A multi-scale finite element method for investigating fiber remodeling in hypertrophic cardiomyopathy

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Опубликовано в::Scientific Reports (Nature Publisher Group) vol. 15, no. 1 (2025), p. 31961-31980
Главный автор: Mehri, Mohammad
Другие авторы: Campbell, Kenneth S., Lee, Lik Chuan, Wenk, Jonathan F.
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Nature Publishing Group
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100 1 |a Mehri, Mohammad  |u Department of Mechanical and Aerospace Engineering, University of Kentucky, Lexington, KY, USA (ROR: https://ror.org/02k3smh20) (GRID: grid.266539.d) (ISNI: 0000 0004 1936 8438) 
245 1 |a A multi-scale finite element method for investigating fiber remodeling in hypertrophic cardiomyopathy 
260 |b Nature Publishing Group  |c 2025 
513 |a Journal Article 
520 3 |a A significant hallmark of hypertrophic cardiomyopathy (HCM) is fiber disarray, which is associated with various cardiac events such as heart failure. Quantifying fiber disarray remains critical for understanding the disease’s complex pathophysiology. This study investigates the role of heterogeneous HCM-induced cellular abnormalities in the development of fiber disarray and their subsequent impact on cardiac pumping function. Fiber disarray is predicted using a stress-based law to reorient myofibers and collagen within a multiscale finite element cardiac modeling framework, MyoFE. Specifically, the model is used to quantify the distinct impacts of heterogeneous distributions of hypercontractility, hypocontractility, and fibrosis on fiber disarray development and examines their effect on functional characteristics of the heart. Our results show that heterogenous cell level abnormalities highly disrupt the normal mechanics of myocardium and lead to significant fiber disarray. The pattern of disarray varies depending on the specific perturbation, offering valuable insights into the progression of HCM. Despite the random distribution of perturbed regions within the cardiac muscle, significantly higher fiber disarray is observed near the epicardium compared to the endocardium across all perturbed left ventricle (LV) models. This regional difference in fiber disarray, irrespective of perturbation severity, aligns with previous DT-MRI studies, highlighting the role of regional myocardial mechanics in the development of fiber disarray. Furthermore, cardiac performance declined in the remodeled LVs, particularly in those with fibrosis and hypocontractility. These findings provide important insights into the structural and functional consequences of HCM and offer a framework for future investigations into therapeutic interventions targeting cardiac remodeling. 
653 |a Mechanical properties 
653 |a Lagrange multiplier 
653 |a Heart attacks 
653 |a Mutation 
653 |a Pathophysiology 
653 |a Cardiomyocytes 
653 |a Congestive heart failure 
653 |a Finite element method 
653 |a Extracellular matrix 
653 |a Cardiomyopathy 
653 |a Hemodynamics 
653 |a Structure-function relationships 
653 |a Fibrosis 
653 |a Blood 
653 |a Shear strain 
653 |a Cardiac function 
653 |a Myocardium 
653 |a Cardiac muscle 
653 |a Therapeutic applications 
653 |a Environmental 
700 1 |a Campbell, Kenneth S.  |u Division of Cardiovascular Medicine, Department of Physiology, University of Kentucky, Lexington, KY, USA (ROR: https://ror.org/02k3smh20) (GRID: grid.266539.d) (ISNI: 0000 0004 1936 8438) 
700 1 |a Lee, Lik Chuan  |u Department of Mechanical Engineering, Michigan State University, East Lansing, MI, USA (ROR: https://ror.org/05hs6h993) (GRID: grid.17088.36) (ISNI: 0000 0001 2195 6501) 
700 1 |a Wenk, Jonathan F.  |u Department of Mechanical and Aerospace Engineering, University of Kentucky, Lexington, KY, USA (ROR: https://ror.org/02k3smh20) (GRID: grid.266539.d) (ISNI: 0000 0004 1936 8438); Department of Surgery, University of Kentucky, Lexington, KY, USA (ROR: https://ror.org/02k3smh20) (GRID: grid.266539.d) (ISNI: 0000 0004 1936 8438); Department of Mechanical and Aerospace Engineering, University of Kentucky, 269 Ralph G. Anderson Building, 40506-0503, Lexington, KY, USA (ROR: https://ror.org/02k3smh20) (GRID: grid.266539.d) (ISNI: 0000 0004 1936 8438) 
773 0 |t Scientific Reports (Nature Publisher Group)  |g vol. 15, no. 1 (2025), p. 31961-31980 
786 0 |d ProQuest  |t Science Database 
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