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.
