Table 10.

Unanswered questions in AF ablation

Topic	Questions
Basic/translational science	What are the mechanisms of AF? What are the best preclinical models of AF for understanding human disease?
Risk factor modification	Treatment of which risk factors (i.e. OSA, obesity, hypertension, physical inactivity) improve outcome after AF ablation? Does maintenance of risk factor modification reduce late AF recurrences? Can pharmacologic prevention of remodelling/fibrosis improve long-term freedom from AF after ablation?
Patient selection—personalized management	Can machine learning and artificial intelligence improve patient selection and downstream clinical outcomes? Can we develop a personalized approach to AF ablation based on risk factors, AF duration, and atrial substrate? Do asymptomatic individuals benefit from catheter ablation, including reductions in cardiovascular adverse events?
Energy sources—ablation tools	What are the optimal settings for cryothermy and radiofrequency ablation in different LA regions? What are the optimal PFA settings for AF ablation (delivery design, dose)? Does PFA improve long-term outcomes when compared with radiofrequency or cryoballoon ablation? Does PFA improve the safety and efficacy of additional substrate modification? Are there unrecognized safety concerns if more extensive PFA leads to greater proportions of atrial myocardium being ablated? Can combined pulsed field and thermal ablation modalities improve AF ablation efficacy and safety?
Ablation strategies	Can we prevent PV reconnection after PVI? What is the optimal ablation approach of persistent AF? Can ablation based upon computer simulations of the interactions between substrate and arrhythmia provide personalized ablation strategies and lesion sets that result in safer, more effective, and more efficient procedures? Can we reproducibly map focal AF drivers and does ablation of these focal sources lead to improved outcomes? Which patients benefit from hybrid ablation? Are outcomes and safety improved compared with catheter ablation?
Endpoints and outcomes after ablation	Can wearable technologies offer reliable monitoring of AF burden after AF ablation? What is the optimal and most pragmatic efficacy endpoint for arrhythmia suppression after AF ablation?

AF, atrial fibrillation; LA, left atrial; OSA, obstructive sleep apnoea; PFA, pulsed field ablation; PV, pulmonary vein; PVI, PV isolation.