Abstract Background The most appropriate ablation strategy for persistent atrial fibrillation (PeAF) has not yet been determined. However, ethanol infusion of the vein of Marshall (VOM) combined with a linear set of ablation lesions (namely the Marshall-PLAN) has yielded encouraging results (1). Purpose Our study aimed at analyzing the relationship between low voltage areas (LVA) and arrhythmias recurrences in a PsAF population treated with the Marshall-PLAN. Methods we conducted a retrospective study on consecutive patients undergoing first catheter ablation (CA) for PsAF between 2021 and 2022 at our center. Pulmonary vein isolation (PVI), mitral isthmus ablation (VOM ethanol infusion, endocardial ablation and epicardial ablation in the great cardiac vein), left atrial (LA) roofline and cavo-tricuspid isthmus ablation were carried out in all the patients. Bidirectional block was validated for all the linear lesions as well as for PVI. Pre-ablation LA electroanatomic maps were built with CARTOv3 system and the PentaRay mapping catheter (minimum 3000 points). LVA were identified as areas >1cm2 (containing ≥3 neighboring points with ≤10mm distance) with bipolar voltage <0.5mV in SR and <0.24 mV in AF (2). All patients were followed for at least 12 months. Results Overall, 93 patients (69±7years, 30% female) with PsAF were included. Their left-ventricle ejection fraction and left atrial volume indexed for body surface area (LAVI) were 57% and 92±20 ml/m2. LA maps demonstrated at least one LVA in 70 subjects (75.3%). The mean relative surface of LA in which a LVA was evidenced was 8±14%. LVA were found within the anterior LA wall in 49 patients (53%), in the posterior wall in 33 patients (35.5%), in the inferior wall in 22 patients (24%), in the lateral wall in 14 patients (15.1%) and in the pulmonary vein region in 44 patients (47.3%). After 19±6 months of follow-up, 28 (30%) patients had AF recurrence. At Cox regression analysis (including LVA burden and LAVI dimensions), LVA localized within the anterior LA wall were predictive of arrhythmia recurrences (hazard ratio [HR] 2.0 [95% CI, 1.1–4.7], P=0.04). Kaplan-Meier estimates of survival free from recurrences at 20 months were 51% and 88% in patients with and without LVAs in the anterior LA wall (Log-rank 0.006). Conclusions The Marshall-PLAN led to a global AF-free survival of 70% after 19±6 months in our cohort of patients with PsAF. Importantly however, the data show that the subset of patients with LVA in the anterior LA wall (i.e., the LA region not targeted by the pre-specified ablation set here evaluated) have a 55%-only AF-free survival while that of patients without LVA in the anterior LA wall was of 88%. As a result, our study supports the relevance of atrial substrate assessment and the possibility of CA strategy optimization in the subset of patients with PsAF and LVA in the anterior LA wall (3).