Bifurcations to transient and oscillatory excitations in inhomogeneous excitable media: Insights into arrhythmogenesis in long QT syndrome.

Abstract

Ventricular arrhythmias are the leading cause of sudden cardiac death. Understanding the mechanisms of arrhythmia initiation is important for developing effective therapeutics for prevention. Arrhythmias can be induced via premature external stimuli or occur spontaneously via dynamical instabilities. Computer simulations have shown that a large repolarization gradient due to regional prolongation of the action potential duration can result in instabilities leading to premature excitations and arrhythmias, but the bifurcation remains to be elucidated. In this study we carry out numerical simulations and linear stability analyses using a one-dimensional heterogeneous cable consisting of the FitzHugh-Nagumo model. We show that a Hopf bifurcation leads to local oscillations, which, once their amplitudes are large enough, lead to spontaneous propagating excitations. Depending on the degree of heterogeneities, these excitations can range from one to many and to be sustained oscillations, manifesting as premature ventricular contractions (PVCs) and sustained arrhythmias. The dynamics depends on the repolarization gradient and the length of the cable. Complex dynamics is also induced by the repolarization gradient. The mechanistic insights from the simple model may help in the understanding of the genesis of PVCs and arrhythmias in long QT syndrome.