Dynamic Echocardiography E-Book
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Dynamic Echocardiography E-Book

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959 pages
English

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Description

Dynamic Echocardiography combines textbook, case-based, and multimedia approaches to cover the latest advances in this rapidly evolving specialty. The experts at the American Society of Echocardiography (ASE) present new developments in 3D echocardiography, aortic and mitral valve disease, interventional and intraoperative echocardiography, new technologies, and more. You’ll have everything you need to apply the latest techniques in echocardiography and get the best results…in print and online at www.expertconsult.com.

  • Stay current on aortic and mitral valve disease, prosthetic heart valve disease, interventional and intraoperative echocardiography, transesophageal echocardiography, CAD, complications of MI, pericardial disease and intracardiac masses, myocardial diseases, heart failure filling pressures, CRT, CHD, and new technologies.
  • Understand the advantages of 3D echocardiography and see how to effectively use this novel technique.
  • Appreciate the visual nuances and details of echocardiography thanks to beautiful, full-color illustrations.
  • Tap into the expertise of authorities from the American Society of Echocardiography.

Sujets

Ebooks
Savoirs
Medecine
Médecine
Cardiac dysrhythmia
Microbubbles
Atrial fibrillation
Myocardial infarction
Hand
Transesophageal echocardiography
Surgical suture
Computed tomography angiography
Myocardial perfusion imaging
Takotsubo cardiomyopathy
Mitral valve replacement
Doppler echocardiography
Pericardiectomy
Pulmonary valve stenosis
Restrictive cardiomyopathy
Magnetic resonance angiography
Dobutamine
Valvular heart disease
Artificial heart valve
Carcinoid
Dysplasia
Revascularization
Exercise intolerance
Global Assessment of Functioning
Guideline
Cardiogenic shock
Blood culture
Neoplasm
Left ventricular hypertrophy
Aortic valve replacement
Coarctation of the aorta
Myxoma
Hypereosinophilic syndrome
Mitral regurgitation
Ventricular septal defect
Congenital heart defect
Allotransplantation
Bicuspid aortic valve
Pericarditis
Pulmonary hypertension
Atrial septal defect
Aortic insufficiency
Mitral stenosis
Stroke
Constrictive pericarditis
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Infarction
Asymptomatic
Coronary catheterization
Patent ductus arteriosus
Infective endocarditis
Chest pain
Mitral valve prolapse
Amyloidosis
Review
Cardiovascular disease
Ischemia
Vasodilation
Myocarditis
Angiography
Device
Echocardiography
Lesion
Scallop
Hemodynamics
Aortic dissection
Cardiac tamponade
Heart failure
Heart murmur
Mitral valve
Alcohol abuse
Pulmonary embolism
Dyspnea
Coronary artery bypass surgery
Aortic valve stenosis
Rare disease
Physical exercise
Embolism
Jet aircraft
Coronary circulation
Artifact
Tissue (biology)
Atherosclerosis
Artificial pacemaker
Sodium chloride
Hypertension
Electrocardiography
Prosthesis
Angina pectoris
Ischaemic heart disease
X-ray computed tomography
Cardiomyopathy
Mechanics
Magnetic resonance imaging
Endocarditis
Chagas disease
Aorta
Acoustics
Abscess
Stress
Cardiology
Palpitation
Perfusion
Testing
Viewpoint
Systole
Fenfluramine
Ablation
Diastole
Torsion
Évaluation
Syncope
Strontium
Copyright

Informations

Publié par
Date de parution 19 juillet 2010
Nombre de lectures 0
EAN13 9781455710034
Langue English
Poids de l'ouvrage 3 Mo

Informations légales : prix de location à la page 0,0788€. Cette information est donnée uniquement à titre indicatif conformément à la législation en vigueur.

Exrait

Dynamic Echocardiography

Roberto M. Lang, MD, FASE, FACC, FAHA, FESC, FRCP
Professor of Medicine, President, American Society of Echocardiography, Director, Noninvasive Cardiac Imaging Laboratories, University of Chicago Medical Center, Chicago, Illinois

Steven A. Goldstein, MD, FACC
Director, Noninvasive Cardiology Lab, Washington Hospital Center, Washington, District of Columbia

Itzhak Kronzon, MD, FASE, FACC, FAHA, FESC, FACP
Professor of Medicine, Director, Non Invasive Cardiology, New York University Medical Center, New York, New York

Bijoy K. Khandheria, MD, FASE, FACC, FESC, FACP
Director, Echocardiography Services, Aurora Health Care, Aurora Medical Group, Aurora/St. Luke Medical Center, Aurora/Sinai Medical Center, Milwaukee, Wisconsin
Saunders
Front Matter

Dynamic Echocardiography
Roberto M. Lang, MD, FASE, FACC, FAHA, FESC, FRCP Professor of Medicine President, American Society of Echocardiography Director, Noninvasive Cardiac Imaging Laboratories University of Chicago Medical Center Chicago, Illinois
Steven A. Goldstein, MD, FACC Director, Noninvasive Cardiology Lab Washington Hospital Center Washington, District of Columbia
Itzhak Kronzon, MD, FASE, FACC, FAHA, FESC, FACP Professor of Medicine Director, Non Invasive Cardiology New York University Medical Center New York, New York
Bijoy K. Khandheria, MD, FASE, FACC, FESC, FACP Director, Echocardiography Services Aurora Health Care, Aurora Medical Group Aurora/St. Luke Medical Center, Aurora/Sinai Medical Center Milwaukee, Wisconsin
Copyright

3251 Riverport Lane
St. Louis, Missouri 63043
Dynamic Echocardiography
ISBN: 978-1-4377-2262-8
Copyright © 2011 by Saunders, an imprint of Elsevier Inc.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions .
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).


Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the author assumes any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
Library of Congress Cataloging-in-Publication Data
Dynamic echocardiography / American Society of Echocardiography ; [edited by] Roberto M. Lang.—1st ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4377-2262-8 (hardcover : alk. paper)
1. Echocardiography. I. Lang, Roberto M. II. American Society of Echocardiography.
[DNLM: 1. Cardiovascular Diseases—ultrasonography. 2. Echocardiography—methods. WG 141.5.E2 D997 2010]
RC683.5.U5D96 2010
616.1′207543—dc22
2010017586
Vice President and Publisher: Linda Belfus
Executive Editor: Natasha Andjelkovic
Editorial Assistant: Bradley McIlwain
Publishing Services Manager: Patricia Tannian
Project Manager: Carrie Stetz
Design Direction: Steven Stave
Printed in the United States of America
Last digit is the print number: 9 8 7 6 5 4 3 2
Preface
For more than a quarter of a century, echocardiography has made unparalleled contributions to clinical cardiology as a major tool for real-time imaging of cardiac dynamics. Echocardiography is currently widely used every day in hospitals and clinics around the world for assessing cardiac function while simultaneously providing invaluable noninvasive information for the diagnosis of multiple disease states.
The American Society of Echocardiography (ASE) is an organization of professionals committed to excellence in cardiovascular ultrasound and its application to patient care through education, advocacy, research, innovation, and service to our members and public. ASE’s goal is to be its members’ primary resource for education, knowledge exchange, and professional development. This comprehensive textbook on echocardiography constitutes a major step toward the achievement of this goal.
Dynamic Echocardiography is a comprehensive project several years in the making. This text and the companion online library of cases together comprise a state-of-the-art publication on all aspects of clinical echocardiography written by more than 100 medical experts affiliated with ASE. The book consists of 111 chapters divided into 14 sections: Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation; Native Valvular Heart Disease: Mitral Stenosis/Mitral Regurgitation; Prosthetic Heart Valve Disease; Interventional/Intraoperative Echocardiography; Transesophageal Echocardiography; Coronary Artery Disease; Mechanical Complications of Myocardial Infarction; Pericardial Disease and Intracardiac Masses; Myocardial Diseases; Heart Failure Filling Pressures/Diastology; Cardiac Resynchronization Therapy; New Technology; Cases From Around the World; and Congenital Heart Disease. Most sections include a commentary chapter written by a leading authority summarizing the current knowledge on each topic as well as a chapter written by a sonographer describing the technical aspects required for optimal data acquisition and display.
Each of the 111 chapters has a companion online library of didactic slides that include multiple cases. Once readers have completed review of the written chapter, we encourage them to review the accompanying slides and case presentations. This exercise will allow the reader to visualize dynamic echocardiographic clips of multiple cardiac pathologies. We believe that this combined approach is the most effective way of learning clinical echocardiography. Our hope is that physicians and cardiac sonographers will use this text and the companion online materials as a reference and self-assessment tool.
The editors and the authors wish to thank the sonographers with whom we have had the privilege of working throughout the years. Without their daily pursuit of quality, hard work, and desire to continuously learn, this project would never have been completed.
We also especially want to thank each of the section editors: Randolph Martin, Patricia Pellikka, Fausto Pinto, Mani Vannan, Neil Weissman, Malissa Wood, and William Zoghbi for their time and expertise in bringing this product to fruition. We owe a great debt to our ASE staff, who has collaborated with us closely in every aspect of this project, including Chelsea Flowers, who helped obtain the required permissions; Hilary Lamb, who assisted us with all aspects of the artwork; and Anita Huffman and Debra Fincham, who assembled the list of contributors. In particular, we would like to acknowledge the tireless and invaluable help of Andrea Van Hoever and Robin Wiegerink, who helped us complete this project in a timely and effective manner. We would like to also thank Dr. Harry Rakowski, who has provided us with practical, positive encouragement and advice.
We also wish to thank our families for their continuous support while we worked on this project—our wives Lili, Simoy, Ziva, and Priti; our children Daniella, Gabriel, Lauren, Derek, Iris, Rafi, Shira, Vishal, and Trishala; and our grandchildren Ella, Adam, Lucy, and Eli.

Roberto M. Lang, MD, FASE, Steven Goldstein, MD, Itzhak Kronzon, MD, FASE, Bijoy Khandheria, MD, FASE
Foreword
It is difficult for contemporary cardiology fellows to imagine a day when echocardiography was not the focal point for patient diagnosis and management, but cardiovascular ultrasound is still a relatively young discipline. It has been less than 60 years since Inge Edler and Helmuth Hertz first directed a shipyard reflectoscope toward their own hearts and noted moving echoes on an oscilloscope screen, a development that the normally clairvoyant Paul Dudley White termed “ingenious” but of little clinical value. Even by the 1980s, when two-dimensional echocardiography and continuous wave Doppler were well established, one of the factors influencing me to choose an echo fellowship over electrophysiology was that echocardiography was so little regarded clinically that echo fellows were never called in at night or on the weekends! I recall the day in 1988 when this all changed for me. I was attending the weekly catheterization laboratory conference at Massachusetts General Hospital, traditionally a setting for pointing out the perceived failings of the echo lab. On that fateful day, however, Peter Block, director of the cath lab, announced that in his mind echo was the gold standard for quantification of aortic stenosis, leading to Ned Weyman nearly falling out of his chair! Flash forward to 2010. At the Cleveland Clinic, we now do approximately 100,000 cardiovascular ultrasound studies, more than five times the combined total of nuclear, magnetic resonance, and computed tomographic studies. The echo lab is the hub of decision making in valvular heart disease, adult and pediatric congenital abnormalities, congestive heart failure, arrhythmia management, aortic and vascular disease, and cardiac ischemia. And, in a cruel irony, it is now the echo lab that is far more likely to be called in after hours than electrophysiology!
As the utility of echocardiography has expanded, the technical and clinical knowledge base required to apply this technique to its fullest potential has grown exponentially. Learning the many nuances of echocardiography must be a lifelong commitment. With this goal in mind, the American Society of Echocardiography has published Dynamic Echocardiography , a comprehensive text and atlas of echocardiography. Conceived and executed by editor in chief Roberto Lang, 2009/2010 President of ASE, and senior editors Steven Goldstein, Itzhak Kronzon, and Bijoy Khandheria, this book provides a comprehensive and practical approach to the basic principles and clinical application of echocardiography. This really is two educational products in one. First is an expansive book with more than 100 chapters that detail the myriad ways that echocardiography can be used to solve clinical problems. Complementing this book is the accompanying online library that provides a wealth of classic examples of the various pathologies likely to be encountered clinically. Combined, the book and online library provide the perfect study guide for fellows initially learning echocardiography, those studying for the echocardiography boards, and practicing cardiologists looking for a refresher and update to improve their clinical echo skills.
In this era of multimodality imaging, many have predicted the decline of echocardiography. Those of us who have spent our careers in the field, however, have long marveled at the capacity of echo for reinvention, most obviously in its technical capabilities but even more impressively in its expanded clinical applications. By publishing Dynamic Echocardiography , the American Society of Echocardiography continues its commitment to educational excellence. I commend this resource to you with great enthusiasm.

James D. Thomas, MD, FACC, FAHA, FESC, Cleveland, Ohio
Contributors

Theodore P. Abraham, MD, FASE, FACC, Director, Hypertrophic Cardiomyopathy Clinic Division of Cardiology Johns Hopkins University Baltimore, Maryland

Harry Acquatella, MD, FASE, FACC, FAHA, Professor of Medicine Universidad Central de Venezuela, Caracas Department of Echocardiography Centro Medico de Caracas Caracas, Venezuela

David Adams, RCS, RDCS, FASE, Cardiac Sonographer Duke Echocardiography Laboratory Duke University Hospital Durham, North Carolina

Deborah A. Agler, RCT, RDCS, FASE, Coordinator of Education and Training Cardiovascular Imaging Cleveland Clinic Cleveland, Ohio

Josef Aichinger, MD, Senior Cardiologist Cardiology, Angiology, Intensive Care Elisabethinen Hospital Linz Linz, Austria

Bilal Shaukat Ali, MD, Fellow in Advanced Cardiac Imaging Division of Cardiology Brigham and Women’s Hospital Boston, Massachusetts

Samuel J. Asirvatham, MD, FACC, FHRS, Consultant, Division of Cardiovascular Diseases and Internal Medicine Division of Pediatric Cardiology Professor of Medicine Mayo Clinic College of Medicine Vice Chair, Cardiovascular Division—Innovations Program Director, EP Fellowship Program Mayo Clinic Rochester, Minnesota

David S. Bach, MD, FASE, Professor Department of Internal Medicine, Division of Cardiovascular Medicine University of Michigan Ann Arbor, Michigan

Sripal Bangalore, MD, MHA, Division of Cardiology Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts

Manish Bansal, MD, DNB, Consultant Cardiologist Indraprastha Apollo Hospital New Delhi, India

Helmut Baumgartner, MD, FACC, FESC, Professor of Cardiology Adult Congenital and Valvular Heart Disease Center University Hospital Muenster Muenster, Germany

Jeroen J. Bax, MD, PhD, Professor of Cardiology Department of Cardiology Leiden University Medical Center Leiden, The Netherlands

S. Michelle Bierig, MPH, RDCS, RDMS, FASE, Manager, Core Echocardiography Laboratory St. John’s Mercy Heart and Vascular Hospital St. Louis, Missouri

Gabe B. Bleeker, MD, PhD, Department of Cardiology Leiden University Medical Center Leiden, The Netherlands

William B. Borden, MD, Assistant Professor of Medicine Cardiovascular Disease Weill Cornell Medical College New York, New York

Darryl J. Burstow, MBBS, FRACP, Senior Staff Cardiologist Associate Professor of Medicine Department of Cardiology The Prince Charles Hospital Brisbane, Queensland, Australia

Scipione Carerj, MD, Professor of Cardiology Department of Medicine and Pharmacology University of Messina Messina, Italy

Hari P. Chaliki, MD, FASE, FACC, Assistant Professor of Medicine Division of Cardiovascular Diseases Mayo Clinic Scottsdale, Arizona

Kwan-Leung Chan, MD, FACC, FRCPC, Professor of Medicine Division of Cardiology University of Ottawa Heart Institute Ottawa, Ontario, Canada

Sonal Chandra, MD, Advanced Imaging Fellow Section of Cardiology University of Chicago Chicago, Illinois

Krishnaswamy Chandrasekaran, MD, FASE, Professor of Medicine Mayo Clinic College of Medicine Consultant, Division of Cardiovascular Diseases Mayo Clinic Scottsdale, Arizona

Nithima Chaowalit, MD, Assistant Professor Division of Cardiology, Department of Medicine Siriraj Hospital Mahidol University Bangkok, Thailand

Farooq A. Chaudhry, MD, FASE, FACC, FAHA, FACP, Associate Professor of Medicine Columbia University College of Physicians and Surgeons Associate Chief of Cardiology Director of Echocardiography St. Luke’s Roosevelt Hospital Center New York, New York

Namsik Chung, MD, PhD, FASE, FAHA, Dean Yonsei University College of Medicine Professor of Cardiology Yonsei University College of Medicine Seoul, Korea

Patrick D. Coon, RDCS, FASE, Program Director, Echocardiography Division of Cardiology, Department of Pediatrics The Cardiac Center at The Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Ronan J. Curtin, MD, MSc, Consultant Cardiologist Department of Cardiology Cork University Hospital Cork, Ireland

Jeanne M. DeCara, MD, FASE, Associate Professor of Medicine University of Chicago Medical Center Chicago, Illinois

Geneviève Derumeaux, MD, PhD, FESC, Professor of Physiology Explorations Fonctionnelles Cardiovasculaires Lyon University Lyon, France

Veronica Lea J. Dimaano, MD, Senior Research Fellow Division of Cardiology Johns Hopkins University, School of Medicine Baltimore, Maryland

Jean G. Dumesnil, MD, FACC, FRCPC, Professor of Medicine Laval University Cardiologist, Quebec Heart and Lung Institute, Laval University Quebec City, Quebec, Canada

Christian Ebner, MD, Senior Cardiologist Cardiology, Angiology, Intensive Care Elisabethinen Hospital Linz Linz, Austria

Holger Eggebrecht, MD, West-German Heart Center University Duisburg-Essen Essen, Germany

Raimund Erbel, MD, FACC, FAHA, FESC, Professor of Medicine/Cardiology European Cardiologist Department of Cardiology West-German Heart Center University Duisburg-Essen Essen, Germany

Rebecca B. Fountain, RN, BSN, Section of Internal Medicine and Cardiovascular Diseases Mayo Clinic Rochester, Minnesota

Andreas Franke, MD, FESC, Medical Clinic I RWTH University Hospital Aachen, Germany

William K. Freeman, MD, FACC, Associate Professor of Medicine Division of Cardiovascular Diseases Mayo Clinic Rochester, Minnesota

Mario J. Garcia, MD, FACC, FACP, Chief, Division of Cardiology Montefiore Medical Center Albert Einstein College of Medicine Bronx, New York

Eulogio García-Fernández, MD, Cardiology Department Hospital General Universitario “Gregorio Marañón” Madrid, Spain

Miguel Angel García-Fernandez, MD, PhD, Cardiology Department Hospital General Universitario “Gregorio Marañón” Madrid, Spain

José Antonio García-Robles, MD, Cardiology Department Hospital General Universitario “Gregorio Marañón” Madrid, Spain

Steven A. Goldstein, MD, FACC, Director, Noninvasive Cardiology Lab Washington Hospital Center Washington, District of Columbia

José Luis Zamorano Gomez, MD, PhD, FESC, Professor of Medicine Universidad Complutense de Madrid Director, Cardiovascular Institute University Clinic San Carlos Madrid, Spain

José Juan Gómez de Diego, MD, Cardiology Staff Laboratorio de Imagen Cardíaca Hospital Universitario La Paz Madrid, Spain

Jose Luis Gutierrez-Bernal, MD, Hospital Español Mexico City, Mexico

Jong-Won Ha, MD, PhD, FESC, Cardiology Division Professor of Medicine Yonsei University College of Medicine Seoul, South Korea

David R. Holmes, Jr., MD, FACC, Consultant, Cardiovascular Diseases Professor of Medicine Mayo Clinic Rochester, Minnesota

Kenneth Horton, RCS, RCIS, FASE, Echo/Vascular Research Coordinator Intermountain Healthcare Salt Lake City, Utah

Judy W. Hung, MD, FASE, Associate Director, Echocardiography Assistant Professor of Medicine Harvard Medical School Cardiology Division, Department of Medicine Massachusetts General Hospital Boston, Massachusetts

Hiroshi Ito, MD, PhD, Department of Cardiovascular Medicine Okayama University Okayama, Japan

James G. Jollis, MD, FACC, Professor of Medicine and Radiology Duke University Durham, North Carolina

Christine Attenhofer Jost, MD, FESC, Professor of Cardiology Cardiovascular Center Zurich Zurich, Switzerland

Gudrun Kabicher, MD, Senior Cardiologist Cardiology, Angiology, Intensive Care Elisabethinen Hospital Linz Linz, Austria

Sanjiv Kaul, MD, FASE, FACC, Professor and Division Head, Cardiovascular Medicine Oregon Health & Sciences University Portland, Oregon

Bijoy K. Khandheria, MD, FASE, FACC, FACP, FESC, Director, Echocardiography Services Aurora Health Care, Aurora Medical Group Aurora/St. Luke Medical Center, Aurora/Sinai Medical Center Milwaukee, Wisconsin

James N. Kirkpatrick, MD, FASE, FACC, Assistant Professor of Medicine Division of Cardiovascular Medicine University of Pennsylvania Philadelphia, Pennsylvania

Allan L. Klein, MD, FASE, FACC, FAHA, FRCP(C), Director of Cardiovascular Imaging Research Director of the Center for the Diagnosis and Treatment of Pericardial Diseases Cardiovascular Medicine Cleveland Clinic Cleveland, Ohio

Smadar Kort, MD, FASE, FACC, Associate Professor of Medicine Director, Cardiovascular Imaging Division of Cardiology Stony Brook University Medical Center Stony Brook, New York

Itzhak Kronzon, MD, FASE, FACC, FAHA, FESC, FACP, Professor of Medicine Director, Non Invasive Cardiology New York University Medical Center New York, New York

Karla M. Kurrelmeyer, MD, FASE, Assistant Professor of Medicine Weill Cornell Medical College Department of Cardiology Methodist DeBakey Heart & Vascular Center Houston, Texas

Roberto M. Lang, MD, FASE, FACC, FAHA, FESC, FRCP, Professor of Medicine President, American Society of Echocardiography Director, Noninvasive Cardiac Imaging Laboratories University of Chicago Medical Center Chicago, Illinois

Pui Lee, MBChB, Advanced Fellow in Echocardiography Echocardiography Laboratory Mayo Clinic Rochester, Minnesota

Vera Lennie, MD, FESC, Cardiologist Department of Cardiac Imaging Hospital Carlos III Madrid, Spain

Steven J. Lester, MD, FASE, FACC, FRCPC, Consultant, Department of Medicine, Division of Cardiology Associate Professor of Medicine, College of Medicine Director of Echocardiography Mayo Clinic Scottsdale, Arizona

Dominic Y. Leung, MBBS, PhD, FACC, FRCP(Edin), FRACP, FHKCP, FCSANZ, Professor of Cardiology, Department of Cardiology Liverpool Hospital, University of New South Wales Sydney, New South Wales, Australia

Jonathan R. Lindner, MD, FASE, Professor and Associate Chief for Education Cardiovascular Division Oregon Health & Science University Portland, Oregon

Joseph A. Lodato, MD, Section of Cardiology Department of Medicine University of Chicago Medical Center Chicago, Illinois

Boris S. Lowe, BHB, MB ChB, FRACP, Consultant Cardiologist Green Lane Cardiovascular Service Auckland City Hospital Auckland, New Zealand

Joan L. Lusk, RN, RDCS, ACS, FASE, Registered Adult and Pediatric Cardiac Sonographer Adult Congenital Heart Disease Clinic Advanced Clinical/Research Sonographer Mayo Clinic Cardiac Ultrasound Imaging and Hemodynamic Laboratory Mayo Clinic Scottsdale, Arizona

Joseph F. Malouf, MD, Professor of Medicine Mayo Clinic College of Medicine Department of Internal Medicine Mayo Clinic Rochester, Minnesota

Randolph P. Martin, MD, FASE, FACC, FESC, Medical Director, Cardiovascular Imaging Piedmont Hospital Chief, Structural & Valvular Heart Disease Piedmont Heart Institute Professor of Medicine, Emeritus Emory University School of Medicine Atlanta, Georgia

Thomas H. Marwick, MBBS, PhD, Professor of Medicine Institution University of Queensland Brisbane, Queensland, Australia

Gerald Maurer, MD, FACC, FESC, Professor of Medicine Director, Division of Cardiology Chair, Department of Medicine II Medical University of Vienna Vienna, Austria

Patrick M. McCarthy, MD, FACC, Chief of Cardiac Surgery Division, Director of the Bluhm Cardiovascular Institute, and Heller-Sacks Professor of Surgery Division of Cardiac Surgery Northwestern University/Northwestern Memorial Hospital Chicago, Illinois

Ivàn Melgarejo, MD, Cardiologist, Echocardiographer Department of Noninvasive Cardiology Fundaciòn A. Shaio Professor of Cardiology Universidad del Rosario Bogotà, Colombia

Hector I. Michelena, MD, FACC, Assistant Professor of Medicine Mayo Clinic College of Medicine Consultant, Division of Cardiovascular Diseases Mayo Clinic Rochester, Minnesota

Victor Mor-Avi, PhD, FASE, Professor Section of Cardiology, Department of Medicine Director of Cardiac Imaging Research University of Chicago Chicago, Illinois

Sherif F. Nagueh, MD, FASE, Professor of Medicine Weill Cornell Medical College Associate Director of Echocardiography Laboratory Methodist DeBakey Heart and Vascular Center Houston, Texas

Hans Joachim Nesser, MD, FASE, FACC, FESC, Professor of Medicine Head, Department of Cardiology, Angiology, Intensive Care Hospital Vice Director Cardiology, Angiology, Intensive Care Elisabethinen Hospital Linz Linz, Austria

Johannes Niel, MD, Senior Cardiologist Cardiology, Angiology, Intensive Care Elisabethinen Hospital Linz Linz, Austria

Steve R. Ommen, MD, Consultant Vice-Chair for Education Director, Hypertrophic Cardiomyopathy Clinic Division of Cardiovascular Diseases Professor of Medicine Mayo Clinic Rochester, Minnesota

Alan S. Pearlman, MD, FASE, FACC, FAHA, Professor of Medicine Division of Cardiology University of Washington School of Medicine Seattle, Washington

Patricia A. Pellikka, MD, FASE, FACC, FAHA, FACP, Professor of Medicine Mayo Clinic College of Medicine Co-Director, Echocardiography Laboratory Division of Cardiovascular Diseases and Internal Medicine Mayo Clinic Rochester, Minnesota

Esther Pérez-David, MD, PhD, Cardiology Department Hospital General Universitario “Gregorio Marañón” Madrid, Spain

Philippe Pibarot, DVM, PhD, FACC, FAHA, Professor of Medicine Department of Medicine Laval University Québec City, Quebec, Canada

Michael H. Picard, MD, FASE, FACC, FAHA, Director, Echocardiography Massachusetts General Hospital Associate Professor Harvard Medical School Boston, Massachusetts

Fausto J. Pinto, MD, PhD, FASE, FACC, FESC, FSCAI, Professor of Cardiology/Medicine Department of Cardiology Lisbon University Medical School Lisbon, Portugal

