The effects of combined thrombolytic and platelet inhibitor therapy on myocardial and microvascular perfusion
James de Lemos, M.D.

Dr. de Lemos is at The University of Texas Southwestern Medical Center, Dauas, Texas.

The primary objective of reperfusion therapy for ST-elevation myocardial infarction (MI) has been to restore normal epicardial blood flow in the infarct-related coronary artery. Even among patients who achieve normal epicardial flow, however, tissue-level perfusion may be inadequate. Using myocardial contrast echocardiography, investigators have demonstrated that many patients with successful epicardial reperfusion have "no reflow" at the level of the myocardium and coronary microcirculation.1 Such patients, with normal epicardial flow but impaired microvascular perfusion, are at high risk for the development of congestive heart failure and death.2 Investigators have extended these findings using other measures of tissue perfusion, including cardiac magnetic resonance imaging (MRI), nuclear scintigraphy, positron emission tomography (PET) scanning, Doppler Flow-Wire studies, and recently an angiographic measurement of microvascular perfusion, called the TIMI Myocardial Perfusion Grade.3

Taken together, these studies challenge the concept that TIMI grade 3 flow alone is indicative of successful reperfusion, and suggest that markers of tissue-level perfusion will provide additive and independent prognostic value. Unfortunately, none of the tests mentioned above is readily available to the clinician. As a result, interest has focused on the analysis of ST resolution on the routine 12-lead electrocardiogram (ECG) as a simple and universally available means of assessing tissue-level reperfusion. We have recently demonstrated that the association between ST resolution and mortality is independent of epicardial blood flow.4 These studies support the hypothesis that ST resolution is a surrogate for tissue-level reperfusion. When complete ST resolution is seen 90 minutes after thrombolysis, successful reperfusion has occurred at both the epicardial and microvascular levels. Incomplete ST resolution, on the other hand, is indicative of either an occluded infarct-related artery or a patent artery with failure of tissue-level reperfusion.

Since failure of tissue-level reperfusion frequently occurs despite successful epicardial reperfusion, specific therapy targeted at the coronary microcirculation may improve outcomes in patients receiving reperfusion therapy. In the TIMI 14 trial, the combination of abciximab and reduced-dose alteplase (tPA) resulted in a significant improvement in epicardial flow (measured by TIMI grade 3 flow rates and TIMI frame counts at 60 and 90 minutes) when compared with tPA alone.5 We sought to evaluate whether combination therapy also resulted in an improvement in myocardial perfusion, as assessed by ST-segment resolution. Patients who received combination therapy had a higher probability of complete ST resolution than those receiving tPA alone.