Effects of long-term treatment with amiodarone on exercise hemodynamics and left ventricular relaxation in patients with hypertrophic cardiomyopathy.

The 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 +/- 11 to 75 +/- 11 beats/min (p less than .05), a rise in mean pulmonary artery pressure from 19 +/- 7 to 25 +/- 10 mm Hg (p less than .02), and a rise in mean pulmonary capillary wedge pressure from 11 +/- 4 to 17 +/- 8 mm Hg (p less than .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 less than .001) at the highest identical workloads and from 26 +/- 10 to 37 +/- 9 (p less than .005) at maximal symptom-limited workloads. Similarly, mean pulmonary artery pressure rose from 37 +/- 15 to 51 +/- 18 mm Hg (p less than .01) at highest identical workloads and from 42 +/- 19 to 51 +/- 18 mm Hg (p less than .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.