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

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 extracellular 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.

Subjects

Cardiac growth and remodeling

Computational modeling

Homogenized constrained mixture model

Hypertension

Mechanobiology

DDC Class

570: Life Sciences, Biology

620: Engineering

Publication version

publishedVersion

Lizenz

https://creativecommons.org/licenses/by/4.0/

Name

s10237-023-01747-w.pdf

Type

Main Article

Size

2.3 MB

Format

Adobe PDF

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