BACKGROUND: 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 (less than 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 infarct-related arteries 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 2,200 patients that is testing the hypothesis that mechanical reperfusion of an occluded infarct-related artery 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 infarct-related artery with an improved prognosis independent of myocardial salvage. The present OAT-EP ancillary study will characterize the effects of late PCI of occluded infarct-related arteries 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.

DESIGN NARRATIVE: The OAT-EP ancillary study will characterize the effects of late percutaneous coronary intervention (PCI) of occluded infarct-related arteries 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 myocardial infarction in order to delineate the effects of late PCI on the autonomic nervous system, ventricular repolarization, and ventricular conduction abnormalities, respectively.

The eligibility criteria for the Occluded Artery Trial (OAT) are recent myocardial infarction (3-28 days, Day 1 is the day of MI onset) and a persistently occluded infarct-related artery defined as Thrombolysis in Myocardial Infarction (TIMI) 0 (no flow beyond the site of occlusion) or TIMI 1 flow (penetration of dye beyond the site of occlusion without dye reaching the distal vessel). The patients should meet the criteria for high risk, which are either left ventricular ejection fraction (LVEF) < 50% or proximal occlusion in a large vessel (see OAT protocol). In addition, to be considered eligible for the OAT-EP ancillary study, the patients must be in normal sinus rhythm, have a QRS duration < 120 ms, and consent to return for follow-up assessment of arrhythmia markers at one month and one year after randomization.

Excluded from participation will be patients with a clinical indication for revascularization (post-MI angina at rest; significant inducible ischemia; or significant left main or triple vessel disease requiring PTCA or CABG). Also excluded from participation will be patients with another serious illness or condition that limits 3-year survival, severe valvular disease, chronic total occlusion, NYHA Class III-IV congestive heart failure, or prior left ventricular aneurysm in the recent MI location. Patients who are poor candidates for PTCA/stent on the basis of angiographic or clinical criteria, or with contraindication to anticoagulation during PTCA/stent or antiplatelet therapy after stent may not participate. All premenopausal women must have a negative pregnancy test.