Endothelin antagonists and heart failure.

Chronic heart failure (CHF) is characterized by impaired left ventricular function, increased peripheral and pulmonary vascular resistance, reduced exercise tolerance, and dyspnea. Despite considerable progress in the treatment of CHF, especially in targeting activated neurohumoral systems, mortality in these patients remains high. Therefore, new treatment approaches are warranted. Endothelin-1 (ET-1) plasma levels are elevated in CHF and correlate with both hemodynamic severity and symptoms. Plasma levels of ET-1 are strong independent predictors of mortality in CHF. Combined ET(A/B) selective ET(A) receptor antagonists have been evaluated in patients with CHF showing impressive hemodynamic improvements. These results indicate that ET receptor antagonists indeed have a potential to improve hemodynamics, symptoms, and potentially prognosis in patients with CHF, which still carries a high mortality.