Date: 10 Mar 2003 23:46:06 To: claerbout _AT_ Stanford.EDU From: Mailer-Daemon@email-delivery.galegroup.com Subject: A comprehensive look at cardiomyopathy. Delivery-Date: Mon Mar 10 20:46:15 2003 Source: Patient Care, June 15, 1999 v33 i11 p210. Title: A comprehensive look at cardiomyopathy. Author: MARY DESMOND PINKOWISH Subjects: Cardiomyopathy, Dilated - Care and treatment Heart diseases - Care and treatment Cardiomyopathy - Care and treatment Magazine Collection: 99B6039 Electronic Collection: A54966865 RN: A54966865 Full Text COPYRIGHT 1999 Copyright Medical Economics Company. All rights reserved. Information is intended for End Users' personal use only and may not be sold, redistributed, or otherwise used for commercial purposes. ARTICLE CONSULTANTS KANU CHATTERJEE, MD, is Professor of Medicine and Lucie Stern Professor of Cardiology, University of California, San Francisco, School of Medicine. MARIA ROSA COSTANZO, MD, is John H. and Margaret V. Krehbiel Professor of Cardiology, Rush Medical College, and Medical Director, Rush Heart Failure Center, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Ill. Because cardiomyopathy can progress to heart failure, no complaint of dyspnea, its major symptom, should be disregarded. Primary care physicians have a pivotal role in diagnosis and the search for reversible causes. The 3 major forms of cardiomyopathy--dilated, hypertrophic, and restrictive-- take a high toll. Cardiomyopathy is second only to coronary artery disease (CAD) as the most common direct cause of sudden death. [1] Dilated cardiomyopathy in its various forms (idiopathic, familial, ischemic, valvular, and hypertensive) is the leading cause of congestive heart failure (CHF), which affects nearly 5 million Americans. Hypertrophic cardiomyopathy is the number 1 cause of sudden death in competitive athletes aged 35 and younger in the United States and has a prevalence of 2 per 1000 in this age-group. The dilated and hypertrophic forms of cardiomyopathy are far more common than restrictive cardiomyopathy, and a discussion of their diagnosis and treatment will comprise the majority of this article. Although many aspects of treatment remain controversial, heart failure specialists have 3 cardinal rules for the diagnosis and management of patients with cardiomyopathy. They are * Never disregard a patient's complaint of dyspnea * Include an echocardiographic examination in the workup * Prescribe angiotensin-converting enzyme (ACE) inhibitors as first-line therapy for most patients with dilated cardiomyopathy. DIAGNOSING DILATED CARDIOMYOPATHY The possibility of dilated cardiomyopathy is raised when patients report any of its 3 cardinal symptoms, which usually have a gradual onset: dyspnea, fatigue, weight gain. Noncongestive symptoms sometimes include palpitations, anginal pain, syncope or near-syncope, light-headedness, nausea, or abdominal pain or distention. Symptom onset is preceded by an asymptomatic period, during which the condition may be suspected because of a history of ischemic heart disease or is detected fortuitously. Signs that may be present include narrow pulse pressure, tachycardia, atrial fibrillation, jugular vein distention, ascites, peripheral edema, a loud third heart sound, or, in patients with primarily diastolic dysfunction, a loud fourth heart sound. A systolic murmur may also be audible. The diagnosis is confirmed by an ejection fraction of less than 40% and evidence of ventricular dilatation or an abnormally large end diastolic dimension of the ventricle. Some controversy exists about the exact ventricular dimensions that should be used in diagnosis, but a general consensus exists that an end diastolic dimension of 6.5 cm or greater defines ventricular dilatation. Chest films, although routine and necessary, are often only moderately helpful in patients with suspected dilated cardiomyopathy. In only about 50% of patients, even ones with low ejection fractions, the film reveals either an enlarged heart or pulmonary congestion. The results of an ECG are nonspecific, perhaps showing ST-segment or T-wave abnormalities. The echocardiogram is probably the most cost-effective test in this situation. It provides information about the dimensions of each heart chamber, usually showing dilatation of the left ventricle. It will also reveal whether a pericardial effusion is present. The echocardiogram provides information about the integrity and function of cardiac valves; valvular abnormalities frequently contribute to the development of dilated cardiomyopathy and are an important reversible cause of the disorder. The ejection