A Guide to Hypertrophic Cardiomyopathy E-Book

Barry J. Maron

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 225

Veröffentlichungsjahr: 2013

Beschreibung

Written by the authority on hypertrophic cardiomyopathy (HCM) and an HCM patient, and fully endorsed by the Hypertrophic Cardiomyopathy Association (HCMA), the leading advocacy and support organization, the 3rd Edition of this best-selling guide offers unparalleled insight into all aspects of living with and treating HCM.

Accessible and practical, A Guide to Hypertrophic Cardiomyopathy For Patients, Their Families and Interested Physicians 3rd Edition:

• Answers the most pressing questions posed by patients, their families, and non-specialists
  health professionals involved in their care
• Covers everything from what is HCM and initial diagnosis of this increasingly prevalent
  condition to the latest treatment options
• Reflects the first-ever HCM guidelines published by the American Heart Association in 2011

Leseprobe

Contents

Acknowledgments and Dedications

Foreword

Introduction: Tips for using this book

What is hypertrophic cardiomyopathy (HCM)

Historical perspective and names

How common is HCM?

What is the cause of HCM?

Structure of the heart

The normal heart

The heart in HCM

Heart conditions that can mimic HCM

Heart function in HCM

Left ventricular outflow obstruction

When does HCM develop?

Gender and race

What are the symptoms of HCM?

Shortness of breath

Chest pain

Fatigue

Palpitations

Lightheadedness, near-fainting, and fainting

How is HCM diagnosed and what tests are used?

Physical examination

Echocardiogram

Electrocardiogram (ECG)

Cardiovascular magnetic resonance imaging (MRI or CMR)

Genetic testing

Other tests that may be useful in assessing HCM in selected patients

Cardiac catheterization

Electrophysiological studies

Exercise testing

Ambulatory ECG monitoring

Radionuclide studies

Inaccurate diagnosis

General outlook for patients with HCM

Complications of HCM

Arrhythmias

Heart failure

The problem of sudden death

Endocarditis

Aneurysms in HCM

Advanced heart failure (“end-stage” phase)

Special considerations: athletes and sports activities

Treatments for HCM

Medical management

Implantable defibrillators

Special considerations for implantable defibrillators

Surgery

Alcohol septal ablation (nonsurgical myectomy)

Heart transplantation and end-stage HCM

Obstructive sleep apnea and HCM

Gene therapy and stem cells

Automated external defibrillators (AEDs)

HCM as a chronic disease: Is a cure available?

Are you newly diagnosed?

Adapting psychologically to HCM

Family screening

What about having children? Pregnancy and delivery

Routine medical care

Diet

Exercise

Alcohol

Sexual activity/erectile dysfunction

Flu vaccination

Weight management and obesity in HCM

Other restrictions

Community screening for HCM

Community outreach

Driving

Traveling

Military service

Social security benefits

Family and Medical Leave Act

Health insurance

Life insurance

Students

HCM Centers

Support and advocacy groups (HCMA)

What research is being conducted?

The 36 most frequently asked questions about HCM that are addressed to the HCMA by patients, caregivers, and family members

Glossary

Further reading

Hypertrophic cardiomyopathy association

Membership application

Index

This edition first published 2014 © 2014 by John Wiley & Sons, Ltd

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Library of Congress Cataloging-in-Publication Data

Maron, Barry J. (Barry Joel), 1941- author.    A guide to hypertrophic cardiomyopathy : for patients, their families, and interested physicians / Barry J. Maron, Lisa Salberg. – Third edition.         p. ; cm.    Preceded by: Hypertrophic cardiomyopathy / by Barry J. Maron, Lisa Salberg. 2nd ed. 2006.    Includes bibliographical references and index.

    ISBN 978-0-470-67504-5 (pbk. : alk. paper) – ISBN 978-1-118-72549-8 – ISBN 978-1-118-72551-1 – ISBN 978-1-118-72552-8 (epdf) – ISBN 978-1-118-72553-5 (epub)    I. Salberg, Lisa, author. II. Maron, Barry J. (Barry Joel), 1941- Hypertrophic cardiomyopathy. Preceded by (work): III. Title.    [DNLM: 1. Cardiomyopathy, Hypertrophic–Popular Works. 2. Patient Education as Topic–Popular Works. WG 280]    RC685.H9    616.1′24–dc23

2013026489

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover image: Cover image courtesy of the authors.Cover design by Andrew Magee Design Ltd.

