journal article·2026-01Open access

A unified finite element framework for cardiac growth and remodeling in mitral regurgitation incorporating fiber reorientation and baroreflex

Mohammad Mehri, Jonathan F. Wenk

Acta Biomaterialia· Volume 210

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.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Elasticity and Material Modeling · Cardiovascular Function and Risk Factors · Cardiac Fibrosis and Remodeling

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (60)

Show source-provided references
1. A single strain-based growth law predicts concentric and eccentric cardiac growth during pressure and volume overload10.1016/j.mechrescom.2011.11.004 ↗
2. Growth and remodeling of the left ventricle: A case study of myocardial infarction and surgical ventricular restoration10.1016/j.mechrescom.2012.03.005 ↗
3. Computational modeling of volumetric soft tissue growth: application to the cardiac left ventricle10.1007/s10237-008-0136-z ↗
4. Using machine learning to characterize heart failure across the scales10.1007/s10237-019-01190-w ↗
5. Computational modeling of growth: systemic and pulmonary hypertension in the heart10.1007/s10237-010-0275-x ↗
6. Multiscale finite element modeling of left ventricular growth in simulations of valve disease10.1007/s10439-024-03497-x ↗
7. A computational model that predicts reverse growth in response to mechanical unloading10.1007/s10237-014-0598-0 ↗
8. Magnetic resonance imaging with 3-dimensional analysis of left ventricular remodeling in isolated mitral regurgitation: implications beyond dimensions10.1161/CIRCULATIONAHA.111.073239 ↗
9. Left ventricular shape predicts different types of cardiovascular events in the general population10.1136/heartjnl-2016-310052 ↗
10. Echocardiographic assessment of mitral regurgitation: discussion of practical and methodologic aspects of severity quantification to improve diagnostic conclusiveness10.1007/s00392-021-01841-y ↗
11. Changes in mitral regurgitation and left ventricular geometry during exercise affect exercise capacity in patients with systolic heart failure10.1093/ejechocard/jeq105 ↗
12. Assessment of left ventricular reverse remodeling by cardiac MRI in patients undergoing repair surgery for severe aortic or mitral regurgitation10.1053/j.jvca.2018.11.013 ↗
13. Left ventricular fibrosis and CMR tissue characterization of papillary muscles in mitral valve prolapse patients10.1007/s10554-023-02985-w ↗
14. Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance10.1186/s12968-020-00674-4 ↗
15. Cardiac remodelling and haemodynamic characteristics in primary mitral valve regurgitation10.1136/openhrt-2018-000919 ↗
16. Characterization of chronic aortic and mitral regurgitation undergoing valve surgery using cardiovascular magnetic resonance10.1016/j.amjcard.2017.03.041 ↗
17. Determination of clinical outcome in mitral regurgitation with cardiovascular magnetic resonance quantification10.1161/CIRCULATIONAHA.115.017888 ↗
18. Computational modeling studies of the roles of left ventricular geometry, afterload, and muscle contractility on myocardial strains in heart failure with preserved ejection fraction10.1007/s12265-021-10130-y ↗
19. Force-dependent recruitment from myosin OFF-state increases end-systolic pressure-volume relationship in left ventricle10.1007/s10237-020-01331-6 ↗
20. Effects of hydrogel injection on borderzone contractility post-myocardial infarction10.1007/s10237-018-1039-2 ↗
21. Multiscale simulations of left ventricular growth and remodeling10.1007/s12551-021-00826-5 ↗
22. Computational investigation of transmural differences in left ventricular contractility10.1115/1.4034558 ↗
23. Coupled agent-based and hyperelastic modelling of the left ventricle post-myocardial infarction10.1002/cnm.3155 ↗
24. Ventricular fiber optimization utilizing the branching structure10.1002/cnm.2753 ↗
25. Using systolic local mechanical load to predict Fiber orientation in ventricles10.3389/fphys.2020.00467 ↗
26. Multiscale Fiber remodeling in the infarcted left ventricle using a stress-based reorientation law10.1016/j.actbio.2024.09.049 ↗
27. M. Mehri, H. Sharifi, K.S. Campbell, J.F. Wenk, Multi-Scale Fiber Remodeling in HCM Using a Stress-Based Fiber Reorientation Law, arXiv preprint arXiv:2409.15508 (2024).10.1016/j.actbio.2024.09.049 ↗
