Shah Rashmi R
Medicines and Healthcare Products Regulatory Agency, Vauxhall, London SW8 5NQ, UK.
J Electrocardiol. 2005 Jan;38(1):10-8. doi: 10.1016/j.jelectrocard.2004.09.001.
Drug-induced delay in ventricular repolarization and proarrhythmias have attracted considerable regulatory attention. The measure of delayed ventricular repolarization most frequently used clinically is the ability of the new chemical entity (NCE) to prolong the QTc interval on surface electrocardiogram. Before they can be approved, new chemical entities with systemic bioavailability require characterization for their potential to prolong the QTc interval. Inevitably, QTc interval prolongation has come to be recognized as a surrogate marker of the risk of torsade de pointes (TdP)--a unique form of potentially fatal polymorphic ventricular tachycardia. Although it is the best and the simplest clinical measure that is available at present, QTc interval is not a reliable surrogate of TdP. Intramyocardial dispersion of repolarization appears to play a more important role both in electrical stability of the ventricles and in arrhythmogenesis. The potential importance of myocardial dispersion of refractoriness in arrhythmogenesis has led to a number of attempts to assess it from the surface electrocardiogram. This review summarizes the evidence for and against the predictive value of one of these attempts-measurement of the so-called QT dispersion. Although the concept of QT dispersion is the best known and most widely investigated, it has also proved to be the least successful in predicting the risks of drug-induced TdP.
药物引起的心室复极延迟和致心律失常作用已引起监管部门的高度关注。临床上最常使用的心室复极延迟指标是新化学实体（NCE）延长体表心电图QTc间期的能力。具有全身生物利用度的新化学实体在获批之前，需要对其延长QTc间期的潜力进行表征。不可避免地，QTc间期延长已被视为尖端扭转型室速（TdP）风险的替代标志物——TdP是一种潜在致命的多形性室性心动过速的独特形式。尽管QTc间期是目前可用的最佳且最简单的临床指标，但它并非TdP的可靠替代指标。复极的心肌内离散度似乎在心室电稳定性和心律失常发生中都起着更重要的作用。不应期心肌离散度在心律失常发生中的潜在重要性促使人们多次尝试从体表心电图评估它。本综述总结了支持和反对其中一种尝试——测量所谓QT离散度的预测价值的证据。尽管QT离散度的概念最为人所知且研究最为广泛，但事实证明它在预测药物诱发TdP的风险方面最不成功。