fraction can be determined based on information provided by the echocardiogram. Information about myocardial contractility, also derived from the echocardiogram, may suggest an etiology for cardiomyopathy. Diffuse global hypokinesia, for example, suggests idiopathic disease. In contrast, segmental focal wall motion abnormalities are more common in patients with ischemic disease. More than half of patients who have dilated cardiomyopathy have ischemic disease, frequently with a history of MI. It should be realized, however, that segmental wall motion abnormalities may be present in nonischemic dilated cardiomyopathy and that diffuse global hypokinesia may occur in patients who have ischemic dilated cardiomyopathy. Other imaging and diagnostic modalities are used less widely. MRI, for example, is rarely helpful in this situation. Radionuclide ventriculography may be useful if the findings of the echocardiogram are equivocal. Angiography is an important step when ischemic or valvular disease is suspected. If cardiomyopathy is ischemic in origin, other tests, especially cardiac catheterization, may be necessary to evaluate the extent of significant obstructive CAD. Cardiac biopsy is usually performed only in the few patients with possible sarcoidosis or other cause of restrictive cardiomyopathy or specific cardiac muscle disease. Cardiologists caution against assuming that a normal or near-normal ejection fraction (40% or greater) rules out dilated cardiomyopathy or heart failure. Relatively normal systolic function does not confirm that cardiac function in general is normal. A large proportion of older patients in particular may have diastolic failure with little or no systolic failure, and a patient with dyspnea and an ejection fraction of 40% could well have moderate to severe diastolic dysfunction. Nuclear medicine techniques often aid the diagnosis, and echocardiography may reveal signs of diastolic dysfunction, which is treated much as systolic dysfunction is. Some laboratory testing is also required. Tests of liver function, fasting plasma glucose, and thyroid function, as well as determination of the lipid profile can be important in guiding adjunctive therapy. Reversible causes of cardiomyopathy Moving too quickly to label dilated cardiomyopathy as idiopathic is a major pitfall in the diagnostic workup. The primary care physician has an important role in the search for reversible causes of cardiomyopathy. In a patient with dilated cardiomyopathy but without evidence of ischemia, several other possibilities merit consideration. Valve disease is a leading contender, and the patient may be a candidate for valve replacement. Among patients with ischemic disease, those who undergo a revascularization procedure may experience an improvement in cardiomyopathy. Alcohol abuse is another common cause of cardiomyopathy and should be considered in any patient who uses alcohol, even in the absence of signs of malnutrition and especially when liver function test results are abnormal. The progress of alcohol-related heart disease may be slowed or even reversed in patients who stop drinking. Cocaine use has also been implicated in some cases of cardiomyopathy. Possibly reversible metabolic causes of cardiomyopathy include selenium deficiency, hypophosphatemia, and hypocalcemia. Acute or chronic infections with viruses or bacteria probably account for at least a small percentage of dilated cardiomyopathy cases. Uncontrolled tachycardia or atrial fibrillation is an important cause of dilated cardiomyopathy. Restoration of sinus rhythm and ventricular rate control can lead to highly significant improvements in symptoms and function. TREATING PATIENTS WITH DILATED CARDIOMYOPATHY The single most important goal of treatment is the prevention of CHF. If CHF is already present in a patient with dilated cardiomyopathy, additional goals include the improvement of symptoms, ventricular function, and prognosis. Treatment is accomplished in part by interrupting the progression of myocardial dysfunction (see Table 1). The first-line treatment of left ventricular dysfunction, and dilated cardiomyopathy in particular has changed in recent years. Diuretics, formerly the mainstay of therapy, now have a distinctly secondary position. Digoxin is reserved for patients who have progressed to heart failure. General principles of treatment include the following: * Patients who have symptoms such as exertional dyspnea and fatigue should be treated initially with ACE inhibitors plus a diuretic. * Most other patients are candidates for ACE inhibitor treatment, as well. * Diuretics should