28. A multi-scale finite element method for investigating fiber remodeling in hypertrophic cardiomyopathy
29. Multiscale Fiber remodeling in the heart using a finite element framework, Mechanical Engineering, University of Kentucky
30. Computational analysis of the myocardial structure: adaptation of cardiac myofiber orientations through deformation10.1016/j.media.2008.06.015 ↗
31. Fiber orientation in hypertrophied canine left ventricle
32. Passive mechanical properties of the left ventricular myocardium and extracellular matrix in hearts with chronic volume overload from mitral regurgitation10.14814/phy2.15305 ↗
33. Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure10.1152/ajpheart.00326.2004 ↗
34. Hemodynamic characteristics in significant symptomatic and asymptomatic primary mitral valve regurgitation at rest and during exercise10.1161/CIRCIMAGING.117.007171 ↗
35. Baroreceptors and the long-term control of blood pressure10.1113/expphysiol.2004.027441 ↗
36. The baroreflex as a long-term controller of arterial pressure10.1152/physiol.00035.2014 ↗
37. Regulation of blood pressure by the arterial baroreflex and autonomic nervous system10.1016/B978-0-444-53491-0.00008-0 ↗
38. The impact of hemodynamic reflex compensation following myocardial infarction on subsequent ventricular remodeling10.1115/1.4043867 ↗
39. Evaluation of stimulus-effect relations in left ventricular growth using a simple multiscale model10.1007/s10237-019-01209-2 ↗
40. Left ventricular systolic function assessment in secondary mitral regurgitation: left ventricular ejection fraction vs. speckle tracking global longitudinal strain10.1093/eurheartj/ehv680 ↗
41. Extracellular matrix remodeling during the progression of volume overload-induced heart failure10.1016/j.yjmcc.2009.06.001 ↗
42. Chronic mitral valve regurgitation alters passive mechanical properties of the left ventricular myocardium in a rodent model10.1080/24748706.2019.1587949 ↗
43. Increased myocardial stiffness due to cardiac titin isoform switching in a mouse model of volume overload limits eccentric remodeling10.1016/j.yjmcc.2014.10.020 ↗
44. A multiscale finite element model of left ventricular mechanics incorporating baroreflex regulation10.1016/j.compbiomed.2023.107690 ↗
45. Dynamic coupling of regulated binding sites and cycling myosin heads in striated muscle10.1085/jgp.201311078 ↗
46. Passive material properties of intact ventricular myocardium determined from a cylindrical model10.1115/1.2894084 ↗
47. The FEniCS project version 1.5
48. Microstructure-based finite element model of left ventricle passive inflation10.1016/j.actbio.2019.04.016 ↗
49. Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort10.1186/s12968-017-0327-9 ↗
50. Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance10.1080/10976640600572889 ↗
51. The NumPy array: A structure for efficient numerical computation10.1109/MCSE.2011.37 ↗
52. SciPy 1.0: fundamental algorithms for scientific computing in Python10.1038/s41592-019-0686-2 ↗
53. Understanding the effects of mitral transcatheter edge-to-edge repair on left ventricular function using pressure-volume loops10.1016/j.jacadv.2025.101627 ↗
54. The mechanisms and pathophysiology of mitral regurgitation: A narrative review10.4103/aca.aca_221_24 ↗
55. Aortic valve area, stroke volume, left ventricular hypertrophy, remodeling, and fibrosis in Aortic stenosis assessed by cardiac magnetic resonance imaging comparison between high and low gradient and normal and low flow Aortic stenosis10.1161/CIRCIMAGING.113.000515 ↗
56. Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia10.1136/heartjnl-2016-309303 ↗
57. Myocardial fibrosis and cardiac decompensation in aortic stenosis10.1016/j.jcmg.2016.10.007 ↗
58. Quantification of left ventricular interstitial fibrosis in asymptomatic chronic primary degenerative mitral regurgitation10.1161/CIRCIMAGING.114.002397 ↗
59. Global longitudinal strain analysis using cardiac MRI in aortic stenosis: comparison with left ventricular remodeling, myocardial fibrosis, and 2- year clinical outcomes10.1148/ryct.2019190027 ↗
60. Determinants of the degree of functional mitral regurgitation in patients with systolic left ventricular dysfunction: A quantitative clinical study10.1161/01.CIR.102.12.1400 ↗