REVIEW ARTICLE
Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion
Matthew T. Roe, MD*,
E. Magnus Ohman, MD, FACC*,
Arthur C. P. Maas, MD*,
Robert H. Christenson, PhD ,
Kenneth W. Mahaffey, MD*,
Christopher B. Granger, MD, FACC*,
Robert A. Harrington, MD, FACC*,
Robert M. Califf, MD, FACC* and
Mitchell W. Krucoff, MD, FACC*
* Duke Clinical Research Institute, Durham, North Carolina, USA
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA
Manuscript received December 8, 1999;
revised manuscript received August 1, 2000,
accepted September 20, 2000.
Reprint requests and correspondence: Dr. Matthew T. Roe, Duke Clinical Research Institute, P.O. Box 17969, Durham, North Carolina 27715
roe0001{at}mc.duke.edu
Successful reperfusion after acute myocardial infarction (MI) has traditionally been considered to be restoration of epicardial patency, but increasing evidence suggests that disordered microvascular function and inadequate myocardial tissue perfusion are often present despite infarct vessel patency. Thus, optimal reperfusion is being redefined to include intact microvascular 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 corrected TIMI frame count and myocardial blush grade, have been used to show that epicardial TIMI flow grade 3 may be an incomplete measure of reperfusion success. Furthermore, evolving noninvasive diagnostic techniques, including measurement of infarct size with cardiac marker release patterns or technetium-99m–sestamibi single-photon emission computed tomographic imaging and analysis of ST segment resolution appear to be useful complements to angiography for the assessment of myocardial tissue reperfusion. Promising adjunctive therapies that target microvascular dysfunction, including platelet glycoprotein IIb/IIIa inhibitors, and agents designed to improve tissue perfusion and attenuate reperfusion injury are being evaluated to further improve clinical outcomes after acute MI. To accelerate development of these new reperfusion regimens, an integrated approach to phase II clinical trials 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-artery hypothesis is expected to shift downstream and guide efforts to further improve myocardial salvage and clinical outcomes after acute MI.
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Abbreviations and Acronyms
| | CK(-MB) | = creatine kinase (MB fraction) | | cTFC | = corrected TIMI frame count | | GUSTO-I | = Global Utilization of Streptokinase and TPA (alteplase) for Occluded coronary arteries | | IRA | = infarct-related artery | | MCE | = myocardial contrast echocardiography | | MI | = myocardial infarction | | MRI | = magnetic resonance imaging | | SPECT | = single-photon emission computed tomography | | 99mTc | = technetium-99m | | TIMI | = Thrombolysis In Myocardial Infarction |
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