High-Rate Pacing Reduces Variability of Repolarization and Prevents Repolarization-Dependent Arrhythmias in Dogs With Chronic AV Block

High‐Rate Pacing Prevents Drug‐Induced Arrhythmias. Introduction: High‐rate pacing may have an inhibitory effect on the initiation of Torsade de Pointes arrhythmias (TdP). However, permanent pacing is only indicated in high‐risk patients. We performed a proof of concept study into automatic overdrive pacing for prevention of drug‐induced TdP, using short‐term variability of repolarization (STV) as a feedback parameter of arrhythmic risk. Methods and Results: The minimal signal sampling frequency required for measuring STV was determined through computer simulation. Arrhythmogenic response to dofetilide (25 μg/kg/5minutes) was tested at two different paced heart rates (60–65 bpm vs 100–110 bpm) in 7 dogs with chronic atrioventricular block, while recording right and left ventricular (LV) monophasic action potential (MAP) and LV electrogram (EGM). Simulations showed a sampling frequency of 500 Hz is sufficient to capture relevant STV values. High‐rate pacing prevented dofetilide‐induced TdP seen at the low rate (low: 6/7 vs high: 1/7). At the low rate, STV from LV MAP duration increased before occurrence of spontaneous, ectopic activity and TdP (1.7 ± 0.6–3.0 ± 1.8 ms, P < 0.05), but at the high‐rate STV did not change significantly (0.9 ± 0.2–1.5 ± 1.4 ms, NS). Regression analysis showed a close relation between STV calculated from LV MAP and from LV EGM (R2= 0.71). Conclusions: High‐rate pacing increases repolarization reserve in dogs with chronic atrioventricular block, preventing dofetilide‐induced TdP. Changes in repolarization reserve are reflected in values of STV. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1384‐1391, December 2010)