Coronary Microvascular Injury in Reperfused Acute Myocardial Infarction: A View From an Integrative Perspective

T aking its incidence and prognostic importance into account, acute ST-segment–elevation myocardial infarction (STEMI) can be regarded as one of the most important challenges faced in the field of clinical cardiology. Coronary artery disease and particularly acute myocardial infarction (AMI) are the leading causes of death and disability worldwide. Despite remarkable progress in the fight, particularly in the past 3 decades, there is still room for improvement. Indeed, the standardized 1-year death rate for STEMI has nearly halved over a 25-year period. This decrease in mortality is attributable to outstanding achievement accomplished in the limitation of final myocardial infarct (MI) size by introduction of efficacious reperfusion methods such as fibrinolysis and primary percutaneous coronary intervention (pPCI) during that period. Currently, reopening of the occluded epicardial coronary artery by timely pPCI is widely accepted as the most effective treatment for patients presenting with an acute STEMI in limiting final MI size and preserving left ventricular (LV) function. However, despite successful reperfusion by pPCI, mortality (15%) and particularly post-MI morbidity still remain significant at 1 year. This disappointing course has been partly attributed to the potential detrimental effects of reperfusion itself. Indeed, reperfusion may lead to a further loss of cardiomyocytes that are succeeded to survive after initial ischemic insult in the subtended myocardial territory. Hemodynamic manifestations of this postreperfusion process include “no-reflow phenomenon”—severe myocardial malperfusion despite restoration of epicardial coronary patency, which has been reported to occur in up to 50% of patients with STEMI following pPCI despite restoration of thrombolysis in myocardial flow 3 in the epicardial coronary artery. In general, myocardial no-reflow phenomenon refers to severe microvascular injury that is known to be associated with impaired LV function and poor prognosis in patients undergoing successful pPCI. In addition, the magnitude of the preserved microvasculature at the acute phase is one of the major determinants of the long-term functional and structural myocardial recovery. Although it occurs in every patient undergoing pPCI at varying intensity, identification of coronary microvascular injury depends on the diagnostic capability of the method used in its detection. Considering this high incidence and its important clinical consequences, a better understanding of the mechanisms underlying severe coronary microvascular injury resulting in myocardial malperfusion (myocardial tissue “no reflow”) after pPCI is mandatory to be able to develop efficacious therapeutic interventions for preventing this complication of STEMI. Nevertheless, our current knowledge on the pathophysiology of microvascular damage after pPCI is poor, and hence recommendation of risk prediction and therapeutic interventions could be premature and limited. Notably, given the repeated failure of recent trials aiming to protect microcirculation during pPCI, it is obvious that identification of an appropriate therapeutic target linked to the underpinning mechanism has utmost clinical importance in the treatment of patients who develop extensive microvascular injury after pPCI. Although there is not yet a widely accepted and proven therapeutic intervention to limit postreperfusion microvascular injury, examination of microvascular integrity in the catheterization laboratory immediately upon completion of pPCI can provide a unique opportunity for timely identification of this patient subset with From the Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey (M.S., B.U., Z.B., S.U.); Radboud University Medical Center, Nijmegen, NL (N.v.R.); The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, London, United Kingdom (H.B., D.J.H.); Papworth Hospital NHS Trust, Cambridge, United Kingdom (H.B., D.J.H.); National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore (D.J.H.); Cardiovascular and Metabolic Disorders Program, DukeNational University of Singapore, Singapore (D.J.H.); Yong Loo Lin School of Medicine, National University Singapore, Singapore (D.J.H.); The National Institute of Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom (D.J.H.); Barts Heart Centre, St Bartholomew’s Hospital, London, United Kingdom (D.J.H.). Correspondence to: Murat Sezer, MD, Department of Cardiology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey. E-mails: sezerm@istanbul.edu. tr, sezermr@gmail.com J Am Heart Assoc. 2018;7:e009949. DOI: 10.1161/JAHA.118. 009949. a 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.