Hohnloser S H
Department of Medicine, J.W. Goethe University, Frankfurt, Germany.
Am J Cardiol. 1997 Oct 23;80(8A):82G-89G. doi: 10.1016/s0002-9149(97)00717-0.
The nature of the proarrhythmic reactions induced by antiarrhythmic drugs is linked to the electrophysiologic effects of these agents. Torsades de pointes is the classic form of proarrhythmia observed during therapy with any drug that prolongs repolarization, for example, the class III agents. Its precise electrophysiologic mechanism is not fully elucidated, although the arrhythmia is generally considered to be due either to early afterdepolarization in the context of prolonged cardiac repolarization or to an increase in spatial or temporal dispersion of repolarization. Among the class III drugs the proarrhythmic risk appears to be lowest for amiodarone, probably due to its complex electrophysiologic profile that may create significant myocardial electrical homogeneity. In the case of d,l-sotalol, the incidence of torsades de pointes increases with dose and the baseline values of the QT interval. Where d-sotalol and other pure class III agents might fall into the varying spectrum of proarrhythmic potential remains unclear. That d-sotalol has been found to increase mortality in postinfarction patients with ventricular dysfunction (the Survival With Oral d-Sotalol [SWORD] trial) is a matter of considerable concern. It raises the possibility that such a phenomenon may be a common property of most, if not all, pure class III compounds. Accordingly, care must be taken to minimize the likelihood of proarrhythmia; in particular, therapy with a class III agent should only be initiated in the presence of a defined indication established on the basis of clinical trials. When class III antiarrhythmic drug-induced proarrhythmia occurs, immediate cessation of therapy with the responsible agent and correction of predisposing factors, such as electrolyte disorders or bradycardia, is mandatory. Intravenous administration of high-dose magnesium sulfate has been demonstrated to be effective in terminating and preventing new episodes of torsades de pointes. Temporary pacing may be necessary.
抗心律失常药物诱发的致心律失常反应的性质与这些药物的电生理效应相关。尖端扭转型室速是在使用任何延长复极的药物（例如Ⅲ类药物）治疗期间观察到的典型致心律失常形式。尽管一般认为该心律失常是由于心脏复极延长情况下的早期后除极或复极的空间或时间离散增加所致，但其确切的电生理机制尚未完全阐明。在Ⅲ类药物中，胺碘酮的致心律失常风险似乎最低，这可能是由于其复杂的电生理特性，可能会产生显著的心肌电均匀性。对于d，l-索他洛尔，尖端扭转型室速的发生率随剂量和QT间期的基线值增加。d-索他洛尔和其他纯Ⅲ类药物在不同的致心律失常潜力范围内的情况尚不清楚。已发现d-索他洛尔会增加心肌梗死后心室功能不全患者的死亡率（口服d-索他洛尔生存[SWORD]试验），这是一个相当令人担忧的问题。这增加了这样一种可能性，即这种现象可能是大多数（如果不是全部）纯Ⅲ类化合物的共同特性。因此，必须注意尽量减少致心律失常的可能性；特别是，Ⅲ类药物的治疗应仅在基于临床试验确定的明确适应症存在时开始。当发生Ⅲ类抗心律失常药物诱发的致心律失常时，必须立即停止使用相关药物治疗并纠正诱发因素，如电解质紊乱或心动过缓。静脉注射高剂量硫酸镁已被证明对终止和预防尖端扭转型室速的新发作有效。可能需要临时起搏。
