The Irregularity Factor: Mechanistic Insights into Beat-to-beat Irregularities in Atrial Fibrillation Cycle Length

BACKGROUND: Measures derived from the atrial fibrillation (AF) cycle length (AFCL) are used to identify regions crucial for AF maintenance or predict (ablation) treatment outcomes. However, mechanisms underlying beat-to-beat irregularities in AFCL are unknown. OBJECTIVE: We aimed to (1) investigate beat-to-beat changes in AFCL (Δ-AFCL) by relating temporal variation in AFCL with quantified beat-to-beat changes in activation patterns and conduction times (Δ-CTs) and (2) test whether the irregularity factor (IF) (standard deviation of the Δ-AFCL histogram) is indicative of the complexity of activation patterns. METHODS: ) of fibrillation waves from the electrode array border toward the mapping area center. RESULTS: The IF was larger during LSPAF (52 ± 17 vs 25 ± 10; P < .001) than during acute AF. Δ-CTs were also larger (25 ± 8 ms vs 19 ± 7 ms; P = .005) and caused by beat-to-beat changes in conduction velocity (36 ± 6 cm/s vs 29 ± 6 cm/s; P = .001) and beat-to-beat changes in direction (94° ± 13° vs 64° ± 22°; P < .001); beat-to-beat changes in path length (13 ± 4 mm vs 14 ± 3 mm; P = .333) were comparable. The IF correlated with conduction block (ρ = 0.887), lines of conduction block lengths (ρ = 0.900), number of fibrillation waves (ρ = 0.889), and prevalence of focal waves (ρ = 0.609) (P < .001 for all). CONCLUSION: The IF indicates the underlying complexity of activation patterns, is higher during LSPAF than during acute AF, and is comparable throughout the atria during LSPAF. It is a novel, easy-to-calculate, objective electrical biomarker, which can be used for, for example, guiding patient-tailored treatment independently of the AF mechanisms.