R013-6438, a new inotrope-vasodilator: Systemic and coronary hemodynamic effects in congestive heart failure

Abstract

Systemic and coronary hemodynamics and transmyocardial norepinephrine release were determined before and after oral administration of RO13-6438, a new inotrope-vasodilator agent, in 12 patients with severe chronic heart failure unresponsive to conventional and vasodilator therapy. improvement in left ventricular (LV) function was evident from a marked increase in cardiac index (from 2.09 ± 0.45 to 3.30 ± 0.73 liters/min/m2, p <0.01), stroke volume index (from 23 ± 7 to 36 ± 11 ml/m2, p <0.01), and stroke work index (from 23 ± 11 to 36 ± 14 g-m/m 2, p <0.01), and concomitant fall in pulmonary capillary wedge pressure (from 26 ± 7 to 16 ± 8 mm Hg, p <0.01). Myocardial oxygen consumption did not change significantly (from 15.3 ± 6.8 to 14.9 ± 6.8 mi/min), but the ratio of minute work/myocardial oxygen consumption, an index of LV efficiency, Increased significantly (p <0.05). Although average coronary sinus flow did not change, coronary sinus oxygen increased (from 3.2 ± 0.8 to 4.2 ± 1.5 vol%, p <0.05), and arterial-coronary sinus oxygen difference decreased (from 11.8 ± 2.1 to 10.4 ± 1.9 vol%, p <0.05), suggesting a primary vasodilating effect of R013-6438 on the coronary vascular bed. Net transmyocardial norepinephrine release did not change despite the marked hemodynamic improvement. These findings suggest that R013-6438 has the potential to cause marked improvement in LV function and LV efficiency in patients with severe, refractory congestive heart failure.