Reducing Cardiac Injury during ST-Elevation Myocardial Infarction: A Reasoned Approach to a Multitarget Therapeutic Strategy

Abstract

The significant reduction in ‘ischemic time’ through capillary diffusion of primary percutaneous intervention (pPCI) has rendered myocardial-ischemia reperfusion injury (MIRI) prevention a major issue in order to improve the prognosis of ST elevation myocardial infarction (STEMI) patients. In fact, while the ischemic damage increases with the severity and the duration of blood flow reduction, reperfusion injury reaches its maximum with a moderate amount of ischemic injury. MIRI leads to the development of post-STEMI left ventricular remodeling (post-STEMI LVR), thereby increasing the risk of arrhythmias and heart failure. Single pharmacological and mechanical interventions have shown some benefits, but have not satisfactorily reduced mortality. Therefore, a multitarget therapeutic strategy is needed, but no univocal indications have come from the clinical trials performed so far. On the basis of the results of the consistent clinical studies analyzed in this review, we try to design a randomized clinical trial aimed at evaluating the effects of a reasoned multitarget therapeutic strategy on the prevention of post-STEMI LVR. In fact, we believe that the correct timing of pharmacological and mechanical intervention application, according to their specific ability to interfere with survival pathways, may significantly reduce the incidence of post-STEMI LVR and thus improve patient prognosis.

IL-6, IL-1RA and Resistin as Predictors of Left Ventricular Remodelling and Major Adverse Cardiac Events in Patients with Acute ST Elevation Myocardial Infarction

“…It occurs as a consequence of an increase in wall stress determined by distension of the infarcted area and cardiomyocyte loss [ 36 , 37 ]. There is clinical and experimental evidence showing that systemic and local inflammation is associated with LVR [ 38 ]. In the setting of acute myocardial ischaemia, the complex inflammatory response accompanied by a release of several cytokines is essential for proper infarct healing and scar formation [ 39 , 40 ].…”

IRF2 contributes to myocardial infarction via regulation of GSDMD induced pyroptosis

“…Despite the use of advanced therapeutic interventions ( 29 , 30 ), MI remains the leading cause of death from cardiovascular disease ( 31 ). Pyroptosis is a newly identified form of programmed cell death that is mediated by inflammatory caspase-1, accompanied by release of a large number of pro-inflammatory factors and induces a cascade of amplified inflammatory responses ( 32 ); it is associated with numerous diseases, including MI and myocardial cell loss following ischemia-reperfusion ( 33 , 34 ).…”

Current Knowledge of MicroRNAs (miRNAs) in Acute Coronary Syndrome (ACS): ST-Elevation Myocardial Infarction (STEMI)

“…As observed, they detain key functions in cardiac biogenesis, development, and progression, and given their stable structure and rapid circulation release after myocardial injury, they were proposed as potential future biomarkers in ACS. More specifically, older and recent evidence point out the potential role of miRNAs as novel biomarkers not only in STEMI, but also in STEMI's secondary complication such as LVR or HF (Table 1), , or even their use as promising new therapeutic targets [180,181] (Table 2). More than that, miRNAs have the potential to be used in the differential diagnosis of ACS [17,182] with: unstable angina [183], NSTEMI [94,184], and acute myocarditis [185].…”