The Achilles heel of successful treatment of acute myocardial infarction: Tackling large thrombus burden and no reflow

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for ST-segment elevation myocardial infarction (STEMI), rapidly restoring coronary blood flow, limiting infarct size, improving survival, and reducing recurrent ischemic events. Advances in interventional techniques and adjunctive therapies have enhanced its safety and efficacy over time, with high rates of successful epicardial reperfusion, however large intracoronary thrombus burden remains a major challenge during primary PCI. Extensive thrombus promotes distal embolization of platelet-fibrin aggregates and atherothrombotic debris, which mechanically occlude the downstream capillary bed during reperfusion triggering microvascular obstruction, inflammation, endothelial dysfunction, and the no-reflow phenomenon. Consequently, restoration of epicardial patency does not always translate into effective myocardial tissue perfusion or myocardial salvage, resulting in larger infarcts and worse clinical outcomes. Contemporary management strategies aim to reduce thrombus burden, preserve microvascular integrity, and improve myocardial salvage through adjunctive pharmacologic therapies, selective mechanical interventions, and optimized procedural techniques. Although routine use of aspiration thrombectomy and many adjunctive intracoronary therapies have not consistently improved clinical outcomes, selective use in carefully chosen patients remains an important component of contemporary practice. Emerging strategies are shifting the focus beyond restoration of epicardial flow toward preservation of the coronary microcirculation. Advances in intracoronary imaging, precision PCI, and therapies targeting inflammation, reperfusion injury, and microvascular dysfunction offer promising opportunities to individualize treatment and further improve outcomes in patients with STEMI and large thrombus burden.