ImportancePulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal AF. The left atrial posterior wall may contribute to maintenance of persistent AF, and posterior wall isolation (PWI) is a common PVI adjunct. However, PWI has not been subjected to randomized comparison.ObjectiveTo compare PVI with PWI vs PVI alone in patients with persistent AF undergoing first-time catheter ablation.Design, Setting, and ParticipantsInvestigator initiated, multicenter, randomized clinical trial involving 11 centers in 3 countries (Australia, Canada, UK). Symptomatic patients with persistent AF were randomized 1:1 to either PVI with PWI or PVI alone. Patients were enrolled July 2018-March 2021, with 1-year follow-up completed March 2022.InterventionsThe PVI with PWI group (n = 170) underwent wide antral pulmonary vein isolation followed by posterior wall isolation involving linear ablation at the roof and floor to achieve electrical isolation. The PVI-alone group (n = 168) underwent wide antral pulmonary vein isolation alone.Main Outcomes and MeasuresPrimary end point was freedom from any documented atrial arrhythmia of more than 30 seconds without antiarrhythmic medication at 12 months, after a single ablation procedure. The 23 secondary outcomes included freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures, freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures, AF burden between study groups at 12 months, procedural outcomes, and complications.ResultsAmong 338 patients randomized (median age, 65.6 [IQR, 13.1] years; 76.9% men), 330 (97.6%) completed the study. After 12 months, 89 patients (52.4%) assigned to PVI with PWI were free from recurrent atrial arrhythmia without antiarrhythmic medication after a single procedure, compared with 90 (53.6%) assigned to PVI alone (between-group difference, –1.2%; hazard ratio [HR], 0.99 [95% CI, 0.73-1.36]; P = .98). Of the secondary end points, 9 showed no significant difference, including freedom from atrial arrhythmia with/without antiarrhythmic medication after multiple procedures (58.2% for PVI with PWI vs 60.1% for PVI alone; HR, 1.10 [95% CI, 0.79-1.55]; P = .57), freedom from symptomatic AF with/without antiarrhythmic medication after multiple procedures (68.2% vs 72%; HR, 1.20 [95% CI, 0.80-1.78]; P = .36) or AF burden (0% [IQR, 0%-2.3%] vs 0% [IQR, 0%-2.8%], P = .47). Mean procedural times (142 [SD, 69] vs 121 [SD, 57] minutes, P < .001) and ablation times (34 [SD, 21] vs 28 [SD, 12] minutes, P < .001) were significantly shorter for PVI alone. There were 6 complications for PVI with PWI and 4 for PVI alone.Conclusions and RelevanceIn patients undergoing first-time catheter ablation for persistent AF, the addition of PWI to PVI alone did not significantly improve freedom from atrial arrhythmia at 12 months compared with PVI alone. These findings do not support the empirical inclusion of PWI for ablation of persistent AF.Trial Registrationanzctr.org.au Identifier: ACTRN12616001436460

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Background: Population studies have demonstrated a range of sex differences including a higher prevalence of atrial fibrillation (AF) in men and a higher risk of AF recurrence in women. However, the underlying reasons for this higher recurrence are unknown. This study evaluated whether sex-based electrophysiological substrate differences exist to account for worse AF ablation outcomes in women. Methods: High-density electroanatomic mapping of the left atrium was performed in 116 consecutive patients with AF. Regional analysis was performed across 6 left atrium segments. High-density maps were created using a multipolar catheter (Biosense Webster) during distal coronary sinus pacing at 600 and 300 ms. Mean voltage and conduction velocity was determined. Complex fractionated signals and double potentials were manually annotated. Results: Overall, 42 (36%) were female, mean age was 61±8 years and AF was persistent in 52%. Global mean voltage was significantly lower in females compared with males at 600 ms (1.46±0.17 versus 1.84±0.15 mV, P <0.001) and 300 ms (1.27±0.18 versus 1.57±0.18 mV, P =0.013) pacing. These differences were seen uniformly across the left atrium. Females demonstrated significant conduction velocity slowing (34.9±6.1 versus 44.1±6.9 cm/s, P =0.002) and greater proportion of complex fractionated signals (9.9±1.7% versus 6.0±1.7%, P =0.014). After a median follow-up of 22 months (Q1–Q3: 15–29), females had significantly lower single-procedure (22 [54%] versus 54 [75%], P =0.029) and multiprocedure (24 [59%] versus 60 [83%], P =0.005) arrhythmia-free survival. Female sex and persistent AF were independent predictors of single and multiprocedure arrhythmia recurrence. Conclusions: Female patients demonstrated more advanced atrial remodeling on high-density electroanatomic mapping and greater post-AF ablation arrhythmia recurrence compared with males. These changes may contribute to sex-based differences in the clinical course of females with AF and in part explain the higher risk of recurrence.

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Background - Endocardial-epicardial dissociation (EED) and focal breakthroughs in humans with atrial fibrillation (AF) have been recently demonstrated using activation mapping of short 10-second AF segments. In the current study we used simultaneous endo-epi phase mapping to characterise endo-epi activation patterns on long segments of human persistent AF (PeAF). Methods - Simultaneous intra-operative mapping of endo- and epicardial lateral RA wall was performed in patients with PeAF using two high-density grid catheters (16 electrodes, 3mm spacing). Filtered unipolar and bipolar electrograms (EGM's) of continuous 2-min AF recordings and electrodes locations were exported for phase analyses. We defined EED as phase difference of ≥20ms between paired endo-epi electrodes. Wavefronts (WF) were classified as rotations, single WF (SWF), focal waves or disorganised activity as per standard criteria. Endo-Epi WF patterns were simultaneously compared on dynamic phase maps. Complex fractionated EGM's were defined as bipolar EGM's with ≥5 directional changes occupying at least 70% of sample duration. Results - Fourteen patients with PeAF undergoing cardiac surgery were included. EED was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganised activity (Endo:41.3% vs Epi:46.8%, p=0.0194) and SWF (Endo:31.3% vs Epi:28.1%, p=0.129) were the dominant patterns. Transient rotations (Endo:22% vs Epi:19.2%, p=0.169; mean duration: 590±140ms) and non-sustained focal waves (Endo:1.2% vs Epi:1.6%, p=0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. EGM fractionation was significantly higher in the epicardium than endocardium (61.2% vs 51.6%, p<0.0001). Conclusions - Simultaneous endo-epi phase mapping of prolonged human PeAF recordings shows significant EED marked temporal heterogeneity, discordant and transitioning WF patterns and complex fractionations. No sustained focal activity was observed. Such complex 3D-interactions provide insight into why endocardial mapping alone may not fully characterise the AF mechanism and why endocardial ablation may not be sufficient.

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