James T. Willerson Center for Cardiovascular Modeling and Simulation, Oden Institute for Computational Engineering and Sciences and the Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Gorman Cardiovascular Research Group, Smilow Center for Translational Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ann Biomed Eng. 2023 Jan;51(1):71-87. doi: 10.1007/s10439-022-03043-7. Epub 2022 Aug 27.
Left ventricular myocardial infarction (MI) has broad and debilitating effects on cardiac function. In many cases, MI leads to ischemic mitral regurgitation (IMR), a condition characterized by incompetency of the mitral valve (MV). IMR has many deleterious effects as well as a high mortality rate. While various clinical treatments for IMR exist, success of these procedures remains limited, in large part because IMR dramatically alters the geometry and function of the MV in ways that are currently not well understood. Previous investigations of post-MI MV remodeling have elucidated that MV tissues have a significant ability to undergo a form of permanent inelastic deformations in the first phase of the post-MI period. These changes appear to be attributable to the altered loading and boundary conditions on the MV itself, as opposed to an independent pathophysiological process. Mechanistically, these results suggest that the MV mostly responds passively to MI during the first 8 weeks post-MI by undergoing a permanent deformation. In the present study, we developed the first computational model of this post-MI MV remodeling process, which we term "mitral valve plasticity." Integrating methodologies and insights from previous studies of in vivo ovine MV function, image-based patient-specific model development, and post-MI MV adaptation, we constructed a representative geometric model of a pre-MI MV. We then performed finite element simulations of the entire MV apparatus under time-dependent boundary conditions and accounting for changes to material properties equivalent to those observed 0-8 weeks post-MI. Our results suggest that during this initial period of adaptation, the MV response to MI can be accurately modeled using a soft tissue plasticity approach, similar to permanent set frameworks that have been applied previously in the context of exogenously crosslinked tissues.
左心室心肌梗死（MI）对心脏功能有广泛而衰弱的影响。在许多情况下，MI 导致缺血性二尖瓣反流（IMR），其特征是二尖瓣（MV）功能不全。IMR 也有许多不良影响，死亡率很高。虽然有各种治疗 IMR 的临床方法，但这些程序的成功率仍然有限，很大程度上是因为 IMR 以目前尚不完全理解的方式极大地改变了 MV 的几何形状和功能。之前对 MI 后 MV 重塑的研究表明，MV 组织在 MI 后的第一阶段具有显著的经历永久性非弹性变形的能力。这些变化似乎归因于 MV 本身的加载和边界条件的改变，而不是独立的病理生理过程。从机制上讲，这些结果表明，在 MI 后 8 周内，MV 主要通过经历永久性变形对 MI 做出被动反应。在本研究中，我们开发了第一个 MI 后 MV 重塑过程的计算模型，我们称之为“二尖瓣可塑性”。我们整合了之前关于绵羊 MV 功能的体内研究、基于图像的患者特定模型开发以及 MI 后 MV 适应的方法学和见解，构建了一个 MI 前 MV 的代表性几何模型。然后，我们在时变边界条件下对整个 MV 装置进行有限元模拟，并考虑到与 0-8 周后观察到的等效的材料性能变化。我们的结果表明，在这个初始适应期，MV 对 MI 的反应可以使用软组织可塑性方法进行准确建模，类似于之前在外源性交联组织中应用的永久设定框架。
