This placebo-controlled, double-blind trial compared the hemodynamic effects of sotalol and quinidine with the use of rest and exercise gated radionuclide angiography. Patients had frequent ventricular premature depolarizations (- 30 VPDs/hour) and depressed cardiac function (mean ejection fraction 43 ± 15%). Resting left ventricular ejection fraction and stroke volume index increased (p < .002, p < .001, respectively) during sotalol therapy, associated with a concomitant fall in heart rate (p < .001). Quinidine also increased mean left ventricular ejection fraction, but less so than did sotalol (p < .05). Quinidine significantly decreased left ventricular end-diastolic (p < .05) and end-systolic (p < .002) volumes, but had no effect on stroke volume index or heart rate. Neither drug affected cardiac index. Quinidine resulted in no symptomatic deterioration in left ventricular function or serious arrhythmia aggravation. In contrast, five patients on sotalol developed either decompensated congestive heart failure (two patients), arrhythmia aggravation (two patients), or hypotension associated with bradyarrhythmia (one patient). These patients had a unique hemodynamic profile that can be used to identify patients likely to have a poor outcome on sotalol. This profile reflected a lack of cardiac reserve, characterized by an inability to increase stroke volume and cardiac output with supine bicycle exercise.