Inhibition of endothelin-1 in patients with congestive heart failure appears to have potential therapeutic value, demonstrating hemodynamic benefit and improvement in cardiac function in human trials.
Does endothelin-1 inhibition improve hemodynamics and cardiac function in patients with heart failure?
Endothelin-1 inhibition shows potential therapeutic value for heart failure by improving hemodynamics and cardiac function in preclinical and early clinical studies.
Endothelin-1 has been appreciated in animals and humans as a potential target for inhibition in patients with acutely decompensated congestive heart failure (CHF), as well as patients with a chronic low-output state. There has been intense interest in determining the effects of endothelin-1 on the cardiovascular system. Elevated plasma levels of endothelin-1 in patients with CHF portend a poorer prognosis than similar patients without elevated levels. Endothelin-1 levels correlate inversely with maximum oxygen consumption, and inhibition of the myocardial endothelin pathway in rats with CHF improves survival. An association between endothelin-1 and the development of CHF has recently been supported. Selectively inhibiting the endothelin A receptors in dogs with CHF produced hemodynamic improvement. Similarly, in rabbits, a structural advantage was demonstrated. Benefits in cardiac remodeling have been demonstrated in several models of CHF by nonselectively antagonizing endothelin receptors. In human trials using nonselective endothelin-1 inhibitors, researchers have demonstrated hemodynamic benefit and improvement in cardiac function in patients with decompensated CHF. Inhibition of endothelin-1 in patients with CHF appears to have potential therapeutic value, and ongoing clinical trials will further investigate the safety, efficacy, and role of this new potential therapeutic target for the treatment of CHF.
Duchman et al. (Mon,) conducted a review in Congestive heart failure (CHF). Endothelin-1 inhibitors was evaluated. Inhibition of endothelin-1 in patients with congestive heart failure appears to have potential therapeutic value, demonstrating hemodynamic benefit and improvement in cardiac function in human trials.