Heidi Pollard, RDCS, Cardiac Sonographer Department of Cardiology University of Chicago Medical Centers Chicago, Illinois

Tamar S. Polonsky, MD, Post Doctoral Fellow Cardiovascular Epidemiology and Prevention Northwestern University Chicago, Illinois

Thomas R. Porter, MD, FASE, Professor of Cardiology Courtesy Professor of Radiology and Pediatric Cardiology Department of Internal Medicine–Division of Cardiology University of Nebraska Medical Center Omaha, Nebraska

Brian D. Powell, MD, Assistant Professor of Medicine Cardiovascular Division Mayo Clinic Rochester, Minnesota

Jose E. Riarte, MD, Staff, Cardiovascular Ultrasound Service Cardiac Imaging Department Instituto Cardiovascular de Buenos Aires Ciudad de Buenos Aires, Argentina

Vera H. Rigolin, MD, FASE, FACC, FAHA, Associate Professor of Medicine Northwestern University Feinberg School of Medicine Medical Director, Echocardiography Laboratory Northwestern Memorial Hospital Chicago, Illinois

Ricardo E. Ronderos, MD, PhD, Associate Professor of Cardiology Director, Instituto de Cardiologia La Plata Chief, Cardiovascular Imaging Department Instituto Cardiovascular de Buenos Aires Universidad Nacional de La Plata La Plata, Buenos Aires, Argentina

Muhamed Saric, MD, PhD, FASE, FACC, Associate Professor of Medicine Noninvasive Cardiology New York University New York, New York

Partho P. Sengupta, MD, DM, Assistant Professor of Medicine Mayo Clinic College of Medicine Cardiovascular Division Mayo Clinic Scottsdale, Arizona

Dipak P. Shah, MD, Cardiology Fellow Section of Cardiology University of Chicago Chicago, Illinois

Stanton K. Shernan, MD, FASE, FAHA, Associate Professor of Anesthesia Director of Cardiac Anesthesia Department of Anesthesiology, Perioperative and Pain Medicine Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts

Kirk T. Spencer, MD, FASE, Associate Professor of Medicine University of Chicago Chicago, Illinois

Monvadi B. Srichai, MD, Assistant Professor Department of Radiology and Medicine, Cardiology Division New York University School of Medicine New York, New York

Kathleen Stergiopoulos, MD, PhD, FASE, FACC, Assistant Professor of Medicine Director, Inpatient Cardiology Consultation Stony Brook University School of Medicine SUNY Health Sciences Center Stony Brook, New York

G. Monet Strachan, RDCS, FASE, Supervisor, Echocardiography Lab University of California San Diego Medical Center San Diego, California

Lissa Sugeng, MD, MPH, Assistant Professor of Clinical Medicine Non-Invasive Cardiovascular Imaging Lab University of Chicago Medical Center Chicago, Illinois

Masaaki Takeuchi, MD, PhD, FASE, Associate Professor Second Department of Internal Medicine University of Occupational and Environmental Health School of Medicine Kitakyushu, Japan

Hélène Thibault, MD, PhD, Docteur of Cardiology Echocardiography Laboratory Hôpital Louis Pradel Lyon, France

Wolfgang Tkalec, MD, Senior Cardiologist Cardiology, Angiology, Intensive Care Elisabethinen Hospital Linz Linz, Austria

Paul A. Tunick, MD, Professor, Department of Medicine Noninvasive Cardiology Laboratory New York University Medical Center New York, New York

Matt M. Umland, RDCS, FASE, RT(R), (CT), (QM), Echocardiography Quality Coordinator Advanced Hemodynamic and Cardiovascular Laboratory Aurora Medical Group Advanced Cardiovascular Services Milwaukee, Wisconsin

Mani A. Vannan, MBBS, FACC, Professor of Clinical Internal Medicine Joseph M. Ryan Chair in Cardiovascular Medicine Director, Cardiovascular Imaging The Ohio State University Columbus, Ohio

Philippe Vignon, MD, PhD, Professor of Critical Care Medicine Medical-Surgical ICU and Clinical Investigation Center Teaching Hospital of Limoges Limoges, France

Hector R. Villarraga, MD, FASE, FACC, Assistant Professor of Medicine Mayo Clinic College of Medicine Division of Cardiovascular Diseases and Internal Medicine Mayo Clinic Rochester, Minnesota

R. Parker Ward, MD, FASE, FACC, Associate Professor of Medicine Non-Invasive Imaging Laboratories Section of Cardiology University of Chicago Medical Center Chicago, Illinois

Nozomi Watanabe, MD, PhD, FACC, Department of Cardiology Kawasaki Medical School Kurashiki, Japan

Kevin Wei, MD, Associate Professor of Medicine Cardiovascular Division Oregon Health & Science University Portland, Oregon

Neil J. Weissman, MD, FASE, Professor of Medicine, Georgetown University President, MedStar Health Research Institute at Washington Hospital Center Washington, District of Columbia

Siegmund Winter, MD, Senior Cardiologist Cardiology, Angiology, Intensive Care Elisabethinen Hospital Linz Linz, Austria

Malissa J. Wood, MD, FASE, FACC, Co-director MGH Heart Center Corrigan Women’s Heart Health Program Assistant Professor of Medicine Harvard Medical School Departments of Medicine/Cardiology Massachusetts General Hospital Boston, Massachusetts

Feng Xie, MD, Associate Professor of Medicine Division of Cardiology University of Nebraska Medical Center Omaha, Nebraska

Hyun Suk Yang, MD, PhD, Division of Cardiovascular Diseases Mayo Clinic Scottsdale, Arizona

Danita M. Yoerger Sanborn, MD, FASE, MMSc, Assistant Physician, Instructor in Medicine Cardiology Division Massachusetts General Hospital Harvard Medical School Boston, Massachusetts

Qiong Zhao, MD, PhD, FASE, Assistant Professor of Medicine Cardiology Division, Department of Medicine Northwestern University, Feinberg School of Medicine Chicago, Illinois

Concetta Zito, MD, Cardiology Assistant Unit of Intensive and Invasive Heart Care Department of Medicine and Pharmacology University of Messina Messina, Italy

William A. Zoghbi, MD, FASE, FACC, FAHA, William L. Winters Endowed Chair in CV Imaging Professor of Medicine Weill-Cornell Medical College Director, Cardiovascular Imaging Institute The Methodist DeBakey Heart & Vascular Center Houston, Texas
Table of Contents
Front Matter
Copyright
Preface
Foreword
Contributors
Section I: Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation
Chapter 1: Morphologic Variants of the Aortic Valve
Chapter 2: Aortic Stenosis Quantitation
Chapter 3: Aortic Stenosis: Subaortic Membrane
Chapter 4: Aortic Stenosis With Low Gradient and Poor Left Ventricular Dysfunction
Chapter 5: Asymptomatic Severe Aortic Stenosis
Chapter 6: Challenges in Aortic Stenosis
Chapter 7: Technical Issues: Aortic Stenosis
Chapter 8: Quantitation of Aortic Regurgitation
Section II: Native Valvular Heart Disease: Mitral Stenosis/Mitral Regurgitation
Chapter 9: Mitral Stenosis
Chapter 10: Exercise Echocardiography in Mitral Stenosis
Chapter 11: Mitral Valve
Chapter 12: Mitral Stenosis: Complex Disease, Situations That Mimic Mitral Stenosis, and Technical Pearls
Chapter 13: Morphologic Basis of Valvular Nonischemic Mitral Regurgitation
Chapter 14: Quantification of Nonischemic Mitral Regurgitation
Chapter 15: Suitability for Nonischemic Mitral Regurgitation Repair
Chapter 16: Exercise Hemodynamics in Nonischemic Mitral Regurgitation
Chapter 17: Nonischemic Mitral Regurgitation in Infective Endocarditis
Chapter 18: Nonischemic Mitral Regurgitation and Left Ventricular Dysfunction
Chapter 19: Ischemic Mitral Regurgitation
Chapter 20: Evaluation of Tricuspid Regurgitation by Two-Dimensional and Doppler Echocardiography: Implications for Management
Section III: Prosthetic Heart Valve Disease
Chapter 21: Valve Prosthesis-Patient Mismatch
Chapter 22: Valve Prosthesis and Pressure Recovery
Chapter 23: Aortic Prosthetic Valve Obstruction
Chapter 24: Mitral Prosthetic Valve Obstruction
Chapter 25: Prosthetic Mitral Regurgitation
Chapter 26: Prosthetic Aortic Regurgitation
Chapter 27: Technical Echo-Doppler Pearls in Prosthetic Heart Valves
Section IV: Interventional/Intraoperative Echocardiography
Chapter 28: Role of Transesophageal Echocardiography and Intracardiac Echocardiography in Atrial Fibrillation Ablation
Chapter 29: Left Atrial Appendage Closure: Alternative Treatment to Prevent Thromboembolism
Chapter 30: Intraoperative Transesophageal Echocardiographic Evaluation of Ischemic Mitral Regurgitation
Chapter 31: Mitral Valve Repair for Myxomatous Disease of the Mitral Valve
Chapter 32: Echocardiography in Left Ventricular Infarct Exclusion Surgery
Chapter 33: Patent Foramen Ovale
Section V: Transesophageal Echocardiography
Chapter 34: Precardioversion Transesophageal Echocardiography in Atrial Fibrillation
Chapter 35: Cardiac Source of Embolus
Chapter 36: Perivalvular Complications in Infective Endocarditis
Chapter 37: Aortic Dissection
Chapter 38: Aortic Intramural Hematoma
Chapter 39: Aortic Atherosclerosis and Embolic Events
Chapter 40: Featured Expert Commentary and Review: Central Role of Transesophageal Echocardiography in Clinical Cardiology
Section VI: Coronary Artery Disease
Chapter 41: Stress Echocardiography in Chest Pain Syndromes
Chapter 42: Exercise Echocardiography in Left Ventricular Hypertrophy (and Other Pitfalls)
Chapter 43: Abnormal Exercise Echocardiography in Coronary Artery Disease
Chapter 44: Abnormal Dobutamine Stress Echocardiography for Ischemia (Preoperative Risk Assessment)
Chapter 45: Myocardial Viability
Chapter 46: Use of Tissue Doppler During Dobutamine Stress Echocardiography
Chapter 47: Diastolic Stress Test for the Evaluation of Exertional Dyspnea
Chapter 48: Featured Expert Commentary and Review: Prognostic Value of Stress Echocardiography
Chapter 49: Featured Expert Commentary and Review: Functional Imaging in the Era of Computed Tomographic Coronary Angiography
Chapter 50: Vasodilator Stress With Myocardial Contrast Echocardiography: Abnormal Test Indicating Acute Ischemia
Chapter 51: Diagnosis of Coronary Artery Disease by Dobutamine Stress Real-Time Myocardial Contrast Perfusion Imaging
Chapter 52: Myocardial Contrast Echocardiography After Myocardial Infarction
Chapter 53: Technical Pearls in Myocardial Contrast Echocardiography
Chapter 54: Featured Expert Commentary and Review: Myocardial Contrast Echocardiography for Chest Pain Syndromes in the Emergency Department
Section VII: Mechanical Complications of Myocardial Infarction
Chapter 55: Mechanical Complications of Myocardial Infarction
Section VIII: Pericardial Disease and Intracardiac Masses
Chapter 56: Pericardial Tamponade
Chapter 57: Constrictive Pericarditis
Chapter 58: Restrictive Cardiomyopathy
Chapter 59: Rare Pericardial Disorders
Chapter 60: Atrial Masses
Chapter 61: Aortic Valve Masses
Chapter 62: Artifacts Masquerading as Intracardiac Masses
Chapter 63: Use of Contrast to Distinguish Intracardiac Masses From Thrombi
Chapter 64: Featured Expert Commentary and Review: Pericardial Disease and Intracardiac Masses
Section IX: Myocardial Diseases
Chapter 65: Hypertrophic Cardiomyopathy
Chapter 66: Technical Issues in Assessing Left Ventricular Outflow Tract Gradient
Chapter 67: Treatment of Hypertrophic Obstructive Cardiomyopathy With Left Ventricular Outflow Tract Obstruction
Chapter 68: Apical Hypertrophic Cardiomyopathy
Chapter 69: Dilated Cardiomyopathy
Chapter 70: Takotsubo Cardiomyopathy
Chapter 71: Heart Failure in Idiopathic Hypereosinophilic Syndrome
Chapter 72: Use of Guidelines to Evaluate Chamber Quantitation
Chapter 73: Right Ventricle: Carcinoid Heart Disease
Chapter 74: Right Ventricular Dysplasia
Chapter 75: Primary Pulmonary Hypertension
Chapter 76: Pulmonary Embolism
Chapter 77: Pulmonary Stenosis
Chapter 78: Fenfluramine Valve Disease
Chapter 79: Featured Expert Commentary and Review: Morphologic and Functional Evaluation of the Right Heart: Progress and Challenges
Section X: Heart Failure Filling Pressures/Diastology
Chapter 80: Evaluation of Diastolic Function
Chapter 81: Mechanics of Heart Failure With Normal Left Ventricular Systolic Function
Chapter 82: Technical Issues in Diastolic Function Evaluation
Section XI: Cardiac Resynchronization Therapy
Chapter 83: Cardiac Resynchronization Therapy: Is it for Everyone?
Chapter 84: Mitral Regurgitation and Cardiac Resynchronization Therapy
Chapter 85: Technical Issues in Evaluating Dyssynchrony
Chapter 86: Featured Expert Commentary and Review: Assessment of Left Ventricular Dyssynchrony in Cardiac Resynchronization Therapy
Section XII: New Technology
Chapter 87: Contrast for Resting Echocardiograms
Chapter 88: Contrast for Stress Echocardiography
Chapter 89: Three-Dimensional Transthoracic and Transesophageal Echocardiography
Chapter 90: Myocardial Tissue Imaging
Chapter 91: Tissue Doppler Imaging: Quantitation of Myocardial Mechanics
Chapter 92: Assessment of Left Ventricular Twist, Rotation, and Torsion
Chapter 93: Hand-Carried Echocardiography Systems
Section XIII: Cases From Around the World
Chapter 94: Familial Isolated Noncompaction Left Ventricle
Chapter 95: Takotsubo-like Left Ventricular Dysfunction
Chapter 96: Chagas Cardiomyopathy
Chapter 97: Cardiovascular Behçet’s Disease
Chapter 98: Use of Three-Dimensional Echocardiography in Stress Testing: Principles and First Studies
Chapter 99: Cardiac Involvement in Hypereosinophilic Syndrome
Chapter 100: Traumatic Disruption of the Aorta
Chapter 101: Left Ventricular Free Wall Rupture After Acute Myocardial Infarction and Thrombolysis
Chapter 102: Transthoracic Coronary Artery Imaging
Chapter 103: A Hole in the Heart
Chapter 104: Transesophageal Echocardiography: In-Procedure Guidance and Follow-up of Percutaneous Closure of Prosthetic Paravalvular Leaks
Section XIV: Congenital Heart Disease
Chapter 105: Congenital Heart Disease in Adults
Chapter 106: Echocardiographic Evaluation of Atrial Septal Defects
Chapter 107: Ventricular Septal Defects and Eisenmenger Syndrome
Chapter 108: Patent Ductus Arteriosus
Chapter 109: Anatomic Features of Corrected Transposition of the Great Arteries
Chapter 110: Coarctation of the Aorta
Chapter 111: Ebstein’s Anomaly
Index
Section I
Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation
Chapter 1 Morphologic Variants of the Aortic Valve

Steven A. Goldstein, MD
Valvular aortic stenosis (AS), a chronic progressive disease, usually develops over decades. The majority of cases of AS are acquired and result from degenerative (calcific) changes in an anatomically normal trileaflet aortic valve that becomes gradually dysfunctional. Congenitally abnormal valves may be stenotic at birth but usually become dysfunctional during adolescence or early adulthood. A congenitally bicuspid aortic valve is now the most common cause of valvular AS in patients younger than 65 years. Rheumatic AS is now much less common than in prior decades and is almost always accompanied by mitral valve disease. Table 1.1 lists the most common causes of valvular AS. These are illustrated in Figs. 1.1 to 1.4 .
Table 1.1 Etiology of Aortic Stenosis
Congenital (unicuspid, bicuspid)
Degenerative (sclerosis of previously normal valve)
Rheumatic

Fig. 1.1 Diagram showing the three major causes of valvular aortic stenosis. Degenerative: commissures not fused; calcium deposits in cusps. Bicuspid: two cusps and a raphe in the fused cusps. Rheumatic: fused commissures with central round or oval opening.

Fig. 1.2 A to C, Degenerative aortic stenosis in the elderly. A, Transesophageal echocardiographic cross-sectional view of an elderly patient with degenerative aortic stenosis illustrating relative absence of commissured fusion. The resulting orifice is composed of three “slits” between each pair of cusps. B, Same view illustrates planimetry of the aortic valve area. C, Pathologic specimen from a different patient illustrates similar rigid leaflets caused by fibrosis and calcium deposition (seen from aortic side of the valve).

Fig. 1.3 Stenotic and calcified bicuspid aortic valve. Note the median raphe (arrow) in the larger, conjoined cusp.

Fig. 1.4 A and B, Typical rheumatic aortic stenosis with commissural fusion resulting in a central triangular (as shown here) or oval or circular orifice. Typical rheumatic aortic stenosis with commissured fusion resulting in a central triangular orifice as shown in the transesophageal echocardiogram ( A ) and a pathologic specimen ( B ).

Bicuspid Aortic Valve
Congenital aortic malformation reflects a phenotypic continuum of unicuspid valve (severe form), bicuspid valve (moderate form), tricuspid valve (normal, but may be abnormal), and the rare quadricuspid forms. Bicuspid aortic valves (BAVs) are the result of abnormal cusp formation during the complex developmental process. In most cases, adjacent cusps fail to separate, resulting in one larger conjoined cusp and a smaller one. Therefore BAV (or bicommissural aortic valve) has partial or complete fusion of two of the aortic valve leaflets, with or without a central raphe, resulting in partial or complete absence of a functional commissure between the fused leaflets. 1
The accepted prevalence of BAV in the general population is 1% to 2%, which makes it the most common congenital heart defect. Information on the prevalence of BAV comes primarily from pathology centers. 1 - 7 The most reliable estimate of BAV prevalence is often considered the 1.37% reported by Larson and Edwards. 3 These authors have special expertise in aortic valve disease and found BAVS in 21,417 consecutive autopsies. An echocardiographic survey of primary schoolchildren demonstrated a BAV in 0.5% of boys and 0.2% of girls. 8 A more recent study detected 0.8% BAVs in nearly 21,000 men in Italy who underwent echocardiographic screening for the military. 9 Table 1.2 summarizes data on the prevalence of bicuspid valves. BAV is seen predominantly in males with a 2-4 : 1 male/female ratio. 10 - 12 Although a BAV may occur in isolation, it may be associated with many forms of congenital heart disease.

Table 1.2 Prevalence of Bicuspid Aortic Valves
Other less common congenital abnormalities of the aortic valve include the unicuspid valve and the quadricuspid valve. The unicuspid valve is dome shaped and has a central stenotic orifice. These valves generally become stenotic during adolescence or early adulthood and are seldom seen in older adults. Quadricuspid valves are rare and may be either regurgitant or stenotic. 13 - 17 With advances in echocardiography, more cases of quadricuspid aortic valves (QAVs) are being diagnosed antemortem. The preoperative diagnosis of QAV is important because it can be associated with abnormally located coronary ostia. 14 Echocardiographic diagnosis can be established by either transthoracic or transesophageal echocardiography ( Fig. 1.5 ). On the short-axis view of the aortic valve in diastole, the commissural lines formed by the adjacent cusps result in an X configuration rather than the Y of the normal tricuspid aortic valve ( Tables 1.3 to 1.5 ).

Fig. 1.5 Quadricuspid aortic valve. Transesophageal echocardiographic short-axis view (37 degrees) illustrates failure of leaflet coaptation in diastole (arrow) with a square-shaped central opening and typical X -shaped configuration of the four commissures.

Table 1.3 Prevalence of Quadricuspid Aortic Valves
Table 1.4 Function of Quadricuspid Aortic Valves Valve Function No. (%) Aortic regurgitation 115 (75) Aortic stenosis + aortic regurgitation 13 (8) Aortic stenosis 1 (1) Normal 25 (16)
From Tutarel O: The quadricuspid aortic valve: a comprehensive review. J Heart Valve Dis 2004;13:534-537.
Table 1.5 Quadricuspid Aortic Valves: Morphologic Types Anatomic Variation: Cusps No. 4 equal 51 3 equal, 1 smaller 43 2 equal larger, 2 equal smaller 10 1 large, 2 intermediate, 1 small 7 3 equal, 1 larger 4 2 equal, 2 unequal smaller 4 4 unequal 5
From Hurwitz LE, Roberts WC: Quadricuspid semilunar valve. Am J Cardiol 1973;31:623-626.

Natural History of Bicuspid Valves
Although BAVs in some patients may go undetected or present no clinical consequences over a lifetime, complications that usually require treatment, including surgery, develop in most patients. The most important clinical consequences of BAV are valve stenosis, valve regurgitation, infective endocarditis, and aortic complications such as dilation, dissection, and rupture ( Table 1.6 ).
Table 1.6 Complications of Bicuspid Aortic Valves Valve Complications Aortic Complications Stenosis Dilation Regurgitation Aneurysm Infection Dissection, rupture
Isolated AS is the most frequent complication of BAV, occurring in approximately 85% of all BAV cases. 10 BAV accounts for the majority of patients aged 15 to 65 years with significant AS. The progression of the congenitally deformed valve to AS presumably reflects its propensity for premature fibrosis, stiffening, and calcium deposition in these structurally abnormal valves. The specific anatomy may influence the propensity for obstruction. Stenosis may be more rapid if the aortic cusps are asymmetric or in the anteroposterior position. 2 Novaro and colleagues 18 suggest that stenosis was more frequent in females and in patients with fusion of the right and noncoronary cusps. In addition, patients with abnormal lipid profiles and those who smoke may be at increased risk of development of significant stenosis. 12 In fact, some recent evidence indicates that statins may slow the progression of AS. 18 , 19 However, more evidence is needed before evidence-based therapy can be recommended.
Aortic regurgitation, present in approximately 15% of patients with BAV, 10 is usually due to dilation of the sinotubular junction of the aortic root, preventing cusp coaptation. It may also be caused by cusp prolapse, fibrotic retraction of leaflet(s), or by damage to the valve from infective endocarditis. Aortic regurgitation tends to occur in younger patients than in those with AS.
Why stenosis develops in some patients with a BAV and regurgitation develops in others is unknown. As mentioned, in rare cases no hemodynamic consequences develop. Roberts et al. 21 reported three congenital BAVs in nonagenarians undergoing surgery for AS. Why some patients with a congenital BAV do not experience symptoms until they are in their 90s and others have symptoms in early life is also unclear.

Infective Endocarditis
Patients with BAVs are particularly susceptible to infective endocarditis. Although the exact incidence of endocarditis remains controversial, the population risk, even in the presence of a functionally normal valve, may be as high as 3% over time. 22 In a series of 50 patients with native valve endocarditis, 12% had a BAV. 23 In a similar study, BAV accounted for 70% of all native valve endocarditis cases and was the single most important predisposing factor. 24
In many cases of BAV, endocarditis is the first indication of structural valve disease, which emphasizes the importance of either clinical or echocardiographic screening for the diagnosis of BAV. Unexplained systolic ejection murmurs, diastolic decrescendo murmurs, and/or aortic ejection sounds (clicks) should prompt echocardiographic evaluation. Bacterial endocarditis prevention is vital for patients with BAV and is highly recommended by the American Heart Association/American College of Cardiology (AHA/ACC) Guidelines. 25

Aortic Complications
BAV is associated with several additional abnormalities, including displaced coronary ostia, left coronary artery dominance, and a shortened left main coronary artery; coarctation of the aorta; aortic interruption; Williams syndrome; and most important, aortic dilation, aneurysm, and dissection. Given these collective findings, BAV may the result of a developmental disorder involving the entire aortic root and arch. Although the pathogenesis is not well understood, these associated aortic malformations suggest a genetic defect. 26
Although they are less well-understood, these aortic complications of BAV disease can cause significant morbidity and mortality. BAV may also be associated with progressive dilation, aneurysm formation, and dissection ( Tables 1.7 and 1.8 ). These vascular complications may occur independent of valvular dysfunction 9 , 11 and can manifest in patients without significant stenosis or regurgitation. According to Nistri and colleagues, 9 50% or more of young patients with normally functioning BAV have echocardiographic evidence of aortic dilation.

Table 1.7 Frequency of Aortic Dissection in Persons With a Bicuspid Aortic Valve
Table 1.8 Frequency of Bicuspid Aortic Valve in Aortic Dissection Author Year No. BAV/ Dissection (%) Gore and Seiwert 38 1952 11/85 (13) Edwards et al. 39 1978 11/119 (9) Larson and Edwards 3 1984 18/161 (11) Roberts and Roberts 37 1991 14/186 (7.5) Totals   54/551 (9.8)
The diameter of the ascending aorta measured at the level of the sinuses of Valsalva appears to be the best predictor of the occurrence of aortic complications. 1 - 3 However, no consensus exists regarding the threshold value of the diameter of the ascending aorta that should not be exceeded. Nevertheless, there is a general trend toward aggressive treatment of ascending aortic dilation in patients with BAV using criteria similar to those for patients with Marfan syndrome. 26 - 34 However, evidence supporting this approach does not exist and the optimal diameter at which replacement of the ascending aorta should be performed in patients with BAV is not known. The recent ACC/AHA guidelines for the management of patients with valvular heart disease recommend surgery to prevent dissection or rupture when the diameter of the ascending aorta exceeds 50 mm (a lower threshold value should be considered for patients of small stature) or if the rate of increase in diameter is ≥5 mm per year. 27 These indications are based largely on criteria from echocardiographic studies.

Coarctation
BAV may occur in isolation or with other forms of congenital heart disease. The association of BAV with coarctation is well documented. 3, 35 - 45 An autopsy study found coexisting coarctation of the aorta in 6% of cases of BAV, 1 and an echocardiographic study found coarctation in 10% of patients with BAV. 43 On the other hand, as many as 30% to 55% of patients with coarctation have a BAV. 42 , 45 Therefore, when a BAV is detected on an echocardiogram, coarctation of the aorta should always be sought.

