Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
J Cardiovasc Pharmacol. 2010 Jun;55(6):544-54. doi: 10.1097/FJC.0b013e3181d6b781.
Over the course of more than a century, visible T-wave alternans (TWA), defined as a beat-to-beat alternation in the morphology and amplitude of the ST segment or T wave, has been observed to occur in close association with life-threatening arrhythmias in patients with acute myocardial ischemia and infarction, heart failure, Prinzmetal's angina, and channelopathies, including Brugada and long QT syndromes. Over 100 studies enrolling a total of more than 12,000 patients support the predictivity of TWA testing for cardiovascular mortality and sudden cardiac death during both exercise and ambulatory electrocardiogram monitoring. To date, the main intended application has been to aid decision-making for cardioverter-defibrillator implantation. The prospect that TWA could be used to guide pharmacologic therapy has not received adequate attention. The literature supporting the utility of TWA as a therapeutic marker of antiarrhythmic effects and proarrhythmia is reviewed for each of the major antiarrhythmic drug classes. Beta-adrenergic and sodium channel blocking agents are the most widely studied drug classes in clinical TWA investigations, which report reductions in TWA magnitude. Patients with Brugada syndrome constitute a significant exception, because sodium channel blockade provokes the diagnostic electrocardiogram changes as well as macroscopic TWA. Calcium channel blockers have undergone extensive research in several animal models, but, surprisingly, no clinical studies on TWA with this class of drugs have been performed. Interestingly, TWA may help to detect the beneficial effects of nonantiarrhythmic agents such as the angiotensin II receptor blocker valsartan, which exert their protective effects through putative indirect actions on myocardial remodeling. There is also suggestive evidence that the proarrhythmic effects associated with cardiovascular and noncardiovascular agents may be disclosed by elevated levels of TWA. Thus, the emerging collective evidence indicates the broad utility of TWA in estimating antiarrhythmic and proarrhythmic effects of diverse agents across differing pathologies. We conclude that quantitative analysis of TWA has considerable potential to guide pharmacologic therapy.
一个多世纪以来，人们观察到一种可见的 T 波电交替（TWA），其定义为 ST 段或 T 波形态和幅度的逐搏交替，它与急性心肌缺血和梗死、心力衰竭、变异性心绞痛和通道病患者的致命性心律失常密切相关，包括 Brugada 和长 QT 综合征。超过 100 项研究共纳入了超过 12000 名患者，支持 TWA 测试对运动和动态心电图监测中心血管死亡率和心源性猝死的预测性。迄今为止，主要的应用目的是帮助决定是否植入心脏复律除颤器。TWA 可用于指导抗心律失常药物治疗的前景尚未得到足够关注。本文回顾了每一大类抗心律失常药物作为抗心律失常作用和致心律失常的治疗标志物的效用的文献。β-肾上腺素能和钠通道阻滞剂是临床 TWA 研究中研究最广泛的药物类别，这些研究报告 TWA 幅度降低。Brugada 综合征患者是一个显著的例外，因为钠通道阻滞剂会引发诊断性心电图变化以及宏观 TWA。钙通道阻滞剂在几个动物模型中进行了广泛的研究，但令人惊讶的是，没有关于此类药物的 TWA 的临床研究。有趣的是，TWA 可能有助于检测非抗心律失常药物如血管紧张素 II 受体阻滞剂缬沙坦的有益作用，后者通过对心肌重构的可能间接作用发挥其保护作用。也有提示性证据表明，心血管和非心血管药物相关的致心律失常作用可能通过升高的 TWA 水平来揭示。因此，新兴的综合证据表明 TWA 在估计不同病理状态下不同药物的抗心律失常和致心律失常作用方面具有广泛的用途。我们得出结论，TWA 的定量分析具有很大的潜力来指导药物治疗。
