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Abstract

Mitral regurgitation (MR) triggers complex cardiac remodeling responses that alter the structure and function of the left ventricle (LV). While several models have been developed to predict myocardial growth in MR, they often neglect key concurrent adaptive mechanisms that influence both the pattern and severity of LV dilation. This study presents a unified finite element framework to systematically evaluate the individual and combined contributions of fiber reorientation (FR) and baroreflex regulation to LV growth and remodeling, along with the effects of myocardial material property changes associated with the acute and chronic phases of MR. A healthy baseline model and multiple MR models were simulated, each incorporating different combinations of these mechanisms. The growth model that included both FR and baroreflex most accurately reproduced clinical measurements of LV geometry, myocardial mass, and pressure-volume loops. Excluding either FR or baroreflex consistently led to underestimation of myocardial growth and less realistic LV shapes. Importantly, FR was essential for capturing the increased chamber sphericity observed in MR, while baroreflex significantly influenced the extent of dilation and pressure compensation. Phase-dependent changes in myocardial material properties further modulated remodeling patterns, capturing distinct features of acute and chronic disease stages. These findings highlight the critical role of integrating concurrent physiological mechanisms to reliably predict cardiac adaptation in MR and provide new insights into the drivers of remodeling patterns observed in patients. This comprehensive approach offers a valuable framework for evaluating therapies that target distinct aspects of cardiac adaptation.

Statement of Significance Mitral regurgitation triggers remodeling responses that alter the structure and function of the left ventricle. This study presents a unified finite element framework that systematically evaluates the individual and combined contributions of fiber reorientation and baroreflex regulation to left ventricular growth and remodeling, along with the effects of myocardial material property changes associated with the acute and chronic phases of mitral regurgitation. The growth model that included both fiber reorientation and baroreflex most accurately reproduced clinical measurements of ventricular geometry (including chamber sphericity), myocardial mass, and pressure-volume loops. These findings highlight the critical role of integrating concurrent physiological mechanisms to reliably predict cardiac adaptation and provide new insights into the drivers of remodeling patterns observed in patients.

Document Type

Article

Publication Date

2026

Notes/Citation Information

1742-7061/© 2025 Acta Materialia Inc. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.actbio.2025.12.012

Funding Information

Support for this research was provided by National Institutes of Health grant R01 HL163977 and as part of the NSF/NIH Smart Health and Biomedical Research in the Era of Artificial Intelligence and Advanced Data Science Program by grant IIS-2406028.

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