Spatially heterogeneous ionic remodelling promotes wavefront instability in simulated atrial tissue.

Electrical remodelling is often seen as a key determinant in the development of atrial fibrillation. From a computational electrical modelling point of view, remodelling is usually incorporated by a global (within a specific atrial region) change of model parameters, e.g., ionic conductances and calcium handling properties. Given the spatially heterogeneous nature of cardiac tissue, one may expect that remodelling develops in a non-uniform manner. Computational models sometimes reflect this when fibrotic regions are considered; however, in the case of spatially heterogeneous electrical remodelling the literature is much sparser. Here we demonstrate that a spatially heterogeneous mixture of remodelled and non-remodelled regions can cause a destabilizing effect in simulated tissue paced at a sufficiently high frequency, indicating a potential mechanism for the initiation of fibrillatory behaviour. In particular, we use an established model of human atrial action potential with parameters based on sinus rhythm and chronic atrial fibrillation, and we distribute these two possible states according to realisations of the 2-dimensional Ising model. We show that there is a window of pacing frequencies where turbulent propagation behaviour (via the break up of incoming wavefronts) is sustained, and that a long turbulent transient can be sustained when adapting to fast pacing from a lower pacing frequency. These results might help us think about the mechanisms embodied in the aphorism 'atrial fibrillation begets atrial fibrillation', namely, that partially remodelled tissue could emerge in an intermediate stage of disease progression, promoting the conditions for the tissue to progress to becoming globally remodelled.