within the myoc­ ardium versus time is measured by noting the increased acoustic intensity for each frame of the image sequence, resulting in a time–acoustic intensity curve. This curve is fitted to a monoexponential function: y = A × (1 – e−bt), y is the video intensity at time t. A is plateau acoustic intensity (maximum concen­ tration of microbubbles). b is the rate constant of acoustic intensity increase of microbubbles (rate of rise of y). t is the time instant. Thus, A is proportional to the volume, and b is proportional to the blood flow velocity in the myocardial microcirculation (Fig. 22.1). The incomplete destruction of microbubbles in the field of ultrasound can lead to underestimation of significant abnormalities in MBF. Models are proposed and validated to correct the plateau myocardial signal intensity, which is subject to inhomogeneity of the ultrasound beam, by dividing the value of the myocardium intensity by the adjacent left ventricular cavity intensity. The product of normalized plateau intensity and the rate of replenishment of micro­ bubbles can be used to measure MBF.

Chapter 22:  Myocardial Perfusion Echocardiography

Based on these principles, software packages specific to quantitative analysis of myocardial contrast have been developed that allow the evaluation of image sequences and quantification of regional MBF, both at rest and after stress. Thus, MBF reserve and MBF velocity reserve or b reserve can be assessed.4 The unique advantage of this technique for assessing myocardial perfusion is that it can be used to measure multiple parameters of tissue perfusion including MBF velocity (b) and myocardial blood volume (A). These measures must be made in ventricular systole, because at this point in the cardiac cycle, many of the larger intramyocardial vessels have already emptied their blood, and hence most of the myocardial blood volume now resides in capillaries, making it a more accurate measure of MBF.

ACUTE CORONARY SYNDROMES Initial work in animals and humans using CE was performed to define the presence and size of the risk area during acute coronary occlusion. These studies showed that sometimes the extent of abnormality of wall motion overestimated the real infarcted area and that a risk area measured with intracoronary contrast was superior to clinical, electrocardiographic, hemodynamic, or angiographic data in determining the actual risk area.5 With the use of intravenous microbubbles associated with new echocardiographic imaging techniques, it is possible to quickly and noninvasively assess potential areas of risk for an acute coronary event. The perfusion defects delineated by intravenous CE correlate with the extent and location of wall motion abnormalities and measures of postmortem risk area.6 Several studies have examined the role of CE in the emergency units. Although the high level of troponin is now the gold standard for the diagnosis of acute myoc­ ardial infarction (AMI), it may be increased or available at the initial presentation of the patient. In this scenario, CE has proved most useful. Data from a study involving a large number of patients admitted to the emergency department with chest pain and nondiagnostic electro­ cardiograms and undergoing CE at rest showed that in patients with a low or moderate clinical risk score, the assessment of myocardial perfusion by CE provided additional prognostic information over resting wall motion abnormalities. Patients who showed both abnormal wall motion and myocardial perfusion at rest had an eventfree survival, early and late, significantly worse compared with patients with abnormal wall motion, but normal

443

myocardial perfusion.7 Therefore, use of CE has been strongly recommended in the emergency room.8

ASSESSMENT OF MYOCARDIAL VIABILITY Contrast echoc­ardiography has been applied to detect myocardial viability based on assessment of the integrity of coronary microvasculature after attempted reperfusion in AMI, through the no-reflow phenomenon (failure of restoration of myocardial tissue flow). This phenomenon was first described in a canine model by Kloner et al. in 1974 and is characterized by the failure of recovery in microvascular perfusion despite successful reopening of the occluded coronary artery by percutaneous intervention or thrombolysis.9 Several studies have demonstrated the no-reflow phenomenon by intravenous CE in patients with AMI following revascularization. In patients undergoing primary angio­plasty with stenting, a homogeneous pattern of myocardial perfusion within the infarct area assessed by resting CE was highly predictive of recovery of regional function.10 In a study of 45 consecutive patients of AMI, a persistent contrast defect in the infarct zone identified patients likely to have systolic dysfunction.11 It correlated reasonably well with TIMI flow grade during coronary angiography12 and measurement of coronary flow reserve. The role of CE in the assessment of myocardial viability in chronic coronary artery disease (CAD) has also been studied. CE was compared with myocardial perfusion scintigraphy with thallium and stress echocardiography with low-dose dobutamine in patients with CAD and regional myocardial dysfunction undergoing coronary bypass surgery. It was found that the sensitivity of CE to predict functional recovery after bypass was 90% and was similar to thallium scintigraphy (92%) and dobutamine stress echocardiography (80%). However, the specificity of CE was much higher (63%) than the other two techniques (45% and 54%).13 Another aspect that may be assessed by CE is the maintenance of myocardial viability in AMI based on adequate collateral MBF. Some authors have shown that revascularization of an occluded coronary artery after AMI resulted in improved function only when good perfusion was observed during CE following an injection of contrast into the opposite coronary artery.14

CHRONIC CORONARY ARTERY DISEASE It has been shown that coronary stenosis can be detected, and MBF reserve accurately measured by CE

444

Section 2:  Echocardiography/Ultrasound Examination and Training

in humans following intravenous administration of micro­ bubbles.15 The detection of CAD during CE is based on the development of reversible perfusion defects during pharmacological or exercise stress. The detection of these underperfused myocardial segments during stress echocardiography can be made qualitatively by visual inspection and quantitatively. The site of abnormal flow reserve in CAD is not the level of the stenosis itself, but rather the level of microcirculation. CE is a method that allows analysis of the microcirculation, determining both components of MBF—myocardial blood volume (A) and the MBF velocity (b). The decrease in MBF volume during stress is demon­ strated only with moderate and significant stenosis. With less severe stenosis, the only abnormality seen in the microcirculation is the absence of MBF velocity to increase adequately during stress, which indicates a reduction in MBF reserve. Fortunately, this quantitative parameter can be evaluated by CE. There are many pathological processes that may impair microvascular blood flow, such as myocardial hypertrophy. What characterizes the reduction of flow reserves in the presence of CAD is its regional nature.15 Some reports have demonstrated that qualitative assessment of myocardial perfusion by CE has the ability to improve accuracy of conventional stress echocard­ iography which depends on the development of wall motion abnormalities to detect CAD.20 There are data demonstrating moderate diagnostic accuracy of quanti­ tative CE in CAD. This degree of accuracy suggests that this technology can be used as an adjunct to other modalities for the diagnosis of CAD.16 Kaul et al. were the first to demonstrate an excellent agreement (90–92%, k = 0.88–0.99) between the location and type of perfusion defect detected by myocardial scintigraphy (single-photon emission computed tomography [SPECT]) and by CE (using intermittent harmonic imaging).17 A multicenter study using dipyridamole-stress compared the diagnostic accuracy of CE (intermittent harmonic imaging) and SPECT in patients with CAD and different degrees of stenosis. This study demonstrated similar sensitivity and specificity between both techniques.18 Real time myocardial perfusion echocardiography (RTMPE) using a lower mechanical index to detect CAD during stress has also been used. Some studies, predominantly single-center, have shown RTMPE to increase the sensitivity of stress test when compared with the analysis of wall motion.19,20

Fig. 22.2: Incremental value of quantitative myocardial per­fusion (MP) over electrocardiography (EKG), abnormal wall motion (WM), and abnormal qualitative MP obtained during dobutaminestress real time myocardial perfusion echocardiography (RTMPE) using a Cox model.

The choice of physical or pharmacological stimuli during CE also deserves consideration. A study of 54 patients with suspected CAD and preserved left ventr­ icular systolic function who underwent the two more common forms of pharmacological stress—adenosinestress and dobutamine-stress—RTMPE demonstrated that the quantitative parameters of MBF velocity reserve (b reserve) and myocardial blood volume reserve were lower in arterial territories with stenosis ≥ 50% than in territories without significant stenosis, for both tests. Adenosine-stress RTMPE showed a similar sensitivity of 88% for both reserves specificity of 72% and 41%, and accuracy of 80% and 63%, respectively. Dobutaminestress RTMPE showed a sensitivity of 84% and 92%, specificity of 76% and 65%, and accuracy of 80% and 78%, respectively. In both tests, the quantitative parameters of myocardial perfusion, especially MBF velocity reserve (b reserve), demonstrated an incremental value over electrocardiography, abnormal wall motion, and abnormal qualitative assessment of myocardial perfusion in detecting CAD (Fig. 22.2).21 This finding may be related to ultrasound beam heterogeneities and attenuation effects as well as the inherent problems of ultrasound that mainly affect the evaluation of blood volume in the ultrasound field. The b value, therefore, seems to be the best echocardiographic parameter for identification of coronary stenosis, because it is relatively independent of these ultrasound variables. Qualitative myocardial perfusion analysis during stress RTMPE has also been shown to improve the ability

Chapter 22:  Myocardial Perfusion Echocardiography

A

445

B

Figs 22.3A and B: Incremental value (expressed on Y-axis as chi-square values with incremental degrees of freedom) of left ventricular ejection fraction (LVEF), left atrial (LA) diameter, and coronary flow velocity reserve (CFVR) (A) or β reserve (B) over clinical variables, using a Cox model, for predicting cardiac death and urgent heart transplantation.

Fig. 22.4: Kaplan–Meier curves of patients with normal β reserve, abnormal β reserve in only one coronary artery territory (CAT), and abnormal β reserve in two or more CAT. (AL: ALL territories; CT: Coronary territories).

of the test to predict cardiac events in the setting of CAD. Tsutsui et al. retrospectively studied 788 patients with suspected CAD undergoing dobutamine-stress RTMPE. The incremental prognostic value of qualitative myocardial perfusion imaging over clinical risk factors and other echocardiography data to predict death or nonfatal myocardial infarction was examined during a median follow-up of 20 months. The qualitative myocardial perfusion analysis provided incremental prognostic infor­ mation over other variables in these patients. The authors also demonstrated that patients with normal myocardial perfusion have a better outcome than patients with normal wall motion.22

Although the visual or qualitative analysis of myo­ cardial perfusion provides additional information over analysis of wall motion, the use of quantitative parameters, especially MBF velocity reserve (b reserve), is a more objective method independent of observer bias in the assessment of patients with CAD. A prospective prognostic study in which patients with suspected CAD and preserved left ventricular function were subjected to dobutaminestress RTMP (168 patients) and adenosine-stress RTMP (227 patients) showed that quantitative variables, espe­ cially MBF reserve, were independent predictors of cardiac events (cardiac death, myocardial infarction, and unstable angina) in both groups (Figs 22.3 and 22.4).23 An example of a patient who had a low MBF reserve and experienced a cardiac event is depicted in Figures 22.5A to E.

Assessment of Nonischemic Dilated Cardiomyopathy Dilated cardiomyopathy (DCM) is a prevalent cardiova­ scular condition associated with left ventricular dysfu­ nction and poor prognosis. Reliable selection of patients with higher risk for hard events is of great importance for their management, especially considering current avail­ able therapeutic approaches, such as implantable cardio­ verter-defibrillator, coupled with limited resources for health care.24 Quantitative CE has been shown useful for assessing global and regional MBF reserve using diffe­ rent pharmacological stimuli. This technique seems feasible for the assessment of mechanistic insights at a microvascular level and has been applied for evaluating

446

A

Section 2:  Echocardiography/Ultrasound Examination and Training

C

B

D

E

Figs 22.5A to E: Apical four-chamber view of a 67-year-old man who underwent stress real time myocardial perfusion echocardiography (RTMPE). At rest (A), wall motion and qualitative myocardial perfusion were normal; (B) Adenosine-stress demonstrated an apical perfusion defect (arrow); (C) Dobutamine-stress in the same patient showed apical dyskinesis and a prominent perfusion defect; (D) Acoustic intensity curves at rest and during both adenosine and dobutamine stress demonstrated a low quantitative β reserve parameter; (E) Coronary angiography revealed significant coronary artery disease. (AP4C: Apical four-chamber; LAD: Left anterior descending coronary artery; LCx: Left circumflex coronary artery; LMA: Left main coronary artery; RTMPE: Real time myocardial perfusion echocardiography).

effects of therapy and predicting mortality in patients with heart failure.25,26 Anantharam et al. were the first to study the prognostic value of quantitative RTMPE in 87 patients with heart failure of ischemic and nonischemic etiology.26 The authors demonstrated that myocardial flow reserve obtained by RTMPE was an independent predictor of mortality. Flow reserve ≥ 1.5 predicted a mortality of 10% over 4 years, which was one-third of the prevalent mortality of 30%. However, out of 87 patients studied, 11 (13%) had heart failure with preserved left ventricular ejection fraction (LVEF) and 43 (49%) had significant CAD on coronary angiography. In a study which included 195 patients with nonischemic DCM and LVEF < 35%, the authors combined the analysis of wall motion and the ability of

two different techniques to assess flow reserve: coronary flow velocity reserve (CFVR) measured by Doppler in the left anterior descending (LAD) coronary artery and parameters of myocardial flow (MBF reserve and b reserve) measured by dipyridamole-stress RTMPE for determining two events (cardiac death and urgent heart transplantation). They demonstrated that patients with events had a higher frequency of depressed CFVR, MBF reserve, and b reserve than patients without events. However, only b reserve and left atrial diameter provided independent prognostic information and b reserve was incremental to other clinical and echocardiographic variables.27 Examples of myocardial perfusion images in patients with DCM with and without events are shown in Figures 22.6A to H.

Chapter 22:  Myocardial Perfusion Echocardiography

A

B

C

D

E

F

G

H

447

Figs 22.6A to H: Echocardiographic images at baseline and during dipyridamole stress in patients with dilated cardiomyopathy. (Upper panel) A 52-year-old man with idiopathic dilated cardiomyopathy. Real time myocardial contrast echocardiography. Apical four-chamber view demonstrated a dilated left ventricle during diastole (A) and systole; (B) with an ejection fraction of 25%. During stress, no changes were observed in wall motion analysis (E and F). However, dipyridamole-induced increase in diastolic velocities in the distal left anterior descending coronary artery (C and G) was noted and the resulting coronary flow versus reserve was calculated as 2.37. Appearance curves of contrast quantification at baseline (D) and during dipyridamole (H) demonstrated a normal β reserve (2.34) and myocardial blood flow reserve (2.51). This patient suffered no events during follow-up.(Lower panel) A 49-year-old man with Chagaś disease. Real time myocardial contrast echocardiograph. Apical four-chamber view demonstrated a dilated left ventricle during diastole (A) and systole (B) with an ejection fraction of 15%. During stress, no changes were observed in wall motion analysis (E and F). There was no significant increase in diastolic velocities in the distal left anterior coronary artery with dipyridamole stress (C and G) resulting in a coronary flow velocity reserve (CFVR) of 1.74. Appearance curves of contrast quantification at baseline (D) and during dipyridamole; (H) demonstrated a reduced β reserve (1.77) and myocardial blood flow reserve (MBFR = 1.90). This patient died 6 months later.

Final Remarks Quantitative RTMPE holds the potential to provide a more accurate estimation of MBF because the various agents used in CE are microvascular flow tracers and, thus, seem to better reflect the microcirculatory physiopathology. Preliminary studies have already demonstrated its usefulness for assessing microcirculatory abnormalities in different groups of patients during stress echocardi­ ography. RTMP is a reality nowadays. However, multicenter studies with a much larger number of patients are required to define its exact role in clinical cardiology.

ACKNOWLEDGMENT This work has received a grant from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), São Paulo, Brazil.

REFERENCES 1. Kaul S. Myocardial contrast echocardiography: a 25-year retrospective. Circulation. 2008;118:291–308. 2. Wei K, Jayaweera AR, Firoozan S, et al. Quantification of myocardial blood flow with ultrasound-induced destr­ uction of microbubbles administered as a constant venous infusion. Circulation. 1998;97:473–83. 3. Tiemann K, Lohmeier S, Kuntz S, et al. Real-time contrast echo assessment of myocardial perfusion at low emission power: first experimental and clinical results using power pulse inversion imaging. Echocardiography. 1999;16: 799–809. 4. Wei K, Ragosta M, Thorpe J, et al. Noninvasive quantifi­ cation of coronary blood flow reserve in humans using myocardial contrast echocardiography. Circulation. 2001; 103:2560–5. 5. Touchstone DA, Nygaard TW, Kaul S. Correlation between left ventricular risk area and clinical, electrocardiographic, hemodynamic, and angiographic variables during acute myocardial infarction. J Am Soc Echocardiogr. 1990;3: 106–17.

448

Section 2:  Echocardiography/Ultrasound Examination and Training

6. Dittrich HC, Bales GL, Kuvelas T, et al. Myocardial contrast echocardiography in experimental coronary artery occlusion with a new intravenously administered contrast agent. J Am Soc Echocardiogr. 1995;8:465–74. 7. Tong KL, Kaul S, Wang XQ, et al. Myocardial contrast echocardiography versus thrombolysis in myocardial infarction score in patients presenting to the emergency department with chest pain and a nondiagnostic electroca­ rdiogram. J Am Coll Cardiol. 2005;46:920–7. 8. Senior R, Ashrafian H. Detecting acute coronary syndrome in the emergency department: the answer is in seeing the heart: why look further? Eur Heart J. 2005;26:1573–5. 9. Kloner RA, Ganote CE, Jennings RB. The “no-reflow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest. 1974;54:1496–508. 10. Balcells E, Powers ER, Lepper W, et al. Detection of myocardial viability by contrast echocardiography in acute infarction predicts recovery of resting function and contr­ actile reserve. J Am Coll Cardiol. 2003;41:827–33. 11. Bolognese L, Antoniucci D, Rovai D, et al. Myocardial contrast echocardiography versus dobutamine echocardi­ ography for predicting functional recovery after acute myocardial infarction treated with primary coronary angioplasty. J Am Coll Cardiol. 1996;28:1677–83. 12. Lepper W, Hoffmann R, Kamp O, et al. Assessment of myocardial reperfusion by intravenous myocardial contrast echocardiography and coronary flow reserve after primary percutaneous transluminal coronary angiography in patients with acute myocardial infarction. Circulation. 2000;101:2368–74. 13. Shimoni S, Fangogiannis NG, Aggeli CJ, et al. Identification of hibernating myocardium with quantitative intravenous myocardial contrast echocardiography comparison with dobutamine echocardiography and thallium-201 scintigraphy. Circulation. 2003;107:538–44. 14. Sabia PJ, Powers ER, Ragosta M, et al. An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N Engl J Med. 1992;327:1825–31. 15. Wei K, Ragosta M, Thorpe J, et al. Noninvasive measurement of coronary blood flow reserve myocardial contrast echocardiography. Circulation. 2001; 103:2560–5. 16. Abdelmoneim SS, Dhoble A, Bernier M, et al. Quanti­tative myocardial contrast echocardiography during pharma­ cological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies. Eur J Echocardiogr. 2009;10:813–25. 17. Kaul S, Senior R, Dittrich H, et al. Detection of coronary artery disease with myocardial contrast echocardiography: comparison with 99mTc-sestamibi single-photon emission computed tomography. Circulation. 1997;96:785–92.

18. Jeetley P, Hickman M, Kamp O, et al. Myocardial contrast echocardiography for the detection of coronary artery stenosis: a prospective multicenter study in comparison with single-photon emission computed tomography. J Am Coll Cardiol. 2006;47:141–5. 19. Shimoni S, Zoghbi WA, Xie F, et al. Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography. J Am Coll Cardiol. 2001;37:741–7. 20. Elhendy A, O’Leary EL, Xie F, et al. Comparative accuracy of real-time myocardial contrast perfusion imaging and wall motion analysis during dobutamine stress echocardiography for the diagnosis of coronary artery disease. J Am Coll Cardiol. 2004;44:2185–91. 21 Kowatsch I, Tsutsui JM, Mathias W Jr, et al. Head-to-head comparison of dobutamine and adenosine stress real-time myocardial perfusion echocardiography for the detection of coronary artery disease. J Am Soc Echocardiogr. 2007;20:1109–17. 22. Tsutsui JM, Elhendy A, Anderson JR, et al. Prognostic value of dobutamine stress myocardial contrast perfusion echocardiography. Circulation. 2005;112(10):1444–50. 23. Alves AA. Prognostic value of real time stress dobutamine and adenosine myocardial perfusion echocardiography in patients with suspected or confirmed coronary artery disease. [Thesis]. The University of São Paulo, School of Medicine, 2010. 24. Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119:1977–2016. 25. Santos JMT, Kowatsch I, Tsutsui JM, et al. Effects of exercise training on myocardial blood flow reserve in patients with heart failure and left ventricular systolic dysfunction. Am J Cardiol. 2010;105:243–8. 26. Anantharam B, Janardhanan R, Hayat S, et al. Coronary flow reserve assessed by myocardial contrast echocardiography predicts mortality in patients with heart failure. Eur J Echocardiogr. 2011;12:69–75. 27. Lima MF, Mathias W, Sbano JCN, et al. Prognostic value of coronary and microvascular flow reserve in patients with nonischemic dilated cardiomyopathy. J Am Soc Echocardiogr. 2013;26(3):278–87.

CHAPTER 23 Endothelial Dysfunction Naveen Garg, Kanwal K Kapur

Snapshot  History  Endothelial Func ons  Endothelial Dysfunc ons  Role of Acetylcholine  Shear Stress and Flow-Mediated Dilata on  Vasoac ve Molecules Involved in Vasoregula on  NO Release  Methodology for Assessing Endothelial Func on

INTRODUCTION Endothelial cells line the innermost part of the blood vessels as a monolayer and are in contact with the circulating blood as well as the blood cells. They form the intima of blood vessels and cover a vast surface area by lining the whole circulatory system from heart to capillaries. The endothelium is considered as “a distributed organ of diverse capabilities,” comprising about 6 × 1013 cells, weighing about 1 kg, and covering an area of more than six tennis courts and could wrap around the globe more than four times if joined end to end.1–3 Endothelial monolayer (as shown in Fig. 23.1) has multifaceted functions that range from simple physical separation between vascular wall and circulating blood components, solute transport between blood and muscle wall, to vasoregulatory and anti-inflammatory properties. Endothelial cells are highly specialized for these functions and also show regional specificity.4,5 Although the endothelial function has been studied mainly in the large conduit arteries, the role of endothelial

 Analysis of Shear Stress and Flow-Mediated Dilata on

Response  Limita ons  Factors Affec ng the Flow-Mediated Dilata on  Clinical U lity  Other Noninvasive Methods to Assess Endothelial Func on  Assessment of Endothelial Func on and Future Direc ons

cells lining the micro-vessels cannot be underestimated. Endothelial dysfunction (ED) also affects the vascular

Fig. 23.1: Endothelium. Illustrative diagram to show the vascular wall microscopic picture. Intimal layer is in contact with the blood and is made up of monolayer of endothelial cells; inset depicts the microscopic picture of endothelial cell.

450

Section 2: Echocardiography/Ultrasound Examination and Training

microcirculation, including the vasa vasorum. Vasa vasorum are microvessels that penetrate the adventitia and outer media of large arteries and veins (host vessels). The vasa vasorum consist of concentric layers of smooth muscle oriented around a single layer of endothelial cells. Thus, ED may develop in the vasa vasorum independent of the host vessel. Thus, endothelial function of vasa vasorum is important in regulating vascular tone of large arteries. The endothelial cells derived from the bone marrow are called endothelial progenitor cells (EPCs). These EPCs are involved in repair of endothelium following vascular injury. The repair of vascular injury with EPCs is associated with normalization of endothelial function. The functioning of EPCs and their ability to participate in vascular repair after vascular injury is impaired in the presence of decreased nitric oxide (NO) activity associated with ED. In patients with ED as seen in type-II diabetes, there is diminished recruitment of EPCs to the site of tissue repair. On the other hand, statins promote the mobilization function of EPCs, thereby improving endothelial function (Fig. 23.2).6,7

HISTORY

cell nuclei lining large and small vessels. In 1865, Wilhelm His, Sr., a Swiss anatomist, first introduced the term “endothelium” to make a distinction from the epithelium. Eugene Landis in 1927 and John Pappenhermier in 1953 introduced the pore theory of capillary permeability. Herdenhalen (1891) described the active secretory nature of these cells. The term “endothelial activation” was coined in the 1960s by Willms Kretschmer who noted that during increased endothelial activity that occurs in delayed hypersensitivity reactions, certain morphological changes occur in the endothelial cells. These include a larger size as well as heightened prominence of endoplasmic reticulum. He used the term “activated” to imply a change in function as well as in morphology. Furchgott (1985) described the vasodilatory effect of acetylcholine (Ach) to be mediated by a relaxing factor and Ferid Murad (1987) described the relaxing factor as endogenous nitrous substance. Subsequently in the same year, Salvador Moncada conclusively showed this endogenous endothelial relaxing factor to be NO. Thus, the term “endothelial dysfunction” became almost synonymous with the decrease in production of NO.8

ENDOTHELIAL FUNCTIONS

It has long been established by von Recklinghausen (1800) that the blood vessels are not just tunnels bored through the tissues but are lined by the cells. Endothelial cells were first described in 1845 by Todd and Bowman as thin wall of

A normal endothelial function is characterized by the fine balance between vasodilators and vasoconstrictors, prothrombotic, antithrombotic, inflammatory, and antiinflammatory chemicals as shown in Figure 23.3.

Fig. 23.2: Role of endothelial progenitor cells (EPCs). Illustrative diagram to show the physiological role of EPCs. EPCs are recruited from bone marrow to repair the endothelial injury (disruption). Their ability to repair is reduced in endothelial dysfunction due to decreased availability of nitric oxide.

Fig. 23.3: This figure depicts some of the important molecules secreted by the endothelium, which help in maintaining homeostasis. (EDHF: Endothelial-derived hyperpolarization factor).

Chapter 23: Endothelial Dysfunction

ENDOTHELIAL DYSFUNCTIONS Endothelium regulates the vasculature by secreting vasodilators (NO, prostacyclin [PGI2], etc.) and vasoconstrictors (endothelin [ET]). NO plays a crucial role in maintaining endothelial function. It is secreted by the endothelial cell and diffuses into the vascular musculature, resulting in its relaxation. It also protects the endothelium from oxygen free radicals and inflammatory insults. NO has anti-aging, anti-atherosclerotic, and antithrombotic properties.9 Endothelial cell dysfunction results in loss of vasodilatation due to decreased production of NO, a heightened vasoconstrictor response due to increased ET activity, and an increased prothrombotic as well as a proinflammatory state. The oxygen free radicals cause endothelial cell injury that could range from loss of vascular reactivity to actual breakdown of the integrity of endothelial cells.10 As a result of the enhanced vasoconstriction and inflammatory response, there is increased propensity to plaque rupture. Therefore, NO is considered a barometer of endothelial function and has gained tremendous attention of research workers.11,12

Factors Affecting Endothelial Function The various determinants of endothelial function and dysfunction are shown in Table 23.1.

451

The major factors that cause ED are aging, atherosclerosis, dyslipidemia, diabetes, smoking, obesity, and heart failure. On the other hand, exercise, low cholesterol diet, antioxidants and various therapeutic drugs, for example, statins, and ACE-inhibitors enhance endothelial function.9,13,14

ROLE OF ACETYLCHOLINE Acetylcholine is an endogenous molecule, which acts on the receptors situated on the endothelial cells (Ach receptors) and activates the release of NO, thus causing vasodilatation.15 However, in the presence of ED, the release of NO is impaired and Ach directly stimulates the smooth muscle of media leading to vasoconstrictive response. Thus, in a healthy endothelium, Ach has a vasodilatory effect via the NO release, while in a diseased endothelium Ach causes vasoconstriction owing to impaired NO activity.16,17 This property of Ach is used to test the endothelial integrity. Intracoronary injection of Ach activates a vasodilatory response in a healthy endothelium while it causes a paradoxical constriction in atherosclerotic arteries (as shown in Figure 23.4 Ach pathway). Similarly, intra-arterial injection of Ach is also used to test the vasodilatory response in peripheral arteries.17,18

Table 23.1: Determinants of Endothelial Function and Dysfunction

Factors Causing Endothelial Dysfunction

Factor Enhancing Endothelial Function

Diabetes mellitus

Exercise

Hypertension

Statins therapy

Dyslipidemia

Ace inhibitors

Smoking

Antioxidants

Heart failure

Vitamins C/D

Mental stress

Fruits/vegetable diet

Changes in sodium, calcium

L-arginine

Hemodialysis

Folic acid

Propanolol

Estrogen

Sepsis

Sodium restriction

Coffee Age Male sex Family history of CAD

Fig. 23.4: Ach pathway. Figure depicts the complex role of acetylcholine (Ach) in vasodilatation. Ach acts on both nitric oxide synthetase (eNOS) and cyclooxygenase (COX) to produce nitric oxide (NO) and prostacyclin (PGI2; vasodilators), respectively. The COX pathway also produces thromboxane-2 (TXA2) that causes vasoconstriction and this pathway becomes important in endothelial dysfunction due to decrease in NO activity. (eNOS: endothelial nitric oxide synthetase; BK: Bradykinin).

452

Section 2: Echocardiography/Ultrasound Examination and Training

Ach also stimulates the release of PGI2 causing vasodilatation. However, this mechanism also activates the thromboxane-2 (TXA2) pathway, thus leading to vasoconstriction.

SHEAR STRESS AND FLOW-MEDIATED DILATATION Shear stress is the force exerted on the vessel wall by the flowing blood, (as shown in Fig. 23.5) and is directly proportional to the viscosity and velocity of blood flow and inversely proportional to the diameter of the blood vessel.19,20 Shear stress (S) can be easily calculated as a product of velocity and viscosity (n) divided by the vessel diameter (S = 4n × V/D) and is measured in dynes/cm2. A more simple index is shear rate (Sr), in which viscosity of blood is excluded (Sr = V/D) and its dimension is “per second.” It has been shown in several pioneering studies that the sudden increase in shear stress leads to dilatation of the blood vessel, and this response is endotheliumdependent and mediated through the release of NO. This phenomenon has been termed flow-mediated dilatation (FMD) and is widely used as a test of endothelial function. This FMD response has been shown in several studies to be an index of endothelial function and indirectly a bioassy

Fig. 23.5: Shear forces. Illustrative representation of shear stress exerted by the flowing blood (after reactive hyperemia) on the endothelium. The force of shear stress on the endothelium is in the direction of blood flow. Increase in blood flow increases shear stress on endothelium.

for NO. This FMD response in the brachial artery is also a surrogate for endothelial function in other vascular beds, especially in coronary arteries.21–26 A FMD response implies an increment in vessel diameter and is expressed as a percentage increase with respect to basal diameter and is thus a dimensionless index. FMD% =

Increment in diameter × 100 Basal diameter

The magnitude of the FMD response is directly proportional to the shear stress and is criticaly dependent on endothelial integrity (which, in effect implies NO release).27,28 The time sequence of events resulting from occlusionrelease shear stress stimulus (inflation–deflation of brachial artery cuff ) shows that the peak dilatory response occurs in the first 60 to 90 seconds following occlusionrelease. This peak dilatory response indicates a maximum FMD effect. The “area under the curve” (AUC; as shown in Figure 23.6) is the region in the graphic between the point of the occlusion release and the maximum dilatory response, and represents the actual overall shear stress. However, this computation is technically demanding, because it entails simultaneous recording and measurement of both blood flow velocity and vessel wall diameter.

Fig. 23.6: Time line of the flow-mediated dilation (FMD) response to shear stress. Description of changes in shear rate (velocity/diameter) after the cuff release. In this example, the peak shear (red line) is seen in the first 10 to 15 seconds after cuff release. Peak rise in diameter (blue line) is observed after 60 to 70 seconds of cuff release. Area under the curve (shaded yellow) is the change in shear stress over time till the peak response (maximum diameter increase) is observed.

Chapter 23: Endothelial Dysfunction

Methods Used for Creation of Shear Stress Stimulus

453

adenosine). This point has been elegantly documented in several studies (Wendelhag et al. 1999 , Agewall et al. 1999, 2002).29–31 In the latter study, it has been shown that the peak dilatory response to handgrip is nonendothelium–dependent, while the AUC response is actually endothelium-dependent.32,33 Thus, the only reliable method to create an endothelialdependent FMD response is reactive hyperemia induced by occlusion–release mechanism or to some extent by the use of Ach infusion.

1. Brachial/radial artery occlusion and release—This stimulus causes reactive hyperemia that stimulates the endothelium to release NO with a consequent FMD response. 2. Peripheral artery or intra-coronary infusion of Ach— Intra-arterial Ach infusion stimulates the vascular endothelium to release NO, thus resulting in FMD response. However, some of this FMD response is not mediated by NO and could be due to release of other vasodilators (PGI-2).16 3. Peripheral hand warming—This also results in a gradual increase in shear stress leading to FMD response, which is largely endothelium-independent. 4. Ischemic handgrip—This has been used in the past to augment the reactive hyperemia response to brachial artery occlusion–release, especially in elderly patients showing a small FMD response. However, the use of this procedure also creates nonNO–dependent responses that are not inhibited by either N-monomethyl arginine (l-NMMA; exogenous inhibitor of nitric oxide synthetase [eNOS]) or by inhibition of cyclooxygenase (COX), and this could be mediated via direct vasodilators (lactic acid,

1. Baseline diameter—Greater the baseline diameter, smaller is the shear stress and therefore, smaller is the FMD response; conversely, shear stress and the consequent FMD response is greater in arteries of smaller diameter19,23,34 (as shown in Figures 23.7 to 23.9). 2. Velocity of flow—Greater the velocity of flow, more is the FMD response. Therefore, in smaller arteries a higher flow velocity for a particular flow rate causes a greater shear stress and stimulates a higher FMD response than in larger arteries with equivalent flow rates.

Fig. 23.7: Flow-mediated dilatation (FMD) versus basal diameter. Graph showing inverse relationship between peak percentage change in diameter (FMD response) and baseline diameter. Thus, smaller arteries show greater FMD response. Source: Adapted with permission from Pyke KE, Tschakovsky ME. The relationship between shear and flow mediated dilation: implications for the assessment of endothelial function. J Physiol. 2005;568(2):357–69.

Fig. 23.8: Flow-mediated dilatation (FMD) versus shear rate. Graph showing relationship between peak shear rate and baseline diameter of artery. Peak shear rate is inversely related to the baseline diameter. Source: Adapted with permission from Pyke KE, Tschakovsky ME. The relationship between shear and flow mediated dilation: implications for the assessment of endothelial function. J Physiol. 2005;568(2):357–69.

Factors Affecting Flow-Mediated Dilatation Response to Shear Stress

454

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 23.9: Flow-mediated dilation (FMD) versus shear. Graph shows direct relationship between the shear stress and the FMD response. Greater the shear stress produced by the flowing blood, more is the FMD response. Source: Adapted with permission from Gnasso A, Carallo C, Irace C, et al. Association between wall shear stress and flow mediated vasodilation in healthy men. Atherosclerosis. 2001;156:171–76.

3. Viscosity of blood—Greater the viscosity of flowing blood, more is the shear stress and higher is the FMD response. 4. Endothelial integrity—ED or injury leads to impaired FMD response to a similar shear stress.

VASOACTIVE MOLECULES INVOLVED IN VASOREGULATION There are several endogenous molecules that are released by the endothelium in response to episodic increase in flow (shear stress causing flow-mediated vasodilatation). Several other molecules directly act on the arterial media causing smooth muscle relaxation independent of endothelial activity (non-endothelium–mediated vasodilatation).

Endothelium-Dependent Vasoregulators 1. Nitric oxide (endothelium-derived relaxing factor)— NO is produced by endothelial cells during the process of conversion of l-arginine to l-citrulline, which is mediated by the enzyme eNOS (type-III NO-synthase). The NO released by the endothelium diffuses into the vascular smooth muscle, causing relaxation by

increasing cGMP (cyclic guanylate monophosphate) production, which in turn reduces intracellular calcium. NO-mediated vasodilatation is critically impaired in several disease states and in patients with one or more risk factors for coronary artery disease (CAD). The NO is inactivated by the superoxide anions (reactive oxygen species [ROS]), which are generated during oxidative stress that occurs in atherosclerosis, hypertension, and diabetes. Inhibitors of the enzyme eNOS cause significant reduction in FMD as shown by Mullen et al.35 One of the best documented endogenous inhibitor of eNOS is ADMA (asymmetrical dimethyl arginine). Increased ADMA level is an independent risk factor for CAD. Intra-arterial infusion of exogenous inhibitors of eNOS, that is, l-NMMA , has been shown to blunt the FMD response to shear stress, thus confirming the critical role of NO in vasodilatation.8,36–38 2. Prostacyclin (PGI-2)—It is also derived from the endothelium and is produced by the metabolism of arachidonic acid catalyzed by COX. It promotes the vasodilatation of conduit and resistance vessels. It could have a greater role in collateral resistance vessels.10,17 3. Endothelium-dependent hyperpolarizing factor (EDHF)—It is a recently described, endotheliumderived mediator causing shear stress–induced vasodilatation. It hyperpolarizes the vascular smooth muscle and opens calcium-activated potassium channels, thus leading to smooth muscle relaxation. The EDHF is probably a C-type natriuretic peptide and could play an important role in the regulation of vascular tone by modulating ion channel activity in the endothelium.39–41 4. Endothelin (ET)—The endothelins (ET-I, ET-II, ET-III) are endothelium-derived vasoconstrictive factors, of which ET-I is the most potent. It also stimulates smooth muscle proliferation and platelet aggregation and thus antagonizes NO, thus making it a proatherogenic molecule. Elevated levels of ET-I due to increased sympathetic activity have been documented in patients with congestive heart failure, hypertension, and other causes of ED. Thus, increased ET-I activity rather than reduced NO bioavailability or both could be the mechanism of blunted FMD response in patients with ED. Inhibitors of ET-A receptors have been shown to improve endothelial function both in experimental models of hypertension and in humans with heart failure.42–46

Chapter 23: Endothelial Dysfunction

A

455

B

Figs 23.10A and B: NO release. (A) Figure shows the shear stress-induced stimulation of mechanoreceptors (MR) by the flowing blood. This heightens the enzymatic activity of nitric oxide synthetase (eNOS) via hyperpolarizing the K+ channels and activating Ca+ influx. The released nitric oxide (NO) diffuses into the smooth muscle and causes conversion of guanyl-triphosphate (GTP) to guanylate monophosphate (GMP), leading to muscle relaxation. Pathways shown in green favor the relaxation, whereas the boxes colored red show inhibiting action on NO production; (B) Figure showing the vasodilator effect of NO after the release from endothelium. (BH4: Tetrahydrobiopterin; PDE: Phosphodiesterase). (Movie clip 23.10B).

NO RELEASE The various stimuli for the NO release are (a) shear stress, (b) Ach, and (c) bradykinin. Shear stress stimulates the activation of endothelial-dependent potassium channels and influx of calcium ions, resulting in production of NO gas, which diffuses into the smooth muscles causing vasodilatation (as shown in Figures 23.10A and B). It has been shown in several studies that this response of the endothelium is blocked by exogenous inhibitors of NO synthetase (l-NMMA).32,38,47 This inhibition validates the hypothesis that shear stress stimulates endothelial-mediated vasodilatation via the release of NO. Endothelial-dependent vasodilatation is promoted by endogenous molecules like Ach, ATP, and bradykinin as well as exogenous chemicals, for example, salbutamol and albuterol, which also activate the release of NO.8,48 On the other hand, vasodilatation could be endothelialindependent, and therefore, not related to NO release. Hypoxia, lactic acid, and other endogenous substances like adenosine cause direct dilatation. Exogenous agents like nitrates, sodium nitroprusside, calcium channel blockers, and papaverine also promote direct vasodilatation without the involvement of endothelium. The release of NO thus indicates a healthy endothelium, while diminished release of NO correlates with risk factors

for CAD like aging, hypertension, smoking, dyslipidemia, and diabetes. Detailed analysis of time sequence of release of various chemicals following shear stress stimulation reveals that the NO release is the earliest event followed by other agents like PGI-2 and EDHF, and probably several other unknown molecules as shown in Figure 23.11.

METHODOLOGY FOR ASSESSING ENDOTHELIAL FUNCTION The basic principle underlying the use of various endothelial function tests is that ED involves multiple vascular beds and each of these can be tested separately.47,48 The reference standards used in the past have been the vasodilatory response to the intracoronary injection of Ach to test the coronary circulation and peripheral arterial infusion of Ach to assess the vasodilatory response in these vessels. Another invasive but less commonly used method to assess the endothelial function in peripheral arteries is venous occlusive plethysmography.49–53 It was introduced by Hewlett and Van Zwaluwenburg in 1909. The basic principle is sphygmomanometric cuff occlusion of venous outflow from the forearm with uninterrupted arterial inflow. Changes in the forearm flow are measured

456

Section 2: Echocardiography/Ultrasound Examination and Training

Over the years, several noninvasive tests for assessment of endothelial function have been devised. These are based on the principal of reactive hyperemia following the occlusion of conduit arteries. The various investigative tools in this category are (a) ultrasound assessment of the percentage change in diameter following reactive hyperemia (FMD response), and (b) changes in the capillary perfusion following conduit artery occlusion and release (peripheral artery tonometry).54–56 The use of the intimal medial thickness, arterial stiffness, and pulse wave analysis do not assess the endothelial function directly, although attempts have been made to correlate these with the established noninvasive methods like FMD (Table 23.2). Fig. 23.11: Time sequence release of chemicals after shear stress. Schematic timeline illustration showing that the stimuli of shear stress in conduit artery causes initial flow-mediated dilatation (FMD) due to release of nitric oxide (NO; during early phase) and later in continuation phase is followed by release of other substances (prostacyclin [PGI2]) via secondary pathways. The delayed or prolonged effect may be the result of other unknown endothelial independent mechanisms.

by strain gauge plethysmography at various venous occlusion pressures. Alterations in the forearm blood flow are also induced by infusion of vasoactive substances into the cannulated peripheral artery. For example, infusion of Ach causes endothelial-dependent vasodilatation and increases the forearm blood flow. This increase is inhibited by infusion of eNOS inhibitor l-NMMA . On the other hand, nitroglycerine infusion causes endothelial-independent increase in the forearm blood flow that is not inhibited by l-NMMA infusion. However, this technique entails arterial cannulation, thus making it semi-invasive. The invasive nature of these methods enumerated above precludes their use for routine endothelial testing and these are, therefore, used only for validation purposes.

Technique of Assessing Flow-Mediated Vasodilatation Using Ultrasound Imaging of Conduit Arteries The conduit arteries that can be studied are brachial artery, radial artery, and femoral arteries. However, the brachial and radial arteries are preferred over the femoral artery because of easier and better imaging, and technically a more effective occlusion using sphygmomanometer cuff.57–60

Proximal Versus Distal Occlusion Both proximal and distal occlusions have been used to image the brachial or radial arteries. However, it has been observed that occluding the conduit artery proximally and measuring the diameter distally provokes a greater and longer lasting FMD response.61 It has also been observed that the major proportion of this response is not mediated through NO (non-endothelial–dependent) and is more related to ischemia/hypoxia distal to occlusion. This endothelial-independent response is probably attributed to the release of direct vasodilators like lactic acid, etc.,

Table 23.2: Methods of Assessing ED

Invasive

Noninvasive

• Intracoronary injection of Ach • Venous occlusive plethysmography (VOP)

Direct methods: • Ultrasound flow-mediated dilatation • Pulse amplitude tonometry • Low flow-mediated constriction Indirect methods: • Pulse wave analysis • Laser Doppler flowmetry • Carotid intimal thickness

Chapter 23: Endothelial Dysfunction

and could also be caused by myogenic responses (natural mechanism of the vessel wall to maintain the vascular tone). Therefore, the imaging of the brachial artery is performed over the distal upper arm, while the brachial artery is occluded distally in the forearm. If the radial artery is used for FMD response, then it is occluded over the wrist distally while the FMD response is quantified proximally in the forearm.

Duration of Occlusion Various periods of occlusion have been studied over the last 2 decades to induce reactive hyperemia. Longer duration of occlusions (10–15 minutes) produce nonspecific responses that are not endothelial-dependent (non-NO–related). More brief occlusions (3–5 minutes) produce a specific NO-related FMD response of similar magnitude. Therefore, most authorities agree on a conduit artery occlusion of 5 minutes duration.62

Cuff Inflation Pressure In most studies, a cuff inflation pressure of 50 to 60 mm Hg above the systolic pressure has been used to create a significant shear stress (on cuff release). However, in some studies cuff inflation pressures up to 250 to 300 mm Hg have also been attempted with similar results.

457

owing to greater consistency and accuracy. The FMD response is then quantified using the formula Δd/d × 100, where Δd is the change in diameter and d is the original diameter. It has been observed that the maximum FMD is attained over a time window of 60 to 90 seconds, although dilatation itself continues up to 180 seconds post cuff deflation 28,57,65 (as shown in Figure 23.12). The standardized technique of creating a shear stress stimulus to elicit a specific endothelial function shown in Table 23.328,65 (Fig. 23.13).

ANALYSIS OF SHEAR STRESS AND FLOW-MEDIATED DILATATION RESPONSE The computed FMD response as shown in the previous section, is usually dependent on patients’ age, presence of various coronary risk factors, as well as presence or absence of cardiovascular events.66,67 Significant interobserver and intraobserver as well as intercenter variability has been observed in the assessment of FMD response. These could be partly due to the inconsistencies in techniques used by various researchers. Analysis of the published data of several studies (as depicted

Quantification of the Shear Stress Immediately after release of conduit artery occlusion, there is reactive hyperemia which produces shear stress. This should be recorded immediately after release of occlusion for a period 15 to 30 seconds. The shear stress then can be quantified using the formula for the shear stress over this time period (AUC Fig. 23.5).62,63

Measurement of Flow-Mediated Dilatation Baseline brachial artery diameter is estimated at the fixed point in the upper arm about 6 cm above the medial epicondyle.64 After the cuff deflation, the brachial artery diameter is recorded continuously over a period varying from 120 to 180 seconds. If continuous video recording is not possible, then the brachial artery diameter is recorded intermittently over the above time period using small time windows of 10-second intervals. Automated measurements are preferred over manual measurements

Fig. 23.12: Flow-mediated dilatation (FMD). Diagram shows typical reactive hyperemic changes in brachial artery diameter. There is no appreciable change in diameter before cuff release. Peak increase in diameter is noted after 60 to 70 seconds of cuff release (deflation). Source: Adapted from Peretz A, Leotta DF, Sullivan HJ, et al. Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization. BMC Cardiovascular Disorder. 2007;7:11.

458

Section 2: Echocardiography/Ultrasound Examination and Training

Table 23.3: The Standard Technique of FMD in Brachial Artery

Requirements Duplex ultrasound using high frequency linear probes of 7–10 MHz for simultaneous measurements velocity of flow and diameter measurement Measurements are taken with electrocardiography (ECG) gating preferably over R-wave Same angle (preferably less than 60°) be used throughout the study Software providing facility of edge detection, automated planimetry of Doppler envelopes as well as computerized mathematical calculation are added advantages Subject Preparations Person should be fasting for at least 6 to 8 hours Should not take any food or drugs that interfere in results [caffeine, nitrates, phosphodiesterase (PDE)-inhibitors, etc.] Drugs to be avoided for more than four half lives Persons should be kept in quiet dark room of comfortable temperature (22–25°C) in supine posture for at least 20 minutes Sphygmomanometer cuff should be placed on the forearm (as in Fig. 23.13) Women should be in 1–7 days of menstrual cycle Handgrip and peripheral warming must be avoided during the procedure Protocol Brachial artery is visualized 5 to 6 cm above the antecubital fossa medially Resting diameter is taken for a period of 1 minute to average it Diameter is assessed at the same time on ECG gating (preferably R-wave) Cuff is inflated up to 250–300 mm Hg of mercury Pulse wave Doppler signals are captured 10 seconds before cuff release to 30 seconds after the deflation B-mode imaging is taken for 180 seconds after cuff release Calculations Peak diameter is measured Both absolute and percentage change is noted Peak shear and total shear stimulus (area under curve-till peak diameter) is calculated

in Table 23.4),23 shows a considerable overlap in FMD response in healthy volunteers, patients with CAD, and CAD risk factors. Thus, it is difficult to define precisely the cut-off points for normal endothelial function verses ED.

LIMITATIONS Although the concept of FMD is novel, is based on sound scientific evidence, and the technique is fairly well standardized, there are several lacunae and limitations that have impeded its wide-spread usage and clinical

application. According to 2010 ACC/AHA guidelines,68 it is considered as class III indication with evidence-B for routine clinical evaluation. 1. Conceptual—The fundamental premise on which the concept of FMD is based is that the increase in the conduit artery diameter following shear stress is mediated via the endothelium. A good FMD indicates a healthy endothelium while an impaired FMD response implies ED. As per our present understanding, NO is the pivotal molecule involved in this mechanism. However, several other vasodilators, some secreted by

Chapter 23: Endothelial Dysfunction

endothelium (PGI-2, EDHF) and some directly acting on the vascular smooth muscle (adenosine, lactic acid), are also involved and could be also one of the factors in the FMD response. Moreover, in patients with ED, sympathetic nervous system activation could promote ET release, thus causing a vasoconstrictor response. Thus, both reduced NO release as well as excess ET could lead to impaired FMD response. 2. Clinical validity—Several published studies have shown a good correlation between an impaired FMD response

and the presence of coronary risk factors. There is also fairly strong evidence implicating ED in cardiovascular events.69 A reduced FMD response has been associated with cardiac death, myocardial infarction, and need for revascularization.70 However, this relationship has not been consistently demonstrated. Moreover, there is a considerable overlap in the quantified FMD response between the normal population, patients with coronary risk factors, and with patients with coronary events. Thus, it becomes difficult to provide

Case Study 1

A

B

C

D

Figs 23.13A to D

459

460

Section 2: Echocardiography/Ultrasound Examination and Training

E

F

G

H

I

Figs 23.13A to I: Demonstrating the technique of producing shear stress and estimating flow-mediated dilation (FMD) response. (A and B) show the technique of flow-mediated vasodilatation in the brachial artery. Pneumatic blood pressure cuff is placed in the forearm; (C) shows the position of Doppler probe being kept 5 to 6 cm above the medial epicondyle; (D) shows color flow signals in brachial artery; (E and F) show the measurement of internal diameter of brachial artery and estimation of peak flow velocity; (G and H) show the cuff occlusion pressure is maintained at suprasystolic levels for 5 minutes (G) and hyperemic response is captured after the cuff release (H); (I) shows the peak vasodilatation observed in a 40-year-old male with no coronary artery disease (CAD) risk factors about 60 to 70 seconds after cuff release and computation of FMD response (FMD% = 11.3), indicating a good endothelial function. FMD calculations: Basal diameter = 0.430 cm, average peak diameter = 0.479 cm. FMD = {(0.479 – 0.430)/0.430} = 0.113 cm; FMD% = 0.113 × 100 - 11.3%.

Chapter 23: Endothelial Dysfunction

461

Case Study 2

J

K

L

M

N

O

Figs 23.13J to O: Showing study of impaired brachial artery flow-mediated dilatation (endothelial dysfunction) of a young 34-yearold male with history of hypertension. (J and K) show basal brachial artery diameter (0.379 cm) and blood velocity (45.8 cm/s); (L and M) Show hyperemic response after cuff deflation, and minimal increase in brachial artery diameter (0.394 cm) at 60 seconds post deflation. FMD% = (0.364 – 0.379/0.379) × 100 = 3.95%. This is consistent with endothelial dysfunction; (N) shows normalization of brachial artery diameter to basal level by 3 minutes of cuff deflation; (O) Timeline graph of case study 2, showing maximum FMD response at 60 seconds post deflation and maximum shear was present during first few seconds (15 seconds) post deflation. Shaded area (yellow) is the area under curve (AUC) and represents the total shear stimulus. (Movie clip 23.13O).

462

Section 2: Echocardiography/Ultrasound Examination and Training

Case Study 3

P

Q

R

S

T

Figs 23.13P to T: (P to S) demonstrates an impaired brachial artery FMD response in a 45-year-old male with a 20-year history of chronic smoking and recent complaint of dyspnea on exertion. His basal brachial artery diameter was 0.428 cm and maximum diameter after cuff release was an average of 0.441 cm. FMD% = (0.441 – 0.428/0.428) × 100 = 3.04%. This finding is consistent with endothelial dysfunction; (T) Timeline graph of case study 3, showing maximum increase in diameter seen after about 1 minute, and the maximum shear was present during first 15 seconds. Shaded area (yellow) is the AUC and represents the total shear stimulus. (Movie clip 23.13T)

Chapter 23: Endothelial Dysfunction

463

Table 23.4: Flow-Mediated Dilatation Measurements

Study

Year

Healthy

Celermajer et al.

1993

10 ± 3

CAD

Corretti et al.

1995

11.3 ± 5.4

1.6 ± 5.2

Lieberman et al.

1996

6.2 ± 0.7

1.3 ± 1.1

Neunteufl et al.

1997

12.6 ± 6.7

5.7 ± 4.8

Takase et al.

1998

Clarkson et al.

1999

2.2 ± 2.4

Allen et al.

2000

7.65 ± 3.97

Berry et al.

2000

5.7 ± 0.7

Imamura et al.

2001

8.2 ± 2.7

Betik et al.

2004

3.4 ± 0.6

CAD-risk 4 ± 3.9

5.6 ± 6.14

4 ± 1.7

(CAD: Coronary artery disease) Source: Adapted with permissions from reference 23, Pyke KE, Tschakovsky ME. J Physiol. 2005;568.2:357–69.

cut-off values that separate out patients with normal endothelial function from those with ED. 3. Technical factors—The technique of producing shear stress and recording the FMD response is tedious and requires meticulous attention to details. Several antihypertensive and antianginal medications could directly interfere with the FMD response and thus need to be avoided during the testing period. Similarly, the intake of vasoactive substances in diet needs to be restricted during the evaluation. A simultaneous display of Doppler spectral data as well as vessel wall diameter is technically challenging and this could compromise the accuracy of the data obtained. The interobserver and intraobserver correlative studies have shown significant variability. The uses of the automated callipers for measurements have shown improved interobserver agreement. It is yet to be ascertained whether the peak dilatory response or the technically more challenging measurement of AUC is of greater clinical utility. 4. Interpretational—The interpretation of the FMD data depends upon the age, sex, and physiological state of the patient (resting vs exercise). It is also affected by factors like hematocrit, level of plasma proteins and body temperature, and other factors affecting the viscosity of blood. Moreover, there is a significant diurnal variation in the FMD response in the same patient performed by the same observer. Thus, the test–retest reproducibility is rather low.

5. Surrogacy of peripheral conduit artery for coronary circulation—The FMD response is evaluated in the healthy conduit artery (usually the brachial artery). The response is assumed to be the representative of the disease in the arteries of other vascular beds (e.g. the coronary circulation). However, atherosclerotic involvement of the conduit vessels in various vascular territories may not always be predicted by the response in the healthy surrogate artery.

FACTORS AFFECTING THE FLOW-MEDIATED DILATATION 1. Age and sex—There is an age-related decline in endothelial function and this is reflected in the diminished FMD response. In the pioneering study by Celermajer et al, there was a decline in the FMD response from a mean of about 8% in younger males ( 15%.111 The PWV and AIx correlates inversely with FMD as shown in Figures 23.19 and 23.20. Increasing PWV signifies ED while an increased FMD implies good endothelial function.112,113 Both the AIx and the PWV show a direct correlation and these indices also show a positive correlation with carotid intimal thickness (as depicted in Figure 23.29 for PWV).

Peripheral Arterial Tonometry This is an emerging innovative technique which assesses the pulsed waveform in the microcirculation and computes the pulse amplitude (PA) before and after hyperemic stress. A reactive hyperemic index (RHI) also called peripheral arterial tonometry (PAT)-index is calculated using the equation

Fig. 23.19: Flow-mediated dilatation (FMD) versus pulse wave velocity (PWV). Graph showing negative correlation between PWV and FMD response; r = 0.373; CI = [0.574, 0.13]. Source: Reproduced from Lunder M, MiodragJanic M, Kejzar N, et al. Associations among different functional and structural arterial wall properties and their relations to traditional cardiovascular risk factors in healthy subjects: a cross-sectional study. BMC Cardiovascular Disorders. 2012;12:29.

468

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 23.20: Flow-mediated dilatation (FMD) versus augmentation index (AIx). Figure shows inverse relation r = −0.38; P < 0.0001, between FMD response and AIx. Source: Adapted from reference 113, Soga J, Nakamura S, Nishioka K, et al. Hypertens Res. 2008;31:1293–1298, with permissions.

RHI =

PA Hyperemic − PA basal PA basal

The methodology involves the use of fingertip plethysmographic device capable of sensing the volume changes in digits with each arterial pulsation. Volume changes in finger tips are recorded, tracked over time, and then quantitatively analyzed.114–116 Digital PAT endothelial test consists of three phases: (a) at base line, (b) during occlusion, and (c) during reactive hyperemia. PAT probes (as shown in Figure 23.21) are positioned on one finger of each hand and inflated to 10 mm Hg below diastolic pressure or 70 mm Hg (whichever is lower). Recordings are simultaneously taken from both the fingers. After acquiring baseline data, the pneumatic cuff is inflated in one arm to suprasystolic pressure for 5 minutes. During the occlusion phase, no signal is recorded in the test finger but baseline signals are continued to be recorded in control finger. Postdeflation, there is increased pulse amplitude in the hyperemic finger, which peaks at 60–120 seconds following cuff release. The PAT amplitude is measured at each 30-second interval following cuff release and compared as a ratio to the base line pulse amplitude for the hyperemic finger. This ratio in hyperemic finger is then divided by the ratio in the controlled finger, (as shown in Figures 23.22A and B). The 60- to 120-second period post cuff deflation is most specific for endothelial function, and therefore, the relation between cardiovascular risk

Fig. 23.21: Peripheral arterial tonometry (PAT) probe. Diagrammatic representation of plethysmographic device (pneumatic cuff) used for PAT analysis. Distal part of cuff has sensors that compute the capillary pulse amplitude before and after hyperemic stress.

factors and PAT hyperemic response is best shown in this time window. A PAT score of more than 2.0 indicates excellent endothelial function, while a score less than 1.67 implies ED. Several studies have examined the relationship between cardiovascular risk factors and hyperemic response. PAT hyperemic ratio is progressively lower with increasing burden of cardiovascular risk factors. The hyperemic response can also be elicited using B2-stimulant (400 μg salbutamol inhalation). Salbutamol inhalation provides a simple noninvasive stress for the release of NO by the vascular endothelium (endothelium-dependent digital vascular function). The direct non-endothelium– dependent PAT hyperemic response can be studied noninvasively using sublingual nitroglycerine (NTG) or semi-invasively using infusion of sodium nitroprusside. Although some studies have shown a fair correlation between the FMD and PAT hyperemic response, a few studies have also reported contradictory results between the two techniques.117–119 There are several limitations in the use of PAT technique for assessing endothelial functions: 1. It should be emphasized that the fingertip PAT assesses the endothelial function in the microcirculation (digital microvascular function) while the FMD evaluates endothelial function (vasodilatory function) in conduit arteries. Thus, this technique gives discordant results with respect to some risk factors such as systolic hypertension (reduced FMD but

Chapter 23: Endothelial Dysfunction

A

469

B

Figs 23.22A and B: Peripheral arterial tonometry (PAT) ratio. Showing PAT signal tracings of healthy person and CAD patient with test finger and control finger (of other hand). PAT ratio is calculated as c/d ÷ a/b. These recordings show that a significantly lesser PAT ratio is in CAD patient than in a healthy person.

high PAT index). In addition, with increasing age the FMD response is low (usually < 7%), while the PAT index is unaffected. However, there is a concordance with respect to increasing body mass index, smoking, hypercholesterolemia, and diabetes with a reduced FMD as well as PAT index responses. 2. This technique needs to be studied across the several ethnic populations. 3. The digital vascular function is highly sensitive to sympathetic stimuli and thus, results from control research settings may not be applicable to the routine clinical environment. 4. The available PAT probes presently are non-reusable and thus, this technique may not be cost-effective for large scale applications for preventive strategies. PAT has been validated with intracoronary Ach studies and have also been compared with FMD indices as shown in Figure 23.23.

