Effects of Chronic Amiodarone on the Electrical Restitution in the Human Ventricle With Reference to Its Antiarrhythmic Efficacy

INTRODUCTION: Dynamic instability of ventricular refractoriness represented by electrical restitution operates synergistically with tissue heterogeneity to increase the propensity for functional reentry leading to ventricular tachycardia/fibrillation (VT/VF). Little is known about the effect of chronic amiodarone on the electrical restitution in the human ventricle. METHODS AND RESULTS: Restitution kinetics of monophasic action potential duration (MAPD(90)) in the right ventricular outflow tract (RVOT) and apex (RVA), and of inverse of conduction time from RVOT to RVA (CT(-1)), were estimated by an S1-S2 protocol in 22 patients treated with amiodarone (180 ± 33 mg/day for 7 ± 9 months) and in 30 without treatment. In the untreated patients, the restitution kinetics of CT(-1) was steeper in the group with structural heart disease (SHD) (UNT(SHD+), n = 18) than without SHD (UNT(SHD-), n = 12), whereas MAPD(90) restitution parameters were comparable. In the amiodarone-treated patients (all with SHD), the shortest diastolic interval to produce a ventricular response (DI(min)) was increased, the maximum slope of MAPD(90) was flattened, and the magnitude of CT(-1) restitution was reduced as compared with UNT(SHD+). Sustained VT/VF was induced in 7 of 18 UNT(SHD+) (38.9%) and in 4 of 22 amiodarone-treated patients (18.2%, P = 0.07). Concomitant presence of increased CT(-1) restitution and dispersion of MAPD(90) restitution was required for the VT/VF induction. The suppression of VT/VF in the amiodarone-treated patients was associated with a smaller magnitude of CT(-1) restitution in the presence of limited dispersion of MAPD(90) restitution. CONCLUSION: Chronic amiodarone flattens restitution kinetics of MAPD(90) and CT(-1) in the human ventricle, which could be antiarrhythmic in patients with limited tissue heterogeneity.