Shifting the open-artery hypothesis downstream: The quest for optimal reperfusion

Successful reperfusion after acute myocardial infarction (MI) has tradition ally been considered to be restoration of epicardial patency, but increasin g evidence suggests that disordered microvascular function and inadequate m yocardial tissue perfusion are often present despite infarct vessel patency . Thus, optimal reperfusion is being redefined to include intact microvascu lar flow and restored myocardial perfusion, as well as sustained epicardial patency. Coronary angiography has been used as the gold standard to define failed reperfusion, according to the Thrombolysis In Myocardial Infarction (TIMI) flow grades. However, new angiographic techniques, including the co rrected TIMI frame count and myocardial blush grade, have been used to show that epicardial TIMI flow grade 3 may be an incomplete measure of reperfus ion success. Furthermore, evolving noninvasive diagnostic techniques, inclu ding measurement of infarct size with cardiac marker release patterns or te chnetium-99m-sestamibi single-photon emission computed tomographic imaging and analysis of ST segment resolution appear to be useful complements to an giography for the assessment of myocardial tissue reperfusion. Promising ad junctive therapies that target microvascular dysfunction, including platele t glycoprotein IIb/IIIa inhibitors, and agents designed to improve tissue p erfusion and attenuate reperfusion injury are being evaluated to further im prove clinical outcomes after acute MI. To accelerate development of these new reperfusion regimens, an integrated approach to phase II clinical trial s that incorporates multiple efficacy variables, including angiography and noninvasive biomarkers of microvascular dysfunction, should be considered. Thus, as the reperfusion era moves into the next millennium, the open-arter y hypothesis is expected to shift downstream and guide efforts to further i mprove myocardial salvage and clinical outcomes after acute MI. (J Am Cell Cardiol 2001;37:9-18) (C) 2001 by the American College of Cardiology.