In acute coronary syndromes (ACS), the pathological state of the heart is primarily gauged by the size of the infarct, which is defined as necrotic tissue. What remains challenging clinically is measuring the full extent of myocardial injury, which can be substantially larger than the infarct, and may significantly impact recovery, remodeling and survival. To address this critical gap, the goal of this project is to establish the concept of "global myocardial injury (GMI)", which defines the total area of myocardium that sustained injury. In preliminary studies, using two independent preclinical models of myocardial ischemia and reperfusion, we demonstrated 1) the feasibility that the GMI can be detected noninvasively using targeted imaging; 2) the extent of myocardial injury indeed can extend far beyond the infarct zone; and 3) the injured-but-noninfarct tissue, which is missed by conventional standards for infarct measurement, contained significant pathological changes that can contribute to adverse remodeling and cardiac events. Based on these findings, we propose two Specific Aims to test the central hypothesis that the measurement of GMI, by detecting a surrogate molecular marker for tissue injury, will provide a more comprehensive assessment of the pathological state of the heart. The hypothesis will be tested with well-defined benchmarks in the swine model, which has a cardiovascular system resembling that of human’s. In Aim 1, we will rigorously investigate the histopathological characteristics of GMI and its contributions to the overall pathophysiological state of the heart. In Aim 2, we will test the hypothesis that the GMI can lead to a better prognostic criterion for assessing the risk of arrhythmias, which is an outstanding challenge in the management of ACS patients. When fully established, the measurement of GMI will help differentiate patients who are at a greater risk for adverse cardiac events, thus can have a broad impact on the diagnosis of ACS and on personalized treatment.
|Effective start/end date||7/1/16 → 6/30/18|
- American Heart Association Midwest Affiliate (16GRNT30990033)