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Cardiac growth and remodeling (G&R) patterns change ventricular size, shape,and function both globally and locally. Biomechanical, neurohormonal, andgenetic stimuli drive these patterns through changes in myocyte dimension andfibrosis. We propose a novel microstructure-motivated model that predictsorgan-scale G&R in the heart based on the homogenized constrained mixturetheory. Previous models, based on the kinematic growth theory, reproducedconsequences of G&R in bulk myocardial tissue by prescribing the direction andextent of growth but neglected underlying cellular mechanisms. In our model,the direction and extent of G&R emerge naturally from intra- and extra cellularturnover processes in myocardial tissue constituents and their preferredhomeostatic stretch state. We additionally propose a method to obtain amechanobiologically equilibrated reference configuration. We test our model onan idealized 3D left ventricular geometry and demonstrate that our model aimsto maintain tensional homeostasis in hypertension conditions. In a stabilitymap, we identify regions of stable and unstable G&R from an identical parameterset with varying systolic pressures and growth factors. Furthermore, we showthe extent of G&R reversal after returning the systolic pressure to baselinefollowing stage 1 and 2 hypertension. A realistic model of organ-scale cardiacG&R has the potential to identify patients at risk of heart failure, enablepersonalized cardiac therapies, and facilitate the optimal design of medicaldevices.

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