Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA.
Department of Molecular Cardiology, Texas Heart Institute, Houston, Texas, USA.
Acta Biomater. 2024 Jan 1;173:109-122. doi: 10.1016/j.actbio.2023.10.027. Epub 2023 Nov 2.
Myocardial infarction (MI) is accompanied by the formation of a fibrotic scar in the left ventricle (LV) and initiates significant alterations in the architecture and constituents of the LV free wall (LVFW). Previous studies have shown that LV adaptation is highly individual, indicating that the identification of remodeling mechanisms post-MI demands a fully subject-specific approach that can integrate a host of structural alterations at the fiber-level to changes in bulk biomechanical adaptation at the tissue-level. We present an image-driven micromechanical approach to characterize remodeling, assimilating new biaxial mechanical data, histological studies, and digital image correlation data within an in-silico framework to elucidate the fiber-level remodeling mechanisms that drive tissue-level adaptation for each subject. We found that a progressively diffused collagen fiber structure combined with similarly disorganized myofiber architecture in the healthy region leads to the loss of LVFW anisotropy post-MI, offering an important tissue-level hallmark for LV maladaptation. In contrast, our results suggest that reductions in collagen undulation are an adaptive mechanism competing against LVFW thinning. Additionally, we show that the inclusion of subject-specific geometry when modeling myocardial tissue is essential for accurate prediction of tissue kinematics. Our approach serves as an essential step toward identifying fiber-level remodeling indices that govern the transition of MI to systolic heart failure. These indices complement the traditional, organ-level measures of LV anatomy and function that often fall short of early prognostication of heart failure in MI. In addition, our approach offers an integrated methodology to advance the design of personalized interventions, such as hydrogel injection, to reinforce and suppress native adaptive and maladaptive mechanisms, respectively, to prevent the transition of MI to heart failure. STATEMENT OF SIGNIFICANCE: Biomechanical and architectural adaptation of the LVFW remains a central, yet overlooked, remodeling process post-MI. Our study indicates the biomechanical adaptation of the LVFW post-MI is highly individual and driven by altered fiber network architecture and collective changes in collagen fiber content, undulation, and stiffness. Our findings demonstrate the possibility of using cardiac strains to infer such fiber-level remodeling events through in-silico modeling, paving the way for in-vivo characterization of multiscale biomechanical indices in humans. Such indices will complement the traditional, organ-level measures of LV anatomy and function that often fall short of early prognostication of heart failure in MI.
心肌梗死 (MI) 伴随着左心室 (LV) 中纤维疤痕的形成，并引发 LV 游离壁 (LVFW) 结构和组成的显著改变。先前的研究表明，LV 适应具有高度个体性，这表明识别 MI 后重塑机制需要一种完全基于个体的方法，该方法可以整合纤维水平的大量结构改变与组织水平的整体生物力学适应改变。我们提出了一种基于图像的细观力学方法来进行重构特征分析，将新的双轴力学数据、组织学研究和数字图像相关数据整合到一个计算框架中，以阐明导致组织水平适应的纤维水平重构机制。我们发现，在健康区域中逐渐扩散的胶原纤维结构和类似紊乱的肌纤维结构导致 MI 后 LVFW 各向异性的丧失，为 LV 适应不良提供了一个重要的组织水平标志。相比之下，我们的结果表明，胶原纤维起伏的减少是对抗 LVFW 变薄的一种适应机制。此外，我们还表明，在建模心肌组织时包含特定于个体的几何形状对于准确预测组织运动学至关重要。我们的方法是朝着识别控制 MI 向收缩性心力衰竭转变的纤维水平重构指标迈出的重要一步。这些指标补充了 LV 解剖和功能的传统器官水平测量，这些测量通常无法早期预测 MI 中的心力衰竭。此外，我们的方法提供了一种综合方法，可以推进个性化干预的设计，例如水凝胶注射，以分别增强和抑制天然适应性和适应性不良机制，从而防止 MI 向心力衰竭的转变。
LVFW 的生物力学和结构适应性仍然是 MI 后一个中心但被忽视的重构过程。我们的研究表明，MI 后 LVFW 的生物力学适应具有高度个体性，由改变的纤维网络结构和胶原纤维含量、起伏和刚度的集体变化驱动。我们的发现表明，通过计算建模推断这种纤维水平重构事件的可能性，为在人类中对多尺度生物力学指标进行体内特征分析铺平了道路。这些指标将补充 LV 解剖和功能的传统器官水平测量，这些测量通常无法早期预测 MI 中的心力衰竭。
