Cardiac and hemodynamic effects of the sinus node inhibitor tedisamil dihydrochloride in patients with congestive heart failure due to dilated cardiomyopathy

Abstract

Clinical and experimental investigations have demonstrated an inverse relation between heart rate and myocardial performance in patients with congestive heart failure. Accordingly, this study was designed to investigate the hemodynamic effect of the novel bradycardic compound tedisamil in patients with heart failure. We hypothesized that tedisamil would reduce heart rate and thereby improve hemodynamic parameters of failing hearts with an inverse force-frequency relation. Tedisamil was administered intravenously in nine patients with dilated cardiomyopathy (NYHA II-III). Hemodynamic measurements by right heart catheterization were carried out at time points -30, 10, 20 min, 1, 2, 4, and 6 h. Tedisamil decreased heart rate significantly from 84 +/- 6 beats/min to 73 +/- 4 beats/min (at 10 min; p < 0.05). Stroke volume index remained unchanged, and cardiac index tended to decrease transiently. Mean blood pressure increased from 98 +/- 5 to 104 +/- 6 mm Hg (p < 0.05) because of an increase in systemic vascular resistance from 1,619 +/- 145 to 2,079 +/- 198 dyn.s.cm(-5) (at 20 min; p < 0.05). Diastolic pulmonary pressure and pulmonary vascular resistance showed similar changes. Pulmonary capillary wedge pressure increased from 12 +/- 3 to 16 +/- 4 mm Hg (at 20 min; p < 0.05). Although tedisamil resulted in a significant heart-rate reduction, this was not associated with an improvement of hemodynamics. This may be due to increased afterload of the left and right ventricle. In these patients, tedisamil increased vascular resistance, which is unwanted in the treatment of congestive heart failure.