Echocardiographic Findings
The importance of diagnosing BAV should be evident from the previous discussions; BAV is common, requires endocarditis prophylaxis, can develop into stenosis or regurgitation, and is associated with aortic complications. Echocardiography remains the most practical and widely available method for detecting BAV. An outline of the role of echocardiography for detecting and evaluating BAVs is listed in Table 1.9 .
Table 1.9 Bicuspid Aortic Valve: Role of Echocardiography
Evaluation for aortic stenosis/regurgitation
Careful measurements of aortic root
Search for coarctation
Consider screening first-degree family members
M-mode echocardiography of a BAV may demonstrate an eccentric diastolic closure line. However, an eccentric closure line also may be seen in patients with a normal tricuspid aortic valve; and a normal, central closure line is often present in patients with a BAV. Therefore two-dimensional echocardiography is required for reliable detection of a BAV. The most reliable and useful views are the parasternal long-axis and short-axis views.
The long-axis view typically shows systolic doming ( Figs. 1.6 to 1.8 ) resulting from the limited valve opening; normally the leaflets are parallel to the aortic walls ( Fig. 1.9 ). In diastole, one of the leaflets (the larger, conjoined cusp) may prolapse. The parasternal long-axis (PLAX) view with color Doppler is also useful to evaluate for aortic regurgitation (diastolic aortic regurgitant jet) and AS (turbulence in the aortic root and ascending aorta in systole). Lastly, the PLAX view is also important for sizing the sinus of Valsalva, sinotubular junction, and ascending aorta.

Fig. 1.6 A to C, Bicuspid aortic valve. A, Short-axis view shows “fish mouth” or football-shaped opening. B, Long-axis view shows systolic doming. C, Color Doppler shows eccentric aortic regurgitant jet.

Fig. 1.7 Bicuspid aortic valve. Systolic doming with small, stenotic opening at the apex of the dome (arrow).

Fig. 1.8 A and B, Bicuspid aortic valve. Transesophageal echocardiography demonstrates several features of BAV: “fish mouth” opening in systole ( white arrow ) and median raphe ( yellow arrow ) ( A ) and systolic doming of the leaflets ( red arrow ) and dilated ascending aorta ( double-headed arrow ) ( B ). AO, Aorta; LVOT, left ventricular outflow tract.

Fig. 1.9 Normal tricuspid valve opens normally. Note that the aortic leaflets are parallel to the aortic walls.
The parasternal short-axis (SAX) view is useful in examining the number and position of the commissures, the opening pattern, the presence of a raphe, and the leaflet mobility. The normal (trileaflet) aortic valve appears like a Y in diastole with the commissures at the 10 o’clock, 2 o’clock, and 6 o’clock positions. When the commissures deviate from these clock-face positions, BAV should be suspected with subsequent careful evaluation. In systole, the BAV opens with a “fish mouth” or football shape appearance ( Figs. 1.10 and 1.11 ). There is typically a raphe (region where the cusps failed to separate), which is usually distinct and extends from the free margin to the base. Calcification generally occurs first along this raphe, ultimately hindering the motion of the conjoined cusp. 46

Fig. 1.10 Transesophageal echocardiographic short-axis view illustrates typical football-shaped opening and median raphe at the 5 o’clock position.

Fig. 1.11 Variations in bicuspid valves. Relative positions of raphe and conjoined cusp.
(Adapted from Sabet HY, Edwards WD, Tazelaar HD, et al. Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases. Mayo Clin Proc 1999;74:14-26.)
False-positive diagnosis of BAV may occur if all three leaflets are not imaged in systole or if their closure lines are not imaged in diastole. If images are suboptimal or heavily fibrotic/sclerotic, then transesophageal echocardiography may be helpful for accurate evaluation of the aortic valve anatomy and confirmation of a BAV. Diastolic images in the parasternal SAX view can also be misleading if the raphe is mistaken for a third commissural closure line.
Aortic root measurements should be made in the PLAX view at four levels: the annulus, sinuses of Valsalva, sinotubular junction, and proximal ascending aorta ( Fig. 1.12 ). The aortic arch and descending thoracic aorta should be imaged from the suprasternal notch view, looking for coarctation.

Fig. 1.12 Aortic dimensions: measurement locations. 1, Annulus; 2, midpoint of sinuses of Valsalva; 3, sinotubular junction; 4, ascending aorta at level of its largest diameter. LV, Left ventricle; Ao, aorta; LA, left atrium.

Surveillance
Because of the risk of progressive aortic valve disease (stenosis and/or regurgitation) and ascending aortic disease, serial echocardiographic monitoring is warranted in patients with BAV even when no symptomatic are reported. The 2006 ACC/AHA guidelines recommend monitoring of adolescents and young adults, older patients with AS, and patients with a BAV and dilation of the aortic root or ascending aorta. 27 If the aortic root is poorly visualized on echocardiography, cardiac computed tomography or magnetic resonance imaging are excellent substitutes.

Indications for Echocardiography for Incidental Murmurs
The 2006 ACC/AHA guidelines on the management of patients with valvular heart disease recommend the use of echocardiography in patients with symptomatic and asymptomatic murmurs and ejection sounds ( Table 1.10 and Fig. 1.13 ). 27 A diagram ( Fig. 1.14 ) and actual phonocardiogram ( Fig. 1.15 ) illustrate typical physical findings in patients with BAV.
Table 1.10 Evaluation of Heart Murmurs: Role of Echocardiography
Differentiate pathologic vs. physiologic cause
Define the etiology
Determine severity of the lesion
Determine the hemodynamics
Detect secondary or coexisting lesions
Evaluate chamber sizes and function
Establish reference point for future
Adapted from Bonow RO, Carabello BA, Chatterjee K, 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. J Am Coll Cardiol 2006;48:e1-e148.

Fig. 1.13 Strategy for evaluating heart murmurs. ECG, Electrocardiogram; CXR, chest x-ray.
(Adapted from Bonow RO, Carabello BA, Chatterjee K, 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. J Am Coll Cardiol 2006;48:e1-e148.)

Fig. 1.14 Valvular aortic stenosis auscultatory features.

Fig. 1.15 Aortic ejection sound in a patient with a bicuspid aortic valve. S 1 , first heart sound; ES, ejection sound ( red arrows ); A 2 , aortic closure; P 2 , pulmonic closure; CAR, carotid pulse; PA MF , pulmonic area, medium frequency; SB MF , left sternal border, medium frequency.

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30. Leggett ME, Unger TA, O’Sullivan CK, et al. Aortic root complications in Marfan’s syndrome: identification of a lower risk group. Heart . 1996;75:389-395.
31. Devereux RB, Roman MJ. Aortic disease in Marfan’s syndrome. N Engl J Med . 1999;340:1307-1313.
32. Ergin MA, Spielvoge D, Apaydin A, et al. Surgical treatment of the dilated ascending aorta: when and how? Ann Thorac Surg . 1999;67:1834-1839.
33. Svensson LG, Kim KH, Lytle BW, et al. Relationship of aortic cross-sectional area to height ratio and the risk of aortic dissection in patients with bicuspid aortic valves. J Thorac Cardiovasc Surg . 2003;26:892-893.
34. Borger MA, Preston M, Ivanov J, et al. Should the ascending aorta be replaced more frequently in patients with bicuspid aortic valve disease? J Thorac Cardiovasc Surg . 2004;128:677-683.
35. Isselbacher EM. Thoracic and abdominal aortic aneurysms. Circulation . 2005;111:816-828.
36. Fenoglio JJ, McAllister HA, DeCastro CM, et al. Congenital bicuspid aortic valve after age 20. Am J Cardiol . 1977;39:164-169.
37. Roberts CS, Roberts WC. Dissection of the aorta associated with congenital malformation of the aortic valve. J Am Coll Cardiol . 1991;17:712-716.
38. Gore I, Seiwert VJ. Dissecting aneurysm of the aorta, pathologic aspects: an analysis of eighty-five fatal cases. Arch Pathol . 1952;53:121-141.
39. Edwards WD, Leaf DS, Edwards JE. Dissecting aortic aneurysm associated with congenital bicuspid aortic valve. Circulation . 1978;57:1022-1025.
40. Liberthson RR, Pennington DG, Jacobs ML, et al. Coarctation of the aorta: review of 234 patients and clarification of management problem. Am J Cardiol . 1979;43:835-840.
41. Folger GMJr, Stein PD. Bicuspid aortic valve morphology when associated with coarctation of the aorta. Cathet Cardiovasc Diagn . 1984;10:17-25.
42. Nihoyannopoulos P, Karas S, Sapsford RN, et al. Accuracy of two-dimensional echocardiography in the diagnosis of aortic arch obstruction. J Am Coll Cardiol . 1987;10:1072-1077.
43. Huntington K, Hunter AG, Chan KL. A prospective study to assess the frequency of familial clustering of congenital bicuspid aortic valve. J Am Coll Cardiol . 1997;30:1809-1812.
44. Warnes CA. Bicuspid aortic valve and coarctation: two villains part of a diffuse problem. Heart . 2003;89:965-966.
45. Fernandes SM, Sanders SP, Khairy P, et al. Morphology of bicuspid aortic valve in children and adolescents. J Am Coll Cardiol . 2004;44:1648-1651.
46. Waller BF, Carter JB, Williams HJJr, et al. Bicuspid aortic valve. Comparison of congenital and acquired types. Circulation . 1973;48:1140-1150.
Chapter 2 Aortic Stenosis Quantitation

Steven A. Goldstein, MD
Aortic stenosis is the most common valvular heart disease requiring valve replacement. The indications for valve replacement depend on symptoms and hemodynamic variables, such as aortic valve area (AVA) and transaortic gradients. Therefore accurate hemodynamic evaluation of the aortic valve is important for clinical decision-making. Transthoracic echocardiography (TTE) is used most frequently in clinical practice to quantify the severity of aortic valve stenosis because it is noninvasive, widely available, and generally reliable. With careful attention to technique, an experienced echocardiography laboratory can accurately measure transaortic pressure gradients and AVA in nearly all patients. The accuracy of both Doppler-determined pressure gradients (using the Bernoulli equation) and the calculation of AVA (using the continuity equation) is well established and provides sufficient information in most instances.
However, these methods are limited in some patients with poor acoustic windows and by several technical issues. 1 , 2 Some of the technical limitations and pitfalls are listed in Table 2.1 . A major source of error can result from imprecision in the measurement of the cross-sectional area of the left ventricular outflow tract (LVOT). Generally measured in the parasternal long-axis view, the LVOT diameter can be difficult to measure in patients for whom limitations are imposed by poor acoustic window(s) or those with heavy calcium deposits in the aortic annulus, especially when the calcium extends onto the anterior mitral leaflet. In the latter case, reverberations can obscure the true dimension. 1 Moreover, the LVOT is assumed to be circular, although this is not always the case. Furthermore, the LVOT diameter can be difficult to measure in patients with subaortic obstruction. Another important source of error is failure to display and measure the highest velocity signals in either the LVOT or the transvalvular velocity. If the echo beam is not parallel to the velocity jet, peak transvalve velocity is underestimated, and thus the calculated peak and mean gradients also are underestimated. On occasion, when the nonimaging transducer (Pedoff transducer) is used, a mitral regurgitant jet or a tricuspid regurgitant jet can be mistaken for the transvalvular aortic jet. This can be recognized since generally both the mitral regurgitant and tricuspid regurgitant jets are longer in duration and begin during isovolumic relaxation.
Table 2.1 Technical Limitations and Pitfalls of Quantitating Valvular Aortic Stenosis by Transthoracic Echo-Doppler
1. Intercept angle between AS jet and Doppler beam
2. Outflow tract diameter
• Heavily calcified aortic annulus
• Upper septal bulge (“sigmoid septum”)
3. Coexisting subaortic obstruction
4. Flow signal origin (AS vs. MR or TR)
5. Beat-to-beat variability (atrial fibrillation, PVCs)
AS, Aortic stenosis; MR, mitral regurgitation; PVCs, premature ventricular contractions; TR, tricuspid regurgitation.

Indications for Transesophageal Echocardiography Planimetry
When the reliability of TTE in estimating the degree of aortic stenosis is questioned, a second noninvasive modality may be necessary. Transesophageal echocardiography (TEE), by providing superior image resolution, enables direct aortic valve planimetry in the majority of patients. 3 - 11 The anatomic area measured with multiplane TEE correlates well with calculation of AVA using the Gorlin formula at catheterization and with the continuity equation. 4 - 8 11 In another study, good correlation was also obtained when the planimetered valve area was compared with direct intraoperative measurement of the anatomic area by the surgeon. 12 The indications for use of TEE to assess the severity of aortic stenosis are listed in Table 2.2 .
Table 2.2 Indications for Using TEE to Assess Severity of Aortic Stenosis
1. Suboptimal transthoracic echo-Doppler study
a. Heavy aortic valve calcification, especially when extending onto base of anterior mitral leaflet
b. Poor-quality LVOT velocity (V 1 ) or transvalvular velocity (V 2 )
c. Coexisting subaortic obstruction
d. “Sigmoid” septum
2. Conflict between invasive and noninvasive date
3. Patients undergoing CABG with coexisting aortic stenosis
CABG, Coronary artery bypass grafting; LVOT, left ventricular outflow tract.

Method for Optimal Transesophageal Echocardiography Planimetry
Optimal positioning for planimetry of the aortic valve first requires visualization of the aortic valve and ascending aorta in the long-axis view (usually between 100 and 150 degrees). Then the leaflet tips should be positioned in the center of the two-dimensional sector (to take advantage of axial resolution). With the TEE probe held stable, the ultrasound beam should be electronically steered to obtain the short-axis view of the aortic valve (generally 90 degrees less than the long-axis view). The true short-axis of the aortic valve is between 30 and 60 degrees in most cases; but in individual patients may be found anywhere between 0 and 90 degrees. Minimal probe manipulations are then made to ensure that the smallest orifice of the aortic valve (at its tips) is identified. In the optimal view for planimetry, the aortic wall has a circular shape and all aortic cusps are visualized simultaneously. Special care should be taken to optimize gain settings. The gain should be reduced to the lowest value that permits complete delineation of the cusps. Maximal opening of the aortic valve generally occurs in early systole. The smallest orifice during maximum opening of the aortic valve in systole should be measured using a magnified image in the zoom mode. The area can then be measured by tracing the contours of the inner cusps with a digitizing caliper. It is advisable to measure and average several consecutive beats. On occasion, color Doppler can be useful in helping to identify the stenotic opening. It is important that the minimal orifice size be measured. This detail is particularly important in congenital bicuspid aortic valves, in which case the smallest orifice is at the apex of a domed valve. Planimetry at a more basal level appears larger and can be misleading. The feasibility of planimetry of the AVA by TEE is listed in Table 2.3 .
Table 2.3 Feasibility of Planimetry of AVA by TEE Author Year Feasibility (%) Hofmann et al. 3 1987 20/24 (83) Stoddard et al. 4 1991 64/67 (95) Hoffmann et al. 5 1993 38/41 (93) Tribouilly et al. 6 1994 51/55 (94) Stoddard et al. 9 1996 81/86 (94) Cormier et al. 8 1996 41/45 (91) Bernard et al. 11 1997 48/52 (92) Chandrasekaran et al. 12 1991 85/95 (89) Tardif et al. 7 1995 32/32 (100)
Although the results obtained with TEE two-dimensional echocardiography planimetry are encouraging, potential sources of error exist with this method. Measuring the smallest AVA accurately requires the imaging plane to be located at the tips of the valve leaflets. The longitudinal motion of the aortic root during the cardiac cycle can make this difficult. Confirmation that the image plane is positioned at the smallest anatomic area is subjective and requires careful manipulation of the TEE probe. Heavy calcification of the aortic valve also presents problems. Acoustic shadowing behind the calcification often projects into the AVA, resulting in gaps in the outline of the orifice. In addition, prominent reverberations may lead to underestimation of the AVA.

Gradients by Transesophageal Echocardiography
Measurement of gradients and valve area by the continuity equation by means of TEE requires proper alignment of the continuous wave Doppler beam to obtain peak aortic valve velocity. Although this measurement is difficult and technically demanding by TEE, it can be performed in many patients. 13 , 14 Stoddard et al. 13 have demonstrated that a significant learning curve exists, but this technique appears feasible in the majority of patients. 14
Continuous wave Doppler of the transaortic valve flow and pulsed wave Doppler of the LVOT flow can be performed from at least two views:
1. Deep transgastric apical four-chamber view
2. Transgastric long-axis view
Ideally, the continuous wave cursor should be parallel to the aortic stenotic jet; color flow Doppler can be used to assist this alignment. The diameter of the LVOT can be measured from an esophageal long-axis view. The zoom mode can be used to maximize the LVOT. The diameter of the LVOT should be measured immediately beneath the insertion of the aortic valve leaflets in the LVOT during early systole using the “inner edge–to–inner edge” technique.
The feasibility of this method is listed in Table 2.4 . The feasibility, accuracy, and reproducibility of measurements of the AVA are being evaluated by three-dimensional echocardiography 15 - 19 and magnetic resonance imaging. 20 - 22 Comparative studies among these different diagnostic methods are needed.
Table 2.4 Feasibility of Determining AVA by TEE Using Continuity Equation Author Year Feasibility (%) Stoddard et al. 14 1996 62/86 (72) First 43 patients   24/43 (56) Last 43 patients   38/43 (88) Blumberg et al. 14 1998 25/28 (89)

Reporting and Classification of Severity
The ACC/AHA Practice Guidelines, revised in 2006, recommend grading the severity of aortic stenosis based on a variety of hemodynamic and natural history data, using definitions of aortic jet velocity, mean pressure gradient, and AVA ( Table 2.5 ). 23 In applying these definitions, the examiner should recognize the potential for imprecision in the measurements for both catheterization and echo-Doppler techniques. Therefore particular attention should be paid to the technical quality of these studies in individual patients. In addition, transvalvular pressure gradients depend on and vary with stroke volume. Decisions about intervention are based predominantly on symptom status, and because symptom onset does not correspond to a single hemodynamic value in all patients, no absolute breakpoints define severity.

Table 2.5 Classification of the Severity of Aortic Stenosis in Adults

References

1. Zoghbi WA, Farmer KL, Soto JG, et al. Accurate noninvasive quantification of stenotic valve area by Doppler echocardiography. Circulation . 1986;73:452-459.
2. Zhou YQ, Faerestrand S, Matre K. Velocity distributions in the left ventricular outflow tract in patients with valvular aortic stenosis. Effect on the measurement of aortic valve area by using the continuity equation. Eur Heart J . 1995;16:383-393.
3. Hofmann T, Kasper W, Meinertz T, et al. Determination of aortic valve orifice area in aortic valve stenosis by two-dimensional transesophageal echocardiography. Am J Cardiol . 1987;59:330-335.
4. Stoddad MF, Arce J, Liddell NE, et al. Two-dimensional echocardiographic determination of aortic valve area in adults with aortic stenosis. Am Heart J . 1991;122:1415-1422.
5. Hoffmann R, Flachskampf FA, Hanrath P. Planimetry of orifice area in aortic stenosis using multiplane transesophageal echocardiography. J Am Coll Cardiol . 1993;22:529-534.
6. Tribouilloy C, Shen WF, Peltier M, et al. Quantitation of aortic valve area in aortic stenosis with multiplane transesophageal echocardiography: comparison with monoplane transesophageal approach. Am Heart J . 1994;128:526-532.
7. Tardif JC, Miller DS, Pandian NG, et al. Effects of variations in flow on aortic valve area in aortic stenosis bases on in vivo planimetry of aortic valve area by transesophageal echocardiography. Am J Cardiol . 1995;76:193-198.
8. Cormier B, Iung B, Porte JM, et al. Value of multiplane transesophageal echocardiography in determining aortic valve area in aortic stenosis. Am J Cardiol . 1996;77:882-885.
9. Stoddard MF, Hammons RT, Longaker RA. Doppler transesophageal echocardiographic determination of aortic valve area in adults with aortic stenosis. Am Heart J . 1996;132:337-342.
10. Kim KS, Maxted W, Nanda NC, et al. Comparison of multiplane and biplane transesophageal echocardiography in the assessment of aortic stenosis. Am J Cardiol . 1997;79:436-441.
11. Bernard Y, Meneveau N, Vuillemenot A, et al. Is planimetry of aortic valve area using multiplane transesophageal echocardiography a reliable method for assessing severity of aortic stenosis? Heart . 1997;78:68-73.
12. Chandrasekaran K, Foley R, Weintraub A, et al. Evidence that transesophageal echocardiography can reliably and directly measure the aortic valve area in patients with aortic stenosis—a new application that is independent of LV function and does not require Doppler data. J Am Coll Cardiol . 1991;17(Suppl A):20A.
13. Stoddard MF, Prince CR, Ammash N, et al. Pulsed Doppler transesophageal echocardiographic determination of cardiac output in human beings: comparison with thermodilution technique. Am Heart J . 1993;126:956-962.
14. Blumberg FC, Pfeifer M, Holmer SR, et al. Quantification of aortic stenosis in mechanically ventilated patients using multiplane transesophageal Doppler echocardiography. Chest . 1998;114:94-97.
15. Nanda NC, Roychoudhry D, Chung S, et al. Quantitative assessment of normal and stenotic aortic valve using transesophageal three-dimensional echocardiography. Echocardiography . 1994;11:617-625.
16. Menzel T, Mohr-Kahaly S, Kolsch B, et al. Quantitative assessment of aortic stenosis by three-dimensional echocardiography. J Am Soc Echocardiogr . 1997;10:215-223.
17. Kasprzak JD, Nosir YFM, dall’Agata A, et al. Quantification of the aortic valve area in three-dimensional echocardiographic datasets: analysis of orifice overestimation resulting from suboptimal cut plane selection. Am Heart J . 1998;135:995-1003.
18. Ge S, Warner JGJr, Abraham TP, et al. Three-dimensional surface area of the aortic valve orifice by three-dimensional echocardiography: clinical validation of a novel index for assessment of aortic stenosis. Am Heart J . 1998;136:1042-1050.
19. Handke M, Shafer DM, Heinrichs G, et al. Quantitative assessment of aortic stenosis by three-dimensional anyplane and three-dimensional volume-rendered echocardiography. Echocardiography . 2002;19:45-53.
20. Friedrich MG, Schulz-Menger J, Poetsch T, et al. Quantification of valvular aortic stenosis by magnetic resonance imaging. Am Heart J . 2002;144:329-334.
21. John AS, Dill T, Brandt RR, et al. Magnetic resonance to assess the aortic valve area in aortic stenosis: how does it compare to current diagnostic standards? J Am Coll Cardiol . 2003;42:519-526.
22. Kupfahl C, Honold M, Meinhardt G, et al. Evaluation of aortic stenosis by cardiovascular magnetic resonance imaging: comparison with established routine clinical techniques. Heart . 2004;90:893-901.
23. Bonow RO, Carabello BA, Chatterjee K, 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. J Am Coll Cardiol . 2006;48:e1-e148.
Chapter 3 Aortic Stenosis
Subaortic Membrane

Vera Lennie, MD, José Luis Zamorano Gomez, MD
Subvalvular (subaortic) stenosis (SAS) is the second most common form of aortic stenosis. It is considered an acquired lesion with genetic predisposition because it is rarely found in the embryologic or neonatal period ( Table 3.1 ). Up to 50% of all cases are associated with other congenital abnormalities (ventricular septal defect, aortic coarctation, atrioventricular septal defect, patent ductus arteriosus, bicuspid aortic valve). 1 SAS can develop after acquired heart diseases in rare instances.
Table 3.1 Subaortic Stenosis: Summary Acquired lesion With strong genetic predisposition ECHOCARDIOGRAPHIC FINDINGS
Morphology (classification)
Congenital defects (50%)
LVOT obstruction: severity
Aortic regurgitation DIFFERENT NATURAL HISTORY DEPENDING ON AGE
Children: rapid hemodynamic deterioration
Adults: slow course INDICATIONS FOR SURGERY: CONTROVERSIAL
Children: LVOT obstruction >30 mm Hg
Adults: LVOT obstruction >40 mm Hg
High incidence of recurrences
Surgery does not prevent the appearance of AR

Morphologic Variants of Subaortic Membrane
An extensive range of lesions has been described to cause SAS. The classification has always been controversial. Kelly’s morphologic classification in type I (thin membrane) and type II (fibromuscular stenosis) lesions is currently underused. 2 Choi and Sullivan 3 presented a classification based on echocardiographic features:
1. Short-segment subaortic obstruction (length less than one third of the aortic valve diameter) includes previous membranous, diaphragmatic, discrete, fixed, fibrous, or fibromuscular stenosis. Short-segment obstruction can be complete (annular) or incomplete (semilunar) ( Fig. 3.1 ), as well as fibrous or muscular ( Fig. 3.2 ).
2. Long-segment subaortic obstruction (length greater than one third of the aortic valve diameter) is usually tunnel-like and diffuse. It usually coexists with hypoplasia of the aortic valve annulus ( Fig. 3.3 ).
3. SAS can result from a malalignment of septal structures in the presence of a ventricular septal defect (VSD) ( Fig. 3.4 ). It can include a posterior malalignment with obstruction above the VSD, usually associated with aortic arch interruption, and anterior malalignment with obstruction below the VSD.
4. SAS resulting from atrioventricular valve tissue in the left ventricular outflow tract (LVOT) ( Fig. 3.5 ) includes accessory mitral valve tissue, anomalous attachment of mitral valve chordae, tricuspid valve tissue prolapsing through a VSD, and abnormal left atrioventricular valve in the atrioventricular septal defect (AVSD).

Fig. 3.1 Subaortic membrane (short segment).

Fig. 3.2 Muscular membrane.

Fig. 3.3 Tunnel-like subaortic membrane (long segment).

Fig. 3.4 Subaortic stenosis caused by malalignment of septal structures in the presence of a ventricular septal defect. RA, Right atrium; LA, left atrium; RV, right ventricle; VSD, ventricular septal defect; LV, left ventricle.

Fig. 3.5 Subaortic stenosis resulting from atrioventricular valve tissue in the left ventricular outflow tract. RA, Right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle.
The clinical features of SAS are determined by the severity of the LVOT obstruction. Patients with mild gradients normally have no symptoms; the defect is often diagnosed when proceeding for surgery of another congenital defect. In patients with symptoms, the most common presentation is limited exercise tolerance, but syncope and angina pectoris have also been described. 4

Diagnosis
On physical examination, a “harsh” systolic ejection murmur—best heard at the left sternal border—is characteristically found. A thrill can be palpable in the same position. An early diastolic murmur is also present in cases of aortic regurgitation. The diagnosis through physical examination remains a challenge because this feature can also be found in other causes of LVOT obstruction. The electrocardiographic findings are usually abnormal, with nonspecific findings including left ventricular hypertrophy (LVH), strain patterns, and left atrial enlargement. Chest radiographic findings are often normal.
The echocardiogram is the cornerstone of diagnosis of SAS. It defines the anatomy and type of defect as well as functioning of the LVOT. Associated cardiac defects can also be diagnosed with this imaging technique. The objective measurements of systolic Doppler pressure gradient, aortic regurgitation, or mitral regurgitation are vital to establishing patient treatment and follow-up. If surgery has already been performed, the echocardiogram should help the physician to determine the type of intervention (simple resection, myotomy, myectomy, Konno’s intervention, valve prosthesis, and so on) and rule out the existence of iatrogenic VSD.

