Electrophysiologic effects of late PCI (OAT-EP)

描述(由申请人提供)： 现在有明确的证据表明，早期使用溶栓剂或直接血管成形术的冠状动脉再通可以降低急性心肌梗死(AMI)患者的长期死亡率。早期再通(发病6小时后)的益处机制最初归因于心肌挽救和由此产生的左心功能的保存。然而，现在很明显，与溶栓治疗相关的生存益处并不总是与左心室射血分数(LVEF)的重大改善相关。这些观察结果导致了“晚期开放动脉假说”的提出，该假说认为急性心肌梗死后晚期再灌注有可能改善临床结果。临床观察性研究表明，溶栓后梗死相关动脉(IRA)的晚期再通与生存期的改善有关，这种延长不依赖于LVEF，因此不能完全用挽救心肌来解释。然而，目前缺乏对晚期开放动脉假说的确凿证据，因为先前评估急性心肌梗死后闭塞IRA的晚期经皮冠状动脉腔内成形术(PTCA)的前瞻性研究得出了相互矛盾的结果。这些考虑导致了闭塞动脉试验(OAT)的组织，这是一项由NHLBI资助的国际随机试验，有3200名患者参加，该试验正在测试一项假设，即在高危患者急性心肌梗死后3-28天，使用PTCA和支架(PCI)对闭塞的IRA进行机械再通将减少死亡率、复发心肌梗死和IV级充血性心力衰竭住院的综合终点。电稳定性的增强是已提出的解释开放的IRA与独立于心肌挽救的预后改善相关的主要机制之一。目前的OAT-EP辅助研究应用将表征闭塞IRA的晚期经皮冠状动脉介入治疗对恶性室性心律失常易感性的最重要和最临床相关的非侵入性标记物的影响：心率变异性、T波变异性和信号平均心电图。这些分析将在基线、心肌梗死后30天和一年后对300名患者进行，以分别描述晚期经皮冠状动脉介入治疗对自主神经系统、心室复极和心室传导异常的影响。

DESCRIPTION (provided by applicant): There is now unequivocal evidence that early coronary reperfusion using either thrombolytics or primary angioplasty results in a long-term mortality reduction among patients who present with acute myocardial infarction (AMI). The mechanism of the benefit of early reperfusion (< 6 hours after AMI onset) was initially attributed to myocardial salvage and the resultant preservation of left ventricular function. However, it is now evident that the survival benefit associated with thrombolytic therapy is not consistently associated with a major improvement in left ventricular ejection fraction (LVEF). These observations led to the formulation of the "late open artery hypothesis", which posits that clinical outcomes can potentially be improved by late reperfusion after AMI. Observational clinical studies have suggested that late patency of the infarct-related artery (IRA) after thrombolysis is associated with a survival benefit that is independent of LVEF and therefore cannot be solely explained by salvage of myocardium. Definitive proof of the late open artery hypothesis is currently lacking, however, because previous prospective studies that have evaluated late percutaneous transluminal coronary angioplasty (PTCA) of occluded IRAs after AMI have produced conflicting results. These considerations led to the organization of the Occluded Artery Trial (OAT), an international, NHLBI-funded randomized trial of 3,200 patients that is testing the hypothesis that mechanical reperfusion of an occluded IRA with PTCA and stenting (PCI) 3-28 days after AMI in high risk patients will reduce a composite endpoint of mortality, recurrent MI, and hospitalization for class IV congestive heart failure. Enhancement of electrical stability is one of the major mechanisms that have been proposed to explain the association of an open IRA with an improved prognosis independent of myocardial salvage. The present OAT-EP ancillary study application will characterize the effects of late PCI of occluded IRAs on the most prognostically important and clinically relevant noninvasive markers of vulnerability to malignant ventricular arrhythmias: heart rate variability, T wave variability, and signal-averaged electrocardiography. These analyses will be performed in 300 patients at baseline, 30 days and one year following MI in order to delineate the effects of late PCI on the autonomic nervous system, ventricular repolarization, and ventricular conduction abnormalities, respectively.