Acknowledgments and Dedications

I would like to acknowledge the constant, unwavering, and good-naturedsupport that made this book (and the many HCM papers) possible over40 years from my wife, Donna, as well as our 2 sons, Dr. Martin Maron and Dr.Bradley Maron, both cardiologists in Boston. I also wish to recognizeour2 grandchildren, Alexis (age 9) and Jack ( age 8), both brilliant and currently preparing applications to medical school and the MCAT examination.

Barry J. Maron, MDDirector, Hypertrophic Cardiomyopathy CenterMinneapolis Heart Institute FoundationMinneapolis, MN, USAAdjunct Professor of MedicineTufts University School of MedicineBoston, MA, USAAdjunct Professor of MedicineMayo Medical SchoolRochester, MN, USA

*****

To those in my family lost to HCM – Dad, Lori, Tom, Alice, Grandpa Larry, Great Grandmother Mary, and others. To those who are living with clinical HCM – Becca, Stacey, John, and Patty. To those who carry the gene for HCM and wonder if it will someday impact them. To my larger HCMA family it is my sincere wish that this book aids in global understanding that one day leads to a cure so other families do not suffer as ours has.

Thank you to Kelly DeRosa, Carolyn Willis and the Board of Directors (past and present) for their dedication to the HCMA and our mission.

To Adam and Becca I love you both to the moon and back… Always.

Lisa SalbergFounder and CEO Hypertrophic Cardiomyopathy Association

Foreword

More than a half century ago, when I was a young cardiologist at the National Institutes of Health (NIH), my colleagues and I encountered two young men with obstruction to the outflow of blood from the heart’s main pumping chamber, the left ventricle. The condition was quite mysterious since the cause of the obstruction was not clear and the available medical literature was unhelpful. With the passage of time, our group at the NIH and other cardiologists and cardiovascular surgeons around the world recognized an increasing number of such patients and learned that this condition, now called hypertrophic cardiomyopathy (HCM), could present in a wide variety of ways. However, it was thought at first that obstruction was a sine qua non of HCM and that the prognosis was guarded.

As a result of extensive and carefully conducted research by many talented scientists and clinicians, the veil surrounding this condition has been lifted, and we now know that rather than a medical curiosity, HCM is, in fact, the most common genetic cardiac disease. It occurs in approximately 1 of every 500 persons, more than a half million patients in the United States alone. The abnormal genes responsible in the majority of patients with HCM have been discovered and can be tested for. Screening and diagnosis can be accomplishedreadily with an ultrasound examination. Perhaps most important, it has beenestablished that most patients can lead normal or near normal lives. Management can be “tailored” to individual patients; many require nothing more than lifestyle modification and careful follow up examinations. In other patients symptoms can be managed with commonly used drugs, such as the familiar beta blockers. Serious disturbances of cardiac rhythm can now be aborted with an implanted defibrillator. An operation, surgical myomectomy, pioneered at the NIH more than fifty years ago, is reserved for patients with severe symptomatic obstruction and has improved steadily over the years. The risk of the procedure is now very low when it is carried out in experienced institutions. Alcohol septal ablation, carried out in the cardiac catheterization laboratory, is an alternative treatment of obstruction. Both procedures must be performed by experts.

This exceptionally well written “short book” on HCM describes the nature of the disease, the implications of genetic transmission, as well as the methods of screening, diagnosis and estimating prognosis. All forms of treatment, their indications and risks are discussed. Importantly, this book provides useful recommendations on lifestyle, sports and pregnancy.

The authors bring their extensive experience to this book. Dr. Maron has devoted his professional life to the study of and research into HCM and is considered a world authority on this condition. He shares his immense knowledge with the reader. Ms. Salberg, a patient with HCM, who is the founder and President of the HCM Association, provides the critically important perspectives of patients and their families. This lucid and understandable book will be of enormous value to patients with HCM, their families and caregivers, including physicians. Dr. Maron and Ms. Salberg deserve profound thanks for devoting their effort and talent to this important project.

Eugene Braunwald, M.D.Brigham and Women’s HospitalHarvard Medical SchoolBoston, Massachusetts

Introduction: Tips for using this book

If you are reading this book, you probably fall into three potential groups: (1) you have HCM, (2) a friend or relative has HCM, or (3) you are a healthcare provider. An effort has been made here to inform each of these groups about HCM in language that is only as scientific as necessary yet at the same time comprehensive, up to date, and complete. Each section of the book is similar with a narrative explanation of the topic and a boxed summary message, where appropriate, at the end of each section. This is intended as a “take home message” to patients and families.