Laser Doppler Flowmetry (Laser Doppler Perfusion Monitoring)

Fig. 23.23: Flow-mediated dilatation (FMD) versus peripheral arterial tonometry (PAT). Graph showing linear relationship between FMD response and PAT response. It depicts fair correlation (r = 0.55, P < 0.0001) between two modalities of detecting endothelial function in vulnerable patients. Source: Adapted with permissions from Kuvin JT, Patel AR, Sliney KA, et al. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146:168–74.

Endothelial dysfunction is a systemic phenomenon which simultaneously affects the coronary and peripheral vascular beds. It has been shown in several studies that ED in conduit arteries, resistance vessels, and the microcirculation can be used as surrogates for endothelial damage in the coronary circulation. Laser Doppler flowmetry is an emerging technique that assesses endothelial function in the skin microcirculation.120

Endothelial-dependent as well as endothelial-independent perfusion changes resulting from vasodilatation of the skin microcirculation are monitored continuously using laser Doppler perfusion monitoring (LDPM) system. Both pharmacological and physiological stimulation are used to study endothelial function. Pharmacological

470

Section 2: Echocardiography/Ultrasound Examination and Training

stimulation is performed using laser Doppler coupled with iontophoresis for the delivery of vasoactive drugs. Ach is delivered for assessment of endothelial-dependent changes in microcirculation, while sodium nitroprusside is used to evaluate endothelial-independent perfusion changes. Physiological stimulation entails the use of postocclusion reactive hyperemia as well as using local heating of the laser probe to 44°C. Microvascular reactivity has been used to demonstrate the existence of ED in several cardiometabolic states, including insulin resistance Type-I and Type-II diabetes mellitus and metabolic syndrome. However, laser digital flowmetry (LDF) has low reproducibility in the human forearm. This technique is still in evolution and further studies will determine its accuracy, incremental value, and cost-effectiveness in the evaluation of human endothelial function. A recent study comparing LDPM skin perfusion imaging stimulated by Ach with FMD in brachial artery shows a high degree of correlation between the endothelial function of large conduit artery with skin microcirculation.120

Low Flow-Mediated Vasoconstriction (LFMC Response) It has been shown over the past 20 years that a low shear stress could result in vasoconstriction rather than vasodilatation. This phenomenon has been well documented

Fig. 23.24: Methodology to demonstrate low flow-mediated vasoconstriction (LFMC). Diagram showing the methodology of LFMC. Basal radial artery diameter is measured before cuff occlusion. Pneumatic cuff is inflated near wrist to suprasystolic level (colored black). Radial artery Doppler study after 3 minutes of cuff occlusion shows decline in blood velocity indicating low flow state. LFMC is observed 30 seconds before deflation. After cuff release, shear stimuli causes FMD response.

by several authors.121–124 The methodology of causing a LFMC response involves a cuff inflation pressure that is 50 mm Hg or more than the systolic blood pressure for a period between 2 and 5 minutes. The LFMC response is assessed as a percentage constriction in the diameter of conduit artery (usually the radial artery; as in Figures 23.24 and 23.25). This usually occurs during the last 30 seconds of the inflation period. The resultant low flow state induces a low shear stress. The mechanism of vasoconstriction induced by low shear stress is considered to be a combination of high ET-1 release and inactivation of COX-dependent prostaglandins as well as inhibition of EDHF release.121,122 The LFMC response is also an indicator of endothelial function and provides information on the endothelial health, which is complementary to FMD. While the FMD response is NO-dependent, the LFMC response is NO-independent and both of these are barometers of endothelial function. The FMD response is a measure of endothelial recruit ability in response to sudden increase in shear stress. On the other hand, the LFMC response is an index of resting endothelial tone, which results from a low shear stress. The complex relationship between FMD response and LFMC response is depicted in Table 23.6. It has been suggested that the natural stimuli that provoke LFMC could include mental stress, a high fat meal, coronary stenting, isometric stress, and possibly

Fig. 23.25: Timeline of low flow-mediated vasoconstriction (LFMC) versus flow-mediated dilatation (FMD). Diagram demonstrating the LFMC response in radial artery before cuff release. This vasoconstriction before FMD response is considered due to endothelin release.

Chapter 23: Endothelial Dysfunction

Table 23.6: FMD vs LFMC

FMD

LFMC

Needs greater shear stress

Less or no shear needed

Endothelial recruit ability

Endothelial tone

NO-dependent

NO-independent

↑PGI2 ↑EDHF ↓ET

↓PGI2 ↓EDHF ↑ET

Blunted by L-NMMA

Blunted by Aspirin, Fluconazole

some medications and environmental influences. A normal LFMC response could actually indicate endothelial activation while a reduced LFMC response could indicate ED. A normal LFMC is between 3.9 and 8.2%, and could be a mechanism for the normal vasomotor tone. An impaired LFMC response could be associated with some of the traditional coronary risk factors (e.g. hypertension, smoking). On the other hand, hypercholesterolemia leads to a heightened LFMC response and impaired FMD response. Thus, a composite endothelial function is a complex interplay of factors promoting FMD as well as LFMC. A heightened LFMC response together with impaired FMD response has been implicated in acute coronary syndrome. An enhanced sympathetic activity could also lead to excessive ET release and an exaggerated LFMC response.123,124 The assessment of LFMC response entails accurate measurement of radial artery diameter by ultrasound imaging proximally in the forearm during radial artery occlusion. The implication of an impaired LFMC response is yet unknown and it is unclear whether it offers additional prognostic information to that provided by traditional coronary risk factors or FMD (Fig. 23.26). The implication of an impaired LFMC response is yet unknown and it is unclear whether it offers additional prognostic information to that provided by traditional coronary risk factors or FMD (Fig. 23.27).

Endothelial Dysfunction and Carotid Intimal Medial Thickness Endothelial dysfunction affects both the short-term and long-term vascular health of the vessel walls. It adversely alters the balance between the vascular injury and repair, and this promotes structural arterial disease. Both endothelial function and structural arterial disease can be assessed noninvasively using high-resolution ultrasound by computing FMD and carotid intimal medial thickness (cIMT), respectively. Carotid IMT is measured using 7.5 to 12 MHz linear probe about 1 cm proximal to the

471

carotid bulb and the far wall intimal medial interface is defined. The leading edge to leading edge measurement is made between the intima and the media–adventitia interface. FMD is assessed using ultrasonic measurement of brachial artery diameter before and after inflation/ deflation hyperemic stimulus as discussed in the previous sections. It has been shown in several studies that annual progression of cIMT is associated with FMD and not with the conventional coronary risk factors.125–127 Some authors have shown a modest inverse correlation between progression of cIMT and FMD response, although as shown in Figure 23.28, the scatter is rather wide.128–133 Similarly, a modest direct correlation has also been demonstrated between cIMT and PWV (as shown in Figure 23.29).

ASSESSMENT OF ENDOTHELIAL FUNCTION AND FUTURE DIRECTIONS The pathophysiological role of ED in atherosclerotic coronary artery and cerebrovascular diseases has been well established. Impaired endothelial function has been linked with increased risk of cardiovascular events. In the pathogenesis of atherosclerosis, there is a long latent asymptomatic preclinical phase during which ED plays a pivotal role. With the advent of several methods to study ED, it is now possible to identify the individuals at risk of developing atherosclerosis and its potentially devastating complications. The use of these endothelial function tests provides specificity to the established risk factors of the CAD and enhances their predictive value. The early detection of ED allows appropriate interventions and thus an opportunity to retard, stop, or even reverse the progression of atherosclerosis and its complications. The concept of incorporating of endothelial function tests in the programs for primary prevention of CAD is thus an attractive proposition. The best established and the most widely used method to assess endothelial function noninvasively is the brachial artery FMD induced by occlusion–cuff–deflation reactive hyperemia. However, the wide spread use of this technique has been hampered by its requirement of a high degree of operator expertise in computing the FMD response. With the recent introduction of several automated techniques involving pulse wave analysis (PWA), it is now possible to provide a relatively rapid noninvasive, accurate, reproducible, and operator-independent methods to evaluate endothelial function. The results of preliminary studies of using PWV, SI, and PAT in this aspect on

472

Section 2: Echocardiography/Ultrasound Examination and Training

Case Study 4

A

B

C

D

E

F

Figs 23.26A to F

Chapter 23: Endothelial Dysfunction

G

H

I

J

K

473

Figs 23.26A to K: (A ) It shows the measurement of the brachial artery diameter in basal state (average diameter is 0.390 cm) (Movie clip 23.26A); (B) shows Doppler velocity wave forms. Peak velocity is 35.6 cm/s (Movie clip 23.26B); (C) Shows a decline in the peak velocity to 28.4 cm/s, during the inflation (occlusion) phase (Movie clip 23.26C); (D) Shows LFMC response with decrease in average luminal diameter to 0.360 cm. LFMC% = 7.7; (E and F) demonstrate the reactive hyperemia following deflation (occlusion-release) (Movie clip 23.26E); (G) Shows a minimal change in luminal diameter in first 30 seconds of deflation. Average diameter is 0.365 cm (Movie clip 23.26G); (H to J) depict FMD response at 90, 105, and 150 seconds with the flow-mediated dilatation (FMD) response at 90 seconds of 0.399 cm. FMD% = 2.3; (K) Shows the timeline of the graphical display of low flowmediated vasoconstriction (LFMC), flow-mediated dilatation (FMD), and change in shear rate. Shaded portions indicate the area under the LFMC and FMD curves.

474

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 23.27: This figure illustrates the fine balance between nitric oxide (NO) and endothelin (ET) production by endothelial cell in healthy state, which could lead to either a flow-mediated dilatation (FMD) or a low flow-mediated vasoconstriction (L-FMC) response.

Fig. 23.28: Figure shows the negative correlation between flowmediated dilatation (FMD) and carotid intimal medial thickness (cIMT) (r = − 0.211, P < 0.05). FMD depicts the response of nitric oxide (NO), whereas cIMT reflects arterial stiffness. Source: Adapted with permissions from Fahrettin Oz F, Elitoka A, Bilgea AK, et al. Relationship between brachial artery flow-mediated dilatation, carotid artery intima-media thickness and coronary flow reserve in patients with coronary artery disease. Cardiol Res. 2012;3(5):214–21.

SUMMARY • •

•

Fig. 23.29: Pulse wave velocity (PWV) versus carotid intimal medial thickness (cIMT). Shows a modest direct correlation between PWV and cIMT. Both modalities are related to structural changes in the arterial wall. Source: Reproduced from Mori J, Krantz MJ, Long CS, et al. Pulse wave velocity and carotid atherosclerosis in White and Latino patients with hypertension. BMC Cardiovascular Disorders. 2011;11:15.

different populations with several risk factors have been encouraging.117,134–136 However, further studies are required before these methods can be recommended for routine clinical use in primary prevention.

• •

•

•

Endothelium is now considered to be the largest organ in the body. Diverse and vital functions like vasoregulation, anti-inflammatory, and hemostatic functions are programed by endothelium. NO is considered as a major antiatherogenic molecule secreted by endothelium, having potent antiaging and vasodilatory properties. Endothelial function declines with the advancing age due to decreased NO production. NO is a barometer of endothelial function. Decreased production of NO defines ED. Shear stimulus is a major stimulant for endotheliumdependent vasodilatation due to release of NO by endothelium. Noninvasive evaluation of ED is possible by evaluating flow-mediated vasodilatation of conduit artery, usually brachial or radial artery. The FMD response is considered a surrogate for endothelial function in other vascular beds including coronary arteries. The FMD response correlates with the presence of risk factors of CAD and cardiovascular events, although this relationship is not consistent.

Chapter 23: Endothelial Dysfunction

•

•

•

•

The FMD response measurement and computation is technically challenging, time consuming, and operatordependent. However, it is regarded as noninvasive “gold standard” for evaluation of endothelial function. Other methods based on plethysmographic and oscillometric techniques have been introduced in the past 5 to 10 years. These include pulse wave velocity (PWV), pulse wave analysis (PWA) with stiffness, and augmentation indices. These are less operativedependent and technically less cumbersome. Although these techniques are gaining popularity, sufficient database as regards to correlation with cardiovascular events and coronary risk factors is lacking. A recently introduced plethysmographic technique assesses the endothelial function of microcirculation at the fingertips and is called PAT. The consistency and reliability of this innovative technology needs further evaluation. LFMC has been recently recognized during sphygmomanometric cuff occlusion and this has been attributed to the release of ET by the vascular endothelium. However, the significance of this phenomenon and its incremental value over the FMD response and the conventional coronary risk factors requires further assessment.

REFERENCES 1. Limaya V, Vadas M. The vascular endothelium: structure and function. In: Fitridge R, Thompson M, editors. Mechanisms of Vascular Disease A Textbook for Vascular Surgeons. 1st ed. Cambridge University Press. 2007;1–14 (excerpt-online). Available from http://assets.cambridge. org/97805218/60635/excerpt/9780521860635_excerpt.pdf 2. Galley, HF, Webster, NR. (2004). Physiology of the endothelium. Br J Anaesth, 93(1), 105–13. 3. William AC. Phenotypic heterogeneity of the Endothelium:!. Struct Function Metabol Circ Res. 2007;100:158–73. 4. Douglas BC, Eleanor SP, Clayton AB, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood. 1998;91:3527–61. 5. Gössl M, Mödder UI, Gulati R, et al. Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells. Eur Heart J. 2010;31(23):2909–14. 6. A Urbich C, and Dimmeler S. Endothelial Progenitor Cells: Characterization and Role in Vascular Biology.Circ Res. 2004;95:343–53. 7. Nina A, Mikirova NA, James A, et al. Circulating endothelial progenitor cells: a new approach to anti-aging medicine? J Transl Med. 2009;7:106. 8. Bryan NS, Bian K, Murad, F. Discovery of the nitric oxide signaling pathway and targets for drug development. Front Biosci. 2009;14, 1–18.

475

9. Ricardo EJ, Ronerto NA, Jorge VO, et al. Endothelial dysfunction: a comprehensive appraisal. Cardiovasc Diabetol. 2006;5:4. 10. Feletou M, Vanhoutte PM. Endothelail dysfunction: a multifaceted disorder (The Wigger Award Lecture). 11. Oufella AH, Maury E, Lehoux S, et al. The endothelium: physiological functions and role in microcirculatory failure during severe sepsis. Intensive Care Med. doi:10.1007/ s00134-010-1893-6. 12. Vita JA. Endothelial function. Circulation. 2011;124(25): e906–e912. 13. Simaitis A, Laycevicius A, Jarasuniene D. Contribution of risk factors to endothelial dysfunction of coronary arteries with minimal lesions. Seminars Cardiol. 2004;10(1). 14. Cooke JP. The endothelium: a new target for therapy. Vasc Med. 2000;5(1):49–53. 15. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–6. 16. Spence VA, Khan F, Kennedy G, et al. Acetylcholine mediated vasodilatation in the microcirculation of patient with chronic fatigue syndrome. Prostaglandins, Leukot Essent Fatty Acids. 2004;70:403–7 17. Holowatz LA, Thompson CS, Minson CT, et al. Mechanisms of acetylcholine-mediated vasodilatation in young and aged human skin. J Physiol. 2005;563(3):965–73. 18. Werns SW, Walton JA, Hsia HH, et al. Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease. Circulation. 1989;79(2):287–91. 19. Gnasso A, Carallo C, Irace C, et al. Association between wall shear stress and flow-mediated vasodilation in healthy men. Atherosclerosis. 2001;156(1):171–6. 20. Traub O, Berk B C. Laminar Shear stress: Mechanism by which endothelial cells transudce an atheroprotective force. Arterioscler Thromb Vasc Biol. 1998;18:677–85. 21. Ohno M, Gibbons GH, Dzau VJ, et al. Shear stress elevates endothelial cGMP. Role of a potassium channel and G protein coupling. Circulation. 1993;88(1):193–7. 22. Pohl U, Holtz J, Busse R, et al. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension. 1986;8(1):37–44. 23. Pyke KE, Tschakovsky ME. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function. J Physiol (Lond). 2005; 568(Pt 2):357–69. 24. Pyke KE, Tschakovsky ME. Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol. 2007;102(4):1510–9. 25. Green D. Point: Flow-mediated dilation does reflect nitric oxide-mediated endothelial function. J Appl Physiol. 2005; 99(3):1233–4; discussion 1237. 26. Pyke KE, Tschakovsky ME. Counterpoint: Flow mediated dilation does not reflect nitric oxide mediated endothelial function. J Appl Physiol. 2005;99:1234–8. 27. Charakida M, Masi S, Lüscher TF, et al. Assessment of atherosclerosis: the role of flow-mediated dilatation. Eur Heart J. 2010;31(23):2854–61.

476

Section 2: Echocardiography/Ultrasound Examination and Training

28. Thijssen DH, Black MA, Pyke KE, et al. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011;300(1):H2–12. 29. Agewall S, Hulthe J, Fagerberg B, et al. Post-occlusion brachial artery vasodilatation after ischaemic handgrip exercise is nitric oxide mediated. Clin Physiol Funct Imaging. 2002;22(1):18–23. 30. Wendelhag I, Fagerberg B, Wikstrand J. Adding ischaemic hand exercise during occlusion of the brachial artery increases the flow-mediated vasodilation in ultrasound studies of endothelial function. Clin Physiol. 1999; 19(4):279–83. 31. Agewall S, Whalley GA, Doughty RN, et al. Handgrip exercise increases postocclusion hyperaemic brachial artery dilatation. Heart. 1999;82(1):93–5. 32. Wray DW, Witman MA, Ives SJ, et al. Progressive handgrip exercise: evidence of nitric oxide-dependent vasodilation and blood flow regulation in humans. Am J Physiol Heart Circ Physiol. 2011;300(3):H1101–H1107. 33. McGowan CL, Levy AS, McCartney N, et al. Isometric handgrip training does not improve flow-mediated dilation in subjects with normal blood pressure. Clin Sci. 2007;112(7):403–9. 34. Jazuli F, Pyke KE. The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress. Am J Physiol Heart Circ Physiol. 2011;301(4): H1667–H1677. 35. Mullen MJ, Kharbanda RK, Cross J, et al. Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo: relevance to endothelial dysfunction in hypercholesterolemia. Circ Res. 2001;88(2):145–51. 36. Davignon J, Ganz P. Role of endothelial Dysfinction in atherosclerosis. Circulation 2004; 109: III-27–III-32. 37. Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000;20(9):2032–2037. 38. Joannides R, Haefeli WE, Linder L, et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation. 1995;91:1314–9. 39. Lee Stoner, Melissa Lynn Erickson, et al. There’s more to flow-mediated dilation than nitric oxide. J Atheroscler Thromb. 2012;19:589–600. 40. Michel Fe´le´tou, Paul M. Vanhoutte. Endothelium-derived hyperpolarizing factor where are we now? Arterioscler Thromb Vasc Biol. 2006;26:1215–25. 41. Ozkor MA, Quyyumi AA. Endothelium-derived hyperpolarizing factor and vascular function. Cardiol Res Pract. 2011;2011:156146. 42. Iglarz M, Clozel M. Mechanisms of ET-1-induced endothelial dysfunction. J Cardiovasc Pharmacol. 2007;50(6):621–8. 43. Lü D, Cao X, Tang S, et al. Regeneration of foreign genes cotransformed plants of Medicago sativa L by Agrobacterium rhizogenes. Sci China, C, Life Sci. 2000;43(4):387–94. 44. William G, Haynes WG, Fiona E, et al. Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation. 1995;92: 357–63.

45. Böhm F, Pernow J. The importance of endothelin-1 for vascular dysfunction in cardiovascular disease. Cardiovasc Res. 2007;76(1):8–18. 46. Masaki T, Sawamura T. Endothelin and endothelial dysfunction. Proc Jpn Acad Ser B. 2006;82(2006). 47. Gilligan DM, Panza JA, Kilcoyne CM, et al. Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation. Circulation. 1994;90(6):2853–58. 48. Chatzizisis YS, Coskun AU, Jonas M, et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J Am Coll Cardiol. 2007;49(25):2379–93. 49. Barac A, Campia U, Panza JA. Methods for evaluating endothelial function in humans. Hypertension. 2007;49(4): 748–60. 50. Tousoulis D, Antoniades C, Stefanadis C. Evaluating endothelial function in humans: a guide to invasive and noninvasive techniques. Heart. 2005;91(4):553–8. 51. Alomari MA, Solomita A, Reyes R, et al. Measurements of vascular function using strain gauge plethysmography: technical considerations, standardization and physiological findings. Am J Physiol Heart Cric Physiol. 2004;286: H99–H107. 52. Flammer AJ, Anderson T, Celermajer DS, et al. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126(6):753–67. 53. Reriani MK, Lerman LO, Lerman A. Endothelial function as a functional expression of cardiovascular risk factors. Biomark Med. 2010;4(3):351–60. 54. Deanfield J, Donald A, Ferri C, et al. Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005;23(1):7–17. 55. Poredos P, Jezovnik MK. Testing endothelial function and its clinical relevance. J Atheroscler Thromb. 2013;20(1):1–8. 56. Lekakis J, Abraham P, Balbarini A, et al. Methods for evaluating endothelial function: a position statement from the European society of cardiology working on peripheral circulation. Eur J Cardiovasc Prevent Rehabil. doi:10. 1177/1741826711398179 57. Peretz A, Leotta DF, Sullivan JH, et al. Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization. BMC Cardiovasc Disord. 2007;7:11. 58. ThijssenDHJ, Rowley N, Padilla J, et al. Relationship between upper and lower conduit artery vasodilator function in humans. J Appl Physiol. 2011;111:244–50. 59. Kooijman M, Thijssen DH, de Groot PC, et al. Flowmediated dilatation in the superficial femoral artery is nitric oxide mediated in humans. J Physiol (Lond). 2008; 586(4):1137–45. 60. Parker BA, Ridout SJ, Proctor DN. Age and flow-mediated dilation: a comparison of dilatory responsiveness in the brachial and popliteal arteries. Am J Physiol Heart Circ Physiol. 2006;291(6):H3043–H3049.

Chapter 23: Endothelial Dysfunction

61. Berry KL, Skyrme-Jones RA, Meredith IT. Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation. Clin Sci. 2000;99(4):261–7. 62. Pyke K, Green DJ, Weisbrod C, et al. Nitric oxide is not obligatory for radial artery flow-mediated dilation following release of 5 or 10 min distal occlusion. Am J Physiol Heart Circ Physiol. 2010;298(1):H119–H126. 63. Atkinson G, Batterham AM, Black MA, et al. Is the ratio of flow-mediated dilation and shear rate a statistically sound approach to normalization in cross-sectional studies on endothelial function? J Appl Physiol. 2009;107(6):1893–9. 64. Harris RA, Nishiyama SK, Wray DW, Richardson RS. Ultrasound assessment of flow-mediated dilation. Hypertension. 2010;55(5):1075–85. 65. Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial dependent flow mediated vasodilation of the brachial artery:a report of the international brachial artery reactivity task force. J Am Coll Cardiol. 2009;39:257–65. 66. Papaioannou TG, Stefanadis C. Vascular wall shear stress: basic principles and methods. Hellenic J Cardiol. 2005;46 (1):9–15. 67. Bots ML, Westerink J, Rabelink TJ, et al. Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response. Eur Heart J. 2005;26(4):363–8. 68. ACC/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults 2010. 69. Qaisi MA, Kharbanda RK, Mittal TK, et al. Measurement of endothelial function and its clinical utility for cardiovascular risk. Vasc Health Risk Manage. 2008,$(3):647–52. 70. Yeboah J, Crouse JR, Hsu FC, et al. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation. 2007; 115(18):2390–7. 71. Celermajer DS, Sorensen KE, Spiegelhalter DJ, et al. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol. 1994;24(2):471–6. 72. Sader MA, Celermajer DS. Endothelial function, vascular reactivity and gender differences in the cardiovascular system. Cardiovasc Res. 2002;53(3):597–604. 73. Paniagua OA, Bryant MB, Panza JA. Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature: diminished activity in hypertensive and hypercholesterolemic patients. Circulation. 2001;103(13): 1752–8. 74. Sudjarwo SA. Mechanisms of endothelial cell protection by quercetin in hypercholesterolemia. Res Pharm Biotechnol. 2011;3(9):123–7. 75. Widlansky ME, Gokce N, Keaney JF Jr, et al. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003;42(7):1149–60. 76. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109:III27–III32.

477

77. Strey CH, Young JM, Lainchbury JH, et al. Short-term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non-ischaemic heart failure. Heart. 2006;92(11):1603–9. 78. Masaaki Ii, Losordo DW. Statins and the endothelium.Vasc Pharmacol. 2007;46 (2007);1–9. 79. Zhang L, Gong D, Li S, et al. Meta-analysis of the effects of statin therapy on endothelial function in patients with diabetes mellitus. Atherosclerosis. 2012;223(1):78–85. 80. Reriani MK, Dunlay SM, Gupta B, et al. Effects of statins on coronary and peripheral endothelial function in humans: a systematic review and meta-analysis of randomized controlled trials. Eur J Cardiovasc Prev Rehabil. 2011;18 (5):704–16. 81. Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000;20(9):2032–7. 82. Kawano H, Motoyama T, Hirashima O, et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999;34 (1):146–54. 83. Higashi Y, Kihara Y, Noma K. Endothelial dysfunction and hypertension in aging. Hypertens Res. 2012;35(11): 1039–47. 84. Gupta AK, Ravussin E, Johannsen DL, et al. Endothelial Dysfunction: An Early Cardiovascular Risk Marker in Asymptomatic Obese Individuals with Prediabetes. Br J Med Med Res. 2012;2(3):413–23. 85. Hashemi M, Kiani Y, Basiratnia R, et al. Endothelial function in adolescents with a history of premature coronary artery disease in one parent. JRMS. 2006;11(1):18–23. 86. Johnson HM, Gossett LK, Piper ME, et al. Effects of smoking and smoking cessation on endothelial function: 1-year outcomes from a randomized clinical trial. J Am Coll Cardiol. 2010;55(18):1988–95. 87. Kim KS, Park HS, Jung IS, et al. Endothelial dysfunction in the smokers can be improved with oral cilostazol treatment. J Cardiovasc Ultrasound. 2011;19(1):21–5. 88. Frey PF, Ganz P, Hsue PY, et al. The exposure-dependent effects of aged secondhand smoke on endothelial function. J Am Coll Cardiol. 2012;59(21):1908–13. 89. Juonala M, Magnussen CG, Venn A, et al. Parental smoking in childhood and brachial artery flow-mediated dilatation in young adults: the Cardiovascular Risk in Young Finns study and the Childhood Determinants of Adult Health study. Arterioscler Thromb Vasc Biol. 2012;32(4): 1024–31. 90. Papamichael CM, Aznaouridis KA, Karatzis EN, et al. Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci. 2005;109(1):55–60. 91. Dickinson KM, Keogh JB, Clifton PM. Effects of a low-salt diet on flow-mediated dilatation in humans. Am J Clin Nutr. 2009;89(2):485–90. 92. Wexler O, Morgan AM, Gough MS, et al. Brachial artery reactivity in patients with severe sepsis: an observational study. Critical Care. 2012;16:R 38.

478

Section 2: Echocardiography/Ultrasound Examination and Training

93. Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood. 2003;101 (10):3765–77. 94. Pierce GL, Beske SD, Lawson BR, et al. Weight loss alone improves conduit and resistance artery endothelial function in young and older overweight/obese adults. Hypertension. 2008;52(1):72–9. 95. Modena MG, Bonetti L, Coppi F, et al. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol. 2002;40(3):505–10. 96. Trott DW, Gunduz F, Laughlin MH, et al. Exercise training reverses age-related decrements in endotheliumdependent dilation in skeletal muscle feed arteries. J Appl Physiol. 2009;106(6):1925–34. 97. DeSouza CA, Shapiro LF, Clevenger CM, et al. Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation. 2000;102(12):1351–7. 98. Higashi Y, Sasaki S, Kurisu S, et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation. 1999;100 (11):1194–202. 99. Celermajer DS, Sorensen KE, Bull C, et al. Endotheliumdependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994;24(6):1468–74. 100. Yeboah J, Folsom AR, Burke GL, et al. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120(6):502–9. 101. Widlansky ME, Gokce N, Keaney JF Jr, et al. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003;42(7):1149–60. 102. Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115(10):1285–95. 103. Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005;111(3):363–8. 104. Neunteufl T, Heher S, Katzenschlager R, et al. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol. 2000;86(2):207–10. 105. Gokce N, Keaney JF Jr, Hunter LM, et al. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation. 2002;105(13):1567–72. 106. Gokce N, Keaney JF Jr, Hunter LM, et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003;41(10):1769–75. 107. Modena MG, Bonetti L, Coppi F, et al. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol. 2002;40(3): 505–10. 108. Naka KK, Tweddel AC, Doshi SN, et al. Flow-mediated changes in pulse wave velocity: a new clinical measure of endothelial function. Eur Heart J. 2006;27(3):302–9.

109. Torrado J, Bia D, Zócalo Y, et al. Hyperemia-Related Changes in Arterial Stiffness: Comparison between Pulse Wave Velocity and Stiffness Index in the Vascular Reactivity Assessment. Int J Vasc Med. 2012;2012:490742. 110. Stoner L, Young JM, Fryer S. Assessments of arterial stiffness and endothelial function using pulse wave analysis. Int J Vasc Med. 2012;2012:903107. 111. Accetto R, Salobir B, Brgulijan J, et al. Clinical implications of pulse wave analysis. Sci J Faculty Med Nis. 2010;27(3): 165–169. 112. Lunder M, Janic M, Kejzar N, et al. Associations among different functional and structural arterial wall properties and their relations to traditional cardiovascular risk factors in healthy subjects: a cross-sectional study. BMC Cardiovasc Disord. 2012;12:29. 113. Soga J, Nakamura S, Nishioka K, et al. Relationship between augmentation index and flow-mediated vasodilation in the brachial artery. Hypertens Res. 2008;31:1293–8. 114. Celermajer DS. Reliable endothelial function testing: at our fingertips? Circulation. 2008;117(19):2428–2430. 115. Hamburg NM, Benjamin EJ. Assessment of endothelial function using digital pulse amplitude tonometry. Trends Cardiovasc Med. 2009;19(1):6–1. 116. Kuvin JT, Patel AR, Sliney KA, et al. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146(1):168–74. 117. Hamburg NM, Palmisano J, Larson MG, et al. Relation of brachial and digital measures of vascular function in the community: the Framingham heart study. Hypertension. 2011;57(3):390–6. 118. Allan RB, Delaney CL, Miller MD, et al. A comparison of flow-mediated dilatation and peripheral artery tonometry for measurement of endothelial function in healthy individuals and patients with peripheral arterial disease. Eur J Vasc Endovasc Surg. 2013;45(3):263–9. 119. Martin BJ, Gurtu V, Chan S, et al. The relationship between peripheral arterial tonometry and classic measures of endothelial function. Vasc Med. 2012;December 21. 120. Tibiriçá E, Matheus AS, Nunes B, et al. Repeatability of the evaluation of systemic microvascular endothelial function using laser doppler perfusion monitoring: clinical and statistical implications. Clinics (Sao Paulo). 2011;66(4): 599–605. 121. Gori T, Dragoni S, Lisi M, et al. Conduit artery constriction mediated by low flow a novel noninvasive method for the assessment of vascular function. J Am Coll Cardiol. 2008; 51(20):1953–8. 122. Weissgerber TL, Davis GAL, Tschakovsky ME. Low flow mediated constriction occurs in radial but not the brachial artery in healthy pregnant and nonpregnant women. J Appl Physiol. 2009;108:1097–105. 123. Gori T, Muxel S, Damaske A, et al. Endothelial function assessment: flow mediated dilation and constriction provide different and complimentary information on the presence of coronary artery disease. Eur Heart J. 2011. Doi:10. 1093/eurheart/ehr361.

Chapter 23: Endothelial Dysfunction

124. Gori T, Parker JD, Munzel T. Flow mediated constriction: further insight into anew measure of vascular function. Eur Heart J. 2010. doi:10. 1093/eurheart/ehq412. 125. Ananthakrishnaa R, Shankarappaa RK, Rangana K, et al. Endothelial function and carotid intimal medial thickness in asymptomatic subjects with and without cardiovascular risk factors. Cardiol Res. 2012;3(4):180–86. 126. Takase B, Matsushima Y, Uehata A, et al. Endothelial dysfunction, carotid artery plaque burden, and conventional exercise-induced myocardial ischemia as predictors of coronary artery disease prognosis. Cardiovasc Ultrasound. 2008;6:61. 127. Frick M, Suessenbacher A, Alber HF, et al. Prognostic value of brachial artery endothelial function and wall thickness. J Am Coll Cardiol. 2005;46(6):1006–10. 128. Halcox JP, Donald AE, Ellins E, et al. Endothelial function predicts progression of carotid intima-media thickness. Circulation. 2009;119(7):1005–12. 129. Yan RT, Anderson TJ, Charbonneau F, et al. Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men. J Am Coll Cardiol. 2005;45(12):1980–6. 130. Fahrettin Oz F, Elitoka A, Bilgea AK, et al. Relationship between brachial artery flow-mediated dilation, carotid artery intima-media thickness and coronary flow reserve in patients with coronary artery disease. Cardiol Res. 2012; 3(5):214–21.

479

131. Yoon HJ, Jeong MH, Cho SH, et al. Endothelial dysfunction and increased carotid intima-media thickness in the patients with slow coronary flow. J Korean Med Sci. 2012; 27(6):614–8. 132. Hashimoto M, Eto M, Akishita M, et al. Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men. Arterioscler Thromb Vasc Biol. 1999;19(11): 2795–800. 133. Mori J Krantz MJ, Long CS, Hosokawa P, et al. Pulse wave velocity and carotid atherosclerosis in White and Latino patients with hypertension. BMC Cardiovasc Disorders. 2011;11:15. 134. Della-Morte D, Gardener H, Denaro F, et al. Metabolic syndrome increases carotid artery stiffness: the Northern Manhattan Study. Int J Stroke. 2010;5(3):138–44. 135. Akiyama E, Sugiyama S, Matsuzawa Y, et al. Incremental prognostic significance of peripheral endothelial dysfunction in patients with heart failure with normal left ventricular ejection fraction. J Am Coll Cardiol. 2012;60(18): 1778–86. 136. Aizer J, Karlson EW, Chibnik LB, et al. A controlled comparison of brachial artery flow mediated dilation (FMD) and digital pulse amplitude tonometry (PAT) in the assessment of endothelial function in systemic lupus erythematosus. Lupus. 2009;18(3):235–42.

CHAPTER 24 How to do a Two-Dimensional Transesophageal Examination Andrew P Miller, Navin C Nanda

Snapshot  PaƟent SelecƟon and Consent  PreparaƟon, Conscious SedaƟon and Esophageal IntubaƟon

INTRODUCTION The transesophageal echocardiographic (TEE) examination offers unmatched resolution for evaluating intracardiac structures and function.1 TEE is commonly employed to discern the presence of left atrial appendage thrombus and function, patent foramen ovale, or valvular lesions in stroke; of vegetations and valvular insufficiency in endocarditis; of prosthetic valvular dysfunction; and of aortic dissection. Additionally, TEE has become useful as a virtual operating suite to assist the electrophysiologist or interventionalist in structural heart procedures. This chapter will review a systematic approach to the twodimensional (2D) TEE examination.

PATIENT SELECTION AND CONSENT Once an indication for TEE has been identified, the examination begins with a patient interview and examination. In the interview, it is important to screen for dysphagia, history of esophagitis or peptic ulcer disease, prior esophageal or gastric surgery, liver disease, and prior cervical spine surgery. These entities do increase the risk for oral, oropharyngeal, laryngeal, esophageal, or gastric injury. In several series, TEE-reported complications occur in 2–5/1,000 procedures and TEE-related mortality is 50 mm2 (sensitivity = 92% and specificity = 87%) for predicting severe AR.35 Thus, 3D echo VC is a promising, simple, and potentially time-saving method of determining AR severity. 3D echo has become an increasingly important tool in the periprocedural planning of transcatheter aortic valve implantation. 3D echo can measure the distance from the aortic annulus to the coronary ostia, which is crucial for optimal placement of prosthetic valves via the percutaneous route. The accuracy of 3D transesophageal echocardiography for assessing the distance between the left main coronary ostium to the aortic annulus was assessed in a series of 122 patients undergoing transcatheter aortic valve implantation.38 The authors found excellent preoperative correlation between 3DTEE measured and multidetector computed tomography (CT) measured aortic annulus to left main distance. 3DE is also valuable in determining the extent and mechanism of aortic regurgitation post-transcatheter aortic valve implantation. For instance, in a recent study of 135 patients with severe symptomatic aortic stenosis who underwent transcatheter aortic valve implantion (TAVI), calcification between the right coronary and noncoronary cusps and the area cover index as determined by 3DTEE were shown to be significant predictors of paravalvular aortic regurgitation following TAVI.39 We know from 3D echo that the aortic valve annulus is geometrically elliptical rather than round, and therefore annular measurements obtained with 3D echo are more accurate than those obtained with 2D methods.40 Accurate estimation of annular size is particularly important in the setting of TAVI to minimize post implantation paravalvular regurgitation. The superior accuracy of 3D imaging techniques in determining

522

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 27.8A to C: (A) Protocol for transthoracic 3D echo acquisition of the pulmonic valve; (B) Parasternal right ventricular outflow tract view with and without color; (C) Parasternal short-axis view with and without color (zoomed and narrow angle acquisitions). (AoV: Aortic valve; PV: Pulmonic valve).

annular size was demonstrated in a series of 49 patients with severe aortic stenosis undergoing transcatheter aortic valve implantation. The authors found that the sagittal diameters determined by 2DTTE and TEE were smaller than coronal diameters measured by 3DTEE and dual source CT. Furthermore, both coronal and sagittal diameters determined by 3DTEE were in high agreement with corresponding measurements by dual source CT.41 3D echo may also allow for better elucidation of the mechanism of aortic insufficiency as well as allow for visualization and measurement of multiple jets and the assessment of prosthetic aortic valve function.22,24 For these reasons, routine clinical use of 3D echo for assessing aortic valve pathology is supported.1

3D ECHO OF THE PULMONIC VALVE To acquire optimal transthoracic 3D echo images of the pulmonic valve, images are best obtained from the

parasternal right ventricular outflow tract view with and without color (narrow angle and zoomed acquisitions; Figs 27.8A to C; Movie clip 27.6). The protocol for acquiring transesophageal echo images of the pulmonic valve (Figs 27.9A and B) involves 90° basal-esophageal acquisitions both with and without color, as well as 120° mid-esophageal long-axis views with and without color (Movie clip 27.7). Whereas 2D imaging allows visualization of only two cusps simultaneously, 3D imaging of the pulmonic valve allows all three leaflets of the pulmonic valve to be evaluated concurrently.42 With 3D imaging of the pulmonic valve, cusp number can be accurately evaluated, as can involvement with carcinoid disease, endocarditis, as well as supravalvular, valvular, and subvalvular measurements.42–47 Kelly et al. performed live 3D transthoracic echocardiography and full-volume 3D transthoracic echocardiography to assess the feasibility of visualizing pulmonic valve morphology in 200 consecutive patients. 3D images were acquired from

Chapter 27: Three-Dimensional Examination to Evaluate Valvular Heart Disease: The Value of an Added Dimension

A

523

B

Figs 27.9A and B: Protocol for transesophageal 3D echo acquisition of the pulmonic valve. (A) 90° high esophageal view with and without color; (B) 120° three-chamber view with and without color. (PV: Pulmonic valve).

the long- and short-axis parasternal and apical fourchamber views with final volumes evaluated off-line to obtain a short-axis view of the pulmonic valve. Pulmonic valve morphology could be obtained in 63% and 23% of patients using live 3D and full-volume 3D techniques. Thus, 3DE can distinguish between tricuspid, bicuspid, and unicuspid leaflet morphology in the majority of cases.42 3D color methods can also quantify pulmonic regurgitation directly through direct measurement of the ERO. Pothineni et al. demonstrated the utility of 3DE in quantitating pulmonary regurgitation severity in 82 patients with at least mild pulmonic regurgitation reported on 2D imaging.44 Pulmonic regurgitation VC area was measured by planimetry with the cropping plane positioned parallel to the VC. The VC was then viewed en face by cropping the 3D data set. The authors found that 3D VC area had good correlation to 2D jet-width to right ventricular outflow tract width (r = 0.71) and 2D VC area (r = 0.79). Although there is no gold standard for the measurement of pulmonary regurgitation severity, the 3D method of measuring VC may circumvent the inaccuracies posed by 2 D echo that only allows visualization of one or two dimensions of the proximal PR jet or VC. The utility of 3D transthoracic and transesophageal echo for assessing carcinoid involvement of the pulmonic valve has been described as case reports in the literature.43,46 Dumaswala et al. reported a case of carcinoid heart disease involving the tricuspid and pulmonic valves.48 3DTTE demonstrated thickening, restricted mobility, and noncoaptation of all three leaflets of the pulmonic valve. In a similar case, 3DTEE permitted en face view of all three pulmonic valve

cusps simultaneously, assessment of leaflet coaptation and delineation of the spatial relationship between the valve, subvalvular apparatus, and the endocardial surface of surrounding chambers.46 Although current American society of echocardiography (ASE) guidelines state there is not sufficient evidence to support the routine use of 3D techniques for assessing pulmonic valve disease, our lab has found it helpful in particular clinical situations, including confirming significant carcinoid involvement of the pulmonic valve in a patient undergoing tricuspid valve replacement for severe carcinoid involvement of the pulmonic valve.48

3D ECHO OF THE TRICUSPID VALVE To acquire optimal transthoracic 3D echo images of the tricuspid valve, images are best obtained from the apical four-chamber view and/or the parasternal right ventricular inflow view, with and without color (narrow angle and zoomed acquisitions; Figs 27.10A and B; Movie clip 27.8). The protocol for acquiring transesophageal echo images of the tricuspid valve (Figs 27.11A and B) involves 0° to 30° mid-esophageal four-chamber zoomed acquisitions both with and without color (Figs 27.12A and B), as well as 40° transgastric views with anteflexion with and without color (zoomed acquisition; Movie clip 27.9). 3D echo of the tricuspid valve has demonstrated that the tricuspid valve is saddle shaped, becoming more planar and circular with functional tricuspid insufficiency. Anwar et al. was able to visualize the tricuspid valve in 90% of 100 consecutive patients undergoing transthoracic

524

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 27.10A and B: 3D transesophageal echo of the pulmonic valve in a patient with carcinoid involvement. (A) Live 3D long-axis view of the pulmonic valve; (B) En face view of the pulmonic valve from the pulmonary artery. Note the markedly thickened and retracted leaflets. (PV: Pulmonic valve).

A

B

Figs 27.11A and B: Protocol for 3D transthoracic echo of the tricuspid valve. (A) Apical four-chamber view with and without color; (B) Parasternal RV inflow view with and without color. (TV: Tricuspid valve).

3DE en face from both the ventricular and atrial aspects to characterize annulus shape and size, leaflet shape, size and mobility, and commissural width. They demonstrated that the tricuspid annulus shape is oval both in the normal and dilated state of the annulus. They also showed that the leaflet visualized at the right ventricular free wall in the apical four-chamber view consistently corresponds to the anterior leaflet.49 The same group demonstrated the value of 3D transthoracic echocardiography in the assessment of the thickness, mobility, and calcification in rheumatic tricuspid stenosis at the level of each individual leaflet. Furthermore, they demonstrated that, unlike 2D transthoracic echocardiography, all three

commissures could be adequately evaluated with 3DE including commissural width during maximal tricuspid valve opening. As expected, they found that patients with tricuspid stenosis had significantly smaller commissural widths at maximal tricuspid valve opening.50 3D echo of the tricuspid valve may help provide clinical insight into mechanisms of tricuspid insufficiency, and can help identify pacer and implantable cardiodefibrillator (ICD) lead position, as it transverses the tricuspid valve.51–55 For instance, Sukmawan et al. used 3D transthoracic echocardiography to show that tricuspid regurgitation secondary to pulmonary hypertension was characterized by enlargement of the tricuspid tenting

Chapter 27: Three-Dimensional Examination to Evaluate Valvular Heart Disease: The Value of an Added Dimension

A

525

B

Figs 27.12A and B: Protocol for 3D transesophageal echo of the tricuspid valve. (A) 0° to 30° mid-esophageal four-chamber view with and without color; (B) 80° transgastric view with anteflexion with or without color. (TV: Tricuspid valve).

volume and dilatation of the annulus. Tenting volume was calculated as the volume enclosed between the annular plane and tricuspid leaflets.52 3D echo can also provide quantification of tricuspid regurgitation through direct measurement of EROA and has provided important insight into the geometrical determinants of the VC in tricuspid regurgitation.56–58 Real time 3D full-volume and color Doppler images were obtained in 52 patients with various degrees of functional TR. The authors demonstrated that the cross-sectional shape of the VC is ellipsoidal (with a relatively longer anteroposterior direction) rather than circular suggesting that different VC cutoff values should be applied according to the plane of view in functional TR (56). Velayudhan et al. measured tricuspid regurgitation (TR) VC area with 3DTTE by systematic and sequential cropping of the acquired 3DTTE data set in 93 consecutive

patients and compared the results to various 2DTTE measurements of TR severity including the ratio of TR regurgitant jet area to right atrial area, right atrial jet area alone, and VC width and calculated VC area. They found close correlation between VC area from 3DTTE and TR regurgitant jet area to right atrial area and right atrial jet area alone as determined from 2D TTE measurements. Furthermore, they found that 3DTTE could differentiate between severe and torrential TR, as there were several patients with VC area > 1.0 cm2.58 As with carcinoid involvement with pulmonic valves, 3DE has proven to be an invaluable tool in providing detailed anatomic information of carcinoid involvement in tricuspid valves.43,46 Current published ASE guidelines support routine use of 3D echo for the evaluation of tricuspid valve disease.

CASE EXAMPLES OF 3D ECHO IN VALVULAR HEART DISEASE CASE STUDY 1: PARAVALVULAR LEAK MECHANICAL MV An 86-year-old male who underwent St. Jude’s mechanical MV replacement in 2010 presented at our hospital complaining of exertional dyspnea and New York Heart Associaton (NYHA) Class II to III heart failure symptoms. Transthoracic echo suggested a possible paravalvular leak. TEE was performed with 3D imaging to confirm the presence of a paravalvular leak, and to also determine

if it was amenable to percutaneous closure. 2DTEE imaging confirmed a St. Jude’s valve to be present in the mitral position, and to be stable. Two paravalvular jets were identified, the largest of which originated from the septal aspect of the MV and was associated with at least moderate MR. Both leaflets were noted to open and close well and normal washing jets were identified. The second paravalvular leak was noted to emanate from the lateral aspect of the prosthesis, and hugged the lateral wall of the left atrium (Movie clip 27.10 and 27.11). Live 3D zoomed

526

Section 2: Echocardiography/Ultrasound Examination and Training

imaging of the mitral prosthesis from the left atrial view confirmed that the prosthesis was well seated without rocking motion. The largest of the two defects was noted to be crescentic in appearance, and was felt to be amenable to percutaneous closure (Movie clip 27.12). The patient was quoted a 10% risk of serious complications associated with percutaneous closure, and ultimately underwent successful percutaneous closure of both paravalvular leaks, without complication, and has clinically improved.

CASE STUDY 2: MV REPAIR AND AORTIC VALVE REPLACEMENT A 63-year-old male with a history of MV repair and aortic valve replacement in 1992 developed fevers and chills, which were associated with positive blood cultures while vacationing in Florida. He was treated for an infected ICD with antibiotics and returned home for further evaluation. TEE was requested at our institution to evaluate for valvular vegetations. 2DTEE imaging confirmed no evidence of valvular vegetation and no evidence of mitral annular abscess. The annuloplasty ring was noted to be partially dehisced and mild valvular MR was present. There was no mitral paravalvular leak (Movie clips 27.13 to 27.15). Live 3D imaging of the mitral ring from the left atrial view, confirmed partial dehiscence of the ring along the posterior mitral annulus (Movie clip 27.16). 2D imaging of the aortic prosthesis demonstrated a moderate to large paravalvular leak that originated posteriorly and was directed anteriorly. There was no evidence of prosthetic aortic vegetation and no evidence of aortic abscess (Movie clip 27.17). 3D imaging confirmed the mitral ring and aortic prosthesis to be stable, with no evidence of rocking (Movie clip 27.18 and 27.19). Despite the partially dehisced mitral ring and moderate posterior aortic paravalvular leak, the patient was clinically asymptomatic, and a decision was made to follow him medically.

CASE STUDY 3: S/P CARDIAC TRANSPLANT WITH RIGHT HEART FAILURE, TRICUSPID VALVE REPLACEMENT A 77 year-old-male with history of cardiac transplant presented to our hospital with worsening right heart failure and renal failure. The patient had a history of a bioprosthetic tricuspid valve replacement, and initial 2D transthoracic imaging revealed a degenerated #31 Carpentier Edwards tricuspid prosthesis with pannus

formation and moderate to severe tricuspid insufficiency. The patient was not deemed to be an open surgical candidate, and was referred to us to determine if a #26 Edwards-Sapien percutaneous valve could be successfully placed within his #31 Carpentier Edwards tricuspid valve. TEE with 3D reconstruction was requested to determine if the pannus had sufficiently reduced the tricuspid annular diameter such that the smaller #26 Edwards-Sapien valve would stick. 2D TEE confirmed the presence of moderate to severe prosthetic tricuspid insufficiency with significant pannus. The mean transtricuspid gradient was markedly elevated at 8 mmHg (Movie clip 27.20 and 27.21). Live 3D imaging of the tricuspid prosthesis was performed from the right atrium (Movie clip 27.22). Full volume multibeat 3D imaging of the tricuspid prosthesis from the mid-esophageal four-chamber view was performed with reconstruction to visualize the tricuspid annulus from the right atrium (Movie clip 27.23). The #31 Carpentier Edwards prosthetic tricuspid valve with pannus was measured at 2.5 cm × 2.2 cm and the patient was deemed to be a suitable candidate for percutaneous #26 mm Edwards Sapien valve in valve replacement, and the patient underwent this procedure successfully without complication. The patient underwent 2D and 3D transthoracic echocardiography postprocedure that confirmed the #26 Edwards-Sapien valve to be in stable position within the #31 Carpentier Edwards bioprosthetic valve. There were no paravalvular leaks and the mean transtricuspid gradient measured 5 mm Hg at a hazard ratio (HR) of 81 bpm. There was mild valvular tricuspid insufficiency (Movie clip 27.24 and 27.25). The patient feels well and progressively stronger postprocedure, and is pleased with the outcome.

CASE STUDY 4: FLAIL MIDDLESCALLOP, POSTERIOR LEAFLET, MV A 70-year-old male in good health with known MV prolapse and severe mitral insufficiency was referred for 3DTEE to further evaluate the mechanism of mitral insufficiency. His pulmonary artery systolic pressure was noted to increase to 56 mm Hg with exercise, and the patient was being considered for elective MV repair. The patient was asymptomatic and reported no shortness of breath, fatigue, or peripheral edema. 2DTEE confirmed severe anteriorly directed mitral insufficiency with a flail posterior segment. Live 3D imaging of the MV from the left atrial perspective confirmed a flail middle scallop of the posterior leaflet of the MV (P2; Movie clip 27.26 and 27.27).

Chapter 27: Three-Dimensional Examination to Evaluate Valvular Heart Disease: The Value of an Added Dimension

Given the favorable anatomy, the patient chose to undergo elective surgery of the MV, and underwent successful repair and quadrangular resection of the P2 scallop. He is currently doing well clinically.

CASE STUDY 5: BILEAFLET MV PROLAPSE, MODERATE TO SEVERE MITRAL INSUFFICIENCY A 65-year-old female with known bileaflet MV prolapse and moderate to severe mitral insufficiency presents to the cardiology clinic complaining of increasing dyspnea on exertion. The patient was referred for exercise stress echo where she exercised for 8 minutes and 45 seconds on a standard Bruce protocol, and her pulmonary artery systolic pressure increased from 36 mm Hg to 56 mm Hg. She was subsequently referred for TEE with 3D imaging to determine if the valve was amenable for repair. TEE confirmed the MV to be diffusely myxomatous with classic bileaflet MV prolapse (Barlow’s valve). At a blood pressure of 115 mm Hg systolic, moderate mitral insufficiency was identified by color Doppler. There were two MR jets, both central in origin and direction. Pulmonary venous flow was normal. Live 3D imaging of the MV confirmed prolapse of A1, A2, A3, P1, P2, and P3 scallops (Movie clip 27.28 and 27.29). The patient was quoted a likelihood of successful MV repair to be 70%. She was also noted to have diastolic dysfunction. Given the complexity of repair and absence of severe mitral insufficiency, a decision was made to treat the patient medically with low doses of lasix and monitor carefully for worsening symptoms and/or regurgitation.

CASE STUDY 6: SEVERE AORTIC STENOSIS, EVALUATE FOR POSSIBLE TAVR A 63-year-old female presents with severe symptomatic aortic stenosis. She has a cardiac history notable for coronary artery bypass grafting (CABG) and MV replacement in 1998, and is referred for TEE in preparation for possible transcatheter aortic valve replacement (TAVR). 2DTEE images confirmed the presence of severe calcific aortic stenosis. The calculated aortic valve area via planimetry and the continuity equation was 0.5 cm2. By 2D methods the aortic annulus was measured at 2.5–2.6 cm. The distance from the aortic annulus to the ostium of the right coronary artery measured 1.5 cm (Movie clips 27.30 and 27.31). 3D imaging with reconstruction was performed

527

to measure the distance from the annulus to the ostium of the left coronary artery from full-volume coronal views. This distance was measured at 1.5 cm (Movie clip 27.32). As a result of these findings, the patient was deemed to be a suitable candidate for TAVR with the larger #26 Edwards Sapien valve. Recently published ASE recommendations for echo in TAVR recommend that in general, a distance of greater than 10 mm is desirable from the aortic annulus to the ostium of the right and left coronary arteries for the #23 Edwards Sapien valve and a distance of greater than 11 mm is desirable for the #26 mm valve.5 2DTEE is able to define the annular-ostial distance for the right coronary artery. In contrast, measurement of the distance from the annulus to the left main coronary artery requires 3DTEE, as the left main lies in the coronal plane. These measurements are crucial, since an improperly sized prosthesis can obstruct coronary flow, resulting in coronary insufficiency, and may be life threatening.

CASE STUDY 7: RHEUMATIC MITRAL STENOSIS An 82-year-old Lebanese female develops acute heart failure following appendectomy. Transthoracic echo confirms the presence of moderate to severe rheumatic mitral stenosis. She presents to cardiology clinic for further evaluation of the need for balloon mitral valvuloplasty or surgical MV replacement. Transthoracic echo confirmed rheumatic MV deformity with moderate mitral stenosis. Her mean transmitral gradient was 8 mm Hg at a HR of 69 bpm, and her MVA was calculated at 1.5 cm2 via pressure half-time and 1.6 cm2 via planimetry. She was also noted to have moderate mitral insufficiency by color Doppler. 3D imaging of the MV confirmed the presence of commissural fusion (Movie clip 27.33). Full-volume 3D reconstructions of the MV were performed to help improve the accuracy of planimetry, and confirmed the MV area to measure 1.5–1.6 cm2 (Movie clip 27.34). Due to the significant mitral insufficiency, she was not deemed to be an ideal candidate for balloon mitral valvuloplasty. For now, she will be treated medically with beta-blockers, with careful clinical and echocardiographic follow-up.

CASE STUDY 8: S/P BALLOON AORTIC VALVULOPLASTY A 76-year-old female with severe calcific aortic stenosis and chronic obstructive pulmonary disease (COPD) is referred for balloon aortic valvuloplasty. Transthoracic

528

Section 2: Echocardiography/Ultrasound Examination and Training

echo is obtained postvalvuloplasty and demonstrates there is now moderate aortic insufficiency. There remains severe aortic stenosis. Live 3DTTE demonstrates that the native aortic valve has been disrupted (Movie clip 27.35).

CASE STUDY 9: MECHANISM AND SEVERITY OF ECCENTRIC MITRAL INSUFFICIENCY A 69-year-old male with hypertension and lower extremity edema is noted to have eccentric and posteriorly directed mitral insufficiency of uncertain severity on transthoracic echo. He is referred for TEE to further evaluate the mechanism of mitral insufficiency and its severity. 2DTEE confirmed an eccentric posteriorly directed jet that by color Doppler appears mild at a BP of 90/60 mmHg and possibly moderate to severe following administration of Neosynephrine at a BP of 151/89 mm Hg (Movie clip 27.36). 3D full-volume imaging with reconstruction was performed with direct measurement of the EROA. This confirmed the presence of severe prolapse of the A3 scallop with moderate mitral insufficiency. The directly measured 3D ERO was 0.3 cm2 (Movie clip 27.37). These results confirmed that there was no need for surgical intervention at the current time.

CASE STUDY 10: QUESTION OF CARCINOID INVOLVEMENT OF THE PULMONIC VALVE A 60-year-old male with a history of carcinoid syndrome presented with severe tricuspid insufficiency and question of severe pulmonic insufficiency on transthoracic echo. Since his overall survival rate was considered reasonable, it was recommended that he undergo surgical valve replacement to preserve his ventricular function. 3DTEE was performed to determine the extent of carcinoid involvement of the pulmonic valve, since this was not adequately visualized by 2D methods. Live 3D imaging of the pulmonic valve from the pulmonary perspective confirmed the valve was severely thickened and retracted with carcinoid involvement and severe wide open pulmonic insufficiency. Live 3D imaging of the tricuspid valve from the right atrial perspective also confirmed severe carcinoid involvement of the tricuspid valve with severe wide open tricuspid insufficiency (Movie clip 27.38). These findings were confirmed at surgery, and the patient underwent successful bioprosthetic tricuspid and pulmonic valve replacement.

