Hearts subjected to volume overload (VO) are prone to detrimental anatomical and functional changes in response to elevated mechanical stretches, ultimately leading to heart failure. Experimental findings increasingly emphasize that organ-scale changes following VO cannot be explained by myocyte growth alone, as traditionally proposed in the literature. Collagen degradation, in particular, has been associated with left ventricular adaptation in both acute and chronic stages of VO. These hypotheses remain to be substantiated by comprehensive mechanistic evidence, and the contribution of each constituent to myocardial growth and remodeling (G&R) processes is yet to be quantified. In this work, we establish a hybrid G&R framework in which we integrate a mixture-based constitutive model with the kinematic growth formulation. This multi-constituent model enables us to mechanistically assess the relative contributions of collagen and myocyte changes to alterations in tissue properties, ventricular dimensions, and growth phenotype. Our numerical results confirm that collagen dynamics control the passive mechanical response of the myocardium, whereas myocytes predominantly impact the extent and the phenotype of eccentric hypertrophy. Importantly, collagen degradation exacerbates myocyte hypertrophy, demonstrating a synergistic interplay that accelerates left ventricular progression toward diastolic dysfunction. This work constitutes an important step towards an integrated characterization of the early compensatory stages of VO-induced cardiac G&R.

翻译：承受容量超负荷的心脏易因升高的机械牵张而发生有害的解剖与功能改变，最终导致心力衰竭。实验发现日益强调，文献中传统提出的仅由心肌细胞生长无法解释容量超负荷后的器官尺度变化。特别是胶原蛋白降解，已被认为与容量超负荷急性和慢性阶段的左心室适应性改变相关。这些假说仍有待通过全面的机制证据加以证实，且各组分对心肌生长与重构过程的贡献尚待量化。在本工作中，我们建立了一个混合生长与重构框架，将基于混合物的本构模型与运动学生长公式相结合。这一多组分模型使我们能够从机制上评估胶原蛋白和心肌细胞变化对组织特性、心室尺寸及生长表型改变的相对贡献。我们的数值结果证实，胶原蛋白动力学控制着心肌的被动力学响应，而心肌细胞主要影响离心性肥厚的程度和表型。重要的是，胶原蛋白降解会加剧心肌细胞肥厚，揭示了一种协同相互作用，加速左心室向舒张功能障碍进展。本工作为整合表征容量超负荷诱导的心脏生长与重构早期代偿阶段迈出了重要一步。