Is human atrial fibrillation stochastic or deterministic?-Insights from missing ordinal patterns and causal...

The mechanism of atrial fibrillation (AF) maintenance in humans is yet to be determined. It remains controversial whether cardiac fibrillatory dynamics are the result of a deterministic or a stochastic process. Traditional methods to differentiate deterministic from stochastic processes have several limitations and are not reliably applied to short and noisy data obtained during clinical studies. The appearance of missing ordinal patterns (MOPs) using the Bandt-Pompe (BP) symbolization is indicative of deterministic dynamics and is robust to brief time series and experimental noise. Our aim was to evaluate whether human AF dynamics is the result of a stochastic or a deterministic process. We used 38 intracardiac atrial electrograms during AF from the coronary sinus of 10 patients undergoing catheter ablation of AF. We extracted the intervals between consecutive atrial depolarizations (AA interval) and converted the AA interval time series to their BP symbolic representation (embedding dimension 5, time delay 1). We generated 40 iterative amplitude-adjusted, Fourier-transform (IAAFT) surrogate data for each of the AA time series. IAAFT surrogates have the same frequency spectrum, autocorrelation, and probability distribution with the original time series. Using the BP symbolization, we compared the number of MOPs and the rate of MOP decay in the first 1000 timepoints of the original time series with that of the surrogate data. We calculated permutation entropy and permutation statistical complexity and represented each time series on the causal entropy-complexity plane. We demonstrated that (a) the number of MOPs in human AF is significantly higher compared to the surrogate data (2.7 ± 1.18 vs. 0.39 ± 0.28, p < 0.001); (b) the median rate of MOP decay in human AF was significantly lower compared with the surrogate data (6.58 × 10^-3 vs. 7.79 × 10^-3, p < 0.001); and (c) 81.6% of the individual recordings had a rate of decay lower than the 95% confidence intervals of their corresponding surrogates. On the causal entropy-complexity plane, human AF lay on the deterministic part of the plane that was located above the trajectory of fractional Brownian motion with different Hurst exponents on the plane. This analysis demonstrates that human AF dynamics does not arise from a rescaled linear stochastic process or a fractional noise, but either a deterministic or a nonlinear stochastic process. Our results justify the development and application of mathematical analysis and modeling tools to enable predictive control of human AF.