dynamic echocardiography expert consult premium edition enhanced online features and print

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 Reg

Dynamic Echocardiography

Dynamic Echocardiography

Professor of Medicine President, American Society of Echocardiography Director, Noninvasive Cardiac Imaging Laboratories University of Chicago Medical Center

Chicago, Illinois

Director, Noninvasive Cardiology Lab Washington Hospital Center

Washington, District of Columbia

Professor of Medicine Director, Non Invasive Cardiology New York University Medical Center New York, New York

Director, Echocardiography Services Aurora Health Care, Aurora Medical Group Aurora/St Luke Medical Center, Aurora/Sinai Medical Center Milwaukee, Wisconsin

3251 Riverport Lane

St Louis, Missouri 63043

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Notices

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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

Last digit is the print number: 9 8 7 6 5 4 3 2

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

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

Echo-cardiography is currently widely used every day in hospitals

and clinics around the world for assessing cardiac function

while simultaneously providing invaluable noninvasive

infor-mation 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

Regur-gitation; Prosthetic Heart Valve Disease; Interventional/

Intraoperative Echocardiography; Transesophageal

Echocar-diography; Coronary Artery Disease; Mechanical

Complica-tions 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

com-mentary 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 presenta-tions 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 frui-tion We owe a great debt to our ASE staff, who has collabo-rated 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 acknowl-edge 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, tive encouragement and advice

posi-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 grand-children Ella, Adam, Lucy, and Eli

Roberto M Lang, MD, FASESteven Goldstein, MDItzhak Kronzon, MD, FASEBijoy 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

ultra-sound 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

“inge-nious” 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

cardio-vascular ultrasound studies, more than five times the

com-bined 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

congeni-tal abnormalities, congestive heart failure, arrhythmia

man-agement, 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 Echocar­

diography, a comprehensive text and atlas of

echocardiogra-phy 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 techni-cal capabilities but even more impressively in its expanded

clinical applications By publishing Dynamic Echocardio­

graphy, 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

Duke Echocardiography Laboratory

Duke University Hospital

Durham, North Carolina

Deborah A Agler, RCT, RDCS, FASE

Coordinator of Education and Training

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

Ann Arbor, Michigan

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

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

Jeanne M DeCara, MD, FASE

Associate Professor of Medicine

University of Chicago Medical Center

Veronica Lea J Dimaano, MD

Senior Research Fellow

Cardiology, Angiology, Intensive Care

Elisabethinen Hospital Linz

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

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 Cardiac Imaging

Hospital Carlos III

Madrid, Spain

Steven J Lester, MD, FASE, FACC, FRCPC

Consultant, Department of Medicine, Division

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

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

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

Québec City, Quebec, Canada

Michael H Picard, MD, FASE, FACC, FAHA

Post Doctoral Fellow

Cardiovascular Epidemiology and Prevention

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

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

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

Figs 1.1 to 1.4.

Bicuspid Aortic Valve

Congenital aortic malformation reflects a phenotypic tinuum of unicuspid valve (severe form), bicuspid valve (moderate form), tricuspid valve (normal, but may be abnor-mal), 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 leaf-lets, with or without a central raphe, resulting in partial or complete absence of a functional commissure between the fused leaflets.1

con-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 esti-mate 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 graphic screening for the military.9Table 1.2 summarizes data

echocardio-on the prevalence of bicuspid valves BAV is seen nantly in males with a 2-4 : 1 male/female ratio.10-12 Although

predomi-a BAV mpredomi-ay occur in isolpredomi-ation, it mpredomi-ay be predomi-associpredomi-ated with mpredomi-any forms of congenital heart disease

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 echocar dio-graphy, 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 trans-esophageal 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 confi guration rather than the Y of the normal tricuspid aortic valve (Tables 1.3 to 1.5)

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)

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 structur-ally 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 posi-tion.2 Novaro and colleagues18 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 based therapy can be recommended

evidence-Native Valvular Heart Disease:

Table 1.1  Etiology of Aortic Stenosis

Congenital (unicuspid, bicuspid) Degenerative (sclerosis of previously normal valve) Rheumatic

COMMON CAUSES OF VALVULAR AORTIC STENOSIS

Bicuspid

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.

A

B

C

Fig.  1.2 A to C, Degenerative aortic stenosis in the elderly A,

Trans-esophageal echocardiographic cross-sectional view of an elderly patient with degenerative aortic stenosis illustrating relative absence of commis- sured 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.

Aortic regurgitation, present in approximately 15% of patients with BAV,10 is usually due to dilation of the sinotu-bular 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 endocar-ditis 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

4 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

Area  0.95 cm 2

Fig. 1.4 A and B, Typical rheumatic

aortic stenosis with commissural

fusion resulting in a central

triangu-lar (as shown here) or oval or

circu-lar orifice Typical rheumatic aortic

stenosis with commissured fusion

resulting in a central triangular

orifice as shown in the

transesopha-geal echocardiogram (A) and a

2D echo: Two-dimensional echocardiography.

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.