SUMMARY This comprehensive review with case presentations demonstrating the current status of 3D echo to evaluate valvular heart disease has hopefully solidified the value of an added dimension in every day clinical decision making using cardiac ultrasound. Although 3D echo currently complements 2D echo in daily clinical practice, it is our belief, that its full potential has yet to be realized. New technology, including single heartbeat full-volume data sets, live color 3D, the ability to make live 3D measurements, continued improvements in 3D spatial and temporal resolution and integration into digital PACS systems, and new automated quantitative tools, will continue to enhance the utility and efficiency of 3D echo for the assessment of valvular heart disease in daily clinical practice.

REFERENCES 1. Lang RM, Badano LP, Tsang W, et al. American Society of Echocardiography; European Association of Echocardiography. EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. J Am Soc Echocardiogr. 2012;25(1):3–46. 2. Sugeng L, Coon P, Weinert L, et al. Use of real-time 3-dimensional transthoracic echocardiography in the evaluation of mitral valve disease. J Am Soc Echocardiogr. 2006;19(4):413–21. 3. Patel V, Hsiung MC, Nanda NC, et al. Usefulness of live/real time three-dimensional transthoracic echocardiography in the identification of individual segment/scallop prolapse of the mitral valve. Echocardiography. 2006;23(6):513–8. 4. Grewal J, Suri R, Mankad S, et al. Mitral annular dynamics in myxomatous valve disease: new insights with real-time 3-dimensional echocardiography. Circulation. 2010;121 (12):1423–31. 5. La Canna G, Arendar I, Maisano F, et al. Real-time threedimensional transesophageal echocardiography for assessment of mitral valve functional anatomy in patients with prolapse-related regurgitation. Am J Cardiol. 2011;107(9): 1365–74. 6. Chikwe J, Adams DH, Su KN, et al. Can three-dimensional echocardiography accurately predict complexity of mitral valve repair? Eur J Cardiothorac Surg. 2012;41(3):518–24. 7. Otani K, Takeuchi M, Kaku K, et al. Evidence of a vicious cycle in mitral regurgitation with prolapse: secondary tethering attributed to primary prolapse demonstrated by three-dimensional echocardiography exacerbates regurgitation. Circulation. 2012;126(11 Suppl 1):S214–21. 8. Little SH. Three-dimensional echocardiography to quantify mitral valve regurgitation. Curr Opin Cardiol. 2012;27(5): 477–84. 9. Benenstein R, Saric M. Mitral valve prolapse: role of 3D echocardiography in diagnosis. Curr Opin Cardiol. 2012; 27(5):465–76.

Chapter 27: Three-Dimensional Examination to Evaluate Valvular Heart Disease: The Value of an Added Dimension

10. Ahmed S, Nanda NC, Miller AP, et al. Usefulness of transesophageal three-dimensional echocardiography in the identification of individual segment/scallop prolapse of the mitral valve. Echocardiography. 2003;20(2):203–9. 11. Biaggi P, Jedrzkiewicz S, Gruner C, et al. Quantification of mitral valve anatomy by three-dimensional transesophageal echocardiography in mitral valve prolapse predicts surgical anatomy and the complexity of mitral valve repair. J Am Soc Echocardiogr. 2012;25(7):758–65. 12. Ben Zekry S, Nagueh SF, Little SH, et al. Comparative accuracy of two- and three-dimensional transthoracic and transesophageal echocardiography in identifying mitral valve pathology in patients undergoing mitral valve repair: initial observations. J Am Soc Echocardiogr. 2011; 24(10):1079–85. 13. Biaggi P, Gruner C, Jedrzkiewicz S, et al. Assessment of mitral valve prolapse by 3D TEE angled views are key. JACC Cardiovasc Imaging. 2011;4(1):94–7. 14. Kahlert P, Plicht B, Schenk IM, et al. Direct assessment of size and shape of noncircular vena contracta area in functional versus organic mitral regurgitation using realtime three-dimensional echocardiography. J Am Soc Echocardiogr. 2008;21(8):912–21. 15. Yosefy C, Hung J, Chua S, et al. Direct measurement of vena contracta area by real-time 3-dimensional echocardiography for assessing severity of mitral regurgitation. Am J Cardiol. 2009;104(7):978–83. 16. Chu JW, Levine RA, Chua S, et al. Assessing mitral valve area and orifice geometry in calcific mitral stenosis: a new solution by real-time three-dimensional echocardiography. J Am Soc Echocardiogr. 2008;21(9):1006–9. 17. Anwar AM, Attia WM, Nosir YF, et al. Validation of a new score for the assessment of mitral stenosis using real-time three-dimensional echocardiography. J Am Soc Echocardiogr. 2010;23(1):13–22. 18. Dreyfus J, Brochet E, Lepage L, et al. Real-time 3D transoesophageal measurement of the mitral valve area in patients with mitral stenosis. Eur J Echocardiogr. 2011; 12(10):750–5. 19. Zamorano J, Cordeiro P, Sugeng L, et al. Real-time threedimensional echocardiography for rheumatic mitral valve stenosis evaluation: an accurate and novel approach. J Am Coll Cardiol. 2004;43(11):2091–6. 20. Schlosshan D, Aggarwal G, Mathur G, et al. Real-time 3D transesophageal echocardiography for the evaluation of rheumatic mitral stenosis. JACC Cardiovasc Imaging. 2011;4(6):580–8. 21. Weyman AE. Assessment of mitral stenosis: role of realtime 3D TEE. JACC Cardiovasc Imaging. 2011;4(6):589–91. 22. Sugeng L, Shernan SK, Weinert L, et al. Real-time threedimensional transesophageal echocardiography in valve disease: comparison with surgical findings and evaluation of prosthetic valves. J Am Soc Echocardiogr. 2008;21(12): 1347–54. 23. Krim SR, Vivo RP, Patel A, et al. Direct assessment of normal mechanical mitral valve orifice area by real-time 3D echocardiography. JACC Cardiovasc Imaging. 2012;5(5): 478–83.

529

24. Singh P, Manda J, Hsiung MC, et al. Live/real time threedimensional transesophageal echocardiographic evaluation of mitral and aortic valve prosthetic paravalvular regurgitation. Echocardiography. 2009;26(8):980–7. 25. de la Morena G, Saura D, Oliva MJ, et al. Real-time threedimensional transoesophageal echocardiography in the assessment of aortic valve stenosis. Eur J Echocardiogr. January, 2010;11(1):9–13. Epub October 4, 2009. 26. Suradi H, Byers S, Green-Hess D, et al. Feasibility of using real time “Live 3D” echocardiography to visualize the stenotic aortic valve. Echocardiography. 2010;27(8):1011–20. 27. Brantley HP, Nekkanti R, Anderson CA, et al. Threedimensional echocardiographic features of unicuspid aortic valve stenosis correlate with surgical findings. Echocardiography. 2012;29(8):E204–7. 28. Unsworth B, Ma A, Barbieri A, et al. Bicuspid aortic valve regurgitation: quantification of anatomic regurgitant orifice area by 3D transesophageal echocardiography reconstruction. Echocardiography. 2008;25(7):797–8. 29. Mikhail GW. Recognising bicuspid aortic stenosis in patients referred for transcatheter aortic valve implantation: routine screening with three-dimensional transoesophageal echocardiography. Heart. 2010;96(8):645. 30. Singh P, Dutta R, Nanda NC. Live/real time three-dimensional transthoracic echocardiographic assessment of bicuspid aortic valve morphology. Echocardiography. 2009; 26(4):478–80. 31. Burri MV, Nanda NC, Singh A, et al. Live/real time threedimensional transthoracic echocardiographic identification of quadricuspid aortic valve. Echocardiography. 2007;24(6): 653–5. 32. Maréchaux S, Juthier F, Banfi C, et al. Illustration of the echocardiographic diagnosis of subaortic membrane stenosis in adults: surgical and live three-dimensional transoesophageal findings. Eur J Echocardiogr. 2011;12(1):E2. 33. Agrawal GG, Nanda NC, Htay T, et al. Live three-dimensional transthoracic echocardiographic identification of discrete subaortic membranous stenosis. Echocardiography. 2003; 20(7):617–9. 34. Perez de Isla L, Zamorano J, Fernandez-Golfin C, et al. 3D color-Doppler echocardiography and chronic aortic regurgitation: a novel approach for severity assessment. Int J Cardiol. 2013;166(3):640–5. 35. Chin CH, Chen CH, Lo HS. The correlation between three-dimensional vena contracta area and aortic regurgitation index in patients with aortic regurgitation. Echocardiography. 2010;27(2):161–6. 36. Pirat B, Little SH, Igo SR, et al. Direct measurement of proximal isovelocity surface area by real-time threedimensional color Doppler for quantitation of aortic regurgitant volume: an in vitro validation. J Am Soc Echocardiogr. March, 2009;22(3):306–13. Epub January 24, 2009. 37. Malagoli A, Barbieri A, Modena MG. Bicuspid aortic valve regurgitation: quantification of anatomic regurgitant orifice area by 3D transesophageal echocardiography reconstruction. Echocardiography. 2008;25(7):797–8.

530

Section 2: Echocardiography/Ultrasound Examination and Training

38. Tamborini G, Fusini L, Gripari P, et al. Feasibility and accuracy of 3DTEE versus CT for the evaluation of aortic valve annulus to left main ostium distance before transcatheter aortic valve implantation. JACC Cardiovasc Imaging. 2012;5(6):579–88. 39. Gripari P, Ewe SH, Fusini L, et al. Intraoperative 2D and 3D transoesophageal echocardiographic predictors of aortic regurgitation after transcatheter aortic valve implantation. Heart. 2012;98(16):1229–36. 40. Gaspar T, Adawi S, Sachner R, et al. Three-dimensional imaging of the left ventricular outflow tract: impact on aortic valve area estimation by the continuity equation. J Am Soc Echocardiogr. 2012;25(7):749–57. 41. Furukawa A, Abe Y, Tanaka C, et al. Comparison of twodimensional and real-time three-dimensional transesophageal echocardiography in the assessment of aortic valve area. J Cardiol. 2012;59(3):337–43. 42. Kelly NF, Platts DG, Burstow DJ. Feasibility of pulmonary valve imaging using three-dimensional transthoracic echocardiography. J Am Soc Echocardiogr. 2010;23(10):1076–80. 43. Lee KJ, Connolly HM, Pellikka PA. Carcinoid pulmonary valvulopathy evaluated by real-time 3-dimensional transthoracic echocardiography. J Am Soc Echocardiogr. 2008;21(4):407.e1–e2. 44. Pothineni KR, Wells BJ, Hsiung MC, et al. Live/real time three-dimensional transthoracic echocardiographic assessment of pulmonary regurgitation. Echocardiography. 2008; 25(8):911–7. 45. Naqvi TZ, Rafie R, Ghalichi M. Real-time 3D TEE for the diagnosis of right-sided endocarditis in patients with prosthetic devices. JACC Cardiovasc Imaging. 2010; 3(3):325–7. 46. Bhattacharyya S, Tarkin J, Prasad S, et al. Multi-modality imaging of apical aortic conduit. Eur J Echocardiogr. 2011; 12(12):975. 47. Tagliareni F, D’Aleo A, Sanfilippo A, et al. Isolated bicuspid pulmonary valve in adult diagnosed by three-dimensional transthoracic echocardiography. J Cardiovasc Med (Hagerstown). 2012;13(6):395–6. 48. Dumaswala B, Bicer EI, Dumaswala K, et al. Live/Real time three-dimensional transthoracic echocardiographic assessment of the involvement of cardiac valves and chambers in carcinoid disease. Echocardiography. 2012;29 (6):751–6.

49. Anwar AM, Geleijnse ML, Soliman OI, et al. Assessment of normal tricuspid valve anatomy in adults by real-time three-dimensional echocardiography. Int J Cardiovasc Imaging. 2007;23(6):717–24. 50. Anwar AM, Geleijnse ML, Soliman OI, et al. Evaluation of rheumatic tricuspid valve stenosis by real-time threedimensional echocardiography. Heart. 2007;93(3):363–4. 51. Schnabel R, Khaw AV, von Bardeleben RS, et al. Assessment of the tricuspid valve morphology by transthoracic realtime-3D-echocardiography. Echocardiography. 2005;22(1): 15–23. 52. Sukmawan R, Watanabe N, Ogasawara Y, et al. Geometric changes of tricuspid valve tenting in tricuspid regurgitation secondary to pulmonary hypertension quantified by novel system with transthoracic real-time 3-dimensional echocardiography. J Am Soc Echocardiogr. 2007;20(5): 470–6. 53. Fukuda S, Saracino G, Matsumura Y, et al. Three-dimensional geometry of the tricuspid annulus in healthy subjects and in patients with functional tricuspid regurgitation: a realtime, 3-dimensional echocardiographic study. Circulation. 2006;114(1 Suppl):I492–8. 54. Ton-Nu TT, Levine RA, Handschumacher MD, et al. Geometric determinants of functional tricuspid regurgitation: insights from 3-dimensional echocardiography. Circulation. 2006;114(2):143–9. 55. Ahlgrim AA, Nanda NC, Berther E, et al. Three-dimensional echocardiography: an alternative imaging choice for evaluation of tricuspid valve disorders. Cardiol Clin. 2007; 25(2):305–9. 56. Song JM, Jang MK, Choi YS, et al. The vena contracta in functional tricuspid regurgitation: a real-time threedimensional color Doppler echocardiography study. J Am Soc Echocardiogr. 2011;24(6):663–0. 57. Sugeng L, Weinert L, Lang RM. Real-time 3-dimensional color Doppler flow of mitral and tricuspid regurgitation: feasibility and initial quantitative comparison with 2-dimensional methods. J Am Soc Echocardiogr. 2007;20 (9):1050–7. 58. Velayudhan DE, Brown TM, Nanda NC, et al. Quantification of tricuspid regurgitation by live three-dimensional transthoracic echocardiographic measurements of vena contracta area. Echocardiography. 2006;23(9):793–800.

531

CHAPTER 28 Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures Muhamed Saric, Ricardo Benenstein

Snapshot  Fluoroscopy Versus Echocardiography in Guiding Percu-

 Device Closure of Cardiac Shunts  Occlusion of the LeŌ Atrial Appendage  Guidance of Electrophysiology Procedures  Miscellaneous Procedures

taneous IntervenƟons  Transseptal Puncture: A Common Element of Many IntervenƟonal Procedures  Valvular Disease

INTRODUCTION Catheter-based transcutaneous repair of both congenital and acquired cardiovascular defects has been performed by interventional cardiologists and other interventional specialists for the past half a century. This therapeutic approach was initially spearheaded by pediatric cardiologists. Atrial balloon septostomy, later referred to as the Rashkind procedure, is generally considered to be the first catheter-based transcutaneous repair procedure. The Rashkind procedure was first reported in 1971 as the initial treatment in neonates with transposition of the great arteries to improve mixing of venous and systemic blood through creation of an iatrogenic atrial septal defect (ASD).1 In the beginning, catheter-based transcutaneous repairs were developed as less invasive alternatives to established surgical procedure but have since evolved into novel ways of treating structural heart defects. Catheterbased transcutaneous procedures to repair structural heart defects can be divided into the following groups:

•

•

•

• •

Valvular disease – Mitral stenosis (percutaneous balloon valvuloplasty) – Mitral regurgitation [mitral valve (MV) clipping] – Aortic stenosis (transcatheter aortic valve replacement) – Closure of paravalvular prosthetic leaks. Device closure of cardiac shunts – ASDs [secundum ASDs; patent foramen ovale (PFO)] – Ventricular septal defects (VSDs; congenital and acquired) – Patent ductus arteriosus (PDA). Occlusion of the left atrial appendage (LAA) – Intracardiac device closure of LAA – Epicardial suturing of LAA. Guidance of electrophysiology ablation procedures – Pulmonary vein isolation for atrial fibrillation. Miscellaneous procedures – Left ventricular pseudoaneurysm closure – Alcohol septal ablation for hypertrophic obstructive cardiomyopathy – Right ventricular endomyocardial biopsy.

532

Section 2: Echocardiography/Ultrasound Examination and Training

In the interventional suites, echocardiography is typically used in conjunction with X-ray-based fluoroscopy in guiding catheter-based transcutaneous repairs in real time. Fluoroscopy and echocardiography images are typically presented side-by-side to interventionalists on adjacent monitors. Recently, commercial products that dynamically combine (coregister) in real time threedimensional (3D) ultrasound and interventional X-ray images into one are becoming available. Computed tomography (CT) and magnetic resonance imaging (MRI)— although often important in establishing the diagnosis of a structural heart defect—typically do not readily provide real time imaging during percutaneous interventions in standard interventional suites. Real time 3D transesophageal echocardiography (3D TEE) and intracardiac echocardiography (ICE) are the most useful echocardiographic techniques for real time procedural guidance as their images are typically superior to and/or more relevant to interventionalists compared to images obtained by either two-dimensional transesophageal echocardiography (2D TEE) or transthoracic echocardiography (TTE).2 In general, percutaneous coronary interventions (such as angioplasty and stenting) are not typically classified as catheter-based transcutaneous procedures to repair structural heart defects and thus will not be discussed in this chapter. The use of intravascular ultrasound (IVUS) techniques in the diagnosis and treatment of vascular disease is provided elsewhere in this textbook.

FLUOROSCOPY VERSUS ECHOCARDIOGRAPHY IN GUIDING PERCUTANEOUS INTERVENTIONS Imaging is essential for the diagnosis, guidance, and assessments of results of all catheter-based transcutaneous procedures to repair structural heart defects. Detailed description of basics of fluoroscopy and echocardiography are beyond the scope of this chapter; here we will discuss their advantages and shortcomings from the perspective of catheter-based transcutaneous interventional procedures. X-ray-based fluoroscopy and contrast angiography have been historically considered as gold standards in guiding percutaneous repairs of structural heart defects. These radiographic techniques, which are very familiar to interventionalists, tend to have poor depth resolution, lack ability to differentiate between various soft tissues, and require the use of ionizing radiation and iodinated contrast agents.

While in principle, TTE can be used to guide catheterbased interventions, its use is limited by both suboptimal imaging of relevant cardiac structures and by difficulties in acquiring TTE images in the sterile environment of an interventional suite. 2D TEE and ICE imaging, although extensively used during percutaneous procedure, suffer from the 2D, cross-sectional nature of their images. As a consequence, movement of wires, catheters, and devices used during interventions cannot be tracked appropriately. In addition, neither 2D TEE nor ICE can typically provide en face views of structures of interest to interventionalists. Furthermore, ICE typically provides only monoplane images. It is also invasive and requires the use of expensive disposable transducers that are advanced under sterile condition into the heart via the venous system. Examples of ICE use are provided in the section on percutaneous ASD closure below. In our practice, modern 3D TEE imaging is the preferred echocardiography technique for guiding interventional procedures as it provides detailed dynamic images (included en face views) of relevant cardiac structures in real time, something that is not easily achievable by any other imaging technique.3 Although 3D TEE has been around for decades (primarily as an offline, postprocessed imaging technique), it has been revolutionized by the introduction of a 3D TEE probe with a matrix-array transducer having 3,000 elements in the first decade of the 21st century. This approximately a 25–50-fold increase in the number of imaging elements compared with a standard 2D TEE probe has allowed for real time 3D imaging, making 3D TEE ideally suited for guidance of cardiac interventions. General aspects of 3D echocardiographic imaging have previously been reviewed4–7 and are also discussed elsewhere in this textbook.

TRANSSEPTAL PUNCTURE: A COMMON ELEMENT OF MANY INTERVENTIONAL PROCEDURES Many catheter-based transcutaneous procedures (such as those involving the MV, LAA, and pulmonary veins) require a transvenous access to the left atrium. In general, the left atrium is accessed after entering a peripheral vein (typically the femoral vein) followed by threading catheters and other hardware into the right atrium and then performing the transseptal puncture to bring the hardware across the interatrial septum into the left atrium.

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

The general technique of transseptal puncture was originally described by Ross in 1959; further refinements were published in 1962 by Brockenbrough and colleagues.8,9 Briefly, a sharp needle that will be used to puncture the interatrial septum (referred to as Brockenbrough needle) is hidden inside a catheter (such as the MullinsTM catheter, Medtronic Inc., Minneapolis, MN). The catheter is advanced through the venous system into the right atrium and then pushed further to cause tenting of the interatrial septum (evagination of the interatrial septum toward the left atrium). Thereafter, the Brockenbrough needle is advanced through the catheter until it punctures the interatrial septum. While the interventionalists’ tactile feedback, fluoroscopy and 2D echocardiography (such as 2D TEE and ICE) have been used for many years to guide transseptal puncture with a good safety record,10 real time 3D TEE provides distinct advantages that may enhance both the safety of the puncture procedure and the success of the subsequent percutaneous intervention in the left heart. Among the several modalities of 3D TEE, biplane and 3D zoom imaging are particularly useful in guiding the transseptal puncture. The key imaging aspect of guiding a transseptal puncture is to demonstrate the exact location of septal tenting prior to actual puncture. Only after proper location of tenting is confirmed by imaging, the Brockenbrough needle is advanced and the transseptal puncture is performed.11 Biplane 3D TEE imaging assures that transseptal puncture is confined to the true interatrial septum while preventing piercing of the aorta, superior vena cava (SVC), and other cardiac structures such as the so-called lipomatous hypertrophy of the interatrial septum (Figs 28.1A to D; Movie clip 28.1A and B). The true interatrial septum is essentially confined to the floor of the fossa ovalis (Latin for “egg-shaped dugout”); the floor is derived from the septum primum. The fossa ovalis is surrounded by the rim (also referred to in Latin as the limbus), which is formed by the septum secundum.12 The location, size, and shape of the fossa ovalis varies widely among individuals.13 The fossa ovalis is readily distinguished on en face views of the right atrial aspect of the interatrial septum as a lighter colored ovoid crater. In contrast, the region of fossa ovalis cannot be readily recognized on the rather featureless left atrial aspect of the interatrial septum when standard image gain settings are used.14 However, at low gain setting, the area of fossa ovalis (which is thinner than the surrounding atrial walls) can be identified as an ovoid area of dropout especially in patients with a concomitant atrial septal aneurysm

533

(ASA; Figs 28.2A to D and Movie clip 28.2). In individuals with PFO, the opening in the floor of the fossa ovalis is present along the antero-superior rim of fossa ovalis. In such individuals, transseptal puncture needle is often directed through the PFO opening. On 3D TEE imaging can also readily characterize the size and the shape of the ASA, defined arbitrarily as a ≥ 10 mm sway of the interatrial septum in either direction from the midline.15 Anatomically, ASA is characterized by redundancy and floppiness of a typically enlarged fossa ovalis floor. The knowledge of an ASA is important to interventionalists; ASA may make transseptal puncture more difficult by requiring septal stretching and/or increased force to traverse the septum.16 These maneuvers may increase the risk for cardiac perforation during transseptal puncture.17 It is important to emphasize that the term lipomatous hypertrophy of the interatrial septum is actually a misnomer as the fat accumulates not in the interatrial septum per se but rather outside of the heart in the groove between the muscular walls of the right and left atrium (Figs 28.3A to C and Movie clip 28.3). The groove is known to surgeons as either the Waterston’s or Søndergaard’s groove.18,19 Puncturing of the lipomatous hypertrophy area is dangerous as the needle exits the heart into the epicardial space. En face 3D zoom views of the interatrial septum from the right and left atrial perspective during tenting allows for better selection of the puncture site. Often transseptal puncture across the foramen ovale is the preferred route; however, for some procedures a puncture of a different portion of the interatrial septum may be more desirable (as, for instance, during closures of mitral paraprosthetic leaks).

VALVULAR DISEASE Mitral Stenosis: Percutaneous Mitral Balloon Valvuloplasty Rheumatic heart disease remains the leading cause of mitral stenosis worldwide. Rheumatic mitral stenosis is the most common form of valvular disease in developing parts of the world. In contrast, rheumatic mitral stenosis in Japan, North America, and Northern and Western Europe is typically seen among immigrants from less developed parts of the world. Rheumatic MV disease is a progressive lifelong autoimmune-like disorder triggered by and further exacerbated by recurrent group A streptococcal infections (typically pharyngitis).20

534

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 28.1A to D: 3D TEE guidance of trans-septal puncture. (A and B) Biplane imaging of the interatrial septum demonstrates tenting of the interatrial septum (arrows) by the catheter containing the Brockenbrough needle. Note that the tenting occurs in the central region of the interatrial septum and away from SVC and the aortic valve. Movie clip 28.1B corresponds to this figure; (C) 3D TEE zoom image demonstrates the en face view of the right atrial aspect of the interatrial septum. The dashed line follows the limbus of the fossa ovalis. Note the location of trans-septal puncture (arrow) in the superior portion of the fossa ovalis; (D) 3D TEE zoom image demonstrates the en face view of the left atrial aspect of the interatrial septum. Note the evagination of the interatrial septum into the cavity of the left atrium caused by the Brockenbrough needle assembly (asterisk). Movie clip 28.1A corresponds to this figure. (AV: Aortic valve; IVC: Inferior vena cava; LA: Left atrium; MV: Mitral valve; RA: Right atrium; RUPV: Right upper pulmonary vein; SVC: Superior vena cava; TV: Tricuspid valve).

Probably the very first description of rheumatic mitral stenosis anatomy was provided in 1668 by the British physician John Mayow (1641–1679), who recorded an “extreme constriction of the mitral orifice in a young man”. 21 In 1715, Raymond Vieussens (1635–1715), a French physician, published the first comprehensive description of mitral stenosis.22 Rheumatic mitral stenosis is notable for several “firsts” in the history of medicine: it was the first valvular heart disease to be treated surgically; it was the first heart disease to be diagnosed by echocardiography and it was the first valvular disease to be treated with balloon valvuloplasty.23 In the 1920s, Elliot Cutler (1888–1947)24 and Sir Henry Souttar (1875–1964)25 working at the Brigham and Women’s

Hospital in Boston were the first to attempt surgical relief of rheumatic mitral stenosis using procedures that they termed “valvulotomy” and “finger dilation,” respectively. In the late 1940s, soon after World War II, techniques of rheumatic mitral stenosis surgery were rediscovered and improved by Charles Bailey and Dwight Harken, who also coined the procedural terms that are still used today.26 Bailey called his procedure “commissurotomy” while Harken coined the term “valvuloplasty.”27 In the 1950s, rheumatic mitral stenosis was the first heart disease visualized echocardiographically by Ingle Edler (1911–2001) and Carl Hertz (1920–1990), inventors of echocardiography.28 In the 1960s, rheumatic mitral stenosis was the first valvular disease to be treated with

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

C

D

535

Figs 28.2A to D: Anatomy of fossa ovalis. There is a large variability in the size, shape and location of the fossa ovalis in humans. In addition, the floor of the fossa ovalis (derived from the septum primum) can be either firm or floppy. A floppy septum leads to formation of an atrial septal aneurysm. These 3D TEE zoom images were obtained from two different patients. (A and B) Images obtained from a patient with a small fossa ovalis (asterisk). (A) demonstrates the right atrial and; (B) the left atrial aspect of the interatrial septum. Note that the fossa ovalis, with a pale floor and its darker rims, is easily recognized on the right atrial aspect of the interatrial septum. In contrast, the location of the fossa ovalis (arrow) is less evident on the rather featureless left atrial aspect of the interatrial septum; (C and D) Images obtained from a patient with a large fossa ovalis and an ASA (C) demonstrates the right atrial and (D) the left atrial aspect of the interatrial septum. In contrast to the patient from (A and B), the location of the fossa ovalis in now easily recognized on the left atrial aspect of the interatrial septum when the ASA protrudes away from the left atrium and into the right atrium as shown in (D). Movie clip 28.2 demonstrates the ASA from the posterior aspect of the left atrium. (AV: Aortic valve; CS: Coronary sinus; IVC: Inferior vena cava; MV: Mitral valve; RUPV: Right upper pulmonary vein; SVC: Superior vena cava).

a mechanical MV by Albert Starr (born 1926) and Lowell Edwards (1898–1982).29 Finally, in the 1980s, Kanji Inoue of Japan developed the ingenious balloon [Inoue balloon, Toray Industries (America) Inc., San Mateo, CA] and the technique of percutaneous mitral balloon valvuloplasty (PMBV), which remains the preferred treatment for the relief of rheumatic mitral stenosis in eligible patients.30 In the absence of contraindications, PMBV is recommended in following instances: • Symptomatic patients with moderate or severe mitral stenosis. • In asymptomatic patients with moderate or severe mitral stenosis, PMBV is indicated when there is

pulmonary artery systolic pressure is > 50 mm Hg at rest or > 60 mm Hg with exercise, or when there is new onset atrial fibrillation. • PMBV may also be considered in symptomatic patient with mild mitral stenosis (valve area > 1.5 cm2) when pulmonary artery systolic pressure greater > 60 mm Hg, pulmonary artery wedge pressure > 25 mm Hg, or mean MV gradient > 15 mm Hg during exercise. Contraindication for PMBV include unfavorable MV Wilkins score (greater than or equal to 10; see below), more than moderate mitral regurgitation and the presence of intracardiac thrombus.31

536

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 28.3A to C: Lipomatous hypertrophy of the interatrial septum. Lipomatous hypertrophy of the interatrial septum (also referred to as lipomatous atrial septal hypertrophy, LASH) is an important finding that should be communicated to the interventionalist performing the trans-septal puncture. LASH represents accumulation of epicardial fat in the interatrial fold and not in the true interatrial septum. Thus, in LASH the fossa ovalis remains thin but its rims appear unusually thick. When there is LASH, the trans-septal puncture should be performed through the fossa ovalis and not through the accumulated fat. (A and B) Biplane 3D TEE image from a patient with marked LASH. Note the dumbbell appearance of the interatrial septum. The fossa ovalis has a thin floor (asterisk); its rims are demarcated by epicardial fat accumulation (arrows). Movie clip 28.3 corresponds to this figure; (B and C) 3D TEE zoom image of the right atrial aspect of the interatrial septum from a patient with LASH. Note how the fossa ovalis (white dashed line) is surrounded by unusually tall rims (arrows). These raised rims are due to accumulation of epicardial fat. (AV: Aortic valve; IVC,: Inferior vena cava; LA: Left atrium; RA: Right atrium; SVC: Superior vena cava).

The role of 3D TEE in PMBV is threefold: confirmation of the diagnosis of mitral stenosis, possible refinement of the MV Wilkins score and guidance of PMBV per se.32 MV planimetry by 3D transthoracic or transesophageal echocardiography is becoming the gold standard for the anatomic assessment of the severity of mitral stenosis.33 The MV is funnel shaped with its narrowest area located in the left ventricle and often in a plane that is not parallel with standard imaging planes of 2D echocardiography. Using 3D echocardiography (3DE) techniques of multiplane reconstructions one can overcome the limitations of 2D planimetry and measure the area of at the very tip of the MV funnel. MV area can also be measured on zoomed en face views of the MV either semiquantitatively using calibrated grids or even quantitatively using newer software techniques of on-image planimetry (Figs 28.4A to D and Movie clip 28.4).

3D TEE may also help in calculating the MV Wilkins’s score, an essential prerequisite for PMBV. The Wilkins’s score was originally developed in the late 1980s using 2D transthoracic echocardiography and is based on mitral leaflet thickness, calcifications, and mobility as well as the thickness of the subvalvular apparatus.34 Each of the four categories is graded on a scale of 0 (normal) to 4 (severely abnormal). A normal MV, thus, has a score of 0. The most unfavorable score is 16. PMBV is contraindicated when mitral score is > 10. Significant thickening, calcifications, and immobility of mitral leaflets and well as significant thickening of the mitral subvalvular apparatus predispose MV to leaflet tear, a known complication of PMBV that may lead to significant de novo mitral regurgitation. 3D TEE may enhance the scoring through its superior ability to visualize leaflet mobility and the details of the subvalvular mitral apparatus.

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

C

D

537

Figs 28.4A to D: 3D TEE diagnosis of mitral stenosis. 3D TEE images obtained from a 53-year-old woman with rheumatic mitral stenosis who grew up in the former Soviet Union. (A), (B) and (C) demonstrate 3D TEE zoom images of the MV from the left ventricular perspective; (D) is a multiplane reconstruction image. (A) 3D TEE image demonstrates typical features of rheumatic mitral stenosis: commissural fusions (arrows) and the doming of the anterior mitral leaflet (AML). On the accompanying Movie clip 28.4 there is also diminished mobility of the posterior mitral leaflet (PML); (B), (C) and (D) demonstrates various 3D TEE methods of calculating the MV area: quantitative on-image planimetry (A), semiquantitative method using a 5 mm grid (B), and the multiplane reconstruction method (C). By all three methods, the patient has severe mitral stenosis with a MV area of approximately 0.6 cm2.

3D TEE provides guidance throughout the PMBV procedure which is performed in the following fashion. After obtained venous access (typically using the femoral vein), transseptal puncture of the interatrial septum is performed as described earlier in this chapter. Subsequently a deflated Inoue valvuloplasty balloon is brought into the left atrium through the transseptal puncture. Given its ability to visualize the left atrial aspect of the MV en face, 3D TEE can precisely guide positioning of the valvuloplasty balloon across the MV. Once positioned across the MV, the balloon is inflated under 3D TEE and fluoroscopy guidance

with the intent to separate the two leaflets of the MV along the commissures fused by the rheumatic process (Figs 28.5A to D and Movie clip 28.5A to C). The outcome of PMBV can be assessed in real time by 3D TEE; en face views of the left ventricular (LV) side of the MV are particularly useful. The desired outcome is a controlled commissural tear that enlarges the MV orifice and does not create de novo or worsens preexisting mitral regurgitation. 3D TEE can also visualize the mechanism of unfavorable outcome, namely a noncommissural leaflet tear often leading to significant de novo acute mitral regurgitation (Figs 28.6A to D and Movie clip 28.6).

538

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 28.5A to D: Guidance of percutaneous mitral balloon valvuloplasty. Percutaneous mitral balloon valvuloplasty (PMBV) is the preferred method for alleviating mitral stenosis in appropriate patients. 3D TEE in conjunction with fluoroscopy provides excellent PMBV guidance. (A), (B), and (C) demonstrate 3D TEE zoom images of MV from the left atrial perspective; (D) is a fluoroscopy image. (A) Following the trans-septal puncture, 3D TEE is used to guide the deflated Inoue valvuloplasty Inoue balloon into the orifice of the MV. Movie clip 28.5C corresponds to this figure; (B) In the next step, the balloon (arrow) is advanced through the mitral orifice and partly inflated; (C) In the final step, the balloon (arrow) is fully inflated in an attempt to relieve the mitral stenosis. Movie clip 28.5B corresponds to this figure; (D) Fully inflated Inoue balloon seen on a fluoroscopy image in the anteroposterior projection. Arrows point to the balloon’s waist which should be in the plane of the mitral orifice. Movie clip 28.5A corresponds to this figure. (AML: Anterior mitral leaflet; AV: Aortic valve; LAA: Left atrial appendage; PML: Posterior mitral leaflet).

Mitral Regurgitation: MV Clipping Medical management improves symptoms but does not alter the natural progression of mitral regurgitation. Current guidelines recommend surgical correction of moderateto-severe or severe mitral regurgitation in patients with symptoms and/or evidence of LV dysfunction.31 In general, surgical MV repair is preferable over surgical valve replacement for correction of mitral regurgitation with lower hospital mortality, longer survival, better preservation of ventricular function, fewer thromboembolic complications, and reduced risk of

endocarditis.35,36 To date, there are no commercially available techniques of percutaneous valve replacements for native MV disease. In contract, there is a commercially available alternative to surgical MV repair, namely MV clipping to treat selected forms of native MV regurgitation. The techniques of MV repair have been pioneered in the 1970s by the French surgeon Alain Carpentier.37 (He also coined the term “bioprosthesis” and was instrumental in developing bioprosthetic valves a few years earlier).38 Most MV repair techniques rely on leaflet reduction, chordal alteration, and annuloplasty ring insertion. These complete repairs cannot be replicated

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

C

D

539

Figs 28.6A to D: Outcomes of percutaneous mitral balloon valvuloplasty. 3D TEE zoom images from patients with rheumatic mitral stenosis demonstrate the left ventricular aspect of the MV. (A) demonstrates severe mitral stenosis before percutaneous mitral balloon valvuloplasty (PMBV); (B) demonstrates the result of a successful PMBV. Note the increase in the MV area due to separation of commissures of the MV (arrows); (C) demonstrates torn AML (arrow), an unfavorable outcome of PMBV which resulted in severe de novo mitral regurgitation seen in figure D. Movie clip 28.6 which corresponds to figure D shows that the jet of mitral regurgitation is eccentric and directed laterally. (AML: Anterior mitral leaflet; LA: Left atrium; LV: Left ventricle; PML: Posterior mitral leaflet RV: Right ventricle).

yet with current commercially available percutaneous techniques although many are in development.39 In the 1990s the Italian surgeon Ottavio Alfieri developed a simple technique for surgical correction of MV regurgitation that entails placement of a surgical stitch to approximate the free edges of the leaflets at the site of regurgitant jet origin. Typically, the stitch is placed centrally between A2 and P2 scallops of the MV that results in a double orifice MV. Alfieri called his technique “edge-to-edge repair” but the technique has since become known colloquially as the Alfieri stitch.40,41

MV clipping is essentially the percutaneous version of the edge-to-edge surgical repair. MV clipping using the MitraClip® device (Abbott Vascular, Abbott Park, IL) is approved for general use in Europe and is undergoing clinical trials in the United States. In the randomized Endovascular Valve Edge-to-Edge Repair Study (EVEREST II) trial, mitral clipping using the MitralClip® device was associated with superior safety and similar improvements in clinical outcomes but was less effective at reducing mitral regurgitation compared to conventional surgery.42

540

Section 2: Echocardiography/Ultrasound Examination and Training

Echocardiography, including 3D TEE, is essential in selecting appropriate patients for MV clipping, guiding of the procedure, and assessing the success of the procedure.

Selection of Patient Eligible for MV Clipping All eligible patients should have the following: • Chronic moderate-to-severe or severe mitral regurgitation originating centrally between A2 and P2 scallops of the MV. • Mitral regurgitation may be functional (due to LV dysfunction) or degenerative (due to prolapsed or flail mitral leaflet) with certain anatomic limitations (for degenerative mitral regurgitation: flail gap < 10 mm; flail width < 15 mm; for functional mitral regurgitation: coaptation depth < 11 mm; coaptation length > 2 mm).43 • Either symptomatic with a left ventricular ejection fraction (LVEF) of more than 25% or asymptomatic with at least one of the following: an LVEF of 25–60%, a LV end-systolic diameter of 40–55 mm, new atrial fibrillation, or pulmonary hypertension. Details of echocardiographic diagnosis of MV prolapse44 or degenerative mitral regurgitation is discussed elsewhere in this textbook. It suffices to say here that 3D TEE (especially its en face views) allow for detailed evaluation of MV anatomy and precise establishment of the mechanism of mitral regurgitation.

3D TEE Guidance of MV Clipping The MitraClip device is a 4 mm-wide polyester-covered cobalt–chromium implant with two arms mounted on a sophisticated catheter-based delivery system. After obtaining femoral venous access and using standard transseptal approach over a guide wire and tapered dilator, the clip delivery system is brought into the left atrium through a guide catheter.45 Echocardiographic guidance for transseptal puncture is provided in a standard fashion as described earlier in the chapter but with an important modification regarding the location of trans-septal puncture. The site of transseptal puncture is extremely important for the success of MV clipping. In general, a more posterior and superior puncture site is preferred. A distance of at least 4 cm between the site of puncture and the clip landing site on the MV is recommended.46 In particular, passage across

PFO—the route commonly used in other percutaneous procedures in the left heart—should be always avoided during MV clipping. Passage through a PFO usually results in a position that is too inferior and anterior. Furthermore, tunnel-type PFOs may impede free movement of the clip delivery system. Following successful transseptal puncture, the clip with its arms closed and attached to the delivery system is brought into the left atrium through the guide catheter. After the clip delivery system emerges into the left atrium through the guide catheter, its tip is then bent toward the MV. The arms of the clip are opened and subsequently oriented perpendicular to the leaflet coaptation line. 3D TEE guidance is absolutely essential in guiding this orthogonal clip orientation (Figs 28.7A to D and Movie clip 28.7). In the next step, the open clip is advanced below the mitral leaflet tips into the left ventricle. The arms of the clip are then partially closed and the delivery system is pulled back until the mitral leaflets are captured in the arms of the clip. Using 3D TEE and color Doppler, the position and the degree of residual mitral regurgitation are assessed as the arms of the clip are gradually closed to complete the edgeto-edge repair and form a double-orifice MV. Occasionally, placement of a second clip may be necessary to treat residual mitral regurgitation. However, this increases the chance of procedure-related mitral stenosis (Figs 28.8 to D and Movie clip 28.8).

Aortic Stenosis: Transcatheter Aortic Valve Replacement Calcification of a seemingly normal trileaflet or a congenital bicuspid valve resulting from an atherosclerosis-like process is the most common form of acquire aortic stenosis. Rheumatic aortic stenosis is rare in the United States and other developed countries. It results from commissural fusion and leaflet calcifications, and is invariable associated with concomitant rheumatic MV disease.47 Once severe aortic stenosis becomes symptomatic, the survival is dismal (only a few years)48 and not much different from many metastatic cancers.49 No medical therapy has ever been shown to alter the natural history of aortic stenosis; aortic valve replacement is the only effective therapy. Surgical aortic valve replacement (SAVR) has been shown to improve symptoms and is generally accepted to prolong survival based on

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

C

D

541

Figs 28.7A to D: Guidance of MV clipping. (A and B) Biplane 3D TEE image demonstrates proper positioning of the mitral clip (arrows) prior to clip closure. The clip should be perpendicular to the MV closure line and placed in the region of A2 and P2 scallops of the MV. Movie clip 28.7. corresponds to this figure; (C and D) 3D TEE zoom image of the MV from the left atrial perspective; (C) demonstrates improper clip positioning (clip is parallel to the mitral coaptation line); (D) demonstrates proper clip positioning (clip is perpendicular to the mitral coaptation line). (AML: Anterior mitral leaflet; AV: Aortic valve; LA: Left atrium; LV: Left ventricle; PML: Posterior mitral leaflet).

historical comparisons and extensive experience over the past 50 years.50 The first orthotopic SAVR, albeit for aortic insufficiency, was performed in 1960 by the American surgeon Dwight Harken.51 Currently, about 13,000 SAVR are performed annually in the United States for relief of aortic stenosis.52 Historically, two percutaneous alternatives to SAVR have been proposed: aortic balloon valvuloplasty (ABV) and transcatheter aortic valve replacement (TAVR) also referred to at transcatheter aortic valve implantation (TAVI). BAV was first performed in 1986 by Alain Cribier in France.53 In contrast to PMBV (which is the treatment of choice for relief of mitral stenosis with good long-term outcomes), percutaneous ABV is used primarily as a

bridge to aortic valve replacement; used alone ABV has high restenosis and complication rates.54 The first TAVR in a human was performed in 2002 by Alain Cribier in France55 using a balloon expandable valve similar in design to the one tested in animals by Danish inventors a decade earlier.56 TAVR is the only intervention for aortic stenosis shown to prolong survival in a randomized trial.57 It is currently indicted for patients with severe aortic stenosis who are at high risk or unsuitable for SAVR. Currently, there are two TAVR valves with or near market approval in various parts of the world: (1) balloon expandable Sapien® valve (Edwards Lifesciences Inc., Irvine, CA); and (2) self-expandable CoreValve® (Medtronic

542

Section 2: Echocardiography/Ultrasound Examination and Training

A

C

B

D

Figs 28.8A to D: Delivery of mitral clip. (A and B) Fluoroscopy images of mitral clips. In (A), the mitral clip is still attached to its delivery catheter and is being opened in preparation for grasping of mitral leaflets; In (B) obtained from a different patient, one mitral clip is already deployed (Clip #1), the other is being deployed (Clip #2). (C and D) 3D TEE zoom images of the MV during diastole with one clip (arrows) fully deployed; (C) demonstrates the left atrial aspect and (D) demonstrates the left ventricular aspect of the MV. Note that clip deployment creates a double-orifice MV. Movie clip 28.8 corresponds to (C). (AML: Anterior mitral leaflet; AV: Aortic valve; PML: Posterior mitral leaflet).

Inc., Minneapolis, MN). Echocardiographers should be familiar with the basic design and mode of delivery of these two valves. Both are bioprosthetic pericardial valves suspended on a metal frame (Figs 28.9A and B).

Sapien® valve is currently made of bovine pericardium suspended on a chrome–cobalt alloy frame. A collapsed Sapien® valve is mounted on a deflated balloon in a similar fashion used for coronary stents. Upon delivery,

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

Figs 28.9A and B: Transcatheter aortic valve prostheses. (A) Sapien™ aortic valve is a balloon expandable prosthesis placed across the aortic annulus; (B) CoreValve™ is a self-expanding aortic valve prosthesis. A deployed CoreValve™ prosthesis extends from the LVOT to the ascending aorta. Source: (A) Image is courtesy of Edwards Lifesciences, Irvine, CA. Source: (B) Image is courtesy of Medtronic Inc., Minneapolis, MN.

the Sapien® valve is balloon expanded across the stenosed native aortic valve. In contrast, CoreValve® is made of porcine pericardium suspended on a nitinol alloy frame. Prior to CoreValve® implantation, balloon valvuloplasty of the native aortic valve is performed. Subsequently, a collapsed CoreValve® is brought into the ascending aorta that then self-expends across the stenosed native valve after it emerges from the delivery sheath. Both valves can be implanted using various arterial access points: the femoral artery, LV apex, or ascending aorta.58 The role of echocardiography including 3D TEE is twofold: to identify appropriate patients and to provide intraprocedural monitoring.

Selection of Patient Eligible for TAVR Echocardiography is essential in establishing the presence of the only currently approved indication for TAVR: severe acquired calcific stenosis of a trileaflet valve (senile calcific aortic stenosis). TAVR is currently not indicated for aortic stenosis of a bicuspid aortic valve although, as mentioned earlier, the very first TAVR performed by Alain Cribier was in a patient with severe bicuspid aortic valve stenosis.53 Can 3DE improve on standard techniques of assessing aortic stenosis severity discussed elsewhere in this chapter? Using the multiplane reconstruction techniques,

543

3D TEE can provide accurate measurements of the left ventricular outflow tract (LVOT), aortic annulus and the aortic annulus-to-left coronary artery ostium distance. Calculation of the aortic valve area (AVA) by continuity equation is the principal echocardiographic method of assessing anatomic severity of aortic stenosis. The major source of error in AVA calculation by continuity equation is miscalculation of the cross sectional area of the LVOT due to mismeasurement of the LVOT diameter and/or faulty geometric assumption of a circular LVOT shape.59 Using multiplane reconstruction techniques of either CT or 3DE (Figs 28.10A to D) one can demonstrate that LVOT is typically ovoid rather than circular in shape.60,61 In addition, it can also be demonstrated that the LVOT “diameter” measured by 2DE is often a geometric chord rather than a true diameter. Since a chord (a line connecting two points on the circumference that does not cross the center) is by definition shorter than a diameter, 2DE will often underestimated the size of LVOT area and thus overestimate the severity of aortic stenosis. The size of the aortic annulus is another measurement that is important for TAVR as the size of the replacement valve is based on the patient’s annular size. 2DE systematically underestimates the annular size compared to CT or MRI.62 In contrast, 3D TEE sizing of the annular size (Figs 28.11A to D) are superior to 2D TEE and may be used when good CT data are unavailable for TAVR sizing.63 Prior to Sapien® valve placement, the annular to left coronary artery ostium height is important as well in selecting appropriate replacement valve size. Echocardiographically, this height cannot be measured by 2D TEE; however, such a measurement is possible with multiplane reconstruction techniques of 3D TEE (Figs 28.12A to D).64 Theoretically, AVA can also be measured by 3D planimetry. However, aortic valve calcifications create image dropout making this measurement imprecise.

TAVR: Intra- and Postprocedural Monitoring by 2D/3D TEE Both 2D and 3D TEE are used during TAVR to help guide the valve insertion, monitor for intraprocedural complications, and assess postimplantation success. In contrast to MV procedures where 3D TEE plays the principal role in guidance, TAVR placement is performed primarily under fluoroscopic and CT guidance. Nonetheless, 2D and 3D TEE is used to provide important

544

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 28.10A to D: 3D TEE assessment of the LVOT. Multiplane reconstruction 3D TEE imaging of the LVOT in a patient prior to CoreValve placement demonstrates an ovoid-shaped LVOT measuring 2.2 × 2.5 cm in diameters and having an area of 4.5 cm2. (LA: Left atrium; LVOT: Left ventricular outflow tract).

A Figs 28.11A and B

B

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

C

545

D

Figs 28.11A to D: 3D TEE assessment of the aortic annulus. Multiplane reconstruction 3D TEE imaging of the aortic annulus in a patient prior to CoreValve placement demonstrates a near-circular aortic annulus measuring 2.3 × 2.4 cm in diameters. (LA: Left atrium; LVOT: Left ventricular outflow tract).

A

B

C

D

Figs 28.12A to D: 3D TEE assessment of the annulo-ostial distance. Multiplane reconstruction 3D TEE imaging of the aortic annulus in a patient prior to Sapien valve placement demonstrates how to measure the distance between the aortic annulus and the left main coronary artery (annulo-ostial distance). Note that the ostium of the left main coronary artery is first localized in the short axis and the distance is then measured in the corresponding long-axis (in this case, Long Axis #2). (LA: Left atrium; LCA: Left main coronary artery; LVOT: Left ventricular outflow tract; RA: Right atrium).

546

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 28.13A to D: TEE guidance of transcutaneous aortic valve replacement. (A) Prior to percutaneous aortic valve replacement, balloon valvuloplasty (arrow) of the native aortic valve is performed; (B) 3D TEE zoom image demonstrates a catheter (arrow) crossing the native aortic valve in preparation for percutaneous aortic valve replacement; (C and D) 3D TEE biplane image of the newly placed CoreValve (arrows) during diastole. In the right portion of this figure, one can seen closed prosthetic leaflets in the short-axis of the valve. (Asc Ao: Ascending aorta; LA: Left atrium; LV: Left ventricle; RA: Right atrium).

real time information regarding aortic valve anatomy and function, and to observe for complications such as pericardial effusion or ventricular dysfunction. Moreover, guide wires, catheters, valvuloplasty balloons and the replacement valve (Figs 28.13A to D) can continuously be observed by echocardiography; in this respect 3D TEE is often superior to 2D TEE. Immediately post TAVR, Doppler echocardiography plays crucial role is assessing the success of the procedure. Color Doppler is used to assess for paravalvular regurgitation (Figs 28.14A to D), which may be present in at least 10% of TAVR patients and which portends poorer

prognosis.65 Spectral Doppler reordered from transgastric windows in used to assess the gradients across the newly implanted TAVR (Figs 28.15A to C).

Closure of Paravalvular Prosthetic Leaks The reported prevalence of clinically important paravalvular leaks (PVL) due to valve dehiscence ranges between 3% and 12.5% of all surgically implanted prosthetic valves.66 In the early postsurgical period, prosthetic valve dehiscence is typically due to procedural mishaps (e.g. a loose suture in a patient with calcified native annulus).

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

C

D

547

Figs 28.14A to D: Assessment of paravalvular aortic regurgitation post-transcutaneous aortic valve replacement. (A) Implanted CoreValve (arrows) seen on fluoroscopy; (B) Mild paravalvular regurgitation (arrow) in a patient with CoreValve. Frequently the paravalvular leak is located adjacent to the AML; (C) Severe paravalvular regurgitation (arrows) in another patient with CoreValve. Note the large amount of color flow along the entire posterior aspect of the prosthetic valve. After placement of another CoreValve using the valve-in-valve technique, the severe aortic regurgitation disappeared; (D) Spectral Doppler of severe paravalvular regurgitation seen in (C). Note the rapid deceleration slope of the aortic regurgitant jet (pressure half-time of 200 ms). (AML: Anterior mitral leaflet. LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle).

Late-onset prosthetic dehiscence is usually due to infective endocarditis. Irrespective of its cause, prosthetic valve dehiscence leads to paravalvular regurgitation and hemolytic anemia. The magnitude of hemolytic anemia does not necessarily correlates with the severity of paravalvular regurgitation.67 Heart failure and transfusion-dependent anemia are major indications for PVL closure. Until recently, redo open heart surgery was the only means of closing clinically significant PVLs. However, reoperation is associated with high morbidity and mortality, with reported in-hospital mortality rates of 13%, 15%, and 37% for the first, second, and third reoperations, respectively.68

It appears that in 1987 the first percutaneous PVL closure was performed.69 Percutaneous closure of PVLs is emerging as an alternative to redo surgery.70 Most initial experience has been with closure of mitral PVLs71 but techniques are being developed for PVLs of prosthetic aortic valves as well.72 Percutaneous closure is becoming the treatment of choice for most clinically significant PVLs; surgery is still reserved for very large PVLs (involving more than 25% of the prosthetic ring circumference) or PVLs related to active endocarditis.73 At present, there are no closure devices that are specifically designed for PVL closure; instead either vascular plugs or occluders designed for ASD, VSD, or PDA closure are used off label.

548

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 28.15A to C: Assessment of aortic valve gradients before and after transcutaneous aortic valve replacement. Aortic valve gradients before (A) and after (C) percutaneous implantation of the Sapien aortic valve; the valve is seen on fluoroscopy in (B).

Depending of PVL size, one or more devices may be needed to successfully close the leak.74 Improvements in 3D TEE imaging are the major driving force behind the development of percutaneous PLV closures. 3D TEE is important both for establishing the precise diagnosis of PVL and for monitoring of percutaneous closure.

3D TEE Diagnosis of PVL The diagnosis of a PVL can be established by 2DE. However, 3D TEE provides incremental information regarding the exact location, size, and shape of a PVL (Figs 28.16A and B). This information is crucial for the success of PVL closure procedure. With its ability to provide en face views of the entire MV, 3D TEE demonstrates PVLs in an intuitive and accurate. It is essential to use color Doppler to confirm the location of PVLs and to avoid mischaracterization of periprosthetic image dropouts as PVLs. In summary, 3D TEE can accurate identify patients with suitable anatomy for percutaneous PVL closure.

3D TEE Monitoring of Percutaneous PVL Closure For percutaneous closure of mitral PVLs, standard transseptal approach is used. 3D TEE is instrumental in guiding transseptal puncture as discussed earlier in this chapter. Occasionally, transaortic or transapical approach may be used. Irrespective of the approach used, 3D TEE is used

intraprocedurally to guide placement of wires, catheters, and closure devices (Fig. 28.17). Without 3D TEE guidance many PVL closure procedures would be either impossible to perform using fluoroscopy alone or would expose the patient significant radiation. Postprocedurally, 2DE and 3DE is used to assess for residual regurgitation and to evaluate for possible prosthetic valve malfunction due to closure device impingement. In general, closure of mitral PVL located laterally (Figs 28.17A to D) is technically easier than the closure of those located medially (Figs 28.18A to C).

DEVICE CLOSURE OF CARDIAC SHUNTS Surgical closure of cardiac shunt predates many other forms of cardiac surgery and was practiced well before the advent of cardiopulmonary bypass in the 1960s. Percutaneous closure has become the treatment of choice for many cardiac shunts including PDA, secundum ASDs, and muscular VSDs with surgery typically being reserved for complex cases.

Closure of PDAs Ductus arteriosus is an arterial communication between the left pulmonary artery and the proximal descending thoracic aorta that develops embryologically from the left sixth aortic arch. Ductus arteriosus is an essential component of the normal fetal circulation; it directs

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

549

B

Figs 28.16A and B: 3D TEE diagnosis of paravalvular mitral regurgitation. (A) 3D TEE en face zoom view of the St Jude mechanical mitral prosthesis; prosthetic leaflets in the open position during ventricular diastole (asterisk) are seen. Arrow points to the location of the paravalvular leak between the aortic valve and the LAA; (B) 3D TEE color Doppler of the St Jude mechanical prosthesis visualized in the same orientation as in figure A. Note the location, size and the shape of the paravalvular leak (arrow). Also note the physiologic (‘washing’) jets inside the prosthetic valve (asterisks). (AV: Aortic valve; LAA: Left atrial appendage).

the blood away from the very high-resistance fetal pulmonic circulation of the collapsed lungs to the lower resistance systemic circulation (physiologic right-to-left shunt). During fetal life, ductus arteriosus is kept open by vasodilators such as prostaglandin PGE2, which is believed to be produced both locally in the ductus and by the placenta. Soon after delivery, pulmonary vascular resistance drops below the systemic vascular resistance leading to shunt reversal; this left-to-right shunt is transient in most infants. The high oxygen content of ductal blood activates an oxygen-sensitive potassium channel that leads to contraction of the ductal muscular layers and cessation of ductal flow. In the majority of infants scarring completely obliterates ductus arteriosus by the end of the neonatal period.75 PDA results from the failure of physiologic closure of ductus arteriosus past the first year of life. It can be isolated or may be associated with a variety of other forms of congenital heart disease. Typically, PDAs presents with a left-to-right shunt; however, shunt reversal can occur if pulmonary vascular resistance rises above the systemic vascular resistance. PDA is the first congenital heart defect to be closed successfully by surgery and was the first congenital heart defect to be closed percutaneously. The first successful ligation of a PDA was performed in 1938 by Robert E Gross, then the chief surgical resident, and John P Hubbard

at Boston Children’s Hospital.76 The first successful percutaneous closure of a PDA was reported by Werner Portsmann and colleagues working at Charité Hospital located in what was then East Germany.77 Percutaneously or surgically closure of a PDA is indicated for the following:78 • Left atrial and/or LV enlargement or if pulmonary arterial hypertension is present, or in the presence of net left-to-right shunt • Prior endarteritis • It is reasonable to close an asymptomatic small PDA by catheter device. Surgical repair by a surgeon experienced in congenital heart disease is recommended when: • PDA is too large for device closure • Distorted ductal anatomy precludes device closure. PDA closure is contraindicated in patients with pulmonary arterial hypertension and net right-to-left shunt. General aspects of PDA diagnosis are discussed elsewhere in this textbook. From the percutaneous or surgical point of view, the role of imaging is to establish the general anatomy of a PDA. Typically, PDAs have a conical shape with the wider opening at the aortic side and the smaller one at the pulmonary artery side. However, a variety of shapes have been described.79 There are limited data on the use of 3DE in the diagnosis of PDA80 and for guidance of PDA closure (Figs 28.19A to D).81,82 In general,

550

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 28.17A to D: 3D TEE guidance of a lateral mitral paravalvular leak closure. 3D TEE en face zoom view of the mitral bioprosthetic valve is seen from the same perspective in all four figures. (A) Arrow points to the location of the lateral paravalvular leak at approximately 10 o’clock (arrow) on the standard surgical view of the MV located between the LAA and the native aortic valve (AV); (B) 3D TEE imaging is used to guide the transseptal catheter (arrow) to the paravalvular leak; (C) A vascular plug (arrow) is placed in the paravalvular leak; (D) Because leak closure was incomplete after first plug placement, another plug is delivered adjacent to the first plug. The two plugs (arrows) were able to close the leak successfully.

