The Cardiomyopathies

Introduction
The cardiomyopathies are a heterogeneous group of entities affecting the myocardium primarily and not associated with the major causes of cardiac disease, ie, ischemic heart disease, hypertension, valvular disease, or congenital defects. Although some have specific causes, many cases are idiopathic. There is now general agreement on a classification based upon general features of presentation and pathophysiology (Table 10-10).

Davies MJ: The cardiomyopathies: an overview. Heart 2000;83: 469.

Franz WM et al: Cardiomyopathies: from genetics to the prospect of treatment. Lancet 2001;358:1627.

1. Primary Dilated Cardiomyopathy

Introduction Essentials of Diagnosis

  • Symptoms and signs of heart failure.
  • ECG may show low QRS voltage, nonspecific repolarization abnormalities, intraventricular conduction abnormalities.
  • X-ray shows cardiomegaly.
  • Echocardiogram confirms left ventricular dilation, thinning, and global dysfunction.

General Considerations
Dilated cardiomyopathies usually present with symptoms and signs of congestive heart failure (most commonly dyspnea). Occasionally, symptomatic ventricular arrhythmias are the presenting event. Left ventricular dilation and systolic dysfunction are essential for diagnosis. A growing number of cardiomyopathies due to genetic abnormalities are being recognized, but these still represent a small minority of cases. Often no cause can be identified, but chronic alcohol abuse and unrecognized myocarditis are probably frequent causes. Amyloidosis, sarcoidosis, hemochromatosis, and diabetes all may present as dilated cardiomyopathies as well as with a restrictive picture. Histologically, the picture is one of extensive fibrosis unless a specific diagnosis is established.

Clinical Findings
A. Symptoms and Signs
In most patients, symptoms of heart failure develop gradually. They may be recognized because of asymptomatic cardiomegaly or electrocardiographic abnormalities, including arrhythmias. The initial presentation may be severe biventricular failure. The physical examination reveals cardiomegaly, S3 gallop rhythm, and often a murmur of functional mitral regurgitation. Signs of left- and right-sided failure may be present on initial examination, a clue to a process involving the heart diffusely.

B. Electrocardiography and Chest X-Ray
The major findings are listed in Table 10-10.

C. Diagnostic Studies
An echocardiogram is indicated to exclude unsuspected valvular or other lesions and confirm the presence of dilated cardiomyopathy. Exercise thallium-201 scintigraphy may suggest the possibility of underlying coronary disease if a large reversible defect is found, but false-positives occur in cardiomyopathy. Cardiac catheterization is seldom of specific value unless myocardial ischemia or left ventricular aneurysm is suspected. The serum ferritin is an adequate screening study for hemochromatosis.

Treatment
Few cases of cardiomyopathy are amenable to specific therapy. Alcohol use should be discontinued. There is often marked recovery of cardiac function following a period of abstinence in alcoholic cardiomyopathy. Endocrine causes (thyroid dysfunction, acromegaly, pheochromocytoma) should be treated. Immunosuppressive therapy is not indicated in chronic dilated cardiomyopathy. The management of congestive heart failure is outlined in the section on heart failure.

Prognosis
The prognosis of dilated cardiomyopathy without clinical heart failure is variable, with some patients remaining stable, some deteriorating gradually, and others declining rapidly. Once heart failure is manifest, the natural history is similar to that of other causes of heart failure. Arterial and pulmonary emboli are more common in dilated cardiomyopathy than in ischemic cardiomyopathy; suitable candidates may benefit from chronic anticoagulation. Those patients whose disease progresses may require treatment for severe dyspnea (see above) and ultimately need high-quality palliative care.

Corrado D et al: Arrhythmogenic right ventricular cardiomyopathy: diagnosis, prognosis, and treatment. Heart 2000;83: 588.

Felker GM et al: Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med 2000;342:1077.

Maisch B et al: Dilated cardiomyopathies as a cause of congestive heart failure. Herz 2002;27:113.

