Objective randomised blinded investigation of therapeutic ablation versus cardioversion for persistent atrial fibrillation- outcomes of the feasibility
Authors: Kanthasamy V , Schilling R , Zongo O , Khan K , Earley M , Monk V , Hunter R , Mangiafico V , Ang R , Creta A , Honarbakhsh S , Ahluwalia N , Dhinoja M , Gupta D , Finlay M 
Published: May 2024

Abstract

Background
Patients with persistent atrial fibrillation (pers.AF) commonly undergo catheter ablation (CA) for symptom relief and improved quality of life(QoL). However,the benefits of CA compared to DC cardioversion (DCCV) or medical therapy lack substantial evidence from blinded randomized trials.

Purpose
Conducting such a large-scale trial presents substantial challenges in terms of recruitment, maintaining blinding, and implementation.To address this, we conducted a pilot study prior to a definitive larger study.

Methods
This feasibility trial is a single-centre, prospective, randomised, double-blinded placebo control study. Patients with early pers AF (&lt;2 years) eligible for pulmonary vein isolation (PVI) or DCCV were enrolled. Twenty patients were recruited, accounting for 10% of the proposed larger trial based on power calculation. The intervention arm (PVI + DCCV) and placebo arm (Placebo + DCCV) were randomised in a 1:1 manner after ultrasound-guided vascular access with local anaesthetic and deep sedation (Midazolam + opioid). All procedures were performed as day cases on uninterrupted oral anticoagulation. Phrenic nerve pacing was performed in the Placebo group, mimicking lab interactions and fluoroscopy system movements. Implantable loop monitors were inserted immediately after heparin reversal and groin sheath removal. A 6-week(wk) blanking period was observed post-procedure. Blinding was assessed using Bang's blinding index (BI) for both patients and medical staff and a successful blinding is considered BI between -0.2 to 0.2. Health-related quality of life (HRQoL) was evaluated using SF12, EQ5D-5L, and AF PROMS. The study obtained ethical approval (REC ref 19/LO/0775),adhered to the principles of the Declaration of Helsinki,and obtained written informed consent from all participants.

Results
A remarkable 92% of patients approached, expressed a willingness to participate in the study. Procedure time and time to discharge were similar between groups. The study successfully achieved blinding among the patients at day0 (BI = PVI-0.2 vs placebo- 0) and was maintained throughout the 6-wk and 3M follow-up, among the patients as well as clinical staff. HRQoL improved in the active group in terms of AF PROMS [Improved difference from baseline PVI 23 (±22); vs Placebo 2 (±10), p=&lt;0.001 and SF-12 mental component (MCS) at 12M (PVI 11.8 (±11) vs placebo 8.54(±11.5), p= 0.017). Over a follow up period of 12M, there was a trend towards greater recurrence (60% vs 30%; p=0.07) and repeat procedures (70% vs 40%; p=0.4) in the placebo group.
Conclusion: Performing a blinded placebo-controlled interventional study to assess the efficacy of PVI is feasible and high recruitment rates are achievable. CA appears to result in better arrhythmic and QoL outcomes;a full-scale follow-on study will assess the true efficacy of CA in patients with early pers.AF and allow consideration of whether there is a role for DCCV in many patients.