Postconditioning during primary percutaneaous angioplasty: is the jury still out?

Abstract

Enrico Favaretto Division of Cardiology, Department of Cardiac, Thoracic & Vascular Sciences, University Hospital of Padua, via Giustiniani, 2, 35128 Padua, Italy IS reduction. To this regard, it is well known that single-proton emission computed tomography is a relatively gross measurement of IS compared with cardiac magnetic resonance (CMR), which has proven to be superior to single-proton emission computed tomography with regard to detection and quantification of myocardial infarction. Moreover, all of these earlier experiences did not stratify the randomization for STEMI location nor related IS to the myocardial area at risk. These adjustments, although not definitive, might be important to reduce bias, in particular when studying a small population. More recently, five randomized trials assessing the impact of PostC on IS, as assessed by CMR, were published [14–19]. Among them, in the study by Lonborg et al., the absolute IS by CMR (3 months post-STEMI, manual delineation; study primary end point) did not differ significantly between groups and the potential benefit in IS reduction was inferred only after use of the infarct endocardial surface area to estimate the myocardial area at risk, in order to estimate myocardial salvage [14]. Although the authors found a good correlation between this parameter and CMR edema imaging, these data remain unpublished. In 2010, Sorensson et al. did not find significant differences between control and PostC groups in IS by CMR performed 6–9 days after index STEMI [15]. In this case, IS was quantified by an automatic CMR algorithm and related to the myocardial area at risk determined by left ventriculo graphy. Freixa et al. found that PostC, during percutaneous coronary intervention, did not reduce IS at both early and late follow-up and it might also have a potential harmful effect [17]. In the POST-AMI randomized trial (stratified for STEMI location), we evaluated the effect of PostC on IS in STEMI patients treating all ST-elevation acute myocardial infarction (STEMI) continues to represent a major cause of mortality and morbidity worldwide [1] and infarct size (IS) is a major determinant of prognosis in these patients [2]. Although rapid reperfusion is the mainstay definitive treatment for ischemic myocardium, it may exacerbate the ischemia-related injury (i.e., reperfusion injury) counteracting the benefit of early reperfusion [3]. Despite major therapeutic advances in STEMI treatment, adjunctive therapies to reduce reperfusion injury and, ultimately, IS are scant in humans [3]. In 1986, Murry et al. first reported the IS-limiting effect of ischemic preconditioning in a landmark study [4]. In 2003, Zhao et al. demonstrated in a dog model that repetitive brief ischemic episodes applied immediately at the onset of reperfusion after a prolonged ischemic insult also can afford cardioprotection, reducing IS and preserving endothelial function similarly to conventional preconditioning, and termed this phenomenon ischemic postconditioning (PostC) [5]. Unlike preconditioning, the experimental design of PostC allows direct application to clinical settings, especially during primary percutaneous coronary interventions. Inflation and deflation of the balloon after reopening the coronary artery can mimic repetitive coronary artery clamping in postconditioned animal models [6]. Notwithstanding, unlike animal models, clinical studies on the prognostic impact of PostC led to conflicting results [7–19]. In 2005, the first studies in humans testing PostC were published by Staat et al. [7] and Laskey [8]. Since then, other small clinical randomized trials have found a benefit of PostC on IS reduction [9–13]. However, these studies used release of biomarkers (serum creatinine kinase) or single-proton emission computed tomography as diagnostic tools for detection of