Fenoglio et al 36 1977 8/152 (5) Necropsy ≥20

years old Larson and

From Tutarel O: The quadricuspid aortic valve: a comprehensive review

J Heart Valve Dis 2004;13:534-537.

Patients with BAVs are particularly susceptible to infective

endocarditis Although the exact incidence of endocarditis

remains controversial, the population risk, even in the

pres-ence 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

diag-nosis of BAV Unexplained systolic ejection murmurs,

dia-stolic decrescendo murmurs, and/or aortic ejection sounds

(clicks) should prompt echocardiographic evaluation

Bacte-rial 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 domi-nance, 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 devel-opmental disorder involving the entire aortic root and arch Although the pathogenesis is not well understood, these asso-ciated aortic malformations suggest a genetic defect.26Although they are less well-understood, these aortic com-plications of BAV disease can cause significant morbidity and mortality BAV may also be associated with progressive dila-tion, aneurysm formation, and dissection (Tables 1.7 and

1.8) These vascular complications may occur independent of valvular dysfunction9 , 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

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 con-sensus 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 ascend-ing aortic dilation in patients with BAV using criteria similar

6 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

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

con-sidered 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

coarcta-tion of the aorta in 6% of cases of BAV,1 and an

echocardio-graphic 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

endocar-ditis 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

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

echocar-diography 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

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

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 junc-tion, and ascending aorta

The parasternal short-axis (SAX) view is useful in ing the number and position of the commissures, the opening pattern, the presence of a raphe, and the leaflet mobility The

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).

A B

LVOT AO

Fig.  1.8 A and B, Bicuspid aortic

valve Transesophageal

echocardio-graphy demonstrates several

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

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

con-joined cusp.46

False-positive diagnosis of BAV may occur if all three

leaf-lets 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

paraster-nal SAX view can also be misleading if the raphe is mistaken

for a third commissural closure line

8 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

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 asymp-tomatic murmurs and ejection sounds (Table 1.10 and

Fig 1.13).27 A diagram (Fig 1.14) and actual gram (Fig 1.15) illustrate typical physical findings in patients with BAV

phonocardio-Aortic root measurements should be made in the PLAX

view at four levels: the annulus, sinuses of Valsalva,

sinotu-bular 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

LA LV

Ao

3

4

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.

Cardiac Murmur

Systolic Murmur Diastolic Murmur Continuous Murmur

Midsystolic, grade 2 or less

• Early systolic

• Midsystolic, grade 3 or more

STRATEGY FOR EVALUATING HEART MURMURS

Catheterization and angiography

if appropriate

Asymptomatic &

no associated findings

Symptomatic or other signs of cardiac disease*

No further workup

* If an ECG or CXR has been obtained and is abnormal, echo is indicated

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.)

S1 S2

a

EC

P A

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 , pulmonic area, medium frequency; SB , left sternal border, medium frequency.

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.

10 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

24 Mills P, Leech G, Davies M, et al: The natural history of a non-stenotic

bicuspid valve Br Heart J 40:951-957, 1978.

25 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 48:e1-e148, 2006.

26 Lamas CC, Eykyn SJ: Bicuspid aortic valve—a silent danger: analysis of 50

cases of infective endocarditis Clin Infect Dis 30:336-341, 2000.

27 Dyson C, Barnes RA, Harrison GA: Infective endocarditis: an

epidemiological review of 128 episodes J Infect 38:87-93, 1999.

28 Fedak PW, Verma S, David TE, et al: Clinical and pathophysiological

implications of a bicuspid aortic valve Circulation 106:900-904, 2002.

29 Gott.VL, Greene PS, Alejo DE, et al: Replacement of the aortic root in

patients with Marfan’s syndrome N Engl J Med 341:1473-1474, 1999.

30 Leggett ME, Unger TA, O’Sullivan CK, et al: Aortic root complications in

Marfan’s syndrome: identification of a lower risk group Heart 75:389-395,

1996.

31 Devereux RB, Roman MJ: Aortic disease in Marfan’s syndrome N Engl J Med 340:1307-1313, 1999.

32 Ergin MA, Spielvoge D, Apaydin A, et al: Surgical treatment of the dilated

ascending aorta: when and how? Ann Thorac Surg 67:1834-1839, 1999.

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 26:892-893, 2003.

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 128:677-683, 2004.

35 Isselbacher EM: Thoracic and abdominal aortic aneurysms Circulation

111:816-828, 2005.

36 Fenoglio JJ, McAllister HA, DeCastro CM, et al: Congenital bicuspid aortic

valve after age 20 Am J Cardiol 39:164-169, 1977.

37 Roberts CS, Roberts WC: Dissection of the aorta associated with congenital

malformation of the aortic valve J Am Coll Cardiol 17:712-716, 1991.

38 Gore I, Seiwert VJ: Dissecting aneurysm of the aorta, pathologic aspects: an

analysis of eighty-five fatal cases Arch Pathol 53:121-141, 1952.

39 Edwards WD, Leaf DS, Edwards JE: Dissecting aortic aneurysm associated

with congenital bicuspid aortic valve Circulation 57:1022-1025, 1978.

