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Recent studies indicate that reversible 201TI perfusion defects, compatible with silent myocardial ischemia, commonly develop during exercise in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy (HCM). To determine whether this represents a dynamic process that may be modified favorably by medical therapy, we studied 29 asymptomatic or minimally symptomatic patients with HCM, aged 12–55 years (mean, 28), with exercise 201TI emission computed tomography under control conditions and again after 1 week of oral verapamil (mean dosage, 453 mg/day). Treadmill time increased slightly during verapamil (21.0±3.6 to 21.9±2.7 minutes, p < 0.005), but peak heart rate-blood pressure product was unchanged (26.3±6.0× 103 compared with 25.0±6.4×103). Two midventricular short-axis images per study were divided into five regions each, and each of these 10 regions was then analyzed on a 0–2 scale by three observers blinded with regard to the patients' therapy. Average regional scores of 1.5 or less were considered to represent perfusion defects, and a change in regional score of 0.5 or more was considered to constitute a significant change. During control studies, 15 patients (52%) developed perfusion defects with exercise (average, 3.7 regions per patient). In 14 of these patients, all perfusion defects completely reversed after 3 hours of rest; one patient had fixed defects. After administration of verapamil, exercise perfusion scores improved in 10 of the 14 patients (71%) with reversible defects; there was overall improvement in 34 of 50 (68%) regions with initially reversible perfusion defects. Verapamil completely normalized all regional perfusion defects that were apparent during exercise under control conditions in eight patients (average, 3.9 regions per patient). No region developed a new or worse perfusion defect during verapamil in any patient. Thus, exerciseinduced regional myocardial perfusion defects improved during verapamil in the majority of asymptomatic patients with HCM and in many cases improved completely. These data suggest that verapamil may prevent or diminish inducible silent ischemia in many asymptomatic patients with HCM.