Cellular heterogeneity and repolarisation across the atria: an in silico study

Abstract

Mechanisms of atrial fibrillation and the susceptibility to reentries can be impacted by the repolarization across the atria. Studies into atrial fibrillation ignore cell-to-cell heterogeneity due to electrotonic coupling. Recent studies show that cellular variability may have a larger impact on electrophysiological behaviour than assumed. This paper aims to determine the impact of cellular heterogeneity on the repolarization phase across the AF remodelled atria. Using a population of models approach, 10 anatomically identical atrial models were created to include cellular heterogeneity. Atrial models were compared with an equivalent homogenous model. Activation, APD90, and repolarization maps were used to compare models. The impact of electrotonic coupling in the tissue was determined through a comparison of RMP, APD20, APD50, APD90, and triangulation between regional atrial tissue and the single cell populations. After calibration, cellular heterogeneity does not impact atrial depolarization. Repolarization patterns were significantly impacted by cellular heterogeneity, with the APD90 across the LA increasing due to heterogeneity and the reverse occurring in the RA. Electrotonic coupling caused a reduction in variability across all biomarkers but did not fully remove variability. Electrotonic coupling resulted in an increase in APD20 and APD50, and reduced triangulation compared to isolated cell populations. Heterogeneity also caused a reduction in triangulation compared with regionally homogeneous atria. Graphical abstract