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 43:835-840, 1979.

41 Folger GM Jr, Stein PD: Bicuspid aortic valve morphology when associated

with coarctation of the aorta Cathet Cardiovasc Diagn 10:17-25, 1984.

42 Nihoyannopoulos P, Karas S, Sapsford RN, et al: Accuracy of dimensional echocardiography in the diagnosis of aortic arch obstruction

two-J Am Coll Cardiol 10:1072-1077, 1987.

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 30:1809-1812, 1997.

44 Warnes CA: Bicuspid aortic valve and coarctation: two villains part of a

diffuse problem Heart 89:965-966, 2003.

45 Fernandes SM, Sanders SP, Khairy P, et al: Morphology of bicuspid aortic

valve in children and adolescents J Am Coll Cardiol 44:1648-1651, 2004.

46 Waller BF, Carter JB, Williams HJ Jr, et al: Bicuspid aortic valve Comparison

of congenital and acquired types Circulation 48:1140-1150, 1973.

4 Wauchope GM: The clinical importance of variations in the number of

cusps forming the aortic and pulmonary valves Quart J Med 21:383-399,

1928.

5 Gross L: So-called congenital bicuspid aortic valve Arch Pathol 23:350-362,

1937.

6 Datta BN, Bhusnurmah B, Khatri HN, et al: Anatomically isolated aortic

valve disease Morphologic study of 100 cases at autopsy Jpn Heart J

29:661-670, 1988.

7 Pauperio HM, Azevedo AC, Ferreira C: The aortic valve with two leaflets

A study in 2000 autopsies Cardiol Young 9:488-498, 1999.

8 Basso C, Boschello M, Perrone C, et al: An echocardiographic survey of

primary school children for bicuspid aortic valve Am J Cardiol 93:661-663,

2004.

9 Nistri S, Basso C, Marzari C, et al: Frequency of bicuspid aortic valve in

young male conscripts by echocardiogram Am J Cardiol 96:718-721, 2005.

10 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 74:14-26, 1999.

11 Keane MG, Wiegers SE, Plappert T, et al: Bicuspid aortic valves are associated

with aortic dilatation out of proportion to coexistent valvular lesions

Circulation 102:1135-1139, 2000.

12 Chan KL, Ghani M, Woodend K, et al: Case-controlled study to assess risk

factors for aortic stenosis in congenitally bicuspid aortic valve Am J Cardiol

88:690-693, 2001.

13 Feldman BJ, Khandheria BK, Warnes CA, et al: Incidence, description and

functional assessment of isolated quadricuspid valves Am J Cardiol

16 Moore GW, Hutchins GM, Brito JC, et al: Congenital malformations of the

semilunar valves Hum Pathol 11:367-372, 1980.

17 Simonds JP: Congenital malformations of the aortic and pulmonary valves

Am J Med Sci 166:584-595, 1923.

18 Novaro GM, Tiong IY, Pearce GL, et al: Features and predictors of ascending

aortic dilatation in association with a congenital bicuspid aortic valve Am J

Cardiol 92:99-101, 2003.

19 Olson LJ, Subramanian MB, Edwards WD: Surgical pathology of pure aortic

insufficiency: a study of 725 cases Mayo Clin Proc 59:835-841, 1984.

20 Tutarel O: The quadricuspid aortic valve: a comprehensive review J Heart

Valve Dis 13:534-537, 2004.

21 Roberts WC, Ko JM, Matter GJ: Isolated aortic valve replacement without

coronary bypass for aortic valve stenosis involving a congenitally bicuspid

aortic valve in a nonagenarian Am J Geriatr Cardiol 15:389-391, 2006.

22 Rosenhek R, Rader F, Loho N, et al: Statins but not angiotensin-converting

enzyme inhibitors delay progression of aortic stenosis Circulation

110:1291-1295, 2004.

23 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

40:1723-1730, 2002.

Aortic stenosis is the most common valvular heart disease

requiring valve replacement The indications for valve

replace-ment depend on symptoms and hemodynamic variables, such

as aortic valve area (AVA) and transaortic gradients

There-fore accurate hemodynamic evaluation of the aortic valve is

important for clinical decision-making Transthoracic

echo-cardiography (TTE) is used most frequently in clinical

prac-tice to quantify the severity of aortic valve stenosis because it

is noninvasive, widely available, and generally reliable With

careful attention to technique, an experienced

echocardiogra-phy 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

informa-tion 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

ante-rior 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

of the anatomic area by the surgeon.12 The indications for use

of TEE to assess the severity of aortic stenosis are listed in

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 com-plete 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

Aortic Stenosis Quantitation

12 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

located at the tips of the valve leaflets The longitudinal motion

of the aortic root during the cardiac cycle can make this ficult 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

dif-in gaps dif-in the outldif-ine of the orifice In addition, promdif-inent 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 techni-cally demanding by TEE, it can be performed in many patients.13 , 14 Stoddard et al.13 have demonstrated that a signifi-cant learning curve exists, but this technique appears feasible

in the majority of patients.14Continuous 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 viewIdeally, 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 echocar-diography15-19 and magnetic resonance imaging.20-22 Compara-tive studies among these different diagnostic methods are needed

Reporting and Classification

of Severity

The ACC/AHA Practice Guidelines, revised in 2006, re commend grading the severity of aortic stenosis based on a variety of hemodynamic and natural history data, using defi-nitions of aortic jet velocity, mean pressure gradient, and AVA

-Table 2.1 Technical Limitations and Pitfalls of

Quantitating Valvular Aortic Stenosis by

AS, Aortic stenosis; MR, mitral regurgitation; PVCs, premature ventricular

contractions; TR, tricuspid regurgitation.