Mohan SB et al: Idiopathic dilated cardiomyopathy: a common but mystifying cause of heart failure. Cleve Clin J Med 2002;69:481.

Piano MR: Alcoholic cardiomyopathy: incidence, clinical characteristics, and pathophysiology. Chest 2002;121:1638.

Wu LA et al: Current role of endomyocardial biopsy in the management of dilated cardiomyopathy and myocarditis. Mayo Clin Proc 2001;76:1030.

————

2. Hypertrophic Cardiomyopathy

Introduction Essentials of Diagnosis

  • May present with dyspnea, chest pain, syncope.
  • Examination shows sustained apical impulse, S4, systolic ejection murmur.
  • ECG shows left ventricular hypertrophy, occasionally septal Q waves in the absence of infarction.
  • Echocardiogram shows hypertrophy, which may be asymmetric; usually shows normal or enhanced contractility and signs of dynamic obstruction.

General Considerations
Myocardial hypertrophy unrelated to any pressure or volume overload tends to impinge upon the left ventricular cavity. The interventricular septum may be disproportionately involved (asymmetric septal hypertrophy), but in some cases the hypertrophy is localized to the apex. The left ventricular outflow tract is often narrowed during systole between the bulging septum and an anteriorly displaced anterior mitral valve leaflet, causing a dynamic obstruction (hence the name idiopathic hypertrophic subaortic stenosis; IHSS). The obstruction is worsened by factors that increase myocardial contractility (sympathetic stimulation, digoxin, postextrasystolic beat) or that decrease left ventricular filling (Valsalva’s maneuver, peripheral vasodilators).

Hypertrophic cardiomyopathy is in some cases inherited as an autosomal dominant trait with variable penetrance caused by mutations of a number of genes, most of which code for myosin heavy chains or proteins regulating calcium handling. It is becoming clear that the prognosis is related to the specific gene mutation. These patients usually present in early adulthood. Others are elderly, and many of those patients have a long history of hypertension. Some cases occur sporadically. BR>
Except in late stages, hypertrophic cardiomyopathy is characterized by a small, hypercontractile left ventricle. Although dyspnea is a common symptom, it results mainly from markedly impaired diastolic compliance rather than systolic dysfunction or outflow obstruction.

Clinical Findings
A. Symptoms and Signs
The most frequent symptoms are dyspnea and chest pain. Syncope is also common and is typically postexertional, when diastolic filling diminishes and outflow obstruction increases. Arrhythmias are an important problem. Atrial fibrillation is a long-term consequence of chronically elevated left atrial pressures and is a poor prognostic sign. Ventricular arrhythmias are also common, and sudden death may occur, often in athletes after extraordinary exertion.

Features on physical examination are a bisferiens carotid pulse, triple apical impulse (due to the prominent atrial filling wave and early and late systolic impulses), and a loud S4. In cases with outflow obstruction, a loud systolic murmur is present that increases with upright posture or Valsalva’s maneuver and decreases with squatting.

B. Electrocardiography and Chest X-Ray
Left ventricular hypertrophy is nearly universal. Exaggerated septal Q waves inferolaterally may suggest myocardial infarction. The chest x-ray is often unimpressive.

C. Diagnostic Studies
The echocardiogram is diagnostic, revealing asymmetric left ventricular hypertrophy, systolic anterior motion of the mitral valve, early closing followed by reopening of the aortic valve, a small and hypercontractile left ventricle, and delayed relaxation and filling of the left ventricle during diastole. Doppler ultrasound reveals turbulent flow and a dynamic gradient across the aortic valve and, commonly, mitral regurgitation. Cardiac catheterization may confirm the gradient but adds little to echocardiographic studies.

