ABSTRACTThe influence of long-term treatment with amiodarone on exercise hemodynamics and on left ventricular relaxation was studied prospectively in patients with hypertrophic cardiomyopathy. Rest-exercise hemodynamics (n = 9) and echocardiographic relaxation indexes (isovolumic relaxation time, dPW/dt) (n = 11) were measured in control conditions and after 5 weeks of oral amiodarone treatment (600 mg daily first week, 400 mg daily second week, 200 mg daily afterwards). Long-term amiodarone treatment in patients at rest caused a significant drop in heart rate from 80 ± 1 1 to 75 ± 11 beats/min (p < .05), a rise in mean pulmonary artery pressure from 19 + 7 to 25 ± 10 mm Hg (p < .02), and a rise in mean pulmonary capillary wedge pressure from 11 ± 4 to 17 ± 8 mm Hg (p < .05). Systemic arterial pressure, cardiac output, and systemic vascular resistance remained unaltered. Exercise tolerance assessed by serial supine bicycle stress testing was reduced in six of nine patients. Amiodarone treatment caused a significant rise in pulmonary capillary wedge pressure from 22 ± 8 to 37 ± 9 mm Hg (p < .001) at the highest identical workloads and from 26 ± 10 to 37 9 (p < .005) at maximal symptom-limited workloads. Similarly, mean pulmonary artery pressure rose from 37 + 15 to 51 ± 18 mm Hg (p < .01) at highest identical workloads and from 42 ± 19 to 51 ± 18 mm Hg (p < .01) at maximal symptom-limited workloads. There were no significant differences at maximal exercise level in heart rate, systemic arterial pressure, cardiac output, or exercise factor. Echocardiographic studies performed before and during long-term amiodarone treatment revealed no change in isovolumic relaxation time, end-diastolic or end-systolic posterior wall thickness, and peak posterior wall thinning rate. A negative inotropic action of amiodarone could explain the worsened rest and exercise hemodynamics observed during long-term treatment of patients with hypertrophic cardiomyopathy. Echocardiographic relaxation indexes remained unaltered despite the elevated left ventricular filling pressures. This finding could suggest a deleterious effect of amiodarone on myocardial inactivation, possibly similar in mechanism to the depressed myocardial inactivation observed in hypothyroidism.