Table 2.2 Indications for Using TEE to Assess

Severity of Aortic Stenosis

CABG, Coronary artery bypass grafting; LVOT, left ventricular outflow tract.

Table 2.3 Feasibility of Planimetry of AVA by

Table 2.4 Feasibility of Determining AVA by

TEE Using Continuity Equation

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

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

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 76:193-198,

1995.

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 77:882-885, 1996.

9 Stoddard MF, Hammons RT, Longaker RA: Doppler transesophageal echocardiographic determination of aortic valve area in adults with aortic

for assessing severity of aortic stenosis? Heart 78:68-73, 1997.

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 17:Suppl A:20A, 1991.

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 126:956-962,

1993.

14 Blumberg FC, Pfeifer M, Holmer SR, et al: Quantification of aortic stenosis

in mechanically ventilated patients using multiplane transesophageal

Doppler echocardiography Chest 114:94-97, 1998.

15 Nanda NC, Roychoudhry D, Chung S, et al: Quantitative assessment of normal and stenotic aortic valve using transesophageal three-dimensional

echocardiography Echocardiography 11:617-625, 1994.

16 Menzel T, Mohr-Kahaly S, Kolsch B, et al: Quantitative assessment of aortic

stenosis by three-dimensional echocardiography J Am Soc Echocardiogr

10:215-223, 1997.

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

rendered echocardiography Echocardiography 19:45-53, 2002.

20 Friedrich MG, Schulz-Menger J, Poetsch T, et al: Quantification of valvular

aortic stenosis by magnetic resonance imaging Am Heart J 144:329-334,

2002.

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 42:519-526, 2003.

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 90:893-901, 2004.

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 48:e1-e148, 2006.

(Table 2.5).23 In applying these definitions, the examiner

should recognize the potential for imprecision in the

mea-surements for both catheterization and echo-Doppler

tech-niques 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

References

1 Zoghbi WA, Farmer KL, Soto JG, et al: Accurate noninvasive quantification

of stenotic valve area by Doppler echocardiography Circulation 73:452-459,

1986.

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 16:383-393, 1995.

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 59:330-335, 1987.

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

122:1415-1422, 1991.

5 Hoffmann R, Flachskampf FA, Hanrath P: Planimetry of orifice area in

aortic stenosis using multiplane transesophageal echocardiography J Am

Coll Cardiol 22:529-534, 1993.

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

128:526-532, 1994.

Table 2.5 Classification of the Severity of

Aortic Stenosis in Adults

Severity

Aortic Jet Velocity (m/sec)

Mean Gradient (mm Hg) Valve Area (cm 2 )

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:e1-148.

Aortic Stenosis:

Subaortic Membrane

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).1SAS can develop after acquired heart diseases in rare instances

Morphologic Variants of Subaortic Membrane

An extensive range of lesions has been described to cause SAS

The classification has always been controversial Kelly’s phologic classification in type I (thin membrane) and type II (fibromuscular stenosis) lesions is currently underused.2 Choi and Sullivan3 presented a classification based on echocardio-graphic features:

mor-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 hypo-plasia of the aortic valve annulus (Fig 3.3)

3 SAS can result from a malalignment of septal tures in the presence of a ventricular septal defect (VSD) (Fig 3.4) It can include a posterior malalign-ment with obstruction above the VSD, usually associ-ated with aortic arch interruption, and anterior malalignment with obstruction below the VSD

struc-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)

The clinical features of SAS are determined by the severity

of the LVOT obstruction Patients with mild gradients mally 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

nor-Diagnosis

On physical examination, a “harsh” systolic ejection mur—best heard at the left sternal border—is characteristi-cally found A thrill can be palpable in the same position

mur-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

diag-nosis of SAS before the development of 2-D

echocardiogra-phy Catheterization provides anatomic and hemodynamic

data but lacks good definition of small anatomic structures

Fig 3.1 Subaortic membrane (short segment).

Fig 3.2 Muscular membrane.

