Hypertrophic Cardiomyopathy



Hypertrophic cardiomyopathy is characterized by myocardial hypertrophy, especially involving the interventricular septum. In many patients a dynamic pressure gradient can be detected in the subvalvular left ventricular outflow tract (hyper­trophic obstructive cardiomyopathy or idiopathic hypertrophic subaortic stenosis). This gradient demonstrates wide fluctuations in severity and often is not present at rest, requiring physiological or pharmacological maneuvers to be precipitated. Even though much attention has been focused on the systolic gradient, the most characteristic path­ophysiological abnormality in this syndrome is not systolic but rather diastolic dysfunction, char­acterized by abnormal stiffness of the left ventri­cle with impaired filling. Therefore, pulmonary venous pressures are elevated, and dyspnea is the most common symptom despite a typically hy-percontractile left ventricle. In many patients the disease appears to be transmitted genetically as an autosomal dominant disorder with a high de­cree of penetrance, but sporadic cases do occur. Hypertrophy can involve predominantly the sep­tum (asymmetric septal hypertrophy) or the sep­tum and free wall equally (concentric left ven­tricular hypertrophy). Hypertrophied and bizarrely arranged myocardial cells are commonly but not always visualized pathologically, espe­cially in the septum.

Signs and symptoms in hypertrophic cardio­myopathy are summarized in . A large jugular venous a wave may be present on physical examination owing to reduced compliance of the right ventricle. The carotid arterial upstroke is brisk and bifid in character with a rapid initial rise, a midsystolic dip, and a second late systolic rise characteristic of the dynamic outflow tract ob­struction (see Fig. 2-2). The systolic outflow mur­mur typically is harsh, crescendo-decrescendo, often heard best between the apex and left sternal border, and radiates to the lower sternum, axilla, and base of the heart but often not into the neck. A murmur of concomitant mitral regurgitation is not uncommon. The systolic outflow murmur is said to be “dynamic” because its intensity varies inversely with the dimensions of the outflow tract. The outflow tract becomes larger with an increase in ventricular diastolic volume, an in­crease in systolic pressure against which the heart must pump, or a decrease in myocardial inotropic state. The outflow tract narrows with reversal of these factors .

Left ventricular hypertrophy is common on ECG, and large Q waves, probably related to ab­normal septal depolarization, may simulate septal myocardial infarction. Atrial fibrillation and other tachyarrhythmias are poorly tolerated owing to the hemodynamic abnormalities.

Echocardiography is the best technique for vis­ualizing the hypertrophic myocardium and asymmetric septal hypertrophy. It is useful for screen­ing family members of patients with hypertrophic cardiomyopathy. Narrowing of the left ventricular outflow tract by systolic anterior motion of the anterior leaflet of the mitral valve is characteristic of patients with obstructive cardiomyopathy, and the degree of systolic anterior motion appears to correlate with the degree of obstruction. The aor­tic valve may close partially in midsystole owing to the dynamic outflow obstruction; this finding, in addition to the systolic anterior motion, may be provoked with pharmacological manipulations (e.g., amyl nitrate, nitroglycerin, or isoproterenol). Mitral valve prolapse is sometimes observed along with evidence of a small left ventricular cav­ity and poor left ventricular compliance.

At cardiac catheterization, the systolic subval-vular gradient may or may not be present at rest, and provocative maneuvers such as nitroglycerin, amyl nitrate, isoproterenol infusion, and induced PVC’s may provoke a gradient. The left ventricular end-diastolic pressure and a wave are elevated. Angiography demonstrates marked thickening of the ventricular septum and left ventricular free wall, with large papillary muscles distorting the ventricular shape and producing a characteristic hourglass configuration. The left ventricular cav­ity is usually small and systolic function vigorous, resulting in virtual obliteration of the ventricular cavity with systole. Mitral regurgitation is com­mon.

The clinical course is variable, although symp­toms may remain stable over a period of several years. Symptoms are often unrelated to the pres­ence or severity of a gradient. Ventricular arrhyth­mias are common and sudden death may occur even in previously asymptomatic individuals. Any protective effect of medical therapy against arrhythmias is unproven.

Interventions that decrease ventricular contrac­tility, increase ventricular volume, increase sys­temic arterial pressure, increase the dimensions of the outflow tract, or increase ventricular com­pliance decrease symptoms and vice versa. Digi­talis should not be used unless atrial fibrillation with a rapid ventricular response or left ventric­ular dilation and dysfunction without a gradient occur. Diuretics should be used with caution as hypovolemia increases obstruction and symp­toms. Beta-adrenergic receptor blockade can pre­vent the increase in outflow tract gradient that may occur with exercise; its efficacy at preventing sudden death has not been estabished. It also has antianginal effects. It can be used in large doses (propranolol >320 mg/day) if not limited by con­traindications, but the overall efficacy of beta blockers is disappointing. Calcium channel block­ers such as verapamil decrease myocardial con­tractility and probably decrease the outflow gra­dient. More importantly, both verapamil and nifedipine appear to improve the diastolic func­tion (i.e., compliance) of the hypertrophic myo­cardium. Verapamil can exacerbate poor left ven­tricular contractility if present. Nifedipine has less negative inotropic effect but is a more potent vasodilator, which may be disadvantageous. Combined administration of a beta blocker and cal­cium antagonist may be effective in some patients. Patients with hypertrophic cardiomyopathy should receive endocarditis prophylaxis, since in­fection may occur on the aortic or mitral valves or on the endocardium at the site of septal contact of the anterior mitral leaflet. In the patient who is markedly symptomatic due to an outflow gra­dient and has not responded to medical manage­ment, septal myotomy-myectomy may be per­formed. This procedure usually relieves obstruction as well as mitral regurgitation.