AMIODARONE REDUCES TRANSMURAL HETEROGENEITY OF REPOLARIZATION IN THE HUMAN HEART

Objectives. The present work was designed to test the effects of amiod arone therapy on action potential characteristics of the three cell ty pes observed in human left ventricular preparations. Background. The e lectrophysiologic basis for amiodarone's exceptional antiarrhythmic ef ficacy and low proarrhythmic profile remains unclear. Methods. We used standard microelectrode techniques to investigate the effects of chro nic amiodarone therapy on transmembrane activity of the three predomin ant cellular subtypes (epicardial, midmyocardial [M] and endocardial c ells) spanning the human left ventricle in hearts explanted from norma l, heart failure and amiodarone treated heart failure patients. Result s. Tissues isolated from the ventricles of heart failure patients rece iving chronic amiodarone therapy displayed M cell action potential dur ation (404 +/- 12 ms) significantly briefer (p < 0.05) than that recor ded in tissues isolated from normal hearts (439 +/- 22 ms) or from hea rt failure patients not treated with amiodarone (449 +/- 18 ms). Endoc ardial cells from amiodarone-treated heart failure patients displayed longer (p < 0.05) action potential duration (363 +/- 10 ms) than endoc ardial cells isolated from normal hearts (330 +/- 6 ms). As a conseque nce, the hetero geneity 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 ventr icular repolarization dispersion and the lower incidence of torsade de pointes observed with chronic amiodarone therapy as compared with oth er class III agents. (C) 1998 by the American College of Cardiology.