As with the prior two editions, this updated version of the book is a collaboration between Dr. Barry J. Maron, an authority with a unique interest in HCM over almost 40 years, and Lisa Salberg, a patient with HCM and the Founder and CEO of the Hypertrophic Cardiomyopathy Association (HCMA) – a patient advocacy organization devoted to this disease. Therefore, this book blends ­scientific data with a first person perspective of this disease.

HCM patients (and their cardiologists) found prior editions of the book helpful and enlightening by offering clarity and guidance. This is particularly important for a complex disease such as HCM, which has attracted so much misunderstanding and uncertainty over the last five decades.

Disease Principles for HCM:

HeterogeneityUnpredictabilityOften without absolute certainty

What is hypertrophic cardiomyopathy (HCM)

Cardiomyopathy is a general term describing any condition in which the heart muscle is structurally and functionally abnormal (the heart itself is, of course, a specialized type of muscle). While there are many types of cardiomyopathy (e.g., dilated, restrictive, and right ventricular), many of which are genetic and familial, we are concerned here with only hypertrophic cardiomyopathy (HCM).

HCM is a genetic disease affecting the heart muscle. The most consistent feature of HCM is excessive thickening (hypertrophy) of that portion of the heart known as the left ventricle. In quantitative terms, hypertrophy is usually defined as a wall thickness of 15 mm or more when measured by ultrasound (echocardiogram) or cardiac magnetic resonance imaging (MRI), but any wall thickness (including normal) is consistent with the presence of a gene causing HCM. The consequences of HCM to patients are related, in part or solely, to the abnormally thickened left ventricular heart muscle, which in turn is a consequence of the basic genetic defect. Hypertrophy may be widespread throughout the left ventricle, but may also be more limited in distribution, involving only very small portions of the wall; there is no single pattern of muscle thickening which is “typical” for HCM. The region of the left ventricle which is usually the site of the most prominent thickening is the ventricular septum, that is, that portion of muscle which separates the left and right ventricular cavities. These patterns of hypertrophy do not represent separate disease states, but are all part of the HCM spectrum.

The heart (specifically the left ventricle) may also thicken in other individuals who do not have HCM, either as a result of high blood pressure, obstructive heart valve disease, or even occasionally with prolonged and intense athletic training in certain sports. The type of hypertrophy of the left ventricle associated with high blood pressure is often referred to as secondary (i.e., a consequence of the increased blood pressure). In HCM, however, the muscular thickening of the heart wall is primary – that is, due to a genetic defect and not a reaction to other factors.

Figure 1 The cell structure and architecture of the HCM heart. Diagrams contrast (a) the regular and parallel alignment of cardiac muscle cells characteristic of the normal heart with (b) the irregular, disorganized alignment of cells (“myocardial disarray”) found in some areas of the HCM heart. At the bottom is a micrograph from an HCM heart (i.e., histologic section) showing the disorganized and chaotic ­arrangement of cardiac muscle cells (myocytes) (c).

In addition, when the heart muscle of HCM is viewed under a light microscope, it usually shows several particular abnormalities, the most prominent of which ismyocardial cell (myocyte) disarray or disorganization, in which the normal parallel alignment of heart muscle cells has been lost and many of the muscle cells are arranged in characteristically chaotic and disorganized patterns (Figure 1). It is likely that this cell disarray ­interferes with normal electrical transmission of impulses and predisposes some patients to irregularities of heart rhythm (and sudden death), as well as altering heart contraction. In addition, there are often collagen scars (i.e., areas of fibrosis of various size and extent within the left ventricular wall), which probably result from inadequate blood supply to the heart muscle.

HCM is a common genetic cardiac disease causing the heart wall to thicken without enlarging the cavities.HCM is diverse in its presentation.Some people with thick hearts may not have HCM and instead the thickness may result from high blood pressure, valve disease, or prolonged athletic training.

Historical perspective and names

The first modern description of HCM was in 1958 by a British pathologist, Dr. Donald Teare, who likened the disease to a tumor of the heart. However, there is some evidence that HCM was initially recognized in the mid-1850s by German and French investigators. Nevertheless, over these many years, the condition has been known by a vast number of names. Indeed, this issue of nomenclatureisoften confusing to patients and even some physicians.

Remarkably, HCM has been given over 75 separate names by individual clinicians and scientists over the last 50 years (Figure 2). Literally, no other disease can make that claim. Why has this occurred? The principal reason for the proliferation of names undoubtedly has been the clinical heterogeneity and diversity with which HCM is expressed, a major point in ultimately understanding this disease. Also, since very few cardiologists have treated large numbers of patients with HCM, they often came to regard the overall disease based solely on their personal (and sometimes limited) experiences.

