Patients and Setting: Consecutive patients referred to the participating institutions, from November 2013 to January 2015, for catheter ablation of symptomatic and drug resistant paroxysmal atrial fibrillation (AF) were enrolled in this observational 12-follow up study. Paroxysmal AF was defined as any episode of AF that terminates spontaneously in less than seven days. Eligibility criteria, as well as outcome measures have been detailed in other sections.

Radiofrequency catheter ablation for AF: All procedures were conducted according to the standard clinical care and North American and European guidelines. Of note, the investigators did not assign specific interventions to the subjects of the study, and all interventions (trans-oesophageal echocardiography, pulmonary vein isolation) are recommended by American Heart Association and European Society of Cardiology. AF catheter ablation were conducted under efficient vitamin K antagonists (INR 2-3) and general anesthesia without discontinuation of anti-arrhythmic drugs (AAD). Trans-esophageal echocardiography was performed for each patient within 48 hours before the procedure to exclude any intra-cardiac thrombi. Two long sheaths (Preface™, Biosense Webster, Diamond Bar, CA or SLO™, Saint Jude Medical, Minnetonka, MN) were advanced into the LA after two trans-septal punctures. Intravenous heparin was administered with a target activated clotting time beyond 320 seconds. Three catheters, inserted through the right femoral vein, were used for mapping and ablation: a 6F non deflectable hexapolar 2.5-2.5-2.5-2.5-247.5 mm interspacing electrodes catheter placed at the high right atrium (RA) or into the coronary sinus (CS) whenever possible (Curve: A-Josephson type, Biosense Webster), with its proximal electrode placed at the level of the inferior vena cava, a 7F circular decapolar mapping catheter (Lasso™) placed into the LA through one of the constantly perfused long sheaths and used to monitor PVI, and a 3.5 mm 7F externally irrigated-tip ablation contact force sensing catheter (SmartTouch™), placed within the LA through the second constantly irrigated long sheath. A LA anatomy shell was created with the aid of the Carto3 system (Biosense Webster). This shell was merged or not with 3D computed tomography scan acquired prior to the ablation procedure depending on operator's choice. Pulmonary veins were isolated two-by-two at their antral level by creating a continuous circular lesion. The carina regions were targeted only if PVs could not be isolated despite complete circular lesion creation around PVs ostia. Radiofrequency ablation settings used were: 30 W/48°C/17 ml per minute except for the posterior LA wall (25W/48°C/17 ml per min) and the ridge (35W/48°C/30 ml per min). Thirty minutes after PVI, entrance and exit blocks were rechecked for each PV. In case of PV reconnection, supplemental RF applications were performed in order to re-isolate PVs following a two-step approach.

Evaluation of the unipolar signal modification: every radiofrequency (RF) delivery was performed with a minimal 10 g of force, through the entire RF application and lasted 10 seconds after the unipolar atrial electrogram, recorded by the ablation catheter, which always demonstrated positive-negative morphology before ablation, became complete positive signal (except on the posterior LA wall where 5 supplemental seconds only were added). During individual RF applications, the modification of the unipolar atrial electrogram was monitored in real-time with the Carto™ system at a sweep speed of 200mm/s. Reference annotation signal was recorded from the bipolar signal of either electrodes 1-2 or 3-4 of the non-deflectable 6F hexapolar catheter, depending on whether the latter was placed into the CS or at the high RA. Unipolar signal was recorded from the 3.5mm distal electrode of the ablation catheter and was filtered on the Carto™ system with a \[0.5-120\] Hz band-pass filter and displayed in the Carto™ annotation viewer. The indifferent electrode was used as the cathode and was located at the level of the inferior vena cava.

Post-ablation Management and Follow-up: All patients were discharged home within 3 days, and enrolled in a 12-month follow-up. Post-procedure, AAD were discontinued while vitamin K antagonists were prescribed for 3 months. Subsequently, vitamin K antagonists were continued or not, depending on the CHA2DS2-VASc score of each patient. Patients were evaluated pre-discharge, at 1, 3, 6, 9 and 12 months post-procedure. Information collected included details of cardiac medications, NYHA functional class and history of any arrhythmias or other adverse events. In addition, a 12-lead ECG and 24-hour Holter monitoring were systematically obtained at each visit. Echocardiography was performed in all cases the day after procedure. No antiarrhythmic medication was prescribed following ablation. If there was documented recurrence of symptomatic AF during the 3-month blanking period and the patient required antiarrhythmic drug therapy, a previously ineffective but tolerated class 1 or class 3 (sotalol) drug was the preferred option. Atrial tachycardia/AF recurrence was considered, any episode lasting \> 30 s (either symptomatic or asymptomatic) subsequent to a 3-month blanking period.