not be used as monotherapy in patients with dilated cardiomyopathy, with or without heart failure. * Some patients are candidates for treatment with a [beta]-blocker. * Reversible causes of heart failure, faulty valves for example, should be corrected. Patients with ischemic disease may benefit from revascularization. All-important ACE inhibitors Cardiologists emphasize that unless a specific contraindication exists, ACE inhibitors are the mainstays of treatment in patients with symptomatic or asymptomatic dilated cardiomyopathy. In this situation, ACE inhibitors act as potent vasodilators, causing hemodynamic and clinical improvements by reducing afterload. As demonstrated by the results of the Study of Left Ventricular Dysfunction (SOLVD), progression to heart failure is reduced in patients with cardiomyopathy who are treated with ACE inhibitors. This conclusion was especially true of those with ejection fractions of less than 35%. [2] Patients should understand at the outset that symptomatic improvements may not be apparent until weeks after the start of treatment. In fact, although ACE inhibitor therapy may significantly reduce progression to heart failure, no symptomatic improvements may be evident at all. [3] The benefits of ACE inhibitors are probably a class effect, so selection of an appropriate agent is rarely a problem. Nonetheless, many cardiologists prefer to use the agents and dosages that have been shown to be effective among patients enrolled in large clinical trials. The 2 most widely used agents are captopril and enalapril, although quinapril and ramipril have also been used successfully. ACE inhibitors are used increasingly in this group of patients, but many who are treated in primary care practices receive dosages that are too low to be effective. Although dosing should start low to prevent hypotension, dosages must be increased to be effective. Cardiologists emphasize that underdosing of ACE inhibitors may be the single most common error made in the treatment of patients with cardiomyopathy and/or heart failure. Examples of appropriate ACE inhibitor maintenance dosages are * Captopril, 50 mg/d in 3 divided doses * Enalapril, 20 mg once daily * Lisinopril, 20 mg once daily. Intractable cough is a common reason cited for discontinuing ACE inhibitor therapy. One of the consultants for this article notes, however, that in 60% to 70% of the patients referred to her clinic because of cough apparently caused by ACE inhibitor treatment, the respiratory symptoms are instead traced to noncompensated heart failure. When this not the case, however, an angiotensin-II receptor blocker (ARB) can be used as an alternative to an ACE inhibitor. [4] ACE inhibitors and ARBs seem to be equally effective, at least in patients with moderate or severe heart failure, although far more clinical experience has accrued with ACE inhibitors. [5] Diuretics, digoxin, [beta]-blockers These agents are no longer the primary treatment for patients with cardiomyopathy and are not used as monotherapy, but diuretics remain an important facet of treatment. By reducing fluid retention, they substantially improve symptoms in most patients. Proper dosing of diuretics is key to the success of treatment and may require the advice of a heart failure specialist. ACE inhibitors and [beta]-blockers are more effective when adequate dosages of diuretics are used. On the other hand, diuretic dosages that are too high, especially in a patient taking an ACE inhibitor, increase the risk of hypotension. In patients with mild congestive symptoms, spironolactone, alone or in combination with a thiazide diuretic such as hydrochiorothiazide or metolazone, is a reasonable choice. Frequent potassium determinations are required, of course, when thiazides are used. Worsening hyperlipidemia can be a complication of treatment, especially when these agents are used with an ACE inhibitor. For patients with more severe congestive symptoms, a loop diuretic, such as furosemide, may need to be added. For patients who still have poor symptom control with an ACE inhibitor and diuretic, the positive inotrope digoxin may be added to the regimen. Digoxin improves symptoms, quality of life, functional capacity, and exercise tolerance. According to the results of the recent Digitalis Investigation Group (DIG), however, the drug has no positive effect on survival and may increase mortality associated with other causes. [6,7] [beta]-Blockers are also used increasingly in patients with cardiomyopathy or class II or III heart failure, and the recent Cardiac Insufficiency Bisoprolol Study (CIBIS-II) showed a