Figure 2 Hypertrophic cardiomyopathy has acquired many names (about 75) in four decades, which primarily reflects the diversity with which the disease is expressed. Hypertrophic cardiomyopathy (HCM) is the preferred name at this time.

Many of the alternate names for HCM emphasize obstruction to left ­ventricular outflow, which is a highly visible feature of the disease. Obstruction is probably present under resting conditions in just 25% of all patients; however, about 70% of all HCM patients have the capacity to ­generate obstruction, either at rest or (if not present at rest) when provoked by physiologic exercise. Therefore, names for this disease in the past have included idiopathic hypertrophic subaortic (stenosis) (IHSS), which was the first popular term used in the United States (“stenosis” means obstruction). The same can be said for hypertrophic obstructive cardiomyopathy (HOCM), which is still widely used in the United Kingdom. Indeed, you may well hear your disease referred to by more than the currently accepted designation –HCM.

Indeed, virtually all HCM experts and other cardiovascular specialists now regard HCM as the single best name for the broad disease spectrum. The term combines hypertrophy (which is the diagnostic marker in most patients) with the fact that this disease is a cardiomyopathy (or heart muscle disorder), and furthermore excludes specific reference to obstruction (which is not present in all patients). Therefore, the terms “HCM with obstruction” or “HCM without obstruction” are preferred.

HCM is a genetic disease based on the recognition 20 years ago that it is caused by mutations in genes coding proteins in the heart muscle. It is also a familial disease because it is transmitted to every generation as a dominant trait (i.e., about 50% of each generation are at risk). HCM is usually inherited, but there is also a phenomenon of de novo mutation when the disease (and mutation) appears for the first time in a family. It is probably not proper to consider HCM a congenital heart disease since it is only the disease-causing mutation which is always present from birth.

HCM has had many names in the past.Hypertrophic cardiomyopathy or “HCM” is the preferred terminology.

How common is HCM?

HCM has had a misleading reputation as a rare disease. It is global in ­distribution, reported from all continents and more than 50 countries. However, a number of recent population studies from the United States and elsewhere in the world show that HCM is a much more common disease thanpreviously regarded. It is now estimated that at least about 1 in 500 indivi­duals within the general population are affected by this disease, equivalent to about 750,000 Americans (Figure 3). HCM is truly a global disease and these prevalence figures come from populations as diverse as the United States, Japan, Africa, and China. These figures relate to adults in whom the disease is recognized by echocardiography (i.e., by visualizing the thickening of the left ventricular wall). However, many other children and adults could carry a mutant gene for HCM and not be easily detectable by echocardiography or not come to clinical recognition for a variety of reasons (including absence of a heart murmur and obstruction), and therefore may be completely unaware of their diagnosis. Indeed, the 1 in 500 prevalence figure is likely to be anunderestimategiven the large number of genetically affected individuals in HCM families with little or no overt clinical evidence of the disease.

Figure 3 The reported prevalence of 1:500 for HCM is based on actual population data from different parts of the world.

Indeed, the currently recognized HCM patient population has been ­likened to the “tip of the iceberg,” with most affected patients undiagnosed and “below the surface” (Figure 4). This helps explain why HCM seems so uncommon in cardiology practice, that is, why cardiologists so often tell HCM patients that they only occasionally see this condition.

The large number of names used to describe HCM may be one factor responsible for the perceived low visibility of HCM in the public sector relative to other less common diseases. In fact, HCM is much more common, and has more impact on the public health, than more visible noncardiac conditions such as cystic fibrosis, multiple sclerosis, muscular dystrophy, and amyotrophic lateral sclerosis (ALS; Lou Gehrig disease), or cardiovascular diseases such as Marfan syndrome (Figure 5). These other conditions are truly rare, occurring in only 1:10,000 or less of the general population while HCM is the most common genetic heart disease and most frequent cause of sudden death in the young – occurring in 1:500 people (Figure 5).

