LAUSR

Infarction is a turning point in the natural history of patients with coronary artery disease. While the event rate in stable coronary artery disease is currently quite low, after infarction, one in eight patients experience a major cardiovascular event. A crucial determinant of long-term outcome is infarct size and, in turn, left ventricular ejection fraction. Accordingly, many attempts have been made to reduce infarct size by educating the public about symptoms, by reducing doorto-balloon time, and by reducing reperfusion injury. Although reperfusion injury has attracted considerable research interest, the clinical application of most strategies was mixed, with a few showing benefit, but most failed. This issue is reviewed by Gerd Heusch from the University of Essen and Bernard J. Gersh from the Mayo Clinic in their article ‘The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continuing and formidable challenge’. They remind us that the incidence of ST-segment elevation myocardial infarction or STEMI has decreased over the last two decades in developed countries, but mortality remains substantial despite widespread access to reperfusion therapy. Furthermore, the development of heart failure, particularly among an expanding older population, is a major issue. In developing countries, the incidence of STEMI is increasing, and interventional reperfusion is often not available. Thus, research on the pathophysiology of acute myocardial infarction and reperfusion, notably the temporal and spatial evolution of ischaemic and reperfusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction remain important. The authors characterize the cardioprotective phenomena of ischaemic pre-conditioning, ischaemic post-conditioning, and remote ischaemic conditioning, and their underlying signal transduction pathways. Heusch and Gersh go on to discuss in detail the attempts to translate conditioning strategies and drug therapy into the clinical setting. Importantly, they discuss why most attempts to reduce infarct size and improve clinical outcomes in STEMI have failed. Currently, it appears that remote ischaemic conditioning and a few drugs such as atrial natriuretic peptide, exenatide, metoprolol, and esmolol reduce infarct size, but studies with clinical outcome as the primary endpoint are still under way. Acute coronary syndromes are associated with activation of platelets and the coagulation cascade. Without such phenomena, plaque rupture or erosion would not lead to acute coronary occlusion as is the case in STEMI. Haemostasis and thrombosis are complex, multifactorial processes that are thoroughly discussed in ‘Thrombosis and platelets: an update’ by Jane Freedman and colleagues from the University of Massachusetts at Worcester, MA. Despite major advances in elucidating the mechanistic pathways mediating platelet function and thrombosis, challenges in the treatment of vascular occlusive diseases persist. Pharmacological advances have greatly affected thrombotic outcomes, but this has led to the unwanted side effect of bleeding. Detailed assessment of the impact of non-thrombotic diseases on haemostasis and thrombosis is necessary to better evaluate thrombotic risk and establish optimal treatment. This review focuses on recent advances in understanding the contribution of evolving risk factors to thrombosis. As outlined in the review above, dual-antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome or ACS, but increases bleeding to a similar extent. In their clinical research manuscript ‘Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial’, Marco Valgimigli and colleagues from the University of Bern in Switzerland sought to determine the prognostic impact of myocardial infarction vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after an ACS. In 12 944 patients with non-ST-segment elevation ACS from the TRACER trial, they investigated the relative impact of myocardial infarction and bleeding occurring >30 days post-ACS and subsequent all-cause mortality.