significant mortality benefit in heart failure patients treated with this agent. [8] [beta]-Blockers may be particularly useful in patients who cannot tolerate ACE inhibitors. Consultation with a subspecialist is urged, however, because not all patients are candidates for treatment. In those for whom [beta]-blocker treatment is indicated, the dosage, which varies widely for different agents, must be carefully selected and slowly titrated, with increases coming only at 2- to 3-week intervals. In general, the lowest possible dosage is used. Evidence accumulated to date suggests that the benefits of [beta]-blockers are a class effect. Antiarrhythmic agents Arrhythmias are common among patients with dilated cardiomyopathy and are treated aggressively. A crucial point to remember is that type I antiarrhythmics, including quinidine, procainamide, lidocaine, encainide, flecainide, and propafenone, among others, must not be considered for long-term use in patients with cardiomyopathy. Type I antiarrhythmic agents are proarrhythmic in this situation, and they become more so as the ejection fraction decreases. The antiarrhythmic agent of choice in patients with dilated cardiomyopathy is the class III agent amiodarone. In patients with atrial fibrillation, cardiologists advise great persistence in restoring sinus rhythm, whether by drugs, cardioversion, or other means. Cardioversion is more likely to be successful in patients with cardiomyopathy when optimal dosages of amiodarone are used before cardioversion is attempted. Patients who do not respond to transthoracic cardioversion may benefit from transesophageal cardioversion. Ablation of the atrioventricular node and pacemaker insertion is an option for patients whose arrhythmia fails to respond to electrical cardioversion. Even more advanced options, such as surgery to reshape the ventricles, can be exercised when the patient is evaluated by physicians at a heart failure treatment unit. Nutrition and lifestyle In general, patients with dilated cardiomyopathy should be advised to follow nutrition, medication, and lifestyle guidelines appropriate for any patient with cardiac disease. Smoking cessation, BP control, and improvements in the lipid profile (preferably with the help of a statin drug) are priorities. The principal dietary restrictions concern sodium and fluid intake in patients with congestive symptoms. A prudent low-fat diet is appropriate for all patients. They should also be encouraged to increase their consumption of fruits and vegetables containing vitamins E and C and other antioxidants. Some patients with severe CHE tend to lose weight, primarily because of the adverse actions of the hormone tumor necrosis factor-[alpha] (TNF-[alpha]). These patients, who tend to lose considerable skeletal mass, should be encouraged to increase their protein intake, if possible. Conditioning of skeletal muscles reduces stress on the myocardium. So, in sharp contrast to advice given in the past, patients with dilated cardiomyopathy are encouraged to adhere to specially designed exercise prescriptions. These typically specify low to moderate intensity aerobic activity that can be accomplished consistently. Mild to moderate physical activity has many benefits in patients with heart disease, of course. In patients with cardiomyopathy or heart failure, one of its most important beneficial effects, though, is to reduce abnormal autonomic tone. A typical exercise prescription might instruct the patient to walk or work out on a stationary bicycle for 15 to 20 minutes 4 to 5 times a week. Patients should be cautioned against exercising to the point of overexertion, however, and to avoid isometric exercise. Bed rest is not recommended for any but the most functionally impaired patients. HYPERTROPHIC CARDIOMYOPATHY Hypertrophic cardiomyopathy is associated with a 2% to 3% annual mortality rate in patients aged 30 years and younger. It accounts for approximately one third of sudden deaths in young athletes and nearly half of all sudden deaths in competitive athletes aged 35 and younger (see Figure 1, page 224). Nonetheless, recent studies from Japan and Minnesota suggest that the course of hypertrophic cardiomyopathy may be less dire than often assumed, especially in asymptomatic patients. [9,10] The most significant findings from these studies included the following: * Rates of annual cardiac mortality and sudden death alone were lower in asymptomatic patients than symptomatic ones. * Survival is apparently worse in patients identified with hypertrophic cardiomyopathy in childhood. * Independent predictors of mortality