Long Term Effects of Enalapril and Losartan on Genetic Heart Disease

INCLUSION CRITERIA HCM of either gender, aged 20-55 years. Non-dilated LV (LVIDd less than 60 mm) with LV wall thickness of greater than or equal to 16 mm measured in any LV segment by NMR. Non-obstructive HCM: A LV outflow gradient of less than or equal to 30 mm Hg gradient at rest and less than or equal to 55 mm Hg following isoproterenol infusion to a heart rate of greater than or equal to 120 beats per minute at cardiac catheterization. New York Heart Association functional class I-III. Patients who have participated in the previous toxicity study may be recruited for this study, if they wish. Patients who have previously taken an ACE inhibitor or losartan could only be included in this study, if they have been off these drugs for a period of 6 months or longer. EXCLUSION CRITERIA Severe cardiac symptoms at rest (NYHA IV). LV outflow tract gradient of greater than 30 mm Hg at rest or greater than 55 mm Hg following isoproterenol infusion to a heart rate of greater than or equal to 120 beats per minute at cardiac catheterization. Systemic diseases (respiratory, neurologic, or locomotor) that prevent exercise testing, echocardiography or NMR, MUGA, thallium studies, and cardiac catheterization. Coronary artery disease (greater than 50% arterial luminal narrowing of a major epicardial vessel) or congenital cardiovascular abnormalities (e.g. ASD, VSD, coronary anomalies). Chronic atrial fibrillation. Bleeding disorder (PTT greater than 35 sec, pro time greater than 14.7 sec, platelet count less than 154 k/mm3). Anemia (Hb less than 12.7 g/dl in males and less than 11.0 g/dl in females); renal impairment (BUN greater than 22 mg/dl and serum creatinine greater than 1.4 mg/dl); K+ less than 3.3 mmol/l or greater than 5.1 mmol/l. Hypertension: basal systolic and diastolic pressures of greater than 160 mm Hg or greater than 95 mm Hg, respectively on two occasions separated by one hour of rest. Hypotension: basal sitting systolic arterial pressure less than 100 mm Hg confirmed 30 minutes later. Must have ability to estimate LV wall thickness. Radiographic evidence of overt cardiac failure (pulmonary edema on chest X-ray). Negative urine pregnancy test. Pregnant or lactating female patients. Diminished LV systolic function (resting or exercise LV ejection fractions estimated by radionuclide angiography less than 50%). Dependence on other cardioactive drugs such as diuretics, verapamil, B-blockers, or antiarrhythmic drugs to control symptoms and arrhythmias. Negative HIV test. Sensitivity to ACE inhibitor e.g. angioedema. Must have ability to set up an outpatient monitoring system.