Importantly, some patients who arrive early, and many who arrive late, develop massive myocardial loss despite revascularization of the epicardial coronary artery. These patients usually present with TIMI flow grade 0 or 124, 25. Not uncommonly, the flow after stent implantation is TIMI 2 or less in the absence of optimal myocardial blush24,25. This phenomenon, known as ‘the no-reflow phenomenon’ is related to the pathophysiology of STEMI. An important observation is that embolization to the downstream microcirculation of micro thrombi and microscopic debris from the ruptured plaque and thrombus occurs as part of the STEMI syndrome. This can transpire many hours before the appearance of STEMI symptoms. A second relevant observation is that microcirculation responds to vasospastic materials released by the thrombus, and prolonged spasm results in very high resistance to flow and possible damage to both endothelial and smooth muscle cells. Third, myocardial edema compresses microcirculation, and prevents flow through microcirculation26-28. The issue of reperfusion injury has been investigated over the course of many years, and its role in irreversible myocardial damage and clinical practice is yet to be determined despite decades long discussions29-31.
In addition to its relation to the significant myocardial loss that leads to the development of heart failure, left ventricular remodeling is a secondary process that initially compensates for myocardial loss. However, at later stages, left ventricular remodeling is associated with ventricular enlargement and secondary phenomenon such as functional mitral valve regurgitation. The latter contributes to the reduced capacity of the heart to respond to physiological demands, and thus to worsening of heart failure17,32,33.
Understanding coronary physiology is key for dealing with STEMI patients at risk for extensive myocardial necrosis. Coronary flow is regulated by myocardial oxygen consumption and can be increased by four-fold in healthy individuals. Increased coronary flow is mandatory for increased oxygen supply to the myocardium, as each molecule of hemoglobin that enters the coronary circulation delivers all the oxygen that is carried during its passage through the myocardium. Thus, only increased flow can provide more oxygen. The rate of flow in the coronary circulation is determined by the intramyocardial resistance of coronary arteries. Vasodilation of these arteries increases coronary flow, which leads to some degree of vasodilation of the epicardial coronary arteries in response to the increased flow. In STEMI, all these physiological mechanisms are disrupted, as detailed above34-38.