included atrial fibrillation, basal outflow obstruction of at least 30 mm Hg, and left ventricular wall thickness exceeding 25 mm. * Some misconceptions about the prognosis of hypertrophic cardiomyopathy may reflect the fact that most studies of the condition have been conducted at tertiary care centers and were not community-based. Hypertrophic cardiomyopathy is an incompletely understood, multifactorial disease, however, and it is second only to CAD as a cause of sudden death. More than 25% of deaths in patients with hypertrophic cardiomyopathy are classified as sudden. [1] Since its first description in the 1950s, hypertrophic cardiomyopathy has gone by various names, including asymmetrical hypertrophic cardiomyopathy, hereditary cardiovascular dysplasia, and muscular aortic stenosis, many of which reflect confusing information about the etiology, diagnosis, and natural history of the disease. Recent investigations have confirmed what was long suspected: Hypertrophic cardiomyopathy is a genetically transmitted condition with an autosomal dominant inheritance pattern. Any one of several gene mutations resulting in defective sarcomere proteins can lead to hypertrophic cardiomyopathy, and all result in defective sarcomere proteins. [11] Pathophysiologic features that are characteristic of hypertrophic cardiomyopathy include * Left ventricular diastolic dysfunction * Left ventricular outflow obstruction * Supraventricular or ventricular arrhythmias * Atrial fibrillation and ventricular tachycardia (VT). Some or all of these features may be present in a patient with hypertrophic cardiomyopathy and, by definition, all affected patients have a thickened left ventricular wall and a normal-sized ventricular cavity. The nonobstructive form of the disorder, in which no subaortic pressure gradient exists, accounts for about 75% of cases. Suspicion and diagnosis The possibility of hypertrophic cardiomyopathy is a major concern when a young patient with a normal-sized heart presents with symptoms of heart failure or reports exertional syncope or near-syncope. A family history of sudden death is even more ominous. Often, the ECG reveals signs of left ventricular hypertrophy, including nonspecific ST-segment and T-wave aberrations. An echocardiographic examination that demonstrates asymmetric thickening of the left ventricular wall is usually diagnostic. If a subaortic pressure gradient is present, outflow obstruction is often apparent, as is evidence of mitral regurgitation. Risk stratification Studies of the natural history of hypertrophic cardiomyopathy have demonstrated that the morbidity and mortality risks vary in different patients (see Figure 2). Patients at low risk include those who are asymptomatic and have the following characteristics: * Little or no ventricular hypertrophy * No evidence of ventricular hypertrophy on Holter monitoring * No hypotensive exercise response * No family history of sudden death or hypertrophic cardiomyopathy. [11] Patients at high risk include those who have ventricular tachycardia, pronounced left ventricular hypertrophy, a family history of sudden death, or a personal history of cardiac arrest or syncope. Lessening the risk of sudden death Hypertrophic cardiomyopathy carries a high risk of sudden death, so prevention is crucial. Upon diagnosis, patients should immediately cease all involvement in competitive sports and avoid strenuous exercise. Consultation with a heart failure specialist is imperative. Some patients may be candidates for treatment with a [beta]-blocker and, occasionally, verapamil. Diuretics benefit patients with significant congestive symptoms. All regimens, however, should be designed in consultation with a heart failure specialist (see "Therapeutic strategies for congestive symptoms in patients with hypertrophic cardiomyopathy," page 228). For patients with atrial fibrillation, which include about 25% of those with hypertrophic cardiomyopathy, amiodarone treatment or electrical cardioversion is recommended, with [beta]-blockers or verapamil given for ventricular rate control. Anticoagulation may also be necessary. Some cardiologists recommend ablation of the AV node and implantation of a dual chamber pacemaker in patients with obstructive hypertrophic cardiomyopathy and ventricular tachycardia. This remains a controversial option, however, and studies are ongoing. Treatment with amiodarone is another possible option, as is ventricular myotomy-myectomy. It is agreed, though, that some treatment, including heart transplantation, should be considered in any patient with an intraventricular pressure gradient