The main purpose of this dissertation is to develop a population-based cellular model of remodeled electrophysiological properties in a single cell of a human ventricle under heart failure conditions. The developed model is used to study ventricular arrhythmia (VA) applications under heart failure (HF) conditions, such as inducing early afterdepolarizations (EADs) in single cells and initiating spiral waves in tissue. Early afterdepolarizations as well as reentrant waves are an important cause of ventricular arrhythmias in heart failure. However, the underlying transmural distribution of alterations in currents is unknown. Therefore, it is important to study the impact of remodeled transmural currents on inducibility of early afterdepolarization in heart failure across population-level variability. We seek to develop a populationbased transmural heart failure electrophysiological model and assess the relative contribution of each ionic current in early afterdepolarization development during HF. We developed an electrophysiological model that incorporates HF-induced remodeling of related currents, pumps and exchangers as documented in the literature, by modifying a recently published model of human ventricular cell electrophysiology, namely the O\u27Hara, Virag, Varro, and Rudy (OVVR) model. To do so, we broke down our work into the following categories: First, we analyzed healthy human models where we implemented six cellular models under normal conditions in tissue to validate the behavior of these models. Second, we developed and analyzed a human heart failure model, where we developed a general HF model in an isolated myocyte and characterized the difference between normal and HF electrophysiological properties in a single myocyte (0D). The analysis included action potential (AP) properties, sodium concentration and calcium dynamics. We used steady-state and S1-S2 protocols to assess the dynamics of the developed HF model. In addition, we built a more human-specific HF model and introduced population-based remodeling variability on the developed human-specific HF model for three cell types as observed experimentally. Then, the developed HF models were extended to include the analysis of a one-dimensional cable (1D) where we measured the conduction velocity (CV) under HF conditions and compared it with the normal case. Since arrhythmia can be caused by abnormal formation and/or propagation of the excitation wave, it is important to investigate the behavior of our developed models under this scenario. Therefore, we induced arrhythmia in a two-dimensional (2D) tissue by initiating spiral waves using a cross-field stimulation protocol. Then, we measured the vulnerability window, stability of reentrant waves, spiral tip trajectory, duration of induced arrhythmias, dominant action potential duration (APD) and rotation period in the myocytes that constituted the tissue during reentry. Third, we assessed the inducibility of EAD for the general HF model as well as the human-specific HF model across population-level remodeling variability for all types of human ventricular cells. Our thesis should help to elucidate the roles of alterations in electrophysiology on ventricular arrhythmia properties during HF
