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.

项目概要/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，其中 患有多支冠状动脉疾病 (CAD) 的患者风险最大。 “活力”成像（以区分 可挽救的心肌梗死）曾被广泛吹捧为预测复苏反应的工具，但其 最近的临床试验对实用性提出了挑战，这是观察到影像学预测缺乏实用性的原因之一。 复苏后左心室功能恢复可能源于用于定义生存能力的影像学方法：之前没有试验表明 解释了看似可行区域的收缩功能障碍、灌注不足或非缺血基质 - 每一个都可以通过心脏 MRI (CMR) 来独特地辨别。我们的小组进行了单中心研究。 表明梗塞的透壁程度是复苏后左心室功能改善的有力预测因素； 我们的成员的技术研究还表明，灌注不足可以预测不良重塑和预后。 研究小组开发了一种新的晚期钆增强 (LGE) CMR 方法，该方法使用血液抑制 （“暗血”）以更好地区分梗塞和血池——可能进一步增强活力，因为- 目前尚不清楚 revasc 策略对 LV 收缩恢复的差异影响是否与以下因素有关： 梗塞或灌注表型，如果非缺血基质（细胞外体积分数、心外膜或中壁 LGE）改变了 revasc 反应，并且左心室收缩恢复是否与预后改善相一致。 为了弥补关键知识差距，这项观察性研究将利用新启动的 STICH3C 试验——一项前瞻性研究 比较经皮 (PCI) 与手术 (CABG) 重建对于 iLVSD 和多中心患者的多中心试验 tivessel/左主干 CAD 将在 200 年的重建前（<1 个月）和重建后（12 个月）进行。 STICH3C 患者并通过中央核心实验室进行分析，我们的中心假设是梗死透壁性。 (LGE) 和低灌注将预测 LV 收缩反应 (EF) 和预后（QOL、HF、死亡率）。 血管，对于这种情况，CABG 与 PCI 对 LV 恢复的治疗效果将按存活但 hy 的比例增加 CMR 上的灌注心肌将测试梗死透壁性和灌注不足以预测 LV。 复苏后的恢复（射血分数改善、应变）；目标 2 将评估是否非缺血组织基质 改变左心室收缩恢复的可能性；目标 3 将测试梗塞、灌注不足和的预后影响 复苏后的非缺血基质，重点关注残余心肌组织特性作为持续的预测因子 我们的团队提供了左心室功能障碍、生活质量受损和临床事件（心力衰竭再入院、死亡率）的信息。 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 - 和临床试验 - 以及富有成效的合作记录 研究结果已做好转变的准备。 通过成像范例评估生存能力并告知持续性左心室功能障碍的机制， 从而改善数百万 iLVSD 患者的治疗决策和临床结果。