Differentiating Drug-Induced Multichannel Block on the Electrocardiogram: Randomized Study of Dofetilide, Quinidine, Ranolazine, and Verapamil
Differentiating Drug-Induced Multichannel Block on the Electrocardiogram: Randomized Study of Dofetilide, Quinidine, Ranolazine, and Verapamil
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DOI：
10.1038/clpt.2014.155
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发表时间：
2014-11-01
影响因子：
6.7
通讯作者：
Strauss, D. G.
中科院分区：
文献类型：
--
作者：
Johannesen, L.;Vicente, J.;Strauss, D. G.
hERG钾通道阻滞和QT间期延长是药物诱导的尖端扭转型室性心动过速的预测因子。然而，阻断hERG钾通道的药物也可能阻断其他降低扭转型室性心动过速风险的通道。我们假设心电图可以通过对早期复极（整体J-T峰）和晚期复极（整体T峰-T末）的单独分析来区分多通道药物阻滞的影响。在这项前瞻性随机对照临床试验中，22例受试者接受了纯hERG钾通道阻滞剂（多非利特）和三种阻滞hERG和钙或晚期钠电流的药物（奎尼丁、雷诺嗪和维拉帕米）。结果表明，hERG钾通道阻断同样地阻断早期和晚期复极，而额外的内向电流阻断（钙或晚期钠）优先缩短早期复极。表征多通道药物对人体心脏复极的影响是可能的，并可能提高心电图在药物相关心脏电生理学评估中的实用性。
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-T-peak) and late repolarization (global T-peak-T-end). 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.