Cardiac Magnetic Resonance Tissue Characterization of Ischemic and Non-Ischemic Myocardium to Predict Left Ventricular Functional Recovery and Outcomes after Multivessel Coronary Revascularization

缺血和非缺血心肌的心脏磁共振组织表征可预测多支冠状动脉血运重建后左心室功能恢复和结果

• 批准号: 10754011
• 负责人: Mario FL Gaudino
• 金额: $ 78.08万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10754011
• 关键词: Address; Adult; American; Area; Blood; Blood flow; Cardiac; Cardiac Surgery procedures; Cessation of life; Clinical; Clinical Trials; Collaborations; Coronary; Coronary Arteriosclerosis; Coronary Vessels; Darkness; Data; Decision Making; EFRAC; Enrollment; Equipoise; Event; Functional disorder; Funding; Gadolinium; Health; Heart failure; Heterogeneity; Hospitalization; Image; Image Enhancement; Impairment; Infarction; Infrastructure; Ischemia; Knowledge; Left; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Left Ventricular Function; Magnetic Resonance; Magnetic Resonance Imaging; Medical; Multicenter Trials; Myocardial Ischemia; Myocardial tissue; Myocardium; Observational Study; Operative Surgical Procedures; Outcome; Pathology; Patients; Perfusion; Phenotype; Physiological; Population; Prediction of Response to Therapy; Productivity; Prognosis; Property; Quality of life; Recovery; Recovery of Function; Research; Residual state; Resolution; Risk; Role; Site; Stroke; Technology; Testing; Therapeutic; Time; Tissues; Uncertainty; Vascularization; Ventricular; cardiac magnetic resonance imaging; clinical decision-making; clinical prognosis; efficacy testing; extracellular; functional outcomes; hospital readmission; hypoperfusion; imaging approach; improved; insight; member; mortality; novel; outcome prediction; prognostic assays; prospective; response; restoration; risk stratification; stem; tool; treatment effect; trial comparing

PROJECT SUMMARY / ABSTRACT Ischemic left ventricular systolic dysfunction (iLVSD) is a leading cause of heart failure (HF) and death, for which risk is greatest in patients with multivessel coronary artery disease (CAD). Coronary revascularization (revasc) provides a potential means to improve iLVSD, but response is highly variable. “Viability” imaging (to differentiate infarcted from salvageable myocardium) had been widely touted as a tool to predict revasc response, but its utility has been challenged by recent clinical trials. One reason for observed lack of utility of imaging to predict LV functional recovery after revasc may stem from imaging approaches used to define viability: No prior trial has accounted for contractile dysfunction, hypoperfusion, or non-ischemic substrate in seemingly viable regions – each of which can be uniquely discerned by cardiac MRI (CMR). Our group has conducted single center studies showing transmural extent of infarction to be a powerful predictor of improved LV function after revasc; we have also shown hypoperfusion to predict adverse remodeling and prognosis. Technical research by members of our group has developed a new late gadolinium enhancement (LGE) CMR approach that uses blood suppression (“dark-blood”) to better discriminate between infarct and blood-pool – potentially further enhancing viability as- sessment. It is unknown if differential impact of revasc strategy on LV contractile recovery varies in relation to infarct or perfusion phenotype, if non-ischemic substrate (extracellular volume fraction, epicardial or mid-wall LGE) modifies revasc response, and if LV contractile recovery parallels improved prognosis. To address these critical knowledge gaps, this observational study will leverage the newly initiated STICH3C trial - a prospective multicenter trial comparing percutaneous (PCI) vs. surgical (CABG) revasc for patients with iLVSD and mul- tivessel/left main CAD. Perfusion CMR will be performed pre- (<1 month) and post-revasc (12 months) in 200 STICH3C patients and analyzed via a centralized core lab. Our central hypothesis is that infarct transmurality (LGE) and hypoperfusion will predict LV contractile response (EF) and prognosis (QOL, HF, mortality) after re- vasc, for which treatment effect of CABG vs. PCI on LV recovery will increase in proportion to viable but hy- poperfused myocardium on CMR. Aim 1 will test infarct transmurality and hypoperfusion for prediction of LV recovery (improved ejection fraction, strain) after revasc; Aim 2 will evaluate if non-ischemic tissue substrate modifies likelihood of LV contractile recovery; Aim 3 will test prognostic impact of infarction, hypoperfusion, and non-ischemic substrate after revasc, with focus on residual myocardial tissue properties as predictors of persis- tent LV dysfunction, impaired quality of life, and clinical events (HF readmission, mortality). Our team provides complementary expertise in key project relevant areas - translational CMR research, cardiac surgery, heart fail- ure, and clinical trials - and a track record of productive collaboration. Study findings are well-poised to transform the imaging paradigm through which viability is assessed and inform mechanism for persistent LV dysfunction, so as to improve therapeutic decision-making and clinical outcomes for millions of patients with iLVSD.

