Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral resistance and increases cardiac power therefore preventing a steep decrease in blood pressure in patients with congestive heart failure

Objective: This study investigated the effect of tezosentan (an intravenous endothelin-1 receptor antagonist) on vascular resistance and cardiac function and determined the dose response in patients with stable congestive heart failure (CHF) due to left ventricular systolic dysfunction. Methods: In a double-blind fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50, 100 mg h^-1) to 38 CHF (NYHA class III) patients with ejection fraction ≥ 35%, cardiac index ≤ 2.7 1 min^-1 m^-2 and pulmonary capillary wedge pressure ≥ 15 mmHg. Systemic vascular resistance index (SVRi) was estimated as mean arterial blood pressure [(MAP-right atrial pressure) ÷ cardiac index (CI)]. Cardiac function was assessed as cardiac power index (Cpi), calculated as pressure × flow (MAP × CI), where MAP represents pressure and CI represents cardiovascular flow. Results and discussion: Compared to the placebo, tezosentan induced a dose-dependent decrease in SVRi (-32%), an increase in Cpi (+20%) and a small decrease in MAP (-9%). By contrast, patients treated with nitrate vasodilators or nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a significant increase in Cpi leading to a steep decrease in MAP. Conclusions: The use of Cpi in the assessment of the hemodynamic effects of tezosentan, provides a useful alternative characterization of the complex influences of vasodilators on cardiac function in patients with CHF.