Amiodarone reduces transmural heterogeneity of repolarization in the human heart

Objectives. The present work was designed to test the effects of amiodarone therapy on action potential characteristics of the three cell types observed in human left ventricular preparations. Background. The electrophysiologic basis for amiodarone’s exceptional antiarrhythmic efficacy and low proarrhythmic profile remains unclear. Methods. We used standard microelectrode techniques to investigate the effects of chronic amiodarone therapy on transmembrane activity of the three predominant cellular subtypes (epicardial, midmyocardial [M] and endocardial cells) spanning the human left ventricle in hearts explanted from normal, heart failure and amiodarone-treated heart failure patients. Results. Tissues isolated from the ventricles of heart failure patients receiving chronic amiodarone therapy displayed M cell action potential duration (404 ± 12 ms) significantly briefer (p < 0.05) than that recorded in tissues isolated from normal hearts (439 ± 22 ms) or from heart failure patients not treated with amiodarone (449 ± 18 ms). Endocardial cells from amiodarone-treated heart failure patients displayed longer (p < 0.05) action potential duration (363 ± 10 ms) than endocardial cells isolated from normal hearts (330 ± 6 ms). As consequence, the heterogeneity of ventricular repolarization in tissues from patients treated with amiodarone was considerably smaller than in the two other groups, especially at long pacing cycle lengths. Conclusions. These findings may explain, at least in part, the reduction of ventricular repolarization dispersion and the lower incidence of torsade de pointes observed with chronic amiodarone therapy as compared with other class III agents.