Cardiomyopathy, Hypertrophic

KEY FEATURES

ESSENTIALS OF DIAGNOSIS

• Chest pain, exertional dyspnea, exercise intolerance, orthopnea, peripheral edema

• Systolic ejection murmur with characteristic changes during bedside maneuvers

• Markedly asymmetric left ventricular hypertrophy on echocardiogram with greatest involvement most commonly of the basal interventricular septum

• Absence of other etiologies causing left ventricular hypertrophy, including abnormal loading conditions, systemic hypertension, aortic stenosis, or physiologic hypertrophy of athletes

• First-degree relatives of patients of hypertrophic cardiomyopathy (HCM) should be screened (clinical, with or without genetic testing)

GENERAL CONSIDERATIONS

• HCM is a primary disorder of the heart caused by mutations in genes that encode the protein components of the cardiac sarcomere

• Single-gene disorder that has an autosomal dominant with incomplete penetrance pattern of inheritance

• Together, mutations in the cardiac myosin-binding protein-C (MYBPC3) and beta-myosin heavy chain (MYH7) genes account for up to 50% of all clinically recognized cases

• The clinical manifestations of the disease vary from asymptomatic carriers to severely disabled patients

• Two-thirds of affected individuals have asymmetric hypertrophy often involving the intraventricular system but occasionally limited to the apex of the left ventricle

• One-third of those affected have diffuse concentric hypertrophy

• Histologic changes include myocyte and cardiac hypertrophy, disarray, and interstitial fibrosis

• The left ventricle cavity is nondilated and usually shows hyperdynamic function

• Patients with symmetric hypertrophy may demonstrate intracavitary gradients that worsen with increased contractile stimuli and improve with increased afterload

• Asymmetric septal hypertrophy often results in systolic anterior motion of the anterior mitral valve leaflet, which narrows the left ventricular outflow tract, producing a gradient and a characteristic systolic murmur that varies in intensity with loading conditions

• Systolic anterior movement of the mitral valve often leads to mitral regurgitation

CLINICAL PRESENTATION

SYMPTOMS AND SIGNS

• May be asymptomatic

• Exertional dyspnea, fatigue

• Chest pain

• Syncope

• Palpitations

PHYSICAL EXAM FINDINGS

• May be unremarkable

• Left ventricle lift; may be bifid

• S₄

• Systolic ejection murmur that increases in intensity with maneuvers that decrease left ventricular filling, such as standing, and softens with increased filling, such as squatting

DIFFERENTIAL DIAGNOSIS

• Left ventricular hypertrophy secondary to other conditions (eg, hypertension, athlete’s heart)

• Aortic stenosis with marked left ventricular hypertrophy

• Restrictive cardiomyopathy with hypertrophy, such as amyloidosis

• Athlete’s heart

DIAGNOSTIC EVALUATION

LABORATORY TESTS

• Elevated brain natriuretic peptide

• Genetic testing

ELECTROCARDIOGRAPHY

• Almost all patients have an abnormal ECG, but the patterns are nonspecific

• Voltage criteria for left ventricular hypertrophy with repolarization abnormalities are common

• Some patients have giant negative T waves in the precordium, especially the apical variant

IMAGING STUDIES

• Echocardiography is recommended in the initial evaluation of all patients with ...