Pure hERG potassium channel block equally prolonged early and late repolarization, whereas additional inward current block preferentially shortened early repolarization.
RCT (n=22)
Randomized
Can the electrocardiogram differentiate the effects of pure hERG block versus multichannel drug block by separate analysis of early and late repolarization in human subjects?
Separate analysis of early and late repolarization on the ECG can differentiate pure hERG block from multichannel block, potentially improving the assessment of drug-induced arrhythmia risk.
Block of the hERG potassium channel and prolongation of the QT interval are predictors of drug-induced torsade de pointes. However, drugs that block the hERG potassium channel may also block other channels that mitigate torsade risk. We hypothesized that the electrocardiogram can differentiate the effects of multichannel drug block by separate analysis of early repolarization (global J-Tpeak) and late repolarization (global Tpeak-Tend). In this prospective randomized controlled clinical trial, 22 subjects received a pure hERG potassium channel blocker (dofetilide) and three drugs that block hERG and either calcium or late sodium currents (quinidine, ranolazine, and verapamil). The results show that hERG potassium channel block equally prolongs early and late repolarization, whereas additional inward current block (calcium or late sodium) preferentially shortens early repolarization. Characterization of multichannel drug effects on human cardiac repolarization is possible and may improve the utility of the electrocardiogram in the assessment of drug-related cardiac electrophysiology.
Johannesen et al. (Wed,) conducted a rct in Drug-induced multichannel block (n=22). Dofetilide, quinidine, ranolazine, and verapamil was evaluated on Early repolarization (global J-Tpeak) and late repolarization (global Tpeak-Tend). Pure hERG potassium channel block equally prolonged early and late repolarization, whereas additional inward current block preferentially shortened early repolarization.