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

• DOI: 10.1007/s10237-023-01747-w
• Publication Date: 2023-07-23T16:01:26Z
• Authors: Amadeus M. Gebauer; Martin R. Pfaller; Fabian A. Braeu; Christian J. Cyron; Wolfgang A. Wall
• Keywords: Heart Failure; 0301 basic medicine; Original Paper; Ventricular Remodeling; Myocardium; Organogenesis; FOS: Physical sciences; Quantitative Biology - Tissues and Organs; Heart; Physics - Medical Physics; 3. Good health; ddc:; Cardiac growth and remodeling, Homogenized constrained mixture model, Computational modeling, Mechanobiology, Hypertension; Original Paper ; Cardiac growth and remodeling ; Homogenized constrained mixture model ; Computational modeling ; Mechanobiology ; Hypertension ; Medical and Health Sciences; 03 medical and health sciences; FOS: Biological sciences; Hypertension; Humans; Medical Physics (physics.med-ph); Tissues and Organs (q-bio.TO)

AbstractCardiac 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.