Abstract
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.