Extracorporeal Membrane Oxygenation Department, Karolinska University Hospital, Stockholm, Sweden.
Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam Universitair Medische Centra, Vrije Universiteit Amsterdam , Amsterdam , The Netherlands.
J Appl Physiol (1985). 2019 May 1;126(5):1377-1389. doi: 10.1152/japplphysiol.00791.2018. Epub 2019 Feb 7.
Remodeling is an important long-term determinant of cardiac function throughout the progression of heart disease. Numerous biomolecular pathways for mechanosensing and transduction are involved. However, we hypothesize that biomechanical factors alone can explain changes in myocardial volume and chamber size in valve disease. A validated model of the human vasculature and the four cardiac chambers was used to simulate aortic stenosis, mitral regurgitation, and aortic regurgitation. Remodeling was simulated with adaptive feedback preserving myocardial fiber stress and wall shear stress in all four cardiac chambers. Briefly, the model used myocardial fiber stress to determine wall thickness and cardiac chamber wall shear stress to determine chamber volume. Aortic stenosis resulted in the development of concentric left ventricular hypertrophy. Aortic and mitral regurgitation resulted in eccentric remodeling and eccentric hypertrophy, with more pronounced hypertrophy for aortic regurgitation. Comparisons with published clinical data showed the same direction and similar magnitudes of changes in end-diastolic volume index and left ventricular diameters. Changes in myocardial wall volume and wall thickness were within a realistic range in both stenotic and regurgitant valvular disease. Simulations of remodeling in left-sided valvular disease support, in both a qualitative and quantitative manner, that left ventricular chamber size and hypertrophy are primarily determined by preservation of wall shear stress and myocardial fiber stress. Cardiovascular simulations with adaptive feedback that normalizes wall shear stress and fiber stress in the cardiac chambers could predict, in a quantitative and qualitative manner, remodeling patterns seen in patients with left-sided valvular disease. This highlights how mechanical stress remains a fundamental aspect of cardiac remodeling. This in silico study validated with clinical data paves the way for future patient-specific predictions of remodeling in valvular disease.
重构是心脏病进展过程中心脏功能的一个重要长期决定因素。涉及许多机械感受和转导的生物分子途径。然而，我们假设仅生物力学因素就可以解释瓣膜疾病中心肌体积和腔室大小的变化。使用经过验证的人类脉管系统和四个心脏腔室模型来模拟主动脉瓣狭窄、二尖瓣反流和主动脉瓣反流。通过自适应反馈模拟重构，以保持四个心脏腔室中的心肌纤维应力和壁切应力。简而言之，该模型使用心肌纤维应力来确定壁厚度，使用心脏腔室壁切应力来确定腔室体积。主动脉瓣狭窄导致向心性左心室肥厚的发展。主动脉瓣和二尖瓣反流导致偏心重构和偏心性肥厚，主动脉瓣反流的肥厚更为明显。与已发表的临床数据进行比较显示，舒张末期容积指数和左心室直径的变化方向相同，幅度相似。在狭窄和反流性瓣膜病中，心肌壁体积和壁厚度的变化均在现实范围内。左侧瓣膜性疾病重构的模拟以定性和定量的方式支持，即左心室腔室大小和肥厚主要由壁切应力和心肌纤维应力的保持来决定。带有自适应反馈的心血管模拟可以定量和定性地预测左侧瓣膜性疾病患者的重构模式，该模拟正常化了心脏腔室中的壁切应力和纤维应力。这突出了机械应力仍然是心脏重构的基本方面。这项经过临床数据验证的计算机研究为瓣膜病中未来的患者特异性重构预测铺平了道路。
