Early, Complete Infarct Vessel Patency: Arriving at a Gold Standard for Future Clinical Investigation in Myocardial...

Early clinical trials of thrombolytic therapy in the setting of acute myocardial infarction (AMI) demonstrated that early angiographic reperfusion correlated with improved survival. This supported the open-artery hypothesis that early reperfusion decreases infarct size, improves left ventricular function, and improves survival. Two subsequent comparative thrombolytic trials showed no difference in left ventricular function or survival between agents with different rates of reperfusion. Additionally, reduction in mortality was demonstrated without improvement in left ventricular function and with the late administration of thrombolytic therapy. Therefore, there was a real question as to the importance of infarct vessel patency, and its relation to clinical outcome. This article discusses the various markers of coronary artery patency, their relation to clinical outcome, and how they reflect perfusion at the tissue level. The coronary angiogram gives a snapshot view of the infarct-related artery (IRA) that does not reflect the dynamic process of vessel reocclusion and recanalization. The patent artery is therefore "open" at only a given time frame, and may undergo cyclic or complete reocclusion. Angiographically characterized flow has been demonstrated to be more clinically meaningful. The GUSTO-I trial was designed to test the open-artery hypothesis. This trial confirmed that improved early IRA patency and optimal (TIMI-3) flow correlated with improved survival. The presence of TIMI-3 flow in the IRA has consistently demonstrated significant improvement in patient morbidity and mortality, and conversely, less than optimal, but still "patent" (TIMI-2) flow in the IRA correlates with clinical outcomes observed in patients with occluded infarct vessels. Even TIMI-3 flow in the IRA does not always confirm perfusion of the myocardium at risk. Therefore, the "patent" IRA can be subsequently compromised by intermittent patency, reocclusion, less than TIMI-3 flow, and a "no-reflow" effect at the tissue level. The development of accurate, reliable non-invasive markers of IRA patency is crucial. This would allow a more selective application of invasive and interventional techniques to restore patency to the IRA. The merits and faults of these noninvasive markers are discussed. The ideal gold standard for establishing the adequacy of therapy in AMI is one that could detect rapid, complete, and sustained coronary reperfusion with adequate myocardial perfusion. Current technologic achievements allow an approach to this ideal; however, as of 1997, the coronary angiogram demonstrating TIMI-3 flow represents the clinically proven standard of optimal therapeutic efficacy.