项目总结/摘要 缺血性左心室收缩功能障碍（iLVSD）是心力衰竭（HF）和死亡的主要原因， 多支冠状动脉疾病（CAD）患者的风险最大。冠状动脉血运重建（血运重建） 提供了改善iLVSD的潜在方法，但反应高度可变。“活力”成像（区分 可挽救心肌梗死）被广泛吹捧为预测血管再通反应的工具，但其 最近的临床试验对效用提出了挑战。观察到缺乏成像预测效用的一个原因是 血运重建后左心室功能恢复可能源于用于定义存活能力的成像方法： 解释了收缩功能障碍、灌注不足或看似可行的区域中的非缺血基质- 每一个都可以通过心脏MRI（CMR）唯一地辨别。我们小组进行了单中心研究 表明梗死的透壁范围是血运重建后左室功能改善的有力预测因素;我们 也显示低灌注，以预测不良重塑和预后。我们的成员进行的技术研究 一个小组开发了一种新的晚期钆增强（LGE）CMR方法， （“暗血”），以更好地区分梗塞和血池-潜在地进一步增强活力，因为- 会议。尚不清楚血运重建策略对LV收缩恢复的不同影响是否与以下因素相关 梗死或灌注表型，如果非缺血基质（细胞外容积分数、心外膜或中壁 LGE）改变了血管再通反应，如果LV收缩恢复与预后改善平行。解决这些 关键的知识差距，这项观察性研究将利用新启动的STICH 3C试验-一项前瞻性研究， 一项比较iLVSD和穆尔患者经皮（PCI）与外科（CABG）血运重建的多中心试验， tivessel/left main CAD.将在200例患者中进行血运重建前（<1个月）和血运重建后（12个月）的灌注CMR STICH 3C患者，并通过中心实验室进行分析。我们的中心假设是梗死透壁性 (LGE)低灌注可预测再灌注后左室收缩反应（EF）和预后（QOL、HF、死亡率）。 血管，CABG与PCI相比对LV恢复的治疗效果将与存活但不稳定的患者成比例增加。 心脏磁共振心肌灌注不足。目的1将检测梗死透壁性和低灌注性以预测LV 血运重建后恢复（射血分数改善，应变）; Aim 2将评价非缺血性组织基质 改变LV收缩恢复的可能性;目标3将测试梗死、低灌注和 血运重建后的非缺血性基质，重点关注残留心肌组织特性作为持续性的预测因子， LV功能障碍、生活质量受损和临床事件（HF再入院、死亡率）。我们的团队提供 在关键项目相关领域的互补专业知识-转化CMR研究，心脏手术，心力衰竭- ure和临床试验-以及富有成效的合作记录。研究结果已经准备好改变 通过成像范例评估存活力并告知持续性LV功能障碍的机制， 从而改善数百万iLVSD患者的治疗决策和临床结果。