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

Table 3.1 Subaortic Stenosis: Summary

Acquired Lesion With Strong Genetic predisposition

16 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

and assessment of mitral apparatus The measurement of the peak-to-peak gradient at catheterization has no good correla-tion with the maximum instantaneous gradient of the echo-cardiogram, and therefore these should not be compared.8The 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 mias could mask the presence of significant gradient across the LVOT Leichter, Sullivan, and Gersony10 described 35 patients with no significant LVOT obstruction at initial cardiac catheterization but who later were shown to have sig-nificant SAS Today catheterization is performed only when multiple levels of obstruction are suspected

arrhyth-pathophysiology and Natural History

The development of a subaortic lesion is genetically enced Nevertheless, various abnormal flow patterns are believed to take part in the process: septal ridge, malalignment

influ-of the septum, elongated or hypoplastic LVOT, apical lar 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

muscu-a result, muscu-a fibrous or musculmuscu-ar structure would displmuscu-ay 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 hemody-namic 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 rela-tionship 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

VSD

RV

LV

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.

RV

LV

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.

3 Choi JY, Sullivan ID: Fixed subaortic stenosis: anatomical spectrum and

nature of progression Br Heart J 65:280-286, 1991.

4 Darcin OT, Yagdi T, Atay Y, et al: Discrete subaortic stenosis Tex Heart Inst J

8 Currie PJ, Hagler DJ, Seward JB, et al: Instantaneous pressure gradient: a

simultaneous Doppler and dual catheter correlative study J Am Coll Cardiol

7:800-806, 1986.

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 64:756-761, 1989.

10 Leichter DA, Sullivan I, Gersony WM: “Acquired” discrete subvalvular aortic

stenosis: natural history and hemodynamics J Am Coll Cardiol

14:1539-1544, 1989.

11 Gersony WM: Natural History of discrete subvalvular aortic stenosis:

management implications J Am Coll Cardiol 38:843-845, 2001.

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 38:835-842, 2001.

13 Brauner R, Laks H, Drinkwater DC, et al: Benefits of early surgical repair in

fixed subaortic stenosis J Am Coll Cardiol 30:1835-1842, 1997.

14 Kitchiner D: Subaortic stenosis: still more questions than answers Heart

82:647-648, 1999.

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

frac-tion, severity of LVOT obstrucfrac-tion, 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

pres-ence 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

recur-rence rate.13 Various studies have shown no clinical benefit for

early surgery in patients with mild gradients.14

Aortic Stenosis With Low Gradient and Poor Left Ventricular Dysfunction

The majority of patients with valvular aortic stenosis (AS) have preserved systolic left ventricular (LV) function Occa-sionally, however, a patient with AS has substantial depression

of LV function, a low ejection fraction (EF), and a low valvular pressure gradient (PG)

trans-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 appar-ently 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 aflet 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 pres-sure, 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 cm2.3 In some patients, however, chronic increases in LV work because the the resistance of the stenotic

trile-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 tion caused by afterload mismatch

func-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 function, a low EF, and abnormal (though not severely ste-notic) aortic leaflets also may have an AVA less than 1.0 cm2and 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

dys-AS is an important diagnostic challenge Data from a patient that illustrate this dilemma are shown in Fig 4.1

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 transval vular PG and to determine AVA using the continuity equa-tion.5 When transthoracic echocardiography cannot assess

-AS severity (usually because of poor image quality), esophageal echocardiography can be used to visualize and measure AVA by planimetry.6 In a patient with LV dysfunc-tion, 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

trans-Native Valvular Heart Disease: Aortic

Stenosis/Aortic Regurgitation

I

I

a recent French multicenter study Monin and colleagues11evaluated 136 patients with low-gradient AS and used dobu-tamine 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 inves-tigators 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 medi-cally; 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, sur-vivors 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 per-centage of patients in whom functional class improved, or in the frequency and degree of improvement in EF On multi-variate 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

In this case, evaluation of aortic valve hemodynamics using

Doppler techniques during dobutamine infusion is quite

valu-able 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

investiga-tors 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

demon-strated contractile reserve In a subsequent report, 8

dobuta-mine 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%)

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

periopera-tive 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

mortali-ties 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

hemo-dynamics, and the outcome after AVR has been evaluated by

Fig 4.1 Transthoracic echo­

cardiographic and Doppler data

obtained at rest from an 85­year­

old man with progressive dyspnea

and evidence of AS on physical

examination Real­time imaging

demonstrated aortic valve calcifica­

tion and reduced leaflet opening

during systole, as well as impaired

LV systolic function (ejection frac­

tion, 23%) By using the continuity

equation and the measures of LV

outflow tract diameter (upper left)

and velocity­time integrals (VTI) in

the LV outflow tract (lower left) and

across the stenotic valve (lower

right), aortic valve area was calcu­

lated as 0.44 cm 2 The mean trans­

valvular gradient was 23 mm Hg

These data show apparent severe

AS, despite being of low gradient,

in a patient with depressed LV

function.

20 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

Fig 4.2 Transthoracic echocardiographic and Doppler data obtained from the same patient in Figure 4.1 during dobutamine infusion Real­time imaging demonstrated an improvement in contractile function with ejection fraction measured at 36% Doppler velocity­time 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.