HCM occurs throughout the world (Figure 6), with most of the scientific interest and reports from North America (United States and Canada), the Far East (Japan, China, Australia), and Europe (United Kingdom, Italy, France, Germany, Switzerland), although there is increasing attention to HCM in Brazil, Argentina, Chile, Israel, and New Zealand. HCM appears to be remarkably similar with regard to its clinical presentation, heart structure, clinical course, and prognosis in patients from these diverseareas of the world. One relatively minor exception is the apical form ofHCM with wall thickening localized to the tip [apex] of the left ventricle, always without obstruction, which seems to be more common in Japan – a distinction which could reflect unique racial, ethnic, and/or environmental factors. This structural form is not a separate disease entity and also occurs in 3% of US (non-Asian) patients, due to the same mutations that cause other forms of HCM.

HCM is common; 1 in 500 people in the general population have HCM but many more may carry the gene and not be aware.HCM affects people of many nationalities, both genders, and all ages.

Figure 4 The HCM patients who are currently recognized clinically represent the “tip of the iceberg” – that is, a minority of the overall HCM population. Therefore, most HCM patients remain undiagnosed.

Figure 6 HCM is a global disease. The expression of HCM throughout the world is largely the same.

What is the cause of HCM?

As emphasized earlier, HCM is a genetically transmitted and usuallyfamilial condition. The pattern of inheritance of HCM is known asautosomal-­dominant, which means that the disease (and the mutant gene) occurs in about 50% of the relatives in each consecutive generation (Figure 7). Therefore, the likelihood of an affected parent transmitting the abnormal gene to their child is statistically about one in two. However, autosomal-dominant ­inheritance does not necessarily mean that in each family if there are four offspring, two must be affected – only that this is the statistical probability. In reality, it could be zero of four or even four of four offspring who will carry the mutant gene. In addition, some individuals with this disease appear to be “sporadic” cases – that is, there are no other relatives in the family known to have evidence of HCM. There is always the possibility of ade novo(new) mutation – that is, the first member of the family with the mutant gene and expressed disease.

Figure 7 Family tree. Shown here are four generations of a family affected by HCM. There is a typical autosomal-dominant inheritance in which the condition is ­transmitted from one generation to another. In each generation, every offspring of an affected person has statistically a 50% chance of inheriting the gene or disease.

Genetic “skipping” of a generation is rare but can appear to occur when an individual who is a gene carrier does not have evidence of HCM on the echocardiogram. In such a circumstance, the defective gene does not actually “skip” a generation – but in reality the HCM gene in that individual simply does not express itself fully so that evidence of the disease cannot be visualized with the echocardiogram or MRI (known asincomplete penetrance).

A multitude of more than 1500 mutations in 11 genes, necessary for the development and contraction of heart muscle cells (in units calledsarcomeres), have been mapped and isolated from members of families with HCM. The 11 genes currently known to cause HCM are (1) beta-myosin heavy chain; (2) myosin-binding protein C; (3) troponin-T; (4) troponin-I; (5) ­troponin-C; (6) alpha-tropomyosin; (7) and (8) essential and regulatory myosin light chains; (9) actin; (10) actin-2; and (11) myozenin-2 (Figure 8).

Figure 8 Genetic basis of HCM. Diagram of the sarcomere, the primary unit of contraction of the heart muscle, showing the location of the genes known to be responsible for HCM, with their frequency noted in parentheses.

Most commonly, HCM is caused by the first two genes on this list while the other nine genes each account for only a small fraction of the patients. Indeed, this is one of the reasons HCM is widely regarded as a diverse and heterogeneous disease. Additional genes and mutations responsible for HCM will be identified in the future since the known mutant genes account for only about 50% of the overall patient population. Not finding a gene mutation does not mean that the test subject does not have HCM, only that they do not carry one of the known mutations.

A mutation is a defect in the deoxyribonucleic acid (DNA) code, the protein structure of the gene. These DNA abnormalities may take many forms, but some can be likened to a “spelling error” in the genetic code of DNA, such as displacement in the order or sequence of just one of the many amino acids (the individual “building blocks” of the gene protein). Indeed, it is perhaps surprising that such seemingly minor-appearing abnormalities in the gene sequence can make such a profound difference in the structure of the heart, as occurs in HCM.

Patients often ask about the cause of their mutation, particularly if the gene abnormality has apparently appeared for the first time in a family. This consideration usually arises when a newly diagnosed child has both parents with normal echocardiograms and no evidence of HCM. Keep in mind that the genetic predisposition to HCM does not always trace back many generations in the same family, but may occur spontaneously for the first time in a member of the most recent generation. At present, the environmental factors that trigger HCM mutations are unknown.

The discovery of the gene defects responsible for HCM (more than 20 years ago) is a major step toward understanding the basic cause of HCM. In addition, laboratory DNA diagnosis from a blood test is now available for the first time commercially from four companies (Table 1