Acute hemodynamic effects of pindolol and propranolol in patients with dilated cardiomyopathy: Relevance of intrinsic sympathomimetic activity

Abstract

The administration of beta-blocking agents to patients with poor left ventricular (LV) function may result in clinical and hemodynamic deterioration. The beta antagonist pindolol has intrinsic sympathomimetic activity (ISA) and therefore may be better tolerated. To test this hypothesis 30 patients with a precatheterization diagnosis of dilated cardiomyopathy were randomly assigned to three groups to receive intravenous injections of placebo, propranolol, or pindolol. The baseline jection fraction and hemodynamics were similar for all groups. For propranolol 1 mg, 2 mg, 3 mg, and 4 mg doses were given 5 minutes apart until a maximum dose of 10 mg was reached, until a 25% reduction in the heart rate or mean arterial pressure occurred, or until clinical deterioration developed. For pindolol 0.1 mg, 0.2 mg, 0.3 mg, and 0.4 mg boluses were used with the same end points. Baseline hemodynamics were measured and repeated 15 minutes after the last dose of each drug was administered. The mean number of doses given was similar for both groups: 3.3 doses for the propranolol group and 3.4 for the pindolol group. Compared to propranolol, pindolol caused less of a reduction in heart rate, cardiac output. cardiac index, stroke volume index, and stroke work index and less of an increase in the mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, left ventriculs end-diastolic pressure, and pulmonary vascular resistance; there was a decrease in systemic vascular resistance. These differences were statistically significant for changes in heart rate, right atrial pressure, cardiac index, and systemic vascular resistance. Although no patients in the pindolol-treated group had clinical deterioration, four in the propranolol-treated group required tomporary intravenous inotropic support. Based on these data we conclude that pindolol as compared to propranolol is better tolerated acutely when given to patients with markedly reduced LV function. It is likely that the ISA of pindolol accounts for this effect. Therefore patients with severely reduced LV function who require beta blockade acutely may better tolerate pindolol or other beta-blocking agents that possess ISA than those that do not. Whether or not these same findings can be extrapolated to the chronic administration of beta blockade in patients with reduced LV function remains unknown and will require further investigation.