Therapeutic interventions for coronary microvascular obstruction after acute myocardial infarction: Developments and challenges

ST-segment elevation myocardial infarction (STEMI) remains a major global cause of mortality and heart failure, even in the era of primary percutaneous coronary intervention (PCI). While timely epicardial reperfusion is routinely achieved, a substantial subset of patients experiences impaired myocardial perfusion due to coronary microvascular obstruction and dysfunction (MVO). MVO is a complex and multifactorial process driven by ischemia-reperfusion injury, endothelial dysfunction, distal embolization, inflammation, and emerging mechanisms such as pericyte-mediated capillary constriction. MVO is associated with larger infarct size, adverse remodeling, and worse long-term outcomes. While a wide range of novel pharmacological and mechanical therapies led to encouraging results in preclinical models and early-phase trials, definitive clinical benefit has yet to be established. Here, we reflect on the pathophysiological mechanisms of MVO, research methodologies, current therapeutic options and future strategies for rational drugs or devices development to limit MVO and improve prognosis in patients with STEMI.