Treatment
ß-Blockers should be the initial drug in symptomatic individuals, especially when dynamic outflow obstruction is noted on the echocardiogram. Dyspnea, angina, and arrhythmias respond in about 50% of patients. Calcium channel blockers, especially verapamil, have also been effective in symptomatic patients. Their effect may be due primarily to improved diastolic function, but their vasodilating actions may also increase outflow obstruction. Excision of part of the myocardial septum has been successful in patients with severe symptoms when performed by surgeons experienced with the procedure. Dual-chamber pacing may prevent the progression of hypertrophy and obstruction. Nonsurgical septal ablation has been performed by injection of alcohol into septal branches of the left coronary artery. Patients with malignant ventricular arrhythmias and unexplained syncope in the presence of a positive family history for sudden death are probably best managed with an implantable defibrillator.

Prognosis
The natural history of hypertrophic cardiomyopathy is highly variable. Several specific mutations are associated with a higher incidence of early malignant arrhythmias and sudden death, and definition of the genetic abnormality provides the best estimate of prognosis. Some patients remain asymptomatic for many years or for life. Sudden death, especially during exercise, may be the initial event. Indeed, hypertrophic cardiomyopathy is the pathologic feature most frequently associated with sudden death in athletes. Other patients have a history of gradually progressive symptoms. A final stage may be a transition into dilated cardiomyopathy.

Maron BJ: Hypertrophic cardiomyopathy: a systematic review. JAMA 2002;287:1308.

Maron BJ: Risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. Cardiol Rev 2002;10:173.

Maron MS et al: Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003;348:295.

Merrill WH et al: Long-lasting improvement after septal myectomy for hypertrophic obstructive cardiomyopathy. Ann Thorac Surg 2000;69:1732.

Qin JX et al: Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery. J Am Coll Cardiol 2001;38:1994.

Roberts R et al: New concepts in hypertrophic cardiomyopathies. Circulation 2001;104:2113, 2249.
————

3. Restrictive Cardiomyopathy

Restrictive cardiomyopathy is characterized by impaired diastolic filling with preserved contractile function. This condition is relatively uncommon, with the most frequent causes being amyloidosis, radiation, and myocardial fibrosis after open heart surgery. In Africa, endomyocardial fibrosis, a specific entity in which there is severe fibrosis of the endocardium, often with eosinophilia (Loffler’s syndrome), is common. Other causes of a restrictive picture are infiltrative cardiomyopathies (eg, sarcoidosis, hemochromatosis, carcinoid syndrome) and connective tissue diseases (eg, scleroderma). Amyloidosis can affect the heart in several ways. Although it is a frequent cause of restrictive cardiomyopathy, it more often produces dilated cardiomyopathy with congestive heart failure. Almost invariably, conduction disturbances are present. Low voltages on the ECG combined with ventricular hypertrophy by echo are suggestive. Rectal, abdominal fat, or gingival biopsies - as well as myocardial biopsy - can be diagnostic. The primary diagnostic problem with restrictive cardiomyopathy is differentiation from constrictive pericarditis. The clinical picture often strongly suggests the diagnosis, but the status of left ventricular function (usually normal with pericarditis, slightly depressed with restrictive cardiomyopathy) can be helpful, as can be evidence of a thickened pericardium. Myocardial biopsies are usually negative with pericarditis but not in restrictive cardiomyopathy. In some cases, only surgical exploration can make the diagnosis. Unfortunately, little useful therapy is available for either the causative conditions or restrictive cardiomyopathy itself. Diuretics can help, but excessive diuresis can produce worsening symptoms. Steroids may be helpful in sarcoidosis but relieve conduction abnormalities more often than heart failure. Ammash NM et al: Clinical profile and outcome of idiopathic restrictive cardiomyopathy. Circulation 2000;101:2490. Asher CR et al: Diastolic heart failure: restrictive cardiomyopathy, constrictive pericarditis, and Cardiac tamponade: clinical and echocardiographic evaluation. Cardiol Rev 2002;10:218. Gertz MA et al: Primary systemic amyloidosis. Curr Treat Options Oncol 2002;3:261. Hancock EW: Differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis. Heart 2001;86:343.

Provided by ArmMed Media
Revision date: July 7, 2011
Last revised: by David A. Scott, M.D.