Abstract

Atrial and ventricular fibrillation (AF/VF) are characterized by the repetitive regeneration of topological defects known as phase singularities (PS). The interaction between phase singularities has not been studied in human AF and VF, but is potentially of profound significance in understanding how cardiac fibrillation self-sustains. In this study we hypothesized that PS population size would influence the rate of PS formation and destruction in human AF and VF, due to an increase in inter-defect interaction. PS population statistics were first studied in (1) computational simulations of spiral defect chaos (Aliev-Panfilov, APV), followed by analysis in (2) human datasets of AF mapped using basket catheters prior to AF ablation & (3) VF mapped using epicardial electrode socks prior to cardiac surgery. The influence of inter-PS interactions was evaluated by comparison between directly modelled discrete time Markov chain (DTMC) transition matrices of the PS population changes, and M/M/∞ birth-death transition matrices of PS dynamics, which assume PS formation and destruction occur effectively independent of other PS. In all systems examined, PS population changes modelled by the DTMC differed from the M/M/∞. In APV simulations the DTMC formation rates decreased with PS population size (β estimate = -1.08 %/ms (95%CI: -1.20,-0.970), p<0.001), the DTMC destruction rates increased (β estimate = 1.78 %/ms (95% CI: 1.66,1.90), p<0.001), and M/M/∞ destruction rates increased at a slightly greater rate (β estimate = 2.00 %/ms (95% CI: 1.83,2.18), p<0.001). In AF (n=15) the DTMC formation rates decreased with PS population (β estimate = -0.179 %/ms (95% CI: -0.253,-0.105), p<0.001), M/M/∞ destruction rates increased (β estimate = 1.57 %/ms (95% CI: 1.43,1.70), p<0.001), and the DTMC destruction rates increased at a greater rate (β estimate = 2.65 %/ms (95% CI: 2.42,2.88), p<0.001). All stages of VF (n=8) demonstrated similar trends as AF, with the DTMC formation rates decreasing (βPerfusion estimate = -1.02 %/ms (95% CI: -1.37,-0.667), p=0.034), the M/M/∞ destruction rates increasing (βPerfusion estimate = 0.970 %/ms (95% CI: 0.780,1.15), p<0.001), and the DTMC destruction rates increasing at a greater rate (βPerfusion estimate = 3.42 %/ms (95% CI: 2.63,4.22), p<0.001). We present evidence of PS interaction in human AF and VF on rotor formation and destruction rates, with evidence for a potential self-inhibitory effect due to increased PS population size.

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