Session S23.2

Simulating the Effects of Atrial Fibrillation in Electrically Heterogenous Human Atria: A Computer Modelling Study

S Kharche*, J Stott, P Law, H Zhang

The University of Manchester
Manchester, UK

Human atria are composed of electrically heterogeneous tissues. We postulated that electrical remodelling induced by chronic atrial fibrillation (AF) facilitates AF.
We modified the Courtemanche et al. model to simulate action potentials (APs) in human atrial cells types, i.e. atrial chambers (CRN), pectinate muscle (PM), cristae terminalis (CT), atrioventricular ring (AV ring) and atrial appendage. We further incorporated experimental data of AF induced electrical remodelling (AFER) based on studies by Bosch et al. (AF1) and Workman et al. (AF2). Single cell models were then incorporated into spatial models with realistic 2D geometry of human atria. Using these models, we quantified the effects of AFER on atrial APs, AP duration (APD90), AP duration restitution (APDr), effective refractory period (ERPr) and conduction velocity restitution (CVr). Effects of AFER on atrial tissue’s vulnerability to uni-directional conduction block (VW) and dynamics of re-entrant waves in 2D electrically heterogeneous realistic models were studied.
AFER abbreviated atrial APD90 in all cell types. However, such a reduction is inhomogeneous among the cell types with the largest reduction in the CT (Control: 333.03 ms; AF1: 136.65 ms; AF2: 181.05 ms). AFER reduced ERP dramatically for all tissue types. AFER reduced atrial excitability leading to slower intra-atrial CV. However, AFER facilitated electrical conduction at higher pacing rates. The measured maximal rates for atrial excitation conduction in CT tissue were 198, 421 and 325 beats per minute under Control, AF1 and AF2 conditions respectively. AFER reduced tissue’s VW. AFER-induced inhomogeneous alterations in the electrical properties had a direct impact on the dynamics of re-entrant waves and under Control conditions, re-entrant excitations self-terminated with a life span of 1400 ms. However, under AF conditions, re-entrant waves persisted and led to sustained erratic propagations.
AFER augmented spatial heterogeneity in atrial electrical properties which is pro-arrhythmic helping sustain re-entry. This study provides an insight into understanding the mechanisms underlying “AF begets AF”.

(Abstract Control Number: 144)