Usefulness of calcium antagonists for congestive heart failure

Abstract

In patients with congestive heart failure (CHF) due to dilated cardiomyopathy, nifedipine, diltiazem and several of the newer calcium antagonists including nicardipine, nitrendipine, felodipine and PN 200-110 (isradipine) improve left ventricular function. Because of its relatively more pronounced negative inotropic and chronotropic actions, verapamil is generally not tolerated by patients with left ventricular failure. In addition, even relatively vascular-selective agents such as nifedipine can occasionally cause significant left ventricular depression, particularly if combined with β-adrenergic blocking agents. Comparative studies using nitroprusside to cause an equivalent decrease in arterial pressure indicate that nifedipine acts predominantly on the arterial vasculature, and that a small but significant decrease in contractility occurs, apparently due to a direct myocardial action. Although diltiazem causes a depression in myocardial contractility in dogs with volume overload heart failure, limited data show no significant negative inotropic action in patients with heart failure. The negative inotropic effects, if any, of newer and possibly more vascular-selective agents are not yet known. Calcium antagonists appear to act predominantly on the limb and coronary vasculature, with relatively less effect on renal and hepatic vessels. In patients with CHF, nifedipine causes an increase in coronary blood flow and a decrease in the aorto-coronary sinus oxygen difference indicating an improvement in myocardial energetics. Although nifedipine causes an increase in cardiac index and decreases in systemic vascular resistance and pulmonary capillary wedge pressure during exercise, the limited data available fail to show a short- or long-term increase in exercise capacity. Nifedipine causes an increase in plasma renin activity, possibly due to a direct action on the kidney. In the Syrian hamster, microvascular spasm, myocyte necrosis and development of heart failure can be prevented by verapamil, suggesting that calcium antagonists could have a role in preventing the development of some cardiomyopathies. The ultimate role of calcium antagonists in the treatment of patients with CHF is not yet clear. These agents are most likely to be of value in patients with both CHF and symptoms of myocardial ischemia, and in many cases, combination with nitrates or converting enzyme inhibitors may substantially improve the clinical response to the calcium antagonist.