Roles of Ischemia and mechanical dyssynchrony in optimizing CRT responses

缺血和机械不同步在优化 CRT 反应中的作用

• 批准号: 9381294
• 负责人: GHASSAN S KASSAB
• 金额: $ 60.43万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9381294
• 关键词: Acute; Affect; Anatomy; Animal Experiments; Animal Model; Animals; Blood Circulation; Blood Vessels; Bundle-Branch Block; Cardiac; Cause of Death; Cicatrix; Clinic; Clinical; Computer Simulation; Consumption; Contracts; Coronary; Coronary Circulation; Development; Diagnosis; Elements; Epidemic; Family suidae; Foundations; Future; Goals; Heart; Heart failure; Impairment; Ischemia; Knowledge; Lead; Left; Left ventricular structure; Location; Maps; Measurement; Measures; Mechanics; Metabolic; Metabolism; Methodology; Modeling; Myocardial Ischemia; Myocardium; Outcome; Patients; Performance; Perfusion; Physics; Positioning Attribute; Procedures; Quality of life; Role; Sampling; Site; Testing; Time; Tissues; Translating; United States; Ventricular; Work; Workload; base; cardiac resynchronization therapy; clinically relevant; cost; experience; experimental study; improved; innovation; interdisciplinary approach; mathematical model; response; tool; treatment responders

Heart failure (HF) is a nationwide epidemic with over 6 million afflicted patients and 600,000 new patients diagnosed each year. Ischemic heart disease continues to be the leading cause of death in the United States. Over the past 16 years, cardiac resynchronization therapy (CRT) has been shown to increase LV performance, quality of life, and overall survival in a large number of (ischemic and non-ischemic) HF patients. Approximately 30% of patients, however, still do not improve after therapy (CRT non-responders) and the percentage of CRT non-responders have remained stable over the past decade. We believe that one of the critical barrier in improving CRT responder rate is the lack of an understanding of the interactions between ischemia and asynchronous activation. In this proposal, we seek to close this gap by using a multi-disciplinary approach that combines large-animal experiments and validated computational modeling. The overall goal of this proposal is to develop an experimentally validated, physics-based cardiac electro-mechanics-perfusion (EMP) computational (finite element, FE) model to predict and optimize CRT response under ischemic conditions. The following specific aims are constructed to accomplish this goal. First, we will couple a cellular-based electromechanical model of the heart to a circulation model of the coronary vasculature that will be validated using experimental measurements in normal pigs. Second, we will validate the EMP model against pig model of acute ischemia and pseudo left bundle branch block (LBBB) to elucidate how the interactions between asynchronous activation and ischemia can affect CRT response. Third, we will use the validated EMP model to optimize CRT by identifying optimal pacing parameters associated with the degree and location of ischemia. The proposed approach and methodologies are innovative. More importantly, the completion of this project will significantly increase our understanding on the interactions between ischemia and asynchronous activation, and how these interactions can affect CRT response. The findings of this project is translational and can serve as a foundation for future development of patient-specific methodologies to optimize long-term CRT response.

心力衰竭（HF）是一种全国性的流行病，有超过600万患者和60万新患者 每年诊断。缺血性心脏病仍然是美国的主要死亡原因。 在过去的16年中，心脏起搏治疗（CRT）已被证明可以提高LV性能， 大量（缺血性和非缺血性）HF患者的生活质量和总生存率。约 然而，30%的患者在治疗后仍然没有改善（CRT无应答者）， 在过去十年中，无反应者的人数保持稳定。我们认为， 提高CRT应答率的原因是缺乏对缺血和 异步激活。在这一建议中，我们试图通过使用多学科方法来缩小这一差距， 结合了大型动物实验和经过验证的计算建模。本提案的总体目标是 开发一种经过实验验证的、基于物理学的心脏电-力学-灌注（EMP） 计算（有限元，FE）模型来预测和优化缺血条件下的CRT响应。的 为实现这一目标，制定了以下具体目标。首先，我们将耦合一个基于蜂窝的 将心脏的机电模型转换为将被确认的冠状血管的循环模型 在正常的猪身上进行实验测量。其次，我们将验证EMP模型对猪模型， 急性缺血和假性左束支分支阻滞（LBBB），以阐明 非同步激活和局部缺血可影响CRT反应。第三，我们将使用经过验证的EMP模型， 通过识别与缺血程度和位置相关的最佳起搏参数来优化CRT。的 拟议的办法和方法具有创新性。更重要的是，该项目的完成将 显著增加我们对缺血和异步激活之间相互作用的理解， 这些相互作用如何影响CRT反应。该项目的研究结果是翻译，可以作为一个 为未来开发患者特异性方法以优化长期CRT反应奠定基础。