Cardiac MRI for Reperfusion Spatial Mapping to Improve Heart Failure Outcomes

Heart failure secondary to acute myocardial infarction (AMI) remains the leading cause of death and disability. As a societal cost burden, heart failure care will be nearing $160 billion by 2030. Although emergent strategies to re-establish coronary blood flow have substantially improved mortality, morbidity remains high. Paradoxically, successful reperfusion may contribute to unintended microvascular injury with subsequent intramyocardial hemorrhage. In 40-50% of patients with ST-elevation myocardial infarction, intramyocardial hemorrhage can occur, leading to adverse effects on the myocardial microstructure. Significant structure-function consequences include persistent cardiac dysfunction, fatal arrhythmias, and heart failure. Of the panoply of imaging biomarkers, intramyocardial hemorrhage and the left ventricular ejection fraction (a marker of cardiac function) have the strongest predictive value for poor cardiovascular outcomes including heart failure. Cardiac magnetic resonance (CMR) offers high spatial resolution and is the preferred modality for the characterization of post-infarct myocardial tissue heterogeneity. However, current CMR approaches to detect myocardial bleeding lack sensitivity and specificity whereas methods to simultaneously detect myocardial bleeding and provide cardiac function assessment in a single fast scan are lacking. We propose to develop a fast, free-breathing, whole-heart cine CMR framework that employs a pure intravascular tracer to track and spatially demarcate acute myocardial bleeding while simultaneously providing information about cardiac function. We will rigorously test our technique in swine models and patients with hemorrhagic AMI by sampling from a large and diverse patient pool. We will integrate high-quality, multiscale, multidimensional data to construct a patient-adaptive disease model for the prediction of post-AMI adverse remodeling and heart failure. We expect our proposed approach to spur therapeutic innovations for the management of hemorrhagic transformation as a complementary pathway for mitigating downstream heart failure. Examples may include controlled reperfusion or adjunctive therapy during interventions. Successful completion of our proposed work will shift the focus from delayed detection of hemoglobin degradation metabolites to early simultaneous depiction of intramyocardial hemorrhage and quantification of cardiac function. Our findings will provide a foundation for further development of a patient- adaptive, image-guided approach based on structure-function relationships to improve heart failure outcomes.