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

Modulation of Electrical Restitution with Amiodarone. 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 . (J Cardiovasc Electrophysiol, Vol. 22, pp. 669‐676, June 2011)