HEMODYNAMICS: REST & STRESS Baseline

0.44 cm 2

78 mmHg

41 mmHg

14 cm 36%

0.7 cm 2 Dobutamine

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 dobu­

tamine infusion (right column) During adrenergic stress, contractile reserve is evident, with an increase in the left ventricular ejection fraction and

velocity­time 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 (ΔP) increase Aortic valve area (AVA) also increases but remains in the critical range These findings demon­ strate 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 , Flow­velocity integral of the left ventricular outflow tract; LVEF, left ventricular ejection fraction.

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 62:42-48, 1980.

2 Cannon JD, Zile MR, Crawford FA Jr, 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 20:1517-1523, 1992.

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 114:e84-e231, 2006.

4 Ross J Jr: Afterload mismatch and preload reserve: a conceptual framework

for the analysis of ventricular function Prog Cardiovasc Dis 18:255-264,

1976.

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 7:509-517, 1986.

6 Hoffmann R, Flachskampf FA, Hanrath P: Planimetry of orifice area

in aortic stenosis using multiplane transesophageal echocardiography

J Am Coll Cardiol 22:529-534, 1993.

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 75:191-194, 1995.

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 106:809-813, 2002.

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 21:1657-1660, 1993.

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 101:1940-1946, 2000.

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

108:319-324, 2003.

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 113:1738-1744, 2006.

13 Lange RA, Hillis LD: Dobutamine stress echocardiography in patients with

low-gradient aortic stenosis Circulation 113:1718-1720, 2006.

These results indicate that dobutamine stress

hemodynam-ics 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

rea-sonable to consider such patients for AVR.13

Table 4.1 Summary of Key Points From a

French Multicenter Study 12

Variable With Contractile Reserve No Contractile Reserve

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 J­P, Monin J­L, Levy F, et al Influence of preoperative left

ventricular contractile reserve on postoperative ejection fraction in low­

gradient aortic stenosis Circulation 2006;113:1738­1744.

Asymptomatic Severe Aortic Stenosis

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 tion older than 65 years has been reported in the range of 2%

popula-to 7% and aortic sclerosis, the precursor of AS, has been found

in 25%.1The 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

During the long latent period with increasing outflow tract obstruction that results in increasing left ventricular (LV) pressure load, patients remain asymptomatic and acute com-plications are rare However, outcome becomes dismal as soon as symptoms such as exertional dyspnea, angina or diz-ziness, 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 sur-vival.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 esti-mated that about 50% of patients who come to medical atten-tion 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 tomatic 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

aof 20 months Both patients, however, had experienced toms at least 3 months before death We have reported one sudden death that was not preceded by any symptoms among

symp-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 asymp-tomatic 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 fol-lowing 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 atic severe AS in whom impaired systolic LV function has

asymptom-Native Valvular Heart Disease:

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 addi-tional 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 regur-gitation, 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 asymp-tomatic patients with severe AS.6 These discrepant results may

be explained by the fact that in some studies patients went surgery without having preoperative symptoms devel-oped while these interventions were, nevertheless, counted as events Thus the event-free survival reported in the literature should be viewed with caution

under-Predictors of Outcome and Risk Stratification in Asymptomatic Severe Aortic Stenosis

Because it appears unlikely from current data that the tial benefit of valve replacement can outweigh the risk of surgery and the long-term risk of prosthesis-related complica-tions in all asymptomatic patients, surgery is not generally recommended in patients with AS before symptom onset.3 , 4

poten-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 progres-sion, and left ventricuclar hypertrophy and ejection fraction have been identified as independent predictors of outcome.4However, these findings were obtained retrospectively and do not allow any specific recommendations on prospective selec-tion of high-risk patients who may benefit from early elective surgery.3,4

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

symp-toms 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

Vpeak 4.6 m/s

p mean 54 mmHg

Vpeak 5.3 m/s

p mean 75 mmHg

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).

or ST-segment depression without occurrence of symptoms remained unclear.

More recently, Das and colleagues15 clarified some of the unanswered questions In 125 patients with asymptomatic AS (effective valve area 0.9 ± 0.2cm2), 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 Abnor-mal 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 symp-toms 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

Aortic valve calcification has become a powerful

indepen-dent 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

hemo-dynamic progression However, even in the presence of

calci-fication 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

Exercise Testing

An abnormal response to exercise has been found to predict

outcome Amato and colleagues14 performed exercise testing

in 66 asymptomatic patients with an aortic valve area <1.0 cm2

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

develop-ment 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,

Fig 5.2 Short-axis views of patients

with severe aortic stenosis and

various degrees of valve

calcifi-cation Left upper panel: No

calcifi-cation; right upper panel: mild

calcification; left lower panel:

moderate calcification; right lower

panel: severe calcification.

