Calcium antagonists in heart failure

Calcium channel blocking drugs improve systolic function, due to a decrease in left ventricular afterload, and may thus be particularly suitable for therapy of patients with concomitant congestive heart failure and myocardial ischaemia. Since ischaemic heart disease is a major cause of congestive heart failure and further ischaemia may contribute to further left ventricular dysfunction, studies were performed to establish the therapeutic role of calcium channel blockers. Concern has been raised that at high doses, calcium channel blockers have a negative inotropic effect and may lead to deterioration of myocardial systolic function. Clinical studies assessing the role of verapamil and diltiazem in congestive heart failure are scarce, because these drugs may result in a further decrease in cardiac output, especially in the presence of pre-existing left ventricular dysfunction. In vitro observations show that nifedipine is more potent on vascular smooth muscle than on myocardium. It has been suggested that in man, nifedipine does not usually reach concentrations high enough to depress myocardium and the vasodilating left ventricular unloading effect becomes dominant. Analysis of the available clinical data is difficult, but published data concerning the oral or sublingual administration of nifedipine in congestive heart failure suggest that the major haemodynamic effect is a decrease in systemic vascular resistance by 33%, resulting in an increase in cardiac output of 24%. Heart rate was generally unchanged. Right atrial pressures showed minimal change, whereas pulmonary capillary wedge pressure decreased by 16%. The response is more favourable if the congestive heart failure is more severe. A new dihydropyridine, nisoldipine, was evaluated during chronic administration over 8 weeks in patients with severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)