Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral resistance and increases cardiac power therefore preventing a steepdecrease 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 funct ion and determined the dose response in patients with stable congestive hea rt failure (CHF) due to left ventricular systolic dysfunction. Methods: In a double-blind fashion, tezosentan or placebo were administered in ascendin g doses (5, 20, 50, 100 mg h(-1)) to 38 CHF (NYHA class III) patients with ejection fraction less than or equal to 35%, cardiac index less than or equ al to 2.7 l min(-1) m(-2) and pulmonary capillary wedge pressure greater th an or equal to 15 mmHg. Systemic vascular resistance index (SVRi) was estim ated as mean arterial blood pressure [(MAP-right atrial pressure) divided b y cardiac index (CI)]. Cardiac function was assessed as cardiac power index (Cpi), calculated as pressure X flow (MAP X CI), where MAP represents pres sure and Cl represents cardiovascular flow. Results and discussion: Compare d 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 contras t, patients treated with nitrate vasodilators or nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a significant increas e 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. (C) 2001 European Society of Cardiol ogy. All rights reserved.