Three-Dimensional Echocardiography of the Subaortic Membrane
Two-dimensional (2-D) transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are the standard techniques for diagnosing SAS. However, these methods are often limited in their ability to visualize the details of SAS and the LVOT. 5 Three-dimensional TEE can accurately diagnose and measure SAS and in the future could be a useful tool for guiding transcatheter interventions. 6 The “aortotomy view” just below the plane of the aortic valve provides an excellent perspective for assessing the entire SAS and quantifying the LVOT obstruction by planimetry. 7
Cardiac catheterization was the classic technique for diagnosis of SAS before the development of 2-D echocardiography. Catheterization provides anatomic and hemodynamic data but lacks good definition of small anatomic structures and assessment of mitral apparatus. The measurement of the peak-to-peak gradient at catheterization has no good correlation with the maximum instantaneous gradient of the echocardiogram, and therefore these should not be compared. 8 The Doppler mean pressure gradient correlated well with mean pressure gradient measured at catheterization, as Bengur et al. 9 studied. The presence of low cardiac output or arrhythmias could mask the presence of significant gradient across the LVOT. Leichter, Sullivan, and Gersony 10 described 35 patients with no significant LVOT obstruction at initial cardiac catheterization but who later were shown to have significant SAS. Today catheterization is performed only when multiple levels of obstruction are suspected.

Pathophysiology and Natural History
The development of a subaortic lesion is genetically influenced. Nevertheless, various abnormal flow patterns are believed to take part in the process: septal ridge, malalignment of the septum, elongated or hypoplastic LVOT, apical muscular band, an abnormality between the LVOT axis and aortic axis, and so on. 4 All such phenomena have the potential to harm the endothelium of the LVOT, where fibrosis would take place as a result of the chronic contact with the flow. As a result, a fibrous or muscular structure would display in the LVOT, causing the clinical and hemodynamic compromise.
Progression of SAS occurs, but the rate is variable and the factors influencing it are unknown. SAS usually causes LVOT obstruction of various degrees. If it manifests during early childhood, it is normally accompanied with a rapid hemodynamic worsening of symptoms and more severe gradient of LVOT obstruction. In adults, it can have a slow course (over several decades). Therefore SAS in patients with initially mild stenosis is likely to progress less rapidly than in those who initially have a higher gradient. Patients with an increasing gradient need early surgery, but surgery in mild cases may be delayed if close follow-up can be ensured. 11
Aortic regurgitation (AR) is present in half of patients with SAS but is usually mild. The mechanism is thought to be damage to the aortic valve resulting from the repetitive trauma of the subvalvular jet or direct extension of subvalvular tissue into the aortic valve. 4 AR is also associated with bicuspid aortic valve. 12 The existing literature shows correlation between the severity of stenosis and the severity of AR in both children and in adults. However, Oliver et al. 12 found no relationship between AR and age. Surgical repair in children does not prevent the development of AR in adults. It appears that significant AR is more likely to be found in patients who have undergone surgical intervention than those who have not had surgery. In some annular forms, extension to the anterior mitral leaflet may exist, causing various degrees of fibrosis and deficits in coaptation. This extension is believed to be related to longer distances from the membrane to the valves.
A high rate of restenosis after surgery also has been reported. The simple resection of the ridge renders it more likely to develop restenosis (the ventricular geometry has not been modified and the hemodynamics of the forces continue to act the same way). In some cases, SAS appears after VSD repair; the risk of endocarditis is especially high among these patients.

Impact of Echocardiographic Findings on Therapeutic Strategies
The decision whether to perform corrective surgery should be based on the presence of LVH, left ventricular ejection fraction, severity of LVOT obstruction, AR, and patient age. The optimal surgical timing remains highly controversial. In patients with severe obstruction (gradient >40 mm Hg), surgery is the recommended option. An infant or child with a gradient of 30 mm Hg or more also should have removal of the subvalvular obstruction. If the gradient is less but the presence of LVH is important, surgery should also be considered. Children with mild gradients should have close follow-up to monitor progression. The same guideline is applicable for adults with stable gradients (<50 mm Hg).
SAS often recurs after surgical resection and early surgery does not prevent it. Reoperation rates vary from 4% to 35%. The higher the preoperative gradient, the higher the recurrence rate. 13 Various studies have shown no clinical benefit for early surgery in patients with mild gradients. 14

References

1. Cilliers AM, Gewillig M. Rheology of discrete subaortic stenosis. Heart . 2002;88:335-336.
2. Kelly DT, Wulfsberg E, Rowe RD. Discrete subaortic stenosis. Circulation . 1972;46:309-322.
3. Choi JY, Sullivan ID. Fixed subaortic stenosis: anatomical spectrum and nature of progression. Br Heart J . 1991;65:280-286.
4. Darcin OT, Yagdi T, Atay Y, et al. Discrete subaortic stenosis. Tex Heart Inst J . 2003;30:286-292.
5. Miyamoto K, Nakatani S, Kanzaki H, et al. Detection of discrete subaortic stenosis by 3-dimensional transesophageal echocardiography. Echocardiography . 2005;22:783-784.
6. Ge S, Warner JG, Fowler KM, et al. Morphology and dynamic change of discrete subaortic stenosis can be imaged and quantified with three-dimensional transesophageal echocardiography. J Am Soc Echocardiogr . 1997;10:713-716.
7. Agrawal GG, Nanda NN, Htay T, et al. Live three-dimensional transthoracic echocardiographic identification of discrete subaortic membranous stenosis. Echocardiography . 2003;20:617-619.
8. Currie PJ, Hagler DJ, Seward JB, et al. Instantaneous pressure gradient: a simultaneous Doppler and dual catheter correlative study. J Am Coll Cardiol . 1986;7:800-806.
9. Bengur AR, Snider AR, Serwer GA, et al. Usefulness of the Doppler mean gradient in evaluation of children with aortic stenosis and comparison to gradient at catheterisation. Am J Cardiol . 1989;64:756-761.
10. Leichter DA, Sullivan I, Gersony WM. “Acquired” discrete subvalvular aortic stenosis: natural history and hemodynamics. J Am Coll Cardiol . 1989;14:1539-1544.
11. Gersony WM. Natural History of discrete subvalvular aortic stenosis: management implications. J Am Coll Cardiol . 2001;38:843-845.
12. Oliver JM, González A, Gallego P, et al. Discrete subaortic stenosis in adults: increased prevalence and show rate of progression of the obstruction and aortic regurgitation. J Am Coll Cardiol . 2001;38:835-842.
13. Brauner R, Laks H, Drinkwater DC, et al. Benefits of early surgical repair in fixed subaortic stenosis. J Am Coll Cardiol . 1997;30:1835-1842.
14. Kitchiner D. Subaortic stenosis: still more questions than answers. Heart . 1999;82:647-648.
Chapter 4 Aortic Stenosis With Low Gradient and Poor Left Ventricular Dysfunction

Alan S. Pearlman, MD, FASE
The majority of patients with valvular aortic stenosis (AS) have preserved systolic left ventricular (LV) function. Occasionally, however, a patient with AS has substantial depression of LV function, a low ejection fraction (EF), and a low transvalvular pressure gradient (PG).
More than 25 years ago, Carabello et al. 1 demonstrated that while surgical aortic valve replacement (AVR) was likely to benefit patients with AS, depressed LVEF, and a mean systolic PG greater than 30 mm Hg, the results were poor and the risk of AVR was high in patients with AS who had depressed LVEF and a PG less than or equal to 30 mm Hg. Subsequently, Cannon et al. 2 described a small group of patients with apparently severe AS who were referred for AVR; in these patients, valve inspection during surgery demonstrated only mild AS. These patients were deemed to have “pseudo-AS,” with reduced systolic opening of the valve leaflets caused by low forward stroke volume. In this setting, the calculated aortic valve orifice area (AVA) was small not because of severe AS, but because of depressed LV function.
Because AVR surgery is clearly indicated in patients with severe AS who have symptoms of angina, syncope, or heart failure and in those with depressed LVEF, 3 it is important to identify those patients with LV dysfunction caused by severe AS and to distinguish them from patients with primary LV dysfunction and mildly thickened aortic leaflets, in whom a reduced AVA and low PG are due to —and not the cause of —depressed LV function.

Pathophysiology
Valvular AS resulting from calcification of a bicuspid or trileaflet valve is characterized by reduced mobility of the aortic valve leaflets, with decreased systolic opening and increased resistance to LV ejection. Typically, LV hypertrophy (LVH) develops over time and results in increased systolic LV pressure, generally maintaining LV wall stress, forward stroke volume, and LVEF at the expense of increased LV mass. LVH may also cause diastolic dysfunction. In severe AS, mean transvalvular gradients typically are greater than 40 mm Hg, and AVAs are <1 cm 2 . 3 In some patients, however, chronic increases in LV work because the the resistance of the stenotic aortic valve leads to reduced LVEF; this phenomenon has been termed afterload mismatch. 4 In such patients, forward stroke volume declines, as do transvalvular gradients. Because transvalvular PGs vary directly with forward volumetric flow, and inversely with AVA, mean gradients are typically less than 30 mm Hg in patients with severe AS and depressed LV function caused by afterload mismatch.
Patients with primary LV contractile dysfunction (due to coronary artery disease or a nonischemic cardiomyopathy) also will have depressed LVEF and reduced forward stroke volume. In such patients, if the aortic valve leaflets become thickened and mildly to moderately stenotic, the valve opening is markedly reduced as a result of LV dysfunction, and not as its cause. Note that valve leaflet opening (even in normal valves) is caused by transvalvular flow—the valve leaflets open widely enough and stay open long enough to allow the volume of flow to pass through. Thus a patient with intrinsic LV dysfunction, a low EF, and abnormal (though not severely stenotic) aortic leaflets also may have an AVA less than 1.0 cm 2 and a mean gradient less than 30 mm Hg. Distinguishing the patient with severe AS causing LV dysfunction from the patient with LV dysfunction and coexisting mild to moderate AS is an important diagnostic challenge. Data from a patient that illustrate this dilemma are shown in Fig. 4.1 .

Fig. 4.1 Transthoracic echocardiographic and Doppler data obtained at rest from an 85-year-old man with progressive dyspnea and evidence of AS on physical examination. Real-time imaging demonstrated aortic valve calcification and reduced leaflet opening during systole, as well as impaired LV systolic function (ejection fraction, 23%). By using the continuity equation and the measures of LV outflow tract diameter ( upper left ) and velocity-time integrals ( VTI ) in the LV outflow tract ( lower left ) and across the stenotic valve ( lower right ), aortic valve area was calculated as 0.44 cm 2 . The mean transvalvular gradient was 23 mm Hg. These data show apparent severe AS, despite being of low gradient, in a patient with depressed LV function.

Diagnosis
Although it is possible to evaluate AS severity by left heart catheterization, this approach is used infrequently in most contemporary practices. Instead, Doppler ultrasonography is used to measure peak instantaneous and mean transvalvular PG and to determine AVA using the continuity equation. 5 When transthoracic echocardiography cannot assess AS severity (usually because of poor image quality), transesophageal echocardiography can be used to visualize and measure AVA by planimetry. 6 In a patient with LV dysfunction, low EF, and calcified aortic valve leaflets with a small calculated AVA, resting hemodynamics do not distinguish severe AS with afterload mismatch from pseudo-AS with LV dysfunction.
In this case, evaluation of aortic valve hemodynamics using Doppler techniques during dobutamine infusion is quite valuable. The feasibility, safety, and potential applicability of this approach were first described by DeFilippi et al. 7 in 1995. Using incremental doses of intravenous dobutamine (from 5 to 20 mcg/kg/min) and monitoring heart rate, blood pressure, heart rhythm, and LV wall motion carefully, these investigators demonstrated improvement in EF in some, but not all, of their patients. Doppler echocardiography demonstrated increases in PG and AVA in patients with, but not in those without, “contractile reserve” (CR). Figs. 4.2 and 4.3 show an example of changing Doppler hemodynamics in a patient with low-gradient AS in whom dobutamine infusion demonstrated contractile reserve. In a subsequent report, 8 dobutamine infusion was used in the cardiac catheterization laboratory in patients with low-gradient AS, and some of these patients underwent subsequent AVR. Those with CR had much lower perioperative mortality than those without CR (7% vs. 33%).

Fig. 4.2 Transthoracic echocardiographic and Doppler data obtained from the same patient in Figure 4.1 during dobutamine infusion. Real-time imaging demonstrated an improvement in contractile function with ejection fraction measured at 36%. Doppler velocity-time integrals (VTI) in the LV outflow tract ( lower left ) have more than doubled, indicating an improvement in stroke volume. By using the continuity equation, aortic valve area was calculated as 0.7 cm 2 , and the mean transvalvular gradient was 41 mm Hg.

Fig. 4.3 Comparison of hemodynamic data obtained from the same patient in Figures 4.1 and 4.2 obtained at rest ( left column ) and during dobutamine infusion ( right column ). During adrenergic stress, contractile reserve is evident, with an increase in the left ventricular ejection fraction and velocity-time integrals measured in the left ventricular outflow tract (this is a surrogate for stroke volume). With increased transvalvular volume flow, the peak and mean pressure gradients (Δ P ) increase. Aortic valve area ( AVA ) also increases but remains in the critical range. These findings demonstrate severe aortic stenosis with depressed left ventricular function at rest, and a low gradient as a consequence, as well as contractile reserve with dobutamine infusion. VTI LVOT , Flow-velocity integral of the left ventricular outflow tract; LVEF, left ventricular ejection fraction.

Treatment
AVR is clearly indicated in patients with severe AS causing symptoms of angina, syncope, or heart failure and in those with AS and afterload mismatch and depressed LV function. 3 The role of AVR in patients with low-gradient AS has been more controversial. Carabello et al. 1 reported high perioperative mortality and poor outcomes in a small group of patients with low-gradient AS who underwent AVR in the 1970s. Other investigators also reported high perioperative mortalities in patients with low-gradient AS, 8 - 10 although results were better in those patients in whom CR was demonstrated. 8
The importance of CR, the role of dobutamine stress hemodynamics, and the outcome after AVR has been evaluated by a recent French multicenter study. Monin and colleagues 11 evaluated 136 patients with low-gradient AS and used dobutamine stress hemodynamics to determine the presence or absence of CR (defined as >20% increase in stroke volume). Perioperative mortality (within 30 days of AVR) was 5% in patients with CR and 33% in those without CR. These investigators also demonstrated that Kaplan-Meier survival curves were significantly better in patients with CR who underwent AVR compared with those with CR but treated medically. Survival was worse in patients without CR than in those with CR; again, patients without CR who nevertheless underwent AVR demonstrated better survival than those treated medically; prognosis was extremely poor in the latter group.
The same group of French investigators has published the results of intermediate-term follow-up after AVR in patients with low-gradient AS. 12 In 80 such patients, perioperative deaths were noted in 6% of those with CR and in 33% of those without CR on preoperative evaluation using dobutamine stress Doppler hemodynamics. Survivor follow-up averaged 26 months, and improvement was the norm. New York Heart Association heart failure symptoms improved by at least one class in 94% of patients, and average EF increased from 29% preoperatively to 47% after AVR. Although operative risk was high in patients with low-gradient AS undergoing AVR, survivors did well. Survival at 2 years was 90% in those with preoperative CR and 92% in those without preoperative CR. When AVR survivors with CR were compared with those without CR, no significant differences were noted in the percentage of patients in whom functional class improved, or in the frequency and degree of improvement in EF. On multivariate analysis, patients with low preoperative PG and those with multivessel coronary artery disease were less likely to demonstrate an improved EF during follow-up. Key study findings are summarized in Table 4.1 .
Table 4.1 Summary of Key Points From a French Multicenter Study 12 Variable With Contractile Reserve No Contractile Reserve Δ Stroke volume with dobutamine infusion 5 → 20 mcg/kg/min >20% increase <20% increase Perioperative mortality rate (AVR) 5% 32% Improved NYHA class post-AVR 96% 90% Change in LVEF post-AVR 28% → 47% 31% → 48% AVR indicated Yes; reasonable risk and good outcome Probably; high risk but good outcome, dismal results without AVR
AVR, Aortic valve replacement; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction.
From Quere J-P, Monin J-L, Levy F, et al. Influence of preoperative left ventricular contractile reserve on postoperative ejection fraction in low-gradient aortic stenosis. Circulation 2006;113:1738-1744.
These results indicate that dobutamine stress hemodynamics are helpful in determining operative risk in patients with low-gradient AS and confirm that perioperative death is much less likely in those with CR. However, most survivors of AVR demonstrate clinical improvement. Since prognosis is “abysmal” in patients with low-gradient AS who do not show CR on dobutamine stress hemodynamic testing, it seems reasonable to consider such patients for AVR. 13

References

1. Carabello BA, Green LH, Grossman W, et al. Hemodynamic determinants of prognosis of aortic valve replacement in critical aortic stenosis and advanced congestive heart failure. Circulation . 1980;62:42-48.
2. Cannon JD, Zile MR, Crawford FAJr, et al. Aortic valve resistance as an adjunct to the Gorlin formula in assessing the severity of aortic stenosis in symptomatic patients. J Am Coll Cardiol . 1992;20:1517-1523.
3. Bonow RO, Carabello BA, Chatterjee K, 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. Circulation . 2006;114:e84-e231.
4. Ross JJr. Afterload mismatch and preload reserve: a conceptual framework for the analysis of ventricular function. Prog Cardiovasc Dis . 1976;18:255-264.
5. Otto CM, Pearlman AS, Comess KA, et al. Determination of the stenotic aortic valve area in adults using Doppler echocardiography. J Am Coll Cardiol. . 1986;7:509-517.
6. Hoffmann R, Flachskampf FA, Hanrath P. Planimetry of orifice area in aortic stenosis using multiplane transesophageal echocardiography. J Am Coll Cardiol. . 1993;22:529-534.
7. DeFilippi CR, Willett DL, Brickner E, et al. Usefulness of dobutamine echocardiography in distinguishing severe from nonsevere valvular aortic stenosis in patients with depressed left ventricular function and low transvalvular gradients. Am J Cardiol . 1995;75:191-194.
8. Nishimura RA, Grantham JA, Connolly HM, et al. Low-output, low-gradient aortic stenosis in patients with depressed left ventricular systolic function—the clinical utility of the dobutamine challenge in the catheterization laboratory. Circulation . 2002;106:809-813.
9. Brogan WC, Grayburn PA, Lange RA, et al. Prognosis after valve replacement in patients with severe aortic stenosis and a low transvalvular pressure gradient. J Am Coll Cardiol . 1993;21:1657-1660.
10. Connolly HM, Oh JK, Schaff HV, et al. Severe aortic stenosis with low transvalvular gradient and severe left ventricular dysfunction: result of aortic valve replacement in 52 patients. Circulation . 2000;101:1940-1946.
11. Monin J-L, Quere J-P, Monchi M, et al. Low-gradient aortic stenosis. Operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics. Circulation . 2003;108:319-324.
12. Quere J-P, Monin J-L, Levy F, et al. Influence of preoperative left ventricular contractile reserve on postoperative ejection fraction in low-gradient aortic stenosis. Circulation . 2006;113:1738-1744.
13. Lange RA, Hillis LD. Dobutamine stress echocardiography in patients with low-gradient aortic stenosis. Circulation . 2006;113:1718-1720.
Chapter 5 Asymptomatic Severe Aortic Stenosis

Helmut Baumgartner, MD
Aortic stenosis (AS) has become the most frequent valvular heart disease and the most frequent cardiovascular disease after hypertension and coronary artery disease in Europe and North America. In the adult population, it primarily presents as calcific AS at advanced age. The prevalence in the population older than 65 years has been reported in the range of 2% to 7% and aortic sclerosis, the precursor of AS, has been found in 25%. 1
The characteristic systolic murmur of AS generally first draws attention and guides the further diagnostic workup into the right direction. Doppler echocardiography is the ideal tool to confirm diagnosis and quantify AS by calculating pressure gradients ( Fig. 5.1 ) and valve area.

Fig. 5.1 Continuous wave Doppler recordings of an asymptomatic patient with severe aortic stenosis. Note that the recording from a right parasternal approach ( lower panel ) yields significantly higher velocities (peak velocity, 5.3 m/s; mean gradient, 75 mm Hg) than that from an apical approach (4.6 m/s, 54 mm Hg).
During the long latent period with increasing outflow tract obstruction that results in increasing left ventricular (LV) pressure load, patients remain asymptomatic and acute complications are rare. However, outcome becomes dismal as soon as symptoms such as exertional dyspnea, angina or dizziness, and syncope occur. Average survival after the onset of symptoms has been reported as less than 2 to 3 years. 2 In this situation, valve replacement not only results in dramatic symptomatic improvement but also in good long-term survival. 2 This improvement applies even for patients with already reduced LV function, as long as functional impairment is indeed caused by AS. Thus there is consensus that urgent surgery must be strongly recommended in symptomatic patients. 3 , 4 In contrast, the management of asymptomatic patients with severe AS remains controversial. 2 , 3 Because of the widespread use of Doppler echocardiography it is estimated that about 50% of patients who come to medical attention with severe AS still have no symptoms. Thus cardiologists are increasingly faced with the difficult decision whether to perform surgery in asymptomatic patients with severe AS. Several criteria including findings of echocardiography and exercise testing have been proposed for risk stratification. Potential arguments for surgery in asymptomatic AS must be reviewed before discussing the value of the risk stratification criteria.

Potential Arguments for Surgery in Asymptomatic Aortic Stenosis

Risk of Sudden Cardiac Death
Sudden death is probably the major concern when asymptomatic patients with severe AS are monitored conservatively. However, this risk appears to be low. In addition to several studies that included patients with nonsevere AS and no sudden deaths, two prospective studies report the outcome of sizable cohorts of patients with exclusively severe AS (peak aortic jet velocity ≥4.0 m/s): Pellikka et al. 5 observed two sudden deaths among 113 patients during a mean follow-up of 20 months. Both patients, however, had experienced symptoms at least 3 months before death. We have reported one sudden death that was not preceded by any symptoms among 104 patients with 27 months of average follow-up. 6 In a recent retrospective study of 622 patients with a mean follow-up of 5.4 ± 4.0 years, Pellikka et al. 7 reported the rate of sudden death as 1% per year. However, in almost half of these sudden deaths, information on patients’ status was missing for the last year before death. Furthermore, a small but still significant risk of sudden death (0.3% to 0.4%) has been reported even after surgery, at least for congenital AS. 8 Thus prevention of sudden death is not a strong argument for surgery in asymptomatic patients.
Unfortunately, patients do not always promptly report their symptoms. In addition, in some countries patients must wait several months for surgery. However, mortality has been reported as already quite significant within the months following symptom onset. In a Scandinavian study, 9 for example, 7 of 99 patients with severe AS who were scheduled for surgery died during an average waiting period of 6 months.

Risk of Irreversible Myocardial Damage
In contrast to valvular regurgitation, patients with asymptomatic severe AS in whom impaired systolic LV function has already developed are rare. It has been speculated, however, that myocardial fibrosis and severe LV hypertrophy that may not be reversible after delayed surgery could preclude an optimal postoperative long-term outcome. To date, no data exist to confirm this hypothesis, 3 and the excellent outcome after valve replacement in patients with isolated AS with normal systolic LV function raises doubts that the risk of developing irreversible hypertrophy and myocardial fibrosis during the asymptomatic phase may bolster the argument for surgery in asymptomatic patients. Further studies are required to clarify this question.

Surgical Considerations
Patients with severe symptoms have a significantly higher operative mortality than those with no or only mild symptoms. According to the Society of Thoracic Surgeons U.S. cardiac surgery database 1997, patients in New York Heart Association (NYHA) classes I or II had an operative mortality of less than 2% compared with 3.7% and 7.0% for patients in NYHA classes III and IV, respectively. 10 In addition, urgent or emergent valve replacement carries a significantly higher risk than elective surgery. 10 Nevertheless, operative risk—even if small—must always be weighed against the potential benefit(s). Although operative mortality can ideally range from 1% to 3%, it may be as high as 10% in older patients and even markedly higher in the presence of significant additional comorbidity. 11 Even more important, not only must operative risk be considered but also prosthetic valve–related long-term morbidity and mortality. Thromboembolism, bleeding, endocarditis, valve thrombosis, paravalvular regurgitation, and valve failure occur at the rate of at least 2% to 3% per year, and death directly related to the prosthesis has been reported at a rate of up to 1% per year. 3

Duration of the Asymptomatic Phase
Some studies reported a rapid disease progression and thus poor outcome with up to 80% of the patients requiring valve replacement within 2 years. 12 Such observations have also questioned the benefit of delaying surgery in still-asymptomatic patients. However, other investigators have reported better overall outcomes with individual outcome varying widely. For example, survival without surgery or with eventual valve replacement indicated by the development of symptoms was 56% ± 5% at 2 years in our series of asymptomatic patients with severe AS. 6 These discrepant results may be explained by the fact that in some studies patients underwent surgery without having preoperative symptoms developed while these interventions were, nevertheless, counted as events. Thus the event-free survival reported in the literature should be viewed with caution.

Predictors of Outcome and Risk Stratification in Asymptomatic Severe Aortic Stenosis
Because it appears unlikely from current data that the potential benefit of valve replacement can outweigh the risk of surgery and the long-term risk of prosthesis-related complications in all asymptomatic patients, surgery is not generally recommended in patients with AS before symptom onset. 3 , 4 In particular, the fact that patients frequently do not present immediately when symptoms develop and that some may need to wait some time for surgery while symptoms are present represents significant risk. The ideal approach would be to refer patients for surgery just before symptom onset. Echocardiography and exercise testing have been of value with this regard.

Rest Echocardiography
Among the rest echocardiographic parameters, peak aortic jet velocity, aortic valve area, the rate of hemodynamic progression, and left ventricuclar hypertrophy and ejection fraction have been identified as independent predictors of outcome. 4 However, these findings were obtained retrospectively and do not allow any specific recommendations on prospective selection of high-risk patients who may benefit from early elective surgery. 3, 4
Aortic valve calcification has become a powerful independent predictor of outcome. 6 Event-free survival at 4 years was 75% ± 9% in patients with no or only mild calcification versus 20% ± 5% in those with moderately or severely calcified valves ( Fig. 5.2 ). The worse outcome in patients with more severe calcification appeared to be paralleled by a more rapid hemodynamic progression. However, even in the presence of calcification the rate of hemodynamic progression varies widely. 2 , 6 In fact, the hemodynamic progression as determined by serial echocardiographic examination appears to yield important prognostic information beyond the degree of calcification. The combination of a markedly calcified valve with a rapid increase in velocity of 0.3 m/s or greater from one visit to the next one scheduled within 1 year has identified a high-risk group of patients. Approximately 80% of patients so identified required surgery or died within 2 years. 6 This criterion has been included in the European recommendations as a IIa indication for valve replacement, 4 whereas the American College of Cardiology/American Heart Association (ACC/AHA) guidelines list “high likelihood of rapid progession” among other features by marked valve calcification as a IIb indication.

Fig. 5.2 Short-axis views of patients with severe aortic stenosis and various degrees of valve calcification. Left upper panel: No calcification; right upper panel: mild calcification; left lower panel: moderate calcification; right lower panel: severe calcification.

