Chronic amiodarone evokes no Torsade de Pointes arrhythmias despite QT lengthening in an animal model of acquired long-QT syndrome

Background-Amiodarone is an effective antiarrhythmic drug rarely associated with tor,,ade de pointes arrhythmias (TdP). The noniodinated compound dronedarone could resemble amiodarone and be devoid of the adverse effects. In the dog with chronic complete atrioventricular (AV) block (CAVB) and acquired Ion-QT syndrome, the electrophysiological and proarrhythmic properties of the drugs were compared after 4 weeks of oral treatment. Methods and Results-Amiodarone (n=7, 40 mg (.) kg(-1) (.) d(-1)) and dronedarone (n=8, 20 mg/kg BID) were started at 6 weeks of CAVB (baseline). Six dogs served as controls. Surface ECGs and endocardially placed monophasic action potential catheters in the left (LV) and right (RV) ventricles were recorded to assess QTc time, action potential duration (APD), interventricular dispersion (Delta APD=LV APD minus RV APD), early afterdepolarizations (EADs), ectopic beats, and TdP. Both amiodarone (+ 21%) and dronedarone (+ 31%) increased QTc time. Amiodarone showed no increase in Delta APD in 4 of 7 dogs, whereas dronedarone augmented Delta APD in 7 of 8 animals. After dronedarone, TdP occurred in 4 of 8 dogs with the highest Delta APD (105 +/- 20 ms). TdP was never seen with amiodarone, not even in the dogs that had Delta APD values comparable to those with dronedarone. Furthermore, a difference existed in EADs and ectopic activity incidence (dronedarone 3 of 8; amiodarone 0 of 7), which was also seen during an epinephrine challenge. Conclusions-In the CAVB dog model, both amiodarone and dronedarone prolong QT time (class III effect). The absence of TdP with amiodarone seems to be related to homogeneous APD lengthening in the majority of dogs and the lack of EADs and/or ventricular ectopic beats in all.