Author ORCID Identifier

https://orcid.org/0009-0000-8429-7865

Date Available

12-11-2024

Year of Publication

2024

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy (PhD)

College

Engineering

Department/School/Program

Mechanical Engineering

Advisor

Dr. Jonathan F. Wenk

Abstract

The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI) or hypertrophic cardiomyopathy (HCM), this organization can become disrupted, leading to alteration in pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and active), both myofibers and collagen fibers are reoriented. Simulations are conducted to predict the baseline fiber configuration in a normal LV as well as the adverse fiber reorientation that occurs due to different size MIs and HCM. For the HCM simulations, leveraging multiscale modeling capabilities, this study quantifies the distinct impacts of hypocontractility, hypercontractility and fibrosis on fiber disarray development and examines how their contributions affect the functional characteristics of the heart.

The baseline model successfully captures the transmural variation of helical fiber angles within the LV wall, as well as the transverse fiber angle variation from base to apex. In the models of MI, the patterns of fiber reorientation in the infarct, border zone, and remote regions closely align with previous experimental findings, with a significant increase in fibers oriented in a left-handed helical configuration and increased dispersion in the infarct region. Furthermore, the severity of fiber reorientation and impairment of pumping performance both showed a correlation with the size of the infarct. In the HCM models, 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. 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 MI and HCM. The proposed multiscale modeling framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2024.464

Funding Information

Support for this research was provided by National Institutes of Health grants R01HL163977 and U01HL133359.

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