CORonary Thrombus Modification to Prevent MIcrovascular Damage in Patients With ST-segment Elevation Myocardial Infarction (The CORMI Trial)

Background: ST-elevation segment myocardial infarction (STEMI) most often occurs when an atherosclerotic plaque ruptures, causing blockage of the epicardial coronary artery leading to transmural ischemia of the myocardium. Due to ongoing ischemia, rapid restoration of blood flow with primary percutaneous coronary intervention (PCI) is vital to prevent further damage to the myocardium.

However, reopening of the coronary artery is by itself associated with damage to the myocardium, known as reperfusion injury. Reperfusion injury is a complex phenomenon mediated by several factors caused by the rapid restoration of blood flow. Oxidative stress, accumulation of intracellular calcium, rapid restoration of pH, and induction of inflammation are some of the underlying biological mechanisms.

Furthermore, the primary PCI procedure can cause distal embolization of the thrombus causing microvascular damage. In STEMI, coronary microcirculation plays a crucial role in myocardial reperfusion and recovery and cannot be visualizable by coronary angiography (CAG). The coronary microvascular dysfunction associated with primary PCI may lead to impaired myocardial reperfusion and worse outcomes. The increased microvascular damage occurs in part due to distal embolization of the thrombus and due to reperfusion injury to the ischemic area.

Coronary thrombus modification might lessen the distal embolization of the thrombus, by less abrupt changes to the thrombus, potentially reducing the damage associated with primary PCI with stent implantation. Ischemic post-conditioning is a coronary thrombus modification that has been introduced to alleviate the injury associated with reperfusion in patients with occluded coronary vessels. Ischemic post-conditioning can be achieved by briefly and repetitively blocking the culprit artery with a balloon inflated at a nominal size before completely reestablishing blood flow to the infarcted artery. The coronary thrombus modification achieved by ischemic post-conditioning could potentially lessen the distal embolization associated with primary PCI also in patient with partially reopened vessels by more slowly modifying the thrombus, and conditioning the damaged microcirculation to better tolerate ischemic damage if distal embolization occurs.

Using the index of microcirculatory resistance (IMR) and the novel microvascular resistance reserve (MRR) microvascular damage and dysfunction can be assessed invasively during primary PCI. Both MRR and IMR can be measured using the thermodilution method, which can be obtained either using continuous (only MRR) or bolus saline injection (MRR and IMR). Continuous thermodilution is obtained using the hyperemic effects of continuous infusion for saline, with minimal influence on hemodynamics, and have previously shown great reproducibility. Meanwhile, bolus thermodilution requires drug-induced hyperemia, usually obtained using intravenous adenosine, without the need for a specialized infusion catheter.