Although HCM can present at any age, it typically manifests during the postpubertal growth spurt. The clinical symptoms can be best understood in the context of the functional abnormalities. It is characterized by massive left ventricular hypertorphy associated with (paradoxically) a markedly reduced stroke volume. This latter occurs as a consequence of impaired diastolic filling and overall smaller chamber size. In addition, roughly 25% of patients have dynamic obstruction to the left ventricular outflow by the anterior leaflet of the mitral valve. Reduced cardiac output and a secondary increase in pulmonary venous pressure cause exertional dyspnea, with a harsh systolic ejection murmur. A combination of massive hypertrophy, high left ventricular pressures, and compromised intramural arteries frequently leads to myocardial ischemia (with angina), even in the absence of concomitant CAD. Major clinical problems include atrial fibrillation with mural thrombus formation, ventricular fibrillation leading to sudden cardiac death, infectious endocarditis of the mitral valve, and CHF. Most patients’ symptoms are improved by therapy that promotes ventricular relaxation; partial surgical excision or controlled alcohol-induced infarction of septal muscle also can relieve the outflow tract obstruction. As mentioned earlier, HCM is an important cause of sudden cardiac death. In almost one third of cases of sudden cardiac death in athletes younger than 35 years of age, the underlying cause is HCM.
Restrictive cardiomyopathy is characterized by a primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole (simply put, the wall is stiffer). This form of cardiomyopathy may be idiopathic or may be associated with systemic diseases that affect the myocardium, for example, radiation fibrosis, amyloidosis, sarcoidosis, or products of inborn errors of metabolism.
Three forms of restrictive cardiomyopathy merit brief mention:
Amyloidosis is caused by the deposition of extracellular proteins with a predilection for forming insoluble β-pleated sheets (Chapter 5). Cardiac amyloidosis can occur in the setting of systemic amyloidosis (e.g., multiple myeloma) or can be predominantly restricted to the heart (e.g., senile cardiac amyloidosis). In the latter case, deposition of normal (or mutant) forms of transthyretin (a liver-synthesized circulating protein that transports thyroxine and retinol) in the hearts of older adult patients results in a restrictive cardiomyopathy. Four percent of African Americans carry a specific mutation of transthyretin that increases the risk of cardiac amyloidosis in that population over fourfold. Besides depositing as amyloid, immunoglobulin light-chains in AL-type amyloid also are directly cardiotoxic and can induce myocardial dysfunction.
Endomyocardial fibrosis is principally a disease of children and young adults in Africa and other tropical areas. It is http://ebooksmedicine.net
Fig. 11.27 Hypertrophiccardiomyopathywithasymmetricseptalhypertrophy.(A)Theseptalmusclebulgesintotheleftventricularoutflowtract,givingrisetoa“banana-shaped”ventricularlumen,andtheleftatriumisenlarged.Theanteriormitralleaflethasbeenmovedawayfromtheseptumtorevealafibrousendocardialplaque(arrow) (seetext).(B)Histologicappearancedemonstratingdisarray,extremehypertrophy,andcharacteristicbranchingofmyocytes,as wellasinterstitialfibrosis.