The assessment of microvascular injury in patients undergoing emergency PCI for ST - elevation myocardial infarction

Despite the interventional and pharmacological advances in treatment in ST elevation myocardial infarction in recent decades, it continues to be a significant cause of morbidity and mortality in Scotland and around the world. The diagnosis and treatment of ST-elevation myocardial infarction has been the subject of intense investigation and the focus of numerous randomised clinical trials over past decades. In an attempt to minimise adverse sequelae it is imperative that in patients with ST elevation myocardial infarction (STEMI) the immediate goal of therapy is to rapidly achieve patency of the epicardial infarct related artery (IRA) and consequently reperfusion of the affected myocardium. Thrombolysis achieves normal flow (TIMI grade 3) in the IRA in around 50% of patients compared to around 90% with primary PCI (pPCI). The successful restoration of epicardial coronary artery patency with TIMI grade 3 flow, however, does not necessarily translate into adequate tissue level perfusion. Inadequate tissue level perfusion in ST – elevation myocardial infarction in the presence of a patent epicardial artery is characterised by myocardial microvascular dysfunction. Evidence of microvascular obstruction (MVO) regardless of how it is assessed is associated with adverse clinical outcomes in this patient group. A series of consistent data has clearly shown that MVO has a strong negative impact on outcome. The index of microvascular resistance is a marker of myocardial microvascular resistance which be validated in vitro and in vivo and has been shown to be independent of variations in haemodynamic state. By incorporating collateral flow IMR has been validated in the presence of an epicardial stenosis and therefore can be calculated prior to and following stenting. Calculation of IMR at the time of emergency PCI for STEMI could potentially provide a marker of microvascular and myocardial injury in the very early post infarct period when further potential interventions would be most beneficial to the patient. Cardiac MRI imaging is the current gold standard for assessment of left ventricular ejection fraction and infarct volumes. Using Gadolinium contrast agent CMR can characterise microvascular obstruction and calculate infarct volumes. This useful information is not normally available at the time of emergency PCI. The principle aim of this thesis is to compare pressure wire derived markers of microvascular obstruction, principally IMR, calculated at the time of emergency PCI for STEMI with evidence of microvascular and myocardial damage as assessed by ceCMR scanning at 2 days and 3 months post PCI. In particular I will look at whether IMR at the time of PCI for STEMI can be used as a predictor of myocardial damage on ceCMR.I will also compare IMR the “traditional” indices currently used to assess microvascular perfusion and assess the impact that stenting itself has on the coronary microvasculature by comparing IMR prior and following PCI. CMR imaging is not commonly available in the early post infarct period. I will therefore also look at the safely, feasibility and clinical utility of ceCMR imaging in the 24 to 48 hour period following PCI for STEMI. Patients who were undergoing emergency PCI for STEMI were recruited. They underwent pressure wire assessment at the time of emergency PCI and had ceCMR scans at 2 days and 3 months following their myocardial infarction. A total of 77 patients were consented for the study between 04/01/2007 and 28/02/2008 and 69 patients had successful coronary physiological studies at the time of PCI. Two hundred patients in total underwent early ceCMR post STEMI over a longer time period. In summary the findings of this thesis are: IMR is significantly higher in patients in whom there is evidence of MVO in ceCMR scanning at 48h but does not predict the amount of MVO present. IMR is a strong independent predictor of LVEF, infarct volumes and LVESV on ceCMR imaging at 48h and 3 months. IMR was an independent predictor of transmurality score on ceCMR IMR does not alter significantly following stenting in emergency PCI indicating that stenting itself does not significantly alter the coronary microvasculature. IMR correlates closely with the “traditional” markers of myocardial damage and myocardial infarction in ST – elevation myocardial infarction. Anatomical site if myocardial infarction and therapeutic interventions at the time of emergency PCI do not significantly influence coronary pressure wire derived markers of microvascular obstruction taken immediately post – procedure. There was a nearly exact relationship between the presence of “early” and “late” MVO assessed by ceCMR imaging 48h post STEMI CMR in the early post infarct period is safe, feasible and provides useful diagnostic information This was the first study to directly compare IMR with ceCMR assessment of MVO and myocardial damage. I feel that my results complement the other work done in this field both in stable patients and in the STEMI population. I have shown that an elevated IMR is linked to microvascular and myocardial damage as revealed by ceCMR in the early post infarction period and at longer term follow up. Accordingly, I suggest measurement of IMR represents a new approach to risk assessment at the very earliest stage of acute MI management, and potentially, therefore enables triage of higher risk patients to more intensive therapy