exceeding 50 mm Hg. Patients with the more common, nonobstructive form of the disease are not considered good candidates for dual chamber pacing or surgical fixes. As CHF develops, standard CHF treatment is initiated. Transplantation is an option among these patients, as well. Genetic and athletic screening Increasing evidence suggests that although hypertrophic cardiomyopathy has genetic components, the disease has substantial genetic heterogeneity, making test interpretation complex. Families with an affected member; especially siblings of the patient, may want their risks assessed. Direct them to an appropriate center, preferably one recommended by experts at a heart failure specialty treatment center. Only certain genetic testing facilities are capable of performing the appropriate testing at this time. In a 1996 statement on preparticipation screening of competitive athletes, the American Heart Association noted the extreme impracticality and expense of performing echocardiograms on all participants in high school and college athletics. [12] Routine ECG screening was also rejected, in part because of its poor specificity in conditioned athletes. The committee did, however, urge preparticipation examinations for athletes in grades 9 through 12 and college. These should be conducted at 2-year intervals and include a complete medical history and physical examination, including determination of the brachial artery BP. In addition, the patient should be asked about * Exertional chest pain, syncope, or near-syncope * History of heart murmurs or elevated BP * Family history of premature death or cardiovascular disease * History of cardiomyopathy, long QT syndrome, Marfan syndrome, or arrhythmias. The recommended physical examination includes * Precordial auscultation in the supine and standing position, with attention to murmurs suggesting dynamic left ventricular outflow obstruction * Examination of the femoral artery pulses for evidence of coarctation of the aorta * An examination for physical signs of Marfan syndrome * Brachial BP measurement taken while the patient is sitting. RESTRICTIVE CARDIOMYOPATHY Restrictive cardiomyopathy, the least common of the major forms of cardiomyopathy, should be suspected in patients with severe heart failure in the absence of significant systolic dysfunction. Restrictive cardiomyopathy is marked by impaired diastolic filling of the ventricles. The most common cause of restrictive cardiomyopathy in this country is amyloidosis. A decrease in exercise tolerance is the predominant symptom of restrictive cardiomyopathy; dyspnea is far less common. In contrast to other forms of cardiomyopathy, the diagnosis of restrictive cardiomyopathy requires endomyocardial biopsy. If the biopsy sample exhibits evidence of amyloidosis, it is necessary to determine whether this represents primary or secondary disease. Cardiac amyloidosis can be a manifestation of several diseases, including multiple myeloma and hypergammaglobulinemia. Restrictive cardiomyopathy is the presenting feature of multiple myeloma in only 10% of cases, however. MRI and CT scans are sometimes necessary to differentiate restrictive cardiomyopathy from constrictive pericarditis. Treatment for patients with restrictive cardiomyopathy is the province of a heart failure specialist. Typically, patients are prescribed diuretics. ACE inhibitors and calcium antagonists are used cautiously, if at all. Other treatments may be appropriate if restrictive cardiomyopathy is secondary to diseases such as amyloidosis, sarcoidosis, Fabry's disease, or hemochromatosis. Mean survival is approximately 9 years in patients with primary restrictive cardiomyopathy. REFERENCES (1.) Zipes OP. Wellens HJJ. Sudden cardiac death. Circulation. 1998:96:2334- 2351. (2.) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions: the SOLVD Investigators published Correction appears in N Engl J Med. 1992:327:1768]. N Engl J Med. 1992:327:685-691. (3.)Packer M. Cohn JN. Consensus recommendations for the management of chronic heart failure. Am J Cardiol 1 999;83(suppl): 1 A-38A. (4.) Cleland JGF, Swedberg K, Poole-Wilson PA. Successes and failures of current treatment of heart failure. Lancet. 1998;352(suppl):19-28. (5.) Lang PM, Elkayem U, Yallen LG, at al. Comparative effects of losartan and enalapril on exercise capacity and clinical status in patients with heart failure: the Losartan Pilot Exercise Study investigators. J Am Coll Cardiol. 1997:30:983-991. (6.) The effect of digoxin on modality and morbidity in patients with head failure: the Digitalis Investigation Group. N Engl J Med. 1997:336:525-633. (7.) Hauptman Pd. Kelly PA. Digitalis. Circulation. 