Southwestern Internal Medicine Conference: Hypertrophic Cardiomyopathy: Current Views on Etiology, Pathophysiology, and Management

ABSTRACT Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease of unknown cause that is characterized by a hypertrophied, nondilated, hypercontractile left ventricle. Its etiology and pathogenesis remain undefined but the three principal factors implicated are a genetic predisposition, a hypersensitivity to catecholamines, and an abnormal calcium metabolism. The hypertrophy typically involves the intraventricular septum to varying degrees, but may also involve the apex or free wall and even be concentric. The disease occurs in either an obstructive or a nonobstructive form depending on whether an intraventricular pressure gradient can be demonstrated at rest or on provocation. The gradient and obstruction to outflow is usually seen in patients with asymmetric septal hypertrophy (ASH) and anterior motion of the mitral valve during systole (SAM). Abnormal left ventricular diastolic function characterized by inadequate filling and impaired relaxation has been shown to be very important in both the obstructive and nonobstructive forms of the disease. In addition, inadequate coronary vasodilator reserve as a result of small vessel disease, microvascular spasm, and/or low capillary density per unit myocardial mass has been implicated as an important cause of ischemia in patients without coronary artery disease. HCM is a disease of young adulthood with relatively slow progression; young patients are often asymptomatic, whereas older patients are more limited by dyspnea, angina, dizziness, or syncope. Supraventricular tachyarrhythmias occur in 30% of patients, and high-grade ventricular arrhythmias occur in over 75%. The annual mortality is 3-5%. The common mode of demise is sudden cardiac death. Therefore, the primary objectives of treatment are the amelioration of symptoms, the control of arrhythmias, and the prevention of sudden death. Beta-adrenoreceptor blocking agents decrease myocardial contractility and oxygen demands and increase ventricular volume; therefore, they are most useful in patients with the obstructive form of HCM. Calcium channel antagonists enhance left ventricular relaxation, relieve microvascular spasm, and improve coronary filling and therefore are the agents of choice in patients with diastolic dysfunction. The ability of the calcium channel antagonists to decrease contractility makes them valuable in patients with obstructive HCM. Arterial vasodilators, diuretics, nitrates, and inotropic agents should be avoided because they can increase the intraventricular gradient. Myomyectomy is reserved for those patients with the obstructive form of HCM whose symptoms are refractory to medical therapy. Surgery is contraindicated in patients with the nonobstructive form of HCM. Supraventricular tachycardia and atrial fibrillation are poorly tolerated in patients with HCM because of the loss of atrial support of ventricular filling and decreased diastolic filling time. Therefore, normal sinus rhythm should be maintained using a Type 1 anti-arrhythmic agent, or rate should be controlled with beta-adrenoreceptor or calcium channel antagonist agents. Digitalis glycosides are contraindicated, since they can increase contractility and the gradient. One subset of patients at high risk of sudden death is those with the combination of young age (under 30 years), a family history of sudden death due to HCM, and nonsustained VT. However, no prospective randomized study with appropriate controls and risk stratification has addressed the issues of which patients require treatment and what constitutes optimal therapy. Studies suggest Ithat initial control of VT might be achieved with propranolol in high dose (> 480 mg/day) in conjunction with a Type 1 antiarrhythmic agent (quinidine, disopyramide, mexilitine). Amiodarone also has been shown to control VT and improve survival in patients with HCM and VT. However, it should not be the initial agent of choice in young patients because of potential serious side effects with long-term treatment.