Exercise Testing
An abnormal response to exercise has been found to predict outcome. Amato and colleagues 14 performed exercise testing in 66 asymptomatic patients with an aortic valve area <1.0 cm 2 who had follow-up for 15 ± 12 months. Criteria for a positive test result were occurrence of symptoms, new ST-segment depression, systolic blood pressure increase less than 20 mm Hg, or complex ventricular arrhythmias. At 24 months, event-free survival (with events defined as development of symptoms in daily life or death) was 85% in 22 patients with negative test results but only 19% (including 4 sudden deaths!) in patients with a positive test result. Although these results seem impressive, they leave many unanswered questions. The majority of patients with a positive test result fulfilled the criterion of symptom development. In particular, three of the patients who died had symptoms during the test. Although the study allowed the conclusion that patients with a negative exercise test result appear to have a good outcome and may not require surgery, whereas those limited by typical symptoms should undergo valve replacement, the positive predictive value of an abnormal blood pressure response and/or ST-segment depression without occurrence of symptoms remained unclear.
More recently, Das and colleagues 15 clarified some of the unanswered questions. In 125 patients with asymptomatic AS (effective valve area 0.9 ± 0.2cm 2 ), they assessed the accuracy of exercise testing in predicting symptom onset within 12 months. Similar to previous reports, in approximately one third of the patients symptoms developed on exercise. Abnormal blood pressure response, more strictly defined as no increase in systolic blood pressure at peak exercise compared to baseline, was found in 23% and ST-segment depression greater than 2 mm in 26% of patients. No deaths occurred during follow-up, but spontaneous symptoms developed in 29% of their patients. The absence of limiting symptoms had a high negative predictive accuracy of 87%. An abnormal blood pressure response or ST-segment depression, however, provided no statistically significant benefit above limiting symptoms with respect to predictive accuracy. In the absence of limiting symptoms, only two patients with abnormal blood pressure response, two with ST-segment depression, and one with both conditions had symptoms develop during follow-up. Negative predictive values were 78% and 77% and positive predictive values 48% and 45%, respectively. These findings suggest that abnormal blood pressure response and ST-segment depression are rather nonspecific findings and are not helpful in identifying asymptomatic patients who may benefit from elective valve replacement. Even limiting symptoms on exercise testing had a positive predictive accuracy of only 57% in the present study when including all patients and all symptoms. When considering only physically active patients younger than 70 years, positive predictive accuracy rose to 79%. Apparently, it also matters which symptoms occur on exercise testing: In the entire study group, 83% of patients with dizziness developed spontaneous symptoms compared with only 50% of patients with chest tightness and 54% of patients with breathlessness. The most likely explanation for these findings is that breathlessness on exercise may be difficult to interpret in patients with only low physical activity and particularly in older patients (>70 years). In this group, it is difficult to decide whether breathlessness on exercise is indeed a symptom of AS.
Thus exercise testing is primarily helpful in physically active patients younger than 70 years. A normal exercise test result indicates a very low likelihood of symptom development within 12 months and watchful waiting is safe. Conversely, clear symptom development on exercise testing indicates in physically active patients younger than 70 years a very high likelihood of symptom development within 12 months and valve replacement should be recommended. However, abnormal blood pressure response and/or ST-segment depression without symptoms on exercise have a low positive predictive value and may not justify elective surgery.

Incremental Value of Exercise Hemodynamics Assessed by Doppler Echocardiography
Exercise hemodynamics have also been reported as predictors of outcome. Lancellotti et al. 13 found the change in mean gradient with exercise to be an independent predictor of event-free survival in asymptomatic AS. Patients with an increase in mean gradient or 18 mm Hg or more had a markedly worse outcome than those with less than 18 mm Hg. In their series, a positive conventional exercise test was again a significant predictor of outcome but they were able to demonstrate that exercise echo was of incremental value. However, the number of patients was small, and the majority had valve replacement while the precise indication for surgery was not clearly stated. Thus further studies are required to define the actual role of adding hemodynamics as assessed by echo to basic exercise testing. Echocardiographic predictors of outcome in AS are summarized in Table 5.1 .
Table 5.1 Echocardiographic Predictors of Outcome in Aortic Stenosis
Rest transvalvular velocity/gradient
Rest aortic valve area
Extent of valve calcification
Hemodynamic progression rate
Increase of gradient with exercise
Left ventricular hypertrophy
Left ventricular ejection fraction
Degree of concomitant functional mitral regurgitation *
Pulmonary artery pressure *
* No data for asymptomatic aortic stenosis.

Other Predictors of Outcome in Asymptomatic Severe Aortic Stenosis
Plasma levels of cardiac neurohormones increase with the hemodynamic severity of AS and with increasing symptoms. More importantly, plasma levels of neurohormones may predict symptom-free survival in AS. 16 In a recent study published by our group, patients with brain natriuretic peptide (BNP) levels <130 pg/mL or N -terminal BNP levels <80 pmol/L were unlikely to develop symptoms within 9 months (symptom-free survival ∼90%), whereas those with higher levels frequently required surgery within this period (symptom-free survival <50%). Thus serial measurements of neurohormones during follow-up may also help identify the optimal time for surgery, but further studies are required to define solid cutoff values.
Current recommendations of the American College of Cardiology and the American Heart Association and those of the European Society of Cardiology, which slightly differ, are summarized in Table 5.2 . Echocardiography plays an important role for management decision making by providing systolic LV function, hemodynamic progression and extent of valve calcification, extent of LV hypertrophy, and actual severity of AS (mean gradient and aortic valve area).
Table 5.2 Recommendations for Isolated Aortic Valve Replacement in Asymptomatic Aortic Stenosis * Class ACC/AHA Guidelines 3 ESC Guidelines 4 I Patients with reduced systolic LV function (LVEF <0.50) Patients with reduced systolic LV function (LVEF <0.50) I   Patients in whom symptoms develop during exercise testing IIa   Patients with moderate to severe valve calcification, a peak jet velocity >4 m/s, and a rate of peak velocity progression ≥0.3 m/s/yr IIa   Patients with a decrease in blood pressure below baseline during exercise testing IIb Patients with abnormal response to exercise (symptoms, hypotension) Patients who develop complex ventricular arrhythmias during exercise testing IIb Patients with high likelihood of rapid progression (age, CAD, calcification)   IIb   Patients with severe LV hypertrophy (≥15 mm) unless due to hypertension IIb Patients with extremely severe AS (valve area <0.6 cm 2 , mean gradient >60 mm Hg) and expected operative mortality ≤1%  
ACC, American College of Cardiology; AHA, American Heart Association; AS, aortic stenosis; CAD, coronary artery disease; EF, ejection fraction; ESC, European Society of Cardiology; LV, left ventricular.
* No indication for bypass surgery, other valve surgery, or aortic surgery.

Does Medical Treatment Prevent Progression of Aortic Setenosis?
Calcific AS is a chronic progressive disease that starts with thickening and calcification of valve cusps without hemodynamic significance (i.e., aortic sclerosis) and eventually ends in heavily calcified stiff cusps causing severe valve stenosis. The progression from aortic sclerosis that can already easily be detected by echocardiography or computed tomography to hemodynamically severe AS takes many years. Thus, clinicians face the rather unique situation in valvular heart disease that the disorder can be diagnosed at an early stage, thereby offering the chance of interfering with its further progression to a clinically relevant valve problem. Although calcific aortic valve disease was until recently considered a degenerative and unmodifiable process basically induced by long-lasting mechanical stress, histopathologic studies have made it clear that it is an active process that shares several similarities with atherosclerosis. 17 Inflammation, lipid infiltration, dystrophic calcification, ossification, platelet deposition, and endothelial dysfunction have been observed in both diseases and hypercholesterolemia, elevated lipoprotein(a), smoking, hypertension, and diabetes have been reported as common risk factors for both disorders. 17 Thus, modification of atherosclerotic risk factors may slow progression of aortic valve calcification. In addition, the renin-angiotensin system that plays a role in atherosclerosis may also be important in the pathogenesis of calcific AS. 17 , 18 Thus drugs that interfere with this system may delay disease progression. However, the agents that have gained most interest in recent years with regard to AS progression prevention are definitely statins.
Indeed, several retrospective studies have consistently demonstrated that statin therapy is associated with markedly lower hemodynamic progression of AS. 19 - 21 The question of whether this effect is dependent on cholesterol lowering (or not), however, remains controversial. Although Novaro et al. 20 have reported an association between AS progression and cholesterol levels, Bellamy and colleagues 19 and the author’s group in Vienna 21 could not find such an association supporting the hypothesis that the effects of statins may rather be caused by their pleiotropic and antiinflammatory properties than by cholesterol lowering. The beneficial effects of statin therapy do not appear to be restricted to the early stage of disease. 21 Since a rapid increase of the peak aortic jet velocity among patients with severe AS and moderately to severely calcified valves has been shown to indicate a poor outcome, 6 slowing disease progression in these patients may still beneficially alter their outcome with respect to the development of symptoms and the necessity of surgery. Thus retrospective data suggested that statin therapy may be indicated in any patient with AS, regardless of AS severity and cholesterol levels.
Surprisingly, the first prospective randomized trial on statin therapy in AS did not show any significant effect on the progression of AS. 22 However, this study may not have included enough patients (N = 155) and the follow-up may have been too short (26 months on average). However, a large recent randomized trial has confirmed that statin treatment, in patients for whom have no otherwise currently recommended indication for such therapy, has no effect on the progression and event rate in aortic stenosis. 24
The fact that angiotensin-converting enzyme (ACE) and angiotensin II can be found in sclerotic but not in normal aortic valves suggests a potential role of the renin-angiotensin system in the pathogenesis of calcific AS. 17 , 18 ACE is also found in atherosclerotic lesions, and angiotensin II is assumed to contribute to the atherosclerotic process via its proinflammatory effects. Clinical trials have demonstrated clinical benefit of treatment with agents that block renin-angiotensin system components in patients who either have had or are at high risk for atherosclerosis, suggesting similar effects in calcific AS. Indeed, ACE inhibitors have indeed been shown to slow the calcium accumulation in aortic valves in a retrospective study using electron beam computed tomography. 23 To date, only one study has evaluated the effects of ACE inhibitors on the hemodynamic progression of AS. 21 This retrospective analysis, however, could not find any difference in progression rates between patients with and without ACE inhibitor treatment. Nevertheless, initiation of ACE inhibitor therapy at an earlier stage of disease and longer treatment still may have positive effects on disease progression. Further studies may therefore be required.
In conclusion, there is no solid evidence that AS progression can be prevented with any medical therapy and it is too early for treatment recommendations.

References

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17. Mohler ER. Mechanisms of aortic valve calcification. Am J Cardiol . 2004;94:1396-1402.
18. O’Brien KD, Shavelle DM, Caulfield MT, et al. Association of angiotensin-converting enzyme with low-density lipoprotein in aortic valvular lesions and in human plasma. Circulation . 2002;106:2224-2230.
19. Bellamy MF, Pellikka PA, Klarich KW, et al. Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community. J Am Coll Cardiol . 2002;40:1723-1730.
20. Novaro GM, Tiong IY, Pearce GL, et al. Effect of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of calcific aortic stenosis. Circulation . 2001;104:2205-2209.
21. Rosenhek R, Rader F, Loho N, et al: Statins but not ACE inhibitors delay progression of aortic stenosis. 110:1291-1295, 2004
22. Cowell SJ, Newby DE, Prescott RJ, et al. Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) investigators. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med . 2005;352:2389-2397.
23. O’Brien KD, Probstfield J, Caulfield MT, et al. Angiotensin-converting enzyme inhibitors and change in aortic valve calcium. Arch Intern Med . 2005;165:858-862.
24. Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med . 2008;359:1343-1356.
Chapter 6 Challenges in Aortic Stenosis

Joseph A. Lodato, MD, Roberto M. Lang, MD, FASE
The natural history of aortic stenosis (AS) is characterized by a prolonged latent period during which patients have no symptoms. During this phase a gradual increase in aortic valve obstruction and compensatory hypertrophy of the myocardium counter the increase in afterload. Morbidity and mortality rates are low during this latent phase, presumably because of preservation of cardiac output. Although historically sudden death has been reported in those without symptoms, several prospective echocardiographic studies indicate that this is a rare event—probably less than 1%. 1 - 6 However, the eventual onset of the classical symptoms of AS—angina, syncope, or heart failure—is a harbinger of a poor outcome without surgical replacement. Once these cardinal symptoms are manifest, the average survival is 2 to 3 years and the risk of sudden death is high. 1, 7 - 9
Hemodynamic progression of AS has been well studied by both cardiac catheterization and echocardiography. Results of invasive and noninvasive testing are concordant. The mean rate of progression is an increase in the jet velocity by 0.3 m/s per year, an increase in mean pressure gradient of 7 mm Hg per year, and a decrease in valve area of 0.1 cm 2 per year. 6, 10 - 14 However, there is considerable heterogeneity in the rate of progression across patients. For example, evidence suggests that calcific degenerative disease progresses more rapidly than congenital or rheumatic AS. 6 - 15 Because progression in an individual patient is unpredictable, frequent and regular follow-up is important in patients with asymptomatic AS.
Clinical progression from asymptomatic to symptomatic disease is common in those with severe AS (jet velocity ≥4 m/s) and is as high as 79% at 3 years. 3 However, often the challenge in patients with AS is identifying those with symptoms, even after careful history taking. This is an important distinction as the morbidity and mortality without valve replacement markedly differs between the two groups. Diminished exercise tolerance may be the initial or only symptom related to AS progression. Because AS is typically a disease of the elderly, reduced exercise tolerance is blamed on aging and other factors. Exercise testing can help in risk stratification of patients previously labeled asymptomatic. 16 - 21 It may also identify patients with an abnormal hemodynamic response to exercise (failure to augment systolic blood pressure >20 mm Hg, or hypotension), which is a poor prognostic finding in severe AS. 17 , 22 It is important to remember that there is no indication for exercise testing in symptomatic patients, and the results of testing are not adequate to diagnose significant coronary artery disease. An additional benefit of exercise testing in asymptomatic patients is that it may help define exercise limitations in those with moderate or severe AS.
Echocardiography has emerged as the primary diagnostic tool for the evaluation of AS because of the ease of operation and relative safety profile compared with heart catheterization. Echocardiography not only provides information on the structure and function of the aortic valve, but it also characterizes the response of the left ventricle to increased afterload and can identify other associated valvular pathology. Recommendations for serial echocardiographic evaluation of patients with asymptomatic AS are every year for severe AS, every 1 to 2 years for moderate AS, and every 3 to 5 years for mild AS. 23
Performing echocardiography to evaluate AS severity mandates careful attention to technical details. Underestimation of AS is common if the study is not performed and interpreted correctly. For the ultrasonographer, the Doppler intercept angle with the AS jet should be less than 15 degrees. Multiple transducer locations and optimal patient positioning is recommended to yield the highest jet velocity. Suggested patient positions and transducer locations are left lateral decubitus with the transducer at the apex; right lateral decubitus with right parasternal transducer location; and suprasternal transducer position with the neck extended. For the interpreter, it is important to correctly identify the origin of the high-velocity jet. The Doppler signal of mitral or tricuspid regurgitation, as well as a ventricular septal defect, and other vascular lesions can mimic the signal of AS. Additionally, accurate measurement of the left ventricular outflow tract diameter is crucial to obtaining reliable estimates of the aortic valve area from the continuity equation. Since this value is squared, it can introduce considerable error in calculation. As always, with any hemodynamic study, heart rate variability from premature beats or atrial fibrillation must be taken into account. 24
The case depicted in Figs. 6.1 and 6.2 illustrates some key points in the evaluation of an “asymptomatic” patient with AS. Aortic stenosis is a progressive disease that necessitates frequent and regular follow-up for the detection of symptoms. Exercise testing can be used for risk stratification of patients when the clinical history is equivocal. Echocardiography, when correctly performed, is the optimal method of assessing severity and hemodynamic progression of disease.

Fig. 6.1 Doppler profile of a 67-year-old woman who was evaluated for a heart murmur. Her echocardiogram demonstrated mild to moderate concentric left ventricular hypertrophy and normal left ventricular systolic function. She insisted that she had no symptoms. Using the continuity equation, her aortic valve area (AVA) is consistent with severe aortic stenosis. TVI LVOT , Velocity-time integral of the left ventricular outflow tract; TVI AV , velocity-time integral of the aortic valve; D, diameter.

Fig. 6.2 Review of an echocardiogram performed 2 years previously shows a marked change in mean gradient and peak velocity, greater than would be expected for the normal rate of progression. Exercise testing confirmed the suspicion that this patient was not truly asymptomatic; she only completed 4 minutes on the Bruce protocol and failed to augment systolic blood pressure more than 20 mm Hg. PG, Peak gradient; V, velocity; VTI, velocity-time integral.

References

1. Kelly TA, Rothbart RM, Cooper CM, et al. Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis. Am J Cardiol . 1988;61:123-130.
2. Kennedy KD, Nishimura RA, Holmes DRJr., et al. Natural history of moderate aortic stenosis. J Am Coll Cardiol . 1991;17:313-319.
3. Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis: clinical, echocardiographic, and exercise predictors of outcome. Circulation . 1997;95:2262-2270.
4. Pellikka PA, Nishimura RA, Bailey KR, et al. The natural history of adults with asymptomatic, hemodynamically significant aortic stenosis. J Am Coll Cardiol . 1990;15:1012-1017.
5. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation . 2005;111:3290-3295.
6. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med . 2000;343:611-617.
7. Iivanainen AM, Lindroos M, Tilvis R, et al. Natural history of aortic valve stenosis of varying severity in the elderly. Am J Cardiol . 1996;78:97-101.
8. Schwarz F, Baumann P, Manthey J, et al. The effect of aortic valve replacement on survival. Circulation . 1982;66:1105-1110.
9. Turina J, Hess O, Sepulcri F, et al. Spontaneous course of aortic valve disease. Eur Heart J . 1987;8:471-483.
10. Brener SJ, Duffy CI, Thomas JD, et al. Progression of aortic stenosis in 394 patients: relation to changes in myocardial and mitral valve dysfunction. J Am Coll Cardiol . 1995;25:305-310.
11. Davies SW, Gershlick AH, Balcon R. Progression of valvar aortic stenosis: a long-term retrospective study. Eur Heart J . 1991;12:10-14.
12. Faggiano P, Ghizzoni G, Sorgato A, et al. Rate of progression of valvular aortic stenosis in adults. Am J Cardiol . 1992;70:229-233.
13. Otto CM, Pearlman AS, Gardner CL. Hemodynamic progression of aortic stenosis in adults assessed by Doppler echocardiography. J Am Coll Cardiol . 1989;13:545-550.
14. Roger VL, Tajik AJ, Bailey KR, et al. Progression of aortic stenosis in adults: new appraisal using Doppler echocardiography. Am Heart J . 1990;119:331-338.
15. Rosenhek R, Klaar U, Schemper M, et al. Mild and moderate aortic stenosis: natural history and risk stratification by echocardiography. Eur Heart J . 2004;25:199-205.
16. Alborino D, Hoffmann JL, Fournet PC, et al. Value of exercise testing to evaluate the indication for surgery in asymptomatic patients with valvular aortic stenosis. J Heart Valve Dis . 2002;11:204-209.
17. Amato MCM, Moffa PJ, Werner KE, et al. Treatment decision in asymptomatic aortic valve stenosis: role of exercise testing. Br Heart J . 2001;86:381-386.
18. Atwood JE, Kawanishi S, Myers J, et al. Exercise testing in patients with aortic-stenosis. Chest . 1988;93:1083-1087.
19. Clyne CA, Arrighi JA, Maron BJ, et al. Systemic and left ventricular responses to exercise stress in asymptomatic patients with valvular aortic stenosis. Am J Cardiol . 1991;68:1469-1476.
20. Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J . 2005;26:1309-1313.
21. Otto CM, Pearlman AS, Kraft CD, et al. Physiologic changes with maximal exercise in asymptomatic valvular aortic stenosis assessed by Doppler echocardiography. J Am Coll Cardiol . 1992;20:1160-1167.
22. Takeda S, Rimington H, Chambers J. Prediction of symptom-onset in aortic stenosis: a comparison of pressure drop/flow slope and haemodynamic measures at rest. Int J Cardiol . 2001;81:131-137.
23. Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2006;48:598-675.
24. Otto CM. Textbook of clinical echocardiography , ed 4. Philadelphia: Elsevier; 2009.
Chapter 7 Technical Issues
Aortic Stenosis

Matt M. Umland, RDCS, FASE
Transthoracic echocardiography provides a comprehensive assessment of aortic stenosis (AS). This allows for confident and proper clinical management decisions. Technical issues can arise in the assessment of the stenotic aortic valve, which reduces the quantitative accuracy of stenosis, thus affecting clinical decision making. These technical pitfalls are listed in Table 7.1 .
Table 7.1 Technical Pitfalls in Echocardiographic Evaluation of Aortic Stenosis Technical Error Consequence LVOT diameter measured incorrectly Incorrect aortic valve area Doppler sample volume placement Incorrect aortic valve area Single window Severity may be underestimated Nonaligned transducer Severity underestimated Doppler signal differentiation Incorrect assessment
Stroke volume across the aortic valve must be calculated to determine aortic valve area. 1 The formula for calculating aortic valve stroke volume is

where LVOT is the left ventricular outflow tract, (d) 2 denotes diameter, and TVI denotes the time-velocity integral.
The diameter should be measured in the parasternal long-axis view during systole. The distance should be measured from the insertion of the anterior aortic cusp to where the posterior cusp meets the mitral valve anterior leaflet ( Fig. 7.1 ). Accurate measurement of the LVOT diameter is crucial to the calculation of the aortic valve area because of squaring of the dimension. Table 7.2 demonstrates corresponding LVOT stroke volumes calculated from various diameters with a constant LVOT TVI of 18 cm.

Fig. 7.1 Measurement of LVOT diameter. Parasternal long-axis view: Insertion of anterior aortic cusp to posterior cusp. Average three cycles (sinus rhythm); average 5 to 8 cycles (atrial fibrillation).
Table 7.2 Corresponding LVOT Stroke Volumes Calculated From Various Diameters With a Constant LVOT TVI of 18 cm LVOT Diameter (cm) Stroke Volume * (mL) 2.0 57 2.1 62 2.2 68 2.3 75 2.4 81
TVI, Time-velocity integral.
* Stroke volume is calculated as LVOT (d) 2 × 0.785 × LVOT TVI.
Correct measurement of the LVOT velocity/TVI ratio is also an integral part of the calculation of aortic valve area when the continuity method is used. The acquisition of the LVOT velocity/TVI ratio should be accomplished in the apical long-axis view. The pulsed wave sample volume should be placed 3 to 5 mm below the aortic valve annulus. 1 If the sample volume is too close to the aortic valve, prestenotic acceleration jet velocity may be recorded. 1 An important consideration during this measurement is to attempt to achieve Doppler cursor placement as parallel to the flow of blood as possible. Color flow imaging may also be useful in aligning the continuous wave Doppler beam parallel with the blood flow.
Once the pulsed wave Doppler has been obtained, the next step is to acquire the continuous wave Doppler through the aortic valve. In achieving this Doppler pattern, it is imperative to be as parallel to flow as possible. Any deviation from parallel to flow results in an underestimation of the Doppler jet velocity. For example, an intercept angle of 30 degrees results in a measured velocity of 4.3 m/s when the actual velocity is 5.0 m/s. 2 If the underestimated velocity is used, it will result in significant errors in the pressure gradient and the valve area calculation. Intercept angles within 15 degrees of parallel result in an error in velocity measurement of ≤5%. 2 , 3
Multiple imaging windows should be used to align the continuous wave Doppler to the blood flow. The most common acoustic windows include the apical, suprasternal notch, right supraclavicular, right parasternal, and subcostal. These acoustic windows may also be obtained using the nonguided continuous wave (Pedoff) transducer. This transducer has a smaller footprint, which allows for easier manipulation around the thoracic cavity. The highest velocity Doppler signal obtained is assumed to represent the most parallel intercept angle. 2
It is important to ensure that the Doppler waveform is correctly identified. 1 - 6 Systolic flow velocities by continuous wave Doppler should be analyzed on the following bases: (1) peak velocity, (2) flow duration or ejection time, (3) location of the Doppler window, (4) accompanying diastolic flow signals, and (5) Doppler flow configuration. The differentiation of Doppler signals may be more beneficial if two-dimensional and continuous wave Doppler is used. 1 The duration of a mitral regurgitation jet is longer than that of AS jets. Aortic stenosis jets occur during ejection time only, whereas the mitral regurgitation occurs during isovolumic relaxation time, ejection time, and isovolumic contraction time. Mitral regurgitation jet velocity is always higher than the AS velocity when they both occur in the same patient. The flow velocity of a dynamic outflow tract obstruction produces a late-peaking dagger-shaped Doppler pattern. Dynamic outflow obstructions should increase while attempting provocable maneuvers, such as the Valsalva maneuver, while the fixed AS obstruction will not change.
The Doppler pattern of pulmonary stenosis is almost identical to that of AS. 1 The pulmonary stenosis signal is best obtained from the subcostal or left upper parasternal window, whereas an AS jet is usually obtained from the apex or right parasternal window. 1
Echocardiography provides a comprehensive hemodynamic and morphologic assessment of stenotic aortic valves. 4, 5 The assessment must be carried out with a concise, thorough examination with no or limited technical pitfalls.

References

1. Oh JK, Seward JB, Tajik AJ. The echo manual , ed 3. Philadelphia: Lippincott Williams & Wilkins; 2006.
2. Otto CM. Textbook of clinical echocardiography , ed 4. Philadelphia: Elsevier; 2009.
3. Edelman SK. Understanding ultrasound physics , ed 2. Bryan, TX: Tops Printing; 1997.
4. Murgo J. Systolic ejection murmurs in the era of modern cardiology. J Am Coll Cardiol . 1998;32:1596-1602.
5. Quinones M, Otto C, Stoddard M, et al. ASE recommendations for quantification of Doppler echocardiography. J Am Soc Echocardiogr . 2002;15:167-184.
6. Bartunek J, Sys S, Rodrigues A, et al. Abnormal systolic intraventricular flow velocities after valve replacement for aortic stenosis. Circulation . 1996;93:712-719.
Chapter 8 Quantitation of Aortic Regurgitation

Hari P. Chaliki, MD, FASE
Aortic regurgitation (AR) can be caused by valvular pathology, aortic root pathology, or a combination of the two. In developed countries, chronic isolated AR is predominantly due to aortic root disease, whereas rheumatic fever is still the leading cause of chronic AR in developing countries. 1 Based on population studies from the United States, the prevalence of moderate or severe AR varies with age. In younger patients (age <45 years) the prevalence is 0.2% and increases to 2% in older patients (age >75 years). 2 Surgery is frequently needed for patients with acute AR while the timing of surgery for chronic AR depends on regurgitation severity, patient’s symptoms, left ventricular (LV) size, and function. 3 As a result of improved surgical techniques, aortic valve surgery is now performed in selected asymptomatic patients with severe AR. Therefore, accurate determination of the cause and severity of AR is crucial when managing patients with AR. Echocardiography is ideal to obtain the necessary information in a majority of patients with AR. Semiquantitative and quantitative techniques should be used in an integrated fashion to assess the severity of AR.

