Collagen and myocyte interplay in cardiac volume overload: a multi-constituent growth and remodeling framework

Abstract

Hearts subjected to volume overload (VO) are prone to detrimental anatomical and functional changes in response to elevated mechanical loading, ultimately leading to heart failure. Experimental findings now 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 VO and assumed to play a central role in both its acute and chronic stages. This hypothesis, however, remains to be substantiated by comprehensive mechanistic evidence, and each constituent contribution to myocardial growth and remodeling (G&R) processes is yet to be quantified. In this work, we present a multi-constituent G&R framework that integrates a mixture-based constitutive model within the kinematic growth formulation. This framework 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 remodeling affects the passive mechanical response of the myocardium, whereas myocytes predominantly influence the extent and phenotype of VO-induced growth. Importantly, collagen degradation exacerbates myocyte hypertrophy, revealing a synergistic interplay that accelerates the left ventricular eccentric growth and thereby promotes systolic dysfunction. This work constitutes an important step towards an integrated characterization of the early compensatory stages of VO-induced cardiac G&R.