Treatment of hypertrophic cardiomyopathy: relation to pathological mechanisms

Abstract

In patients with hypertrophic cardiomyopathy, clinical symptoms such as exertional dyspnea, angina and collapse are considered to be rather the consequence of diastolic than of systolic dysfunction of the left ventricle. Beta-blocker therapy is aimed at reducing systolic overcontraction while calcium blockers predominantly therapy is aimed at reducing systolic overcontraction while calcium blockers predominantly improve diastolic filling characteristics. Therefore 61 consecutive patients with well defined hypertrophic cardiomyopathy were treated with calcium channel blockers: 60 patients with verapamil at average dose 530 mg (320 to 720 mg/d) and one patient received 30 mg nifedipine. All patients had clinical, noninvasive and cardiac catheterization evaluation at the time of entry into the study. Therapy was continued for an average of 54 months (10 to 96). Follow-up studies were performed at 6-month intervals. Subjective improvement was achieved in 47 of 55 symptomatic patients (85%). Heart size, judged as heart volume from tele-chest X-ray in supine position, showed a reduction in 36/61, no change in 15/61 and increase in 10/61. On average in all 61 patients, a significant reduction from 947 to 833 ml/1.73 m2 was seen. Twenty-six patients who had been followed for an average of 24 months prior to verapamil therapy on beta blockers or no treatment had heart volume increases averaging 12% in the pre-verapamil period. Electrocardiography (ECG) showed a significant reduction in QRS amplitude and a tendency towards normalization of ST/T segments. Serial echocardiography study showed small but significant reduction in left atrial diameter. Repeat catheterization was performed in 19 patients and a significant reduction in intraventricular pressure gradient, left ventricular muscle mass and coronary artery diameter was demonstrated. Three patients died during the study (256 patient-treatment-years) for an annual mortality rate of 1.3%. This mortality is considerably lower than reported for patients receiving no treatment, beta-blockade, or surgery. Of all 61 patients only one had surgery related to the hypertrophic cardiomyopathy. One patient had the dose of verapamil reduced because of the occurrence of heart block. No patient discontinued the drug because of side-effects. Utilizing serial noninvasive and invasive studies, we conclude that verapamil therapy in hypertrophic cardiomyopathy results in objective and subjective improvement, a low death rate and little need for operation as compared to standard therapy.