CMR Myocardial Tissue Based Prediction of Ischemic MR Revascularization Response

基于 CMR 心肌组织的缺血 MR 血运重建反应预测

• 批准号: 9294105
• 负责人: Jonathan W. Weinsaft
• 金额: $ 76.47万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-20 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9294105
• 关键词: Address; Adverse event; Arrhythmia; Breathing; Cardiac; Cessation of life; Clinical; Computer Simulation; Computing Methodologies; Coronary; Coronary Arteriosclerosis; Data; Decision Making; Development; Dimensions; Echocardiography; Elements; Fibrosis; Foundations; Geometry; Goals; Heart failure; Infarction; Intervention; Ischemia; Lateral; Left; Left Ventricular Function; Left Ventricular Remodeling; Link; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Methods; Mitral Valve; Mitral Valve Insufficiency; Modeling; Morbidity - disease rate; Myocardial; Myocardial Infarction; Myocardial tissue; Myocardium; Operative Surgical Procedures; Patients; Perfusion; Physiology; Property; Public Health; Reference Standards; Reporting; Research; Risk; Severities; Stress; Structure; Technology; Testing; Therapeutic; Time; Tissues; Training; Uncertainty; United States National Institutes of Health; Validation; Vascularization; Ventricular; Ventricular Remodeling; base; clinical practice; cohort; design; effective therapy; extracellular; improved; improved outcome; indexing; insight; mortality; novel; perfusion imaging; predictive modeling; prevent; prospective test; public health relevance; repaired; response; stem; tool; valve replacement

 DESCRIPTION (provided by applicant): Mitral regurgitation (MR) is present in one in five coronary artery disease (CAD) patients undergoing revascularization, conferring markedly increased morbidity and mortality. In prior research by our group and others, MR in patients with CAD has been strongly linked to ischemia and infarction in myocardium underlying the mitral valve. Ischemia can be reversed with revascularization, whereas infarction cannot. However, in clinical practice, MR response to revascularization is poorly understood. In nearly half of patients, MR improves with surgical or percutaneous coronary revascularization alone - in the remainder MR persists or worsens. Uncer- tainty as to which patients with MR will respond to revascularization alone limits the ability to optimize therapy. Cardiac magnetic resonance (CMR) imaging is a powerful tool to identity ischemia and infarction, as well as function and geometry. CMR tissue characterization is known to predict revascularization-induced improvement in LV function and remodeling, but has never before been tested as a planning tool for MR. Our central hypothesis is that MR response to revascularization can be predicted prior to therapy via CMR, with MR improvement dependent on presence and magnitude of ischemia in viable (alive) myocardium supporting the mitral valve. Additionally, we hypothesize that non-ischemic fibrosis in patients with CAD is associated with persistent MR after revascularization, attributable to adverse global myocardial remodeling that blunts the ability of the mitral valve to respond to revascularization. To test these hypotheses, we will study at least 156 CAD patients with advanced (≥moderate) MR undergoing coronary revascularization alone. Stress perfusion CMR will be performed pre and post-revascularization to assess baseline myocardial tissue properties and revascularization induced change in ischemia. Echocardiography (pre, 3, and 6 months post) will be the reference for MR, so as to apply a well-validated standard concordant with prior NIH studies and widespread clinical practice. Aim 1 will compare presence and magnitude of ischemia and infarction between patients with and without improved MR. Aim 2 will compare non-ischemic fibrosis between groups, including focal mid-wall fibrosis and global extracellular volume. Aim 3 will develop predictive models for MR response to revascularization, using both primary CMR data and finite element modeling. Our track record in CMR, echocardiography, mitral valve physiology, and computational modeling makes us uniquely poised to address these issues. The novel information to be gained from this research will enable development of predictive models to differentiate a priori those patients in whom MR will improve with revascularization alone from those in whom MR will persist (thereby warranting ancillary interventions to treat MR and potentially avoid its long term clinical consequences). Results will provide key foundational insights concerning MR physiology, and thus will inform the design of future research focused on optimization of established and emerging therapeutic strategies to treat MR in patients unresponsive to revascularization alone.