Derivation of a novel angiography-based method to assess coronary microvascular dysfunction in patients with acute myocardial infarction

ST-segment elevation myocardial infarction (STEMI) is still associated with a 10% one-year mortality and up to 25% risk of heart failure. The pressure-wire index of microcirculatory resistance (IMR) may have an important role in the assessment of the downstream microcirculatory function of the IRA, providing prognostically relevant information and identifying patients at risk of suboptimal reperfusion who are eligible for additional novel therapies. However, the penetration of IMR in the clinical practice is still limited mainly because of the technical complexity of the procedure and increased costs and procedural time. Nevertheless, the implementation of a risk stratification using coronary physiology in patients with STEMI would be highly desirable to further improve the clinical outcomes. In this PhD thesis we aimed to assess the long-term prognostic implications of CMD investigated using IMR. Furthermore, we aim to develop alternative methods to simplify the assessment of CMD in the catheterization laboratory and increase the penetration of physiology in the clinical practice. The current thesis consists of five main chapters. In Chapter one we explored the long-term clinical outcome of patients with STEMI stratified according to IMR and cardiovascular magnetic resonance imaging (CMR) in the cohort of the OxAMI Study. Importantly, CMD defined by IMR>40 U or by MVO demonstrated a more than 4-fold increase in mortality, heart failure or cardiac arrest at a median follow-up of 40 months. In Chapter two, pressure-bounded coronary flow reserve (pb-CFR), an index derived using standard pressure-wire technology was compared with IMR and CFR in predicting microvascular obstruction and the extent of the infarct size at CMR imaging. Pb-CFR provided a fair prognostic stratification identifying a subgroup of patients with satisfactory myocardial reperfusion after PPCI. Nonetheless, the prognostic value of pb-CFR was inferior compared with IMR. Chapter three reports the derivation of an angiography-derived pressure-wire free index of microcirculatory resistance (IMRangio). IMRangio has been developed to overcome some of the limitations of IMR, using the Quantitative Flow Ratio (QFR) algorithm to obtain Pd and contrast frame count to estimate coronary flow. IMRangio demonstrated to be significantly correlated with invasive IMR in a prospective 3 cohort of patients with STEMI. Importantly, IMRangio was also correlated with the presence of MVO at CMR. In Chapter four, IMRangio was assessed in a prospective cohort of patients across the spectrum of acute and chronic coronary syndromes. Interestingly, IMRangio was well-correlated with IMR not only in STEMI but also in patients with NSTEMI e stable coronary syndromes. Moreover, we observed that IMRangio measured in non- hyperemic conditions (NH-IMRangio) provided good diagnostic performance in the subgroup of patients with STEMI. Chapter five reports on the long-term prognostic implications of patients with STEMI stratified according to NH-IMRangio in a retrospective analysis of the OxAMI Study. Notably, NH IMRangio demonstrated a prognostic value equivalent to invasively measured IMR. In conclusion, CMD has important prognostic implications at long-term after STEMI. IMRangio has the potential to guide additional novel additional therapies in patients undergoing PPCI. Abolishing the need for pressure-wire, IMRangio may increase the penetration of CMD assessment in the catheterization laboratory and physiology-guided additional therapies. Further additional data are needed to explore the role of IMRangio as a routine addition to diagnostic and interventional procedures in STEMI patients.