TEE allows for continuous monitoring of PDA flow during percutaneous closure; this minimizes X-ray exposure of concomitant fluoroscopy (Figs 28.20A and B).83

Closure of ASDs There are at least four different types of ASDs in the descending order of prevalence: secundum ASD, primum ASD, sinus venosus ASD (which may be of the superior or inferior vena cava type), and unroofed coronary sinus. Following bicuspid aortic valve, ASD is the most common congenital anomaly in adults occurring in approximately 1 out of 1,000 individuals.84

Successful surgical closure of ASDs predates the advent of cardiopulmonary bypass. In 1952, closure of an ASD in a 5-year-old girl by F John Lewis was the first successful open heart operation (performed under general hypothermia and inflow occlusion) at the University of Minnesota.85 In 1953, ASD closure by John Gibbon in Philadelphia was the very first successful cardiac surgery using cardiopulmonary bypass.86 The first percutaneous closure of an ASD was performed in 1975 by King and Mills at Ochsner Medical Center in New Orleans, LA.87 At present, closure of secundum ASDs is the only approved indication for current percutaneous closure devices.

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

Major indications for surgical or percutaneous ASD closure are as follows:78 • Right atrial and right ventricular enlargement with or without symptoms • Closure of an ASD is reasonable in the presence of paradoxical embolism or orthodeoxia-platypnea. Closure of an ASD is contraindicated in patients with severe irreversible pulmonary hypertension and no evidence of a left-to-right shunt. 3D TEE is instrumental in both the diagnosis of an ASD and guidance of percutaneous ASD closure.

A

551

3D TEE Diagnosis of ASDs Appropriate patient selection is of utmost importance for the success of percutaneous ASD closure.88 One should first establish the diagnosis of a secundum ASD, the only ASD type amenable to percutaneous closure at present.89 After obtaining 3D TEE images of the interatrial septum, we use the so-called TUPLE (tilt up then left) maneuver to obtain en face images of the interatrial septum in anatomically correct orientations (Figs 28.21A to C and Movie clip 28.21A and Movie clip 28.21B). Briefly, the TUPLE maneuver is a

B

C

Figs 28.18A to C: 3D TEE guidance of a medial mitral paravalvular leak closure. (A) 3D TEE color Doppler en face zoom view of the mitral bioprosthetic valve demonstrates a medial paravalvular leak at approximately 3 o’clock (arrow) on the standard surgical view of the MV. The leak is located adjacent to the interatrial septum (IAS) and away from the aortic valve (AV); (B) 3D TEE en face zoom view of the mitral bioprosthesis demonstrates two vascular plugs (arrows) used to close the medial paravalvular leak successfully; (C) The appearance of the two vascular plugs on fluoroscopic image in the cranially angulated right anterior oblique projection.

A Figs 28.19A and B

B

552

Section 2: Echocardiography/Ultrasound Examination and Training

C

D

Figs 28.19A to D: 2D/3D TEE diagnosis of PDA. (A) 3D TEE biplane image demonstrating the aortic side (arrows) of a PDA; (B) Spectral Doppler tracings demonstrate flow velocity pattern typical of a PDA with a left-to-right shunt and normal pulmonary artery pressures. There is high pressure gradient between the aorta and the pulmonary artery throughout the cardiac cycles (higher in systole than in diastole); (C) 3D TEE en face zoom view of the aortic orifice of the PDA (arrow); (D) 3D TEE zoom view demonstrates the PDA in its long axis. The PDA appears as a tube between the aorta (Ao) and the pulmonary artery (PA).

A

B

Figs 28.20A and B: Fluoroscopy during PDA closure. (A) Prior to PDA closure, PDA is imaged using contrast injection into the descending aorta. The contrast exits the aorta (Ao) into the pulmonary artery (PA) via the PDA (arrows); (B) A PDA closure device (arrows) is being deployed into the PDA. The device is still attached to its delivery cable seen in the pulmonary artery (PA).

three-step process in which the initial 3D zoom image of the interatrial septum is tilted up to reveal the right atrial aspect of the interatrial septum. The image is then rotated counterclockwise in the Z-axis until the SVC is located at 12 o’clock. Finally, the image is then rotated to the left to reveal the left atrial aspect of the interatrial septum.90 After using the TUPLE maneuver one can easily determine ASD type, location, shape, and size. Secundum ASDs (Figs 28.22A to D) are located in the fossa ovalis and come in a variety of shapes (circular, ovoid,

triangular).91 They may contain fenestrations (cribriform ASD) or may be associated with an atrial septal aneurysm.92 Sizing of an ASD involves measuring of ASD diameters and determining the size of surrounding ASD rims; these data are essential for choosing an appropriate closure device. The three most commonly used ASD closure devices (Figs 28.23A to C) are as follows: • AmplatzerTM atrial septal occluder (St Jude Medical, St Paul, MN). It consists of two discs (the left atrial disc being larger than the right atrial disc) connected

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

553

C

Figs 28.21A to C: TUPLE maneuver for orienting the interatrial septum. TUPLE (Tilt-Up-Then-Left) is a simple maneuver for orienting the interatrial septum into an anatomically correct orientation. (A) Interatrial septum is first visualized on 2D TEE at 0°. Then the corresponding 3D TEE zoom image of the interatrial septum is obtained; (B) The 3D TEE image is tilted up to reveal the right atrial aspect of the interatrial septum. Note that the superior vena cave is located at 12 o’clock; (C) The 3D TEE image is then rotated to the left to reveal the left atrial side of the interatrial septum. Movie clip 28.21A corresponds to this Figure. Note: If the 2D TEE image is obtained at any angle other than 0° the 3D TEE image is figure 2 is not only tilted up but also rotated counterclockwise until the SVC is at 12 o’clock. Movie clip 28.21B demonstrates this modification of the TUPLE maneuver. (ASD: Atrial septal defect; SVC: Superior vena cava).

by a waist; it comes in a variety of sizes based on waist diameter (from 4 mm to 38 mm). Device selection is based on the measured diameter of the defect, which should correspond to the waist diameter of the device. This device is used to close nonfenestrated secundum ASDs. • AmplatzerTM multifenestrated septal occluder (St Jude Medical, St Paul, MN) is used to close fenestrated (cribriform) secundum ASDs. It contains two discs of equal diameter connected by a thin shaft; it comes in a variety of size based on the diameter of the left atrial disc (from 18 mm to 35 mm). Device selection is ultimately based on the measured diameter of the defect, which should be proportional to the disc diameter of the device. • Gore-Helex atrial septal occluder (W L Gore & Associates, Inc., Flagstaff, AZ) contains two equal-sized discs mounted on a spiral shaft; it comes in a variety sizes based on the disc diameter (from 15 mm to 35 mm). The occluder size selected for the defect should achieve at least a 2:1 ratio between disc diameter and defect diameter. When selecting an ASD closure device, the maximum diameter of a secundum ASD cannot exceed devicespecific cutoff value and there should be sufficient ASD rim to anchor the device. Historically, the device size was selected based on an invasive measurement of ASD

diameter using sizing balloons placed across an ASD (Figs 28.24A and B) and gradually inflated until no color Doppler flow across the ASD is seen on 2D TEE (so-called stop-flow diameter). More recently, device selection is based on direct ASD diameter measurements by 3D TEE (Figs 28.25A to C). The maximum ASD diameter amenable to closure with an AmplatzerTM atrial septal occluder is 38 mm; for a Gore-Helex device the maximum ASD diameter is 18 mm. 3D TEE imaging is also important in measuring rims that surround a secundum ASD (Figs 28.26A and B). There are several different nomenclatures of ASD rims; we prefer the system that labels rims based on the surrounding structure (e.g. aortic rim)93 rather than on their anatomic orientation (e.g. antero-superior rim).94 In general, there are five distinct ASD rims listed in a clockwise direction: SVC rim, aortic room (adjacent to the aortic valve), atrioventricular rim (adjacent to the tricuspid and MV), inferior vena cava (IVC) rim, and posterior rim (the rim opposite the aortic rim). In general, the rims should be “sufficient”—that is, they have to exceed certain minimum distance. This minimum rim size is device specific. For instance, for the AmplatzerTM septal occluder the rims should be at least 5 mm. For the AmplatzerTM multifenestrated septal occluder, the SVC and the aortic rim should be at least 9 mm. Absence of the inferior vena cave rim is considered a contraindication for device closure of a secundum ASD.

554

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 28.22A to D: Anatomic variations of secundum ASDs. 3D TEE zoom images of the right atrial side of the interatrial septum demonstrate variations in the size, shape and location of secundum ASDs. In each image the SVC is located at approximately 12 o’clock. (A) Secundum ASD asterisk) has a near circular shape; (B) Secundum ASD (asterisk) has a triangular shape; (C) Secundum ASD (asterisk) has an ovoid shape and is located in the superior portion of the fossa ovalis. The inferior portion of the fossa ovalis floor is aneurismal (arrow); (D) Fenestrated secundum ASD with multiple holes (asterisks) separated by remnants of the fossa ovalis floor.

3D TEE Monitoring of Percutaneous ASD Closure 3D TEE allows for continuous visualization of the tip of the guiding catheter, as well as of the closure device as it is being delivered. After the secundum ASD is sized and deemed amenable to percutaneous repair by 3D TEE, the interventionalist may decide to confirm the ASD size using a balloon. Color Doppler echocardiography is used during balloon inflation. When no flow between the balloon and ASD margins is seen by color Doppler, the interventionalist measures the ASD diameter on fluoroscopy image (stopflow diameter). Subsequently, a delivery catheter is brought into the left atrium across the ASD using a transvenous approach

(typically via the femoral vein). A collapsed ASD closure device is advanced through the catheter into the left atrium. The left atrial disc is opened first and apposed against the left atrial side of the defect. The right atrial disc is then opened and maneuvered until the device is firmly attached to the rims of the ASD. 3D TEE imaging is used to ascertain proper positioning of the closure device. Both discs can be visualized by 3D TEE although right atrial disc may be more difficult to visualize than left atrial disc. This is due to the fact that relative to the TEE probe located in the esophagus the right atrial disc in the far field and partly shadowed by the left atrial disc (Figs 28.27 and 28.28). In addition, 3D TEE helps determine if sufficient tissue rim is caught in between the two plates of the device. When

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

555

C

Figs 28.23A to C: ASD closure devices. (A) Amplatzer™ atrial septal occluder (St Jude Medical, St Paul, MN); (B) Amplatzer™ multifenestrated septal occluder (St Jude Medical, St Paul, MN); (C) Gore-Helex atrial septal occluder (W L Gore & Associates, Inc., Flagstaff, AZ).

rim capture is insufficient, 3D TEE can be used to guide repositioning of the device. At the end of the procedure, the device is fully deployed after its release from the delivery shaft. 2D- and 3D TEE color Doppler imaging is crucial for assessing the success of percutaneous ASD closure. On color Doppler, ideally there should be no residual para-device leak (i.e. flow around the device between ASD rims and the edge of the device); the absence of such a leak is indicative of a complete ASD closure. Small amounts of color Doppler flow across rather than around the device may be normal; such flows will cease upon endothelialization of the device. ICE is an alternative to 3D TEE for monitoring of ASD closure (Figs 28.29A to C).

Closure of PFOs Foramen ovale, a communication between the right and left atrium at the level of fossa ovalis, is an essential part of fetal circulation. It allows for shunting of oxygen-rich blood (arriving into the right atrium via umbilical veins) to systemic circulation. After birth, the communication closes in the majority of children but remains open in about a quarter of adult population.95 The persistence of this communication is referred to as PFO. PFO has been implicated in the pathogenesis of cryptogenic stroke96 and its surgical or percutaneous closure has been advocated in prevention of recurrent systemic embolism. The role of 3D TEE in percutaneous PFO closure is similar to that described for ASD closure.

556

A

Section 2: Echocardiography/Ultrasound Examination and Training

B

Figs 28.24A and B: ASD sizing balloon. (A) ASD sizing balloon seen on fluoroscopy extending from the right atrium (RA) to the left atrium (LA). Note that the central portion of the balloon (waist) is located in the ASD. The balloon is inflated gradually until color flow across the ASD ceases on TEE imaging. At that moment, the waist diameter is measured; it represents the so-called stop-flow diameter and is used to choose appropriate ASD closure device size; (B) 3D TEE zoom image demonstrates the left atrial aspect of the sizing balloon. (AV: Aortic valve; MV: Mitral valve; RUPV: Right upper pulmonary vein; SVC: Superior vena cava).

A

B

C

Figs 28.25A to C: 3D TEE sizing of ASDs. ASDs can be sized on 3D TEE using a variety of methods. In this figure the ASD is seen from the right atrial perspective. (A) ASD sizing using an overlay grid; in this instance the distance between the dots is 2 mm; (B) ASD sizing using direct on-image calipers; (C) ASD sizing using the multiplane reconstruction method. Also note the difference between the true ASD diameters and a chord. Distances presumed to be diameters on 2D TEE are frequently chords rather than true diameters.

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

557

B

Figs 28.26A and B: 3D TEE visualization of ASD rims. 3D TEE zoom view of the interatrial septum and surrounding structures from the right atrial (A) and left atrial perspective (B). Five ASD rims are depicted in each figure: (1) SVC rim; (2) aortic rim next to the aortic valve (AV); (3) atrioventricular rim next to the tricuspid and mitral valve; (4) IVC rim; and (5) posterior rim.

A

B

Figs 28.27A and B: 3D TEE appearance of Amplatzer ASD occluder. Amplatzer ASD occluder (arrow) is well visualized from the right atrial side (A) and the left atrial side (B). (AV: Aortic valve; IVC: Inferior vena cava; RUPV: Right upper pulmonary vein; SVC: Superior vena cava).

PFOs are typically closed percutaneously with devices that are specifically designed for PFO closure (Figs 28.28A to C) such as the STARFlex occluder (previously referred to as CardioSEAL device; NMT Medical, Boston, MA) and Amplatzer PFO Occluder (St Jude Medical, St Paul, MN). Percutaneous PFO closure was first reported in 1992 using the Bard Clamshell Septal Occluder, a predecessor of the STARFlex device.97 Randomized trials have thus far failed to demonstrate clear benefit of PFO closure with either STARFlex or Amplatzer PFO Occluder.98,99

Closure of VSDs There are several types of VSDs: perimembranous (infracristal); muscular (further subdivided into inlet, trabecular and infundibular, or supracristal); and atrioventricular defect (a communication between the left ventricle and the right atrium).100 Perimembranous VSDs often have a windsock appearance due to evagination of the membranous septum.101 Colloquially, the term “muscular VSD” if often used synonymously with the trabecular VSD. Muscular VSD

558

A

Section 2: Echocardiography/Ultrasound Examination and Training

B

C

Figs 28.28A to C: 3D TEE and fluoroscopic appearance of ASD and PFO closure devices. (A) Gore-Helex atrial septal occluder (W L Gore & Associates, Inc., Flagstaff, AZ); (B) Amplatzer™ multifenestrated (“cribriform”) septal occluder (St Jude Medical, St Paul, MN); (C) STARFlex occluder (previously referred to as CardioSEAL device; (NMT Medical, Boston, MA).

may be congenital or acquired (e.g. following myocardial infarction or trauma).102 Closure of a VSD should be considered if one of the following criteria is present: • Qp/Qs (pulmonary-to-systemic blood flow ratio) ≥ 2.0 and clinical evidence of LV volume overload. • History of infective endocarditis Closure of a VSD may also be considered if: • Qp/Qs > 1.5 with pulmonary artery pressure less than two thirds of systemic pressure and pulmonary vascular resistance less than two-thirds of systemic vascular resistance. • Net left-to-right shunting is present at Qp/Qs > 1.5 in the presence of LV systolic or diastolic failure. Closure of a VSD is contraindicated in patients with severe irreversible pulmonary arterial hypertension (who typically present with pulmonary vascular resistance greater than two-thirds of systemic vascular resistance).

Percutaneous closure of a VSD was first performed in 1987 at Harvard Medical School.103 At present, percutaneous closure devices in the United States are approved for use in patients who are at high risk for standard surgical VSD closure and whose VSD is not in the proximity of cardiac valves. Thus, percutaneous closure is primarily performed in patients with congenital muscular VSDs. Nonetheless, off-label use for percutaneous closure of postinfarction VSDs has been reported.104 One such device approved in the United States is the AmplatzerTM ventricular septal occluder (St Jude Medical, St. Paul, MN). It consists of two discs of equal diameter (a LV disc and a right ventricular disc) separated by a waist that fits within the VSD. Device comes in a variety of sizes based on the waist diameter (from 4 mm to 18 mm). Outside the United States, a specially designed device with eccentric discs is used to close perimembranous VSDs.105

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

559

A

B

C

Figs 28.29A to C: Guidance of ASD closure using intracardiac echocardiography (ICE). ICE images demonstrate steps in secundum ASD closure using an Amplatzer ASD occluder. (A) The ASD closure assembly is brought into the left atrium and the left atrial disc is unfurled; (B) The right atrial disc is unfurled and the closure device is placed within the ASD. The device is still attached to the delivery cable; (C) The ASD device is fully deployed and released from its delivery cable. Color Doppler imaging demonstrates no residual shunt.

3D TEE is important for both the diagnosis and for guidance of percutaneous closure of a VSD.106 With its unique ability to provide en face views, 3D TEE allows for accurate visualization of the VSD location, size, and shape (Figs 28.30A to E). The information is important in establishing the feasibility of device closure and selecting the proper size of the closure device. During percutaneous VSD closure, the role of 3D TEE imaging is similar to that described for percutaneous ASD closures. 3D TEE visualization of intracardiac wires and catheters is helpful in guiding placement of a closure device into the defect. Postdeployment, 2D and 3D TEE color Doppler imaging is crucial for assessing whether VSD closure was successful or not (Figs 28.31A to D). With complete VSD closure there should be no residual paradevice leak (i.e. flow around the device between VSD rims and the edge of the device) on color Doppler imaging. In contrast, small amounts of color Doppler flow across

rather than around the device may be normal; such flows will disappear upon endothelialization of the device.

OCCLUSION OF THE LEFT ATRIAL APPENDAGE Atrial fibrillation, the most common sustained cardiac arrhythmia, is a risk factor for intracardiac thrombus formation and thromboembolism; it accounts for approximately 15% of all ischemic strokes.107 In nonvalvular atrial fibrillation, the LAA is the primary site of thrombus formation accounting for 91% of all atrial fibrillationassociated intracardiac thrombi. Even in valvular atrial fibrillation (which is related to rheumatic heart disease and this uncommon in high-income countries) LAA thrombi account for 57% of all thrombi.108 Anticoagulation with warfarin or other oral agents is the standard of care

560

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

E

Figs 28.30A to E: Echocardiographic diagnosis of perimembranous VSD. (A) 2D TEE image obtained at 145° demonstrates a perimembranous VSD with left to right shunt (arrow) from the left ventricular outflow tract (LVOT) to the right ventricle (RV); (B) 3D TEE color Doppler visualization of the VSD jet. The arrow points to the vena contract of the jet at the level of VSD; (C) Spectral Doppler demonstrates flow typical of a restrictive VSD. Note the high velocity systolic flow and only a low-velocity diastolic flow; (D and E) 3D TEE en face zoom view of the VSD orifice (arrow) from the left ventricular; (D) and the right ventricular side (E). The VSD measures 8 × 7 mm and has an area of 36 mm2. (LA: Left atrium; LCC: Left coronary cusp of the aortic valve; NCC: noncoronary cusp; PV: Pulmonic valve; RCC: Right coronary cusp).

for prevention of thromboembolism in atrial fibrillation. In patients who cannot take anticoagulant, exclusion of LAA from the body of the left atrium is an alternative for prevention of thromboembolism.

LAA exclusion can be achieved either surgically or percutaneously. Surgical techniques of LAA exclusion include LAA amputation,109 clipping,110 and ligation.111 Surgical LAA exclusion is usually performed only as

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

C

D

561

Figs 28.31A to D: Echocardiographic visualization of a VSD closure device. The patient underwent perimembranous VSD closure in China; such a procedure is not available in the United States unless part of an investigational study. (A and B) 2D transthoracic echocardiography demonstrates a closure device obliterating a perimembranous VSD in the parasternal long-axis (A) and the parasternal short-axis view (B); (C and D) 3D TEE en face zoom view of a VSD closure device (arrow) obliterating a perimembranous VSD seen from the left ventricular perspective (C) and the right ventricular perspective (D). (AV: Aortic valve; LA: Left atrium; LV: Left ventricle; NCC: Noncoronary cusp of the aortic valve; RA: Right atrium; RCC: Right coronary cusp; RV: Right ventricle).

an adjunct to another cardiac surgery (such coronary bypass grafting or valvular surgery) that limits the number of patients who could benefit from LAA exclusion. Furthermore, surgical LAA exclusion is frequently incomplete.112 Percutaneous LAA exclusion can be achieved either by implantation of an endocardial occluder device or via transpericardial placement of an epicardial suture at the LAA ostium. 2D and 3D TEE imaging is important for patient selection and guidance of percutaneous LAA exclusion.113

Endocardial Device Closure of LAA Although several occluders have been used, general principles of percutaneous closure of LAA using the

endocardial approach are the same. Using a venous access (typically the femoral vein) and the previously described transseptal puncture, a delivery catheter is advanced through the venous system into the right atrium and then across the interatrial septum into the left atrium near the ostium of the LAA. Subsequently, the occluder is brought through the catheter into the LAA and deployed. LAA occluders consist of a nitinol wire frame covered with cloth. To date, they have only been approved for investigational use in the United States. Three LAA occluders have been evaluated in clinical trials: PLAATO, WatchmanTM, and AmplatzerTM cardiac plug (Figs 28.32A to C).114 PLAATO (Appriva Medical, Inc., Sunnyvale, CA) was the first device that was specifically designed for percutaneous LAA occlusion. Despite promising results,

562

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 28.32A to C: Devices used for percutaneous closure of LAA. The greatest clinical experience to date is with the Watchman device. The PLAATO device is no longer available. The Amplatzer cardiac plug is currently in clinical trials in the United States.

A

B

Figs 28.33A and B

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

C

563

D

Figs 28.33A to D: Sizing of LAA by 2D TEE. On 2D TEE, LAA is visualized on multiple acquisition angles (typically 0°, 45°, 90° and 135°). Both the orifice diameter and the appendage depth are measured in each view.

PLAATO device has been discontinued. Enrollment for the AmplatzerTM cardiac plug (St Jude Medical, St Paul, MN) trial is in progress. WatchmanTM (Boston Scientific, Natick, MA) is the only LAA occluder whose clinical trials have been completed. In the PROTECT-AF trial, LAA exclusion with a WatchmanTM device was shown to be noninferior to warfarin therapy.115 However, it is important to emphasize that all patients who received Watchman device were also treated with warfarin for 6 weeks and dual antiplatelet therapy (aspirin and clopidogrel) for 6 months postdevice implantation. Aspirin therapy was then continued for life. 2D- and 3D TEE in used for both patient selection and procedure guidance. TEE imaging can be used to accurately visualize the LAA prior to the procedure and to measure its size.116 For device placement, both the orifice size and LAA length are important. Historically, LAA was sized using 2D TEE imaging at various acquisition angles, typically at 0°, 45°, 90°, and 135° (Figs 28.33A to D). 3D TEE imaging allows for more precise sizing of the LAA; both 3D zoom and multiplane reconstruction imaging are helpful (Figs 28.34A to D). On 3D TEE en face views, the LAA orifice is often ovoid rather than circular in shape. Using on-image calipers, the orifice diameters can be measured precisely. For proper device implantation, LAA must have a minimum length (the distance between the LAA orifice and LAA tip). This distance can be measured very accurately on multiplane reconstruction of 3D TEE images of LAA. Multiplane imaging allows for keeping the plane of the LAA orifice constant across imaging planes, something that is very difficult with 2D TEE imaging.

3D TEE is used in conjunction with fluoroscopy during LAA device closure (Figs 28.35A to C). 3D TEE allows for visualization of intracardiac trajectories of catheters and introducers, which helps with the transseptal puncture and deployment of an LAA occluder device (Figs 28.36A to D). An LAA occluder device is properly placed when its long axis is parallel to the long-axis of the LAA. Improper off-angle positions of the occluder are much easier to demonstrate by 3D TEE than by 2D techniques. 2D and 3D color Doppler imaging is crucial for ascertaining that no significant residual communication between the LAA and the left atrium (para-device leak) persists after occluder device placement. For the WatchmanTM device, the residual para-device jet should be either absent or at least no larger than 5 mm in width. If the device is placed improperly at first attempt, 3D TEE is used to guide recapture and redeployment of the device.

Epicardial Suturing of LAAs (Lariat Procedure) The major downside of above described endocardial LAA occluders is the need for continued use of anticoagulation and antiplatelet therapy for several weeks postimplantation. In contrast, the Lariat procedure—in which LAA is occluded epicardially—does not require the use of postprocedural anticoagulation therapy. The Lariat procedure utilized both endocardial and epicardial access. The endocardial portion of the procedure is conceptually similar to the Watchman procedure except

564

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 28.34A to D: Sizing of LAA by 3D TEE. 3D TEE provides for more precise sizing of the LAA using either the multiplane imaging (A, B and C) or 3D TEE en face zoom imaging and utilizing on-image calipers.

A Figs 28.35A and B

B

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

565

C

Figs 28.35A to C: Guidance of Watchman procedure by fluoroscopy. (A) After trans-septal puncture, a sheath is brought from the right atrium (RA) into the left atrium (LA) in preparation for the Watchman procedure. A pigtail catheter is advanced through the sheath and its tip is then placed into the LAA; (B) Iodinated contrast is then injected through the pigtail catheter to obtain the LAA gram; (C) In the final step the pigtail catheter is removed and the delivery catheter containing the Watchman device is advanced through the sheath and delivered into the LAA.

A

B

C

D

Figs 28.36A to D: Guidance of Watchman procedure by 2D/3D TEE. (A) LAA orifice (arrow) is visualized en face on 3D TEE; (B) 3D TEE aids in guiding the pigtail catheter (arrow) into the LAA; (C) 3D TEE is then used to guide deployment of the Watchman device. Arrow points to a fully deployed Watchman device obliterating the LA orifice; (D) On 2D TEE color Doppler imaging, no residual communication between the LA and LAA is seen indicative of a successful Watchman procedure.

566

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 28.37A and B: Lariat procedure guidance by fluoroscopy. (A) Two magnet-tipped wires are seen connected to each other in preparation for Lariat-based obliteration of the LAA. On the left side is the endocardial wire with its tip in the apex of the LAA. This wire is deployed into the LAA transvenously after a transseptal puncture. On the right side is the epicardial wire which is advanced through the pericardial space until it meets the endocardial wire; (B) After the two wires are connected magnetically, a snare is placed over the orifice of the LAA epicardially. To prevent slippage of the snare, a balloon attached to the endocardial wire is inflated inside the LAA. Thereafter, the snare is tightened and a stitch is placed epicardially to complete exclusion of the LAA from the body of the left atrium.

that no occluder device is placed in the LAA. Using established transvenous and transseptal techniques, a magnet-tipped guide wire is threaded through the venous system, passed across the interatrial septum, and placed in the tip of the LAA. Another magnet-tipped guide wire is threaded epicardially through a pericardial access until it binds magnetically to the already placed LAA wire (Figs 28.37A and B). Due to the need for this pericardial access, prior history of pericardial adhesions (such as due to pericardiotomy or pericarditis) is a contraindication for the Lariat procedure. In the next step, the LariatTM Suture Delivery Device (SentreHEART, Inc.; Palo Alto, CA) is introduced into the pericardial space over the epicardial wire to deliver a pretied suture loop over the LAA. This delivery device was not specifically designed for LAA occlusion; it has been used for soft tissue closure in other organ systems. As the suture loop is being lassoed over the LAA orifice, a balloon attached to the endocardial wire is inflated at the LAA orifice to prevent the suture from slipping away from the orifice. When the suture is nearly completely tied, the endocardial wire is removed from the LAA (Figs 28.38A to D). At the end of the procedure, the suture is completely tied and the LAA is excluded from the body of the left atrium (Figs 28.39A and B). 2D and 3D color Doppler imaging is crucial for ascertaining that no significant residual communication between the LAA and the left

atrium is present. In addition, TEE imaging is crucial in monitoring for possible procedure-related pericardial effusion. The feasibility and safety of the Lariat procedure has been demonstrated in case series but the outcomes data are still lacking.117 Specifically, there are no long-term data on the risk of pericardial injury related to pericardial access used in the Lariat procedure.

GUIDANCE OF ELECTROPHYSIOLOGY PROCEDURES The role of TEE prior to or during electrophysiology procedures is well established. 2D- and 3D TEE is routinely used to exclude left heart thrombus prior to cardioversion118 or to guide transseptal puncture. 3D TEE is valuable in visualizing the right atrial structures of special interest to electrophysiologists such as the cavotricuspid isthmus and crista terminalis.119 In addition, 3D TEE is now being utilized to guide pulmonary vein isolation during atrial fibrillation ablation.

Pulmonary Vein Isolation for Atrial Fibrillation As pointed out in the section on the LAA exclusion, atrial fibrillation is the most common sustained cardiac arrhythmia whose prevalence increases in age

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

C

D

567

Figs 28.38A to D: Lariat procedure guidance by 3D TEE. (A) After a trans-septal puncture, the endocardial wire and its sheath (arrow) are guided toward the orifice of the LAA (LAA); (B) The endocardial wire (arrow) is seen entering the LAA; (C) In preparation for snaring of the LAA from the epicardial side, a balloon attached to the endocardial wire (arrow) is inflated at the orifice of the LAA; (D) 3D TEE en face zoom image of the ligated LAA orifice (arrow) after completion of the Lariat procedure. (MV: Mitral valve).

A Figs 28.39A and A1

A1

568

Section 2: Echocardiography/Ultrasound Examination and Training

B

B1

Figs 28.39A and B: LAA appearance before and after Lariat procedure. Appearance of the LAA before (A) and after the Lariat procedure (B). Each figure has a 3D TEE en face zoom image (left) and 2D TEE image (right). (LA: Left atrium; LAA: Left atrial appendage; LV: Left ventricle).

(from 1% in general population to about 10% in the octogenarians).120 Atrial fibrillation may present with disabling symptoms, thromboembolism and tachycardiainduced cardiomyopathy. Despite its disorderly rhythm, atrial fibrillation is often triggered in an orderly fashion by ectopic beats in the region of pulmonary vein ostia. This insight led to development of techniques for catheterbased pulmonary vein isolation121 and isolation of other atrial foci.122 Collectively these procedures are referred to as atrial fibrillation ablation. Catheter-based atrial fibrillation ablation has been shown in a randomized trial to be more effective than drug therapy in preventing recurrence of paroxysmal atrial fibrillation.123 At present, catheter ablation is indicated for maintenance of sinus rhythm in selected patients with significantly symptomatic paroxysmal atrial fibrillation who have failed treatment with an antiarrhythmic drug and have normal or mildly dilated left atria, normal or mildly reduced LV function, and no severe pulmonary disease. Additionally, catheter ablation is reasonable to treat symptomatic persistent atrial fibrillation or symptomatic paroxysmal atrial fibrillation in patients with significant left atrial dilatation or with significant LV dysfunction.124 In a typical clinical scenario, prior to atrial fibrillation ablation patients undergo either CT or MRI of the chest to define the anatomy of the pulmonary veins and other cardiac structures. Subsequently, patients are brought the electrophysiology suite where 2D TEE imaging is used primarily to exclude intracardiac thrombus and to further delineate cardiac anatomy.125 Patients then undergo atrial

fibrillation ablation guided by electrical mapping and fluoroscopy. The major shortcomings of such a scenario that CT, MRI, TEE, fluoroscopy, and electrical mapping are not done simultaneously and image integration from various modalities is still a challenge. Some electrophysiologists opt to use ICE for real time imaging during the ablation procedure.126,127 In addition to imaging cardiac structures, ICE can also visualize the esophagus and thus monitor for esophageal injury (left atrio-esophageal fistula), a rare but serious complication of the ablation procedure.128 However, ICE has its own shortcomings: it is invasive, costly, and provides only 2D cross-sectional images. 3D TEE imaging during atrial fibrillation imaging overcomes more of the shortcomings of other imaging modalities. It can provide en face views of pulmonary veins and other cardiac structures in real time.129 Thus, one can determine the number and location of pulmonary vein ostia. There are typically two pulmonary vein ostia on the right and two ostia on the left (Figs 28.40A to D). However, there are many variations; the most frequent one being the common ostium (antrum) of the two left pulmonary veins or three pulmonary ostia on the right (with the right middle pulmonary vein entering the left atrium directly rather than being a tributary of the right upper pulmonary vein (RUPV; Figs 28.41A and B).130 During the ablation procedure, 3D TEE can be used to guide the transseptal puncture. In addition, 3D TEE can provide real time 3D anatomic guidance for placement of mapping and ablation catheters that cannot be achieved at present by any other imaging technique (Figs 28.42A to C).131,132

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

B

C

D

569

Figs 28.40A to D: 3D TEE appearance of typical pulmonary vein ostia. 3D TEE zoom views of pulmonary vein ostia in the left atrium (LA). With current 3D TEE, all four pulmonary vein ostia cannot be seen at once. Instead one visualizes separately right-sided then left-sided pulmonary vein ostia. (A and B) Ostia of the right-sided pulmonary veins seen en face (A) and in the long axis (B); (C and D) Ostia of the left-sided pulmonary veins seen en face (A) and in the long axis (B). (LUPV: Left upper pulmonary vein; LLPV: Left lower pulmonary vein RUPV: Right upper pulmonary vein; RLPV: Right lower pulmonary vein).

2D and 3D TEE can also be used to monitor for procedural complications such as the pericardial effusion. Doppler imaging is used to assess for pulmonary vein stenosis, a long-term complication of pulmonary vein ablation. Pulmonary vein stenosis is defined as a combination of a diminished diameter of the pulmonary vein ostium (< 0.7 cm; normal ~1.5 cm) and an increase in the peak velocity of the pulmonary vein diastolic (D) wave (> 100 cm/sec; normal 40-60 cm/sec).125

MISCELLANEOUS PROCEDURES The utility of 3DE has also been demonstrated in a variety of other percutaneous procedures such as the closure of

the LV pseudoaneurysm, alcohol septal ablation, and right ventricular endomyocardial biopsy.

Left Ventricular Pseudoaneurysm Closure LV pseudoaneurysm is a rare but potentially serious complication of myocardial Infarction or cardiac surgery. It represents a rupture of the LV free wall that is contained by adherent pericardium or scar tissue. The goal of therapy is to prevent conversion of this contained rupture into complete rupture leading to pericardial tamponade and possibly death. Unrepaired LV pseudoaneurysm has high mortality.

570

A

Section 2: Echocardiography/Ultrasound Examination and Training

B

Figs 28.41A and B: 3D TEE appearance of common pulmonary vein variants. (A) 3D TEE zoom en face image demonstrates the most common variant of right sided pulmonary vein ostia, namely the right middle pulmonary vein (RMPV) having a separate left atrial ostium. This is in contrast to most normal individuals in whom the RMPV is a tributary of the RUPV; (B) 3D TEE zoom en face image of the most common variant of left-sided pulmonary ostia, namely the common antrum created by the confluence of the left upper pulmonary vein (LUPV) and the left lower pulmonary vein (LLPV). Irrespective of whether there is one common or two separate left-sided pulmonary ostia, the ligament of Marshall, also known as the left atrial or Coumadin ridge (arrow) separates the pulmonary ostia from the LAA. (RLPV: Right lower pulmonary vein).

A

B

C

Figs 28.42A to C: 3D TEE guidance of atrial fibrillation ablation. 3D TEE zoom images demonstrate steps of the atrial fibrillation ablation procedure using pulmonary vein isolation; (A) In the first step, the mapping catheter referred to as the lasso catheter is paced into the ostium of a pulmonary vein (PV); (B) After the lasso catheter is deployed inside a pulmonary vein, electrical mapping is performed. Thereafter, an ablation catheter is guided toward a pulmonary vein ostium to deliver lesions along the perimeter of a pulmonary vein ostium; (C) In the final step, lesions to additional left atrial structures are delivered. This image demonstrates the ablation catheter delivering lesions to the carina, the left atrial tissue between the pulmonary ostia. (PV: Pulmonary vein; RUPV: Right upper pulmonary vein; RLPV: Right lower pulmonary vein).

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

A

571

B

Figs 28.43A and B: 2D/3D appearance of left ventricular pseudoaneurysm. (A) 2D TEE transgastric view demonstrating a large left ventricular (LV) pseudoaneurysm (PsA) in a patient with prior inferior wall myocardial infarction. Note the appearance of spontaneous echo contrast (“smoke”) in the pseudoaneurysm space; (B) Full-volume 3D TEE image of the LV pseudoaneurysm. The external wall of the pseudoaneurysm is cropped out to reveal the defect in the inferior wall which creates the orifice of the LV pseudoaneurysm. There is spontaneous echo contrast (“smoke”) in the pseudoaneurysm space. (Movie clip 28.43B corresponds to Figure 28.43B). Courtesy: Images in this figure by Jan R Purgess, Department of Anesthesiology, New York University School of Medicine and New York Veterans Affairs Hospital, New York, NY.

Historically, surgery has been the only means of repairing LV pseudoaneurysm (Figs 28.43A and B and Movie clip 28.43B); however, such surgeries themselves have significant mortality and morbidity as well.133 Percutaneous closure of an LV pseudoaneurysm was first reported in 2004 from a hospital in the United Kingdom with an off-label use of the AmplatzerTM atrial septal occluder.134 Experience with percutaneous LV pseudoaneurysm closures is limited to case series, the largest to date consisting of seven patients.135 Multimodality imaging, including 3DE, is essential for the success of percutaneous LV pseudoaneurysm closure.136 Utility of 3D TEE of LV pseudoaneurysm closure is similar to that of VSD closure described earlier in this chapter.

Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy Alcohol septal ablation, first reported in 1995, is an alternative to surgical myomectomy used for relief of LV obstruction is hypertrophic obstructive cardiomyopathy.137 It entails intracoronary injection of alcohol into the septal perforator branch supplying the myocardium in the region asymmetric septal hypertrophy. Successful alcohol septal ablation leads to limited iatrogenic septal infarction, septal thinning, and subsequent diminution of mitral septal contact and LV outflow obstruction. The role of 2DE is well established including the off-label use of microbubble echo contrast injected intra-arterially into the septal perforator branch.138

3D TEE imaging may improve localization of the mitral-septal contact, which is often displaced eccentrically within the LVOT. However, in contrast to most other percutaneous interventions, 3D TEE imaging cannot provide immediate assessment of procedural success of alcohol septal ablation since LV obstruction relief is expected to occur hours or days after septal infarct completion.

Right Ventricular Endomyocardial Biopsy Right ventricle (RV) is the primary site of endomyocardial biopsies which are used in the diagnostic workup of myocarditis, infiltrative cardiomyopathies, cardiac transplant rejection, and other myocardial disorders. Although endomyocardial biopsy is often performed using fluoroscopic guidance alone, both TEE and ICE139 may help define the anatomy better, guide the deployment of the bioptome tip to the desired region of the heart, and potentially increase the safety of the procedure [by avoidance of the tricuspid valve (TV) apparatus, for instance]. The utility of 3DE in RV endomyocardial biopsy has been shown in case reports and case series.140,141

ACKNOWLEDGMENTS We would like to express our gratitude to Dr James Slater, Director of Cath Lab, Dr Larry Chinitz, Director of the Electrophysiology Lab, and Dr Doff McElhinney of Pediatrics and their teams at New York University Langone Medical Center for their collaboration performing the percutaneous procedures described in this chapter.

572

Section 2: Echocardiography/Ultrasound Examination and Training

REFERENCES 1. Rashkind WJ. Palliative procedures for transposition of the great arteries. Br Heart J. 1971;33(Suppl):69–72. 2 Saric M, Gila P, Ruiz C, et al. Chapter 11: Catheter-based procedures to repair structural heart diseases. In: Lang RM, Shernan SK, Shirali G, editors. Comprehensive Atlas of 3D Echocardiography. 1 Har/Psc ed. Philadelphia, PA: Lippincott Williams & Wilkins; December 20, 2012:219–54. 3 Garcia Fernandez MA, Perk G, Saric M, et al. Chapter 12: Real time three-dimensional transesophageal echocardiography for guidance of catheter based interventions. In Badano LP, Lang RM, Zamorano JL, editors. Textbook of Real time Three-Dimensional Echocardiography. 1st ed. New York, NY: Springer; March 9, 2011: 121–34. 4. Houck RC, Cooke JE, Gill EA. Live 3D echocardiography: a replacement for traditional 2D echocardiography? AJR Am J Roentgenol. 2006;187(4):1092–106. 5. Sugeng L, Shernan SK, Salgo IS, et al. Live 3-dimensional transesophageal echocardiography initial experience using the fully-sampled matrix array probe. J Am Coll Cardiol. 2008;52(6):446–9. 6. Salcedo EE, Quaife RA, Seres T, et al. A framework for systematic characterization of the mitral valve by real time three-dimensional transesophageal echocardiography. J Am Soc Echocardiogr. 2009;22(10):1087–99. 7. Sudhakar S, Khairnar P, Nanda NC. Live/real time threedimensional transesophageal echocardiography. Echocardiography. 2012;29(1):103–11. 8. Ross J Jr. Transeptal left heart catheterization: a new method of left atrial puncture. Ann Surg. 1959;149(3): 395–401. 9. Brockenbrough EC, Braunwald E, Ross J Jr. Transseptal left heart catheterization. A review of 450 studies and description of an improved technic. Circulation. 1962;25:15–21. 10. De Ponti R, Cappato R, Curnis A, et al. Trans-septal catheterization in the electrophysiology laboratory: data from a multicenter survey spanning 12 years. J Am Coll Cardiol. 2006;47(5):1037–42. 11. Silvestry FE, Kerber RE, Brook MM, et al. Echocardiographyguided interventions. J Am Soc Echocardiogr. 2009;22(3): 213–31; quiz 316. 12. Ho SY, Chang SD, Liang CC. Simultaneous uterine and urinary bladder rupture in an otherwise successful vaginal birth after cesarean delivery. J Chin Med Assoc. 2010; 73(12):655–9. 13 Ho SY. Embryology and anatomy of the atrial septum. In: Thakur R, Natale A, (editors). Transseptal catheterization and interventions. Minneapolis, MN: Cardiotext; 2010:| 11-26. 14. Faletra FF, Nucifora G, Ho SY. Imaging the atrial septum using real time three-dimensional transesophageal echocardiography: technical tips, normal anatomy, and its role in transseptal puncture. J Am Soc Echocardiogr. 2011;24(6):593–9. 15. Webster MW, Chancellor AM, Smith HJ, et al. Patent foramen ovale in young stroke patients. Lancet. 1988;2(8601):11–2.

16. Tomlinson DR, Sabharwal N, Bashir Y, et al. Interatrial septum thickness and difficulty with transseptal puncture during redo catheter ablation of atrial fibrillation. Pacing Clin Electrophysiol. 2008;31(12):1606–11. 17. Wieczorek M, Hoeltgen R, Akin E, et al. Use of a novel needle wire in patients undergoing transseptal puncture associated with severe septal tenting. J Interv Card Electrophysiol. 2010;27(1):9–13. 18 Waterston DS. Léčení Fallotovy tetralogie u děí do jednogo roku věki. [Treatment of Fallot’s tetralogy in infants under the age of one year.] [Article in Czech] Rozhl Chir. 1962;41:181–3. 19 Søndergaard T, Gotsche H, Ottoson P, et al. Surgical closure of interatrial septal defects by circumclusion. Acta Chir Scand. 1955;109:188–96. 20 Kronzon I, Saric M, Lang RM. Chapter 9: Mitral stenosis. In: Lang R, Goldstein SA, Kronzon I, Khanderia BK, editors. Dynamic Echocardiography: A Case-Based Approach. 1 ed. New York, NY: Springer; July 1, 2010:38–45. 21 Fleming PR. A Short History of Cardiology. Amsterdam, Netherlands—Atlanta, GA: Editions Rodopi Bv; January 1997. 22 Vieussens R. Traité nouveau de la structure et des causes du mouvement naturel du coeur [Treatise on the structure of the heart and the causes of its natural motion]. Toulouse, France;1715. 23. Chandrashekhar Y, Westaby S, Narula J. Mitral stenosis. Lancet. 2009;374(9697):1271–83. 24 Cutler EC, Levine SA. Cardiotomy and valvulotomy for mitral stenosis. Experimental observations and clinical notes concerning an operated case with recovery. Boston Med Surg J. 1923;188:1023–7. 25. Souttar HS. The surgical treatment of mitral stenosis. Br Med J. 1925;2(3379):603–6. 26. Gonzalez-Lavin L. Charles P. Bailey and Dwight E. Harken— the dawn of the modern era of mitral valve surgery. Ann Thorac Surg. 1992;53(5):916–9. 27. Matthews AM. The development of the Starr-Edwards heart valve. Tex Heart Inst J. 1998;25(4):282–93. 28. Edler I, Hertz CH. The use of ultrasonic reflectoscope for the continuous recording of the movements of heart walls. 1954. Clin Physiol Funct Imaging. 2004;24(3):118–36. 29 Starr A, Herr RH, Wood JA. The present status of valve replacement. Special issue on the VII Congress of the International Cardiovascular Society held Sept 14–18, 1965, in Philadelphia. J Cardiovasc Surg. 1965:95–103. 30. Inoue K, Owaki T, Nakamura T, et al. Clinical application of transvenous mitral commissurotomy by a new balloon catheter. J Thorac Cardiovasc Surg. 1984;87(3):394–402. 31 Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

32.

33

34.

35. 36. 37. 38.

39.

40.

41.

42.

43

44.

45.

46.

47

Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation. August 1, 2006;114(5):e84–231. Schlosshan D, Aggarwal G, Mathur G, et al. Real-time 3D transesophageal echocardiography for the evaluation of rheumatic mitral stenosis. JACC Cardiovasc Imaging. 2011; 4(6):580–8. Perk, G., Ruiz, C., Saric, M., et al. Real-time threedimensional transesophageal echocardiography in transcutaneous, catheter-based procedures for repair of structural heart diseases. Curr Cardiovasc Imaging Rep. 2009;2(5):363–74. Wilkins GT, Weyman AE, Abascal VM, et al. Percutaneous balloon dilatation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilatation. Br Heart J. 1988;60(4):299–308. Yun KL, Miller DC. Mitral valve repair versus replacement. Cardiol Clin. 1991;9(2):315–27. Oliveira JM, Antunes MJ. Mitral valve repair: better than replacement. Heart. 2006;92(2):275–81. Carpentier A. Cardiac valve surgery–the “French correction.” J Thorac Cardiovasc Surg. 1983;86(3):323–37. Binet JP, Carpentier A, Langlois J, et al. [Implantation of heterogenic valves in the treatment of aortic cardiopathies]. CR Hebd Seances Acad Sci, Ser D, Sci Nat. 1965;261(25):5733–4. Feldman T, Cilingiroglu M. Percutaneous leaflet repair and annuloplasty for mitral regurgitation. J Am Coll Cardiol. 2011;57(5):529–37. Fucci C, Sandrelli L, Pardini A, et al. Improved results with mitral valve repair using new surgical techniques. Eur J Cardiothorac Surg. 1995;9(11):621–6; discuss 626. Alfieri O, Maisano F, De Bonis M, et al. The doubleorifice technique in mitral valve repair: a simple solution for complex problems. J Thorac Cardiovasc Surg. 2001; 122(4):674–81. Feldman T, Foster E, Glower DD, et al.; EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011;364(15):1395–406. Maisano F, Michev I, La Canna G, et al. Brief description of the percutaneous mitral repair procedure using the MitraClip® device. http://www.ctsnet.org/portals/ endovascular/evolvingtechnology/exp_tech1.html, accessed on April 13, 2013. Benenstein R, Saric M. Mitral valve prolapse: role of 3D echocardiography in diagnosis. Curr Opin Cardiol. 2012;27(5):465–76. Feldman T, Wasserman HS, Herrmann HC, et al. Percutaneous mitral valve repair using the edge-to-edge technique: six-month results of the EVEREST Phase I Clinical Trial. J Am Coll Cardiol. 2005;46(11):2134–40. Faletra FF, Pedrazzini G, Pasotti E, et al. Role of real-time three dimensional transoesophageal echocardiography as guidance imaging modality during catheter based edge-toedge mitral valve repair. Heart. 2013;99(16):1204–15. Saric M, Kronzon I. Aortic stenosis in the elderly. Am J Geriatr Cardiol. 2000;9:321–9, 345.

573

48. Ross J Jr, Braunwald E. Aortic stenosis. Circulation. 1968; 38(1 Suppl):61–7. 49. Schwarz F, Baumann P, Manthey J, et al. The effect of aortic valve replacement on survival. Circulation. 1982;66(5): 1105–10. 50. Webb JG, Wood DA. Current status of transcatheter aortic valve replacement. J Am Coll Cardiol. 2012;60(6):483–92. 51. Harken DE, Soroff HS, Taylor WJ, et al. Partial and complete prostheses in aortic insufficiency. J Thorac Cardiovasc Surg. 1960;40:744–62. 52. Brown JM, O’Brien SM, Wu C, et al. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J Thorac Cardiovasc Surg. 2009;137(1):82–90. 53. Cribier A, Savin T, Saoudi N, et al. Percutaneous transluminal valvuloplasty of acquired aortic stenosis in elderly patients: an alternative to valve replacement? Lancet. 1986;1(8472):63–7. 54. Ben-Dor I, Pichard AD, Satler LF, et al. Complications and outcome of balloon aortic valvuloplasty in high-risk or inoperable patients. JACC Cardiovasc Interv. 2010;3(11): 1150–6. 55. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106(24):3006–8. 56. Andersen HR, Knudsen LL, Hasenkam JM. Transluminal implantation of artificial heart valves. Description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs. Eur Heart J. 1992;13(5):704–8. 57. Smith CR, Leon MB, Mack MJ, et al.; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011; 364(23):2187–98. 58. Forrest JK. Transcatheter aortic valve replacement: design, clinical application, and future challenges. Yale J Biol Med. 2012;85(2):239–47. 59 Gila P, Kronzon I, Saric M. Chapter 9: Aortic valve. In: Lang RM, Shernan SK, Shirali G, editors. Comprehensive Atlas of 3D Echocardiography. 1 Har/Psc ed. Philadelphia, PA: Lippincott Williams & Wilkins; December 20, 2012: 183–200. 60. Gaspar T, Adawi S, Sachner R, et al. Three-dimensional imaging of the left ventricular outflow tract: impact on aortic valve area estimation by the continuity equation. J Am Soc Echocardiogr. 2012;25(7):749–57. 61. Otani K, Takeuchi M, Kaku K, et al. Assessment of the aortic root using real-time 3D transesophageal echocardiography. Circ J. 2010;74(12):2649–57. 62. Jabbour A, Ismail TF, Moat N, et al. Multimodality imaging in transcatheter aortic valve implantation and post-procedural aortic regurgitation: comparison among cardiovascular magnetic resonance, cardiac computed tomography, and echocardiography. J Am Coll Cardiol. 2011;58(21):2165–73.

574

Section 2: Echocardiography/Ultrasound Examination and Training

63. Jilaihawi H, Doctor N, Kashif M, et al. Aortic annular sizing for transcatheter aortic valve replacement using crosssectional 3-dimensional transesophageal echocardiography. J Am Coll Cardiol. 2013;61(9):908–16. 64. Smith LA, Dworakowski R, Bhan A, et al. Real-time threedimensional transesophageal echocardiography adds value to transcatheter aortic valve implantation. J Am Soc Echocardiogr. 2013;26(4):359–69. 65. Jilaihawi H, Chakravarty T, Weiss RE, et al. Meta-analysis of complications in aortic valve replacement: comparison of Medtronic-Corevalve, Edwards-Sapien and surgical aortic valve replacement in 8,536 patients. Catheter Cardiovasc Interv. 2012;80(1):128–38. 66. Latson LA. Transcatheter closure of paraprosthetic valve leaks after surgical mitral and aortic valve replacements. Expert Rev Cardiovasc Ther. 2009;7(5):507–14. 67. Maraj R, Jacobs LE, Ioli A, et al. Evaluation of hemolysis in patients with prosthetic heart valves. Clin Cardiol. 1998;21(6):387–92. 68. Echevarria JR, Bernal JM, Rabasa JM, et al. Reoperation for bioprosthetic valve dysfunction. A decade of clinical experience. Eur J Cardiothorac Surg. 1991;5(10):523–6; discussion 527. 69. Hourihan M, Perry SB, Mandell VS, et al. Transcatheter umbrella closure of valvular and paravalvular leaks. J Am Coll Cardiol. 1992;20(6):1371–7. 70. Sorajja P, Cabalka AK, Hagler DJ, et al. Percutaneous repair of paravalvular prosthetic regurgitation: acute and 30-day outcomes in 115 patients. Circ Cardiovasc Interv. 2011;4(4):314–21. 71. Kronzon I, Sugeng L, Perk G, et al. Real-time 3-dimensional transesophageal echocardiography in the evaluation of post-operative mitral annuloplasty ring and prosthetic valve dehiscence. J Am Coll Cardiol. 2009;53(17):1543–7. 72. Hoffmayer KS, Zellner C, Kwan DM, et al. Closure of a paravalvular aortic leak: with the use of 2 AMPLATZER devices and real-time 2- and 3-dimensional transesophageal echocardiography. Tex Heart Inst J. 2011;38(1):81–4. 73. Rihal CS, Sorajja P, Booker JD, et al. Principles of percutaneous paravalvular leak closure. JACC Cardiovasc Interv. 2012;5(2):121–30. 74. Ruiz CE, Jelnin V, Kronzon I, et al. Clinical outcomes in patients undergoing percutaneous closure of periprosthetic paravalvular leaks. J Am Coll Cardiol. 2011;58(21):2210–7. 75 Saric M, Kronzon I. Chapter 108: Patent ductus arteriosus. In: Lang R, Goldstein SA, Kronzon I, Khanderia BK, editors. Dynamic Echocardiography: A Case-Based Approach. 1 ed. New York, NY: Springer; July 1, 2010: 451–4. 76 Gross RE, Hubbard JP. Surgical ligation of a patent ductus arteriosus. Report of first successful case. JAMA. 1939; 112(8):729–31. 77. Porstmann W, Wierny L, Warnke H. [The closure of the patent ductus arteriosus without thoractomy. (preliminary report)]. Thoraxchir Vask Chir. 1967;15(2):199–203. 78. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 Guidelines for the Management of Adults with Congenital Heart Disease: a report of the American College

79.

80

81.

82.

83.

84

85.

86.

87. 88.

89.

90.

91.

92.

of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease). Circulation. 2008;118(23):e714–833. Krichenko A, Benson LN, Burrows P, et al. Angiographic classification of the isolated, persistently patent ductus arteriosus and implications for percutaneous catheter occlusion. Am J Cardiol. 1989;63(12):877–80. Roushdya A, El Fikyb A, Ezz el Dine D. Visualization of patent ductus arteriosus using real-time threedimensional echocardiogram: Comparative study with 2D echocardiogram and angiography. Journal of the Saudi Heart Association. 2012;24(3):177–86. Marek T, Zelizko M, Kautzner J. Images in cardiovascular medicine. Real-time 3-dimensional transesophageal echocardiography imaging: adult patent ductus arteriosus before and after transcatheter closure. Circulation. 2009;120(12):e92–3. Chuang YC, Yin WH, Hsiung MC, et al. Successful transcatheter closure of a residual patent ductus arteriosus with complex anatomy after surgical ligation using an amplatzer ductal occluder guided by live three-dimensional transesophageal echocardiography. Echocardiography. 2011;28(5):E101–3. Lam J, Tanke RB, van Oort A, et al. The use of transesophageal echocardiography monitoring of transcatheter closure of a persistent ductus arteriosus. Echocardiography. 2001; 18(3):197–202. Saric M, Kronzon I. Chapter 105: Congenital heart disease in adults. In: Lang R, Goldstein SA, Kronzon I, Khanderia BK, editors. Dynamic Echocardiography: A Case-Based Approach. 1 ed. New York, NY: Springer; July 1, 2010:438–9. Lewis FJ, Taufic M. Closure of atrial septal defects with the aid of hypothermia; experimental accomplishments and the report of one successful case. Surgery. 1953;33(1):52–9. Gibbon JH Jr. Application of a mechanical heart and lung apparatus to cardiac surgery. Minn Med. 1954;37(3):171– 85; passim. King TD, Mills NL. Nonoperative closure of atrial septal defects. Surgery. 1974;75(3):383–8. Vaidyanathan B, Simpson JM, Kumar RK. Transesophageal echocardiography for device closure of atrial septal defects: case selection, planning, and procedural guidance. JACC Cardiovasc Imaging. 2009;2(10):1238–42. Roberson DA, Cui W, Patel D, et al. Three-dimensional transesophageal echocardiography of atrial septal defect: a qualitative and quantitative anatomic study. J Am Soc Echocardiogr. 2011;24(6):600–10. Saric M, Perk G, Purgess JR, et al. Imaging atrial septal defects by real-time three-dimensional transesophageal echocardiography: step-by-step approach. J Am Soc Echocardiogr. 2010;23(11):1128–35. Vettukattil JJ, Ahmed Z, Salmon AP, et al. Defects in the oval fossa: morphologic variations and impact on transcatheter closure. J Am Soc Echocardiogr. 2013;26(2):192–9. Razzouk L, Saric M, Slater JN. Placement of a large GoreHelex atrial septal occluder device in a patient with

Chapter 28: Three-Dimensional Echocardiographic Guidance of Percutaneous Procedures

93. 94.

95.

96.

97.

98.

99.

100. 101.

102

103. 104.

105.

