Abstract Body (Do not enter title and authors here): Background: Compared to drugs, pulmonary vein isolation (PVI) reduces AF recurrences and AF burden. But all prior studies (but 1) of PVI vs drugs were unblinded (and none used pulsed field ablation [PFA]), raising concerns of a placebo effect of PVI. This trial compared PFA to Sham in patients (pts) with symptomatic AF.
Methods: PFA-SHAM (NCT05717725) is a single-blind 2-center trial of symptomatic paroxysmal or persistent AF pts with AFEQT (Atrial Fibrillation Effect on Quality-of-Life) score < 50. Exclusion criteria included structural heart disease and long-standing persistent AF. At enrollment, all pts received implantable cardiac monitors (ICMs, [Biomonitor III]; Figure), and an EP study was scheduled 30d later. After excluding AVNRT/AVRT as a cause of AF, pts were randomized to either Sham or PVI using a pentaspline PFA catheter (Farawave). The 2 co-primary endpoints at 6M (post-2M blanking) were: 1) freedom from recurrent AF/AT/AFL lasting > 30 sec, assessed as time-to-recurrence, and 2) change in AFEQT. Cross-over was permitted for significant symptom worsening-per pre-specified rules. Key secondary endpoints were: 1) AF/AT/AFL burden, and 2) change in the Hospital Anxiety and Depression Scale (HADS). The primary analysis is by ITT. The study uses Bayesian statistics with a non-informative prior distribution. The sample size for the 1^st co-primary endpoint assumed 65% freedom from AF/AT/AFL with PVI, and 25% with Sham: with β=80% and α=0.025, 25 pts/group are required. For the 2^nd co-primary endpoint, assuming AFEQT=50 with Sham (SD=20), and improvement to 70 with PVI, 25 pts/group are required. Due to expected crossover (outside protocol), a total of 60 pts was planned. But the study uses an adaptive Bayesian design with interim analyses of predictive probabilities after 30, 40, 50, 60 (option up to 80) pts with pre-defined stopping rules for extreme probability of superiority or futility.
Results: Enrollment in the study began in Sept 2023, and by Apr 2025, 60 pts were randomized and underwent the allocated procedure. Baseline characteristics (Table) are: mean age 64, paroxysmal AF in 77%, 53% female, and LVEF 61%. PVI was successful in all pts, with no complications. Thus far, 48 pts completed follow-up; follow-up of the last pt will complete in early Oct 2025.
Conclusion: PFA-SHAM compares PFA to Sham to treat AF, with follow-up by continuous monitoring (ICMs), to assess the effect of PVI on both AF recurrence and quality-of-life.