Impact of alternative efficacy endpoint definitions on reported outcomes after ablation of paroxysmal atrial fibrillation - insights from the COMPARE-CRYO study using continuous rhythm monitoring.

Background: Recurrence after atrial fibrillation (AF) ablation is commonly defined as any atrial arrhythmia lasting >30sec. It is unclear how alternative efficacy endpoint definitions would change the observed success rates and how they would relate to patients' disease burden or healthcare utilization metrics.

Objective: To evaluate the impact of alternative endpoint definitions after AF ablation based on AF-burden, duration or number of episodes using implantable cardiac monitors (ICM).

Methods: This is a prespecified substudy of the COMPARE-CRYO study, which enrolled patients with paroxysmal AF undergoing cryoballoon ablation. All patients underwent ICM implantation and the blanking period was 90 days. Details were collected on timing, duration and number of episodes and AF-burden between 91-365 days. Outcome measures were redo ablations and AF-related hospitalizations.

Results: The primary endpoint of any recurrence lasting >30 sec occurred in 89 of 201 patients (44%). One-year success rates increased with increasing arrhythmia duration thresholds from 56% (≥30 sec) to 97% (≥24h), with number of episode thresholds from 56% (≥1 episode) to 98% (≥100 episodes) and with AF-burden thresholds from 56% (AF-burden >0%) to 93% (AF-burden >2%). Rates of redo ablations and AF-related hospitalizations increased for AF-episode durations >1h, >6 AF-episodes and an AF-burden >0.1%, and were highest for AF-episode durations >24h, >33 AF-episodes and an AF-burden >1%.

Conclusion: Alternative efficacy endpoint definitions have a significant impact on reported outcomes and healthcare utilization metrics after AF ablation. These findings are important when considering endpoint definitions other than the traditional 30 seconds in the design of future AF-ablation trials.