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) 是一种全国范围内的流行病，有超过 600 万患者受累，新增患者达 60 万 每年都会确诊。缺血性心脏病仍然是美国的首要死因。 在过去的 16 年里，心脏再同步治疗 (CRT) 已被证明可以提高左心室功能， 大量（缺血性和非缺血性）心力衰竭患者的生活质量和总体生存率。大约 然而，30% 的患者在治疗后仍然没有改善（CRT 无反应者）以及 CRT 的百分比 过去十年来，无反应者一直保持稳定。我们认为，关键障碍之一是 提高 CRT 反应率的原因是缺乏对缺血和缺血之间相互作用的了解 异步激活。在本提案中，我们寻求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模型。该提案的总体目标是 开发经过实验验证、基于物理的心脏机电灌注 (EMP) 计算（有限元，FE）模型可预测和优化缺血条件下的 CRT 反应。这 为了实现这一目标，制定了以下具体目标。首先，我们将耦合一个基于蜂窝的 心脏的机电模型到将被验证的冠状脉管系统的循环模型 使用正常猪的实验测量。其次，我们将针对猪模型验证 EMP 模型 急性缺血和假性左束支传导阻滞 (LBBB) 之间的相互作用 异步激活和缺血会影响 CRT 反应。第三，我们将使用经过验证的 EMP 模型来 通过确定与缺血程度和位置相关的最佳起搏参数来优化 CRT。这 提出的方法和方法具有创新性。更重要的是，该项目的完成将 显着增加我们对缺血和异步激活之间相互作用的理解，并且 这些相互作用如何影响 CRT 响应。该项目的研究结果具有转化性，可以作为 为未来开发针对患者的特定方法以优化长期 CRT 反应奠定了基础。