A homogenized constrained mixture model of cardiac growth and remodeling: Analyzing mechanobiological stability and reversal

TL;DR

This paper introduces a novel microstructure-based model for cardiac growth and remodeling that predicts organ-scale changes driven by cellular processes, aiming to improve understanding of stability and reversal in hypertensive conditions.

Contribution

The paper presents a new homogenized constrained mixture model that naturally derives growth directions from cellular turnover, unlike previous models that prescribed growth externally.

Findings

Model maintains tensional homeostasis in hypertension

Identifies stable and unstable G&R regions via stability map

Demonstrates G&R reversal after pressure normalization

Abstract

Cardiac growth and remodeling (G&R) patterns change ventricular size, shape, and function both globally and locally. Biomechanical, neurohormonal, and genetic stimuli drive these patterns through changes in myocyte dimension and fibrosis. We propose a novel microstructure-motivated model that predicts organ-scale G&R in the heart based on the homogenized constrained mixture theory. Previous models, based on the kinematic growth theory, reproduced consequences of G&R in bulk myocardial tissue by prescribing the direction and extent of growth but neglected underlying cellular mechanisms. In our model, the direction and extent of G&R emerge naturally from intra- and extra cellular turnover processes in myocardial tissue constituents and their preferred homeostatic stretch state. We additionally propose a method to obtain a mechanobiologically equilibrated reference configuration. We test our model on an idealized 3D left ventricular geometry and demonstrate that our model aims to maintain tensional homeostasis in hypertension conditions. In a stability map, we identify regions of stable and unstable G&R from an identical parameter set with varying systolic pressures and growth factors. Furthermore, we show the extent of G&R reversal after returning the systolic pressure to baseline following stage 1 and 2 hypertension. A realistic model of organ-scale cardiac G&R has the potential to identify patients at risk of heart failure, enable personalized cardiac therapies, and facilitate the optimal design of medical devices.