1 999:99:1265-1270. (8.) The Cardiac insufficiency Bisoprolof Study II (CIBIS-ll): a randomised trial. Lancet. 1999;353:9-13. (9.) Maron BJ Casey SA, Poliac LC. at al. Clinical course of hypertrophic cardiomyopathy in a regional United Staten cohort. JAMA. 1999:261:650-655. (10.) Takagi E, Yarnakado T, Nakano T. Prognosis of completely asymptomatic adult patients with hypertrophic cardiomyopathy. J Am Colt Cardiol. 1999:33: 206-211. (11.) Maron BJ. Hypertrophic cardiomyopathy. Lancet. 1997:350:127-133. (12.) Maron Rd. Thompson PD. Puffer JC, at al. Cardiovascular prepaticipation screening of competitive athletes: a statement for health professionals from the Sudden Death Committee (Clinical Cardiology) and Congenital Cardiac Defects Committee (Cardiovascular Diseases in the Young). American Head Association. Circulation. 1 996;94:850-856. SUGGESTED READING Bristow MR. Why does the myocardium tail? insights from basic science. Lancet. 1998 ):8-14. Cheitlin MD, Al pert JS, Armstrong WF, et al. ACC/AHA guidelines for the clinical application of echocardiography: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography) Developed in collaboration with the American Society of Echocardiography. Circulation. 1997:95: t 666-1744. Cohn JN. Goldstein SC, Greenberg BH, et at. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. N Engl U Med. 1998:339:1810-18 16. Guidelines for clinical use of cardiac radionuclide imaging: report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Radionuclide Imaging). J Nucl Cardiol. 1995:2:1 72-t 92. Guidelines for the evaluation and management of heart failure: report of the American College of Cardiology/American Head Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). J Am Cardiol. 1995:26:1376-1398. Maron BJ, Casey SA, Poliac LC, at al. Clinical course of hypertrophic cardiomyopathy in a regional United States cohort. JAMA. 1999:281:650-655. Pogwizd SM, McKenzie UP, Cain ME. Mechanisms underlying spontaneous and induced ventricular arthythmias in patients with idiopathic dilated cardiomyopathy. Circulation. 1998:98:2404-2414. Sharpe N, Doughty P. Epidemiology of heart failure and ventricular dysfunction. Lancet. 1998:352(suppl 1):3-7. Spirito P. Saidman CE, McKenna WJ, et at. The management of hypertrophic. cardiomyopathy. N Engl J Med 1997:336:775-785. Stevenson LW. Isotropic therapy for head failure. N Engl J Med. 1996:339:1848-1850. Drugs mentioned in this article Wigle ED, Rakowski H, Kimball BP, at al. Hypertrophic cardiomyopathy: clinical spec1mm and treatment. Circulation. 1995:92:1680-1 692. Amiodarone (Cordarone, Pacerone) Bisoprolol (Zebeta) Captopril (Capoten) Digoxin (Lanoxicaps, Lanoxin) Diltiazem (Cardlzem, Dilacor XR, Tiazac) Disopyramide (Norpace) Enalapril (Vasotec) Encainide (Enkaid) Flecainide (Tambocor) Furosemide (Lasix) Hydrochlorothiazide Lidocaine Lisinopril (Prinivil, Zestril) Metolazone (Mykrox, Zaroxolyn) Procainamide (Procanbid, Pronestyl) Propafenone (Rythmol) Quinapril (Accupril) Quinidine Ramipril (Altace) Spironolactone (Aldactone) Verapamil Cardiac hypertrophy: Causes and consequences Signaling pathway Compensatory effects Adrenergic Increased heart rate, contractility, volume expansion, hypertrophy Angiotensin II Volume expansion, hypertrophy Endothelin Hypertrophy TNF-[alpha] Hypertrophy Stretch/Wall stress Volume expansion, hypertrophy Signaling pathway Adverse biological effects Adrenergic Myocyte toxic effects, apoptosis, growth and remodeling, altered gene expression Angiotensin II Apoptosis, growth and remodeling, altered gene expression, collagen deposition Endothelin Growth and remodeling, altered gene expression TNF-[alpha] Apoptosis, inflammation, growth and remodeling, altered gene expression, metalloproteinase activation Stretch/Wall stress Apoptosis, growth and remodeling, altered gene expression Key: TNF-[alpha], tumor necrosis factor-[alpha]. Adapted with permission from Bristow MR. Why does the myocardium fail? Insights from basic science. Lancet. 1998;352(suppl 1):8-14. [less than or equal to]35 years Hypertrophic cardiomyopathy 48% Coronary HD 10% Idiopathic LVH 18% Coronary anomalies 14% Ruptured aorta 7% Unexplained 3% [greater than]35 years Unexplained 5% MVP 5% Valvular HD 5% Coronary HD 80% Hypertrophic cardiomyopathy causes nearly half of all sudden deaths in competitive athletes aged 35 years and younger. In contrast, coronary heart disease accounts for 80% of sudden death in older competitive athletes. Key: HD, heart disease; LVH, left ventricular hypertrophy; MVP, mitral valve prolapse. -- End --