In-silico modeling of atrial repolarization in normal and atrial fibrillation remodeled state

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total number of AF patients is constantly increasing. The mechanisms leading to and sustaining AF are not completely understood yet. Heterogeneities in atrial electrophysiology seem to play an important role in this context. Although some heterogeneities have been used in in-silico human atrial modeling studies, they have not been thoroughly investigated. In this study, the original electrophysiological (EP) models of Courtemanche et al., Nygren et al. and Maleckar et al. were adjusted to reproduce action potentials in 13 atrial regions. The parameter sets were validated against experimental action potential duration data and ECG data from patients with AV block. The use of the heterogeneous EP model led to a more synchronized repolarization sequence in a variety of 3D atrial anatomical models. Combination of the heterogeneous EP model with a model of persistent AF-remodeled electrophysiology led to a drastic change in cell electrophysiology. Simulated Ta-waves were significantly shorter under the remodeling. The heterogeneities in cell electrophysiology explain the previously observed Ta-wave effects. The results mark an important step toward the reliable simulation of the atrial repolarization sequence, give a deeper understanding of the mechanism of atrial repolarization and enable further clinical investigations.

Effects of Fibroblasts coupling on the Electrophysiology of Cardiomyocytes from Different Regions of the Human Atrium: a Simulation Study

“…In order to describe cells from different regions of the atrium, the variations of the healthy, non-remodeled CRN model proposed by Krueger et al were used [2]. The 10 different regions are the right and left atrial working myocardium (RA and LA), the right and left atrial appendage (RAA and LAA), Bachmann's bundle (BB), the crista terminalis (CT), pulmonary veins (PV), the septum (Sep), and the mitral and tricuspid valve ring (MVR and TVR).…”

“…This manifests in action potential (AP) morphology changes and in action potential duration (APD) variations. This heterogeneity of the AP seems to play an important role for the normal repolarization process leading to an overall more homogeneous repolarization as early activated cells tend to have a longer APD than late activated cells [2]. During progression of AF, the remodeling processes involve the activation of fibroblasts and an increase in fibrosis in addition to electrophysiological remodeling.…”

“…Cardiac myocytes from different regions of the atrium show differences in ion channel density [2]. This manifests in action potential (AP) morphology changes and in action potential duration (APD) variations.…”

“…Substrate changes, e.g., by fibroblasts coupling to myocytes, disturb the normal repolarization process. This might play a significant role in the perpetuation of AF.Cardiac myocytes from different regions of the atrium show differences in ion channel density [2]. This manifests in action potential (AP) morphology changes and in action potential duration (APD) variations.…”

Three-dimensional Multiscale Modelling and Simulation of Atria and Torso Electrophysiology

“…Thus, the first LA activation, produced through the BB, and the latest RA and LA activation times at 38 ms, 109 ms and 132 ms, respectively, are within the experimental ranges given by 31±13 ms, 93±17 ms and 116±18 ms respectively registered at the same locations (Lemery et al 2007). This is the common approach followed in other computational models (Dong-dong Krueger et al 2013;Colman 2014).…”