106

107

deficient aortic rim and large atrial septal aneurysm. Closing Remarks Newsletter, Spring 2013; Issue XXII. Amin Z. Transcatheter closure of secundum atrial septal defects. Catheter Cardiovasc Interv. 2006;68(5):778–87. Mathewson JW, Bichell D, Rothman A, et al. Absent posteroinferior and anterosuperior atrial septal defect rims: Factors affecting nonsurgical closure of large secundum defects using the Amplatzer occluder. J Am Soc Echocardiogr. 2004;17(1):62–9. Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc. 1984;59(1):17–20. Lechat P, Mas JL, Lascault G, et al. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med. 1988;318(18):1148–52. Bridges ND, Hellenbrand W, Latson L, et al. Transcatheter closure of patent foramen ovale after presumed paradoxical embolism. Circulation. 1992;86(6):1902–08. Furlan AJ, Reisman M, Massaro J, et al.; CLOSURE I Investigators. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012; 366(11):991–99. Meier B, Kalesan B, Mattle HP, et al.; PC Trial Investigators. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368(12):1083–91. Minette MS, Sahn DJ. Ventricular septal defects. Circulation. 2006;114(20):2190–7. Razzouk L, Applebaum RM, Okamura C, et al. The windsock syndrome: subpulmonic obstruction by membranous ventricular septal aneurysm in congenitally corrected transposition of great arteries. echocardiography. 2013 Jul 1. doi: 10.1111/echo.12279 [Epub ahead of print]. Saric M, Kronzon I. Chapter 107: Ventricular septal defect and Eisenmenger syndrome. In: Lang R, Goldstein SA, Kronzon I, Khanderia BK, editors. Dynamic Echocardiography: A Case-Based Approach. 1 ed. New York, NY: Springer; July 1, 2010:446–50. Lock JE, Block PC, McKay RG, et al. Transcatheter closure of ventricular septal defects. Circulation. 1988;78(2):361–8. Holzer R, Balzer D, Amin Z, et al. Transcatheter closure of postinfarction ventricular septal defects using the new Amplatzer muscular VSD occluder: Results of a U.S. Registry. Catheter Cardiovasc Interv. 2004;61(2):196–201. Masura J, Gao W, Gavora P, et al. Percutaneous closure of perimembranous ventricular septal defects with the eccentric Amplatzer device: multicenter follow-up study. Pediatr Cardiol. 2005;26(3):216–9. Halpern DG, Perk G, Ruiz C, et al. Percutaneous closure of a post-myocardial infarction ventricular septal defect guided by real-time three-dimensional echocardiography. Eur J Echocardiogr. 2009,10:702–3. Anonymous. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med. July 11, 1994;154(13):1449–57.

575

108. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61(2):755–9. 109. Cox JL, Sundt TM 3rd. The surgical management of atrial fibrillation. Annu Rev Med. 1997;48:511–23. 110. Salzberg SP, Plass A, Emmert MY, et al. Left atrial appendage clip occlusion: early clinical results. J Thorac Cardiovasc Surg. 2010;139(5):1269–74. 111. Kim R, Baumgartner N, Clements J. Routine left atrial appendage ligation during cardiac surgery may prevent postoperative atrial fibrillation-related cerebrovascular accident. J Thorac Cardiovasc Surg. 2013;145(2):582–9; discussion 589. 112. Katz ES, Tsiamtsiouris T, Applebaum RM, et al. Surgical left atrial appendage ligation is frequently incomplete: a transesophageal echocardiograhic study. J Am Coll Cardiol. 2000;36(2):468–71. 113. Perk G, Biner S, Kronzon I, et al. Catheter-based left atrial appendage occlusion procedure: role of echocardiography. Eur Heart J Cardiovasc Imaging. 2012;13(2):132–8. 114. Cruz-Gonzalez I, Yan BP, Lam YY. Left atrial appendage exclusion: state-of-the-art. Catheter Cardiovasc Interv. 2010;75(5):806–13. 115. Holmes DR, Reddy VY, Turi ZG, et al.; PROTECT AF Investigators. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet. 2009;374(9689):534–42. 116. Shah SJ, Bardo DM, Sugeng L, et al. Real-time threedimensional transesophageal echocardiography of the left atrial appendage: initial experience in the clinical setting. J Am Soc Echocardiogr. 2008;21(12):1362–8. 117. Bartus K, Han FT, Bednarek J, et al. Percutaneous Left Atrial Appendage Suture Ligation Using the LARIAT Device in Patients With Atrial Fibrillation: Initial Clinical Experience. J Am Coll Cardiol. 2013;62(2):108–18. 118. Klein AL, Grimm RA, Murray RD, et al.; Assessment of Cardioversion Using Transesophageal Echocardiography Investigators. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med. 2001;344(19):1411–20. 119. Faletra FF, Ho SY, Auricchio A. Anatomy of right atrial structures by real-time 3D transesophageal echocardiography. JACC Cardiovasc Imaging. 2010;3(9):966–75. 120. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285(18):2370–75. 121. Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339(10):659–66. 122. Pappone C, Rosanio S, Oreto G, et al. Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation. Circulation. 2000;102(21):2619–28.

576

Section 2: Echocardiography/Ultrasound Examination and Training

123. Wilber DJ, Pappone C, Neuzil P, et al.; ThermoCool AF Trial Investigators. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010;303(4):333–40. 124. Fuster V, Rydén LE, Cannom DS, et al.; American College of Cardiology Foundation/American Heart Association Task Force. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on practice guidelines. Circulation. 2011;123(10):e269–367. 125. To AC, Gabriel RS, Park M, et al. Role of Transesophageal Echocardiography Compared to Computed Tomography in Evaluation of Pulmonary Vein Ablation for Atrial Fibrillation (ROTEA study). J Am Soc Echocardiogr. 2011;24(9): 1046–55. 126. Marrouche NF, Martin DO, Wazni O, et al. Phasedarray intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications. Circulation. 2003; 107(21):2710–6. 127. Jongbloed MR, Bax JJ, de Groot NM, et al. Radiofrequency catheter ablation of paroxysmal atrial fibrillation; guidance by intracardiac echocardiography and integration with other imaging techniques. Eur J Echocardiogr. 2003;4(1):54–8. 128. Schmidt M, Nölker G, Marschang H, et al. Incidence of oesophageal wall injury post-pulmonary vein antrum isolation for treatment of patients with atrial fibrillation. Europace. 2008;10(2):205–9. 129. Faletra FF, Nucifora G, Regoli F, et al. Anatomy of pulmonary veins by real-time 3D TEE: implications for catheterbased pulmonary vein ablation. JACC Cardiovasc Imaging. 2012;5(4):456–62. 130. Pinheiro L, Nanda NC, Jain H, et al. Transesophageal echocardiographic imaging of the pulmonary veins. Echocardiography. 1991;8(6):741–8.

131 Purgess JR, Bernstein S, Saric M. Real-time 3D transesophageal echocardiography: development of a protocol for use in atrial fibrillation ablation procedures. Anesth Analg. 2012;114(Suppl):1–94. 132. Ottaviano L, Chierchia GB, Bregasi A, et al. Cryoballoon ablation for atrial fibrillation guided by real-time threedimensional transoesophageal echocardiography: a feasibility study. Europace. 2013;15(7):944–50. 133. Frances C, Romero A, Grady D. Left ventricular pseudoaneurysm. J Am Coll Cardiol. 1998;32(3):557–61. 134. Clift P, Thorne S, de Giovanni J. Percutaneous device closure of a pseudoaneurysm of the left ventricular wall. Heart. 2004;90(10):e62. 135. Dudiy Y, Jelnin V, Einhorn BN, et al. Percutaneous closure of left ventricular pseudoaneurysm. Circ Cardiovasc Interv. 2011;4(4):322–26. 136. Kapadia SR, Tuzcu EM. Plugging holes: expanding horizon for structural interventions. Circ Cardiovasc Interv. 2011;4(4):308–10. 137. Sigwart U. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet. 1995;346(8969):211–4. 138. Faber L, Seggewiss H, Gleichmann U. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: results with respect to intraprocedural myocardial contrast echocardiography. Circulation. 1998;98(22):2415–21. 139. Silvestry FE, Kerber RE, Brook MM, et al. Echocardiographyguided interventions. J Am Soc Echocardiogr. 2009; 22(3):213–31; quiz 316. 140. McCreery CJ, McCulloch M, Ahmad M, deFilippi CR. Realtime 3-dimensional echocardiography imaging for right ventricular endomyocardial biopsy: a comparison with fluoroscopy. J Am Soc Echocardiogr. 2001;14(9):927–33. 141. Scheurer M, Bandisode V, Ruff P, et al. Early experience with real-time three-dimensional echocardiographic guidance of right ventricular biopsy in children. Echocardiography. 2006;23(1):45–9

CHAPTER 29 Three-Dimensional Echocardiography in the Operating Room Ahmad S Omran

Snapshot  Mitral Valve Disease  AorƟc Valve Disease  Tricuspid Valve Disease  NaƟve Valve EndocardiƟs

INTRODUCTION Three-dimensional echocardiography is a new dimension in cardiac ultrasound representing a major innovation in cardiovascular imaging. Three-dimensional transesophageal echocardiography (3D TEE) is the only available imaging modality in the cardiac operating room for preoperative assessment of cardiac pathology and facilitates appropriate surgical intervention. Immediate postoperative assessment ensures the cardiac surgery team of the operation outcome. In this chapter, the role of 3D TEE in the operating room in different cardiac pathologies is discussed. In each section, examples of pre- and postoperative images and related movie clip(s) have been provided. I have attempted to present echo images of every case with related surgical clips for correlation. It is worth mentioning that all cases discussed in this chapter have been operated in the last 4 years in our cardiac center.

MITRAL VALVE DISEASE The mitral valve (MV) lies between the left atrium (LA) and the left ventricle (LV). Normal area of the MV is

 ProstheƟc Valve DysfuncƟon  Cardiac Masses  LimitaƟons of 3D TEE, Future DirecƟons

typically about 4 to 6 cm2. The MV consists of mitral leaflets (which resembles Bishop’s miter), saddle-shaped mitral annulus, and subvalvular apparatus composed of chordae tendineae and two papillary muscles attached to the wall of LV. Mitral annulus is a part of the cardiac skeleton with four dense bands or fibrous rings which surround all four heart valves, the pulmonary trunk, and the aorta. Figure 29.1B demonstrates an anatomic diagram of the transverse section of the heart (viewed from the posterior of the heart) showing relation of the mitral with other valves (Sobotta Atlas of Human Anatomy, 1998, Williams & Wilkins, Baltimore). Figure 29.1A and Movie clip 29.1, show the correlation between anatomy and 3D TEE fullvolume acquisition. Pulmonic valve (PV) cannot be shown in the same cut plane because location of this valve is slightly higher than other valves. The MV consists of two leaflets. The anterior MV leaflet (AMVL) is the longer leaflet and is attached to the anterior mitral annulus which consists of one third of the mitral annular circumference. The posterior MV leaflet (PMVL) is shorter and is attached to the posterior annulus which occupies about two third of the mitral annulus. The anterior mitral annulus extends from the

578

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.1A and B: Four-valve view of the heart at the base, correlation between 3D TEE full-volume acquisition of the base of the heart with anatomical diagram. (A) 3D TEE view shows severely stenotic mitral valve (arrow), normal tricuspid, and aortic valves. Note: pulmonic valve (PV) cannot be visualized in the 3D TEE at the same cut-plane because PV location is higher than the level of the other three valves; (B) Anatomic diagram of the heart at the same level. 3D TEE, three-dimensional transesophageal echocardiography. (AMVL: Anterior mitral valve leaflet; AT: Anterior tricuspid leaflet; IVC: Inferior vena cava; LAA: Left atrial appendage; LCC: Left coronary cusp of the aortic valve; NCC: Noncoronary cusp; P: Posterior tricuspid leaflet; PMVL: Posterior mitral valve leaflet; RCC: Right coronary cusp; RVOT: Right ventricular outflow tract; S: Septal tricuspid leaflet).

right to the left fibrous trigones and is adjacent to the tricuspid valve (TV) and noncoronary sinus of Valsalva on the right and left coronary sinus of the Valsalva and left main coronary artery on the left. Mitral leaflets are attached to the papillary muscles by about 25 primary chordae tendineae and several secondary chordae. AMVL has about 9 chordae and PMVL about 14. Chordae of each mitral leaflet are equally distributed between the two papillary muscles. Each commissure of the MV is attached to a corresponding papillary muscle by a large fan-shaped chord. In some patients, a small commissural leaflet can be seen. Coronary sinus runs beside the right posterior annulus, and circumflex artery is behind the left posterior annulus. Functional anatomy and classification of the MV were described by the pioneering cardiac surgeon Alain Carpentier and published in 1983 as the “French correction.”1 It was believed for many years that anterior mitral annulus could not dilate because of its connection with firm right and left fibrous trigones; therefore, insertion of a posterior annuloplasty ring during repair of the degenerative MV was assumed to be sufficient to prevent future dilatation. Recent autopsy and 3D imaging studies have proven that, in fact, anterior annulus dilates in pathologic conditions and a complete annuloplasty ring is likely the better choice.2 Many studies have shown that two-dimensional (2D) TEE can accurately predict MV anatomy and

suitability for repair.3 This assessment is very operator dependent and requires 3D mental reconstructions for decision making about preoperative pathology, the best appropriate technique for repair and postoperative evaluation of the result.4 Moreover, because of the 3D nature of the MV anatomy, 2D demonstration of the valve in preoperative assessment is not very attractive for the operating cardiac surgeon. The 3D TEE surgical view of the MV creates a “common language” for the surgeons and makes it easy for them to understand the pathology and apply the best technique to tackle it. MV is the best ideal structure inside the heart to be assessed by 3D TEE because of its location and orientation which is perpendicular to the ultrasound beam coming from the TEE probe inside the esophagus. Thicker leaflets of the MV compared to aortic and TVs as well as their slow opening and closing, makes the MV more compatible with low resolution and low frame rate existing in current 3D echocardiography technology. The 3D TEE en face view of MV can create a surgical view exactly as the surgeon would see during inspection after left atriotomy.5 If prolapse of the mitral scallops and segments is not severe, detection of the abnormality is difficult in en face view. Angled views, in which the images can be assessed obliquely from medial, lateral, anterior, or posterior angulation, are very useful to recognize mild prolapses.6 After 180°

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

579

B

Figs 29.2A and B: Three-dimensional transesophageal echocardiography (3D TEE) surgical view (surgeon’s view) of the normal mitral valve (A) with anatomic correlation after left atriotomy (B). Based on Carpentier’s classification, mitral valve leaflets consist of eight segments and scallops. Posterior mitral leaflet (PMVL) has three scallops with indentation between them which sometimes are very deep and mimic a congenital cleft. Anterior mitral leaflet (AMVL) does not have scallops but can be divided arbitrarily in to three segments corresponding with posterior scallops. There are two commissural segments which in some cases consist of small leaflets. Each commissure is attached to the papillary muscles by one fan-shaped chorda, and rupturing of these chorda can cause mitral regurgitation. Note: aortic valve (AV) is located anterior to the surgeon and should be positioned at the top of the 3D image, and the left atrial appendage (LAA) is located to the left hand of the surgeon. (A1: Lateral segment of the AMVL; A2: Middle segment of AMVL; A3: Medial segment of the AMVL; ALC: Anterolateral commissure; Lat: Lateral; Med: Medial; P1: Lateral scallop of the PMVL; P2: Middle scallop of the PMVL; P3: Medial scallop of the PMVL; PMC: Posteromedial commissure).

A

B

Figs 29.3A and B: (A) Angled view of the mitral valve (MV) in the previous image. Medial anterior angulation of the surgical view demonstrates very mild prolapse of A3 and P3, which were not appreciated in en face view; (B) Rotating previous image, showing left ventricular side of the MV. Note: fish-mouth opening of the mitral valve in diastole with long anterior and short posterior mitral leaflets can be appreciated. This view provides a good chance for planimetry of the mitral valve orifice by 3D image grid or direct measurement which is available in the newer version of the echo machines. (Lat: Lateral side of the MV; LVOT: Left ventricular outflow tract; Med: Medial aspect of the MV).

rotation of the image, MV can be seen by 3D TEE from LV side; however, the surgeon does not have this advantage (Figs 29.2 and 29.3 and Movie clips 29.2 and 29.3A and B).

Degenerative MV disease (myxomatous changes) is the most common cause of mitral regurgitation in the Western world. Prolapse and flail posterior mitral leaflet

580

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.4A and B: En face view (surgical view) of the mitral valve with degenerative changes (myxomatous) in a patient with severe mitral regurgitation (MR). (A) Flail, large, bulky P2 with ruptured chorda; (B) Same view with full-volume color mode demonstrates severe anteriorly directed jet of mitral regurgitation (MR). There is no prolapse of other segments of the mitral valve. (AV: Aortic valve; LAA: Left atrial appendage; P2: Middle scallop of the posterior mitral leaflet).

due to ruptured chordae are more common than anterior mitral leaflet. Flail middle scallop (P2) of the posterior mitral leaflet constitutes about 70% of the pathology in all myxomatous MV and is the easiest pathology to repair compared to more extensive bileaflet disease (Barlow’s disease). Alain Carpentier was the first to describe the repair technique of flail P2 in “French correction” based on quadrangular resection of the P2 and sliding plasty of other scallops of the posterior leaflet. Later, many modification techniques were introduced based on less resection or no resection of the leaflets. This concept is called “American correction” which is “respect the tissues not resects or resect with respect.” After the repair of posterior mitral leaflet, the remaining height of the leaflet should not exceed 1 cm; otherwise, chances of having SAM (systolic anterior motion of the mitral leaflets) and LV obstruction increase. Figures 29.3 to 29.10 and Movie clips 29.4A and B, 29.6A to G, and 29.10A and B demonstrate series of examples of pathology in the posterior mitral leaflet and their surgical repair. Partial flail of the anterior mitral leaflet or complete flail with ruptured chordae tendineae need skills of a more experienced surgeon to repair. Chordal transfer of the posterior leaflet to the anterior was the initial technique developed in Europe. Chordal replacement by the artificial chordae (GoreTex) was introduced by Tirone David in Toronto and other centers in North America and is currently the standard technique to repair the flail anterior

leaflet.7 Figures 29.11 to 29.17 and Movie clips 29.11A to G and 29.17A to C demonstrate the examples of flail anterior mitral leaflet or bileaflet prolapse and the role of the 3D TEE to help the surgeon to repair these more demanding mitral pathologies. Three-dimensional transesophageal echocardiography has a great role in preoperative assessment of the rheumatic MV and decision making for repair or replacement. Thickening and calcification of the leaflets and fusion of the commissures can be appreciated well. It is possible to calculate the MV area by direct 3D planimetry of the MV orifice from the left atrial side or the LV side. This calculation is available by calibrating 3D grid in older generation echo machines but in newer machines can be measured directly. Calculation of the MV area is possible using multiplanar reconstruction (MPR) mode of 3D QLAB as well. The two above-mentioned techniques for calculation of the MV area (MVA) are added by 3D echocardiography to previous standard techniques of pressure half-time (PHT) and 2D planimetry for measuring MVA. These 3D techniques are validated by many studies and do not have the limitations of the PHT in catheterization laboratory during percutaneous mitral balloon valvuloplasty.8,9 3D TEE is very useful to assess the function of the bioprosthetic and mechanical MV after valve replacement.10 Any paravalvular regurgitation can be detected with exact size and location of the leak (Figs 29.18 to 29.24 and Movie clips 29.18A to E and 29.21A to D).

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

581

B

Figs 29.5A and B: Surgical repair of the mitral valve in the previous case. (A) Myxomatous posterior mitral valve leaflet (PMVL) is seen with large flail middle scallop (P2). Multiple ruptured chorda is shown attached to the P2 scallop (blue arrows); (B) Classic surgical technique of quadrangular resection of P2 scallop is demonstrated. Sliding plasty of the base of PMVL for shortening of the leaflet and insertion of an annuloplasty ring are other parts of this technique which were initially described by Carpentier in 1980 as the so-called French correction. (P1: Posterolateral scallop; P3: Posteromedial scallop; Quad. rese: Quadrangular resection).

A

B

Figs 29.6A and B: Three-dimensional transesophageal echocardiography (3D TEE) of mitral valve with surgical correlation in a 45-year-old man. (A) Flail middle scallop of the posterior mitral valve leaflet (P2) with ruptured chorda (white arrow); (B) Corresponding surgical view of the same patient demonstrating large floppy P2 with ruptured chorda (black arrow). (AV: Aortic valve; LAA: Left atrial appendage).

In functional mitral regurgitation which is because of mitral leaflets tethering with or without mitral annular dilation, 3D TEE has a major role in preoperative and postoperative assessment of the MV.11 The 3D TEE en face view shows the exact origin of the mitral regurgitation.

The size of the annuloplasty ring can be estimated by measuring the length of the anterior mitral leaflet in 2D TEE long-axis view or the distance between two mitral commissures in 3D TEE surgical view. This view is very similar to the surgical measurement of the size of ring by

582

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.7A and B: Three-dimensional transesophageal echocardiography (3D TEE) full-volume color acquisition of the mitral valve (MV) in the previous patient. (A) Surgical view of the MV shows severe eccentric anteriorly directed jet of mitral regurgitation (between two arrows); (B) Color-suppress mode of the same view demonstrating large gap (between two arrows) because of flail middle scallop of the posterior mitral valve leaflet causing severe regurgitation.

A

B

Figs 29.8A and B: Carpentier’s technique of mitral valve repair in the previous patient. (A) Quadrangular resection (Quad. rese) of the flail middle scallop of the posterior mitral leaflet (P2); (B) Insertion of a complete semi-rigid annuloplasty ring (Physio ring) to prevent future mitral annular dilatation.

the operating surgeon (Figs 29.25 to 29.27). Postoperative evaluation of the result of the repair by 3D TEE is very useful to detect any transvalvular or para-annular residual mitral regurgitation. Calculation of the MV area by PHT immediately after repair is not valid but mean gradient across the valve should be measured. Many surgeons use posterior annuloplasty band or half-ring to secure the posterior mitral annulus but the new trend now is toward

using full semirigid ring (Physio ring) to prevent further mitral annular dilatation (Figs 29.25 to 29.30 and Movie clips 29.25A to K).

AORTIC VALVE DISEASE Aortic valve (AV) is not an ideal structure of the heart to be assessed by 3D TEE as compared to MV. The AV lies obliquely toward the ultrasound beam coming from TEE

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

583

B

Figs 29.9A and B: Postoperative mitral valve repair assessment by three-dimensional transesophageal echocardiography (3D TEE) in the previous patient. (A) Semi-rigid, complete annuloplasty ring (Physio ring) is seen well seated; (B) Full-volume, 3D color Doppler demonstrates trivial residual mitral regurgitation (Res. MR). Note: saddle shape of the ring, number, and position of the suture lines can be appreciated nicely by 3D TEE images.

A

B

Figs 29.10A and B: Three-dimensional transesophageal echocardiographic (3D TEE) en face view of the mitral valve in a patient with severe mitral regurgitation and corresponding surgical view. Multiple ruptured chorda (black arrows) attached to the middle scallop of the posterior mitral valve leaflet (P2) can be seen in 3D view (A) and during surgical direct inspection (B).

probe inside the esophagus. Aortic cusps are very thin and open in less than 20 milliseconds. Therefore, with low resolution and low frame rate available 3D echo technology it is difficult to acquire a good image. Extra hole appears at the middle of cups (when gain is too low) due to artifact, which should not be taken as fenestrations, and always be correlated with same view of color Doppler.

Preoperative evaluation of the AV can be done by 2D TEE but 3D TEE can provide surgical view as is seen in Figure 29.31 and Movie clip 29.31. Aortic surgical view is obtained by 3D TEE long-axis view and rotation of the image in a way that noncoronary cusp (NCC) is located at the bottom of the picture. This cusp is the closest cusp to the surgeon during conventional aortotomy. In this

584

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.11A and B: Three-dimensional transesophageal echocardiography (3D TEE) surgery correlation in a patient with flail middle segment of the anterior mitral valve leaflet (A2). (A) Surgical view of the mitral valve shows flail A2 with multiple ruptured chorda (black arrows); (B) Direct surgical inspection confirmed the diagnosis of flail A2 with multiple ruptured chorda (black arrows). (AV: Aortic valve; LAA: Left atrial appendage).

A

B

Figs 29.12A and B: Three-dimensional (3D) full-volume color acquisition of mitral valve in the previous patient. (A) Severe eccentric anteriorly directed jet of mitral regurgitation (MR) is demonstrated because of flail middle segment (A2) of the anterior mitral valve leaflet; (B) Color-suppress mode of the same view confirmed the origin of the MR. Note: two ruptured chorda (Rup chord) attached to the tip of A2 (arrows).

view, the right coronary cusp (RCC) and the right sinus of Valsalva are located to the front and right of the surgeon, while the left coronary cusp (LCC) and the left sinus of Valsalva are located to the front and left of the surgeon.12 Preoperative assessment of the AV with rheumatic aortic regurgitation or stenosis through the use of 3D

TEE is very informative. Aortic leaflets retraction, lack of coaptation, commissural fusion, and leaflets calcification can be evaluated. 3D TEE underestimates the degree of calcification compared to 2D TEE and surgical inspection. Aortic annular dimensions for selecting suitable size prosthesis are more accurate by 2D TEE measurement.13–15

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

585

B

Figs 29.13A and B: Three-dimensional (3D), full-volume color demonstrating severe mitral regurgitation (MR) for quantitating degree of MR by proximal isovelocity surface area (PISA) method. (A) Severe MR jet is noted from left ventricle (LV) to the left atrium (LA). Color sector bar has been moved toward the MR jet shows Nyquist limit of +39.4 cm/s; (B) PISA hemisphere is visualized in 3D view and radius (r) is measured by calibrating 3D grid which shows r = 1.1 cm. In newer versions of echo machines, this measurement of radius can be done directly without calibrating the 3D grid.

A

B

Figs 29.14A and B: Surgical repair of the previous mitral valve (MV). (A) Flail middle segment of the anterior mitral valve leaflet (A2) is shown. Ruptured chorda is replaced by synthetic GoreTex materials (blue arrows), which connect leaflet’s tip to the corresponding papillary muscle; (B) Saline test by syringe filled the left ventricle and is bulging the mitral leaflets toward the left atrium. This is the technique that a surgeon can use to initially assess the result of mitral valve repair. Mitral leaflet coaptation line (closure line) should show a regular “happy face” appearance with no flail tip. Degree of the residual regurgitation and origin of the leak can be appreciated by the surgeon in this saline test; however, evaluation is not as accurate as post-op echo study because the former is assessing the residual leak in an arrested heart and the latter in a physiologic, dynamic status.

Vena contracta of the aortic regurgitation (AI) jet to quantitate the degree of AI can be measured by 3D TEE in different angles (Figs 29.32 to 29.35 and Movie clips 29.32A

and B and 29.34A to F). 3D TEE adds two more methods to calculate aortic valve area (AVA) beside the previous conventional methods of continuity equation and direct

586

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.15A and B: Measuring mitral annuloplasty ring size by preoperative three-dimensional transesophageal echocardiographic (3D TEE) assessment of mitral valve in the previous patient and comparison with surgical direct measurement. (A) Ring size can be measured during mitral leaflets closure and full extension of the anterior mitral leaflet. Diameter between two commissures (ALC-PMC) can be measured by 3D grid or directly by new version echo machine; (B) Surgically direct measurement from commissure to commissure or trigon to trigon (right and left fibrous trigon) by commercially available ring sizer (M 30, black arrows). Suitable ring should fit the length between two commissures and the area of the ring should be same as the area of the surface of the anterior mitral valve leaflet (AMVL). Mismatching of these two areas may cause postoperative mitral regurgitation, mitral stenosis, or systolic anterior motion of the mitral valve (SAM). Note: in this patient both methods correlate very well and showed ring size of 30 mm. (ALC: Anterolateral commissure; PMC: Posteromedial commissure).

A

B

Figs 29.16A and B: Three-dimensional transesophageal echocardiographic (3D TEE), postoperative assessment of the mitral valve repair in the previous patient. (A) Complete semi-rigid annuloplasty ring (Physio ring) is seated well; (B) 3D full-volume color showed no residual mitral regurgitation.

planimetry. The first is direct planimetry of the AV in en face view after cropping the image to the level of leaflets tips. The second method, which is probably more accurate,

is MPR method. In this method, AVA can be traced at the level of the tips of leaflets in short axis (Figs 29.35 to 29.40 and Movie clips 29.36A to D and 29.39A to D).

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

587

B

Figs 29.17A and B: Extensive myxomatous changes (Barlow’s disease) in a patient presented with severe mitral regurgitation. (A) Three-dimensional transesophageal echocardiographic (3D TEE) surgical view of the mitral valve demonstrating “lumpy bumpy” appearance of all scallops and segments. Excessive leaflet tissue, increasing surface area of both leaflets and severe dilatation of the mitral annulus are the hallmark of Barlow’s disease. Note: severe prolapse of P2 and P3 scallops with deep indentation (deep indent) or cleft at the middle. Middle segment of anterior mitral valve leaflet (A2) is showing moderate prolapse as well; (B) Surgical inspection of the mitral valve confirmed 3D TEE findings. No ruptured chorda was found during surgical exploration but most of them were thickened and elongated. Although this type of mitral valve pathology is difficult to repair, this patient had successful repair by quadrangular resection of P2 and multiple chordal replacement of the anterior leaflet. (A3: Medial segment of the anterior mitral valve leaflet; P2: Middle scallop of the posterior mitral valve leaflet (PMVL); P3: Medial scallop of the PMVL).

A

B

Figs 29.18A and B: Three-dimensional transesophageal echocardiography (3D TEE) demonstration of severely stenotic mitral valve (MV) in a 68-year-old male patient. (A) Surgical view of the MV showing severe calcification (Ca++) of the leaflets and commissures; (B) Same view of the MV with 3D full-volume color in diastole visualizing mitral orifice from the left atrial (LA) side. Mitral valve area (MVA) is calculated by calibrated 3D grid which came 0.6 cm2. In the latest version of the echo machine, this orifice area can be traced directly without using the 3D grid. (AV: Aortic valve; LAA: Left atrial appendage).

588

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.19A and B: Excised mitral valve (MV) in the previous patient. (A) Mitral valve is demonstrated from the left atrial side with severe calcification (Ca++) of both leaflets at the body and free margins. Commissures are fused; (B) Same specimen is seen from left ventricular side with multiple calcification and thickened, fused chorda (Chor), and subvalvular apparatus. (AMVL: Anterior mitral valve leaflet; PMVL: Posterior mitral valve leaflet).

A

B

Figs 29.20A and B: Mitral valve replacement of the previous patient with a bioprosthetic valve. (A) Bioprosthetic valve visualized in systole from the left atrial side appears well seated. Prosthetic valve cusps and surgical suture lines are well recognized; (B) The valve seen from the left ventricular side in diastole shows three equal-sized cups opened well. Struts of the valve and their orientation are visualized. Note: proximity of the prosthetic valve with left ventricular outflow tract (LVOT) can be visualized in this view and is evaluated in different angles to be sure there is no LVOT obstruction by the prosthetic mitral valve and its struts.

Three-dimensional TEE is very helpful during preoperative assessment of the patient with aortic regurgitation due to fenestration of leaflets secondary to endocarditis or foreign body-like protruding stents of the coronary arteries (Figs 29.41 to 29.43 and Movie clips

29.41A to H). Role of 3D TEE in endocarditis is discussed in the relevant subsection. 3D TEE can help the surgeon to choose the suitable size of newer generation valves like suture-less valves and assess their postoperative function (Fig. 29.44 and Movie clips 29.44A and B).

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

589

B

Figs 29.21A and B: Three-dimensional transesophageal echocardiographic (3D TEE) surgical view of the mitral valve in a 52-year-old male patient and correlation with surgical inspection in the operating room. (A) Severely stenotic mitral valve with tight orifice viewing from the left atrial side. Leaflets are calcified and both commissures are fused; (B) Surgical exploration of the valve confirmed 3D TEE findings. (ALC: Anterolateral commissure; AMVL: Anterior mitral valve leaflet; LAA: Left atrial appendage; PMC: Posteromedial commissure).

A

B

Figs 29.22A and B: Multi-planar reconstruction view (MPR) of the mitral valve in the previous patient. (A) Simultaneously display of sagittal, coronal, and transverse slices of the mitral valve to obtain cross-section of the mitral orifice; (B) Magnified blue box. Mitral valve area can be calculated by 3D QLAB software built in the echo machine to trace the area of mitral orifice (MVA = 0.5 cm2).

TRICUSPID VALVE DISEASE The TV, “the forgotten valve,” is composed of the annulus, leaflets and chordal, and papillary muscle apparatus.16 Anterior tricuspid valve leaflet (ATVL) is the largest cusp and in echocardiography views is always located beside

the right atrial appendage (RAA). Septal tricuspid valve leaflet (STVL) is located beside the aortic root and superior vena cava (SVC) and coronary sinus (CS). Posterior tricuspid valve leaflet (PTVL) is the smallest cusp and is located beside the inferior vena cava (IVC). PTVL is the most posteriorly located part of the TV. In 2D TEE, it is

590

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.23A and B: Three-dimensional (3D) planimetry of the mitral valve orifice in the previous patient. (A) 3D planimetry from the left atrial side. After calibration of the image by 3D grid, mitral valve area (MVA) can be traced easily, which came to 0.5 cm2 in this patient; (B) Same planimetry is done from the left ventricular side, which showed the same MVA. Based on unpublished data from our echo lab, this direct planimetry of 3D image for MVA has excellent reproducibility compared to the conventional method of pressure half-time (PHT) but underestimates the MVA. This method is very useful for the calculation of MVA in cath lab after mitral balloon valvuloplasty while PHT is not valid because in the former method, pre- and postoperative MVA are measured by the same method. Note: in newer versions of 3D echo machines, this planimetry can be done directly without calibrating by 3D grid.

A

B

Figs 29.24A and B: Mitral valve replacement in the previous patient with mechanical double disc (Carbomedics) prosthesis. (A) Threedimensional (3D) zoom mode shows discs in a closed position; (B) Mechanical discs are open symmetrically during diastole (arrows). Note: The normal anatomic orientation of the mitral valve leaflets is parallel to the aorta. Most surgeons implant mechanical mitral valves with the two discs perpendicular to the aorta. This is referred to as "anti-anatomic orientation. (LAA: Left atrial appendage).

impossible to visualize three cusps of the TV at the same time but in 3D TEE, it is possible to obtain a good en face view (surgical view) of the TV in about 60% to 70% of patients.17 It is easier to obtain good 3D images of TV when

leaflets are thickened and diseased. Limitations of 3D TEE in imaging TV are because of thin and fast moving cusps and location of TV being far away from the TEE probe in the esophagus. In secondary tricuspid regurgitation (TR)

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

591

B

Figs 29.25A and B: Three-dimensional transesophageal echocardiographic (3D TEE) surgical view of the mitral valve (MV) in a 74-year-old female undergoing coronary artery bypass grafting (CABG) and MV repair. (A) Mitral leaflets structurally appear normal but are functionally abnormal. Lack of coaptation of leaflets is noted with two large gaps creating severe mitral regurgitation (MR); (B) Full-volume color acquisition demonstrates severe ischemic (functional or secondary) MR, originating from two gaps. Cause of MR in this type of pathology is functional due to the downward displacement of the papillary muscles (as a result of ischemia or infarction) and “tethering” of the mitral leaflets. This tethering is causing systolic restriction and lack of coaptation of the leaflets.

A

B

Figs 29.26A and B: Preoperative measurement of annuloplasty ring size in the previous patient. (A) Two-dimensional transesophageal echocardiographic (2D TEE) long-axis view of the mitral valve (MV) for estimation of the size of annuloplasty ring that surgeons may use during MV repair. While this is the optimal view for measurement of the mitral annulus there are few studies that confirm this with direct sizing by the surgeon (white arrow = 28 mm); (B) Three-dimensional (3D) TEE surgical view of the MV showing the distance between two mitral commissures or two trigons (right and left fibrous trigon), which is the same (28 mm) as was measured by 2D TEE. Note: ring sizer should cover the area of the AMVL as demonstrated in this 3D view. Implantation of a larger size ring may leave residual mitral regurgitation (MR) and a smaller size ring may create systolic anterior motion of the MV (SAM) in postoperative. In ischemic MR, surgeons like to downsize the ring one or two as is shown in the next figure.

592

A

Section 2: Echocardiography/Ultrasound Examination and Training

B

Figs 29.27A and B: Direct surgical inspection of the mitral valve in the previous patient. (A) Surgical demonstration of the mitral valve (MV) shows that both the anterior and posterior mitral valve leaflets (AMVL and PMVL) are normal in structure. Chorda tendina (arrows) are intact and not elongated or ruptured. In the moving heart, these chorda are tethered and have systolic restriction; (B) Direct measurement of annuloplasty ring size by a Cosgrove-Edward ring sizer. Although annuloplasty ring size should be #28, by preoperative 2D and 3D measurement shown in the previous figure, the operating surgeon preferred to downsize the ring to #26.

A

B

Figs 29.28A and B: Surgical repair of the mitral valve in the previous patient. (A) Sutures have been placed in the posterior mitral annulus for securing the annuloplasty ring. No resection of the leaflets was done because there is no excessive tissue; (B) The annuloplasty ring size #26 is being prepared for placement. The operating surgeon preferred to place a half-ring (Cosgrove-Edwards ring) to decrease the circumference of the annulus and to prevent future dilatation. Some surgeons believe that mitral annular dilatation occurs mostly from posterior annulus (from trigon to trigon) and that protecting this part of the annulus is enough, as opposed to a second group that thinks that the entire annulus may dilate and a complete ring is an appropriate choice. (AMVL: Anterior mitral valve leaflet; PMVL: Posterior mitral valve leaflet).

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

593

B

Figs 29.29A and B: Surgical demonstration of the repaired mitral valve in the previous patient and three-dimensional (3D) image correlation. (A) Posterior annuloplasty ring in position. Note: mitral leaflets are visualized after surgical saline test, which shows nice coaptation and no residual leak; (B) 3D transesophageal echocardiography (TEE) immediately after coming off the pump showing the half-ring well seated (between two arrows). Surgical suture lines can be recognized clearly. (AV: Aortic valve).

A

B

Figs 29.30A and B: Immediate postoperative assessment of the mitral valve (MV) repair in the previous patient. (A) Dual volume layout option of the new version of echo machine can display MV from two sides simultaneously. (A) MV is shown from the left atrial side and the left ventricular side; (B) Full-volume color acquisition reveals successful result with no residual mitral regurgitation.

which is mostly because of lack of leaflets coaptation, tricuspid annulus dilates in axes from anteroseptal commissure to the anteroposterior commissure. Based on ECS guidelines, surgery should be considered in patients with mild to moderate secondary TR and dilated tricuspid annulus (>40 mm or 21 mm/m2) undergoing left-sided

valve surgery.18 Etiology of the TR in 90% of the cases is secondary.19 The 3D TEE surgical view of the TV can be obtained by long-axis view (120°) and rotation of image to bring the septal leaflet below the picture. This leaflet is the closest cusp to the surgeon during TV inspection (Figs 29.45 to 29.47 and Movie clips 29.46A to E).

594

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.31A and B: Two- and three-dimensional transesophageal echocardiographic (2D TEE and 3D TEE) views of normal aortic valve. (A) 2D TEE long-axis view in systole shows trileaflet aortic valve (AV). Interatrial septum (IAS) is a good landmark in both views because the noncoronary cusp (NCC) is always adjacent to it; (B) Surgical view of the AV by 3D TEE. NCC is the closest cusp in this view to the surgeon and located at the bottom of the image of three cusps. In the moving loop of this view, ostia of the right and left coronary arteries can be appreciated. (LA: Left atrium; LCC: Left coronary cusp; NA: Nodule of Aranti (small nodules at the free margins of cusps which are normal findings); RA: Right atrium; RCC: Right coronary cusp; RV: Right ventricle; TV: Tricuspid valve).

A

B

Figs 29.32A and B: Three-dimensional (3D) intraoperative transesophageal echocardiography (TEE) in a 24-year-old man with severe aortic regurgitation (AI). (A) 3D TEE echo view (not surgical view) of the aortic valve (AV) showing trileaflet valve with mildly thickened and retracted cusps and large gap at the middle causing severe aortic regurgitation (AI); (B) 3D TEE long-axis view with color Doppler demonstrates severe eccentric AI. Vena contracta of AI can be measured in this view (arrow) by 3D grid or direct measurement in newer machines. (LA: Left atrium; LCC: Left coronary cusp; NCC: Noncoronary cusp; RCC: Right coronary cusp).

Tricuspid annular dimensions and area can be measured by 3D grid or direct measurement in recent generation of echo machines. This evaluation can be

repeated after TV repair and annuloplasty.20 There is no widely accepted surgical method of TV repair among the surgeons. Classic De Vega repair, reducing annular

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

595

B

Figs 29.33A and B: Preoperative three-dimensional transesophageal echocardiography (3D TEE) surgical view of the aortic valve (AV) in the previous patient with surgical correlation. (A) AV in systole shows mildly thickened cusps with retracted free margins compatible with rheumatic AV with predominantly aortic regurgitation in a young patient; (B) Direct surgical inspection showed no commissural calcification. This valve was attempted to repair but failed 1 week later and had to be replaced. (LCC: Left coronary cusp; NCC: Noncoronary cusp; RCC: Right coronary cusp).

A

B

Figs 29.34A and B: Three-dimensional (3D) intraoperative transesophageal echocardiography (TEE) in a 41-year-old man with rheumatic mixed lesion of aortic stenosis and aortic regurgitation (AS and AI). (A) Long-axis view shows thickened aortic leaflets with severe systolic doming. Aortic annulus in this view is measured by 3D grid as 21 mm, which will be the size of the prosthetic valve; (B) 3D full-volume color acquisition in diastole demonstrating severe AI with vena contracta of 7 mm.

dimensions by placing purse sutures at the annulus without ring, is abounded by most surgeons. Key-stitch annuloplasty and bicuspidization technique without insertion of the ring are used in our center by some surgeons. C-shape annuloplasty ring which spares A–V

node area is another widely accepted annuloplasty ring for repair of the TV (Figs 29.48 to 29.55 and Movie clips 29.48A to H, 29.51A to D, and 29.53A to E). Blunt chest trauma is one cause of primary tricuspid regurgitation and happens because of rupture of the anterior leaflet

596

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.35A and B: Preoperative three-dimensional transesophageal echocardiography (3D TEE) surgical view of the aortic valve in the previous patient, correlating with direct inspection. (A) 3D view shows trileaflet valve with fused commissure between NCC and LCC creating a “functional bicuspid” aortic valve; (B) Direct surgical inspection demonstrates severely calcified leaflets with fusion line (Fus) between NCC and LCC. (LCC: Left coronary cusp; NCC: Noncoronary cusp; RCC: Right coronary cusp).

A

B

Figs 29.36A and B: Comparison between 3D TEE echo view and surgical view of the aortic valve (AV) in a 53-year-old female with severe aortic stenosis. (A) 3D TEE echo view of the AV is obtainable at short axis (40–50°). NCC is always beside the interatrial septum (IAS). RCC can be visualized adjacent to the right ventricle; (B) 3D TEE surgical view of the AV can be acquired in long-axis view (120°). This view is always recommended in the operating room because it creates a "common language" with the surgeon. In this view, the NCC is located closest to the surgeon at the bottom of the image. RCC is located at the right and anterior and LCC is located at the left and anterior of the surgeon. Ostia of the left main and right coronary arteries can be visualized in both echo and surgical views. 3D TEE, three-dimensional transesophageal echocardiography. (LA: Left atrium; LCC: Left coronary cusp; NCC Noncoronary cusp; RA: Right atrium; RCC: Right coronary cusp; RVOT: Right ventricular outflow tract).

or of the papillary muscle.21 Clinical manifestations may present many years after the initial trauma because of tolerable nature of the TR in a patient with no other

cardiac abnormality. Ruptured papillary muscle can be resuspended successfully (Figs 29.56 and 29.57 and Movie clips 29.56A to C). In patients with long-standing severe TR

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

597

B

Figs 29.37A and B: Calculation of the aortic valve area (AVA) in the previous patient with two different methods in 3D TEE. (A) Planimetry of aortic valve in short-axis surgical view by calibrated grid; (B) Multiplanner reconstruction (MPR) method which can obtain short axis of the valve at the level of the cusps tip and measure the area. In both the methods, AVA is in the critical aortic stenosis range. Note: in preoperative transthoracic echo study, this patient had a peak gradient of 140 mm Hg across the aortic valve. 3D TEE, threedimensional transesophageal echocardiography. (LCC: Left coronary cusp; NCC: Noncoronary cusp; RCC: Right coronary cusp).

A

B

Figs 29.38A and B: Surgical inspection of the aortic valve in the previous patient. (A) Surgical aortotomy to explore the aortic valve (AV); (B) Demonstration of the aortic cups. Severe inflammation of the leaflets is noted without calcification. Result of pathology was reported as myxoid fibrinoid degeneration. This patient underwent aortic valve replacement. (IVC: Inferior vena cava; LCC: Left coronary cusp; NCC: Noncoronary cusp; RCC: Right coronary cusp).

or redo surgery TV may not be preserved and needs to be replaced. Mechanical prosthesis is not a good option for tricuspid position because of higher chance of clotting. Although bioprosthetic valve has a chance of degeneration it is still a better choice (Figs 29.58 to 29.60 and Movie clips 29.58A to F).

NATIVE VALVE ENDOCARDITIS Echocardiography is diagnosis of infective criteria. It is also the complications of IE,

the major imaging modality for endocarditis (IE) based on Duke’s best available technique to detect which often necessitate surgical

598

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.39A and B: Three-dimensional transesophageal echocardiography (3D TEE) imaging compared with surgical inspection of the same patient in a 39-year-old male with severe aortic stenosis undergoing valve replacement. (A) Preoperative 3D full-volume acquisition shows bicuspid aortic valve with tight orifice (arrows). Calcifications may be underestimated in 3D echo imaging compared to 2D imaging due to inferior resolution in 3D echo; (B) Surgical inspection demonstrates severely stenotic bicuspid aortic valve. (Inset: B) Aortic valve after resection is zoomed from left ventricular side which shows severely calcified valve. (LA: Left atrium; RA: Right atrium).

A

B

Figs 29.40A and B: Three-dimensional transesophageal echocardiography (3D TEE) of calcific aortic stenosis in a 68-year-old patient compared with the surgical finding. (A) 3D TEE echo view (not surgical view) showing trileaflet aortic valve. Calcifications of the cusps are less appreciated compared to surgical demonstration; (B) Direct inspection shows heavy calcification of the entire aortic valve except for the leaflet free margins and commissures. The contrasts sharply with the appearance of rheumatic aortic stenosis where the free margins and commissures are more diseased.

intervention and strongly affects patient outcomes. 3D TEE provides enhanced display of anatomic–spatial relationships allowing more precise delineation of complex pathology, particularly of the complications of

native valve endocarditis (NVE)-like perforation of the leaflets, perivalvular abscess formation, and fistulous communications with neighboring structures.22 Sensitivity of the 3D TEE to detect small vegetations is less than that of

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

599

B

Figs 29.41A and B: Three-dimensional transesophageal echocardiography (3D TEE) views of aortic root in a 36-year-old lady with severe aortic regurgitation. This patient had myocardial infarction 9 month ago and had a stent deployed in the right coronary artery (RCA) and the left main coronary artery (LMCA). (A) 3D zoom mode showing stent in RCA protruding in to the lumen of aortic root. Wire of the stent is visualized, touching the right coronary cusp (RCC) of the aortic valve during systole; (B) Same long-axis view of the aortic root with angulation demonstrates stent in the ostium of LMCA. Note: stent is protruding in to the lumen slightly and is not touching any cusps.

A

B

Figs 29.42A and B: Three-dimensional transesophageal echocardiography (3D TEE) with full-volume color acquisition showing mechanism of aortic regurgitation (AI) in the previous patient. (A) Long-axis view of the aortic root demonstrates protruding stent pushing downward the right coronary cusp resulting in prolapse of this cusp and severe AI; (B) Multiplanner reconstruction (MPR) mode of the same view shows origin of the AI in long-axis, short-axis, and coronal view.

2D TEE because of lower spatial and temporal resolution. Low frame rate 3D TEE acquisition (Zoom mode) may miss fast moving, oscillating vegetations on the valves; therefore, a combined use of these two methods is necessary for decision making.

Bicuspid AV, previous dental manipulation, underlying rheumatic and degenerative valvular heart diseases, and diabetes mellitus are the risk factors for NVE. The most common microorganism identified in a group of patients who underwent operation for NVE, were Streptococcus

600

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.43A and B: Surgical inspection of the aortic root in the previous patient. (A) Stent of the right coronary artery is shown protruding in to the aortic root lumen about 1.5 cm from the ostium. Stent wire pushes over the RCC. Extra portion of the stent was resected by the surgeon. RCC was examined and showed extensive damage of this cusp, not amenable to repair. A decision was made to replace this aortic valve with a bioprosthetic valve; (B) Three-dimensional transesophageal echocardiography (3D TEE) immediately after surgery shows bioprosthetic aortic valve (AVR) in long-axis view. (LA: Left atrium; LV: Left ventricle; RCC: Right coronary cusp).

A

B

Figs 29.44A and B: Sutureless Perceval (Sorin Group) bioprosthetic aortic valve in a 78-year-old high-risk female patient. (A) Medium size valve in place. This valve is made of porcine pericardium and is self-expandable. The valve has only three sutures which are connected to three commissural posts of the native aortic annulus and positioned by a special holder through a conventional aortotomy. Pump time of replacing an aortic valve with a Perceval valve is less than half the time of a conventional aortic valve replacement; (B) Three-dimensional transesophageal echocardiography (3D TEE) surgical view of the same patient. (LA: Left atrium; RA: Right atrium).

viridans and Staphylococcus. AV was more common than MV and men were more affected than women in this group of patients.23

One of the rare causes of the NVE is brucella endocarditis. Early diagnosis and appropriate antibiotic therapy may preserve the integrity of the involved valves. Delay in

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

601

B

Figs 29.45A and B: Diagram of surgical view of the tricuspid valve. (A) Diagram of normal tricuspid valve (TV). During operation on TV, the surgeon rotates the heart in a way that the right atrium is at the top and the left atrium is located at the bottom. Septal leaflet of the TV is the closest cusp to the surgeon. The large anterior leaflet is in front of the surgeon and the smaller posterior leaflet is located toward the right hand of the surgeon. The A–V node is located at the triangle of the Koch and should be avoided from manipulation during TV repair; (B) Diagram shows the longest axis of the tricuspid annular dilatation secondary to tricuspid regurgitation (TR). Dilatation happens in axis from anteroseptal commissure to anteroposterior commissure (red arrow). In recent European Society of Cardiology (ESC) guidelines, dilation in this axis more than 4 cm even with the presence of mild to moderate TR is an indication for TV repair if the patient is going for left side heart surgery.

A

B

Figs 29.46A and B: Comparison between three-dimensional transesophageal echocardiography (3D TEE) echocardiographic view and surgical view of a normal tricuspid valve (TV). (A) 3D TEE echocardiographic view obtained from long-axis view (120°) showing TV, IVC, and CS; (B) 180° counterclockwise rotation of same image provides surgical view of TV. CS is a landmark for septal leaflet, and IVC is a landmark for posterior leaflet of the TV due to their close proximity. Note: SVC and aorta are parallel to each other and both are running on the left side of the surgeon. (CS: Coronary sinus; IVC: Inferior vena cava; SVC: Superior vena cava).

medical treatment can lead to complications of infection, such as perivalvular abscess formation. In case of the aortic root abscess, surgical radical resection of the abscess and AV replacement are recommended. Aortic homograft

with coronary reimplantation is a superior choice.24–26 Preoperative assessment of the infected valve by 3D TEE can show the degree of the valvular destruction, location, and extension of the perivalvular abscess. At the same

602

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.47A and B: Surgical view of the tricuspid valve (TV) in the previous patient with different angulation. (A) 3D TEE of the TV with more clear visualization of the IVC; (B) Same view with more rotation away from the surgeon to show aortic root. (A: Anterior TV leaflet; IVC: Inferior vena cava; LA: Left atrium; P: Posterior TV leaflet; RAA: Right atrial appendage; S: Septal TV leaflet; SVC: Superior vena cava).

A

B

Figs 29.48A and B: Intraoperative 3D TEE in a 36-year-old male with severe rheumatic mitral stenosis and severe tricuspid regurgitation (TR). (A) 3D TEE en face view (surgical view) of the tricuspid valve (TV) from right atrial side showing all three cusps with dilated annulus and lack of leaflets coaptation; (B) Tricuspid leaflets are seen from the right ventricular side. 3D TEE, three-dimensional transesophageal echocardiography; (An: Anterior tricuspid valve leaflet; LA: Left atrium; P: Posterior tricuspid valve leaflet; S: Septal tricuspid valve leaflet).

time postoperative evaluation can delineate the function of the prosthetic root, LV function, and possible coronary reimplantation complications (Figs 29.61 to 29.63 and Movie clips 29.61A to F).

As was discussed earlier, bicuspid AV is the most common risk factor for NVE. Recent studies have shown that annual incidence of IE in this common congenital heart disease is about 2%.27 Compared to other NVE, bicuspid

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

603

B

Figs 29.49A and B: Pre- and postoperative three-dimensional transesophageal echocardiography (3D TEE) with full-volume color of previous patient. (A) Preoperative surgical view shows severe tricuspid regurgitation (TR) due to lack of leaflets coaptation; (B) Immediate postoperative TEE demonstrates trivial residual TR.

A

B

Figs 29.50A and B: Surgical technique to repair previous tricuspid valve (TV). “Key-stitch repair,” which is a couple of interrupted pledget sutures (Pled. Sut) positioning at the tricuspid annulus, was used in this patient. (A) Surgical examination of the leaflets prior to the repair; (B) Pledget sutures in place at the annulus around the anterior and posterior leaflets. (An: Anterior tricuspid leaflet; P: Posterior tricuspid leaflet; S: Septal tricuspid leaflet).

AV endocarditis has more chance of complications, such as cusp perforation, valve destruction, valvular, perivalvular, and myocardial abscess. Acute heart failure may happen as a consequence of these complications. Extension of perivalvular abscess to the A–V node and bundles can create bundle branch block or a complete

A–V block. Mortality rate and recurrence of the infection in patients with aortic root abscess is high. Early detection and prompt surgical intervention are crucial.28,29 3D TEE is very helpful for detection and visualization of valve perforation, degree of aortic regurgitation, and extension of the aortic root abscess. Preoperative full assessment

604

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.51A and B: Three-dimensional transesophageal echocardiography (3D TEE) surgical view of the tricuspid valve (TV) in a 53-year-old female diagnosed with idiopathic severe tricuspid regurgitation (TR). (A) En face view of the TV shows severely dilated tricuspid annulus with thin pliable leaflets; (B) 3D TEE with full-volume color acquisition demonstrated severe TR due to lack of leaflets coaptation.

A

B

Figs 29.52A and B: Surgical exploration and repair of the tricuspid valve (TV) in the previous patient. (A) Direct inspection shows dilated tricuspid annulus with no primary leaflet disease; (B) Repair of the TV using “bicuspidization technique,” which converts trileaflet valve in to a bicuspid valve by suturing anteroposterior commissure with septal posterior commissure. With this suture, posterior leaflet would be ligated and inactive. (An: Anterior tricuspid leaflet; P: Posterior tricuspid leaflet; S: Septal tricuspid leaflet).

of the AV and root can help the surgeon choose the best surgical option. In patients with early medical treatment of endocarditis, small perforation can happen on the cusps and patients may present with chronic aortic regurgitation

later (Figs 29.64 to 29.68 and Movie clips 29.64A to D, 29.66A to H). Preoperative delineation of this perforation by 3D TEE may help the surgeon to repair the cusp and preserve the AV.

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

605

B

A

Figs 29.53A and B: Intraoperative assessment of the tricuspid regurgitation (TR) in a 50-year-old male with severe aortic stenosis. (A) Three-dimensional transesophageal echocardiography (3D TEE) surgical view of the tricuspid valve with severely dilated tricuspid annulus; (B) Full-volume color acquisition shows severe TR due to lack of leaflets coaptation.

B

A

Figs 29.54A and B: Immediate postoperative assessment of the tricuspid valve (TV) repair in the previous patient. (A) Three-dimensional transesophageal echocardiography (3D TEE) surgical view shows TV repair with insertion of annuloplasty ring. Edwards MC3 ring was used for this repair. Ring is seated well. The open part of the ring is toward the location of the A–V node to prevent A–V block; (B) 3D full-volume color acquisition confirmed no residual tricuspid regurgitation. Many studies have shown that repair with annuloplasty ring has the best long-term outcome among the different techniques introduced for TV repair.

PROSTHETIC VALVE DYSFUNCTION In the Euro Heart Survey, 28% of patients with valvular heart disease had undergone previous valvular intervention 18% of which was valve repair and 82% valve replacement.30 In mitral and TV repair, most surgeons

use prosthetic annuloplasty rings for prevention of future annular dilatation. These rings can be only a pericardial band, commercial half-ring, or complete flexible or rigid rings. Ring dehiscence is one of the uncommon complications which bring patients back to the hospital because of new valvular regurgitation. Valve replacement

606

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.55A and B: Surgical demonstration of the tricuspid valve repair with insertion of annuloplasty ring. (A) Edwards MC3 #32 is being prepared for placement. This ring is oval-shaped conforming to the configuration of a normal tricuspid orifice. Ring size is selected based on the measurement of the septal leaflet attachment; (B) Ring is in position and appears seated well. Open portion of the ring is toward the anteroseptal commissure.

A

B

Figs 29.56A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 68-year-old man with a history of blunt chest trauma and signs of right side heart failure. (A) 3D TEE modified surgical view shows flail tip of the anterior tricuspid valve leaflet (arrow) due to ruptured head of right ventricular papillary muscle; (B) Same view with full-volume color demonstrates severe tricuspid regurgitation.

is possible by mechanical or bioprosthetic valves. Xenograft valves are either stented or stentless but both types have limited durability and after 10 to 15 years will be degenerated and calcified and need to be re-replaced. Suture-less valves are newly developed technology. These

valves need only three reference sutures to implant the valve and save the pump-time to almost half; therefore, they are an ideal option for high risk patients. Suture-less valves are currently available for aortic position. None of the abovementioned prosthetic valves is perfect to substitute native

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

607

B

Figs 29.57A and B: Surgical repair of the tricuspid valve (TV) in the previous patient. (A) Flail tip of anterior (An) tricuspid leaflet is seen due to ruptured head of anterior papillary muscle of right ventricle. This finding is not uncommon in patients who have had blunt chest trauma because the TV is a very anteriorly located structure compared to the other valves; (B) Flail tip was sutured to the papillary muscle and repair was completed by insertion of a size #34 MC3 annuloplasty ring. Postoperative TEE showed excellent result. (S: Septal tricuspid leaflet).

