Electrophysiological Effects of Late PCI After MI

BACKGROUND:

There is now unequivocal evidence that early coronary reperfusion using either thrombolytics
or primary angioplasty results in a long-term mortality reduction among individuals who have
had a heart attack. The benefit of early reperfusion (less than 6 hours after the heart
attack) was initially attributed to myocardial salvage and the resultant preservation of left
ventricular function. However, it is now known 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 suggests that clinical outcomes can potentially be improved by
late reperfusion after a heart attack. 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 studies that have evaluated late percutaneous transluminal
coronary angioplasty (PTCA) of occluded IRAs after a heart attack have produced conflicting
results.

These findings led to the organization of the Occluded Artery Trial (OAT), an international,
NHLBI-funded, randomized trial of 2,200 participants. OAT is testing the hypothesis that
mechanical reperfusion of an occluded IRA with PTCA and percutaneous coronary intervention
(PCI) 3 to 28 days after a heart attack in high-risk individuals will reduce mortality,
recurrent heart attacks, and hospitalization for class IV congestive heart failure.
Enhancement of electrical stability is one of the major mechanisms that has been proposed to
explain the association of an open IRA with an improved prognosis independent of myocardial
salvage.

DESIGN NARRATIVE:

This study is an ancillary study of OAT. It will characterize the effects of late PCI of
occluded IRAs on the most 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
participants at baseline, 30 days, and 1 year following a heart attack in order to determine
the effects of late PCI on the autonomic nervous system, ventricular repolarization, and
ventricular conduction abnormalities.

Inclusion Criteria:

- Has experienced a heart attack 3 to 28 days prior to study entry

- Persistently occluded IRA defined as either: 1) Thrombolysis in Myocardial Infarction
(TIMI) 0, with no flow beyond the site of occlusion; or 2) TIMI 1, with penetration of
dye beyond the site of occlusion without dye reaching the distal vessel

- LVEF less than 50% or proximal occlusion in a large vessel

- Normal sinus rhythm

- QRS duration less than 120 ms

- Able to return for follow-up assessment of arrhythmia markers one month and one year
after study entry

Exclusion Criteria:

- Has a clinical indication for revascularization (post-heart attack angina at rest;
significant inducible ischemia; or significant left main or triple vessel disease
requiring PTCA or CABG)

- Current serious illness or condition that limits 3-year survival

- Severe valvular disease

- Chronic total occlusion

- New York Heart Association Class III-IV congestive heart failure

- Prior left ventricular aneurysm in the recent heart attack location

- Is a poor candidate for PTCA/stent on the basis of angiographic or clinical criteria

- Cannot medically survive anticoagulation during PTCA/stent or antiplatelet therapy
after stent

- Pregnant