Simulating the Effects of Atrial Fibrillation Induced Electrical Remodeling: A Comprehensive Simulation Study

Mechanisms underlying atrial fibrillation (AF) are poorly understood. In this study, we computationally evaluated the functional roles of AF induced electrical remodeling (AFER) on atrial electrical excitations. Experimental data of AFER on human atrial myocytes were incorporated into a biophysically detailed model of human atrial cells to simulate the effects of AFER at cellular and tissue levels. Our results show that AFER dramatically abbreviated atrial action potential duration (APD(90)) and effective refractory period that were quantitatively consistent with experimental data. A typical feature of loss in rate dependent accommodation of APD90 was observed. AFER slowed down atrial conduction velocity, but facilitated atrial conduction at high excitation rates. AFER increased tissue's spatial vulnerability for initiation and maintenance of AF remarkably. The overall susceptibility of human atrium to arrhythmia was increased. Most Importantly AFER increased the stability of reentrant waves in 2D and 3D models prolonging their lifespan. While reentrant excitation waves self-terminated under Control conditions, the same became persistent or degenerated Into multiple wavelets leading to spatio-temporal chaos under AFER conditions with accelerated re-entrant excitation rates. There was an increase in dominant frequency. In conclusion, our simulations substantiated a link between AFER and persistence of AF, providing mechanistic insights towards better understanding of "AF begets AF".