Quantitation of Aortic Regurgitation

Semiquantitative Methods
Currently Doppler color flow imaging is widely used to determine the severity of AR despite its limitations and semiquantitative nature. 4 Parasternal long-axis, short-axis, and apical views can demonstrate the color Doppler recording of the AR nicely. Maximal length and area of the aortic regurgitant jet showed poor correlation with aortic angiography. Short-axis jet area at the high left ventricular outflow tract relative to the left ventricular outflow tract (LVOT) area correlated well with angiography. Also, jet width at this location compared with the LVOT width measured from the parasternal long-axis view correlated with the angiographic grade of AR. The proportion of either jet area or jet width compared with the LVOT area or width in excess of 60% to 65% indicates severe AR. 4 Although appealing, it is important to note that this method requires careful attention to gain settings and Nyquist limits to avoid overestimating or underestimating the severity of regurgitation. In general, this method provides only a rough estimate of the severity of AR. This method is of limited utility in patients with eccentric jets, diffuse jets, and jets originating along the entire coaptation line. 5
Both continuous and pulsed wave Doppler techniques are useful for the semiquantitative assessment of AR. Denser continuous wave Doppler signal implies a greater quantity of regurgitation, whereas faint signals generally represent mild regurgitation. Pressure half-time , the time for the pressure gradient to drop by half of its original value, is another measure of severity AR obtained by continuous wave Doppler. 6 , 7 It is expected that the pressure half-time will be shorter (<200 ms) in patients with severe AR as a result of the rapid rise in LV pressure from a large amount of regurgitant volume. Conversely, in patients with mild AR, pressure half-time is longer (>500 ms) because of the more gradual rise in LV pressure. Pressure half-time cannot be used alone to determine the severity of AR because it is dependent on chronicity of the regurgitation, systolic blood pressure, and LV compliance. 5
Another frequently used Doppler technique involves pulse wave Doppler of the proximal descending thoracic aorta. Significant holodiastolic flow reversals in the descending thoracic aorta, diastolic velocity time integral similar to systolic velocity time integral, and relatively high end-diastolic velocity (>20 cm/sec) are indicative of moderate to severe AR ( Fig. 8.1 ). 8 - 11 In some older patients, diastolic flow reversal is a less reliable indicator of the severity of AR because of stiffening of the aorta. It is also common to see short early diastolic flow reversal with or without severe AR. 5

Fig. 8.1 Holodiastolic flow reversal in proximal descending thoracic aorta in a patient with severe aortic regurgitation.
It has been proposed that the smallest area of the aortic regurgitant jet hydrodynamically represents vena contracta (VC). 12 From parasternal views, using the zoom function, the proximal flow convergence zone, flow at the aortic valve, and flow below the aortic valve can be visualized. 13 In early to mid-systole VC is then measured, which is defined as the width of the narrowest portion of the aortic regurgitant jet. VC width greater than 6 mm is indicative of severe AR with a sensitivity of 81% and specificity of 94%. 13 , 14 VC area greater than 7.5 mm 2 obtained by transesophageal echocardiography also correlates well with severe AR. 14 In some patients, a right parasternal transthoracic window 15 or transesophageal echocardiography 14 may be required to obtain adequate VC measurement.

Quantitative Methods
The continuity method uses the principle of conservation of mass to determine AR. Assuming there is no or minimal mitral regurgitation, the amount of AR can be precisely calculated by subtracting the flow through the mitral valve from the flow. 16 - 19 This method uses the combination of two-dimensional (2-D) information and Doppler technique. Flow through the mitral annulus and LVOT can be calculated by multiplying the mitral annular area and LVOT areas with their corresponding time velocity integrals (TVIs). Assuming a circular mitral annulus and LVOT, the following formulas are used to determine the mitral flow, LVOT flow, and aortic regurgitant volume (RV) 16 :



RV >60 mL is considered severe. Even though this technique is based on solid principles, it is a challenging technique to master and attention to detail is mandatory. A small error in mitral annular or LV measurement can greatly affect the calculations. Similarly, if the modal mitral inflow velocity (brightest signal) is not traced, this can result in an erroneous estimate of regurgitant volume. 5 , 19
Similar to the continuity method, the proximal isovelocity surface area (PISA) method or the flow convergence method is based on the conservation of mass principle. 20 Unlike the continuity method, the presence of mitral regurgitation will not affect the quantitation of AR. As the flow approaches a regurgitant orifice, flow accelerates with resultant isovelocity surfaces proximal to the regurgitant orifice. Using the conservation of mass principle, the effective regurgitant orifice area, 21 and finally RV, can be calculated by assuming a hemispheric shape of the proximal isovelocity. By baseline shifting of the color scale, the isovelocity surface can be viewed and resultant flow convergence radius and velocity can be obtained ( Fig. 8.2 ). 21 The zoom feature in combination with either the parasternal view or apical long-axis view is used to optimize the images. The aortic regurgitant flow rate is calculated as 2π × r 2 × V r , where r is the radius of the flow convergence measured in early diastole and V r is the corresponding aliasing velocity. Doppler tracing of the aortic regurgitant jet can then be used to calculate the effective regurgitant orifice area (ERO) and RV as follows 21 :

Fig. 8.2 The proximal isovelocity surface area (PISA) is visualized.


ERO >0.3 cm 2 and RV >60 mL are considered severe. Selected ranges for grading of the severity of AR are shown in Table 8.1 . In a few patients with dilated ascending aortas, the flow convergence zone may occupy more than 220 degrees around the aortic valve leaflets and leads to underestimation of ERO and RV by this method. 21

Table 8.1 Semiquantitative and Quantitative Measures for the Assessment of Severity of Aortic Regurgitation

Left Ventricular Measurements
Chronicity and severity of AR determine the LV response to volume overload. In acute severe AR, the left ventricle would not be expected to be large in the absence of other causes. On the contrary, in chronic severe AR, the left ventricle is dilated. The LV end-diastolic and systolic dimensions should be measured using either 2-D method or 2-D–targeted M-mode echocardiography at the mitral chordal level 22 as the current guidelines for surgery in asymptomatic patients are based on these measurements. 3 In selected cases, LV volume measurements using biplane method of disks (modified Simpson rule) 22 without foreshortening the left ventricle (using contrast if needed) is necessary to verify the stroke volume obtained by the continuity method and to confirm a large left ventricle when quantitative methods suggest severe AR.

Role of Transesophageal Echocardiography
In a few patients transesophageal echocardiography may be necessary if the cause and extent of aortic valve and/or the root pathology causing AR is not fully discernible from transthoracic imaging. This is especially true in cases of aortic valve endocarditis and dissection. In addition, as mentioned earlier, VC in some patients is better visualized during transesophageal echocardiography to complement the quantitation of AR from transthoracic imaging. 14

Role of Three-Dimensional Echocardiography
Current efforts in three-dimensional (3-D) echocardiography are now focused on validation of LV volumes and function, as well as improved visualization of valvular anatomy in real time. 23 , 24 One study in animals reported quantitation of AR by accurately measuring left and right ventricular volumes using 3-D echocardiography. 25 Few studies also reported quantitation of AR by measuring VC and proximal flow convergence using real-time 3-D echocardiography in animal models and adult patients. 26 - 28 Results from these studies show promise for the use of 3-D echocardiography in the near future for the assessment of AR.

Conclusions
Assessment of AR requires an integrative approach with attention to anatomy and physiology. Both semiquantitative and quantitative techniques (see Table 8.1 ) should be used for the final determination of the severity of AR. Transesophageal echocardiography is necessary only in a few patients. Future studies are needed to confirm the utility of 3-D echocardiography in improving the assessment of AR.

References

1 Enriquez-Sarano M, Tajik AJ. Clinical practice. Aortic regurgitation. N Engl J Med . 2004;351:1539-1546.
2 Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet . 2006;368:1005-1011.
3 Bonow RO, Carabello MO, Chatterjee K, et al. ACC/AHA 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. J Am Coll Cardiol . 2006;48:1486-1588.
4 Perry GJ, Helmcke F, Nanda NC, et al. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol . 1987;9:952-959.
5 Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr . 2003;16:777-802.
6 Teague SM, Heinsimer JA, Anderson JL, et al. Quantification of aortic regurgitation utilizing continuous wave Doppler ultrasound. J Am Coll Cardiol . 1986;8:592-599.
7 Griffin BP, Flachskampf FA, Siu S, et al. The effects of regurgitant orifice size, chamber compliance, and systemic vascular resistance on aortic regurgitant velocity slope and pressure half-time. Am Heart J . 1991;122:1049-1056.
8 Nishimura RA, Vonk GD, Rumberger JA, et al. Semiquantitation of aortic regurgitation by different Doppler echocardiographic techniques and comparison with ultrafast computed tomography. Am Heart J . 1992;124:995-1001.
9 Reimold SC, Maier SE, Aggarwal K, et al. Aortic flow velocity patterns in chronic aortic regurgitation: implications for Doppler echocardiography. J Am Soc Echocardiogr . 1996;9:675-683.
10 Touche T, Prasquier R, Nitenberg A, et al. Assessment and follow-up of patients with aortic regurgitation by an updated Doppler echocardiographic measurement of the regurgitant fraction in the aortic arch. Circulation . 1985;72:819-824.
11 Tribouilloy C, Avinee P, Shen WF, et al. End diastolic flow velocity just beneath the aortic isthmus assessed by pulsed Doppler echocardiography: a new predictor of the aortic regurgitant fraction. Br Heart J . 1991;65:37-40.
12 Yoganathan AP, Cape EG, Sung HW, et al. Review of hydrodynamic principles for the cardiologist: applications to the study of blood flow and jets by imaging techniques. J Am Coll Cardiol . 1988;12:1344-1353.
13 Tribouilloy CM, Enriquez-Sarano M, Bailey KR, et al. Assessment of severity of aortic regurgitation using the width of the vena contracta: a clinical color Doppler imaging study. Circulation . 2000;102:558-564.
14 Willett DL, Hall SA, Jessen ME, et al. Assessment of aortic regurgitation by transesophageal color Doppler imaging of the vena contracta: validation against an intraoperative aortic flow probe. J Am Coll Cardiol . 2001;37:1450-1455.
15 Shiota T, Jones M, Agler DA, et al. New echocardiographic windows for quantitative determination of aortic regurgitation volume using color Doppler flow convergence and vena contracta. Am J Cardiol . 1999;83:1064-1068.
16 Enriquez-Sarano M, Bailey KR, Seward JB, et al. Quantitative Doppler assessment of valvular regurgitation. Circulation . 1993;87:841-848.
17 Rokey R, Sterling LL, Zoghbi WA, et al. Determination of regurgitant fraction in isolated mitral or aortic regurgitation by pulsed Doppler two-dimensional echocardiography. J Am Coll Cardiol . 1986;7:1273-1278.
18 Lewis JF, Kuo LC, Nelson JG, et al. Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window. Circulation . 1984;70:425-431.
19 Quinones MA, Otto CM, Stoddard M, et al. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr . 2002;15:167-184.
20 Enriquez-Sarano M, Miller FAJr., Hayes SN, et al. Effective mitral regurgitant orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. J Am Coll Cardiol . 1995;25:703-709.
21 Tribouilloy CM, Enriquez-Sarano M, Fett SL, et al. Application of the proximal flow convergence method to calculate the effective regurgitant orifice area in aortic regurgitation. J Am Coll Cardiol . 1998;32:1032-1039.
22 Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr . 2005;18:1440-1463.
23 Lang RM, Mor-Avi V, Sugeng L, et al. Three-dimensional echocardiography: the benefits of the additional dimension. J Am Coll Cardiol . 2006;48:2053-2069.
24 Sugeng L, Mor-Avi V, Weinert L, et al. Quantitative assessment of left ventricular size and function: side-by-side comparison of real-time three-dimensional echocardiography and computed tomography with magnetic resonance reference. Circulation . 2006;114:654-661.
25 Li X, Jones M, Irvine T, et al. Real-time 3-dimensional echocardiography for quantification of the difference in left ventricular versus right ventricular stroke volume in a chronic animal model study: improved results using C-scans for quantifying aortic regurgitation. J Am Soc Echocardiogr . 2004;17:870-875.
26 Mori Y, Shiota T, Jones M, et al. Three-dimensional reconstruction of the color Doppler–imaged vena contracta for quantifying aortic regurgitation: studies in a chronic animal model. Circulation . 1999;99:1611-1617.
27 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;22:775-781.
28 Shiota T, Jones M, Delabays A, et al. Direct measurement of three-dimensionally reconstructed flow convergence surface area and regurgitant flow in aortic regurgitation: in vitro and chronic animal model studies. Circulation . 1997;96:3687-3695.
Section II
Native Valvular Heart Disease: Mitral Stenosis/Mitral Regurgitation
Chapter 9 Mitral Stenosis

Itzhak Kronzon, MD, FASE, Muhamed Saric, MD, PhD, FASE, Roberto M. Lang, MD, FASE

History
The earliest observations on mitral stenosis (MS) were made in Great Britain and France. 1 The anatomic findings were first noted in 1668 by John Mayow, who recorded an “extreme constriction of the mitral orifice in a young man.” In 1715, Raymond Vieussens, a French physician, gave the first comprehensive description of MS. 2 It took another 140 years until the first description in 1806 of the physical findings: Jean-Nicolaus Corvisart is credited with the first description of a palpable thrill that resembled that experienced with the hand while stroking a cat. The invention of the stethoscope by René Laënnec (1781-1826) gradually led to the description of the characteristic heart sounds and murmurs.
Henry Soutar and Elliot Cutler led the first (unsuccessful) attempts to perform mitral commissurotomy in the 1920s. Their technique was improved by Charles Bailey and Dwight Harken, 3 who successfully performed large numbers of mitral commissurotomies since 1948.
Inge Edler and Carl Hellmuth Hertz invented echocardiography in 1952. 4 Later that year, they described the first clinical use of echocardiography: the diagnosis of MS ( Fig. 9.1 ).

Fig. 9.1 First echocardiographic recording. In 1954, Edler and Hertz published the first paper on echocardiography from which this original recording is reproduced. The figure demonstrates the movement of the left auricular wall in a case of mitral stenosis with auricular fibrillation.
(Edler I, Hertz CH. The use of ultrasonic reflectoscope for the continuous recording of movements of heart walls. Kungl Fysiogr Sallsk i Lund Forhandl 1954;24:5.)

Etiology
The most common caust of MS is postinflammatory, secondary to group A beta-hemolytic streptococcal infection, which results in acute rheumatic fever. Over years, the pathologic changes, which include valvular fibrosis, thickening, calcification, and commissural fusion, lead to progressive decline of the mitral orifice area. Interestingly, a history of clinical rheumatic fever cannot be depicted in a large percentage of patients with MS.
Congenital MS is rare (1% of all patients with MS). It may be the result of a parachute mitral valve or a subvalvular membrane, which may be part of the Shone syndrome (multiple left heart obstruction).
Degenerative MS is occasionally observed in older adults (>65 years) with severe mitral annular calcification. The calcification may extend to the base of the mitral leaflets and may decrease the effective mitral orifice. Unlike rheumatic MS, there is no commissural fusion. Other rare causes of acquired MS include lupus erythematosus, carcinoid tumors, rheumatoid arthritis, and radiation valvular injury.

Epidemiology
In developed countries the incidence of rheumatic fever has declined dramatically since the invention of antibiotics. New cases of MS are therefore rare. It is estimated that the prevalence of rheumatic fever in the United States is less than 1 case per 100,000 people. 5 In developing countries the prevalence is much higher. In India, the prevalence of acute rheumatic fever is 150 cases per 100,000, and the prevalence of rheumatic valvular disease may reach as high as 15 cases per 1000. The progression of MS appears to be more rapid in developing countries, where severe, symptomatic MS may be observed in children and adolescents. In developed countries the disease is detected 20 to 30 years after the onset of rheumatic fever. Although rheumatic fever affects both sexes equally, MS is more likely to develop in women than in men (3 : 1).

Pathophysiology
In the adult, the normal mitral valve area (MVA) is 4 to 6 cm 2 . Narrowing of the valve area <2 cm 2 results in an abnormal pressure gradient between the left atrium (LA) and the left ventricle (LV). The gradient is inversely related to the valve area and is directly related to the blood flow across the valve. Conditions known to increase cardiac output, such as exercise, fever, and pregnancy, increase the blood flow and the gradient across the valve. In addition, tachycardia, which is frequently present in these conditions, shortens the duration of diastole and therefore interferes with LA emptying, further increasing the LA-LV gradient.
The result of the high gradient across the mitral valve (MV) is elevated LA pressure, which is responsible for the symptoms of left heart failure in patients with MS. These symptoms may range from shortness of breath on exertion to frank pulmonary edema.
Elevation of LA pressure leads to obligatory elevation of pulmonary artery (PA) pressure. In addition, pulmonary arteriolar spasm, medial hypertrophy, and intimal thickening increase the pulmonary vascular resistance (PVR), resulting in more severe pulmonary hypertension. In some patients with MS, PA pressure reaches systemic arterial pressure. High PVR results in lower cardiac output, with symptoms that range from tiredness to poor organ perfusion and cardiac cachexia.
High PA pressure (and therefore high systolic right ventricular [RV] systolic pressure) increase the RV afterload and may lead to RV failure, with RV dilatation and elevation of RV diastolic and right atrial (RA) pressures. The resulting symptoms and findings are those of right heart failure: venous engorgement, leg edema, cardiac cirrhosis, ascites, and protein-losing enteropathy. In addition, the elevation of RV systolic pressure and RV dilatation cause tricuspid regurgitation, which further contributes to the elevation of RA pressure and increase right heart failure.
High LA pressure leads also to dilatation of the atrium, which may be further complicated by atrial fibrillation (AF). AF, together with LA outflow obstruction, leads to stagnation of blood, LA clots, and systemic embolization ( Fig. 9.2 ).

Fig. 9.2 Pathophysiology of mitral stenosis. The central feature of pathophysiology of mitral stenosis is the elevated diastolic gradient between the left atrium and the left ventricle.

Physical Examination
The characteristic finding of MS can be obtained by cardiac auscultation. The first heart sound (S 1 ) is frequently loud. An opening snap (OS) is frequently heard after the second heart sound (S 2 ). The duration of the interval between the aortic component of the S 2 and the OS is inversely related to the severity of MS (a shorter interval suggests severe MS). A characteristic diastolic rumble is frequently heard best at the apex. These findings may also be observed on phonocardiography ( Fig. 9.3 ).

Fig. 9.3 Phonocardiography in mitral stenosis. Schematic representation of a typical phonocardiogram in mitral stenosis. S1, First heart sound; S2, second heart sound; OS, opening snap.
In patients with normal sinus rhythm, there is also an end-diastolic (“presystolic”) accentuation of the rumble. Unfortunately, the auscultatory findings are subtle and can be frequently missed by an inexperienced ear. When cardiac output declines, the murmurs may become softer. The pulmonic component of the S 2 is loud in cases of pulmonary hypertension. Less specific findings include malar flush, signs of left and right heart failure, and signs of low cardiac output. Atrial fibrillation is present in 40% percent of all patients with AS.

Diagnostic Testing

Electrocardiography
Electrocardiography (ECG) may demonstrate signs of LA enlargement (P-mitrale) with wide, saddle-shaped P wave in leads I and II, as well as late, deep P wave inversion in lead V1 ( Fig. 9.4 ). In more advanced cases there is also evidence of RV hypertrophy. AF is frequently present.

Fig. 9.4 Electrocardiogram in mitral stenosis. Note the left atrial enlargement characterized by a wide, saddle-shaped P wave in lead II (P-mitrale, arrow ), as well as late, deep P-wave inversion in lead V 1 (arrowhead).

Chest Radiography
Chest radiography usually demonstrates LA enlargement with straightening of the left cardiac silhouette as a result of an enlarged LA appendage ( Fig. 9.5 ). RV enlargement, signs of pulmonary venous engorgement, and MV calcification may also be seen.

Fig. 9.5 Chest radiograph in a patient with mitral stenosis. On the posteroanterior film ( left panel ), note the straightening of the left heart border as a result of left atrial appendage enlargement and the double density indicative of left atrial enlargement. On the lateral film ( right panel ), note the posterior displacement of the left lower lobe bronchus caused by left atrial enlargement.

Echocardiography
Echocardiography is the diagnostic modality of choice.

M-Mode Echocardiography
M-mode echocardiography has high sensitivity and specificity for the diagnosis of MS. It demonstrates thickened mitral leaflets and flat EF slope of the anterior leaflet; after the initial opening (E point), the leaflet does not travel backward toward the closing position because the LA-LV pressure gradient maintains the valve in the fully opened position. The smaller posterior leaflet, which is fused with the larger anterior leaflet, has an abnormal diastolic anterior motion. M-mode imaging can also show evidence of LA and RV dilatation.
The rate and pattern of LA emptying can also be calculated. Normally, most atrial emptying (or LV filling) occurs at early diastole, but in MS the LA emptying is gradual and lasts throughout diastole.

Two-Dimensional Echocardiography
Two-dimensional (2-D) echocardiography can further improve the diagnosis. In the long-axis view, both mitral leaflets are clearly demonstrated. Commissural fusion results in bowing of the anterior mitral leaflet (hockey-stick appearance). The short-axis view can allow planimetry of the cross-sectional diastolic MVA. 2-D Images can assess the leaflet thickness, mobility, calcification, and involvement of the subvalvular apparatus. The MV score for suitability for valvuloplasty can be calculated with this information ( Table 9.1 ).

Table 9.1 Mitral Valve Scoring

Doppler Echocardiography
Doppler echocardiography provides accurate assessment of MS hemodynamics. The gradient across the valve can be easily measured by pulsed and continuous wave Doppler. The best approach for transmitral flow evaluation and gradient determination should be with the transducer at the apex, imaging the four-chamber or two-chamber views. Color flow imaging can be helpful for the assessment of the exact direction of the transmitral flow. The angle between the interrogating beam and the transmitral jet should be 0 degrees. Gradient can be assessed by pulsed Doppler with the sample volume at the tips of the leaflets or by continuous wave Doppler. Using the simplified Bernoulli equation, 6 the gradients are calculated from the spectral blood flow velocity tracings as follows:

where Δ P is the pressure gradient in millimeters of mercury and V is the flow velocity in meters per second.
Built-in algorithms are available in most modern echocardiographs; these allow evaluation of the mean MV gradient, as well as the evaluation of the pressure half-time, mitral deceleration time, and MVA.

Mitral Valve Area
The gradient across the MV is directly related to transvalvular flow. Low gradient may be measured in mild MS but is also present in severe MS with low decreased transvalvular flow as a result of low cardiac output. Thus, measuring the gradient alone may be inaccurate in the evaluation of MS severity. Better estimation of the severity can be achieved with the evaluation of MVA ( Table 9.2 ); this value is independent of transvalvular flow and gradient.
Table 9.2 Methods for Calculating Mitral Valve Area
Pressure half-time
Deceleration time
Continuity equation (simple method, or PISA)
Planimetry (2-D or 3-D)
PISA, Proximal isovelocity surface area.

Pressure Half-Time
Pressure half-time (PHT) is defined as the length of time required for the maximal early diastolic transmitral gradient to reach half its value. The PHT is quite short in patients without significant MS because the LA-LV pressure gradient declines rapidly and the pressures in these two chambers equalize quickly. On the other hand, with severe MS the pressure gradient declines slowly and the PHT is prolonged. The Hatle equation 7 describes the relation between PHT and MVA:

Thus in a patient with a PHT of 220 ms, the MVA is 1 cm 2 , which indicates severe MS.

Mitral Deceleration Time
Mitral deceleration time (DT) is defined as the length of time from the peak mitral early diastolic flow velocity (and gradient) to the end of antegrade transvalvular flow (velocity 0). The length of DT is also inversely related to the MVA (i.e., longer DT indicates smaller MVA) ( Fig. 9.6 ). The relation between MVA and DT can be expressed by the following formula:

Fig. 9.6 The mitral valve area in the same patient is calculated by the pressure half-time method ( A ) and the deceleration time method ( B ).

The relation between PHT and DT can be expressed by the formula:


Limitations of Pressure Half-Time and Deceleration Time in the Measurement of Mitral Valve Area
Measurements of PHT and DT can accurately define the MVA in patients with isolated MS. However, in some cases other hemodynamic abnormalities may interfere with accurate estimation.
In patients with MS and significant aortic regurgitation the rise of LV end-diastolic pressure decreases the late diastolic LA-LV gradient and overestimates MVA measured by PHT or DT.
In patients with atrial septal defect, a significant left-to-right shunt decompresses the atrium and decreases the LA-LV gradient, which overestimates MVA measured by PHT or DT.
In patients with abnormal LV relaxation, DT and PHT are both prolonged; this may lead to underestimation of MVA.
Occasionally, the deceleration of the transmitral flow is not homogeneous. Early in diastole the deceleration is steep, while later it slows. This phenomenon is seen in patients with MS and mitral regurgitation. The initial part of the slope (initial 300 ms) can be ignored, and the PHT measurement should be best obtained for the later, less steep deceleration part.

Mitral Valve Area Calculation Based on the Continuity Equation

1. The simple continuity method is based on the assumption that the volume of blood that crosses the mitral inflow at the level of the annulus in diastole equals the amount that crosses the valve orifice. The flow across the annulus ( F 1 ) is the product of the inflow area at the annular level ( A 1 ) and the velocity time integral of the flow at that level (VTI 1 ):

The flow across the MV orifice ( F 2 ) is the product of the orifice area ( A 2 ) and the VTI of the flow across the MV orifice (VTI 2 ):


then

or

The left ventricular outflow tract (LVOT) flow can be substituted for the mitral annular flow. However, such a substitution should not be performed in patients with significant aortic regurgitations.
2. The proximal isovelocity surface area (PISA) method is based on similar principles. The method is described in detail elsewhere in this text. MVA is calculated from the flow rate across the PISA hemisphere, which equals the flow rate across the stenotic valve orifice. 8 The flow rate across the PISA ( F PISA ) can be estimated by the formula

where A PISA is the surface area of the PISA hemisphere in square centimeters and V a is the PISA aliasing velocity in centimeters per second.
The PISA area can be calculated if its radius ( r ) is known:

The flow rate across the mitral orifice ( F MV ) can be expressed as

where MVA is the mitral valve area expressed in square centimeters, and MFV is the mitral flow velocity in centimeters per second.
Since

we can use the largest PISA radius and the fastest mitral velocity:

or

This equation can be rearranged to solve MVA:

Another correction has yet to be introduced to this equation: Because the angle between the MV leaflets is usually less than 180 degrees, that angle (θ) should be measured to correct the equation ( Fig. 9.7 ):

Fig. 9.7 The PISA method for calculation of mitral valve area. Note the use of angle correction for calculation of mitral valve area.


Three-Dimensional Echocardiography to Determine Mitral Valve Area
The planimetry of MVA using the short-axis view images may be inaccurate because there is no certainty that the smallest valve area is depicted. Newer technologies, which include volume rendering and real-time three-dimensional (3-D) imaging, overcome this problem. New software allows the selection and the measurement of the smallest MVA ( Fig. 9.8 ). This technology is considered by many the gold standard for the assessment of MVA ( Table 9.3 ). 9

Fig. 9.8 3-D Image of mitral stenosis. Real-time 3-D transesophageal echocardiogram ( TEE ) from a patient with mitral stenosis.

