A novel approach to the development of positive inotropic agents for chronic heart failure.

Although positive inotropic agents exert favorable hemodynamic effects, long-term therapy with these drugs has not produced clinical benefits and has increased the mortality of patients with chronic congestive heart failure (CHF). This experience has led many physicians to suggest that positive inotropic therapy be abandoned as a therapeutic approach for this condition. However, positive inotropic drugs can produce clinical benefits in many patients but, ironically, this improvement may be principally seen at doses that produce negligible effects on cardiac contractility. This apparent discrepancy may be explained by the fact that many positive inotropic agents exert actions on the circulation in addition to stimulating the heart, and these ancillary properties may be particularly important with the use of low doses of these drugs. If the noninotropic actions of low doses are responsible for the therapeutic benefits of these drugs, the positive inotropic effects seen at high doses may be primarily responsible for their adverse (rather than their favorable) effects. Therefore, hemodynamic activity should not be viewed as a prerequisite for the selection of the dose of a drug for CHF. The ideal dose of a positive inotropic agent may be one that exerts no positive inotropic effect at all.