VIRTUAL TOOLS FOR CARDIAC VENTRICULAR REMODELING SURGERY

描述（由申请人提供）：目前有 500 万美国人被诊断患有心力衰竭 (HF)，每年新增病例 55 万例。目前，大多数心力衰竭病例是心肌梗塞 (MI) 引起的左心室 (LV) 重构的结果。由于缺乏成熟有效的治疗方法，导致心衰患者姑息治疗的医疗和手术选择不断增加。利用我们的心肌材料特性软件工具（MMPST；在初始资助期间开发和验证）和 MI 绵羊模型，我们为心脏病专家和心脏外科医生提供了关于 MI 诱发心力衰竭机制的新见解，将他们的注意力集中在紧邻 MI（边界区）的正常灌注心肌中发生的变化。我们的 MMPST 表明，与远离 MI 的 LV 区域相比，边界区 (BZ) 心肌收缩力显着降低。拟议研究的总体目标是验证我们的 MMPST 的临床应用，并证明局部心肌收缩力和疾病状态之间存在很强的临床相关性。有五个具体目标：（1）使用我们的MMPST，测量心脏移植前患者的体内局部心肌收缩力； (2) 测量从目标 #1 中研究的心脏获得的带皮纤维制剂的离体局部心肌收缩力。我们将使用这些直接主动力测量来验证 MMPST 的临床应用； (3) 使用扩散 MRI (dMRI)，测量目标 #1 中研究的心脏以及正常人类心脏和患有 MI 的人类心脏的离体局部肌纤维取向。如果这些临床相关的测量结果没有显着差异（正如我们之前在正常与梗死的绵羊心脏中发现的那样），那么我们的 MMPST 的临床应用不需要体内 dMRI； (4)测量MI后患者的体内局部心肌收缩力，并将BZ收缩力与远端左心室区域的收缩力进行比较。如果这些临床测量也显示 BZ 收缩性显着降低，那么旨在在重塑过程后期恢复更正常的 LV 几何形状的程序可能是无效的（正如我们在修复 LV 动脉瘤的绵羊中也发现的那样）； (5) 测量正常人类受试者的体内局部心肌收缩力，并将这些测量结果与目标 #1 和目标 #4 中获得的测量结果进行比较。如果这些临床测量可以与疾病状态和治疗干预的潜在效果相关联，那么心脏病学界将能够在其有关患者护理方案的设备中添加重要的新方法。 公共卫生相关性：心血管疾病（尤其是心力衰竭）的药物和/或手术治疗将极大地提高寿命和生活质量。具有心脏组织标记的磁共振成像 (MRI) 或心脏标记的 MRI 与基于物理的数学（有限元）建模相结合，可以对心壁机械特性进行非侵入性量化。如果这些机械特性可以与疾病状态和治疗干预的潜在效果相关联，那么心脏病学界将能够在其有关患者护理方案的设备中添加一种重要的新方法。

DESCRIPTION (provided by applicant): There are currently 5 million Americans with diagnosed heart failure (HF) and 550,000 new cases every year. The majority of HF cases are now the result of myocardial infarction (MI)-induced left ventricular (LV) remodeling. The lack of a well-established effective treatment has lead to a continually expanding list of medical and surgical options for the palliation of HF patients. Using our Myocardial Material Property Software Tool (MMPST; developed and validated during the initial funding period) and an ovine model of MI, we have provided cardiologists and cardiac surgeons with new insights into the mechanism of MI-induced HF by focusing their attention on changes that occur in the normally perfused myocardium immediately adjacent to the MI (the borderzone). Our MMPST demonstrates that borderzone (BZ) myocardial contractility is substantially reduced in comparison to that in LV regions remote from the MI. The overall goals of the proposed research are to validate clinical application of our MMPST and demonstrate a strong clinical correlation between regional myocardial contractility and disease state. There are five specific aims: (1) Using our MMPST, measure in-vivo regional myocardial contractility in patients before heart transplantation; (2) Measure ex-vivo regional myocardial contractility in skinned fiber preparation obtained from the hearts studied in Aim #1. We will use these direct active force measurements to validate clinical application of our MMPST; (3) Using diffusion MRI (dMRI), measure ex-vivo regional myofiber orientation in the hearts studied in Aim #1, as well as in normal human hearts and human hearts with an MI. If these clinically relevant measurements are not significantly different (as we previously discovered in normal versus infarcted sheep hearts), then clinical application of our MMPST does not require in-vivo dMRI; (4) Measure in-vivo regional myocardial contractility in patients after MI and compare BZ contractility with that in remote LV regions. If these clinical measurements also demonstrate significantly depressed BZ contractility, then procedures designed to restore a more normal LV geometry late in the remodeling process may be ineffective (as we also discovered in sheep with repaired LV aneurysm); (5) Measure in-vivo regional myocardial contractility in normal human subjects and compare these measurements with those obtained in Aim #1 and Aim #4. If these clinical measurements can be correlated to disease state and the potential effect of therapeutic intervention, then the cardiology community will be able to add a significant new methodology to its armamentarium regarding patient care protocols. PUBLIC HEALTH RELEVANCE: Medical and/or surgical treatment of cardiovascular disease, especially heart failure, stands to vastly improve both the longevity and quality of life. Magnetic resonance imaging (MRI) with heart tissue tagging or cardiac tagged MRI combined with physics-based mathematical (finite element) modeling allows for non-invasive quantification of heart wall mechanical properties. If these mechanical properties can be correlated to disease state and the potential effect of therapeutic intervention, then the cardiology community will be able to add a significant new methodology to its armamentarium regarding patient care protocols.