Table 9.3 Grading of Mitral Stenosis

Evaluation of Right Heart Hemodynamics
Evaluating right heart dynamics is an integral part of the evaluation of each patient with MS, and should include the following:
1. Estimation of RA pressure. Images of the inferior vena cava (IVC) can be obtained with the transducer at the subxiphoid position. The diameter of the IVC is directly related to RA pressure. A collapsed IVC suggests low RA pressure, whereas plethoric (diameter >2.5 cm) without respiratory variations is suggestive of RA pressure of ≥20 mm Hg ( Table 9.4 ).
2. Estimation of RV systolic pressure, which in the absence of pulmonic stenosis equals PA systolic pressure, can be estimated in most patients with the measurement of the tricuspid regurgitation jet velocity and calculation of the RV-to-RA gradient:
Table 9.4 Estimation of Right Atrial Pressures IVC Diameter (cm) Inspiratory Collapse RAP (mm Hg) <1.5 Total 0-5 1.5-2.5 >50% 6-10   <50% 11-15 >2.5 <50% 16-20
IVC, Inferior vena cava; RAP, right atrial pressure.


3. Estimation of RV diastolic pressure. In the absence of tricuspid stenosis, the RV diastolic pressure equals RA pressure.
4. PA diastolic pressure can be calculated in many patients by assessing the end-diastolic velocity of the pulmonic regurgitation jet and calculating the PA-to-RV diastolic gradient:


5. The pulmonary vascular resistance (PVR) is directly related to PA pressure and inversely related to the pulmonary blood flow velocity integral measured at the RV outflow tract (TVI RVOT ). PVR can be calculated by the equation:

where PVR is expressed in Wood units, peak TR velocity in meters/second, and VTI RVOT in centimeters. Normal PVR is ≤2 Wood units. 10

Transesophageal Echocardiography in the Evaluation of Patients With Mitral Stenosis
The routine echocardiographic evaluation of MS does not require transesophageal echocardiography (TEE). However, TEE should be considered when the image quality and the Doppler information is suboptimal or do not correlate with the clinical impression. TEE is also useful in the evaluation of complications of MS, such as LA clot or endocarditis. TEE is frequently used before and during MV balloon valvuloplasty. This topic is discussed in the next chapter.

Therapy
Treatment options for MS include medical therapy, percutaneous mitral balloon valvuloplasty (PMBV), surgical mitral commissurotomy, and MV replacement. In patients with symptoms, echocardiography plays a major role in the decision making and the guidance of the various treatment modalities. The American Heart Association/American College of Ccardiology guidelines are presented in Table 9.5 11 ; extensive discussion of these modalities is beyond the scope of this text.

Table 9.5 Treatment of Mitral Stenosis

References

1. Fleming PR. A short history of cardiology . Amsterdam: Rodopi BV; 1997.
2. Vieussens R. Treatise on the structure of the heart and the causes of its natural motion [in French] . France: Toulouse; 1715.
3. Gonzalez-Lavin L, Bailey CP, Harken DE. The dawn of the modern era of mitral valve surgery. Ann Thorac Surg . 1992;53:916-919.
4. Edler I, Hertz CH. The use of ultrasonic reflectoscope for the continuous recording of movements of heart walls, Kungl Fysiogr Sallsk i Lund Forhandl 1954;24:5. Reproduced in Clin Physiol Funct Imaging, 24, 2004, 118-136
5. Stollerman GH. Rheumatic fever. Lancet . 1997;349:935-942.
6. Hatle L. Doppler ultrasound in cardiology: physical principles and clinical applications . Philadelphia: Lea & Febiger; 1982.
7. Hatle L, Angelsen B, Tromsdal A. Noninvasive assessment of atrioventricular pressure half-time by Doppler ultrasound. Circulation . 1979;60:1096-1104.
8. Rodriguez L, Thomas JD, Monterroso V, et al. Validation of the proximal flow convergence method. Calculation of orifice area in patients with mitral stenosis. Circulation . 1993;88:1157-1165.
9. Zamorano J, Pedro Cordeiro P, Sugeng L, et al. Real-time three-dimensional echocardiography for rheumatic mitral valve stenosis evaluation: an accurate and novel approach. J Am Coll Cardiol . 2004;43:2091-2096.
10. Abbas AE, Fortuin FD, Schiller NB, et al. A simple method for noninvasive estimation of pulmonary vascular resistance. J Am Coll Cardiol . 2003;41:1021-1027.
11. Bonow RO, Carabello BA, Chatterjee K, 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. J Am Coll Cardiol . 2006;48:e1-e148.
Chapter 10 Exercise Echocardiography in Mitral Stenosis

Kathleen Stergiopoulos, MD, PhD, FASE, Smadar Kort, MD, FASE
Intervention in patients with mitral stenosis (MS) is indicated in symptomatic patients with a mitral valve area (MVA) ≤1.5 cm 2 . 1 - 3 Symptoms are defined as New York Heart Association class II, III, or IV indications. In addition, referral for intervention is also appropriate in patients with a similar valve area and concomitant pulmonary hypertension, with a pulmonary artery systolic pressure of ≥50 mm Hg at rest, or >60 mm Hg with exercise. 1 In patients in whom MS is present with persistent symptoms but not considered severe, it may be necessary to measure exercise hemodynamics. Conversely, in patients in whom the degree of MS is considered severe yet few symptoms are present, it is useful to perform stress testing to determine the patient’s exercise performance. Moreover, symptoms of dyspnea on exertion may be more proportionally related to obstructive coronary artery disease or intrinsic pulmonary disease rather than to advanced MS.

Role of Exercise Hemodynamics: When and How?
Exercise Doppler testing is useful in the following situations: (1) to confirm that an asymptomatic patient is able to achieve a workload that is equivalent to activities of daily living and/or uncover symptoms that appear covert, (2) to assess exercise hemodynamics in symptomatic patients with mild or moderate resting gradient measurements, and (3) to evaluate exercise pulmonary artery systolic pressure. 1
The transmitral gradient is related to the degree of anatomic obstruction and the volume of flow across the valve. Increasing cardiac output and heart rate with exercise results in augmentation of the volume of flow and a decrease in diastolic filling rate. This results in increased transmitral pressure gradients for any degree of obstruction. Dyspnea on exertion in MS is related to elevation of left atrial and pulmonary capillary wedge pressures, as well as development of pulmonary hypertension and secondary afterload on the right ventricle. 3
Exercise is the ideal way to evaluate the symptomatic patient with less than severe stenosis because activity is usually what precipitates symptoms. 2 , 4 The patient can exercise on a treadmill or supine bicycle. Pharmacologic stress with dobutamine has been reported useful in patients with MS who cannot exercise. 5 There is potential for fewer technical issues, such as respiratory activity and chest motion, when dobutamine is used. With any of these techniques, Doppler echocardiography can be used to accurately assess the hemodynamic severity of a stenotic mitral valve at rest and with exercise ( Figs. 10.1 and 10.2 ). 1 , 4 The mean transmitral gradient can be accurately and reproducibly measured by using a continuous wave Doppler across the mitral valve, typically in an apical four-chamber view. Color Doppler can be used to direct the continuous wave signal to avoid underestimation of the mean gradient. Diastolic pressure half-time or the continuity equation can be used to estimate the MVA, although pitfalls exist for both methods. Atrial fibrillation is common in patients with MS, and in these patients hemodynamic variables should be averaged over 5 to 10 cardiac cycles. Exaggerated or pronounced worsening of hemodynamic variables may explain exertional symptoms in patients with less than severe MS.

Fig. 10.1 Resting mitral valve mean gradient.

Fig. 10.2 Postexercise mean transmitral gradient.

Optimal Doppler Evaluation of Right Heart Pressure
Doppler echocardiography can be used to estimate the peak pulmonary artery systolic pressure using the tricuspid regurgitant jet. 6 , 7 Immediately after peak exercise is achieved, repeat measurements of the mean transmitral gradient and peak pulmonary artery systolic pressure are repeated.
Exercise results in an increase in pulmonary artery systolic pressures. 8 These increases are due to increased heart rate, decreased diastolic filling period, and increased left atrial pressure. It is important to compare the increase in pulmonary artery systolic pressure with that expected for a healthy individual. Exercise-induced increase in pulmonary artery pressure is expected even in healthy, young individuals ( Fig. 10.3 ). It is known that even healthy individuals can have increased pulmonary artery systolic pressure with exercise ( Fig. 10.4 ).

Fig. 10.3 Resting pulmonary artery systolic pressure.

Fig. 10.4 Postexercise pulmonary artery systolic pressure.

Change in Mitral Valve Area With Exercise
The degree of change in MVA with exercise is likely related to the degree of flexibility of the mitral leaflets. In general, an increase in MVA would likely be associated with a resting MVA >1.4 cm 2 . In more severe MS with more severe valvular deformity (MVA <1.0 cm 2 ), there would likely be no significant change in the MVA with exercise. Thus a relatively fixed mitral orifice would be associated with a blunted hemodynamic response to exercise, as augmenting stroke volume is limited. In addition, a more exaggerated increase in transmitral mean gradient and pulmonary artery systolic pressure would be expected for more stenotic lesions.

Conclusion
Exercise hemodynamics can be helpful in the determination of the hemodynamic severity of MS, particularly in patients with exertional symptoms and less than severe stenosis. 1 , 9 Exercise testing can be performed with a supine bicycle or treadmill with Doppler recordings of transmitral and tricuspid velocities. This allows for determination of the mean transmitral gradient and pulmonary artery pressure at rest and with exercise. Indications for intervention in anatomically suitable patients include (1) limitation of exercise tolerance, (2) pulmonary artery systolic pressure >60 mm Hg, and (3) rise in transmitral gradient >15 mm Hg with exercise.

References

1. Bonow RO, Carabello B, Chatterjee K, 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. Circulation . 2006;114:e84-e231.
2. Carabello BA. Modern management of mitral stenosis. Circulation . 2005;112:432-437.
3. Cheitlin MD. Stress echocardiography in mitral stenosis: when is it useful? J Am Coll Cardiol . 2004;43:402-404.
4. Cheriex EC, Pieters FA, Janssen JH, et al. Value of exercise Doppler-echocardiography in patients with mitral stenosis. Int J Cardiol . 1994;45:219-226.
5. Reis G, Motta MS, Barbosa MM, et al. Dobutamine stress echocardiography for noninvasive assessment and risk stratification of patients with rheumatic mtiral stenosis. J Am Coll Cardiol . 2004;43:393-401.
6. Himelman RB, Stulbarg M, Kircher B, et al. Noninvasive evaluation of pulmonary artery systolic pressure during exercise by saline-enhanced Doppler echocardiography in chronic pulmonary disease. Circulation . 1989;79:963-971.
7. Leavitt JI, Coats MH, Falk RH. Effects of exercise on transmitral gradient and pulmonary artery pressure in patients with mitral stenosis or a prosthetic mitral valve: a Doppler echocardiographic study. J Am Coll Cardiol . 1991;17:1520-1526.
8. Otto CM. Mitral stenosis. In Otto CM, editor: Valvular heart disease , ed 2, Philadelphia: WB Saunders, 2004.
9. Tunick PA, Freedberg RS, Gargiulo A, et al. Exercise Doppler echocardiography as an aid to clinical decision making in mitral valve disease. J Am Soc Echocardiogr . 1992;5:225-230.
Chapter 11 Mitral Valve

Jose Luis Gutierrez-Bernal, MD, José Luis Zamorano Gomez, MD

Definition and Etiology
Mitral stenosis (MS) is an obstruction to left ventricular (LV) inflow at the level of the mitral valve (MV) as a result of a structural abnormality of the MV apparatus, which prevents proper opening during diastolic filling of the left ventricle. The ratio of women to men presenting with isolated MS is 2 : 1. 1 - 3 The most common cause of MS is rheumatic heart disease. Congenital malformation of the MV occurs rarely and is observed mainly in infants and children. Acquired causes of MV obstruction, other than rheumatic heart disease, are rare. These include calcific MS, left atrial (LA) myxoma, LA thrombus, mucopolysaccharidosis, Cafergot toxicity, hypereosinophilia, and vegetation.
Rheumatic disease predominantly affects the MV, producing characteristic commissural fusion, leaflet thickening and calcification, chordal fusion, or a combination of these processes, 4 , 5 which results in bowing or doming of the valve leaflets in diastole. The base and midsections of the leaflets move toward the apex, while the motion of the leaflet tips is restricted as a result of fusion of the anterior and posterior leaflets along the commissures. Thickening at the leaflet tips occurs frequently, but the remainder of the leaflets can show variable degrees of thickening or calcification. The rheumatic process also typically affects the subvalvular region with fusion, shortening, fibrosis, and calcification of the mitral chordae. The result is a funnel-shaped mitral apparatus in which the orifice of the mitral opening is decreased in size. Interchordal fusion obliterates the secondary orifices, and commissural fusion narrows the principal orifice. 4 , 5
Mitral annular calcification is a common incidental finding on echocardiography in older patients. Mild annular calcification appears as an isolated area of calcification on the LV side of the posterior annulus, near the base of the posterior mitral leaflet. In more severe mitral annular calcification, increased echogenicity is seen in a hemi-elliptical pattern involving the entire posterior annulus. The area of fibrous continuity between the anterior mitral leaflet and the aortic root rarely is involved. The cause of mitral annular calcification is considered as a “degenerative” age-related process. It can result in mild to moderate mitral regurgitation as a result of the increased rigidity of the mitral annulus. Occasionally, the calcification extends into the base of the mitral leaflets themselves, resulting in functional MS caused by narrowing of the diastolic flow area. Calcific MS can be distinguished from rheumatic disease by careful imaging techniques to demonstrate thin and mobile mitral leaflet tips without commissural fusion.

Pathophysiology
The normal mitral valve area (MVA) is 4.0 to 5.0 cm 2 . Narrowing of the valve area to less than 2.5 cm 2 typically occurs before the development of symptoms. 6 With a reduction in valve area by the rheumatic process, blood can flow from the left atrium to the left ventricle only if propelled by a pressure gradient. This diastolic transmitral gradient is the fundamental expression of MS and results in elevation of LA pressure, which is reflected back into the pulmonary venous circulation. 7 An increased pulmonary endothelin-1 spillover rate may also contribute to increased pulmonary venous pressure. 8 Increased pressure and distention of the pulmonary veins and capillaries can lead to pulmonary edema. In patients with chronic MV obstruction, however, even when it is severe and pulmonary venous pressure is very high, pulmonary edema may not occur owing to a marked decrease in pulmonary microvascular permeability. The pulmonary arterioles may react with vasoconstriction, intimal hyperplasia, and medial hypertrophy, which lead to pulmonary arterial hypertension.
An MVA >1.5 cm 2 usually does not produce symptoms at rest. 9 However, if there is an increase in transmitral flow or a decrease in the diastolic filling period, a rise in LA pressure occurs and symptoms develop. From hydraulic considerations, at any given orifice size, the transmitral gradient is a function of the square of the transvalvular flow rate and is dependent on the diastolic filling period. 6 Thus the first symptoms of dyspnea in patients with mild MS are usually precipitated by exercise, emotional stress, infection, pregnancy, or atrial fibrillation with a rapid ventricular response. 9 As the obstruction across the MV increases, decreasing effort tolerance occurs. As the severity of stenosis increases, cardiac output becomes subnormal at rest 9 and fails to increase during exercise. 10 The degree of pulmonary vascular disease is also an important determinant of symptoms in patients with MS. 8, 9, 11 A second obstruction to flow develops from increased pulmonary arteriolar resistance, which may protect the lungs from pulmonary edema. 11 , 12 The low cardiac output and increased pulmonary arteriolar resistance, which results from functional and structural changes (alveolar basement membrane thickening, adaptation of neuroreceptors, increased lymphatic drainage, and increased transpulmonary endothelin-1 spillover rate), contribute to the ability of a patient with severe MS to remain minimally symptomatic for prolonged periods. 9, 11, 12

Natural History
The natural history of patients with untreated MS has been defined from studies in the 1950s and 1960s. 1 - 3 MS is a continuous, progressive, lifelong disease and usual consists of a slow, stable course in the early years followed by a progressive acceleration later in life. 1 - 3 13 In developed countries, there is a long latent period of 20 to 40 years from the occurrence of rheumatic fever to the onset of symptoms. Once symptoms develop, there is another period of almost a decade before symptoms become disabling. 2 Overall, the 10-year survival of patients presenting with untreated MS is 50% to 60%, depending on the severity of symptoms at presentation. 1 , 3 In patients with no or minimal symptoms, survival is greater than 80% at 10 years, with 60% of patients having no progression of symptoms. 1, 3, 13 However, once significant limiting symptoms occur, there is a dismal (0% to 15%) 10-year survival rate. 1 - 3 ,13 ,14 Once pulmonary hypertension is severe, mean survival rate drops to less than 3 years. 14 Death of patients with untreated MS is from progressive pulmonary and systemic congestion in 60% to 70%, systemic embolism in 20% to 30%, pulmonary embolism in 10%, and infection in 1% to 5%. 1 , 4 In Europe and North America, this classic history of MS has been replaced by an even milder delayed course with the decline in incidence of rheumatic fever. 13 , 15 The mean age of presentation is now in the fifth to sixth decade of life 13 , 15 ; more than one third of patients undergoing valvuloplasty are older than 65 years. 16 Serial hemodynamic and Doppler echocardiographic studies have reported annual loss of MVA ranging from 0.09 to 0.32 cm 2 . 17 , 18

Severity of Mitral Stenosis
Although no single parameter is sufficient to define severity, the American Heart Association/American College of Cardiology guidelines 19 define MS severity based on a variety of hemodynamic and natural history data using mean gradient, pulmonary artery systolic pressure, and valve area ( Table 11.1 ). 20

Table 11.1 Grading of MS Severity

Two-Dimensional Echocardiolgraphy and Doppler Evaluation

Pressure Gradients
MS is defined mainly by the diastolic transmitral gradient, 7 which enables a proper LV filling in diastole. The mean diastolic transmitral gradient can be determined from the transmitral velocity curve ( Fig. 11.1 ) by using the simplified Bernouilli equation:

Fig. 11.1 Tracing of the transmitral flow curve, to calculate the transmitral mean gradient.


Potential Pitfalls

1. Accurate pressure gradient calculations rely on accurate velocity measurements, which require a near-parallel intercept angle between the direction of blood flow and the Doppler beam. Color Doppler may be helpful in defining the jet direction in a tomographic plane and contributes to better transducer positioning and alignment. Velocity can be measured with continuous wave Doppler or conventional pulsed Doppler. Pulsed Doppler recordings usually show better definition of the maximum velocity and early diastolic slope because of the better signal-to-noise ratio.
2. Patients in atrial fibrillation represent a challenge because of the beat-to-beat variability of the mean gradient. In these patients, several beats should be averaged.
3. A mean trasmitral gradient >10 mm Hg is a criterion of severity, although with severe stenosis the gradient may be as high as 20 to 30 mm Hg or as low as 5 mm Hg. This variability is due to their dependence on volume flow rate and valve area. Severe MS may be associated with a low stroke volume (due to the limitation of LV diastolic filling), resulting in a relatively low mean gradient. If volume flow rate increases—for example, with exercise—an increase in transmitral gradient is seen. As for other types of valvular stenosis, calculation of valve area, taking both pressure gradient and volume flow rate into account, is helpful in quantitation of MS severity.

Mitral Valve Area

Planimetry
The anatomy of rheumatic MS is normally simpler than that of aortic stenosis and consisting of a planar elliptical orifice that is relatively constant in position in mid-diastole and with quite good acoustic definition in two-dimensional (2-D) echocardiography. Thus parasternal short-axis view allows direct planimetry of the valve area ( Fig. 11.2 ). This approach has been well validated compared with measurement of valve area at surgery and with invasive measurement using Gorlin’s equation. 21 - 23 Because the mitral inflow region is funnel shaped, with the narrowest cross-sectional area at the leaflet tips, it is important to begin the 2-D scan at the apex, slowly moving the image plane toward the MV to identify the smallest orifice. With a low overall gain, the inner edge of the black/white interface is traced. This quantitation method is highly accurate and this area should be measured in every patient with MS whenever image quality is adequate.

Fig. 11.2 Planimetry of the mitral orifice in parasternal short axis view.

Potential Pitfalls

1. Definition of the valve area may be difficult if the image quality is poor.
2. Quite often the valvular anatomy is severely distorted, so it is difficult to obtain a tomographic plane of the true orifice, obtaining instead a biased section that usually overestimates the area. Real-time three-dimensional (3-D) echocardiography is a useful tool to overcome this limitation and improve the accuracy of this method. 24
3. If gain settings are too high, the MV area might be underestimated.

Pressure Half-Time
This method is based on the concept that the rate of pressure decline across the stenotic mitral orifice is determined by the cross-sectional area of the orifice. The narrower the orifice, the slower is the rate of pressure decline. The pressure half-time (PHT) is defined as the time interval between the maximum early diastolic transmitral pressure gradient and the time point where this gradient reaches half its value. This parameter has been initially evaluated invasively, measuring LA and LV pressures. PHT was found to be constant for a given individual, even with exercise-induced changes in volume flow rate and transmitral gradient, suggesting that it is constant marker of stenosis severity for a given valve area. 25 This concept was then adapted to transmitral Doppler flow. Because the relation between pressure gradient and velocity is quadratic, according to the Bernouilli equation, the half-time is determined from a Doppler velocity curve as the time interval from the maximum mitral velocity ( V max ) to the point where the velocity has fallen to , following the early diastolic slope of the Doppler ( Fig. 11.3 ). Initial studies comparing Doppler half-time data with invasively determined Gorlin valve areas found a linear relationship, with a half-time of about 220 ms corresponding to a valve area of 1 cm 2 . 26 , 27 An empirical formula has been proposed to estimate MVA as a function of PHT ( ) as follows:

Fig. 11.3 Calculation of pressure half-time with pulsed Doppler: from the point of maximal transmitral velocity in diastole, trace the line that best fits the early diastolic deceleration slope.

The area calculated by this method is well correlated with invasively calculated areas in several clinical studies.

Potential Pitfalls

1. Aortic regurgitation: When coexisting aortic regurgitation is present, LV filling occurs both antegrade across the MV and retrograde across the aortic valve. This may result in a more rapid rise in LV diastolic pressure than if no aortic regurgitation was present, resulting in a shorter half-time measurement, which could overestimate MVA. Conversely, if severe aortic regurgitation impairs mitral leaflet opening, functional MS may be superimposed on anatomic MS, with lengthening of the half-time measurement and underestimation of mitral area. In clinical practice, when mild or moderate aortic regurgitation is present, the PHT method remains a reliable and useful approach for evaluation of MS severity, but it should be questioned in presence of severe aortic regurgitation.
2. Postvalvuloplasty: A major assumption of this method is that LA and LV compliances do not significantly affect the rate of pressure gradient decline across the stenotic orifice. This seems to be warranted in clinically stable patients with MS, but it is not at all justified in the period immediately after percutaneous mitral balloon valvuloplasty. After relief of MS, the fall in LA pressure and the increase in LV filling are accompanied by directionally opposite changes in LA and LV compliance. During the 24 to 72 hours after the procedure, equilibrium has not been reached, and the PHT may not be an accurate reflection of orifice area. In this setting, planimetry is the method of choice, and 3D-echo planimetry has proved to be the most accurate method in this particular scenario. 28 After this adjustment period, compliances stabilize, and the PHT method again provides useful information.
3. Good transmitral velocity curve: While a parallel intercept angle is somewhat less important than for pressure gradient calculations (since the shape of the curve is the same even at a nonparallel angle), it is important that the intercept angle be constant throughout diastole, to avoid artifactual distortion in the shape of the curve.
4. Nonlinear early diastolic velocity slope: Pressure half-times are most easily and reproducibly measured if the deceleration slope is linear, but quite often a linear slope cannot be obtained even after careful adjustment of transducer position and angulation. In these cases, the maximum early diastolic velocity is normally followed by a pronounced early diastolic slope, and then followed by a softer mid-diastolic slope. Half-time should be measured then according to mid-diastolic slopes ( Fig. 11.4 ).
5. Atrial fibrillation: Although half-time will be relatively constant despite variation in the length of diastole, only beats where the diastolic filling period is long enough to show the early diastolic slope clearly are appropriate for measurement. Average of several beats is hence also advisable.
6. Tachycardia: In sinus rhythm, a markedly increased heart rate may obscure the early diastolic slope, due to superimposition of atrial contraction wave. Accuracy of this method requires controlled heart rate.

Fig. 11.4 Calculation of pressure half-time with pulsed Doppler in patients with nonlinear early diastolic deceleration slope. In these cases, pressure half-time is best calculated with the mid-diastolic slope.

Continuity Equation
The continuity principle for area calculation of stenotic valves can also be applied to mitral orifice. Assuming a circular shape of the left ventricular outflow tract (LVOT), the area of the LVOT can be calculated by the formula:

Since the LVOT diameter (instead of the radius) is measured directly, the formula gets transformed:

The stroke volume (SV) can then be calculated from this area plus the time-velocity integral (TVI) in the LVOT (TVI LVOT ):


SV can also be calculated from the pulmonary artery flow according to the same rationale. Once SV is calculated, the continuity principle is applied:





Potential Pitfalls

1. Mitral regurgitation: The continuity equation method is not valid if significant mitral regurgitation is present because SV (wherever obtained from) cannot be equalled then to transmitral filling volume. On a similar manner, significant aortic regurgitation represents a challenge because SV should be then obtained from right ventricular outflow tract (pulmonary artery flow). Finally, significant pulmonary regurgitation sets the opposite situation, in which SV must be measured from LVOT.
2. In clinical practice, accurate measurement of SV is not always easy and depends on accurate measurement of multiple parameters. Cumulative errors in the measurement of these parameters often impair the overall reliability of this method.

PISA Method
When blood flow in the left atrium approaches the mitral stenotic orifice, it suffers a progressive acceleration to reach a maximal velocity at the mitral orifice level. When this phenomenon is observed with color Doppler, a clear hemisphere in the atrial face can be seen, defining the area where the flow velocity equals the Nyquist limit. This phenomenon is the basis of the proximal isovelocity surface area (PISA) method, which also assumes the instantaneous continuity principle for a given flow rate.
The first step is therefore to calculate the instantaneous volume flow rate at the level of the hemisphere. For this aim, the image and color Doppler parameters must be properly adjusted first. Zoom of the MV and shifting the color Doppler zero line upward to get a larger hemisphere are useful tips ( Fig. 11.5 ). The image is frozen, and the frame where an optimal PISA radius (r) can be measured, from the mitral leaflets to the aliasing limit, is reviewed.

Fig. 11.5 PISA method to calculate area in MS. The image is zoomed on the mitral valve, and the zero line of the color Doppler is shifted upward, with the aim to obtain a larger hemisphere.
Because the area of the surface of a sphere is 4πr 2 , the area of the surface of this hemisphere will be:

where r is the radius measured in the aliasing hemisphere. The instantaneous volume flow rate is then:

The instantaneous continuity principle for the flow rate is then applied so that:



An angular correction factor is added, determining the angle between the two mitral leaflets (α) because the hemisphere might be slightly reduced by the angulation of the leaflets. The final formula is therefore:

This correction factor may not be necessary if the bottom surface of hemispheric PISA is relatively flat, which occurs if the aliasing velocity is set high (α ≈ 180 degrees).

