Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy

Verapamil improves exercise capacity in patients with hypertrophic cardiomyopathy (HCM), but its mechanisms of action are unknown. We examined the effects of oral verapamil (320-480 mg/day) on resting left venticular (LV) systolic and diastolic function in patients with HCM. High-temporal-resolution time-activity curves from gated technetium-99m radionuclide angiograms were analyzed before and after verapamil therapy in 40 patients, of whom 16 were also studied during propranolol therapy (80-960 mg/day). All but one patient had normal or supranormal systolic function, but 70% had evidence of diastolic dysfunction, defined as peak LV filling rate (PFR) <2.5 end-diastolic volumes (EDV)/sec or time to PFR >180 msec. Verapamil did not change LV ejection fraction, peak elevation rate or ejection time, but did increase PFR (control 3.3 ± 1.0 EDV/sec, verapamil 4.1 ± 1.1 EDV/sec; p<0.001) and reduce time to PFR (control 187 ± 56 msec, verapamil 159 ± 34 msec; p<0.001). Only 30% of patients had evidence of diastolic dysfunction during verapamil. In contrast, propranolol did not change LV ejection fraction, PFR or time to PFR, but did prolong ejection time and reduce peak ejection rate. Thus, LV diastolic filling is abnormal in a high percentage of patients with HCM, and verapamil normalizes or improves these abnormalities without altering systolic function. This mechanism may contribute to the clinical inprovement of many HCM patients during verapamil therapy.