Improving myocardial injury, infarct size, and myocardial salvage in the era of primary PCI for STEMI

Abstract

ST-segment elevation myocardial infarction (STEMI) is a major cause of mortality and disability worldwide. Reperfusion therapy by thrombolysis or primary percutaneous coronary intervention (PPCI) improves survival and quality of life in patients with STEMI. Despite the proven efficacy of timely reperfusion, mortality from STEMI remains high, particularly among patients with suboptimal reperfusion. Reperfusion injury following opening of occluded coronary arteries mitigates the efficacy of PPCI by further accentuating ischemic damage and increasing infarct size (IS). On the basis of experimental studies, it is assumed that nearly 50% of the final IS is because of the reperfusion injury. IS is a marker of ischemic damage and adequacy of reperfusion that is strongly related to mortality in reperfused patients with STEMI. Many therapeutic strategies including pharmacological and conditioning agents have been proven effective in reducing reperfusion injury and IS in preclinical research. Mechanistically, these agents act either by inhibiting reperfusion injury cascades or by activating cellular prosurvival pathways. Although most of these agents/strategies are at the experimental stage, some of them have been tested clinically in patients with STEMI. This review provides an update on key pharmacological agents and postconditioning used in the setting of PPCI to reduce reperfusion injury and IS. Despite intensive research, no strategy or intervention has been shown to prevent reperfusion injury or enhance myocardial salvage in a consistent manner in a clinical setting. A number of novel therapeutic strategies to reduce reperfusion injury in the setting of PPCI in patients with STEMI are currently under investigation. They will lead to a better understanding of reperfusion injury and to more efficient strategies for its prevention.

Manual thrombectomy efficiency in relationship to the area at risk in patients with myocardial infarction with TIMI 0‐1 coronary flow: Insights from an all comers registry

“…Another aspect that makes thrombectomy less usable is its inability to negotiate tortuous vessels with heavy calcification preventing it from reaching the occlusion . Final and most important, there are several determinants of final infarct size well beyond epicardial thrombus removal and coronary patency restoration, like the reperfusion injury phenomenon and the role of the microvascular environment . Simply put, thrombectomy targets only one aspect of reperfusion and it seems plausible that smaller AAR, longer ischemic time, ineffective thrombectomy and use in an already patent artery, may be associated with very small, or clinically unapparent benefits.…”

Does heart rate variability correlate with long-term prognosis in myocardial infarction patients treated by early revascularization?

“…The timely reperfusion strategy, with consequent reduction of infarct size and salvage of more heart muscle, as well as the multiple pharmacological therapy used, may have contributed to the better long-term survival of our STEMI patients[35]; the period of intensive and comprehensive exercise-based cardiac rehabilitation followed by our patients may also have contributed to their better prognosis[36]. …”

Remote ischemic conditioning improves myocardial parameters and clinical outcomes during primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials

“…However, the incidence of heart failure (≈ 25%) and cardiac death (≈ 10%) after PPCI remains high, partly due to myocardial ischemia/reperfusion (I/R) injury [ 17 ]. Paradoxical injury during reperfusion may cause irreversible cardiomyocyte damage and myocardial stunning, resulting in elevated cardiac enzymes, delayed cSTR, and limited myocardial salvage potential [ 18 , 19 ]. High levels of cardiac enzymes and insufficient cSTR have been recognized as an important predictor of long-term mortality in STEMI patients after PCI [ 20 – 22 ].…”