A

B

Figs 29.58A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 54-year-old female with a history of mitral valve replacement and long-standing tricuspid regurgitation (TR). (A) Surgical view of the tricuspid valve shows severely dilated annulus with a large gap at the middle in systole; (B) The same view during diastole demonstrates how the tricuspid annulus can be measured by calibrated 3D grid or directly in newer echo machines. Tricuspid annulus in this case was measured at 5.3 × 5.3 cm.

valves. In fact, we are changing one disease (diseased native valve) to another type of disease (prosthetic valve). Patient-prosthesis mismatch, thrombosis of the mechanical discs, pannus formation of the sewing ring,

prosthetic valve endocarditis (PVE), periprosthetic abscess formation, and dehiscence of the valve are the most common complications in mechanical valves which create prosthetic valve dysfunction (PVD). Transvalvular

608

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.59A and B: (A) Intraoperative three-dimensional transesophageal echocardiography (3D TEE) with full-volume color acquisition in the previous patient shows severe tricuspid regurgitation (TR); (B) The same after tricuspid valve replacement by a bioprosthetic valve.

A

B

Figs 29.60A and B: (A) Modified surgical view of the tricuspid valve in the previous patient shows insertion of the suture lines to implant a bioprosthetic valve inside the native valve (valve-in-valve). Severe dilatation of the tricuspid annulus and third redo-surgery was the main reason to decide to replace this valve as opposed to repair; (B) Bioprosthetic valve size #33 Magna was placed. Postoperative transesophageal echocardiography (TEE) showed normal functioning prosthetic valve.

or paravalvular regurgitation may happen following the above-mentioned complications. Transesophageal echo and 3D TEE are the only available imaging modality in the operating room which can detect PVD immediately after surgery and provide the surgeon with an opportunity to go back on pump and solve the problem. This modality is an

ideal imaging technique to assess prosthetic valves which are 3D objects in nature. Annuloplasty ring dehiscence is one of the uncommon late complications of the MV repair.31,32 It may happen because of endocarditis but in most cases it is because of the small size ring used during repair. Mitral annular

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

609

B

Figs 29.61A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 15-year-old boy with a history of brucella endocarditis and aortic root abscess. (A) Long-axis view of the aortic root shows large vegetation on the aortic valve. Huge abscess cavity is visualized at the posterior aspect of the aortic root adjacent to the roof of the LA. Abscess cavity has communication with the left ventricular outflow tract (arrow) and is bulging toward the LA; (B) 3D TEE with full-volume color demonstrates to and fro flow to the abscess cavity through the communication site. (Abs: Abscess; AV: Aortic valve; LA: Left atrium; LV: Left ventricle.

A

B

Figs 29.62A and B: Three-dimensional transesophageal echocardiography (3D TEE) of the previous patient showing abscess cavity. (A) 3D TEE short-axis view shows bicuspid aortic valve with multiple vegetations. Large abscess cavity (Abs. cavi) is visualized posterior to the aortic root with multiple septation (honeycomb appearance); (B) 3D full-volume reconstruction of the base of the heart demonstrates location of the abscess cavity (between two black arrows). Abscess is bulging toward the left atrium (LA) from its roof but does not communicate with LA. This 3D view is well correlated with surgical exploration showed in Figure 29.63. (AOV: Aortic valve; BAV: Bicuspid aortic valve; MV: Mitral valve; TV: Tricuspid valve).

geometry changes during cardiac cycle and tension on the ring is the likely cause of suture dehiscence. 3D TEE can detect the site and extension of the suture dehiscence

and evaluate the degree of the para-annular mitral regurgitation (Figs 29.69 to 29.73 and Movie clips 29.69A to H and 29.69A to H).

610

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.63A and B: Surgical exploration of the aortic root in the same patient. (A) Aortic root is visualized through the conventional aortotomy. Cauliflower-shaped multiple vegetations are seen; (B) The aortic root is demonstrated after resection of the vegetations. The internal communication site between the abscess cavity and the posterior aortic root is shown (red arrow). Body of the cavity can be seen from outside toward the roof of the left atrium (black arrows). This patient underwent aortic root replacement by a homograft. Left main coronary artery (LMCA) button is prepared for reimplantation.

A

B

Figs 29.64A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 41-year-old male patient with a history of long-standing infective endocarditis and aortic regurgitation. (A) The bicuspid aortic valve is shown in systole. The larger conjoin cusp is located anteriorly, and the smaller cusp is located posteriorly; (B) Same view in diastole demonstrates large fenestration at the middle of the posterior cusp (red arrows). (LA: Left atrium; RV: Right ventricle).

Bioprosthetic valves degenerate within 10 to 15 years. Some conditions in patient may accelerate this natural process.33 Preoperative 3D TEE can investigate the degree of degeneration, presence of leaflets fenestration and calcification, and degree of the transvalvular regurgitation

(Figs 29.74 to 29.76 and Movie clips 29.74A to C and 29.76A and B). Paravalvular regurgitation (PVR) after surgical valve replacement is more common in mitral position. Early PVR may happen immediately in the operating room because

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

611

B

Figs 29.65A and B: Preoperative three-dimensional transesophageal echocardiography (3D TEE) showing aortic regurgitation (AI) and surgical confirmation. (A) 3D TEE with full-volume color acquisition shows two jets of AI. The larger jet is originated from the large fenestration at the middle of the posterior cusp (red arrow) and the smaller jet is coming from severe prolapse of the conjoined cusp (white arrow); (B) Surgical demonstration of the aortic valve after resection. Fenestration can be seen at the middle of the posterior cusp (red arrow). Note: conjoined cusp at the left coronary side is damaged by endocarditis (white arrow) and was prolapsing during diastole.

A

B

Figs 29.66A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 67-year-old man with endocarditis of aortic valve (AV) and severe aortic regurgitation. (A) Long-axis view of the aortic valve shows multiple vegetations on the right and left coronary cusps (white arrows). (B) Same view with slight counterclockwise rotation demonstrates perforation on the body of the right coronary cusp of AV (black arrow). (LA: Left atrium; LV: Left ventricle).

of technical factors. 3D TEE can detect the location and size of the PVR. If it is hemodynamically significant, the surgeon can go back on pump and solve the problem (resuturing or re-replacement). Late-appearing PVR is associated with suture dehiscence because of infection,

previous annular calcification, or friable/weak tissue at the site of suturing. Small paravalvular leak can create hemolysis but large PVR has hemodynamic consequences and may cause heart failure. Surgical reoperation is the standard choice but if the patient is high risk and leak site

612

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.67A and B: (A) Preoperative three-dimensional transesophageal echocardiography (3D TEE) with full-volume color shows severe eccentric posteriorly directed jet of aortic regurgitation (AI) secondary to a large perforation on RCC; (B) Short-axis view of the aortic valve (surgical view) demonstrates the perforation at the body of the aortic valve (Per). This finding correlates with surgical inspection showed in Figure 29.68. (LCC: Left coronary cusp; NCC: Noncoronary cusp; RCC: Right coronary cusp).

A

B

Figs 29.68A and B: Surgical inspection of the previous patient. (A) Large vegetations are seen at the ventricular side of RCC and LCC; (B) Large perforation on the body of RCC is demonstrated at the same location as was described in three-dimensional transesophageal echocardiography (3D TEE) short-axis view in Figure 29.67. (LCC: Left coronary cusp; NCC: Noncoronary cusp; RCC: Right coronary cusp).

is small and regular, device closure is an alternative choice. Multiple leaks can be closed by multiple devices as well if they have favorite sites and sizes. 3D TEE has a great role in catheterization laboratory to guide the interventionist for PVR device closure.34,35 In the operating room, preoperative

assessment of the prosthetic valve dehiscence by 3D TEE is crucial for decision making.36 After accurate mapping of the entire sewing ring by 3D TEE, the surgeon may decide to resuture the dehisced area or re-replace the prosthetic valve (Figs 29.77 to 29.79 and Movie clips 29.77A to C).

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

613

B

Figs 29.69A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in an 18-year-old boy with a history of mitral valve (MV) repair 1 year ago. (A) 3D TEE surgical view shows large dehiscence of posterior aspect of annuloplasty ring (arrows); (B) Triple display of the same view demonstrates 3D view at the top (a), original 2D TEE view at the bottom left (b), and orthogonal view of that at the bottom right (c). (AV: Aortic valve; CS: Coronary sinus).

A

B

Figs 29.70A and B: Three-dimensional transesophageal echocardiography (3D TEE) full-volume color in the previous patient. (A) Mitral valve from left atrial (LA) side shows that severe para-annular mitral regurgitation (MR) originates mostly through the large dehiscence gap (black arrows). Only a small jet of MR is transvalvular (red arrow); (B) Looking at the MV from the left ventricular side (LV) demonstrates large preflow acceleration (arrows).

Prosthetic MV obstructive and nonobstructive thrombosis may happen because of inadequate anticoagulation or other factors, such as prosthesis thrombogenicity and patientrelated risk factors. Recent European guidelines ranked echocardiography (TTE+TEE)/fluoroscopy as first line for detection and follow up of these patients.18 3D TEE has

an advantage over the fluoroscopy for mitral prosthesis because it can visualize restricted disc motion or total stuck disc, as well as the size and burden of the clots. If medical anticoagulation or fibrinolytic therapy was the preferred choice for the patient, 3D TEE is the best tool to follow the disc motion or size of the clot.37 If surgical option was the choice,

614

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.71A and B: Surgical exploration of the mitral valve in the previous patient. (A) Annuloplasty ring is shown totally dehisced from posterior circumference (arrows); (B) Edward-Physio ring is extracted and demonstrated in surgical orientation. Saddle shape of this ring is very compatible with physiologic function of the mitral annulus. Note: anterior (An) wing of the ring is higher than the other wings. Lateral (L) and medial (M) wings have different height as well. This patient underwent redo mechanical mitral valve replacement. (P: Posterior wing).

A

B

Figs 29.72A and B: Preoperative three-dimensional transesophageal echocardiography (3D TEE) in a 46-year-old male patient with a history of coronary artery bypass grafting (CABG) and mitral valve repair with annuloplasty ring 6 months ago. (A) 3D TEE short-axis view at the level of base of the heart shows dehisced annuloplasty ring (arrows); (B) Surgical zoomed view of the mitral valve with clear visualization of the dehiscence. (AV: Aortic valve; LAA: Left atrial appendage; TV: Tricuspid valve).

again 3D TEE is the best imaging modality for preoperative and postoperative assessment of the procedure (Figs 29.80 and 29.81 and Movie clips 29.80A and B). Aortic valve (AV) replacement with a pulmonary autograft (valve switch or Ross procedure) is a complex

operation which provides excellent hemodynamic results in most patients. This surgery is a good choice for children and young child-bearing females who do not want to use anticoagulation. Dilatation of the pulmonary autograft in aortic position is the most common late complication.38

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

615

B

Figs 29.73A and B: (A) Three-dimensional transesophageal echocardiography (3D TEE) with full-volume color acquisition of previous patient shows two large jets of mitral regurgitation (MR), paravalvular (para. MR), and transvalvular (Val. MR); (B) Surgical inspection confirmed preoperative TEE findings (arrow). Patient underwent mechanical mitral valve replacement.

A

B

Figs 29.74A and B: Three-dimensional transesophageal echocardiography (3D TEE) surgical view of bioprosthetic mitral valve in a 72-year-old female who had mitral valve replacement 15 years ago. (A) Bioprosthetic valve leaflets are severely degenerated with prolapse of two cusps (arrows); (B) Severe mitral regurgitation seen due to prolapsed leaflets (arrows).

False aneurysm formation of the LV outflow tract and aortic autograft because of dehiscence of the sutures is another uncommon late complication of this procedure.39 Preoperative assessment by 3D TEE can delineate exact site of this suture dehiscence and guide the surgeon for re-repair of this complication (Figs 29.82 to 29.84 and Movie clips 29.82A to E).

Prosthetic valve endocarditis (PVE) is the most severe and dangerous form of IE. PVE happens in 1% to 6% of all replaced valves and occurs equally in mechanical and bioprosthetic valves. Aortic PVE is more common in men, whereas prosthetic MV endocarditis is more common in female patients.40 TTE is the first line imaging modality for diagnosis but TEE is mandatory when PVE

616

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.75A and B: Surgical extraction of the bioprosthetic valve in the previous patient. (A) Prosthetic valve from left atrial side shows degeneration and severe prolapse of two cusps (arrows); (B) Same valve from the left ventricular side.

A

B

Figs 29.76A and B: Three-dimensional transesophageal echocardiography (3D TEE) surgical view of bioprosthetic mitral valve in a 69-year-old male who had mitral valve replacement 10 years ago. Patient presented with severe mitral regurgitation. (A) Preoperative 3D TEE shows degenerated bioprosthetic mitral valve with torn leaflet; (B) Surgical inspection of the valve confirmed the preoperative findings. This patient underwent redo mechanical mitral valve replacement. (LAA: Left atrial appendage).

is suspicious. Negative TEE does not rule out PVE. Based on ESC guidelines, surgical intervention is urgent when signs of uncontrolled local infection, such as abscess, false aneurysm, fistula, and enlarging vegetations are present.41 3D TEE is the best imaging modality to detect all of these lethal complications and facilitates decision making for urgent surgical intervention (Figs 29.85 to 29.87 and Movie clips 29.85A to E).

Thrombosis of mechanical AV is less common than mitral position but echocardiographic diagnosis is more challenging than prosthetic MV obstruction. Direct visualization of two aortic discs and opening and closing of them by TTE and even TEE is not easy in every patient. Fluoroscopy is superior to TEE in this complication. Any sudden increase in transvalvular aortic gradient should increase the suspicion (Figs 29.88 to 29.92 and Movie clips

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

617

B

Figs 29.77A and B: Three-dimensional transesophageal echocardiography (3D TEE) in a 35-year-old male patient who had mechanical mitral valve replacement (MVR) 23 years ago. (A) 3D TEE angled view shows dehiscence of large area of sewing ring adjacent to the left atrial appendage (LAA) down to the posterior annulus (arrows); (B) En face view of the MVR demonstrates the large gap created at the dehisced segment (arrows).

A

B

Figs 29.78A and B: (A) Same view of the previous patient with full-volume color shows severe paravalvular mitral regurgitation (MR) originating from the large gap at dehisced area; (B) Color-suppressed mode to confirm the origin of the MR. (LAA: Left atrial appendage).

29.88A and B). Based on ESC guidelines, treatment options for thrombosis of aortic and mitral prosthesis are same; however, fibrinolytic therapy may be slightly superior to surgical treatment in aortic position.42–44 Cardiac CT without contrast is an excellent alternative imaging modality to assess function of double-disc mechanical AV and serial follow up during medical treatment.45

CARDIAC MASSES There are several normal structures inside the heart which may mimic cardiac masses during echocardiography study, such as Eustachian valve, lipomatous hypertrophy of the interatrial septum, Warfarin ridge, inverted left atrial appendage (LAA), spinal cord, and Lambl’s

618

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.79A and B: Surgical exploration of the mechanical mitral valve in the previous patient. (A) Surgical view of the valve shows area of the sewing ring dehiscence exactly as demonstrated by three-dimensional transesophageal echocardiography (3D TEE) (between two arrows); (B) Excised valve from the left atrial side. This patient underwent redo mechanical mitral valve replacement.

A

B

Figs 29.80A and B: Three-dimensional transesophageal echocardiography (3D TEE) of mechanical mitral valve in a 30-year-old female patient who presented to our center with acute pulmonary edema. (A) 3D TEE surgical view of the prosthetic valve in diastole shows that the medial disc is stuck (stuck disc). Lateral disc (moving disc) opened well; (B) Same view with a slight angulation demonstrates that the medial disc is stuck at the semi-open position (arrow). (LAA: Left atrial appendage).

excrescence. Massive hiatus hernia may mimic a left atrial mass. Abnormal intracardiac masses are thrombi and vegetations, and primary and secondary tumors. Echocardiography plays a major role in initial diagnosis of cardiac masses; however, other imaging modalities, such

as CT and cardiac MRI, may have a complementary role for final decision making. Intraoperative TEE, especially 3D TEE, is again the only imaging tool available in the operating room to help the surgeon if resection of the mass is indicated.

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

619

B

Figs 29.81A and B: (A) Same surgical view of the previous patient with color flow in diastole shows large flow from the left atrium to the left ventricle through the lateral disc (LD) but only small flow is crossing the medial disc (small flow); (B) Fluoroscopy of the same patient confirms 3D TEE findings. As demonstrated in this image, during diastole, the lateral disc is fully open but the medial disc is stuck at the semi-open position. This patient was discharged with medical treatment. Note: orientation of the image in fluoroscopy is different from 3D TEE surgical view.

A

B

Figs 29.82A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 25-year-old lady with a history of Ross operation 2 years ago. (A) Long-axis view shows dilated aortic autograft with large communication at the site of suturing to the previous native aortic annulus (black arrow). Huge false aneurysm (False aneu) pocket seen at the posterior aspect of the aortic root between the aorta and the roof of the left atrium; (B) False aneurysm pocket between the aortic root and the left atrium (red arrow). (AV: Aortic valve (autograft); LA: Left atrium; LVOT: Left ventricular outflow tract; RA: Right atrium).

Left atrial appendage is a common site for clot formation if pressure inside the LA is high or the patient is in atrial fibrillation. Visualization of the LAA clot by 2D TTE is not very sensitive. 3D TTE with its ability to

acquire entire LAA in 3D, increases this sensitivity and specificity.46,47 3D TEE is the modality of choice to detect the clot, site of its attachment and differentiation with normal pectina muscle (Fig. 29.93 and Movie clip 29.93). It

620

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.83A and B: Three-dimensional transesophageal echocardiography (3D TEE) with full-volume color showing communication between false aneurysm and aortic autograft. (A) Long-axis view of the aortic root in systole shows flow from LVOT going into false lumen through the two entrances (black arrows). False aneurysm is expanded in systole due to collection of blood inside the pocket; (B) During diastole, blood from the false aneurysm goes back into the left ventricle (black arrows) acting like an aortic regurgitation. Autograft aortic valve (AV) has valvular regurgitation as well due to geometric changes (red arrow). Note: the false aneurysm pocket became smaller in diastole. (AOV: Aortic valve; LA: Left atrium; LVOT: Left ventricular outflow tract).

A

B

Figs 29.84A and B: Surgical inspection of the aortic root in the same patient. (A) All three cusps of aortic autograft seen intact and clean. There is a large whole (between red arrows) just beneath the NCC which communicates the left ventricular outflow tract to the false aneurysm posterior to the aortic root; (B) Communication site was patched by a bovine pericardial patch. After closing the aortic root, a false aneurysm pocket was opened from the outside, the blood inside was drained, and the aneurysm was sutured. (LCC: Left coronary cusp; NCC: Noncoronary cusp; RCC: Right coronary cusp).

is now routinely used before percutaneous mitral balloon valvuloplasty and in the operating room before surgery for rheumatic MV. 3D TEE can detect clot in IVC, right atrium, and pulmonary arteries; however, TEE is not the first

line imaging modality for diagnosis of acute pulmonary embolism (Fig. 29.94 and Movie clip 29.94). Preoperative TEE can detect unnoticed massive pulmonary embolism occurring in the operating room during preparation of the

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

621

B

Figs 29.85A and B: Three-dimensional transesophageal echocardiography (3D TEE) in a 74-old-male patient with a history of bioprosthetic aortic valve replacement (AVR) 6 years ago. Patient presented with 1 month history of fever. (A) Bioprosthetic AVR seen in long-axis view with dehiscence from anterior circumference (red arrow); (B) 3D TEE in short-axis view shows honeycomb appearance all around the bioprosthetic AVR compatible with aortic root abscess (red arrows). (Asc. Aorta: Ascending aorta; LA: Left atrium; NCC: Noncoronary cusp; RA: Right atrium; RCC: Right coronary cusp).

A

B

Figs 29.86A and B: Three-dimensional transesophageal echocardiography (3D TEE) in the same previous patient. (A) Transgastric view shows dehiscence of the bioprosthetic aortic valve (Bio AVR) from posterior aspect (red arrow); (B) 3D TEE with color demonstrates severe paravalvular and transvalvular aortic regurgitation (between arrows). (LA: Left atrium; LVOT: Left ventricular outflow tract).

patient with legs rising.48 The chance of developing an LV clot after an acute myocardial infarction depends on the size and location of the infarction. Large anterior transmural infarction with subsequent LV aneurysm is a risk factor for mural clot formation.49 2D TTE is the main imaging modality, but 3D TTE has additional benefits in terms of identifying the exact location, liquefaction of the clot, and its mobility which

has prognostic implications.50 3D TEE can provide better image quality in the operating room especially if there is any suspicion for primary or secondary cardiac tumor (Fig. 29.95 and Movie clips 29.95A to D). Primary cardiac tumors are rare compared to secondary (metastatic) involvement of the heart. Most of the primary tumors are benign. Myxoma, lipoma, and

622

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.87A and B: Surgical inspection of the aortic root in the previous patient. (A) Bioprosthetic aortic valve seen degenerated with multiple vegetations and abscess cavities. Almost two-thirds of the circumference of the sewing ring is dehisced from native aortic annulus (red curve). Valve is connected with small attachment to the annulus and preoperative TEE during systole showed flying jerky motion of the valve toward the ascending aorta; (B) Explanted valve demonstrates left ventricular side of the prosthetic valve with extensive pannus formation. (SR: Sewing ring).

A

B

Figs 29.88A and B: Two-dimensional transesophageal echocardiography (2D TEE) in a 37-year-old man who presented with shortness of breath. This patient had mechanical aortic valve replacement (AVR) 13 years ago in our center and in all previous echo studies, the gradient across the AVR was less than 30 mm Hg. (A) Long-axis view shows severe systolic turbulence across the AVR; (B) In transgastric view, peak gradient (PIG) across the AVR was measured at 57 mm Hg. (LA: Left atrium; LV: Left ventricle).

fibroelastoma are the three most common benign tumors in adults. Myxoma accounts for 25% of all and is located in the LA in 75% of the cases. Eighteen percent of myxoma is in right atrium, 4% in LV, and 4% in RV. LA myxoma is

usually attached to interatrial septum but it can originate from other parts of LA like the roof, the posterior wall, or MV. A large LA myxoma may obstruct LV filling and present with clinical manifestations of mitral stenosis. Smaller LA

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

623

B

Figs 29.89A and B: Three-dimensional transesophageal echocardiography (3D TEE) of the previous patient. (A) Live 3D TEE in shortaxis view shows only one disc is opening and closing (moving disc); other disc was not well seen; (B) 3D TEE zoom mode in short-axis view again showed only one disc moving. Note: 3D TEE for assessing opening and closing of the mechanical aortic valve discs is not as good as in mechanical mitral valve due to low frame rate of 3D echocardiography. Fluoroscopy and likely CT are the best modalities for aortic position as is shown in the next figures.

A

B

Figs 29.90A and B: Fluoroscopy of mechanical aortic valve in the previous patient. (A) In this view only one disc is seen and was moving. The other disc was not seen well; (B) Both discs are seen but are not very clear. Moving disc (MD) and stuck disc (SD) are demonstrated.

myxoma may be discovered during echocardiography for other indications. Surgical resection is the only choice for treatment. The 3D TEE preoperative assessment can play a crucial role in terms of confirmation of the diagnosis, size, location, and site of attachment of the mass in relation with

other structures, such as MV, aortic root, and pulmonary veins. LA myxoma can have a broad base attachment. The 3D TEE images are very important for the surgeon to apply best approach to access the tumor (left or right atriotomy).51–53 LA myxoma should be resected from the base with some

624

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.91A and B: Noncontrast CT in previous patient. (A) In systole, one disc showed reasonable opening (moving disc, MD), but the other disc is stuck (SD); (B) In diastole, the moving disc is closed but the other disc is stuck (SD) in a semi-open position. Courtesy: Dr Ahmed AL Saileek, KACC.

A

B

Figs 29.92A and B: Surgical inspection of the prosthetic valve in the previous patient. (A) Mechanical prosthesis is shown with one clean moving disc and second stuck disc covered by clots; (B) Valve was explanted. The mechanical valve is shown from left ventricular outflow tract (LVOT) side. The stuck disc is covered with clots. Note: No significant pannus formation was seen at the LVOT side of the valve after 13 years.

normal tissue (safety margin) to prevent recurrence (Figs 29.96 to 29.104 and Movie clips 29.96A and B, 29.98A and B, 29.100A to C, and 29.103A to C). Papillary fibroelastoma or papilloma is the third most common benign tumor of the heart in adults. Its appearance is like sea anemones. It is attached to the valve most of the time.

AV is the most common involved valve. Fibroelastoma can be multiple on one valve or multiple valves. Its size varies from 2 mm to 7 cm. Fibroelastoma has tendency for embolization especially in aortic position. Surgery is recommended in patients who had embolic events, if tumor is larger than 1 cm, or if it is highly mobile.54–56

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

625

B

Figs 29.93A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 36-year-old man with severe mitral stenosis undergoing mitral valve replacement. (A) Short-axis view at the base of the heart shows the four valves together. A large clot is seen in the left atrial appendage (LAA) protruding into the left atrium (LA); (B) 3D TEE surgical view of the LAA demonstrates the same clot toward the left of the surgeon. (AOV: Aortic valve; MV: Mitral valve; MPA: Main pulmonary artery; TV: Tricuspid valve).

A

B

Figs 29.94A and B: Three-dimensional transesophageal echocardiography (3D TEE) in a 65-year-old male patient admitted in to the cardiology ward to have coronary artery bypass grafting (CABG). The patient developed sudden onset of shortness of breath and hypotension when walking to the bath room. (A) TEE showed multiple clots in the right atrium, right ventricle, and pulmonary arteries; (B) The patient was taken to the operating room and all of these clots were removed from the right side chambers. (RA: Right atrium; RV: Right ventricle).

Preoperative 3D TEE assessment is the best tool to evaluate the size, location, and degree of invasion to the leaflet which are necessary information for the surgeon to preserve the valve (Figs 29.105 to 29.108 and Movie clips 29.105A and B and 29.108A and B).

Metastatic involvement of the heart is relatively common compared to primary malignant tumor of the heart. In one of the largest autopsy series of patients dying of cancer, 8% had metastasis of the heart.57 Metastasis to the heart can happen from direct invasion from the

626

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.95A and B: Three-dimensional transesophageal echocardiography (3D TEE) and surgical exploration in a 38-year-old male with a history of myocardial infarction 8 months ago. The patient has a history of right leg amputation due to peripheral embolic event. (A) 3D TEE full volume shows a large mass attached to the left ventricular apex likely representing a clot (black arrows); (B) After 3 weeks of treatment with heparin, a decision was made to take the patient to the operating room and the mass was resected. Pathology examination confirmed diagnosis of organized clot. (LA: Left atrium; LV: Left ventricle).

A

B

Figs 29.96A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 68-year-old female who presented with palpitations. (A) 3D TEE surgical view of the left atrium (LA) shows broad base mass (arrows) attached to the roof of the LA adjacent to the aortic root; (B) Long-axis view demonstrates location of the mass in relation with the aortic valve (AOV). (IAS: Interatrial septum; MV: Mitral valve; TV: Tricuspid valve).

mediastinum to the pericardium and the heart, tumor growth from IVC or hematogenous invasion. Most common metastatic tumors of left heart are melanoma, lung cancer, and breast cancer. Metastasis to the right side of the heart are more common from soft tissue sarcomas,

renal cell carcinoma and hypernephroma, esophageal cancer, hepatocellular carcinoma, thyroid cancer, and leiomyomatosis and leiomyosarcoma. There is high prevalence of metastasis to the heart with leukemia and lymphoma. Metastatic osteosarcomas of the heart are not

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

627

B

Figs 29.97A and B: Three-dimensional transesophageal echocardiography (3D TEE) surgical view of the mass in the previous patient compared to excised mass. (A) Mass weight can be estimated by calibrated 3D grid. Mass dimensions are about 2.2 × 2.0 × 1.5 cm, which gives mass weight of about 7 to 8 g; (B) Surgically excised mass is demonstrated with a weight of 8 g. Result of pathology was left atrial myxoma. (AOV: Aortic valve; MV: Mitral valve; TV: Tricuspid valve).

A

B

Figs 29.98A and B: Large left atrial myxoma in a 57-year-old man who presented with palpitations. (A) Two-dimensional (2D) TEE fourchamber view shows large left atrial myxoma attached to the fossa ovalis; (B) Three-dimensional (3D) TEE full volume demonstrates large myxoma with wide pedicle attached to the fossa ovalis. Weight of the mass can be estimated by 3D grid. (LA: Left atrium; LV: Left ventricle; TEE: Transesophageal echocardiography).

common but can happen in right and left heart. Palliative surgery and debulking of the tumor combined with chemotherapy is recommended.58 Leiomyosarcoma is a rare tumor with poor survival. It can metastasize the right and left heart. In the LA mimics LA myxoma but usually pulmonary veins are involved.59 Follicular

carcinoma of the thyroid metastasizing the heart is extremely rare. Extended tumor thrombus may cause SVC syndrome. Radical resection of the tumor and reconstruction of SVC is the treatment of choice60,61 (Figs 29.109 to 29.111 and Movie clips 29.109A and B, 29.110A and B, 29.111A).

628

Section 2: Echocardiography/Ultrasound Examination and Training

B

A

Figs 29.99A and B: Three-dimensional transesophageal echocardiography (3D TEE) surgical view of the left atrial myxoma in the previous patient compared to excised mass. (A) 3D TEE in long-axis view shows that mass drops into the mitral orifice during diastole; (B) Surgically excised mass is demonstrated with weight of about 100 g. Result of pathology was left atrial myxoma. (LA: Left atrium; LV: Left ventricle; AOV: Aortic valve).

B

A

Figs 29.100A and B: Intraoperative transesophageal echocardiography (TEE) in a 39-year-old male presented to our center due to stroke. (A) 2D TEE long-axis view shows large left atrial myxoma attached to the base of the aortic root; (B) 3D TEE in a triple-display format demonstrates broad base attachment of myxoma to the roof of the left atrium and aortic root. Tumor does not interfere with the function of the mitral valve. (AOV: Aortic valve; LA: Left atrium; LV: Left ventricle).

LIMITATIONS OF 3D TEE, FUTURE DIRECTIONS Three-dimensional (3D) echocardiography and 3D TEE like any other new technique has its own limitations such as the following:

1. It is a transitional technique; therefore, 2D TEE is still needed for confirmation of diagnosis. 2. It has a challenging learning curve. 3. It has lower spatial and temporal resolutions compared to 2D TEE.

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

629

B

Figs 29.101A and B: (A) Triple-display of three-dimensional transesophageal echocardiography (3D TEE) in the same patient to demonstrate exact location of the myxoma attachment. This view shows that mass is away from the mitral valve (MV) but relation with interatrial septum (IAS) is not clear; (B) Surgical view of the myxoma demonstrates that most of the attachment of the myxoma is with left atrial roof and aortic root (black arrows). Only a small portion of the mass is attached to the IAS (red arrow). Definition of this attachment is important for the surgeon to choose right or left atriotomy for mass resection. (CS: Coronary sinus; MV: Mitral valve).

A

B

Figs 29.102A and B: (A) Excised myxoma from the posterior side shows broad attachment site to the roof of the left atrium and aortic root (black arrows). Only a small portion was attached to the interatrial septum (red arrows) as was defined by preoperative threedimensional transesophageal echocardiography (3D TEE). Myxoma was resected via right atriotomy; (B) Mass is shown from anterior side with gelatinous appearance.

4. Motion and stitch artifacts during full-volume acquisition with or without color are a substantial limitation (Fig. 29.112 and Movie clips 29.112A and B). This problem can be overcome in the operating room by stopping the breathing machine for 10 to 20 seconds and acquiring the image.

5. There is no valid direct measurement on 3D images. Existing 3D grid and calibration measures 2D distance on a 3D image without measuring the depth of the image. Future direction of 3D echocardiography should be toward improving spatial resolution and single beat acquisition with a high frame rate.

630

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.103A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 49-year-old man who presented to our hospital with stroke. (A) A mass is seen attached to the left atrial (LA) side of the interatrial septum (IAS). A second highly mobile mass was seen (black arrow), which appeared in some view as another separate mass; (B) 3D triple-display format demonstrates that there is only one mass but has a long snake-shaped tail. The base of the mass is attached to the posterior fossa ovalis close to the entrance of the inferior vena cava (IVC). (LA: Left atrium; RA: Right atrium).

A

B

Figs 29.104A and B: Excellent correlation between preoperative three-dimensional transesophageal echocardiography (3D TEE) image of the previous patient and surgical specimen. (A) Preoperative image shows attachment of the mass, bulky base, and 4- to 5-cm long snake-shaped tail; (B) At surgery from right atrial approach, all 3D findings were confirmed. A small segment of interatrial septum (between black arrows) were resected with the mass and then directly sutured. Mass was sent to pathology which confirmed diagnosis of left atrial myxoma.

SUMMARY AND CONCLUSION Three-dimensional echocardiography provides a new dimension in cardiovascular imaging. In fact, it has been a revolution in the field of echocardiography to assess cardiac pathology and guide the appropriate intervention.

3D TEE creates a common language between cardiologist, cardiac surgeon, and interventionist in the operating room and in the cath laboratory for decision making. Like any other new technique, 3D echo has its own limitations and needs further technical improvement.

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

631

B

Figs 29.105A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in an 81-year-old man who presented to our hospital with acute pulmonary edema. Preoperative echo showed normal systolic function. Coronary angiography was normal. (A) Long-axis view shows two mobile masses on the aortic side of the leaflets (arrows); one measured at 1.0 × 0.5 cm and the second at 0.5 × 0.5 cm; (B) In short-axis view, a larger mass is connected to the commissure between the left coronary cusp (LCC) and the right coronary cusp (RCC). (LA: Left atrium; LV: Left ventricle; NCC: Noncoronary cusp; RA: Right atrium; RV: Right ventricle).

A

B

Figs 29.106A and B: Surgical findings in the previous patient. (A) A larger mass is seen attached to the commissure between the left coronary cusp (LCC) and the right coronary cusp (RCC) by a long pedicle. Mass was resected; (B) A second smaller mass was seen attached to the LCC and was resected. Aortic valve needs some minor repair which was done. Postoperative TEE showed no aortic regurgitation. Frozen section pathology examination was done in the operating room and the result was fibroelastoma in both masses. (NCC: Noncoronary cusp). Note: cause for presenting acute pulmonary edema in this patient was likely intermittent closure of the ostium of the left main coronary artery by the larger mass. During 1 year follow-up, this pulmonary edema has not occurred again.

632

A

Section 2: Echocardiography/Ultrasound Examination and Training

B

Figs 29.107A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 40-year-old man who presented to our center with stroke. (A) Long-axis view shows a large mass measured at 1.5 × 1.8 cm attached to the left ventricular (LV) side of the anterior mitral valve leaflet (AMVL); (B) Mass seen from the LV side and appears to invade into the AMVL tissue (red arrows). No Doppler signs of mitral regurgitation or stenosis were found. (LA: Left atrium; LVOT: Left ventricular outflow tract).

A

B

Figs 29.108A and B: Surgical exploration of the previous patient. (A) Surgical view from the left atrial side demonstrates mass invasion to the ventricular side of the anterior mitral valve leaflet (AMVL) tip. Care was given to resect the mass with part of the AMVL tissue to have a safety margin to prevent recurrence; (B) This view shows at least two chorda (black arrows) are involved by the mass which had to be resected. Mass was sent to the pathology laboratory inside the operating room for initial diagnosis. Result was reported as fibroelastoma. AMVL was reconstructed by a treated autologous pericardial patch and two chorda were replaced. Postoperative transesophageal echocardiography (TEE) showed no mitral stenosis or regurgitation.

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

A

633

B

Figs 29.109A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 22-year-old lady with osteosarcoma metastasis to the right atrium (RA). (A) 3D TEE bicaval view shows large mass filling the inferior vena cava (IVC) and invading into the RA. Due to risk of obstruction to the tricuspid valve, this patient was taken to the operating room for debulking the tumor; (B) Surgical resection of the mass from IVC (black arrows). Pathology confirmed the metastasis. (LA: Left atrium; SVC: Superior vena cava).

A

B

Figs 29.110A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) in a 50-year-old female with 4 years’ history of leiomyosarcoma. (A) Preoperative TEE shows a huge mass occupying the entire left atrium (LA). Mass is likely attached to the posterior wall of the LA; (B) Mass was resected surgically. Pedicle was attached to the junction of the right upper pulmonary vein to the LA. Mass weighing 110 g. Pathology examination confirmed the diagnosis of metastatic leiomyosarcoma to the LA. (AOV: Aortic valve; RA: Right atrium).

634

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 29.111A and B: Intraoperative three-dimensional transesophageal echocardiography (3D TEE) assessment of a 53-year-old female patient with a history of follicular cancer of the thyroid. (A) 3D TEE shows a large mass invading from superior vena cava (SVC) to the right atrium (RA). Mass demonstrates liquefaction at the middle likely due to necrosis; (B) Tumor was resected.

A

B

Figs 29.112A and B: Stitch artifact in three-dimensional (3D) full-volume acquisition when machine is stitching 7, 10, or 14 beats together to create a full-volume 3D data set. This artifact is one of the most common limitations of 3D echocardiography. It is more common in patients with arrhythmia or due to cardiac motion and translation. Asking the patient to hold breath for 10 to 20 seconds or stopping the anesthesia machine in the operating room may decrease the chance of this artifact. (A) Stitch artifact after Amplatzer device implantation for atrial septal defect (black arrows); (B) Stitch artifact in a patient after mechanical mitral valve replacement (black arrows).

ACKNOWLEDGMENTS I would like to thank Dr Hani Najm, Head of Cardiac Surgery at our center, for the majority of the surgical cases in this chapter and his great effort in providing quality surgical movies. I would also like to thank our other talented surgeons, Dr Al-Khaldi, Dr Arifi and Dr Al-Ghamdi for their contributions.

I would like to offer special thanks to the operating room nursing team who made the extra effort to expertly record movies of these surgical cases. The support of the chairman of the cardiac center, Dr Muayed Al-Zaibag, my colleagues and cardiac sonographers while preparing this chapter is greatly appreciated. I am grateful for the patience and encouragement of my wife Rokhsareh and my children, Sina and Setareh which made this work possible.

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

REFERENCES 1. Carpentier A. Cardiac valve surgery—the “French correction.” J Thorac Cardiovasc Surg. 1983;86(3):323–37. 2. Ahmad RM, Gillinov AM, McCarthy PM, et al. Annular geometry and motion in human ischemic mitral regurgitation: novel assessment with three-dimensional echocardiography and computer reconstruction. Ann Thorac Surg. 2004;78(6):2063–8; discussion 2068. 3. Omran AS, Woo A, David TE, et al. Intraoperative transesophageal echocardiography accurately predicts mitral valve anatomy and suitability for repair. J Am Soc Echocardiogr. 2002;15(9):950–7. 4. Omran AS. Role of transesophageal echocardiography in mitral valve repair. In: Hutchison SJ, editor. Principles of Echocardiography and Intracardiac Echocardiography. 1st ed. Philadelphia: Elsevier-Saunders; 2012:337–69. 5. Lang RM, Badano LP, Tsang W, et al.; American Society of Echocardiography; European Association of Echocardiography. EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. J Am Soc Echocardiogr. 2012;25(1): 3–46. 6. Biaggi P, Gruner C, Jedrzkiewicz S, et al. Assessment of mitral valve prolapse by 3D TEE angled views are key. JACC Cardiovasc Imaging. 2011;4(1):94–7. 7. David TE, Omran A, Armstrong S, Sun Z, Ivanov J. Longterm results of mitral valve repair for myxomatous disease with and without chordal replacement with expanded polytetrafluoroethylene sutures. J Thorac Cardiovasc Surg. 1998;115(6):1279–85; discussion 1285. 8. Dreyfus J, Brochet E, Lepage L, et al. Real-time 3D transoesophageal measurement of the mitral valve area in patients with mitral stenosis. Eur J Echocardiogr. 2011; 12(10):750–5. 9. Schlosshan D, Aggarwal G, Mathur G, Allan R, Cranney G. Real-time 3D transesophageal echocardiography for the evaluation of rheumatic mitral stenosis. JACC Cardiovasc Imaging. 2011;4(6):580–8. 10. Scandura S, Cammalleri V, Caggegi A, et al. Threedimensional echocardiographic and surgical findings in mitral mechanical valve dysfunction. J Cardiovasc Med (Hagerstown). 2013;14(4):317–18. 11. Greenhouse DG, Dellis SL, Schwartz CF, et al. Regional changes in coaptation geometry after reduction annuloplasty for functional mitral regurgitation. Ann Thorac Surg. 2012;93(6):1876–80. 12. Haj-Ali R, Marom G, Ben Zekry S, et al. A general threedimensional parametric geometry of the native aortic valve and root for biomechanical modeling. J Biomech. 2012; 45(14):2392–7. 13. Sohmer B, Hudson C, Atherstone J, et al. Measuring aortic valve coaptation surface area using three-dimensional transesophageal echocardiography. Can J Anaesth. 2013; 60(1):24–31.

635

14. Furukawa A, Abe Y, Tanaka C, et al. Comparison of twodimensional and real-time three-dimensional transesophageal echocardiography in the assessment of aortic valve area. J Cardiol. 2012;59(3):337–43. 15. Calleja A, Thavendiranathan P, Ionasec RI, et al. Automated quantitative 3-dimensional modeling of the aortic valve and root by 3-dimensional transesophageal echocardiography in normals, aortic regurgitation, and aortic stenosis: comparison to computed tomography in normals and clinical implications. Circ Cardiovasc Imaging. 2013; 6(1):99–108. 16. Mascherbauer J, Maurer G. The forgotten valve: lessons to be learned in tricuspid regurgitation. Eur Heart J. 2010; 31(23):2841–3. 17. Anwar AM, Soliman OI, Nemes A, et al. Value of assessment of tricuspid annulus: real-time three-dimensional echocardiography and magnetic resonance imaging. Int J Cardiovasc Imaging. 2007;23(6):701–5. 18. Vahanian A, Alfieri O, Andreotti F, et al.; ESC Committee for Practice Guidelines (CPG); Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg. 2012;42(4):S1–44. 19. Badano LP, Muraru D, Enriquez-Sarano M. Assessment of functional tricuspid regurgitation. Eur Heart J. 2013;34(25): 1875–85. 20. Kirkpatrick JN, Lang RM. Surgical echocardiography of heart valves: a primer for the cardiovascular surgeon. Semin Thorac Cardiovasc Surg. 2010;22(3):200.e1–200.22. 21. Aykut K, Kaya M, Acikel U. Rupture of the tricuspid valve due to smashing the chest into the steering wheel. Ann Thorac Cardiovasc Surg. 2013;19(3):222–4. 22. Castonguay MC, Burner KD, Edwards WD, Baddour LM, Maleszewski JJ. Surgical pathology of native valve endocarditis in 310 specimens from 287 patients (19852004). Cardiovasc Pathol. 2013;22(1):19–27. 23. Sedgwick JF, Burstow DJ. Update on echocardiography in the management of infective endocarditis. Curr Infect Dis Rep. 2012;14(4):373–80. 24. Raju IT, Solanki R, Patnaik AN, Barik RC, Kumari NR, Gulati AS. Brucella endocarditis - A series of five case reports. Indian Heart J. 2013;65(1):72–7. 25. Sadat K, Joshi D, Sudhakar S, et al. Incremental role of three-dimensional transesophageal echocardiography in the assessment of mitral-aortic intervalvular fibrosa abscess. Echocardiography. 2012;29(6):742–4. 26. Okada K, Okita Y. Surgical treatment for aortic periannular abscess/pseudoaneurysm caused by infective endocarditis. Gen Thorac Cardiovasc Surg. 2013;61(4):175–81.

636

Section 2: Echocardiography/Ultrasound Examination and Training

27. Siu SC, Silversides CK. Bicuspid aortic valve disease. J Am Coll Cardiol. 2010;55(25):2789–800. 28. Ruparelia N, Lawrence D, Elkington A. Bicuspid aortic valve endocarditis complicated by mitral valve aneurysm. J Card Surg. 2011;26(3):284–6. 29. Hara T, Soeki T, Niki T, et al. Bicuspid aortic valve endocarditis complicated by perivalvular abscess. J Med Invest. 2012;59(3-4):261–5. 30. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J. 2003;24(13):1231–43. 31. Kronzon I, Sugeng L, Perk G, et al. Real-time 3-dimensional transesophageal echocardiography in the evaluation of post-operative mitral annuloplasty ring and prosthetic valve dehiscence. J Am Coll Cardiol. 2009;53(17):1543–7. 32. Aggarwal G, Schlosshan D, Mathur G, et al. Recurrent ischaemic mitral regurgitation post mitral annuloplasty due to suture dehiscence evaluated using real time three dimensional transoesophageal echocardiography. Heart Lung Circ. 2012;21(12):844–6. 33. Meyer SR, Suri RM, Wright RS, et al. Does metabolic syndrome influence bioprosthetic mitral valve degeneration and reoperation rate? J Card Surg. 2012;27(2):146–51. 34. Zamorano JL, Badano LP, Bruce C, et al. EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. J Am Soc Echocardiogr. 2011;24(9):937–65. 35. Nikolic A, Schranz D, Hristov N, et al. Amplatzer occlusion of paravalvular leak of mitral mechanical prosthesis following a reoperation for thrombosed mitral mechanical prosthesis. Interact Cardiovasc Thorac Surg. 2008;7(5): 941–2. 36. Yildiz M, Duran NE, Gökdeniz T, et al. The value of realtime three-dimensional transesophageal echocardiography in the assessment of paravalvular leak origin following prosthetic mitral valve replacement. Turk Kardiyol Dern Ars. 2009;37(6):371–7. 37. Armellini I, Rubimbura V, Morocutti G, et al. Thrombotic obstruction of mechanical prosthetic valve in mitral position the old “x-ray” fights the new 3-dimensional transesophageal echocardiography. J Am Coll Cardiol. 2012;59(6):e11. 38. David TE, Omran A, Ivanov J, et al. Dilation of the pulmonary autograft after the Ross procedure. J Thorac Cardiovasc Surg. 2000;119(2):210–20. 39. Shahid MS, Al-Halees Z, Khan SM, Pieters FA. Aneurysms complicating pulmonary autograft procedure for aortic valve replacement. Ann Thorac Surg. 1999;68(5):1842–3. 40. Lee JH, Burner KD, Fealey ME, et al. Prosthetic valve endocarditis: clinicopathological correlates in 122 surgical specimens from 116 patients (1985-2004). Cardiovasc Pathol. 2011;20(1):26–35. 41. Habib G, Hoen B, Tornos P, et al.; ESC Committee for Practice Guidelines. Guidelines on the prevention, diagnosis, and

42.

43.

44. 45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009;30(19):2369–413. Cáceres-Lóriga FM, Pérez-López H, Morlans-Hernández K, et al. Thrombolysis as first choice therapy in prosthetic heart valve thrombosis. A study of 68 patients. J Thromb Thrombolysis. 2006;21(2):185–90. Yay K, Boysan E, Irdem A, et al. Treatment of mechanical aortic valve thrombosis: fibrinolytic treatment versus surgical intervention: result of eight cases. Innovations (Phila). 2010;5(6):439–43. Shapira Y, Vaturi M, Sagie A. Obstructive left-sided prosthetic valve thrombosis. Acute Card Care. 2009;11(3):160–8. Chan J, Marwan M, Schepis T, et al. Images in cardiovascular medicine. Cardiac CT assessment of prosthetic aortic valve dysfunction secondary to acute thrombosis and response to thrombolysis. Circulation. 2009;120(19):1933–4. Kumar V, Nanda NC. Is it time to move on from twodimensional transesophageal to three-dimensional transthoracic echocardiography for assessment of left atrial appendage? Review of existing literature. Echocardiography. 2012;29(1):112–16. Manjunath CN, Srinivasa KH, Panneerselvam A, et al. Incidence and predictors of left atrial thrombus in patients with rheumatic mitral stenosis and sinus rhythm: a transesophageal echocardiographic study. Echocardiography. 2011;28(4):457–60. Jha NK, Rezk AI, Omran AS, et al. Acute pulmonary thromboembolism during mitral valve repair. Heart Lung Circ. 2008;17(2):159–61. Visser CA, Kan G, Meltzer RS, et al. Embolic potential of left ventricular thrombus after myocardial infarction: a two-dimensional echocardiographic study of 119 patients. J Am Coll Cardiol. 1985;5(6):1276–80. Duncan K, Nanda NC, Foster WA, et al. Incremental value of live/real time three-dimensional transthoracic echocardiography in the assessment of left ventricular thrombi. Echocardiography. 2006;23(1):68–72. Pearce AW, Rana BS, O’Donovan DG. Lesson of the month. (2). Stroke in a 53-year-old woman: getting to the heart of the problem. Diagnosis. LA myxoma. Clin Med. 2013;13(1):106–9. Aroca A, Mesa JM, Dominguez F, et al. Multiple recurrence of a “sporadic” (non-familial) cardiac myxoma. Eur J Cardiothorac Surg. 1996; 10(10):919–21. Garatti A, Nano G, Canziani A, et al. Surgical excision of cardiac myxomas: twenty years experience at a single institution. Ann Thorac Surg. 2012;93(3):825–31. Evans AJ, Butany J, Omran AS, et al. Incidental detection of an aortic valve papillary fibroelastoma by echocardiography in an asymptomatic patient presenting with hypertension. Can J Cardiol. 1997;13(10):905–8.

Chapter 29: Three-Dimensional Echocardiography in the Operating Room

55. Buppajarntham S, Satitthummanid S, Chantranuwatana P, et al. Aortic valve papillary fibroelastoma associated with severe aortic regurgitation: a comprehensive assessment with 2- and 3-dimensional transesophageal echocardiography. J Am Coll Cardiol. 2012;60(23):e41. 56. Val-Bernal JF, Mayorga M, Garijo MF, et al. Cardiac papillary fibroelastoma: Retrospective clinicopathologic study of 17 tumors with resection at a single institution and literature review. Pathol Res Pract. 2013; Feb 27 [Epub ahead of print] 57. Silvestri F, Bussani R, Pavletic N, et al. Metastases of the heart and pericardium. G Ital Cardiol. 1997;27(12): 1252–5.

637

58. Iyigun T, Ciloglu U, Ariturk C, et al. Recurrent cardiac metastasis of primary femoral osteosarcoma: a case report. Heart Surg Forum. 2010;13(5):E333–5. 59. Deniz H, Koruk S, Kirbas A, et al. Leiomyosarcoma protruding into the left ventricle during diastole: report of a case. Heart Surg Forum. 2011;14(2):E133–4. 60. Catford SR, Lee KT, Pace MD, et al. Cardiac metastasis from thyroid carcinoma. Thyroid. 2011;21(8):855–66. 61. Wada N, Masudo K, Hirakawa S, et al. Superior vena cava (SVC) reconstruction using autologous tissue in two cases of differentiated thyroid carcinoma presenting with SVC syndrome. World J Surg Oncol. 2009;7:75.

CHAPTER 30 Epiaortic Ultrasonography Dheeraj Arora, Yatin Mehta

Snapshot ¾¾ Background for Epiaortic Ultrasonography

Examination ¾¾ Indications ¾¾ Epiaortic Probe and Preparation

INTRODUCTION Intraoperative echocardiography, particularly transeso­ phageal echocardiography (TEE) has become an important diagnostic and monitoring tool in cardiac surgery. However, the diagnosis and extent of pathology in the distal ascending aorta and aortic arch are not accurately assessed by TEE due to interposition of the right main stem bronchus with air between probe and ascending aorta.1 The most common finding in these areas is the atherosclerotic plaque which is often missed by TEE or underestimated by surgical palpation. Atherosclerosis of the ascending aorta and arch is an important determinant of neurological events after cardiac surgery particularly in elderly population.2 Therefore, epiaortic ultrasonography (EAU) since a decade has gained importance in detecting aortic pathology intraoperatively. Recently, the Society of Cardiovascular Anesthesiologists (SCA), the American Society of Anesthesiologists (ASA), and the American Society of Echocardiography (ASE) have published guidelines specifically focused on acquisition techniques and indications for EAU.3

BACKGROUND FOR EPIAORTIC ULTRASONOGRAPHY EXAMINATION The incidence of perioperative neurological morbidity, especially stroke, varies from 1.9% to 8.8% after a variety

¾¾ Imaging Views/Planes ¾¾ Role of Epiaortic Ultrasonography in Aortic Pathology ¾¾ Advantages of Three-Dimensions over

Two-Dimensions in Epiaortic Ultrasonography

of cardiac surgical procedures.4,5 Advanced age, female sex, history of cerebrovascular disease and/or peripheral vascular disease, diabetes, hypertension, previous cardiac surgery, preoperative infection, urgent surgery, cardio­ pulmonary bypass (CPB) duration > 2 hours, massive transfusion of blood or blood products, and proximal aortic atherosclerosis or a calcified aorta are major risk factors for perioperative stroke.6,7 Identification of aortic atheromatous plaque has been found to be superior with EAU examination than with TEE8 and surgical techniques have also been modified by the use of EAU.9

INDICATIONS3 • Increased risk for perioperative embolic stroke includ­ ing those patients with a history of cerebrovascular or peripheral vascular disease. • Evidence of aortic atherosclerosis or calcification by other imaging modalities like TEE, magnetic resonance imaging, CT scan, or chest radiograph.

EPIAORTIC PROBE AND PREPARATION Epiaortic ultrasonography requires placement of the ultrasonic probe on the surface of aorta under strict aseptic precautions. Due to the proximity of the probe to the aorta, these techniques typically use higher frequency probes (5–12 MHz; Fig. 30.1). The images may only be

Chapter 30:  Epiaortic Ultrasonography

639

Fig. 30.1: Ultrasonic probes for epiaortic scanning.

Fig. 30.2: Placement of ultrasonic probe on the ascending aorta.

obtained by a surgeon or echocardiographer under aseptic precautions wearing a sterile gown and gloves. The probe is placed in a sterile sheath along with sterile ultrasound transmission gel or saline in order to optimize acoustic transmission. Warm sterile saline should also be poured into the mediastinal cavity to further enhance acoustic transmission from the probe to the aortic surface (Figs 30.2 and 30.3). Depth, transmit focus, gain, and transducer frequency may further be adjusted. Three types of transducers are used for EAU examination providing different quality of aortic images: • Linear sequential array transducer: It creates a rectan­ gular image and the entire aorta is not included in a single image. • Phased array transducer: The probe (>7 MHz) is placed approximately 1 cm above the aorta for an optimal fan or sector shape image. The entire aorta can usu­ ally be seen in a single long-axis (LAX) imaging plane. • Matrix-array transducer: It gives real time, threedimensional (3D) images in the form of a pyramidal volume. It enables two-dimensional (2D) images in two planes, thus avoiding physically turning the probe to obtain LAX and short-axis (SAX) image. Moreover, it provides better resolution of the ascending aorta.

of the ascending aorta from the sinotubular junction to the origin of the innominate artery, and the aortic arch.3 The SAX and LAX views (Figs 30.4 and 30.5) should examine the ascending aorta in proximal, mid, and distal segments. LAX view should also include visualization of the proximal arch and origin of the three arch vessels. The ASE/SCA guidelines also recommend that the ascending aorta be divided into 12 areas including the anterior, posterior, left, and right lateral walls within the proximal, mid, and distal ascending aorta segments (Figs 30.4 and 30.5). • Proximal segment: It is defined as the region from the sinotubular junction to the proximal intersection of the right pulmonary artery (RPA). • Mid segment: It is the portion of the aorta that is adjacent to the RPA. • Distal segment: It extends from the distal intersection of the RPA to the origin of the innominate artery. SAX—The ultrasound probe is positioned on the ascending aorta proximal to the aortic valve (AV), with the orientation marker directed toward the patient’s left shoulder to obtain an imaging window that is perpen­ dicular to the LAX of the aorta. After identifying the proximal ascending aorta and AV, slowly advancing the probe distally in a cephalad direction along the aorta allows visualization of the mid ascending aorta, and the distal ascending aorta toward the aortic arch at the origin of the innominate artery. Further advancement will lead to visualization of proximal aortic arch.3

IMAGING VIEWS/PLANES ASE/SCA-recommended epiaortic ultrasound exami­ nation includes a minimum of five views for the evaluation

640

Section 2:  Echocardiography/Ultrasound Examination and Training

Fig. 30.3: Placement of probe in a sterile sheath.

Fig. 30.5: Long-axis view of ascending aorta showing proximal, mid, and distal segments. (RPA: Right pulmonary artery).

LAX—This view can be achieved by rotating the probe 90° from the SAX orientation. Sinus of Valsalva, sinotubular junction, and AV can be visualized proximally and the probe can be advanced cephalad keeping the aorta in LAX. Imaging of the aorta should further extend toward the aortic arch with visualization of the innominate, left common carotid, and left subclavian artery origins.

ROLE OF EPIAORTIC ULTRASONOGRAPHY IN AORTIC PATHOLOGY Aortic Atherosclerosis A primary advantage of EAU examination is grading and quantification of aortic atherosclerosis. It is an important

Fig. 30.4: Short-axis view of ascending aorta showing right lateral (RL), left lateral (LL), anterior (A), and posterior (P) walls. (RPA: Right pulmonary artery; SVC: Superior vena cava).

tool to quantify the degree of plaque formation within the aorta.10 Moreover, the degree of atherosclerosis has been shown to predict the incidence of postoperative renal dysfunction, long-term neurological outcome, and mortality.11 Intraoperative aortic manipulation like cannulation or cross clamping can also be guided by ultrasonography to the plaque-free sites.12 In a survey, EAU of the ascending aorta increased from 45.3% in 2002 to 89.4% in 2009 and aortic cross clamp use decreased from 97.7% of cases to 72.7%.13 Grading of atherosclerosis is done by various authors depending upon the size and site of atheroma or presence of any mobile component. Some institutions follow their own protocols for the grading of atheroma. Katz et al.14 introduced the grading system based on TEE on a fivepoint scale with outcome as stroke. • Grade I: Normal to mild intimal thickening • Grade II: Severe intimal thickening without protru­ding atheroma • Grade III: Atheroma protruding ≤ 5 mm into lumen • Grade IV: Atheroma protruding ≥ 5 mm into lumen • Grade V: Any thickness with a mobile component or components. Nohara et al.15 also studied the plaque density of aortic atheroma in coronary artery bypass grafting and the incidence of stroke. They suggested that a computer analysis of aortic atheromatous plaque was useful in patients who had a high risk of postoperative stroke or embolism and helped in decreasing its incidence. • Grade I: Normal or thickening of the intima extending < 3 mm into the aortic lumen

Chapter 30:  Epiaortic Ultrasonography

641

important for DeBekay type II dissection, which is usually missed in the region of distal ascending aorta and aortic arch.17

Role of Three-Dimensional Epiaortic Ultrasonography

Fig. 30.6: Short-axis view of aorta showing plaque height.

