Book Description

Heart diseases, which approximately account for 31% of all human mortality every year, are the leading cause of death worldwide. Computational cardiac models have gained increasing popularity and become an indispensable and powerful tool in elucidating the pathological process of different heart diseases. They can be used to estimate important physiological and clinically relevant quantities that are difficult to directly measure in experiments. The broad goals of this thesis were to develop 1) a microstructure-based constitutive model of the heart and 2) patient-specific computational models that would ultimately help medical scientists to diagnose and treat heart diseases.Heart diseases such as heart failure with preserved ejection fraction (HFpEF) are characterized by abnormalities of ventricular function that can be attributed to, changes in geometry, impaired myocyte (LV) relaxation, cardiac fibrosis and myocyte passive stiffening. Understanding how LV filling is affected by each of the many microstructural pathological features in heart diseases is very important and may help in the development of appropriate treatments. To address this need, we have developed and validated a microstructure-based computational model of the myocardium to investigate the role of tissue constituents and their ultrastructure in affecting the heart function. The model predicted that the LV filling function is sensitive to the collagen ultrastructure and the load taken up by the tissue constituents varies depending on the LV transmural location. This finding may have implications in the development of new pharmaceutical treatments targeting individual cardiac tissue constituents to normalize LV filling function in HFpEF.Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by elevated pulmonary artery pressure (PAP) and pulmonary artery vascular resistance, with limited survival rate and can affect patients of all ages. The increased pressure or afterload in the right ventricle (RV) can result in pathological changes in RV mechanics, which are currently not well-understood. To fill this void, we have developed patient-specific computational models to investigate effects of PAH on ventricular mechanics. Specifically, we have quantified regional ventricular myofiber stress, myofiber strain, contractility, and passive tissue stiffness in PAH patients, and compare them to those found in age- and gender-matched normal controls. Our results showed that RV longitudinal, circumferential and radial strain were depressed in PAH patients compared with controls; RV passive stiffness increased progressively with the degree of remodeling as indexed by the RV and LV end-diastolic volume ratio (RVEDV/LVEDV); Peak contractility of the RV was found to be strongly correlated, and had an inverse relationship with RVEDV/LVEDV. These results provide the mechanical basis of using RVEDV/LVEDV as a clinical index for delineating disease severity and estimating RVFW contractility in PAH patients.