Hemodynamic and electrophysiologic effects of verapamil and nifedipine in patients on propranolol

Because the combined use of a beta-adrenergic blocking agent and a calcium antagonist may be beneficial in patients with severe angina, we assessed the hemodynamic and electrophysiologic effects of verapamil or nifedipine in patients receiving oral propranolol. In 26 patients with stable angina receiving oral propranolol (234 ± 230 mg/day, mean ± standard deviation), cardiac catheterization was performed, and variables were measured at baseline and 5 to 10 minutes after (1) intravenous saline solution, 10 ml (n = 6); (2) intravenous verapamil, 0.15 mg/kg body weight to a maximal dose of 10 mg (n = 10); and (3) sublingual nifedipine, 10 mg (n = 10). Cardiac output (by thermodilution) was unchanged after saline solution and verapamil but increased with nifedipine (4.3 ± 1.1 to 5.0 ± 1.4 liters/min, p < 0.05). Mean arterial pressure did not change with saline solution or nifedipine but decreased with verapamil. Peak-positive dP/dt was reduced only by verapamil (from 1,086 ± 175 to 926 ± 167 mm Hg/s, p < 0.05). Coronary sinus blood flow (by thermodilution) was not altered by saline solution, nifedipine, or verapamil. Verapamil reduced the heart rate (from 63 ± 8 to 60 ± 9 beats/min, p < 0.05) and increased the A-H interval (from 108 ± 14 to 129 ± 23 ms, p < 0.05). In contrast, nifedipine increased the heart rate (from 65 ± 8 to 71 ± 8 beats/min, p < 0.05) but did not change the A-H interval. Left ventricular ejection fraction (by radionuclide ventriculography) was unaltered by saline solution or verapamil but increased with nifedipine (from 0.52 ± 0.13 to 0.57 ± 0.13, p < 0.05). In summary, when administered to patients with normal or only mildly depressed left ventricular function who are receiving oral propranolol, nifedipine improves cardiac output and left ventricular ejection fraction without affecting intracardiac filling pressure or atrioventricular conduction. In contrast, verapamil diminishes left ventricular contractility and slows atrioventricular conduction. Thus, the combination of verapamil and propranolol must be used with caution in patients with underlying left ventricular dysfunction or conduction system disease.