• Grade II: Smooth-surfaced plaques and thickening of the intima extending >3 mm into the aortic lumen • Grade III: Marked irregularity of the intimal surface and thickening of the intima extending >3 mm into the aortic lumen • Grade IV: Plaque with a mobile element. In summary, whatever grading system is used, chances of neurological injury increase with a plaque height/ thickness > 3 mm, presence of mobile components, or an ascending aortic location of plaque.16 Comprehensive EAU examination should include an evaluation of each of the following measurements for each of the SAX segments of ascending aorta and arch.3 • Maximal plaque height/thickness (Fig. 30.6) • Location of the maximal plaque within the ascending aorta • Presence of mobile components. The extent of atheroma burden should be assessed as: • Plaque area: Circumferential area of maximal plaque obtained by planimetry. • Plaque area to aortic area ratio: Aortic diameter should also be noted to quantify atheroma burden as a ratio of plaque area to aortic area. • Multiple plaques: Measurements should be repeated as necessary.

Aortic Dissection Epiaortic ultrasonography scanning is a valuable tool for detection of aortic dissection as well as the detection of diastolic collapse of the true lumen. It is particularly

3D allows two basic imaging modes—a live 3D mode and a full volume mode. Full volume mode: It acquires a larger image by gating the ultrasound acquisition to the heart beat, using eight cardiac cycles; the probe itself must remain motionless during the acquisition phase. Live 3D mode: The images are displayed live, allowing the probe to be manipulated, but limiting the size of the interrogated area. Live 3D is useful in identifying and localizing the position of plaque within the aorta and directs aortic cross clamping and cannulation. Following this, the full volume mode can be used to evaluate the proposed sites completely and ensure no plaque was missed during the live scanning process.

ADVANTAGES OF THREE-DIMENSIONS OVER TWO-DIMENSIONS IN EPIAORTIC ULTRASONOGRAPHY18 • 3D imaging demonstrates the full extent of the plaque. • Relative distribution of plaque within the aorta and diffusely dispersed plaques are assessed. • The inclusion of discernible landmarks within the aorta (sinotubular junction, AV) makes it easier to evaluate the relative position of the plaques.

CONCLUSION Epiaortic scanning is an important intraoperative diag­ nostic tool that acts as an adjuvant to TEE to detect the atheroma burden. Its use is associated with a change in treatment strategies by 4.1% that includes a change in the technique for inducing cardiac arrest during CPB in 1.8%, aortic atherectomy or replacement surgery in 0.8%, requirement for off-pump coronary artery bypass grafting in 0.6%, avoidance of aortic cross clamping and use of ventricular fibrillatory arrest in 0.5%, change in arterial cannulation site in 0.2%, and avoidance of aortic cannulation in 0.2%.19 It can be performed rapidly and may reduce neurological complications associated with aortic manipulation.

642

Section 2:  Echocardiography/Ultrasound Examination and Training

REFERENCES 1. Konstadt SN, Reich DL, Quintana C, Levy M. The ascending aorta: how much does transesophageal echocardiography see? Anesth Analg. 1994;78(2):240–4. 2. Dávila-Román VG, Murphy SF, Nickerson NJ, Kouchoukos NT, Schechtman KB, Barzilai B. Atherosclerosis of the ascending aorta is an independent predictor of longterm neurologic events and mortality. J Am Coll Cardiol. 1999;33(5):1308–16. 3. Glas KE, Swaminathan M, Reeves ST, et al. Council for Intraoperative Echocardiography of the American Society of Echocardiography; Society of Cardiovascular Anesthesiologists. Guidelines for the performance of a comprehensive intraoperative epiaortic ultrasono­ graphic examination: recommendations of the American Society of Echocardiography and the Society of Cardio­ vascular Anesthesiologists; endorsed by the Society of Thoracic Surgeons. J Am Soc Echocardiogr. 2007;20(11): 1227–35. 4. Bucerius J, Gummert JF, Borger MA, et al. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg. 2003;75(2):472–8. 5. Cleveland JC Jr, Shroyer AL, Chen AY, Peterson E, Grover FL. Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity. Ann Thorac Surg. 2001;72(4):1282–8; discussion 1288. 6. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cere­ bral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med. 1996;335(25):1857–63. 7. John R, Choudhri AF, Weinberg AD, et al. Multicenter review of preoperative risk factors for stroke after coronary artery bypass grafting. Ann Thorac Surg. 2000;69(1):30–5; discussion 35. 8. Marshall WG Jr, Barzilai B, Kouchoukos NT, Saffitz J. Intraoperative ultrasonic imaging of the ascending aorta. Ann Thorac Surg. 1989;48(3):339–44. 9. Hangler HB, Nagele G, Danzmayr M, et al. Modification of surgical technique for ascending aortic atherosclerosis: impact on stroke reduction in coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003;126(2):391–400.

10. Ribakove GH, Katz ES, Galloway AC, et al. Surgical impli­ cations of transesophageal echocardiography to grade the atheromatous aortic arch. Ann Thorac Surg. 1992;53(5): 758–63. 11. Royse AG, Royse CF, Ajani AE, et al. Reduced neuropsycho­ logical dysfunction using epiaortic echocardiography and the exclusive Y graft. Ann Thorac Surg. 2000;69(5):1431–8. 12. Trehan N, Mishra M, Dhole S, Mishra A, Karlekar A, Kohli VM. Significantly reduced incidence of stroke during coro­ nary artery bypass grafting using transesophageal echocar­ diography. Eur J Cardiothorac Surg. 1997;11(2):234–42. 13. Daniel WT 3rd, Kilgo P, Puskas JD, et al. Trends in aortic clamp use during coronary artery bypass surgery: Effect of aortic clamping strategies on neurologic outcomes. J Thorac Cardiovasc Surg. 2013 Mar 8;pii:S0022-5223(13) 00171-2. doi:10.1016/j.jtcvs.2013.02.021. [Epub ahead of print]. 14. Katz ES, Tunick PA, Rusinek H, Ribakove G, Spencer FC, Kronzon I. Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography. J Am Coll Cardiol. 1992;20(1):70–7. 15. Nohara H, Shida T, Mukohara N, Obo H, Higami T. Ultrasonic plaque density of aortic atheroma and stroke in patients undergoing on-pump coronary bypass surgery. Ann Thorac Cardiovasc Surg. 2004;10(4):235–40. 16. van der Linden J, Hadjinikolaou L, Bergman P, Lindblom D. Postoperative stroke in cardiac surgery is related to the location and extent of atherosclerotic disease in the ascending aorta. J Am Coll Cardiol. 2001;38(1):131–5. 17. Demertzis S, Casso G, Torre T, Siclari F. Direct epiaortic ultrasound scanning for the rapid confirmation of intraoperative aortic dissection. Interact Cardiovasc Thorac Surg. 2008;7(4):725–6. 18. Bainbridge DT, Murkin JM, Menkis A, Kiaii B. The use of 3D epiaortic scanning to enhance evaluation of atherosclerotic plaque in the ascending aorta: a case series. Heart Surg Forum. 2004;7(6):E636–E638. 19. Rosenberger P, Shernan SK, Löffler M, et al. The influence of epiaortic ultrasonography on intraoperative surgical management in 6051 cardiac surgical patients. Ann Thorac Surg. 2008;85(2):548–53.

CHAPTER 31 Intracardiac Echocardiography Krishnaswamy Chandrasekaran, Donald Hagler, James Seward

Snapshot  Equipment and the Catheters  Imaging SpecificaƟons  Intracardiac Echocardiography: Clinical ApplicaƟons

INTRODUCTION Intracardiac echocardiography (ICE) is an extension of ultrasound imaging in cardiology. Advances in the transducer, computer, and catheter technologies have permitted miniaturizing ultrasound crystal, embedding the electronics into a small catheter, which permits high-resolution echo-Doppler ultrasound images and physiological features of the intra- and extra-cardiothoracic structures. In order to gainfully use ICE, an in-depth knowledge of cardiothoracic anatomy and physiology is essential. ICE is invasive, which mandates a novel support environment. The cardiovascular community has also successively transitioned ICE technologies to other subspecialties (e.g. electrophysiologists, surgical subspecialties, interventional cardiologists, pediatric cardiologists, and others) who have recognized the invaluable assistance provided by in-body ultrasound morphology and physiology. A second invasive ultrasound technology is intravascular ultrasonography (IVUS), which typically uses higher frequency transducers to image intravascular and adjacent anatomy. IVUS is most commonly used to

 Intracardiac Echocardiography During Electrophysiology

(EP) IntervenƟon  Intracardiac Echocardiography During Structural

IntervenƟon

visualize structural details of the coronary artery as well as peripheral vessels. This technology usually does not have the diverse Doppler imaging attributes of ICE.

EQUIPMENT AND THE CATHETERS There are two basic imaging systems for ICE and IVUS. Mechanical system with rotating ultrasound transducer(s) or an array of piezoelectric elements at the tip of the catheter are used clinically.

Mechanical System A typical device uses mechanical ultrasound transducertipped catheter along with the imaging console, (e.g. Cardiovascular Imaging Systems Inc, Fremont, CA, USA; Boston Scientific Corp, San Jose, CA, USA). This catheter can be used for both intravascular and intracardiac imaging. A 9-MHz single element transducer incorporated in an 8F catheter is used for ICE. In this system, the piezoelectric crystal rotates at 1,800 rpm in the radial dimension perpendicular to the catheter shaft. This provides crosssectional 360° tomographic images perpendicular to the catheter. The depth of view is about 5 cm.

644

Section 2: Echocardiography/Ultrasound Examination and Training

Table 31.1: AcuNav Ultrasound Catheter Specifications

Size (F)

Length (cm)

10

90

8

110

Phased Array Ultrasound System A typical device uses 64 miniaturized ultrasound crystals in a longitudinal array at the tip of the catheter (e.g. Sequoia ultrasound system [Acuson Corporation], which is currently part of Siemens Medical Solutions, USA; AcuNav Diagnostic Ultrasound Catheter (Fig. 31.1A), Acuson Corporation, Mountain View, CA, USA). Types of catheters and imaging platforms are shown in Table 31.1.

IMAGING SPECIFICATIONS ICE catheter provides high resolution images similar to transesophageal long-axis two-dimensional images. Vector wide-view imaging format for wider anatomical information. Sequoia system two-dimensional (2D) imaging frequencies: 10.0 MHz, 8.5 MHz, 7.5 MHz, and 5.5 MHz. Cypress system image frequencies: 7.0 MHz and 6.0 MHz. CV70 system 2D imaging frequencies: 9.0 MHz, 7.0 MHz, and 5.0 MHz. Aspen system 2D imaging frequencies: 8.5 MHz, 7.0 MHz, and 5.0 MHz. The imaging sector is 90° and parallel to the long axis of the catheter and the penetration depth is approximately 15 cm. The frequency of the phased array transducer can be changed from 5.5 to 10 MHz. Hence, high resolution imaging of both near-field and far-field structures can be done by using the frequency according to the depth of the structure that is being imaged. Furthermore, the catheter can be steered in anterior–posterior and left–right, each in a direction of 160° by using a mechanism on the handle of the catheter (Figs 31.1A to C). The transducer-catheter can be advanced up and down, rotated laterally along its long axis providing innumerable 2D sector images. Although this can be obtained within in any cardiac chamber, generally imaging is performed from the right atrium (RA), right ventricle (RV), and at times from within the coronary sinus. This system also provides Doppler color flow imaging and hemodynamics.

Advantages and Limitations of the Mechanical Versus Phased Array Ultrasound Catheters for Intracardiac Echocardiography Mechanical ultrasound catheter imaging system is less expensive than phased array catheter imaging system. The tomographic cross-sectional images are not as easy to comprehend for the cardiologist who is more accustomed to tomographic anatomy. The lack of multifrequency capability limits the depth of imaging. Furthermore, lack of color flow imaging and Doppler limits clinical utility.

INTRACARDIAC ECHOCARDIOGRAPHY: CLINICAL APPLICATIONS ICE technology is commonly used by the pediatric, interventional cardiologist and electrophysiologists. The ICE is used to assess the morphology of a lesion, suitability of the lesion for intervention and guidance during intervention, and to assess the efficacy of the intervention. Hence, the imaging views are tailored for the specific intervention. However, basic cardiovascular views are nicely described by Earing et al.1

INTRACARDIAC ECHOCARDIOGRAPHY DURING ELECTROPHYSIOLOGY (EP) INTERVENTION Atrial Septal Puncture ICE provides high frequency excellent realtime imaging of the atrial septum. The major focus is on the morphology of the fossa ovalis and the surrounding limbus (Figs 31.2A to D).

Imaging View The catheter is advanced into the RA with the tip of the catheter straight and the face of the transducer facing the left side. This can be recognized by gently rotating the catheter clockwise along its long axis if the catheter was facing anteriorly looking at right atrial appendage or by counterclockwise rotation if it was facing the posterior wall of the RA. One can obtain a family of images demonstrating the relationship of the inferior vena cava (IVC), superior vena cava (SVC), fossa ovalis, coronary sinus, crista terminalis, right atrial appendage, and Eustachian ridge/ valve. One may need to flex or extend the tip of the catheter to refine the image; usually this is not needed unless the

Chapter 31: Intracardiac Echocardiography

645

A

B

C

Figs 31.1A to C: (A) Diagnostic ultrasound catheter (AcuNav) placed adjacent to a pediatric transesophageal echocardiography probe shows the relatively small size of the 10F catheter. (B) Close-up of the 3.3 mm diameter catheter tip (arrows) shows the longitudinally oriented crystal array (palette). (C) Overhead view of the four-way tip maneuverability of the diagnostic catheter. Source: With permission from Mayo Proceedings.

RA is enlarged. Typically, the image needed for atrial septal puncture is similar to bicaval view obtained by transesophageal echocardiography (TEE). This can be obtained by keeping the catheter in the middle of the RA rotating clockwise or counterclockwise until the SVC, fossa ovalis membrane, and IVC are well seen. During the atrial septal puncture,2 the tip of the trans-septal needle tenting of the fossa ovalis toward the left atrium (LA) should be seen to avoid complications (Fig. 31.3).

Pulmonary Vein Isolation for Atrial Fibrillation (AF) Ablation ICE provides excellent imaging of the pulmonary veins (Fig. 31.4), permitting recognition of the number of veins and their entrance, whether they enter the LA via separate ostium or via a common ostium.3,4

Imaging View Left atrium and pulmonary veins can be imaged with the catheter tip straight in the body of the RA and facing inter atrial septum. Left pulmonary veins are easily imaged by gently rotating the catheter clockwise. If the LA is enlarged, then the catheter tip may require flexion or extension to look at the left pulmonary veins. Right pulmonary veins, on the other hand, require catheter manipulation to image their entrance into the LA. Since the right pulmonary veins are adjoining the SVC, they can be imaged from the SVC, SVC–RA junction, or from the high RA. In the SVC and SVC–RA junction, the catheter must be slightly flexed to look down. Generally, the superior limbus of the fossa ovalis is seen adjoining the entrance of the pulmonary vein from this position. Very rarely they can be imaged from the lower RA with the catheter extended looking up at the SVC and superior limbus region.

646

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 31.2A to D: (A) IVC-RA junction with the Eustachian valve (arrow); (B) SVC-RA junction with crista terminales (arrow); (C) RA wall (arrow) and (D) Atrial septum with superior (SFL) and inferior fatty limbus (IFL).

Fig. 31.3: Note the tenting (arrow head) of the atrial septum during trans-septal puncture (left) and the color Doppler demonstrating right to left shunt after the septostomy.

Fig. 31.4: Color flow Doppler of the left inferior (LIPV) and superior (LSPV) Pulmonary veins (left) and pulsed wave Doppler of the LIPV (right).

Chapter 31: Intracardiac Echocardiography

During ablation, ICE provides realtime monitoring of adequate contact of the ablation catheter with atrial wall, and delivery of radio frequency (RF) energy results in cavitation seen as bubbles on the ICE5 and lesion development as there is a change in the tissue texture (Figs 31.5A and B). ICE monitoring during ablation avoids unnecessary slippage of the catheter into the pulmonary and also recognize proper tissue contact. This prevents over use of the energy and unnecessary complications.

RF Ablation at Other Locations Right Ventricular Outflow Tract Tachycardia ICE has demonstrated structural abnormalities such as focal muscle tissue underneath the anterior pulmonary valve cusp or ridge in the right ventricular outflow tract (RVOT) that may be responsible for the ventricular tachycardia (VT).6 Imaging the RVOT can be achieved either from the RA or from the RV. From the RA, the catheter should be flexed and rotated clockwise until the RVOT is well seen. To image from the RV, catheter has to be flexed to enter the RV; once in the RV, the catheter should be flexed more and rotated counterclockwise facing upward until the RVOT and the pulmonary valve is well seen (Figs 31.6A and B). The extreme flexion and navigation from one chamber to the other needs fluoroscopic monitoring.

647

fluoroscopy; however, they can easily be verified and monitored by ICE during ablation (Figs 31.7A to D). In this situation, the LMCA and the aortic root can be imaged from the mid-RA with the catheter flexed, looking down, and rotated clockwise until the aortic root and the LMCA ostium are well seen.

Ventricular Tachycardia from Left Ventricle ICE can allow recognition of anatomical substrate as well as guide mapping and ablation catheter location in the left ventricle (LV).8 It avoids unnecessary catheter entrapment in the mitral apparatus and potential complication. ICE can also confirm tissue contact of the ablation catheter and monitor lesion development. ICE catheter has to be advanced into the RV apex. This can be achieved either by flexion or extension. Once in the RV, if the anterior wall of the RV is seen rotating gently, clockwise will bring interventricular septum and the LV in view, or if the posterior wall of the RV is seen, then gentle counterclockwise rotation will bring the septum and LV in view. Fine refinement of the catheter position is needed to locate the mapping and ablation catheter. It is also used for monitoring and guiding ablation of VT foci from the epicardial surface (Figs 31.8A to D).

VT Foci from the Great Vessels

Intracardiac Echocardiography During EP Procedures

VT foci arising from the adnexa of left main coronary artery ostium (LMCA) from the cusps of the aortic valve7 are difficult to assess for their closeness to LMCA from

The usefulness of ICE in EP procedures has been well recognized during trans-septal puncture,2 pulmonary vein isolation,3,4 and other complex RF ablative procedures

A

B

Figs 31.5A and B: Radio frequency (RF) ablation catheter in the left inferior pulmonary vein (A) and microbubbles and tissue changes during ablation (B).

648

Section 2: Echocardiography/Ultrasound Examination and Training

to monitor ablation and lesion development,5–8 and to avoid complications. The fluoroscopic time as well as complications rates have decreased.

One of the primary applications of ICE imaging to be rapidly adopted into clinical practice was for guidance of

device closure of atrial septal defects, such as secundum atrial septal defect (ASD) or patent foramen ovale (PFO). Transcatheter placement of closure devices for ASD or PFO is facilitated by ICE guidance in the cardiac catheterization laboratory. Intracardiac images provide superior imaging of the atrial septum (see Figs 31.2 and 31.3). Assessment of the defect(s) and relationship to the surrounding cardiac structures is critical to a successful deployment of the closure device and is facilitated by the ICE. Documentation of normal pulmonary venous return to the LA (Fig. 31.9) is an important aspect of ASD closure and is easily accomplished by ICE.1,9,10,11

A

B

INTRACARDIAC ECHOCARDIOGRAPHY DURING STRUCTURAL INTERVENTION Patent Foramen Ovale/Atrial Septal Defect Closure

Figs 31.6A and B: (A) Intracardiac ultrasound image showing the close relationship between the pulmonary valve and the aortic valve close to the ostium of the left main coronary artery. This image was obtained by placing the intracardiac ultrasound probe in the right ventricle and the probe directed upward to view the pulmonary artery aorta relationship; (B) Intracardiac ultrasound image showing the cross-sectional view of the aortic valve with the ablation catheter in the left coronary cusp (LCC). His indicates His catheter; ABL: Ablation catheter. (AO: Aortic valve; LMCA: Left main coronary artery ostium; PA: Pulmonary artery; PV: Pulmonary valve). Source: Reproduced with permission from AHA Circ Arrhythmia Electrophysiol. 2009;2:316–26.

A Figs 31.7A and B

B

Chapter 31: Intracardiac Echocardiography

C

649

D

Figs 31.7A to D: Intracardiac echocardiography (ICE) images of the ablation catheter at the level of the aortic valve (A and B) and pulmonary valve (C and D). (A) Shows the catheter between the left and noncoronary cusps of the aortic valve; (B) Shows a longitudinal section of the aortic valve in which the catheter is in the right coronary cusp with the left coronary cusp inferior; (C) Shows the catheter above the pulmonary valve targeting. This image shows the proximity of this site to those that are above the aortic valve; (D) Shows the catheter just below the pulmonary valve. (ABL: Ablation catheter; LA: Left atrium; LV: Left ventricle; MV: Mitral valve; PV: Pulmonary valve). Source: Reproduced with permission from Circ Arrhythmia Electrophysiol. 2008;1:30–38.

A

B

C

D

Figs 31.8A to D: (A) Intracardiac echocardiography (ICE) image with increased echogenicity in epicardium (white arrows) identified on the posterolateral wall. Pericardium is noted by the red arrow; (B) Left ventricle (LV) endocardial voltage map with normal voltage; (C) LV epicardial voltage map with area of low voltage on the posterolateral wall; (D) Late potentials identified on LV epicardium (fractionated, split, and isolated). Source: Reproduced with permission from Circ Arrhythm Electrophysiol. 2011;4:667–73.

650

Section 2: Echocardiography/Ultrasound Examination and Training

Fig. 31.9: Intracardiac echocardiography (ICE) in the right atrium (RA) demonstrating the patent foramen ovale (PFO; arrow) on the left and the color flow demonstrating a left to right shunt (arrow) on the right. Source: Reproduced with permission from Mayo proceedings.

Long-axis and short-axis views aid in dimensional analysis of the septal defect and allow very accurate measurement of both static diameter, and, more importantly, balloon-stretched diameter (typically used to select the appropriate device size) when compared to fluoroscopy.9,10 Spatial relationships of devices in relationship to surrounding cardiac structures are better visualized by ICE compared to TEE (Fig. 31.10). During deployment and subsequent delivery of an occlusion device, there is no shadowing of the right atrial disc of the device by the left atrial disc when ICE guidance is utilized. Therefore, ICE imaging provides superior visualization of septal rims in relationship to device position before final deployment is accomplished, reducing the risk of device embolization. In contrast, when TEE is used for evaluation of device placement, significant acoustic shadowing from the left atrial disc may preclude adequate imaging of each disc and its relationship to the atrial septum, increasing the time needed for imaging prior to delivery of the device in an optimal position. Balloon sizing is performed and monitored with ICE and fluoroscopy. Usually, the best images for clear measurement of balloon size were obtained with the long-axis view of the atrial septum. Multiple views of the inflated balloon and atrial septum with color flow imaging were obtained to show complete defect occlusion and to exclude other associated atrial defects. By fluoroscopy, the balloon size was obtained in both the anterior and lateral imaging planes. Once deployed but before release, the device was again imaged with ICE in both the long- and short-axis planes

Fig. 31.10: Intracardiac echocardiography (ICE) catheter in the right atrium (RA) demonstrating moderate shunt (arrow) across the atrial septal defect in the long-axis view of the atrial septum (top left) and the Amplatzer atrial septal defect (ASD) closure device across the defect seen in the short-axis view just behind the aortic root (top right). Color flow Doppler demonstrating the device (arrows) and the residual central trivial shunt in the longaxis view. Source: Reproduced with permission from Mayo proceedings.

to determine appropriate device positioning in the atrial septum, to exclude the presence of additional defects, and to ensure that the device did not interfere with the surrounding structures (Fig. 31.10).

Ventricular Septal Defect Closure Transcatheter closure of muscular ventricular septal defect (VSD) congenital or postmyocardial infarction is now possible.11,12 In a patient with postmyocardial infarction VSD, TEE imaging may not be tolerated by the more clinically compromised patient. ICE is an additional imaging modality that can be used to aid visualization of cardiac structures during defect sizing, delivery, and deployment of a septal closure device. Monitoring of tricuspid valve regurgitation is facilitated by ICE during such procedures. In order to visualize the VSD properly, manipulation of the ICE catheter through the right atrioventricular valve orifice into the right-sided ventricle may be needed as described above and seen in Figure 31.11.

Periprosthetic Valve In patients who had undergone valve replacement for both acquired heart disease and congenital heart disease, perivalvular leak is a reported phenomenon.

Chapter 31: Intracardiac Echocardiography

651

Fig. 31.11: Intracardiac echocardiography (ICE) image obtained from within a right-sided morphological left ventricle (LV) in a young man with congenitally corrected transposition of the great arteries. Image on the left demonstrates an iatrogenic ventricular septal defect (VSD) observed (arrow) near the inlet ventricular septum (VS). Color flow imaging on the right demonstrates a large left-to-right shunt originating in the morphological right ventricle (RV). A prosthetic atrioventricular valve is observed near the left atrium (LA). (A: Anterior; S: Superior). Source: Reproduced with permission from Mayo proceedings.

Fig. 31.12: Intracardiac echocardiography (ICE) image from the right atrium (RA) in a patient with a left ventricular (LV) to RA shunt following mitral valve (MV) replacement. The image on the left demonstrates the crux of the heart and the entrance (arrow) of the fistula in the RA. Color flow image on the right demonstrates a moderate shunt from LV to RA. (L: Left; LA: Left atrium; S: Superior.

Often, acoustic shadowing by the mechanical valve precludes adequate echo imaging from one side of the valve. Depending on the intracardiac anatomy, both ICE and TEE may be needed to facilitate evaluation of such defects for location, proximity to the mechanical valve, and size of the defect.13 In addition, during deployment of closure devices, assurance of valve function during and after device placement is critical. Evaluation of leaflet mobility is important, and the device must not interfere with normal valve function. Continuous monitoring during device deployment, positioning, and delivery is easily accomplished by ICE (Fig. 31.12). Judicious use of TEE may be needed to fully evaluate some patients during closure of perivalvular leak but can then be minimized to facilitate patient comfort during supine imaging with the additional use of ICE.

imaging plane toward the pulmonary outflow tract, one can obtain excellent images of the conduit and Melody valve implant. Imaging can demonstrate the competency of the valve and exclude residual paravalvular leaks. From within the RA, similar views and assessment of the Melody valve implanted in a previous tissue valve implant can be obtained.

Melody Valve ICE imaging has been described to assess the function of percutaneously implanted “Melody valves” both in the pulmonary and in the tricuspid position. By placing the catheter within the RV and directing the catheter tip

Extracardiac Use of the Intracardiac Echocardiography Probe The intracardiac echo probe has also been used for transesophageal imaging in small infants during congenital cardiac surgery.14 The small size of this probe facilitates its placement in children < 3.0 kg. In these small infants, standard biplane pediatric TEE probe cannot be advanced into the esophagus due to the patient’s small size. High quality 2D and Doppler images are obtained by the use of ICE (Figs 31.13A and B). The major disadvantage of the ICE probe is that it is monoplane. Longitudinal imaging is effective; however, the crux of the heart and the inlet ventricular septum are not adequately visualized.

652

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

Figs 31.13A and B: (A) Demonstrates a transesophageal echocardiography (TEE) image with the intracardiac echocardiography (ICE) catheter obtained in a small infant with critical discrete coarctation (arrow) of the aorta (Ao); (B) Shows the color flow image demonstrating aliased flow through the obstruction with a 4-m/s velocity recorded with continuous wave Doppler. Source: Reproduced with permission from Mayo proceedings.

Advantages and Limitations of Intracardiac Echocardiography During Interventional Procedures

Limitations 1. 2.

ICE compliments fluoroscopy during percutaneous intervention, by providing anatomical details of the structure intervened as well as guiding the mainpulation of catheters and guide wires whose spatial location at times are difficult to locate by fluoroscopy.

3.

4.

Advantages of Intracardiac Echocardiography 1.

2.

3.

4.

Use of ICE for trans-septal puncture and locating the catheter position has significantly reduced the radiation. The need for general anesthesia for TEE and associated patient discomfort is less with the use of ICE. Furthermore, this allows communication with the patient during the procedure. With the use of ICE, there is no need to invade the sterile field, which may be needed with the use of TTE for structural assessment. ICE provides real time information about the catheter position, device details, recognizes complications such as development of thrombus on the catheter, pericardial effusion, etc.

The size of the catheters is relatively large and as such vascular injuries are a potential problem. Phased array catheter is expensive when used only one time. Reuse has received limited attention. The single-plane imaging requires extreme catheter manipulation that has the potential for complications. Three-dimensional (3D) ICE is currently under clinical investigation. No standard imaging planes.

Three-Dimensional Intracardiac Echocardiography Imaging Three- and four-dimensional ICE imaging is now commercially available with the Siemens SC2000 platform. The 3D ICE probe currently is only available in the 10F size but also has the same functionality as the 2D catheter. The hub of the catheter connecting to the imaging console is different (Figs 31.14A and B). The four-dimensional (4D) images provide realtime 20° 3D images. With similar catheter positioning as described with the 2D images, 3D images of the atrial septum, atrioventricular valves, and semilunar valves can be obtained. A large recurrent ASD is better demonstrated with 3D ICE imaging as noted in Figures 31.15A to D.

Chapter 31: Intracardiac Echocardiography

A

653

B

Figs 31.14A and B: AcuNav 8F two-dimensional (2D) intracardiac echocardiography (ICE) and 10F three-dimensional (3D) ICE catheters (A) and the magnified view of the electronic connections of the hub (B) demonstrates the difference between 2D and 3D catheters.

A

B

C

D

Figs 31.15A to D: Two-dimensional (2D) sector image short-axis view of a secundum atrial septal defect (ASD) obtained from the threedimensional (3D) intracardiac echocardiography (ICE) catheter with the corresponding 3D view (A). Note the slightly rotated view of the 3D image demonstrating the spatial relations of the ASD (arrow) in Figure B; (C) Demonstrates the 3D image of the ASD (arrow) from the left atrium (LA) perspective, and (D) represents the ASD closure device in the same perspective.

654

Section 2: Echocardiography/Ultrasound Examination and Training

REFERENCES 1. Earing MG, Cabalka AK, Seward JB, et al. Intracardiac echocardiographic guidance during transcatheter device closure of atrial septal defect and patent foramen ovale. Mayo Clin Proc. 2004;79(1):24–34. 2. Szili-Torok T, Kimman G, Theuns D, et al. Transseptal left heart catheterisation guided by intracardiac echocardiography. Heart. 2001;86(5):E11. 3. Verma A, Marrouche NF, Natale A. Pulmonary vein antrum isolation: intracardiac echocardiography-guided technique. J Cardiovasc Electrophysiol. 2004;15(11): 1335–40. 4. KhaykinY, Marrouche NF, Saliba W, et al. Pulmonary vein antrum isolation for treatment of atrial fibrillation in patients with valvular heart disease or prior open heart surgery. Heart Rhythm. 2004;1:4. 5. Wood MA, Shaffer KM, Ellenbogen AL, et al. Microbubbles during radiofrequency catheter ablation: composition and formation. Heart Rhythm. 2005;2(4): 397–403. 6. Tabatabaei N, Asirvatham SJ. Supravalvular arrhythmia: identifying and ablating the substrate. Circ Arrhythm Electrophysiol. 2009;2(3):316–26. 7. Srivathsan KS, Bunch TJ, Asirvatham SJ, et al. Mechanisms and utility of discrete great arterial potentials in the ablation of outflow tract ventricular arrhythmias. Circ Arrhythm Electrophysiol. 2008;1(1):30–8.

8. Bala R, Ren JF, Hutchinson MD, et al. Assessing epicardial substrate using intracardiac echocardiography during VT ablation. Circ Arrhythm Electrophysiol. 2011;4(5):667–73. 9. Khositseth A, Cabalka AK, Sweeney JP, et al. Transcatheter Amplatzer device closure of atrial septal defect and patent foramen ovale in patients with presumed paradoxical embolism. Mayo Clin Proc. 2004;79(1):35–41. 10. Hijazi Z, Wang Z, Cao Q, et al. Transcatheter closure of atrial septal defects and patent foramen ovale under intracardiac echocardiographic guidance: feasibility and comparison with transesophageal echocardiography. Catheter Cardiovasc Interv. 2001;52(2): 194–9. 11. Jongbloed MR, Schalij MJ, Zeppenfeld K, et al. Clinical applications of intracardiac echocardiography in interventional procedures. Heart. 2005;91(7):981–90. 12. Holzer R, Balzer D, Amin Z, et al. Transcatheter closure of postinfarction ventricular septal defects using the new Amplatzer muscular VSD occluder: Results of a U.S. Registry. Catheter Cardiovasc Interv. 2004;61(2):196–201. 13. Cabalka AK, Hagler DJ, Mookadam F, et al. Percutaneous closure of left ventricular-to-right atrial fistula after prosthetic mitral valve rereplacement using the Amplatzer duct occluder. Catheter Cardiovasc Interv. 2005;64(4): 522–7. 14. Bruce CJ, O’Leary P, Hagler DJ, et al. Miniaturized transesophageal echocardiography in newborn infants. J Am Soc Echocardiogr. 2002;15(8):791–7.

CHAPTER 32 Intravascular Ultrasound Imaging Sachin Logani, Charles E Beale, Luis Gruberg, Smadar Kort

Snapshot ¾¾ Principles of Ultrasound Technology ¾¾ Image Acquisition ¾¾ Intravascular Ultrasound Examination ¾¾ Image Interpretation

INTRODUCTION Intravascular ultrasound (IVUS) is an invasive imaging modality based on the principles of ultrasound that can be used in conjunction with coronary angiography to further assist the interventional cardiologist in decision making, especially in patients with complicated coronary anatomy. This chapter discusses the principles of this technology, image acquisition and interpretation, the role of IVUS in clinical practice, and future direction.

PRINCIPLES OF ULTRASOUND TECHNOLOGY An understanding of image acquisition using IVUS requires an understanding of the fundamental principles of ultrasound wave transmission. A detailed discussion of this topic is beyond the scope of this chapter. However, a brief review is provided here. Moving ultrasound waves used for imaging cardiac structures have a frequency of > 20,000 cycles/s, making them undetectable to the human ear.1 The velocity at which sound travels through the human soft tissue remains essentially constant at 1,540 m/s. Transducers are involved in the conversion of electrical energy into ultrasound waves and vice versa. Emission of an ultrasound wave is followed by a generated impulse traveling away from the transducer. As it travels, the ultrasound impulse may encounter an

¾¾ Utility of Intravascular Ultrasound in Clinical Practice ¾¾ Safety Considerations ¾¾ Future Perspectives

interface between two different types of tissues, causing it to be partially reflected and partially transmitted. The degree of reflection depends on the impedance of the tissues. The passage of an impulse through the tissue interface leads to a decrease in its energy. Thus, only a small proportion of the emitted impulse returns to the transducer. The transducer converts the received signal into electrical energy, which is then amplified by an image processing system and converted into a graphic. Resolution is defined as the ability to discriminate two closely placed objects. Thus, two objects that are closer than the resolution of the device cannot be reliably discerned on ultrasound. Image quality is described by spatial resolution as well as contrast resolution. Spatial resolution is the ability to display, as separate images, two objects that are very close to each other. Contrast resolution is the ability to display, as distinct images, areas that differ in density by a small amount.

IMAGE ACQUISITION An IVUS catheter consists of a miniaturized transducer and a console responsible for image reconstruction. Monorail rapid exchange IVUS catheters have an outer diameter ranging between 2.6 and 3.5 Fr. These catheters can be advanced to the coronaries through a 6-Fr guide catheter. Currently, two different types of IVUS transducers are available in the United States: Mechanically rotating

656

Section 2:  Echocardiography/Ultrasound Examination and Training

Table 32.1: Overview and Comparison between Mechanical IVUS and Phased-Array Transducers

Mechanical Transducers

Phased-Array Transducers

Uses a single transducer firing an ultrasound beam as it rotates

Uses multiple transducers fixed in an annular array sequentially firing

Requires larger caliber catheters

Can be used with smaller caliber catheters

Rigid structure requires the use of guide wires to pass the aortic bifurcation, more difficult to pass through torturous vessels

Increased flexibility allows for accessibility in smaller tortuous vessels and passage through aortic bifurcation

Increased difficulty/technical skill to use in conjunction with other interventional devices

Relative ease of compatibility with other interventional devices

Presence of drive cable and moving parts can lead to nonuniform rotational distortion

Nonuniform rotational distortion is not present due to arrangement of multiple transducers

Decreased cost when compared to phased-array transducers

Increased cost when compared to mechanical IVUS transducer

transducer (mechanical IVUS system) and electronically switched multielement array system (solid-state design IVUS system; Table 32.1). Mechanical systems have a single transducer rotating at 1,800 rpm driven by a flexible drive cable. By sending and receiving pulses of ultrasound signals, the rotating transducer provides 256 individual radial scans for each image. Appropriate image creation requires the absence of air bubbles in the IVUS sheath. Conversely, in the electronic transducer system, multiple transducer elements (as many as 64 in currently available systems) are arranged in an annular array. These phased array transducers are activated in sequence in order to generate an image. These systems allow the image to be manipulated, thereby enabling optimal focus at various ranges of depths. Additionally, Doppler effect may be used to provide coloration while depicting blood flow. Table 32.1 provides a comparison between mechanical and phased array transducers. Most currently available IVUS systems include an imaging console equipped with the necessary hardware and software, a monitor, and recording devices for digital recording of obtained images. Artifacts on IVUS images can lead to misinterpretation. Therefore, prompt detection and correction of artifacts is crucial for obtaining high-quality images. The ringdown artifact is manifested as disorganization of the image closest to the face of the transducer or the catheter surface. These artifacts are more commonly seen with the electronic array systems than with mechanical systems, and they usually appear as bright haloes surrounding the catheter. Optimal transducer design and digital subtraction may minimize the ring-down effect. Another type of artifact is nonuniform rotational distortion (NURD) that is only seen with mechanical IVUS imaging systems. NURD results from asymmetric friction along the drive-shaft mechanism, leading to a lag during rotation.

This in turn results in geometric distortion of the image, which affects circumferential resolution. NURD may lead to, for example, inaccurate cross-sectional measurements of an implanted stent. Because of the lack of a mechanical rotational component in the phase-array IVUS, NURD does not occur.

INTRAVASCULAR ULTRASOUND EXAMINATION IVUS is an invasive procedure performed in the cardio­ vascular catheterization laboratory. The IVUS is intro­ duced into the coronary artery that is to be imaged over a guide wire. The patient must be treated with an anticoagulant (usually unfractionated heparin) prior to guide wire insertion. To avoid catheter-induced spasm, intracoronary nitroglycerin (200 µg) is administered prior to the introduction of the catheter. The IVUS catheter is advanced over the guide wire until it has reached a point beyond the lesion to be imaged. Then, the transducer tip is pulled back through the target lesion by either a mechanical device or manually. This maneuver creates a series of tomographic, cross-sectional images of the coronary artery. A pullback device is usually utilized to provide a steady pullback speed at 0.5 or 1 mm/s. IVUS probes are handled similarly to over-thewire percutaneous transluminal coronary angioplasty catheters. The position of the guiding catheter must be stable in order to provide support for large profile IVUS catheters. The tip of the guide wire must be positioned distal in the target vessel. Care must be taken not to advance the IVUS catheter over the floppy end of the guide wire in order to avoid catheter prolapse. When imaging aorto-ostial lesions in the left main coronary artery, it is important to disengage the guiding catheter from the ostium before pullback. If this is not

Chapter 32:  Intravascular Ultrasound Imaging

done, the true aorto-ostial lumen may be masked or covered by the guiding catheter, and this may hamper the detection of significant ostial lesions. To prevent damage to the vessel wall, the IVUS catheter should not be advanced to the smaller distal coronary branches. In addition, caution must be exercised when crossing recently deployed stents in order to avoid disruption of the fragile stent struts. As briefly mentioned earlier, IVUS catheters may be manipulated either by the motorized approach or manually. Regardless of the method selected, target imaging should include a length of at least 10 mm of the distal vessel, the lesion site, and the entire proximal segment of the vessel back to the aorta. A major advantage of motorized pullback is that it allows steady and stable catheter withdrawal, thereby providing uniform images and accurate measurement of the length of the segment that is being evaluated. Manual transducer pullback needs to be performed slowly. It allows the operator to concentrate on specific regions that may be of greater interest, as the transducer motion can be paused at the desired location(s). However, a disadvantage of manual pullback is that the process is uneven, which could adversely affect image uniformity. Once images have been obtained, they may be viewed as individual cross-sectional images or as a video sequence. Through computerized image reconstruction, a series of IVUS images can be made to depict the longit­ udinal appearance of the artery.

IMAGE INTERPRETATION Coronary angiography is currently regarded as the primary modality used to assess coronary artery anatomy and morphology. However, since IVUS provides crosssectional images of the coronary vessel, it also enables depiction of vessel anatomy and identification of the lumen, plaque, and vessel wall. Proper interpretation of IVUS images plays a key role in the use of this invaluable imaging modality for assessing lesion severity and guiding complex percutaneous coronary interventions (PCIs). In order to interpret IVUS images, two key structures must be identified: the vessel lumen and the vessel wall.2 A specific echogenic pattern known as “speckle” is created by flowing blood within the coronary artery. It is visible as fine echoes moving in swirling patterns. Blood speckle is invaluable in image interpretation since it allows distinct identification of the lumen and vessel wall. Changes in acoustic

657

impedance are observed as ultrasound waves reflect on coronary artery wall tissue. The first of such changes is observed at the border of the blood and arterial intima. The second change occurs at the external elastic membrane (EEM) located at the media-adventitia border (Fig. 32.1A). Although coronary angiography is the primary mode of imaging of the coronary arteries and the basis for PCI, given the two-dimensional nature of the images obtained by coronary angiography, there are certain limitations with regard to lesion observation. The degree of luminal stenosis can only be assessed by comparing a lesion with a “normal” coronary artery segment. Furthermore, it cannot provide information regarding plaque type or burden.3 Conversely, the two-dimensional, tomographic nature of IVUS can better evaluate atherosclerotic disease severity, plaque morphology and composition, progression or regression of coronary disease, and cardiac allograft vasculopathy (CAV).4,5 A low echogenicity signal is observed in soft lipid-rich lesions on IVUS (Fig. 32.1B). The term “soft” in this case refers to low echo density and not the specific structural characteristics of the plaque.6 Such soft plaques are often seen in high-risk patients and represent potentially unstable lesions. Echo dense (“hard”) plaques have a high fibrous tissue content and show intermediate echogenicity (Fig. 32.1C).7 The greater the fibrous content of the plaque, the higher its echo density. Most coronary artery lesions are mixed plaques whose components have varying echogenic properties. Calcium deposits within lesions appear as bright echoes (Fig. 32.1D). Calcium prevents the penetration of ultrasound waves, resulting in acoustic shadowing, as clearly depicted in Figure 32.1D. Extensive calcification usually indicates plaque stability whereas microcalcifications within lipid-rich lesions may indicate plaque vulnerability.8 Features associated with increased risk of rupture include thin-cap fibroatheromas, a large plaque burden, and a small lumen area.9 Intraluminal thrombus may be identified on IVUS as a layered, lobulated, or pedunculated mass in the arterial lumen. However, we need to be cautious because such thrombi are often echolucent and may be confused with a lipidrich “soft” plaque. A more detailed analysis of plaque composition is achieved by IVUS with virtual histology (IVUS-VH). This technique is based on advanced radiofrequency analysis of reflected ultrasound signals in a frequency domain analysis, and displays a reconstructed color-coded tissue map of plaque composition superimposed on cross-sectional images of the coronary artery obtained by grayscale IVUS.10 Images obtained using IVUS-VH are depicted in Movie clip 32.1.

658

Section 2:  Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 32.1A to D: (A) The elastic membrane is labeled as EM and is demarcated by small arrows outlined in red; (B) Soft plaque (SP) enclosed by a dotted red outline; (C) Dense or fibrous plaque (FP) outline by a blue line; (D) A calcium deposit is demarcated by a arrow outline in white, seen to the left is a dark area, known as the acoustic shadow or calcium shadow (CS).

Neointimal tissue growth within stented segments may lead to the development of in-stent restenosis, which could be identified by IVUS. Early in-stent restenosis shows low echogenicity, while late in-stent restenosis appears more echogenic. IVUS can also be used to identify and

assess the severity of coronary artery dissections. A disse­ction involving the coronary artery may be intimal, medial, or adventitial. Flow limiting coronary artery dissections following PCI are associated with increased frequency of long-term adverse cardiac events.11

Chapter 32:  Intravascular Ultrasound Imaging

A

659

B

Figs 32.2A and B: (A) Coronary angiography showing the aneurysm at the center of a black circle; (B) Intravascular ultrasound (IVUS) imaging showing an aneurysm of a coronary artery.

Additionally, IVUS can identify other PCI-related compli­ cations that may be missed by angiography, including intramural hematomas, aneurysms, and pseudoaneurysms as shown in Figures 32.2A and B.

UTILITY OF INTRAVASCULAR ULTRASOUND IN CLINICAL PRACTICE Although coronary angiography remains the primary imaging modality for defining coronary anatomy and for guiding interventions, the increasingly complex nature of interventions has highlighted its limitations as an imaging modality. Limited resolution and the two-dimensional nature of the images obtained hamper its ability to depict the severity of intermediate lesions accurately. In addition, angiography provides no information regarding plaque composition, which may be useful for prognosis and treatment.12,13 IVUS provides an accurate assessment of plaque burden and its components. Various other clinical utilities of IVUS are listed in Table 32.2. However, the use of IVUS in clinical practice remains limited. This has been attributed to an increase in cost, procedure time, and radiation exposure. The widespread use of IVUS is also limited by operator experience. During PCI, IVUS is a useful supplemental modality that helps plan an

interventional strategy and optimize stent deployment, overcoming some of the shortcomings of coronary angio­ graphy. A recent meta-analysis by Parise and collea­ gues showed that IVUS-guided PCI is associated with a significant reduction in restenosis and target vessel revascularization with similar mortality and myocardial infarction rates.14 IVUS-guided PCI is of critical importance during intervention of unprotected left main coronary artery lesions. The dire consequences of a poorly deployed stent in the left main coronary artery was demonstrated in the MAIN-COMPARE trial that showed a significant reduction in mortality rates in patients who underwent IVUS-guided PCI.15 IVUS is especially useful in assessing diffusely diseased segments.16 A minimum lumen area (MLA) < 4 mm2 on IVUS indicates significant coronary stenosis.17 This information provided by IVUS may be combined with coronary artery physiologic data to facilitate clinical decisions in the cardiac catheterization laboratory. A Doppler-tipped guide wire, which permits measurement of translesional pressure gradient can be used to calculate the fractional flow reserve which is derived from the ratio of distal coronary pressure to aortic pressure at maximum hyperemia (induced by adenosine). During diagnostic angiography, coronary flow reserve can replace out-oflaboratory stress testing for single lesion assessment.18,19

660

Section 2:  Echocardiography/Ultrasound Examination and Training

Table 32.2: Clinical Utility of Intravascular Ultrasound (IVUS)

Identification of plaque composition, allowing for identification and possible differentiation of stable opposed to high-risk unstable plaque Accurate identification of lesion size, length, eccentricity, and significance, thereby enabling improvement in interventional planning in complex lesions Improvement in stent outcomes by identifying balloon under expansion, stent and edge malapposition, therefore leading to decreased thrombosis Improved identification of indeterminate lesions Can be used to monitor progression or regression of plaque accumulation Identification of coronary structural abnormalities such as dissections, aneurysm, or hematomas

Fig. 32.3: The struts of the stent are indicated by the arrows outlined in white. The area of poor stent apposition is demarcated by three blue arrows.

IVUS also provides important prognostic information for lesions in the left main coronary artery.20 Further, it plays a role in the assessment and treatment of lesions in previously stented coronary artery segments.21 A study reported that information regarding plaque composition and morphology provided by IVUS may change therapy in up to 40% of lesions.22 The histologic characteristics of the target lesion may need to be considered in order to select the most appropriate treatment strategy. While angiography can identify calcium in a lesion in only 15% cases, IVUS can do so in 85% cases23 and therefore, for optimal treatment, a calcified lesion may require high-pressure balloon inflations or plaque modification

strategies (cutting balloon or rotational atherectomy) prior to stenting. In addition to calcification, other lesion characteristics assessed by IVUS that may change the strategy include the presence of arterial remodeling, dissections, and thrombus. After stent deployment, the stent must be properly expanded with all struts apposed to the wall of the vessel in order to allow adequate blood flow (Fig. 32.3). IVUS may improve stenting outcomes by ensuring proper stent expansion and apposition and thereby minimizing the risk of stent thrombosis.24,25 Routine use of IVUS during stent implantation is not the standard of care at most centers, but it may prove useful in complex cases involving high-risk patients in order to ensure proper stent expansion. Thereby, the risk of thrombosis and in-stent restenosis and the need for repeat revascularization can be reduced, as aforementioned, for unprotected left main artery intervention.26–28 Coronary angiography is not an effective tool for assessing atherosclerosis progression or regression. IVUS is better able to quantify the extent of disease and atheroma volume, which may be useful in measuring the effectiveness of antiatherosclerotic agents such as statins.29 CAV is a unique and accelerated form of atherosclerosis and is the leading cause of morbidity and mortality following heart transplantation, but it is often silent, making it difficult to diagnose. It usually affects the large epicardial vessels and also the microcirculation leading to a significant reduction in coronary blood flow. Coronary angiography is unable to recognize the disease in 20% of patients and has a negative predictive value of 50%. Conversely, IVUS has shown to be more sensitive than angiography and is currently recommended for heart transplant recipients for early detection of CAV.30 In addition to its utility in the detection and treatment of coronary artery disease, IVUS has also been proven useful in detecting lesions within saphenous vein grafts.31

Chapter 32:  Intravascular Ultrasound Imaging

SAFETY CONSIDERATIONS The safety of IVUS is well documented by numerous randomized studies and years of experience. The most commonly encountered complication is focal coronary artery spasm, occurring in up to 3% of cases. However, such spasms are rapidly reversible with intracoronary nitroglycerin. The rate of other complications related to IVUS, including coronary artery dissection, perforation, intramural hematoma, vessel thrombosis, and fracture of the IVUS catheter was reported to be low, at 0.4%.32

FUTURE PERSPECTIVES As mentioned previously, grayscale IVUS enables the operator to obtain a tomographic high-resolution visual­ ization of the vessel. Grayscale IVUS, however, is limited in its ability to determine plaque composition. Plaque analysis can be accomplished with the use of IVUS-VH or high frequency IVUS, which can provide advanced images of atherosclerotic tissue composition. Information regarding plaque composition may allow early identi­ fication of plaques vulnerable to rupture. Even more recent advances in IVUS technology include acquisition of computational images of IVUS in three dimensions, known as three-dimensional (3D) IVUS. However, at the present time, 3D IVUS remains primarily a research tool and is not routinely utilized in clinical setting at most centers. Forward-looking intravascular ultrasound (FL-IVUS) utilizes a special catheter that emits ultrasound waves distally from the catheter tip. Given its ability to visualize the vessel in a forward-looking configuration, FL-IVUS holds particular promise in percutaneous revascularization of chronic total occlusions. Although, chronic total occlusions are frequently encountered in clinical practice, they are rarely revascularized due to the complexity of the case and the risk of complications such as vessel dissection, perforation, guide wire injury, embolization, myocardial infarction, and even death.33 Also, the success rate has never been excellent because of the inability to re-enter the true vessel lumen. The enhanced visualization provided by FL-IVUS can be used for crossing chronic total occlusions while minimizing risk of vessel dissection by maintaining the catheter and the guide wire in the true lumen. Such advances in IVUS technology have ensured that IVUS will continue to play an integral role in our understanding and management of coronary artery disease in the future.

661

REFERENCES 1. Nishimura RA, Edwards WD, Warnes CA, et al. Intravascular ultrasound imaging: in vitro validation and pathologic correlation. J Am Coll Cardiol. 1990;16(1):145–54. 2. Schoenhagen P. Atherosclerosis imaging with intravascular ultrasound. Validating acquisition and measurement tools to assure meaningful results. Int J Cardiovasc Imaging. 2006;22(5):615–8. 3. Mintz GS, Nissen SE, Anderson WD, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001; 37(5):1478–92. 4. Berry C, L’Allier PL, Grégoire J, et al. Comparison of intra­ vascular ultrasound and quantitative coronary angiography for the assessment of coronary artery disease progression. Circulation. 2007;115(14):1851–7. 5. Kawasaki M, Bouma BE, Bressner J, et al. Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques. J Am Coll Cardiol. 2006;48(1):81–8. 6. Palmer ND, Northridge D, Lessells A, et al. In vitro analysis of coronary atheromatous lesions by intravascular ultrasound; reproducibility and histo­logical correlation of lesion morphology. Eur Heart J. 1999;20(23): 1701–6. 7. Potkin BN, Bartorelli AL, Gessert JM, et al. Coronary artery imaging with intravascular high-frequency ultrasound. Circulation. 1990;81(5):1575–85. 8. Ehara S, Kobayashi Y, Yoshiyama M, et al. Spotty calcifi­ cation typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation. 2004;110(22):3424–9. 9. Stone GW, Maehara A, Mintz GS. The reality of vulnerable plaque detection. JACC Cardiovasc Imaging. 2011;4(8): 902–4. 10. Nair A, Kuban BD, Tuzcu EM, et al. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation. 2002; 106(17):2200–6. 11. Maluenda G, Lemesle G, Ben-Dor I, et al. Impact of intravascular ultrasound guidance in patients with acute myocardial infarction undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv. 2010;75(1):86–92. 12. Kotani J, Mintz GS, Castagna MT, et al. Usefulness of preprocedural coronary lesion morphology as assessed by intravascular ultrasound in predicting Thrombolysis In Myocardial Infarction frame count after percutaneous coronary intervention in patients with Q-wave acute myocardial infarction. Am J Cardiol. 2003;91(7):870–2. 13. Hausmann D, Erbel R, Alibelli-Chemarin MJ, et al. The safety of intracoronary ultrasound. A multicenter survey of 2207 examinations. Circulation. 1995;91(3):623–30.

662

Section 2:  Echocardiography/Ultrasound Examination and Training

14. Parise H, Maehara A, Stone GW, et al. Meta-analysis of randomized studies comparing intravascular ultrasound versus angiographic guidance of percutaneous coronary intervention in pre-drug-eluting stent era. Am J Cardiol. 2011;107(3):374–82. 15. Park SJ, Kim YH, Park DW, et al.; MAIN-COMPARE Investigators. Impact of intravascular ultrasound guidance on long-term mortality in stenting for unprotected left main coronary artery stenosis. Circ Cardiovasc Interv. 2009;2(3):167–77. 16. Jensen LO, Thayssen P, Mintz GS, et al. Comparison of intravascular ultrasound and angiographic assessment of coronary reference segment size in patients with type 2 diabetes mellitus. Am J Cardiol. 2008;101(5):590–5. 17. Nishioka T, Amanullah AM, Luo H, et al. Clinical validation of intravascular ultrasound imaging for assessment of coronary stenosis severity: comparison with stress myo­ cardial perfusion imaging. J Am Coll Cardiol. 1999; 33(7):1870–8. 18. Miller DD, Donohue TJ, Younis LT, et al. Correlation of pharmacological 99mTc-sestamibi myocardial perfusion imaging with poststenotic coronary flow reserve in patients with angiographically intermediate coronary artery stenoses. Circulation. 1994;89(5):2150–60. 19. Joye JD, Schulman DS, Lasorda D, et al. Intracoronary Doppler guide wire versus stress single-photon emission computed tomographic thallium-201 imaging in assess­ ment of intermediate coronary stenoses. J Am Coll Cardiol. 1994;24(4):940–7. 20. Abizaid AS, Mintz GS, Abizaid A, et al. One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms. J Am Coll Cardiol. 1999;34(3):707–15. 21. Prati F, Pawlowski T, Sommariva L, et al. Intravascular ultrasound and quantitative coronary angiography assessment of late in-stent restenosis: in vivo human correlation and methodological implications. Catheter Cardiovasc Interv. 2002;57(2):155–60. 22. Mintz GS, Pichard AD, Kovach JA, et al. Impact of preintervention intravascular ultrasound imaging on transcatheter treatment strategies in coronary artery disease. Am J Cardiol. 1994;73(7):423–30. 23. St Goar FG, Pinto FJ, Alderman EL, et al. Intravascular ultrasound imaging of angiographically normal coronary

arteries: an in vivo comparison with quantitative angio­ graphy. J Am Coll Cardiol. 1991;18(4):952–8. 24. Ziada KM, Tuzcu EM, De Franco AC, et al. Intravascular ultrasound assessment of the prevalence and causes of angiographic “haziness” following high-pressure coronary stenting. Am J Cardiol. 1997;80(2):116–21. 25. Gil RJ, Pawlowski T, Dudek D, et al.; Investigators of Direct Stenting vs Optimal Angioplasty Trial (DIPOL). Comparison of angiographically guided direct stenting technique with direct stenting and optimal balloon angioplasty guided with intravascular ultrasound. The multicenter, randomized trial results. Am Heart J. 2007;154(4):669–75. 26. Bourantas CV, Naka KK, Garg S, et al. Clinical indications for intravascular ultrasound imaging. Echocardiography. 2010;27(10):1282–90. 27. Roy P, Waksman R. Intravascular ultrasound guidance in drug-eluting stent deployment. Minerva Cardioangiol. 2008;56(1):67–77. 28. Weissman NJ, Koglin J, Cox DA, et al. Polymer-based paclitaxel-eluting stents reduce in-stent neointimal tissue proliferation: a serial volumetric intravascular ultrasound analysis from the TAXUS-IV trial. J Am Coll Cardiol. 2005;45(8):1201–5. 29. Nissen SE. Application of intravascular ultrasound to characterize coronary artery disease and assess the progression or regression of atherosclerosis. Am J Cardiol. 2002;89(4A):24B–31B. 30. Logani S, Saltzman HE, Kurnik P, et al. Clinical utility of intravascular ultrasound in the assessment of coronary allograft vasculopathy: a review. J Interv Cardiol. 2011; 24(1):9–14. 31. Jain SP, Roubin GS, Nanda NC, et al. Intravascular ultra­ sound imaging of saphenous vein graft stenosis. Am J Cardiol. 1992;69(1):133–6. 32. Pinto FJ, St Goar FG, Gao SZ, et al. Immediate and oneyear safety of intracoronary ultrasonic imaging. Evaluation with serial quantitative angiography. Circulation. 1993;88 (4 Pt 1):1709–14. 33. Srinivas VS, Brooks MM, Detre KM, et al. Contemporary percutaneous coronary intervention versus balloon angioplasty for multivessel coronary artery disease: a comparison of the National Heart, Lung and Blood Institute Dynamic Registry and the Bypass Angioplasty Revascularization Investigation (BARI) study. Circulation. 2002;106(13):1627–33.