Table 5.1 Echocardiographic Predictors of

Outcome in Aortic Stenosis

* No data for asymptomatic aortic stenosis.

patients with dizziness developed spontaneous symptoms

compared with only 50% of patients with chest tightness and

54% of patients with breathlessness The most likely

explana-tion 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

exer-cise 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

develop-ment within 12 months and watchful waiting is safe

Con-versely, 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

gra-dient 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

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 diology 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 impor-tant role for management decision making by providing sys-tolic LV function, hemodynamic progression and extent of valve calcification, extent of LV hypertrophy, and actual sever-ity of AS (mean gradient and aortic valve area)

Car-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 hemody-namic 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 offer-ing 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 hyper-cholesterolemia, elevated lipoprotein(a), smoking, hyperten-sion, 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 progres-sion prevention are definitely statins

Indeed, several retrospective studies have consistently onstrated 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 choles-terol levels, Bellamy and colleagues19 and the author’s group

dem-in Vienna21 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

26 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

rates between patients with and without ACE inhibitor ment 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

treat-In conclusion, there is no solid evidence that AS sion can be prevented with any medical therapy and it is too early for treatment recommendations

progres-References

1 Stewart BF, Siscovick D, Lind BK, et al: Clinical factors associated with

calcific aortic valve disease Cardiovascular Health Study J Am Coll Cardiol

29:630-634, 1997.

2 Rosenhek R, Maurer G, Baumgartner H: Should early elective surgery

be performed in patients with severe but asymptomatic aortic stenosis

Eur Heart J 23:1417-1421, 2002.

3 Bonow RO, Carabello DA, 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 e1-e48, 2006.

4 Vahanian A, Baumgartner H, Bax J, et al: Guidelines on the management

of valvular heart disease: The Task Force on the Management of Valvular

Heart Disease of the European Society of Cardiology Eur Heart J

28:230-268, 2007.

5 Pellikka PA, Nishimura RA, Bailey KR, Tajik AJ: The natural history of adults with asymptomatic, hemodynamically significant aortic stenosis

J Am Coll Cardiol 15:1012-1017, 1990.

6 Rosenhek R, Binder T, Porenta G, et al: Predictors of outcome in severe,

asymptomatic aortic stenosis N Engl J Med 343:611-617, 2000.

7 Pellikka PA, Sarano ME, Nishimura RA, et al: Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged

follow-up Circulation 111:3290-3295, 2005.

8 Keane JF, Driscoll DJ, Gersony WM, et al: Second natural history study of congenital heart defects Results of treatment of patients with aortic valvar

stenosis Circulation 87(suppl):I16-I27, 1993.

9 Lund O, Nielsen TT, Emmertsen K, et al: Mortality and worsening of prognostic profile during waiting time for valve replacement in aortic

stenosis Thorac Cardiovasc Surg 44:289-295, 1996.

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

pro-gression 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

proinflamma-tory 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

Table 5.2 Recommendations for Isolated Aortic Valve Replacement in Asymptomatic

IIb Patients with high likelihood of rapid progression (age,

CAD, calcification)

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.

hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and

progression of aortic stenosis in the community J Am Coll Cardiol

A randomized trial of intensive lipid-lowering therapy in calcific

aortic stenosis N Engl J Med 352:2389-2397, 2005.

23 O’Brien KD, Probstfield J, Caulfield MT et al: Angiotensin-converting

enzyme inhibitors and change in aortic valve calcium Arch Intern Med

165:858-862, 2005.

24 Rossebø AB, Pedersen TR, Boman K, et al: Intensive lipid lowering with

simvastatin and ezetimibe in aortic stenosis N Engl J Med 359:1343-1356,

2008.

10 STS national database: STS U.S cardiac surgery database: 1997 Aortic valve

replacement patients: preoperative risk variables Chicago: Society of

Thoracic Surgeons, 2000 available at http://www.ctsnet.org/doc/3031.

11 Otto CM: Timing of aortic valve surgery Heart 84:211-218, 2000.

12 Otto CM, Burwash IG, Legget ME, et al: Prospective study of asymptomatic

valvular aortic stenosis Clinical, echocardiographic, and exercise predictors

of outcome Circulation 95:2262-2270, 1997.

13 Lancellotti P, Lebois F, Simon M, et al: Prognostic importance of quantitative

exercise Doppler echocardiography in asymptomatic valvular aortic stenosis

Circulation 112(Suppl):1377-1382, 2005.

14 Amato MC, Moffa PJ, Werner KE, et al: Treatment decision in asymptomatic

aortic valve stenosis: role of exercise testing Heart 86(4):381-386, 2001.

15 Das P, Rimington H, Chambers J: Exercise testing to stratify risk in aortic

stenosis Eur Heart J 26:1309-1313, 2005.

16 Bergler-Klein J, Klaar U, Herger M, et al: Natriuretic peptides predict

symptom-free survival and postoperative outcome in severe aortic stenosis

Circulation 109:2302-2308, 2004.

17 Mohler ER Mechanisms of aortic valve calcification Am J Cardiol

94:1396-1402, 2004.

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 106:2224-2230, 2002.

