Bifurcation Analysis of Cardiac Alternans Using δ-Decidability

We present a bifurcation analysis of electrical alternans in the two-current Mitchell-Schaeffer (MS) cardiac-cell model using the theory of δ-decidability over the reals. Electrical alternans is a phenomenon characterized by a variation in the successive Action Potential Durations (APDs) generated by a single cardiac cell or tissue. Alternans are known to initiate re-entrant waves and are an important physiological indicator of an impending life-threatening arrhythmia such as ventricular fibrillation. The bifurcation analysis we perform determines, for each control parameter τ of the MS model, the bifurcation point in the range of τ such that a small perturbation to this value results in a transition from alternans to non-alternans behavior. To the best of our knowledge, our analysis represents the first formal verification of non-trivial dynamics in a numerical cardiac-cell model. Our approach to this problem rests on encoding alternans-like behavior in the MS model as a 11-mode, multinomial hybrid automaton (HA). For each model parameter, we then apply a sophisticated, guided-searchbased reachability analysis to this HA to estimate parameter ranges for both alternans and non-alternans behavior. The bifurcation point separates these two ranges, but with an uncertainty region due to the underlying δ-decision procedure. This uncertainty region, however, can be reduced by decreasing δ at the expense of increasing the model exploration time. Experimental results are provided that highlight the effectiveness of this method.