Exercise Hemodynamics
For patients who have mainly exertional symptoms and in whom resting hemodynamics do not clearly indicate severe MS, it is helpful to perform the Doppler hemodynamic assessment during cycle exercise or immediately after treadmill exercise. Although the MVA does not change with exercise, the increase in cardiac output and heart rate will result in a significant increase in the transmitral gradient, LA pressure, and pulmonary arterial pressure. The exercise capacity in patients with MS has an inverse correlation with the pulmonary arterial pressure. 29 Therefore significant worsening of hemodynamics with exercise can be helpful in explaining the patient’s symptoms in the setting of a mild to moderate resting hemodynamic abnormality.

Problems Other Than Severity of Stenosis

Left Atrial Enlargement and Thrombus
Chronic pressure overload in MS leads to gradual enlargement of the left atrium. Left atrial size can become extremely large in long-standing, severe MS. Left atrium measures should be routinely obtained and reported in MS.
The enlargement, in conjunction with the low flow rate due to the stenotic valve, results in stasis of blood and favors thrombus formation. Thrombi are located preferentially in the LA appendage but also can be found in the body of the atrium as protruding or laminated thrombi along the atrial wall or interatrial septum. Left atrial thrombi are most common when atrial fibrillation is present but may occur also in sinus rhythm.
Transthoracic echocardiography has a high specificity for detection of LA thrombus, but its sensitivity is <50%. In part, this relates to the difficulty of imaging the LA appendage in adults. Most of times it cannot be visualized at all, and when it is seen the image is often too poor, so that a thrombus in the LA appendage cannot be ruled out with reliability. Transesophageal echocardiography is the tool of choice to search for thrombi in the left atrium, particularly in the LA appendage. It has both a high sensitivity and specificity (>99%), allowing quite precise imaging of the LA appendage with multiplane probes ( Fig. 11.6 ).

Fig. 11.6 Thrombus in left atrial appendage visualized with transesophageal echocardiography, multiplane probe.

Mitral Regurgitation
Some degree of coexisting mitral regurgitation is common in patients with MS. Its severity must be carefully evaluated because it is an important factor in deciding on appropriate therapy, precluding, for example, valvotomy. Coexisting mitral regurgitation elevates transmitral pressure gradients (from increased transmitral flow rate), but planimetry and PHT methods remain accurate for valve area calculation. Continuity equation, on the other hand, is not valid in the presence of significant mitral regurgitation.

Rheumatic Involvement of Other Valves
Although rheumatic heart disease affects mainly the MV, it can also affect the aortic (second in frequency) or even the tricuspid valves. Aortic involvement may result in some degree of stenosis or regurgitation, which can interfere with the precise evaluation of MS. Detailed aortic evaluation, as well as Doppler study of the tricuspid valve searching for an eventual stenosis, should be routinely performed.
In patients with MS some degree of tricuspid regurgitation is commonly found, even in the absence of rheumatic involvement of the tricuspid valve, because of pulmonary hypertension and subsequent right ventricular annular dilation. Its careful evaluation is very important, mainly preoperatively, if tricuspid annuloplasty is needed at the time of MV surgery.

Prevalvuloplasty Evaluation
Percutaneous mitral balloon valvulotomy is currently an accepted technique for the treatment of patients with MS. It produces an increase in MVA and a significant clinical improvement with acceptable morbidity and mortality rates. 30 , 31 In the potential candidate for valvulotomy, precise echocardiographic depiction of MV morphology is very important both in terms of predicting the hemodynamic results of the intervention and the risk of procedural complications. Currently there is widespread consensus in considering leaflet mobility, leaflet thickening, leaflet and commissural calcification, and subvalvular involvement as the most important features to consider in a candidate for balloon valvuloplasty. In 1988, Wilkins 32 developed a score ( Table 11.2 ) that takes into account these four features and is useful to predict which patients are more likely to have a suboptimal result after the intervention. Those patients with a total score >8 are more prone to a disappointing result. However, some patients with a relatively unfavorable morphology do have relief of MS symptoms after the intervention.

Table 11.2 Determinants of the Echocardiographic Mitral Valve Score
Another factor to consider in these patients is the degree of coexisting mitral regurgitation because percutaneous valvulotomy is contraindicated if moderate or severe mitral regurgitation is present.
Severe mitral regurgitation remains one of the most important procedural complications of this technique, with an incidence between 1.4% and 19%. 33 , 34 This complication confers an adverse prognosis and frequently requires intensive treatment and urgent MV surgery. 35 Mild mitral regurgitation after percutaneous mitral valvulotomy occurs in 40% of patients undergoing percutaneous mitral valvulotomy and is usually produced by commissural splitting, 36 the same mechanism for the increase in MVA. 37 , 38 In contrast, severe mitral regurgitation after percutaneous mitral valvulotomy is typically caused by leaflet rupture and less frequently by subvalvular apparatus damage, including papillary muscle rupture. 37 In 1996, Rodríguez-Padial 39 developed a score specifically aimed to predict which patients are more prone to have this complication ( Table 11.3 ). Patients with a total score ≥10 were more likely to have acute severe mitral regurgitation during the procedure. 39
Table 11.3 Padial’s Score for Severe Mitral Regurgitation After Percutaneous Mitral Valvulotomy Parameters Description I-II Valvular thickening (score each leaflet separately)   1. Leaflet near normal (4-5 mm) or with only a thick segment   2. Leaflet fibrotic and/or calcified evenly; no thin areas   3. Leaflet fibrotic and/or calcified with uneven distribution; thinner segments are mildly thickened (5-8 mm)   4. Leaflet fibrotic and/or calcified with uneven distribution; thinner segments are near normal (4-5 mm) III Commissural calcification   1. Fibrosis and/or calcium in only one commissure   2. Both commissures mildly affected   3. Calcium in both commissures, one markedly affected   4. Calcium in both commissures, both markedly affected IV Subvalvular disease   1. Minimal thickening of chordal structures just below the valve   2. Thickening of charade extending up to one third of chordal length   3. Thickening to the distal third of the chordate   4. Extensive thickening and shortening of all chordae extending down to the papillary muscle
The total score is the sum of these echocardiographic features (maximum 16).
From Padial LR, Freitas N, Sagie A, et al: Echocardiography can predict which patients will develop severe mitral regurgitation after percutaneous mitral valvulotomy. J Am Coll Cardiol 1996;27:1225-1231.

Postvalvuloplasty Evaluation
After percutaneous valvuloplasty, echo Doppler allows identification of complications, permits assessment of hemodynamic results, and provides a baseline for future disease progression. Potential complications include an increase in the severity of mitral regurgitation (as explained above) and the presence of an atrial septal defect (usually small) at the transeptal catheter puncture site. Hemodynamic results of the intervention can be evaluated with conventional echo Doppler methods, again with awareness of the potential inaccuracies in the PHT in the immediate postvalvuloplasty period. In this particular setting, planimetry is the method of choice. 3-D echocardiographic planimetry has proved to be the most accurate and reliable technique in this particular setting. 28 Doppler evaluation of postprocedure pulmonary artery systolic pressure also can be helpful.

Pulmonary Hypertension
The degree of pulmonary hypertension can be quantitated from the velocity in the tricuspid regurgitant jet by using the simplified Bernouilli’s equation to calculate the right ventricular to right atrial gradient, with continuous wave Doppler in the tricuspid regurgitant jet ( Fig. 11.7 ). The size and respiratory variation of the inferior vena cava as it enters the right atrium is useful to estimate right atrial pressure, which will be added to the calculated gradient. Pulmonary hypertension out of proportion to the degree of MS must raise the suspicion of coexisting pulmonary disease. Pulmonary vascular resistance cannot be determined with echo Doppler techniques.

Fig. 11.7 Tricuspid regurgitation and estimation of pulmonary artery pressure with continuous wave Doppler.
With severe pulmonary hypertension, 2-D echo may show right ventricular hypertrophy or enlargement, paradoxic septal motion, and tricuspid regurgitation (without rheumatic involvement of the tricuspid valve) secondary to annular dilatation.

Transesophageal Echocardiography
Transesophageal echocardiography (TEE) is not routinely used in the evaluation of MS. It is, however, the tool of choice to search for thrombi in the left atrium, particularly in the LA appendage, because its sensitivity and specificity for this aim surpass 99%. Thus it is mandatory before performance of balloon valvuloplasty because any LA thrombi may be dislodged by the catheters during the procedure.
TEE will also be very useful when precise evaluation of the severity of coexisting mitral regurgitation is needed. For instance, before balloon valvuloplasty, an exhaustive evaluation of the grade of mitral regurgitation may give a result of great importance because the procedure would be contraindicated if moderate or severe regurgitation existed. Immediately after the procedure, if significant mitral regurgitation appears as a complication, TEE may also play an important role.

Real-Time 3-D Echocardiography
Real-time 3-D echocardiography (RT3D) has emerged recently as a novel, user-friendly, and accurate tool able to depict in full detail the mitral anatomy. It allows optimal spatial handling of the image in real time as well as the possibility to confront the MV from perspectives that were unattainable for conventional 2-D echo so far. Thus 3-D echo enormously facilitates the performance of direct mitral orifice planimetry: it permits a direct 3-D view of the funnel-shaped mitral apparatus, so that the real stenotic orifice is easily identified and measured without bias ( Fig. 11.8 ). The area calculated with 3-D echo planimetry in MS is the best correlated of all noninvasive methods with the area invasively calculated using Gorlin’s formula, surpassing conventional 2-D echo planimetry and PHT. 24, 40 - 42 Furthermore, it is also the best method to assess the result of valvuloplasty immediately after the procedure, when the results of other conventional methods such as PHT may be invalid or misleading. 28

Fig. 11.8 RT3D echo in rheumatic MS. The modality “full volume,” which requires four cardiac cycles to reconstruct the entire image, allows an easy and accurate planimetry of the real stenotic mitral orifice, avoiding positioning inaccuracies. RV, Right ventricle; AL, anterolateral; PM, posteromedial.
The RT3D modality most widely used to perform planimetry of MS is not exactly real time: full-volume acquisition requires four cardiac cycles to reconstruct the image. This near–real-time modality is the easiest and most accurate approach in rhythmic patients, but it cannot be properly performed in patients with atrial fibrillation. In these patients a strict real-time modality, focusing on the mitral orifice, should be performed ( Figs. 11.9 and 11.10 ).

Fig. 11.9 Another example of RT3D echo in rheumatic MS.

Fig. 11.10 RT3D echo in rheumatic MS, “real-time” modality. Patients in atrial fibrillation cannot be studied with full volume because the reconstruction of four irregular cycles will render many artifacts. In these cases, planimetry in “real-time” modality must be attempted.

References

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16. Tuzcu EM, Block PC, Griffin BP, et al. Immediate and long-term outcome of percutaneous mitral valvotomy in patients 65 years and older. Circulation . 1992;85:963-971.
17. Dubin AA, March HW, Cohn K, et al. Longitudinal hemodynamic and clinical study of mitral stenosis. Circulation . 1971;44:381-389.
18. Gordon SP, Douglas PS, Come PC, et al. Two-dimensional and Doppler echocardiographic determinants of the natural history of mitral valve narrowing in patients with rheumatic mitral stenosis: implications for follow-up. J Am Coll Cardiol . 1992;19:968-973.
19. Bonow RO, Carabello BA, Chatterjee K, 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. J Am Coll Cardiol . 2006;48:e1-e148.
20. Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr . 2003;16:777-802.
21. Nichol PM, Gilbert BW, Kisslo JA. Two-dimensional echocardiographic assessment of mitral stenosis. Circulation . 1977;55:120-128.
22. Wann LS, Weyman AE, Feigenbaum H, et al. Determination of mitral valve area by cross-sectional echocardiography. Ann Intern Med . 1978;88:337-341.
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24. Zamorano J, Cordeiro P, Sugeng L, et al. Real-time three-dimensional echocardiography for rheumatic mitral valve stenosis evaluation: an accurate and novel approach. J Am Coll Cardiol . 2004;43:2091-2096.
25. Libanoff AJ, Rodbard S. Atrioventricular pressure half-time. Measure of mitral valve orifice area. Circulation . 1968;38:144-150.
26. Hatle L, Angelsen B, Tromsdal A. Noninvasive assessment of atrioventricular pressure half-time by Doppler ultrasound. Circulation . 1979;60:1096-1104.
27. Hatle L, Brubakk A, Tromsdal A, et al. Noninvasive assessment of pressure drop in mitral stenosis by Doppler ultrasound. Br Heart J . 1978;40:131-140.
28. Zamorano J, Perez DI, Sugeng L, et al. Non-invasive assessment of mitral valve area during percutaneous balloon mitral valvuloplasty: role of real-time 3D echocardiography. Eur Heart J . 2004;25:2086-2091.
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31. Vahanian A, Michel PL, Cormier B, et al. Results of percutaneous mitral commissurotomy in 200 patients. Am J Cardiol . 1989;63:847-852.
32. 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;60:299-308.
33. McKay RG, Lock JE, Safian RD, et al. Balloon dilation of mitral stenosis in adult patients: postmortem and percutaneous mitral valvuloplasty studies. J Am Coll Cardiol . 1987;9:723-731.
34. Abascal VM, Wilkins GT, Choong CY, Block PC, Palacios IF, Weyman AE. Mitral regurgitation after percutaneous balloon mitral valvuloplasty in adults: evaluation by pulsed Doppler echocardiography. J Am Coll Cardiol . 1988;11:257-263.
35. Herrmann HC, Lima JA, Feldman T, et al. Mechanisms and outcome of severe mitral regurgitation after Inoue balloon valvuloplasty. North American Inoue Balloon Investigators. J Am Coll Cardiol . 1993;22:783-789.
36. Essop MR, Wisenbaugh T, Skoularigis J, et al. Mitral regurgitation following mitral balloon valvotomy. Differing mechanisms for severe versus mild-to-moderate lesions. Circulation . 1991;84:1669-1679.
37. Ribeiro PA, al Zaibag M, Rajendran V, et al. Mechanism of mitral valve area increase by in vitro single and double balloon mitral valvotomy. Am J Cardiol . 1988;62:264-269.
38. Reid CL, McKay CR, Chandraratna PA, et al. Mechanisms of increase in mitral valve area and influence of anatomic features in double-balloon, catheter balloon valvuloplasty in adults with rheumatic mitral stenosis: a Doppler and two-dimensional echocardiographic study. Circulation . 1987;76:628-636.
39. Padial LR, Freitas N, Sagie A, et al. Echocardiography can predict which patients will develop severe mitral regurgitation after percutaneous mitral valvulotomy. J Am Coll Cardiol . 1996;27:1225-1231.
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42. Sugeng L, Weinert L, Lammertin G, et al. Accuracy of mitral valve area measurement using transthorascic rapid freehand 3-dimensional scanning: comparison with noninvasive and invasive methods. J Am Soc Echocardiogr . 2003;16:1292-1300.
Chapter 12 Mitral Stenosis
Complex Disease, Situations That Mimic Mitral Stenosis, and Technical Pearls

Steven A. Goldstein, MD

Mitral Annular Calcification
Rheumatic mitral stenosis (MS) is the most common cause of left ventricular (LV) inflow obstruction. Less common causes are listed in Table 12.1 . Among these, a heavily calcified mitral annulus is the most often encountered. Calcium deposits in the mitral annulus are extremely common, 1 mainly in older persons or “prematurely” in patients with chronic renal disease receiving long-term dialysis. 2 , 3 Despite the frequency with which such deposits are encountered, hemodynamic consequences are relatively uncommon. Large deposits, however, may produce mild or moderate degrees of mitral regurgitation and uncommonly severe mitral regurgitation. 1 , 4 The valvular mitral regurgitation results from splinting of the physiologic contraction of the mitral annulus during systole and by stiffening of the leaflets. MS due to severe mitral annular calcification (MAC) is much less common 2 - 11 and is believed to be caused by decreased mobility of the valve leaflets due to extension of calcific deposits into/onto the leaflets. 5 Hammer et al. 3 believed that the diastolic gradients resulted from a combination of a small, thick-walled, noncompliant left ventricle and the large mitral annular calcific deposits. Hakki and Iskandrian 8 supported this hypothesis. However, Osterberger et al., 6 noting dilated ventricles in several patients, believed that the mitral annular calcification alone was sufficient to cause a pressure gradient across the mitral valve.
Table 12.1 Causes of Mitral Stenosis
Rheumatic heart disease
Nonrheumatic acquired mitral stenosis
Massive mitral annular calcification
Ergotamine induced and methysergide induced
Infective endocarditis with obstructive vegetations
Systemic lupus erythematosus
Antiphospholipid antibody syndrome
Carcinoid heart disease
Rheumatoid arthritis
Whipple’s disease
Pseudoxanthoma elasticum
Left atrial myxoma and other tumors
Cor triatriatum
Other congenital causes of mitral stenosis
Gross pathologic differences exist between rheumatic MS and MS associated with MAC ( Tables 12.2 and 12.3 ). Similarly, the echocardiographic appearance of the mitral apparatus can distinguish these entities. The echocardiographic features of MS caused by MAC are summarized as follows: calcification is prominent in the basal portion of both mitral leaflets with sparing of the free edges of the leaflets. This is precisely opposite the pattern seen in rheumatic MS, in which the tips/free edges are the thickest portion of the leaflets. 12 In addition, unlike rheumatic MS, in which the mitral leaflets move in tandem (parallel) as a result of commissural fusion, the leaflets in MAC have qualitatively normal (anti-parallel) diastolic motion, although the amplitude of leaflet motion is reduced. These features are best imaged with the parasternal long-axis and apical four-chamber views. Finally, in rheumatic MS, there is commissural fusion best imaged by the short-axis view. Commissural fusion is absent in MS caused by MAC. This feature has important clinical relevance because these patients do not benefit from percutaneous balloon mitral valvotomy, which derives its benefit from splitting the fused commissure(s).
Table 12.2 Cardinal Anatomic Changes in Rheumatic Mitral Valve Stenosis
Leaflet thickening (diffuse, especially free edges)
Commissural fusion
Shortening, thickening, and fusion of chordae
Oval or slitlike orifice (“fish mouth”)
Table 12.3 Anatomic Changes in Nonrheumatic Mitral Stenosis Caused by Mitral Annular Calcification
Leaflet thickening (focal, avoids free edges)
No commissural fusion
No chordal shortening, thickening, or fusion
Calcium deposition in other intracardiac sites (aortic valve, aortic annulus, sinotubular junction, papillary muscles)

Other Nonrheumatic Forms of Acquired Mitral Stenosis
The type of valve dysfunction caused by infective endocarditis is nearly always regurgitation and is often new. The occurrence of an obstructive or “functionally” stenotic mitral valve caused by endocarditis is rare. 13 - 15 Tiong et al. 15 reviewed the literature from 1966 to 2002 and found only 20 cases of significant native valve obstruction secondary to endocarditis. Although fungal endocarditis is usually suspected in this setting, bacterial endocarditis also causes obstruction.
The overuse of ergot alkaloids (e.g., ergotamine and methysergide) may cause plaquelike lesions on the mitral valve, leading to MS. 16 , 17 In addition, appetite suppressants can cause lesions that resemble those associated with ergot alkaloids. 18 Carcinoid syndrome is a rare disease that usually involves only the valves on the right side of the heart. However, left-sided involvement can occur (presumably either because of bronchial metastases 19 or patent foramen ovale). Carcinoid valvular disease can cause either regurgitant or stenotic lesions. 20
Large left atrial (LA) myxomas (and less commonly sarcomas) can prolapse into the mitral valve “funnel” in diastole and produce inflow obstruction due to their bulk. Malignant neoplasms, such as sarcomas and lymphomas, can mechanically deform and obstruct the mitral valve.
Mediastinal radiation may result in fibrocalcific valve disease and either mitral regurgitation or stenosis. 21 MS is an infrequent complication of systemic lupus erythematosus or the antiphospholipid syndrome. 22 - 24 MS has been reported in patients with familial pseudoxanthoma elasticum, in which histologic sections of the valve show irregular, coarse-fibered, abnormally fragmented elastic fibers similar to those seen in skin lesions. 25

Cor Triatriatum
Cor triatriatum is a rare congenital anomaly in which a perforated fibrous or fibromuscular membrane divides the left atrium into two chambers. The posterosuperior (common pulmonary venous chamber) chamber receives the pulmonary veins and the anterior-inferior (true left atrium) chamber receives the LA appendage. One or more openings in the fibrous membrane permit flow of blood from the pulmonary veins into the true left atrium. The opening(s) may be small, producing obstruction to flow, or large with little or no obstruction. The extent of obstruction determines the age of onset and severity of symptoms. Cor triatriatum may become manifest at any time from infancy to adulthood but usually becomes apparent in childhood, either as an isolated abnormality or associated with other congenital heart defects. 26 , 27 The clinical manifestations depend on the size of the opening of the membrane and are similar to MS. In adults, perforations are usually large, and nonobstrucive or fenestrated membranes may be detected fortuitously in asymptomatic patients who undergo echocardiography for an unrelated indication.
Two-dimensional (2-D) echocardiography, including transesophageal echocardiography (TEE), has become the procedure of choice for diagnosing cor triatriatum. 27 - 31 The echocardiographic features are characteristic and consist of a linear echo-density that stretches across the left atrium at a level midway between the mitral annulus and the superior border (or roof) of the left atrium. 32 This membrane may show phasic motion, moving inferiorly toward the mitral orifice in diastole and superiorly toward the superior LA border during systole. 32 The membrane can be seen in multiple views, including the parasternal long-axis, the subcostal long-axis, or the apical four-chamber or long-axis views. The four-chamber view is usually preferable because it places the membrane perpendicular to the echo beam. The perforation is most often posterior and, as stated, can be multiple. Color Doppler aids in demonstrating the number, location, and size of the openings in the membrane. Spectral Doppler (either pulsed or continuous wave) provides hemodynamic assessment. 33 Peak instantaneous and mean gradients can be calculated using the modified Bernoulli equation and the size of the orifice(s) can be calculated by the continuity equation. If the turbulent jet produced by the midcavitary obstruction strikes the mitral valve, it can produce fluttering of the mitral leaflets, best seen on M-mode echocardiography.
When the transthoracic study is suboptimal, TEE may be used to evaluate cor triatriatum. 29 , 34 Three-dimensional (3-D) echocardiography has also been used to evaluate cor triatriatum. 35

Other Congenital Causes of Mitral Stenosis
Cor triatriatum must be distinguished from a mitral supravalvular stenosing ring, another rare cause of MS. 36 , 37 In contrast to cor triatriatum, membranes in this condition are closer to the mitral valve (and may actually adhere to the valve leaflets) and are characterized by their position inferior to the LA appendage. The proximity of the membrane to the valve can lead to leaflet damage resulting from high-velocity turbulent flow. Leaflet thickening and mitral regurgitation can develop as a consequence. Color Doppler is useful to identify flow acceleration and turbulence at the level of the annulus rather than at the leaflet tips (as in rheumatic mitral valve stenosis). Continuous wave Doppler can be used to assess the severity of the obstruction. Caution must be used when diagnosing a supravalvular stenosing ring. Differentiating this entity from a calcified mitral annulus may be difficult, leading to both false-positive and false-negative diagnosis. 38
A parachute mitral valve, another congenital cause of MS, 36, 37, 39, 40 results when only one papillary muscle is present (or two are very close together). As a consequence, interchordal spaces are narrowed, producing subvalvular obstruction. This abnormality may be associated with other congenital cardiac anomalies or may occur as an isolated lesion. Parachute mitral valve may be part of the Shone syndrome, which also includes subaortic stenosis and coarctation of the aorta. 37 - 39

Pitfalls and Limitations of the Pressure Half-Time Method for Estimating Mitral Valve Area in Mitral Stenosis
Planimetry of the mitral valve orifice and mitral pressure half-time (PHT) derived from Doppler data are currently the most widely used echocardiographic techniques for measuring mitral valve area in patients with MS. The Doppler PHT method was first described by Hatle et al. 41 in 1979. Because of its simplicity, this method is widely used in clinical practice. Although the accuracy of the PHT method has been established. 2 - 46 several potential limitations are known and should be understood. 47 - 52 These pitfalls and limitations are listed in Table 12.4 . Accurate PHT measurements require careful recording of the MS velocity curve from the apical four-chamber view. Ideally the echo beam should be parallel to the mitral stenotic inflow jet, and the maximum early diastolic velocity and the diastolic deceleration slope should be well defined. Fortunately, good-quality Doppler tracings can almost always be obtained. Nevertheless, in some instances, the deceleration slope is nonlinear ( Figs. 12.1 to 12.3 ). In Hatle’s experience, a linear slope can usually be obtained with careful manipulation of the transducer position and angulation (personal communication). When a linear slope cannot be obtained, the choice of which suboptimal slope to use is not well established. Recommendations include using the slope with the longer duration 53 or using the mid-diastolic portion of the slope 54 , 55 ( Fig. 12.4 ). If sinus rhythm is present, the mitral E and A waves may be merged, especially in patients with tachycardia or prolonged PR interval. In this situation, the PHT method cannot be used.
Table 12.4 Mitral Valve Area in Mitral Stenosis: Limitations of Pressure Half-Time Method
Clear definition of V max and diastolic slope
Nonlinear diastolic velocity deceleration
Merging E and A waves in sinus rhythm
Influence of coexisting aortic regurgitation
Influence of reduced left ventricular compliance
Changing left ventricular and left atrial compliances immediately after balloon commissurotomy

Fig. 12.1 Diagram illustrating three patterns of nonlinear deceleration slopes ( A, B, C ).

Fig. 12.2 Continuous wave Doppler shows nonlinear deceleration slope.

Fig. 12.3 Continuous wave Doppler shows nonlinear deceleration slope in a patient with atrial flutter.

Fig. 12.4 Correlation with mitral valve area by Gorlin equation. r, Correlation coefficient.
(From Smith M. 22 patients with non-linear spectral pattern from 120 consecutive patients with mitral stenosis, Circulation 78(suppl II):31, 1988.)
The PHT can also be affected by concomitant aortic regurgitation or decreased LV compliance. The rapid increase in LV diastolic pressure in either of these conditions may shorten the PHT and cause an underestimation of the severity of MS. In this and the instances listed above, alternative methods (e.g., 2-D echocardiographic planimetry, continuity equation, proximal isovelocity surface area [PISA] method) should be used.
The PHT method depends not only on the degree of obstruction, but also on the compliances of the left atrium and left ventricle and the LA pressure. Because acute atrioventricular compliance changes are reputed to occur immediately after balloon mitral valvuloplasty, 50 the PHT method may be less accurate after this procedure. 47 - 52

Gradients and Mitral Valve Area in Atrial Fibrillation
Atrial fibrillation is common in patients with MS. In atrial fibrillation, the PHT is relatively constant despite the variation in the length of diastole. However, very short R-R intervals may not permit a clear early diastolic slope and such beats should be avoided. Averaging 5 to 10 cardiac cycles is recommended. Unlike the PHT, mean gradients vary with the R-R interval ( Fig. 12.5 ), and 5 to 10 consecutive cardiac cycles should be averaged.

Fig. 12.5 Illustration of mean gradient variation.

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