Von Willebrand factor, ADAMTS13, and coronary microvascular obstruction: beautiful hypotheses, ugly facts

This editorial refers to ‘The role of ADAMTS13 in acute myocardial infarction: cause or consequence?’ by E.S. Eerenberg et al. , pp. 194–203. The great tragedy of Science—the slaying of a beautiful hypothesis by an ugly fact. ST-segment elevation myocardial infarction (STEMI) usually results from acute thrombotic occlusion of a coronary artery and continues to be, despite preventive and therapeutic advances, a leading cause of death. 2 An important therapeutic goal in STEMI is reperfusion of the infarct-related artery, achievable with either fibrinolytic drugs or primary percutaneous coronary intervention (PCI). This in most cases results in the restoration of blood flow to the ischaemic, but still viable, myocardium, reducing infarct size. Accordingly, reducing time to treatment and maximizing myocardial salvage—in keeping with what has been termed the mantra ‘time is muscle’—represent a major challenge in the management of STEMI. 3 However, although national and individual hospitals' door-to-balloon times—now taken as a measure of the efficiency of the in-hospital treatment of STEMI—have improved significantly over the past years for patients undergoing primary PCI, in-hospital mortality of STEMI has remained virtually unchanged, 4 and the introduction of additional strategies to reduce in-hospital mortality in this population has been advocated. It has been stated that attention has to be turned to the development of systems addressing the continuum of STEMI care, from symptom onset through return to community. 5 To this regard, one unmet need is to address the coronary microvascular functional and structural dysfunction and obstruction (CMVO), which occurs frequently even after prompt epicardial recanalization of the infarct-related artery. CMVO has been shown to increase the risk of cardiovascular events regardless of the epicardial disease status. 6–8 Hence, at the time of reperfusion, patients with pre-existent microvascular dysfunction and CMVO will benefit less from prompt reopening of the epicardial vessel. Thus, preventing or relieving CMVO is a crucial target of innovative therapies for STEMI.