Important differences between short- and long-term hemodynamic effects of amiodarone in patients with chronic ischemic heart disease at rest and during ischemia-induced left ventricular dysfunction

To assess and compare the hemodynamic profile of short-and long-term amiodarone administration in the same set of patients and to investigate hemodynamic mechanisms responsible for the antianginal effect of this drug, 10 patients with documented coronary artery disease and stable angina pectoris were studied. Simultaneous right heart catheterization and equilibrium radionuclide angiocardiography were performed at rest and during exercise before therapy (control), after a 5 minute intravenous infusion of 7.5 mg/kg of amiodarone and after 21.0 ± 4.3 days of peroral therapy (10 days 800 mg/day, 7 days 400 mg/day and then 200 mg/day). After acute drug administration, ejection fraction, stroke index and systolic blood pressure decreased, whereas heart rate, left and right ventricular filling pressures and systemic vascular resistance increased. These effects were reversed after long-term therapy; all measured values returned to control levels except for heart rate, which decreased below the control value, and right atrial pressure, which remained slightly elevated. Amiodarone drug levels decreased from 4.8 ±1.8 after intravenous infusion to 1.2 ± 0.6 mg/liter after long-term therapy. After adjustment for hemodynamic changes at rest, there were still significant reductions in heart rate, mean arterial pressure and rate-pressure product during exercise.It is concluded that the marked negative inotropic effect of amiodarone administered acutely in the dose applied calls for cautious use of this drug when administered intravenously. In contrast, long-term oral amiodarone therapy seems hemodynamically safe, even in patients with moderately depressed left ventricular function. Amiodarone also exerts a mild but significant anti-ischemic effect, mainly through afterload reduction and improvement in myocardial oxygen consumption