Relationship Between Time-to-First Atrial Tachyarrhythmia Recurrence and Atrial Fibrillation Burden: Implications for Trial Design

BACKGROUND: Atrial tachyarrhythmia recurrence remains the primary end point of clinical trials evaluating therapeutic pharmacological and nonpharmacological interventions for atrial fibrillation (AF). We sought to examine the relationship between the timing of first atrial tachyarrhythmia recurrence and subsequent AF burden. METHODS: We performed a patient-level analysis of 2 multicenter prospective parallel-group, single-blinded randomized clinical trials that used continuous rhythm monitoring after rhythm intervention. Patients with paroxysmal AF were stratified based on the month where the first recurrence of atrial tachyarrhythmia was observed, after a 2-month blanking period. AF burden was calculated as the time spent in AF at 1 year after first recurrence and over 3 years of follow-up. RESULTS: A total of 56.5% of patients experienced a first recurrence of atrial tachyarrhythmia within the third month post treatment initiation, with 79.5% of all recurrences detected by month 6 and 90.2% detected by month 9. The median postrecurrence AF burden was significantly greater in those with first recurrence in month 3 (1.04% [interquartile range, 0.23–5.05]) when compared with those patients with first recurrence between months 4 to 12 (0.13% [interquartile range, 0.04–0.63]; P <0.0001 versus month 3) and those with first recurrence after month 12 (0.05% [interquartile range, 0.01–0.20]; P <0.0001 versus month 3). CONCLUSIONS: Atrial tachyarrhythmia recurrence after rhythm control intervention for paroxysmal AF is not uniform, with earlier recurrences being associated with higher long-term AF burden. These findings suggest that the timing of arrhythmia recurrence is of critical importance, with later recurrences being of progressively lesser clinical significance.