19 Bellamy MF, Pellikka PA, Klarich KW, et al: Association of cholesterol levels,

Challenges in Aortic Stenosis

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 myocar-dium counter the increase in afterload Morbidity and mortal-ity 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.1,7-9Hemodynamic 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 cm2 per year.6,10-14However, 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 pres-sure >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 cant 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 catheteriza-tion Echocardiography not only provides information on the structure and function of the aortic valve, but it also charac-terizes the response of the left ventricle to increased afterload and can identify other associated valvular pathology Recom-mendations for serial echocardiographic evaluation of patients with asymptomatic AS are every year for severe AS, every 1 to

signifi-2 years for moderate AS, and every 3 to 5 years for mild AS.23Performing echocardiography to evaluate AS severity man-dates 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 rec-ommended 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 trans-ducer position with the neck extended For the interpreter,

it is important to correctly identify the origin of the velocity jet The Doppler signal of mitral or tricuspid regur-gitation, 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

high-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

Native Valvular Heart Disease:

6 Rosenhek R, Binder T, Porenta G, et al: Predictors of outcome in severe,

asymptomatic aortic stenosis N Engl J Med 343:611-617, 2000.

7 Iivanainen AM, Lindroos M, Tilvis R, et al: Natural history of aortic

valve stenosis of varying severity in the elderly Am J Cardiol 78:97-101,

1996.

8 Schwarz F, Baumann P, Manthey J, et al: The effect of aortic valve

replacement on survival Circulation 66:1105-1110, 1982.

9 Turina J, Hess O, Sepulcri F, et al: Spontaneous course of aortic valve

disease Eur Heart J 8:471-483, 1987.

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 25:305-310, 1995.

11 Davies SW, Gershlick AH, Balcon R Progression of valvar aortic stenosis:

a long-term retrospective study Eur Heart J 12:10-14, 1991.

12 Faggiano P, Ghizzoni G, Sorgato A, et al: Rate of progression of valvular

aortic stenosis in adults Am J Cardiol 70:229-233, 1992.

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 61:123-130, 1988.

2 Kennedy KD, Nishimura RA, Holmes DR Jr., et al: Natural history of

moderate aortic stenosis J Am Coll Cardiol 17:313-319, 1991.

3 Otto CM, Burwash IG, Legget ME, et al: Prospective study of asymptomatic

valvular aortic stenosis: clinical, echocardiographic, and exercise predictors

of outcome Circulation 95:2262-2270, 1997.

4 Pellikka PA, Nishimura RA, Bailey KR, et al: The natural history of adults

with asymptomatic, hemodynamically significant aortic stenosis J Am Coll

Cardiol 15:1012-1017, 1990.

5 Pellikka PA, Sarano ME, Nishimura RA, et al: Outcome of 622 adults with

asymptomatic, hemodynamically significant aortic stenosis during prolonged

follow-up Circulation 111:3290-3295, 2005.

D  1.9

AVA  D 2 (1.9)  0.785  TVILVOT(26cm)  0.6 cm 2

TVIAV(124cm)

Fig 6.1 Doppler profile of a

67-year-old woman who was

evalu-ated for a heart murmur Her

echo-cardiogram demonstrated mild to

moderate concentric left ventri

-cular 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

echocardio-gram 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

asymp-tomatic; 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.

30 Section I—Native Valvular Heart Disease: Aortic Stenosis/Aortic Regurgitation

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 68:1469-1476, 1991.

20 Das P, Rimington H, Chambers J Exercise testing to stratify risk in aortic

stenosis Eur Heart J 26:1309-1313, 2005.

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 20:1160-1167, 1992.

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 81:131-137, 2001.

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 48:598-675, 2006.

24 Otto CM: Textbook of clinical echocardiography, ed 4, Philadelphia, 2009,

Elsevier.

13 Otto CM, Pearlman AS, Gardner CL: Hemodynamic progression of aortic

stenosis in adults assessed by Doppler echocardiography J Am Coll Cardiol

13:545-550, 1989.

14 Roger VL, Tajik AJ, Bailey KR, et al: Progression of aortic stenosis in adults:

new appraisal using Doppler echocardiography Am Heart J 119:331-338,

1990.

15 Rosenhek R, Klaar U, Schemper M, et al: Mild and moderate aortic stenosis:

natural history and risk stratification by echocardiography Eur Heart J

25:199-205, 2004.

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 11:204-209, 2002.

17 Amato MCM, Moffa PJ, Werner KE, et al: Treatment decision in

asymptomatic aortic valve stenosis: role of exercise testing Br Heart J

86:381-386, 2001.

18 Atwood JE, Kawanishi S, Myers J, et al: Exercise testing in patients with

aortic-stenosis Chest 93:1083-1087, 1988.

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.Stroke volume across the aortic valve must be calculated to determine aortic valve area.1 The formula for calculating aortic valve stroke volume is

0 785

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 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)

long-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 con-stant LVOT TVI of 18 cm

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 con-sideration 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 lel to flow results in an underestimation of the Doppler jet velocity For example, an intercept angle of 30 degrees results

paral-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 tinuous wave Doppler to the blood flow The most common acoustic windows include the apical, suprasternal notch, right supraclavicular, right parasternal, and subcostal These acous-tic 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

con-It is important to ensure that the Doppler waveform is rectly 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

cor-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 tical 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

iden-Echocardiography provides a comprehensive namic and morphologic assessment of stenotic aortic valves.4,5The assessment must be carried out with a concise, thorough examination with no or limited technical pitfalls

hemody-Native Valvular Heart Disease: