Abstract 13875: Torsade de Pointes Arrhythmias Arise at the Site of Maximal Heterogeneity of Repolarization in the Chronic Complete AV-block Dog

Abstract

Introduction: The chronic complete atrioventricular block (CAVB) dog model is highly sensitive for drug-induced Torsade de Pointes (TdP) arrhythmias. Focal mechanisms have been considered as trigger for the onset of TdP, however, its exact mechanism remains unclear. In this study, detailed mapping of the heart was performed to assess intraventricular heterogeneity of repolarization in relation to the initation of TdP. Methods: In 6 animals, 48 needles, each containing 4 electrodes, were inserted in the ventricles. During right ventricular apex pacing (cycle length: 1000-1500ms) local unipolar electrograms were recorded before and after administration of dofetilide. Activation- and repolarization times (RT) were measured at baseline and before occurrence of the first TdP or at 5 minutes after start of dofetilide infusion in inducible and non-inducible dogs. Maximal RT differences were calculated in the left ventricle 1) within adjacent electrodes in different planes (transmural, apex-base, anterior-posterior) and 2) within a square of 4 needles (3D dispersion). Results: TdP could be induced in 3 out of 6 animals. No difference in mean RT was observed between inducible and non-inducible dogs both at baseline (343±30 vs. 345±17ms) and after dofetilide administration (582±73 vs. 508±15ms). Maximal dispersion of RT was not different between both groups at baseline: 36±32 vs. 32±7ms (transmural), 50±20 vs. 42±9ms (apex-base), 71±28 vs. 47±13ms (anterior-posterior), 83±19 vs. 70±6ms (3D dispersion). After dofetilide infusion anterior-posterior (203±28 vs. 142±34ms, p=0.04) and 3D dispersion (268±41 vs. 176±48ms, p=0.03) showed a higher RT difference in the inducible animals. No differences were observed for transmural (124±14 vs. 116±18ms, p=0.557) and apex-base dispersion (142±12 vs. 121±23ms, p=0.229). The initiating beat of the TdP arose consistently from the region with the largest local spatial dispersion of repolarization moments. Conclusion: TdP arises from a region with maximal heterogeneity of repolarization and animals susceptible for TdP demonstrate higher RT differences. These results suggest that a certain gradient of repolarization moments is required in order to initiate TdP in CAVB dogs.