CHAPTER 33 Peripheral Vascular Ultrasound Ricardo Benenstein, Muhamed Saric

Snapshot  Ultrasound Diagnosis of CaroƟd Artery Diseases

INTRODUCTION Atherosclerosis is a systemic disease of the medium and large arteries. It affects not only the coronaries—the main focus of cardiologists—but also aorta, carotids, and other major peripheral vessels. It is a dynamic disease that makes prevention and treatment a highly complex process, and it is the leading cause of cardiovascular morbidity and mortality worldwide. Physicians who fashion themselves as providers of health care to people with cardiac illnesses, frequently encounter patients who may have sought their expertise for treatment of ischemic heart disease but whose lives are also affected by peripheral vascular disease. Thus, there is an increasing trend for these practitioners—who, if board-certified, are deemed experts in “cardiovascular diseases”—to be more involved in the vascular medicine component of their subspecialty. The rapid growth in percutaneous peripheral vascular interventions has contributed to this trend. With the fast pace of noninvasive imaging technology, there has been burgeoning interest among cardiologists, and particularly echocardiographers, in performing vascular ultrasound studies, in an attempt to refine both risk stratification and the need for more aggressive preventive strategies.1,2 Furthermore, there is a growing desire among cardiology trainees to acquire more experience in vascular medicine and vascular imaging

 Ultrasound Diagnosis of Femoral Access ComplicaƟons

modalities. The effort to strengthen the understanding of vascular diseases among cardiologists is reflected in a recent joint statement by the Society for Cardiovascular Angiography and Interventions and the Society of Vascular Medicine: “The essentials of vascular medicine should be taught to all cardiology fellows. Vascular medicine training should be integrated into the fellowship program and include the evaluation and management of vascular diseases, exposure to noninvasive diagnostic modalities, angiography, and peripheral catheter-based interventions.”3 In our experience at the New York University Langone Medical Center’s Noninvasive Cardiology Laboratory, two areas of vascular ultrasound use have fostered particular interest among clinical and interventional cardiologists— the assessment of the extracranial cerebrovascular circulation and the evaluation of complications of femoral access during percutaneous interventions. Both topics will be discussed in detail in this chapter.

ULTRASOUND DIAGNOSIS OF CAROTID ARTERY DISEASES Introduction In the United States, stroke ranks as the third leading cause of death, after ischemic heart disease and cancer, and is the

664

Section 2: Echocardiography/Ultrasound Examination and Training

leading cause of permanent disability. Every year, there are >700,000 new stroke cases in the United States, resulting in >150,000 deaths. The economic burden imposed on society, estimated to be more than $58 billion in direct and indirect costs annually, is enormous. Carotid artery occlusive disease accounts for 15–20% of the ischemic strokes, of which three quarters involve the anterior carotid circulation and the remaining quarter the posterior vertebrobasilar system. Because most of these cerebrovascular accidents, resulting in significant morbidity and mortality, occur without any warning sign, attention has turned to the detection and management of asymptomatic carotid stenosis, the prevalence of which is on the rise.4 The overall prevalence of asymptomatic carotid artery disease (defined as >50% luminal reduction by duplex ultrasound) varies considerably. In the general population, it is between 2% and 8%. But among patients with known coronary artery disease, the prevalence is reported to be 11–26%. It is even higher in patients with recognized peripheral vascular disease.5 The risk of stroke is highly dependent on the degree of carotid stenosis and the presence of symptoms. Landmarkrandomized multicenter trials have determined that the combination of carotid endarterectomy (CEA) and best medical therapy significantly reduces the risk of stroke in symptomatic patients with ≥70% carotid artery stenosis, as well as in asymptomatic patients with ≥60% carotid stenosis.6–8 At the same time, AbuRahma et al have shown that the heterogeneity of the plaque is more closely related to symptoms than the degree of stenosis, and they have suggested that plaque characteristics be considered when selecting patients for CEA, particularly in asymptomatic carotid disease.9 The principal role of carotid duplex ultrasound examination is the detection of stenosis in the internal carotid artery (ICA). But, because of studies demonstrating the prognostic significance of plaque morphology, characterizing plaque by analyzing the gray-scale appearance of the arterial wall, with particular attention to the ultrasonic features of the plaque in the carotid bulb, has important implications. At the same time, the fact that no diagnostic method has been proven to predict which asymptomatic plaques will lead to cardiovascular events makes carotid duplex ultrasound a fertile ground for research in patients with cardiovascular disease.10 This chapter will emphasize fundamental aspects of the carotid ultrasound examination, including cerebrovascular anatomy and physiology, scanning protocol,

intima-media thickness (IMT) and plaque characterization, criteria for grading stenosis of native arteries, and standards for follow-up evaluation of vessels after endarterectomy and stenting. It should be noted that the accuracy of carotid duplex studies depends on the technical skills of the sonographer, on consistent adherence to the examination protocol, and on the experience of the physician interpreting them.

Cerebrovascular Anatomy Thorough knowledge of the anatomy of the cervical arteries, including vessel origin and trajectory, branches, and main collateral pathways, is paramount to understanding cerebrovascular hemodynamics, particularly when there is significant stenosis or total occlusion of one the carotid and/or vertebral arteries (VAs). What follows is a basic overview of the cervical arteries and the complex intracranial connections between the anterior and posterior circulations through the Willis circle and main collateral pathways. Four vessels supply the brain: two internal carotid arteries, which provide circulation to the anterior cerebrum; and two VAs, which provide circulation to the posterior brain. Distally, both circulations join at the base of the brain forming an arterial loop known as the Circle of Willis. The presence of significant flow abnormalities of the origin of the carotid or subclavian arteries (SAs) will have great impact on the Doppler spectrum and direction of the flow in the cervical arteries. Therefore, knowledge of the anatomy and ultrasound interrogation techniques of the aortic arch vessels is necessary to ensure complete assessment and understanding of the duplex findings.

Aortic Arch The aortic arch is approximately 4–5 cm long and 2.5–3.0 cm in diameter. Morphologically, the aortic arch is classified as one of three types, based on its relationship to the innominate artery. This assessment, however, is more important to the interventionalist than to the vascular technologist performing ultrasound examination.11 In type I aortic arch, all three great vessels originate in the same horizontal plane as the outer curvature of the aortic arch. In the type II aortic arch, the innominate artery originates between the horizontal planes of the outer and inner curvatures of the arch.

Chapter 33: Peripheral Vascular Ultrasound

Fig. 33.1: Types of aortic arch. Type I aortic arch—all three great vessels originate in the same horizontal plane as the outer curvature of the aortic arch. Type II aortic arch—the innominate artery originates between the horizontal planes of the outer and inner curvatures of the arch. Type III aortic arch—the innominate artery originates below the horizontal plane of the inner curvature of the arch. Courtesy: Illustration created by Melissa LoPresti and Robert Spencer, NYU).

In the type III aortic arch, the innominate artery originates below the horizontal plane of the inner curvature of the arch (Fig. 33.1). The arch gives rise to three great vessels. From right to left, the first branch is the innominate or brachiocephalic artery, which in turn branches into the right SA and the right common carotid artery (CCA). In approximately 70% of the population, the second branch is the left CCA, and the last branch is the left SA (Figs 33.2A to C). The remaining 30% of the population exhibit any of the several anatomical variations, which may lead to difficulty in the identification of a stenotic vessel.12 The most common variant, seen in nearly 15% of the population, is the so-called bovine arch in which the innominate artery and the left CCA share a common origin. Anecdotally, the term bovine arch is a misnomer, as this type of branching is actually exceedingly rare or perhaps nonexistent among cattle (a true bovine aortic arch has no similarity to any of the common human aortic arch variations: the aortic arch branching pattern found in cattle has a single brachiocephalic trunk arising from the aortic arch, which ultimately splits into the bilateral SAs and a bicarotid trunk)12 (Figs 33.3A and B). The second most common variant, seen in approximately 10% of the population, involves the left

665

CCA originating directly from the innominate artery at a distance of 1–2.5 cm from the aortic arch (this variant is similar to the common origin variant, except that the left CCA originates more distally from the innominate artery, rather than as part of a common trunk).12 A much less common aortic arch anomaly is a left aortic arch with an aberrant right SA that arises from the arch distally, near the origin of the left SA, and crosses in the posterior mediastinum, usually behind the esophagus, on its way to the right upper extremity (0.5–2.0% of the aortic arch anomalies). When an aneurysmal dilatation of the proximal portion of the aberrant right SA is present, the pouch-like aneurysmal dilatation is called a diverticulum of Kommerell. A similar aneurysm can be seen with an aberrant left SA associated with a right aortic arch.13 More rare aortic arch anomalies are beyond the scope of this chapter. The innominate or brachiocephalic artery is the first and largest aortic arch branch. It originates near the midline and travels superiorly and slightly posteriorly toward the right supraclavicular fossa (from where it is best interrogated by Doppler ultrasound). It divides, about 4–5 cm after its origin and just above the right sternoclavicular junction, into the right SA and the right CCA. The left CCA is the second branch of the aortic arch. It too originates within the thorax immediately after the innominate artery, running anteriorly toward the left side of the neck. Its origin can be evaluated from either the suprasternal notch or the left supraclavicular fossa. The left SA is the last arch branch; it originates laterally and posteriorly to the left common carotid, and ascends through the thoracic outlet. Its origin is usually interrogated from the left supraclavicular fossa.

Anterior Circulation Both CCAs ascend straight through the neck behind the sternocleidomastoid muscles, usually posterior and medial to the internal jugular veins. But their trajectories can become quite tortuous with age and long-standing hypertension. The CCAs are 6–8 mm in diameter. Generally speaking, they do not give rise to branches proximal to the bifurcation; but it is not uncommon to see the superior or inferior thyroid arteries arise from the CCA near the origin of the external carotid arteries. The CCA bifurcates into the ICA and the external carotid artery (ECA) at the level of C4 to C5 in approximately 50% of patients. In 10% of patients, this bifurcation is lower in the

666

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 33.2A to C: Branches of the aortic arch. (A) Three-dimensional (3D) volume rendering computed tomography angiography (CTA) demonstrates the normal origin of the great vessels. From right to left: the innominate artery, which in turn branches into the right subclavian and common carotid arteries, the left CCA, and the left subclavian artery. This common variant is present in approximately 70% of the population; (B and C) Magnetic resonance angiography images demonstrate the origin of the great vessels from an anterolateral view (B) and from an anterior view (C). (CCA: Common carotid artery; INN art: Innominate artery; Subcl: Subclavian artery; Vert: Vertebral artery).

A

B

Figs 33.3A and B: “Bovine Arch.” (A) Demonstrates the most common configuration of the aortic arch; (B) The innominate artery and the left common carotid artery share a common origin. This variant is present in 15% of the population and is so-called “Bovine Arch”. This term in fact is a misnomer, as this type of branching is actually extremely rare among cattle. Courtesy: Illustration created by Melissa LoPresti and Robert Spencer, NYU).

neck (lowest seen at T1–T2), and in about 40% of patients, the bifurcation is higher (highest seen at C1–C2).14,15 This variance presents a diagnostic challenge for the vascular technologist performing duplex interrogation of the ICA (Figs 33.4A to C). The ECA originates at the bifurcation and supplies blood flow to neck, face, scalp, maxilla, and thyroid. It courses superiorly and anteriorly, and gives off a highly variable number of branches before it divides into the maxillary artery and superficial temporal artery. Both terminal vessels are important as collateral pathways, providing known pre-Willisian extracranial–intracranial anastomoses between the ECA and ICA (discussed later in this chapter). The ICA runs cranially, posterior and lateral to the ECA, and supplies blood to the anterior cerebral hemispheres as well as the ipsilateral eye.

Chapter 33: Peripheral Vascular Ultrasound

A

B

667

C

Figs 33.4A to C: Right side vessels. (A) This three-dimensional (3D) volume rendering computed tomography angiography (CTA) demonstrate the relationship of the CCA and the vertebral artery on the right side. The common carotid runs anteriorly behind the sternocleidomastoid muscle, until it bifurcates into the internal and external carotid arteries. The vertebral artery runs posterior and lateral to the common carotid and ascends in the neck within the transverse foramens of the cervical vertebrae C6 to C2. The right subclavian artery originates from the innominate artery bifurcation and runs behind the clavicle bone toward the arm. Indicated with a “star” is the left carotid system. 3D reconstruction courtesy of NYU Langone Medical Center Radiology Lab; (B) Diagram showing the origin and relationship of the anterior and posterior circulations; (C) 3D volume rendering CTA of the CCA and bifurcation. The proximal ICA presents its bulbous, fusiform dilatation known as the “carotid bulb”. (CCA: Common carotid artery; ECA: External carotid artery; ICA: Internal carotid artery; INN: Innominate artery; SCM: Sternocleidomastoid muscle). Courtesy: Illustration created by Melissa LoPresti and Robert Spencer, NYU).

Typically, the ICA is larger than the external, and its proximal portion has a fusiform dilatation known as the “carotid bulb” because of its particular shape (Figs 33.5A to C). The carotid bulb begins at the level of the CCA bifurcation and extends 1.5–2 cm into the ICA measuring approximately 7–9 mm in its larger diameter. This structure, known also as the carotid sinus, is heavily innervated, and contains baroreceptors involved in arterial blood flow regulation. In the posterior aspect of the carotid bulb, there is a small cluster of chemoreceptors known as the carotid body, which is responsible for sensing changes in pH, temperature, partial pressure of O2, and CO2. The carotid bulb is the most common site of atheroma formation in the cervical segment of the ICA. The atherosclerotic disease process, as well as revascularization techniques (either surgical or endovascular), may affect the regulatory functions of the carotid bulb. Distal to the bulb, the ICA is generally straight and measures 4–6 mm in diameter. This vessel turns medially before entering the carotid canal in the petrous bone. The

mid and distal cervical segments of the ICA tend to have only mild curvatures, but it is not uncommon for the ICA to undergo some elongation and to become tortuous with aging or in the presence of hypertension. Three morphological variants may be present:15,16 • Loops are described as “S” or “C” shaped elongations or curved arteries. • Coils are pronounced, redundant “S” shaped curves (or complete circle of the vessel). Loops and coils are thought to be congenital variations. They are usually bilateral and do not cause symptoms unless exaggerated by aging or aggravated by atherosclerotic disease. • Kinks are sharp angulations of the artery, usually causing some degree of luminal narrowing, but rarely producing hemodynamically significant stenosis. Aging, atherosclerosis, and hypertension are considered predisposing factors (Figs 33.6 and 33.7 and Movie clip 33.1). The ICA enters the carotid canal in the temporal bone without giving off any branches in its cervical extracranial

668

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

Figs 33.5A to C: Left side vessels. (A) The left common carotid and left subclavian have independent origin in the aortic arch. Threedimensional (3D) reconstruction courtesy of NYU Langone Medical Center Radiology Lab; (B) Diagram shows the origin and relationship of the anterior and posterior circulations; (C) 3D volume rendering computed tomography angiography (CTA) of the CCA and bifurcation. The carotid bulb is evident in this view. (CCA: Common carotid artery; ECA: External carotid artery; ICA: Internal carotid artery). Courtesy: Illustration created by Melissa LoPresti and Robert Spencer, NYU).

and the middle cerebral artery, which are part of the Circle of Willis.

Posterior Circulation

Fig. 33.6: Morphological variants of internal carotid artery (ICA) elongation and tortuosity. Diagram demonstrates the three most common types of curvatures and tortuosity of the ICA. Courtesy: Illustration created by Melissa LoPresti and Robert Spencer, NYU).

segment. The ophthalmic artery and the posterior communicating artery are the main intracranial branches of the ICA. Both constitute critical collateral pathways in the setting of significant stenosis or total occlusion of the cervical ICA. After a short segment known as the supraclinoid ICA, the artery divides into the anterior cerebral artery

The VAs arise from the posterosuperior aspect of the SAs, and they ascend in the neck within the transverse foramens of the cervical vertebrae C6 to C2—producing a characteristic imaging during color duplex interrogation— before entering the cranium through the foramen magnum. VAs are frequently asymmetric. In 50% of cases the left VA is larger and dominant, in 25% the right VA is larger, and in the remaining 25% they are codominant. In a small fraction of patients, one of the vessels is hypoplastic or even absent.17 The basilar artery is a short vessel formed by the convergence of the intracranial segments of both VAs, at the base of the medulla oblongata, and which then courses the median groove of the pons. The posterior inferior cerebellar arteries and the anterior inferior cerebellar arteries—branches of the vertebral and basilar arteries, respectively—provide blood flow to the lower medulla, pons, lower cerebellum, and fourth ventricle.

Chapter 33: Peripheral Vascular Ultrasound

669

B

A

C

Figs 33.7A to C: Left ICA loop. (A) Magnetic resonance angiography of the left carotid system demonstrate an “S” loop of the mid-distal ICA (within the yellow dotted circle); (B) Color duplex ultrasound image of the mid-distal ICA “S” loop of the left, obtained with a curvilinear C6-2 MHz transducer array. This large footprint transducer provides a large field of view of the neck. Movie clip 33.1 corresponds to this panel; (C) Corresponding computed tomography angiography (CTA) image of the “S” loop in the same orientation as the ultrasound image. The black dotted arrow indicates a moderate stenosis in the carotid bulb. (ECA: External carotid artery; IA: Innominate artery; ICA: Internal carotid artery; LCCA: Left common carotid artery; LSA: Left subclavian artery).

Ultimately, the basilar artery bifurcates into the posterior cerebral arteries, which supply blood to the brain stem, superior cerebellum, and cerebral cortex. The anterior and posterior circulations are interconnected at the base of the brain via the posterior communicating arteries, each of which connect its ipsilateral ICA with its ipsilateral posterior cerebral artery17,18 (Figs 33.8A and B).

Collateral Pathways With advanced atherosclerosis, the capacity of the cerebral circulation to distribute flow becomes increasingly compromised. However, whether neurological deficits appear depends partly on how well-developed the builtin reserve cerebral collateral circulation is. The ability of the collateral pathways to supply blood depends not only on the age of the patient but also on the speed of the arterial occlusion. This is because atherosclerotic disease may involve collateral pathways in older individuals; or the collateral vessels may not adapt fast enough in the case of sudden occlusions, such as those resulting from embolism.19

Several routes for collateral circulation have been described: The major intracranial collateral pathway of the brain is the “Circle of Willis.” Thomas Willis (1621–75) is credited with the first description of this structure—a large interarterial connection between the anterior and posterior circulations. Several possible configurations of the Circle of Willis have been described in the human anatomy, and a complete ring is found in 1.5 mm as measured from the media–adventitia interface to the intima–lumen interface.”23 Plaques should be evaluated with high-resolution gray-scale images without color flow mapping. Both longitudinal and transverse views are required to completely assess a plaque’s size and extension. It is important to determine the location, size and extent of the plaque, as well as its thickness, echogenicity, and texture. The degree of luminal narrowing produced by a plaque’s encroachment should also be assessed.36 Plaques may progress from small intraluminal protrusions lacking any significant hemodynamic effects to high degree stenosis or total occlusion of the vessel. Larger carotid plaque size is associated with a higher risk of stroke and major adverse cardiovascular events. In a 5-year prospective study of 1,600 patients, Spence et al found an adjusted relative risk of 2.9 for a combined stroke and acute coronary event end point in patients with large carotid plaque area.37 Based on ultrasonographic and histological correlations, plaques that are classified as echogenic have increased calcified and fibrous tissue; and those that are echolucent have higher lipid content, increased macrophage density, and a thin fibrous cap.

Studies have shown that the presence of echolucent (hypoechoic) plaques is highly predictive of stroke and cardiovascular events.37–39 In fact, the more echolucent a plaque appears on ultrasound, the more likely the patient will sustain a TIA or stroke in the future. Surface irregularities and intraplaque hemorrhage are characteristics of complicated plaques. While intraplaque hemorrhage is a marker of plaque inflammation and instability, its role as an independent predictor of future ischemic events is not well established35 (Figs 33.16A to D and Movie clips 33.6 and 33.7). Calcification is very common in carotid plaques. Calcification provides the plaque with structural stability, making it less likely to rupture, and cause symptoms than a noncalcified plaque would be.40 Gray-scale images do not reliably identify plaque ulceration. But focal depression associated with irregularities in the plaque’s surface may suggest the presence of an ulcerated plaque, and color Doppler may help to demonstrate the ulceration (Figs 33.17A to F). The ultrasonic plaque classification used most frequently today is based on the Gray-Weale criteria. Modified by Geroulakos in 1993, is known as the “Geroulakos classification”:41 Type 1: Uniformly echolucent plaque, with or without a visible thin fibrous cap.

Chapter 33: Peripheral Vascular Ultrasound

A

B

C

D

679

Figs 33.16A to D: Intraplaque hemorrhage and protruding plaque. (A and B) Duplex ultrasound shows a small, nonobstructing echolucent plaque in the carotid bulb, with an anechoic area within (yellow arrow), very suggestive of intraplaque hemorrhage. There is no hemodynamic disturbance of the blood flow as demonstrated by the absence of color flow acceleration and the presence of normal physiological turbulence. Movie clip 33.6 corresponds to this panel; (C and D) Duplex ultrasound shows a heterogeneous, irregular protruding plaque in the carotid bulb in a patient admitted for recurrent transient ischemic attacks. Note in Movie clip 33.7 the mobile component of this plaque.

Type 2: Predominantly echolucent plaque, < 50% of which contains echogenic areas. Type 3: Predominantly echogenic plaque, < 50% of which contains echolucent areas. Type 4: Uniformly echogenic plaque. Type 5: Unclassified plaque in which heavy calcification and acoustic shadows precludes adequate visualization (Figs 33.18A to F). Ultrasound examination and plaque characterization are highly subjective. The use of disparate gain, filter, and compression settings by different operators may result in poor reproducibility. B-mode image normalization by computer-assisted measurements of plaque echodensity has helped to overcome this problem.

For the most part, this innovation remains a research tool used in the identification of vulnerable plaques and in large studies of carotid stenting. But the software is expected to become commercially available for duplex scanners in the near future.

Grading Carotid Stenosis: How much is Severe? Internal Carotid Artery Stenosis The criteria for defining a hemodynamically significant ICA stenosis by duplex ultrasound have been debated for decades. Digital angiography is still considered the

680

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

E

F

Figs 33.17A to F: Ulcerated plaque. (A and B) The gray-scale and color flow images demonstrate a heterogeneous plaque in the posterior wall of the carotid bulb with a focal depression suggestive of ulceration (short red arrow). The color flow imaging shows helps to demonstrate the ulceration. The Doppler interrogation in (C) demonstrates normal velocities. There is no hemodynamically significant stenosis associated with this plaque; (D) The gray-scale and color flow images show a large, predominantly echolucent plaque in the posterior wall of the carotid bulb, with a deep depression and interruption of the fibrous cap (white long arrow). The color flow fills the cavity in (E), and shows evidence of flow disturbance characterized by a flow convergence (“pisa” flow) in the distal segment of the bulb; (F) demonstrates significant increase in systolic and diastolic velocities, consistent with moderate degree of stenosis.

Chapter 33: Peripheral Vascular Ultrasound

A

B

C

D

E

F

681

Figs 33.18A to F: The Geroulakos classification. (A) Normal carotid bifurcation and carotid bulb free of disease; (B) Type 1: Uniformly echolucent plaque, with or without visible thin fibrous cap. (C) Type 2: Predominantly echolucent plaque, 4.0

> 100

50%–69% ≥ 70% to near occlusion Near occlusion

High, low, or undetec able

Visible

Variable

Variable

Total occlusion

Undetectable

Visible, no detectable lumen

N/A

N/A

(CCA: Common carotid artery; EDV: End-diastolic velocity; ICA: Internal carotid artery; PSV: Peak systolic velocity; ICA/CCA PSV ratio: Internal carotid artery to common carotid artery peak systolic velocity ratio).

A 70% include ICA/CCA PSV ratio > 4 and ICA EDV > 100 cm/s. While the EDV threshold value is very suggestive of lesions > 70%, this parameter is not very sensitive because EDV varies with the heart rate and other systemic factors (Figs 33.23A to E and Movie clips 33.10 to 33.13). As the degree of luminal narrowing increases, the increase in the intrastenotic flow velocity becomes the most important direct criterion for diagnosing a flowlimiting lesion. The ICA/CCA ratio and the EDV velocity increase as well. However, as the lesion progresses in severity, the resistance through the tight stenosis greatly affects the blood flow, causing a paradoxical low flow velocity (“string sign”).

This corresponds to the critical Grade III–IV stenosis in the Spencer’s curve, wherein significant decreases in the flow velocity and blood flow volume occur with >80% diameter stenosis (or more than 95% in cross-sectional area stenosis).48 In cases of near occlusion of the ICA, the diagnostic velocity parameters may not apply, and velocities may be high, low, or undetectable. This diagnosis is therefore established primarily by demonstrating a markedly narrowed lumen with color or power Doppler ultrasound. Total occlusion of the ICA should be suspected when there is no detectable patent lumen on grayscale ultrasound and no flow with spectral, power, or color Doppler modalities. MRA, CTA, or conventional angiography may be used for confirmation in this setting.

Validation of the 2003 Carotid Duplex SRU Consensus Criteria During a 3-year period, AbuRahma et al analyzed 376 carotid arteries, for which both duplex examinations and digital angiography were available. Duplex scans were interpreted in accordance with the 2003 SRU Consensus Criteria for carotid artery stenosis, and arteriographic evaluations were performed using the NASCET method. The study found that the consensus criteria had a sensitivity (Sn) of 93%, a specificity (Sp) of 68%, and an overall accuracy (OA) of 85% for detecting an angiographic stenosis in the range of 50–69%. The authors concluded that the consensus criteria for diagnosing 50–69% stenosis could be significantly improved by using an ICA PSV of 140–230 cm/s (instead of 125–230 cm/s), which would have provided a Sn of 94%, a Sp of 92%, and an OA of 92%. The consensus criteria performed well for stenosis ≥ 70%, with a Sn of 99%, a Sp of 86%, and an OA of

Chapter 33: Peripheral Vascular Ultrasound

A

B

C

D

685

Figs 33.20A to D: Carotid bulb plaque with 70% stenosis. (A) There is a large, heavily calcified plaque in the posterior wall of the carotid bulb, right at the origin of the ICA. Movie clips 33.10 and 33.11 demonstrate significant luminal reduction and high aliasing flow during both systole and diastole, indicating high velocities at the stenosis during the entire cardiac cycle. There is also evident poststenotic turbulent flow. Movie clip 33.12 is a transverse view of the carotid bulb showing similar the heavily calcified plaque and the high velocity flow across the residual lumen; (B) The Power Angio mode enhances the flow across the stenosis and in the remaining ICA, which matches exactly to the three-dimensional computed tomography angiography (3D CTA) reconstruction shown in Figure E. Movie clip 33.13 corresponds to this figure. (C and D) The duplex study exhibits a peak systolic velocity in the distal CCA of 85 cm/s, and a peak systolic velocity in the ICA of 410 cm/s. The carotid artery/common carotid artery (ICA/ CCA) ratio is 4.8 (>4.0), and the end diastolic velocity in the ICA is 105 cm/s. This data is consistent with severe >70% stenosis in the carotid bulb. (CCA: Common carotid artery; ECA: External carotid artery; EDV: End-diastolic velocity; ICA: Internal carotid artery; PSV: Peak systolic velocity).

contralateral high-grade carotid stenosis or occlusion, and this overestimation appears to be proportional to the severity of the contralateral disease.53,54 The increased velocities may be a consequence of increased collateral flow that is thought to represent a compensatory mechanism in the ipsilateral carotid system aimed at maintaining a stable cerebral circulation via the Circle of Willis.54–56 This phenomenon must be considered when applying established duplex velocity criteria to an ICA stenosis, as high velocities may be misconstrued as reflecting a higher degree of stenosis than is actually the case.

Assessment after Carotid Artery Endarterectomy and Stenting The traditional standard of care in treating cervical carotid artery occlusive disease has been CEA, a procedure initially described in the 1950s by Scott, DeBakey, and Cooley. In 1991, landmark NASCET demonstrated a reduction in stroke and death rates at 2 years from 26% to 9% after endarterectomy. Since then, several other studies have suggested the superiority of the surgical approach to medical therapy for stenosis > 70%. In the 1980s, angioplasty was pioneered for cervical carotid artery disease treatment, and the subsequent introduction of stent technology advanced nonsurgical interventional management of carotid artery disease. At present, there are two randomized clinical trials and six registries evaluating the safety and efficacy of carotid artery stenting (CAS).57 Recently, the CREST trial showed that stenting and endarterectomy result in similar rates of the primary composite outcome (stroke, myocardial

Chapter 33: Peripheral Vascular Ultrasound

689

C

A

B

D

Figs 33.24A to D: Occlusion of the ICA. (A) The color duplex image of the right carotid bifurcation demonstrates a large heterogeneous plaque filling the entire carotid bulb. There is no flow across the ICA, which is occluded. Movie clips 33.14 and 33.15 correspond to this figure; (B) Shows two cross-sectional views of the bifurcation demonstrating patency of the ECA, and the occlusion of the ICA (white arrows); (C) The ECA has increased compensatory flow velocity (“internalization of the ECA”). The temporal tap helps to confirm its identity and patency. The yellow arrows indicate the fluctuations in the baseline tracing of the ECA; (D) The brain computed tomography angiography (CTA) in this patient shows total or near total occlusion of the right ICA. A diminutive segment of the right middle cerebral artery (black arrow) is filled via Circle of Willis collaterals, and the right anterior cerebral artery (blue arrow) is filled via the anterior communicating artery. The left middle cerebral artery (yellow arrow) is of normal caliber. (ECA: External carotid artery; ICA: Internal carotid artery).

infarction, and death) among men and women with either symptomatic or asymptomatic carotid stenosis.58 Duplex ultrasound is a reliable tool for surveillance post carotid artery endarterectomy and CAS , and criteria have been established for follow-up of both interventions. However, the timing and frequency of postintervention studies remains controversial. Several published reports have shown that most cases of restenosis occur within the first 2 years after CEA, and recommend an initial survey 6 months after surgery.59–61 Following CEA, the intima-media layer at the surgical site is not seen. An “intimal step” at the proximal end is often seen, followed by bright reflectors in the anterior wall, which arise from the arteriotomy closure sutures.

Persistent flow disturbances and high velocities are usually the result of residual plaque and stenosis, which may be attributable to technically inadequate surgery that may have been prevented with placement of a synthetic or vein patch. Restenosis at the surgical site within the first year is usually due to neointimal proliferation (overgrowth of smooth muscle and fibrous tissue in place of the striped intima-media following carotid intervention). In contrast, recurrence seen 3 years after CEA is usually due to the uninterrupted process of atherosclerosis. Duplex ultrasonography is the standard technique for surveillance after CEA. In 2011, AbuRahma reported follow-up in 200 patients who had undergone CEA

690

Section 2: Echocardiography/Ultrasound Examination and Training

A

B

C

D

Figs 33.25A to D: Carotid stenting. (A) Severe left ICA stenosis confirmed by CT angiography. The white arrow indicated the large plaque in the carotid bulb with small residual lumen. Movie clips 33.16 and 33.17 correspond to this figure; (B) Spectral velocity analysis shows the increased peak systolic and end-diastolic velocities in the ICA, with a carotid artery/common carotid artery (ICA/CCA) ratio of 4.8, consistent with severe >70% stenosis in the left carotid bulb; (C) The patient underwent angiography and carotid stenting with adequate lumen postintervention. Movie clip 33.18 shows the significant lesion in the left carotid bulb, and Movie clip 33.19 exhibits adequate residual lumen after stent deployment. (ICA: Internal carotid artery); (D) The color duplex ultrasound post intervention shows the stent (white arrows) with normalization of the vessel lumen and velocities.

with patching during a recent 2-year period. PSVs, EDV, and ICA/CCA ratios were correlated with angiography (ICA PSVs of ≥ 130 cm/s underwent carotid CTA and/or conventional carotid arteriograms to confirm the presence of post-CEA stenosis). The findings were:62 • An ICA PSV > 213 cm/s optimally detected restenosis ≥ 50% with a Sn of 99%, Sp of 100%, and OA of 99%. An ICA EDV > 60 cm/s had a Sn, Sp, and OA of 93, 97, and 93%, respectively for detecting ≥ 50% restenosis. A PSV ICA/CCA ratio > 2.3 optimally detected restenosis of ≥ 50%.

•

An ICA PSV > 274 cm/s was optimal for identifying ≥ 80% restenosis with a Sn of 100%, Sp of 91%, and OA of 100%. An ICA EDV > 94 cm/s had a Sn, Sp, and OA of 98, 100, and 98%, respectively for detecting ≥ 80% restenosis. A PSV ICA/CCA ratio > 3.4 was best for identifying restenosis ≥ 80%. It must be noted that the placement of a stent in a carotid artery alters the mechanical properties of the vessel, producing higher velocities in the absence of residual stenosis or technical error. Because the reduced

Chapter 33: Peripheral Vascular Ultrasound

compliance of a stented carotid artery may produce falsely elevated velocities relative to the native nonstented carotid artery, established ultrasound criteria for ICA stenosis are not appropriate for assessing restenosis after CAS.63 The incidence of carotid restenosis may vary widely depending on the definition of restenosis and the method used to calculate the degree of stenosis. While several groups have proposed restenosis criteria, to date there is no consensus regarding what constitutes significant restenosis. AbuRahma et al. have confirmed the need for revised velocity criteria in stented carotid arteries. They reported on 144 patients who had undergone CAS as part of clinical trials. Follow-up consisted of carotid duplex ultrasound immediately after and 1 month after stenting, as well as every 6 months thereafter. Patients whose ICA PSVs were > 130 cm/s underwent carotid computed tomography (CT) or angiography to corroborate the presence of stenosis. In this study, the PSVs, EDVs, and ICA/CCA ratios were recorded, and ROC analysis was used to determine the optimal velocity criteria for the diagnosis of angiographic in-stent restenosis of ≥30%, ≥50%, and ≥80%.64 • To detect a stenosis of at least 30%, an ICA PSV of > 154 cm/s was optimal with a Sn of 99%, Sp of 89%, and OA of 96%. An ICA EDV of 42 cm/s had a Sn, Sp, and OA of 86, 62, and 80%, respectively. An ICA/CCA ratio of 1.5 was optimal. • To identify a stenosis > 50%, an ICA PSV of >224 cm/s was optimal with a Sn of 99%, Sp of 90%, and OA of 98%. An ICA EDV of 88 cm/s had Sn, Sp, and OA of 96, 100, and 96%, respectively. An ICA/CCA ratio of 3.5 was optimal. • To diagnose a >80% stenosis, an ICA PSV of > 325 cm/s was optimal with a Sn of 100%, Sp of 99%, and OA of 99%. An ICA EDV of 119 cm/s had Sn, Sp, and OA of 99, 100, and 99%, respectively. An ICA/CCA ratio of 4.5 was optimal. For all strata, the PSV of the stented artery was a better predictor of in-stent restenosis than the end-diastolic velocity or ICA/CCA ratio. In 2008, Lal et al. reported similar findings after reviewing 255 CAS procedures. Available for analysis were 189 pairs of duplex ultrasound and either carotid angiography (29) or CT angiogram (99), during a median follow up of 4.6 years post-stenting.65

691

Residual stenosis after CAS was defined as ≥ 20% luminal reduction, the presence of in-stent restenosis was defined as ≥ 50% luminal reduction, and hemodynamically significant high-grade in-stent restenosis was defined as ≥80% luminal reduction. ROC analysis demonstrated the following optimal threshold criteria: • For residual stenosis > 20%, PSV > 150 cm/s, and ICA/ CCA ratio > 2.2; • For in-stent restenosis > 50%, PSV > 220 cm/s, and ICA/CCA ratio > 2.7; and, • For in-stent restenosis > 80%, PSV 340 cm/s, and ICA/ CCA ratio > 4.2. While both types of studies have limitations, these criteria are guidelines that may suggest the need for additional imaging when in-stent restenosis is suspected. With the exponential rise in carotid stenting, intrastent restenosis is expected to become increasingly prevalent, and these patients will require close monitoring and ultrasound follow-up. Until new standardized duplex ultrasound criteria for CAS are established, follow-up velocities must be compared with earlier results after stenting. Persistent or recurrent elevation of PSVs may indicate progressive in-stent carotid restenosis and should warrant further investigation and appropriate clinical management.64,65 Furthermore, because variants in the observed velocities may result from biomechanic alterations in the stented artery, it is possible that future modifications in stent composition and design may result in different velocity profiles. Whether or not these changes will be important enough to merit further revisions in the velocity criteria thresholds remains unknown65 (Figs 33.26A to D and Movie clips 33.16 to 33.19).

Assessment of the Vertebral Arteries The VAs provide approximately 20% of the total cerebral blood flow, and the vertebrobasilar system is not an uncommon site for acute ischemic events. However, the understanding of the mechanism of ischemia in the posterior circulation is less developed and there are fewer studies validating the diagnostic criteria for significant vertebrobasilar lesions than there are confirming the diagnostic criteria for carotid disease.66 Nonetheless, Doppler interrogation of the proximal SAs and the extracranial portion of the VAs are integral parts of the cervical artery duplex ultrasound study and not infrequently a source of interesting hemodynamic findings.

692

A

Section 2: Echocardiography/Ultrasound Examination and Training

B

C

D

Figs 33.26A to D: Vertebral artery and subclavian stenosis. (A) Normal vertebral artery spectral Doppler waveform: sharp systolic upstroke followed by forward diastolic flow. There is no evidence for significant stenosis in the proximal subclavian artery (or innominate artery in the right side); (B) Latent or partial subclavian steal. The vertebral Doppler waveform shows an early, rapid deceleration or “systolic dip” (yellow arrow), followed by a second more rounded diastolic forward flow (white arrow). This corresponds to a moderate degree of subclavian artery stenosis; (C) Bidirectional “to-and-fro” flow in the vertebral artery is seen with higher degree of stenosis in the ipsilateral subclavian artery. There is systolic reversal of flow in the vertebral artery (yellow arrow), followed by antegrade diastolic flow (white arrow); (D) Complete retrograde flow in the vertebral artery is seen with complete occlusion or near-occlusion of the ipsilateral subclavian artery.

As mentioned earlier, the VAs are frequently asymmetric. In 50% of patients the left VA is dominant, in 25% the right VA is larger, and in the remaining 25% the two vessels are codominant. Examination should be performed in multiple planes, to accurately demonstrate patency and direction of the flow. Almost all atherosclerotic stenosis of the VA occurs at its origin, making it crucial to follow the artery lower in the neck. A PSV > 100 cm/s usually suggests a ≥50% stenosis. High-grade stenosis is diagnosed when there is a marked increase in PSV of >150 cm/s. Since there is wide variation in flow volume across these vessels, and velocities through the VAs are affected by differences in caliber (some vessels even being hypoplastic), the diagnosis of stenosis may be challenging. This is often of limited clinical impact since collateralization from the spinal arteries and contralateral VA tend to protect against posterior circulation ischemic insult.67 Of greater hemodynamic significance is the presence of subclavian steal syndrome—flow reversal in one of the VAs in the setting of significant stenosis or occlusion of the ipsilateral proximal SA.

With significant stenosis in the SA, the pressure in the arm distal to the stenosis becomes lower than the pressure in the vertebral system. During systole, flow proceeds retrograde in the VA into the distal SA. In diastole, the gradient across the lesion is low and the pressure in the distal SA increases. Antegrade flow in the VA follows, producing a characteristic bidirectional Doppler waveform.20 Symptoms suggesting transient posterior circulation ischemia may be occur, but the subclavian steal phenomenon seldom leads to cerebrovascular events.66 The severity of the subclavian steal syndrome varies with the degree of the occlusive process in the SA and the relative role of the VA in supplying collateral flow to the arm. Several waveforms have been described indicating different grades of subclavian steal:20,67–69 • A latent or partial subclavian steal is characterized by antegrade flow with an early systolic “dip” in the vertebral Doppler waveform, followed by a second more rounded systolic peak, and subsequent forward diastolic flow. This so-called “bunny rabbit waveform” (because of its resemblance to the profile of a rabbit) generally corresponds to a SA of ≥50% stenosis. A high velocity jet created by the proximal ipsilateral

Chapter 33: Peripheral Vascular Ultrasound

SA lesion, leads to a pressure drop in the VA, and the resulting transient siphoning of flow from the contralateral VA, producing this sharp deceleration after the first systolic upstroke. A “retrograde” dip in midsystole indicates a more severe stenosis in the SA. • With higher degrees of SA stenosis, there is greater deceleration of flow in the VA. This produces a characteristic bidirectional “to-and-fro” flow, with initial retrograde systolic flow toward the arm, and subsequent antegrade diastolic flow toward the brain. The alternating Doppler signal indicates a high-grade ipsilateral SA stenosis. • Complete retrograde flow in the VA is seen when there is complete occlusion or near-occlusion of the ipsilateral proximal SA (Figs 33.26A to D). Subclavian steal syndrome can be caused by a lesion in either SA. It is important to note, however, that on in the right side, when there is a significant stenosis or nearocclusion in the innominate artery, a “parvus and tardus” Doppler waveform (diminished amplitude and rounding of the systolic peak with delayed or prolonged systolic acceleration) will be seen in the right CCA as well. The flow in the ipsilateral VA will exhibit either bidirectional or the parvus and tardus characteristics, depending on the state of the contralateral VA. A significant stenosis in the origin of the left CCA will result in a dampened monophasic waveform in the cervical segment of the vessel, with a typical parvus and tardus spectral display. Any of the above findings during examination of the cervical arteries warrants thorough Doppler interrogation of the aortic arch vessels as described earlier in this chapter. In our experience, sonographers skilled in both adult echocardiography and vascular studies are better equipped to understand the significance of these hemodynamic riddles and to perform a more comprehensive examination of the entire supra-aortic circulation (Figs 33.27A to D).

Cardiac Pathology and Carotid Ultrasound Findings During a routine carotid duplex study, atypical flow patterns not related to peripheral vascular disease may be encountered. Although, as echocardiographers, we have a thorough knowledge and understanding of cardiac disease entities, their hemodynamic alterations to flow in

693

the cervical arteries may lead to faulty interpretation of the peripheral arterial studies, if the association between the two is not established during the examination. • Aortic stenosis: The flow pattern of a normal carotid artery usually has a fast upstroke with rapid acceleration time, a prominent dicrotic notch, and a diastolic wave. Mild to moderate aortic stenosis is unlikely to affect the carotid and subclavian velocity profiles. In patients with severe aortic stenosis, however, increased acceleration time, decreased peak velocity, delayed upstroke, and rounded waveforms may occur in the common carotid and SAs. When disease is not present in the cervical arteries, the presence of “parvus and tardus” changes in the cervical arteries should alert the examiner to the possibility of aortic stenosis. The velocity profile of the internal carotid arteries does not seem to be affected.70 • Aortic insufficiency: Retrograde diastolic flow has been described in the ascending, descending, and abdominal aorta in patients with severe aortic regurgitation. Diastolic reversal of flow is always an abnormal finding in the carotid arteries, and it has been reported in patients with severe aortic insufficiency and with patent ductus arteriosus. The vessels most likely to exhibit diastolic reversal of flow are the proximal SAs, and to some extent, the common and external carotid arteries, presumably because they supply vascular beds with high resistance. In contrast, the ICA flow is directed to a low resistance bed, and while it may show decreased antegrade diastolic flow, it is unlikely to exhibit diastolic reversal of flow. The presence of a “bisferiens pulse” (two distinct systolic peaks) in the CCAs may also suggest significant aortic regurgitation. However, a similar Doppler pattern may be seen in the carotid arteries of patients with hypertrophic obstructive cardiomyopathy and significant left ventricular outflow tract gradients.71 • Intra-aortic balloon pump: An IABP will limit the Doppler evaluation of the carotid arteries. As the balloon inflates and deflates with each cardiac cycle (1:1 setting), it creates a second, typically higher peak that coincides with diastolic balloon counterpulsation. The disruption of blood flow by the balloon, thus precludes the use of standard velocities and waveforms in the assessment of carotid stenosis22,72 (Figs 33.28A to D). • Left Ventricular Assist Device (LVAD): LVADs are increasingly being implanted for heart failure

694

Section 2: Echocardiography/Ultrasound Examination and Training

A

C

B

D

Figs 33.27A to D: Subclavian steal syndrome. This is part of the study performed in a 72-year-old man, referred for a transthoracic echocardiogram, to assess the degree of aortic stenosis after a significant murmur was heard during routine examination. The twodimensional (2D), color flow, and Doppler evaluation of the aortic valve did not reveal significant pathology. (A) During color flow and Doppler interrogation of the aortic arch and great vessels, high velocity flow is found in the innominate artery; (B) The sonographer then proceeds to evaluate the right side cervical arteries. During a transverse scan of the neck, the CCA and the vertebral artery exhibit opposite flow direction (CCA in red and vertebral artery in blue) during systole. Indicated by the yellow arrows there is evidence for systolic reversal of flow in the right vertebral artery (bidirectional “to-and-fro” flow), consistent with subclavian steal syndrome; (C) The right CCA and the distal right subclavian artery exhibit characteristic “parvus and tardus” spectral Doppler tracings, which in fact strongly suggests the location of the lesion in the innominate artery (the innominate artery divides into the right common carotid and right subclavian arteries); (D) Magnetic resonance angiography of the aortic arch and great vessels confirm the presence of a severe stenosis in the innominate artery (yellow arrow). (CCA: Common carotid artery). Courtesy: Illustration created by Melissa LoPresti and Robert Spencer, NYU.

refractory to medical therapy—as bridges to myocardial recovery, or cardiac transplantation, or as destination therapy for patients who are not candidates for heart transplant. The HeartMate II is the device most frequently used in our institution. Doppler waveforms in the carotid and VAs resemble “parvus and tardus” flow, being characterized by monophasic flow with dampened PSV, round-shaped systolic peak, and prolonged acceleration.73 The marked alteration in waveform morphology and velocities created by the device renders the diagnosis of stenosis impossible by velocity criteria. Sonographers should, therefore, emphasize the gray-scale features to elucidate the presence of carotid disease.

ULTRASOUND DIAGNOSIS OF FEMORAL ACCESS COMPLICATIONS In the last decade, medicine has witnessed an exponential growth in percutaneous coronary, peripheral arterial, and now structural heart disease interventions, as well as cardiac electrophysiology procedures. The common femoral artery and vein continue to be the preferred and most commonly used access sites for the performance of these techniques. Although the use of arterial closure devices has increased the safety of vascular cannulation, femoral access-site complications remain a major cause of morbidity, patient discomfort, and prolonged length of hospital stay.

Chapter 33: Peripheral Vascular Ultrasound

695

A

B

C

D

Figs 33.28A to D: Cardiac pathology and carotid Doppler findings. (A) In the absence of significant disease in the cervical arteries, the finding of “parvus and tardus” Doppler waveforms in several vascular territories in the neck suggests the possibility of severe aortic stenosis as cause of the altered tracings. Note the significant delay and round shape of the systolic upstroke, and the prolonged deceleration; (B) Patient with severe aortic regurgitation exhibits diastolic reversal of flow in the descending thoracic aorta and in the subclavian artery (white arrows). The common carotid artery may show cessation of the forward diastolic flow (as shown in this particular case in [B]) or reversal of flow; (C) Spectral Doppler tracing in a patient with an intra-aortic balloon pump. After the initial systolic upstroke (white arrow), there is a second, typically higher peak (red arrow) that coincides with diastolic balloon counterpulsation. There is a third, short, retrograde waveform, which coincides with balloon deflation (dotted arrow). A simultaneous electrocardiogram tracing helps to correlate events and differentiate from premature atrial or ventricular activity (D).

Duplex ultrasound has become the “gold standard” and first-line diagnostic imaging modality to assess for vascular access-site complications, particularly those using the femoral approach. It is important that physicians caring for patients returning from the catheterization laboratory be able to recognize the presentation and ultrasonographic features of the most common postprocedural complications, and be mindful of the different treatment options.

The overall incidence of vascular access-site complications ranges broadly from 0.7% to 9%. This wide variation is related to whether the procedures are purely diagnostic or include therapeutic interventions. Prolonged interventions, the use of larger sheath size, and the aggressive use of antiplatelets agents and anticoagulants, make hemostasis more difficult to achieve, and result in an increased incidence in complications at the puncture site.74

696

Section 2: Echocardiography/Ultrasound Examination and Training

Vascular complications can be divided into:75 • Minor complications: – Minor bleeding – Ecchymosis – Stable small hematomas. • Major complications: – Pseudoaneurysm – Arteriovenous (AV) fistulas – Large hematomas requiring transfusion – Retroperitoneal hematoma – Arterial dissection – Infection – Thrombosis – Limb ischemia. Several patient and procedure-related risk factors may contribute to the development of complications at the femoral access site.75–77 • Patient-related risk factors: – Older age – Female gender – Obesity or low body weight – Peripheral vascular disease – Hypertension – Chronic renal failure – Low platelet count. • Procedure-related risk factors: – High puncture site (above the inguinal ligament) – Low puncture site (below common femoral bifurcation) – Through-and-through puncture/multiple punctures – Prior catheterizations at the same site – Large sheath size – Concomitant venous sheath – Prolonged procedure time – Long indwelling sheath time – Use of antiplatelet therapy (ASA, clopidogrel, GPIIb/IIIa, etc.) – Use of anticoagulants – Inadequate postprocedure compression to achieve hemostasis – Premature ambulation. Bleeding and hematoma are the most common complications of the transfemoral approach. They may occur during the intervention because of failed puncture of the artery, during sheath removal, or subacutely hours after the procedure.77 Ecchymosis and small hematoma are common. They are often superficial, originate from the anterior aspect of the vessel, and generally resolve

spontaneously over a few weeks as the blood degrades and by-products are reabsorbed. However, persistent uncontrolled bleeding can lead to large hematomas with significant swelling and discomfort in the femoral region, and may take several weeks or months to resolve (Figs 33.29A to C and Movie clips 33.20–33.23). Large hematomas can cause compression of the femoral or iliac veins leading to lower extremity edema or even deep venous thrombosis, and femoral nerve compression may result in muscle weakness. Bleeding from a high arterial puncture above the inguinal ligament or a deep puncture after posterior transfixion of the artery may have catastrophic consequences if overlooked. Retroperitoneal bleeding is a life-threatening complication that has been reported to occur in 0.12–0.44% of percutaneous interventions,78 and should be suspected in any postcatheterization patient who develops ipsilateral flank, abdominal or back pain, profound hypotension, or a drop in hematocrit without a clear source. The retroperitoneal space can accommodate an enormous amount of blood before local signs become manifest or hemodynamic deterioration occurs.75,76 A pseudoaneurysm is a collection of blood and thrombus encapsulated by the adjacent soft tissue that remains connected to the artery by way of a neck created by the needle track. The reported incidence of pseudoaneurysm is 0.5–1.5% after diagnostic catheterizations and 2.1–6% following interventional procedures. It has been found to be as high as 7.7% when duplex examinations are routinely performed after all procedures.79–82 Pseudoaneurysm usually originates at the site of femoral access and is associated with punctures below the bifurcation of the common femoral artery, difficult hemostasis due to lack of bony structures beneath the superficial and profunda arteries, and inadequate compression. The clinical presentation is usually that of an enlarging painful mass in the groin area surrounded by extensive ecchymosis. On examination, there is typically a palpable, tender, pulsatile mass, with or without a systolic bruit, but the presenting signs vary. The presence of a palpable ‘thrill” or auscultation of a continuous bruit over the groin should raise concern for coexistent AV fistula.83 Any clinical suspicion warrants further investigation with ultrasound. Color duplex ultrasound is considered the modality of choice to establish the diagnosis of femoral pseudoaneurysm and is nearly 100% accurate. The Sn of

Chapter 33: Peripheral Vascular Ultrasound

697

B

A

C

Figs 33.29A to C: (A) Hematoma after femoral artery access; (B and C) These large field of view images from a C6-2 MHz curvilinear transducer demonstrate normal superficial femoral artery and vein, with no connection to the hematoma (no residual tract). The hematoma is completely thrombosed. Movie clips 33.20 and 33.21 demonstrate normal common femoral artery and vein, with no evidence of AV fistula. Movie clips 33.22 and 33.23 demonstrate normal superficial femoral artery and vein in longitudinal and transverse scan, with no visible tract connecting with the thrombosed hematoma. Courtesy: Illustration created by Melissa LoPresti and Robert Spencer, NYU.

duplex ultrasound to identify pseudoaneurysm is 94% with a Sp of 97%.84 Typically, the patient is placed supine with the ipsilateral leg externally rotated to better expose the groin area. A 5–7 MHz linear array transducer may be used, but extensive soft tissue edema may limit resolution. A curved array probe with lower frequency is therefore preferable to improve penetration and create a larger field of view.85 As with any other vascular structure, both longitudinal and transverse views of the external iliac and femoral arteries and veins should be obtained. We recommend starting exploration high in the external iliac territory and moving downward toward the proximal superficial and profunda femoral artery and veins. Adequate spectral Doppler samples of both arteries and veins should be obtained. Even when the presumptive diagnosis is pseudoaneurysm, the coexistence of other complications must be excluded.

The characteristic features of a pseudoaneurysm by duplex ultrasonography are best described as three main structures:83,85 The false aneurysm sac—an irregular, occasionally multilobulated, vascularized cavity that usually measures 3–6 cm (but is sometimes larger), containing a swirling pattern of flow. The location of the cavity and presence of thrombus should be noted, and the size measured in at least two dimensions. It is not uncommon for more than one or two interconnected chambers to be seen. The neck—an irregular, cylindrical tract that connects the cavity with the artery. A pathognomonic feature exhibited by the neck, when interrogated with pulsed wave Doppler, is a “to-and-fro” flow. This characteristic spectral Doppler pattern reflects the changes within the cardiac cycle: In systole, the pressure in the artery is higher than the pressure in the sac, directing the flow toward the false aneurysm cavity. In diastole, the pressure in the sac is

698

Section 2: Echocardiography/Ultrasound Examination and Training

B

A

C

D

Figs 33.30A to D: Pseudoaneurysm after femoral artery access. (A) Duplex ultrasound with Power Angio show the three components of a pseudoaneurysm, (S) the aneurysmal sac, (N) the neck or needle tract, and (A) the feeding artery; (B) Shows the aneurysmal sac with typical swirling of flow. Movie clips 33.24 and 33.25 correspond to this figure; (C) These gray-scale and color flow images show an irregular tract that constitutes the neck of the pseudoaneurysm and (D) demonstrates the characteristic “to-and-fro” flow during Doppler interrogation: in systole, the pressure in the artery is higher than the pressure in the sac; therefore, the flow is toward the aneurysmal sac. During diastole, the flow is directed backward toward the artery. Movie clips 33.26 and 33.27 demonstrate the typical “to-and-fro” flow through an irregular neck created by the needle tract. Courtesy: Illustration created by Melissa LoPresti and Robert Spencer, NYU.

higher than the pressure in the feeding artery, so the flow empties from the cavity. The identification of such a high pulsatility tract makes the diagnosis of pseudoaneurysm a certainty. It is essential to record the length and the width of the neck, since both have therapeutic implications.86 The feeding artery—usually the common femoral or superficial femoral artery. The disruption of all three layers of the artery happens more often in the anterior aspect of the vessel, but is not uncommon in cases of posterior transfixion of the artery for the tract to have a deeper trajectory. In such cases, the diagnosis of pseudoaneurysm may become more challenging. Careful attention should be paid to the depth of the field of view, so deep tracts and cavities are not overlooked. In cases in which access was difficult and multiple puncture attempts were required, more than one tract may be found (Figs 33.30A to D and Movie clips 33.24 to 33.27).

Small pseudoaneurysms (3 cm or less) in asymptomatic patients can be followed up with serial ultrasound examinations, as they usually spontaneously close within few weeks. Toursarkissian et al. followed up 286 lesions including 196 pseudoaneurysms, 81 AV fistulae, and 9 combined lesions. They reported spontaneous closure of the pseudoaneurysm in 86% of the patients who were selected for conservative management.87 Several other small studies have shown similar results. In the literature, there are no specific duplex ultrasound findings described other than size < 3 cm, as valid predictor of spontaneous resolution. Larger pseudoaneurysms (> 3 cm or expanding hematomas), combined lesions, or patients who are symptomatic or require chronic anticoagulation should be managed with a different strategy.

Chapter 33: Peripheral Vascular Ultrasound

In 1991, Fellmeth et al described the use of ultrasoundguided compression—a nonsurgical approach for those patients who are not eligible to be managed conservatively.88 The technique consists of the manual compression of the pseudoaneurysm by a physician or an experienced sonographer under direct ultrasound visualization. It is recommended the use of a 5 MHz curvilinear probe, which provides a wide and deep field of view, and facilitates the task of exerting continuous pressure. Pressure to the cavity and the neck of the pseudoaneurysm should be applied for about 10–15 minute intervals, until the “to-and-fro” flow is completely stopped. Careful attention should be paid to ensure adequate flow in the femoral artery while preventing flow into the pseudoaneurysm; however, some degree of compression of the artery may be unavoidable. After completion of the first interval, the pressure is slowly released and blood flow into the lesion is reassessed. If there is persistent flow through the neck, the same procedure may be repeated once or twice until thrombosis of the neck and pseudoaneurysm is accomplished or it exceeds a discretionary failure time. In general, patients should be given analgesia or sedation before procedure to minimize the discomfort created by exerting pressure in the affected groin area.83,85,86 The success rate for ultrasound-guided compression ranges from 60% to 90%, but in patients who are on anticoagulation therapy, complete resolution can be achieved only in 30–75% of the cases.89,90 The most important predictors of successful treatment are the size of the pseudoaneurysm, and the length and width of the neck. Larger aneurysm sacs, and short and wide tracts have the least rate of success. A major disadvantage of ultrasound-guided compression is the time to achieve obliteration. It has been reported in compression times exceeding 1 hour81 (Figs 33.31A and B). Another technique—ultrasound-guided thrombin injection—is a safe alternative to ultrasound-guided compression therapy, and it has been used frequently since first described by Cope and Zeit in 1986.91 A 0.1–0.3 mL saline dilution of 1000 U/mL bovine thrombin is slowly injected into the pseudoaneurysmal sac under direct ultrasound visualization. Thrombosis of the pseudoaneurysm cavity is achieved, usually, within 5–10 seconds after injection. Complete obliteration of the sac should be confirmed by color-flow Doppler, as well as patency of the femoral artery and vein. In general, an interventionalist or a vascular surgeon performs this

699

procedure. It is very important to position the needle tip just inside the sac, and as far as technically possible away from the neck, to avoid forcing thrombin into the tract and therefore into the femoral artery.83 Embolization to the femoral artery following thrombin injection has been reported in