This is a prospective, single-center, study. A targeted number of 181patients with persistent AF will be included according to pre-defined criteria. The ablation procedure consists on the identification of the arrhythmic substrate using a novel integrated mapping technique. We hypothesize that such approach may potentially lead to a mechanisms-targeted ablation strategy of persistent AF.

This is a prospective, single-center, study enrolling a total of 181patients with persistent AF according to well defined inclusion and exclusion criteria. The ablation procedure consists on the identification of the arrhythmic substrate using a novel integrated 3D mapping technique followed by standard CPVA at the end of the procedure. We will ablate substrates showing fast and regular electrical activities, starting from areas with the fastest mean cycle length and/or areas that have consistent rotational or focal propagation pattern and/or areas that comprise the slow conduction zone of possible arrhythmia circuits. After substrate ablation and AF termination, arrhythmia inducibility will be assessed and, if not inducible, the procedure will be completed by standard CPVA. If AF is still inducible, a new 3D map will be performed to identify further targets to be eliminated. Electrical cardioversion may be done at the end of the procedure. We hypothesized that such approach may potentially lead to a mechanisms-targeted ablation strategy leading to elimination of arrhythmic sources in individual patients, thus improving their clinical outcome. We will also characterize, identify and target the real pathophysiological substrates. After ablation, AF recurrence will be assessed by implantable loop recorder or thans-telephonic ECG recording from the end of the 3 months blanking period to 12 months following the procedure.The duration of this study is expected to be 24 months, from the first patient enrollment to the last patient follow-up.

Inclusion Criteria: Age (18-85 years), persistent AF according to ESC/EHRA guidelines, first or second ablation procedure, ability to provide informed written consent.

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Exclusion Criteria: Secondary AF, Hyperthyroidism, LVEF<30%, NYHA functional class IV, uncorrected valvular heart diseases, contraindication to anticoagulation, left atrial thrombus, recent (<6 months) myocardial infarction, thoracic surgery for congenital, valvular diseases, History of cerebrovascular events, pregnancy, cancer or other significant comorbidities.

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A total of 181 subjects suffering from persistent Atrial Fibrillation will be enrolled. Subject screening and enrollment will be carried out for approximately 12 months. A subject, who mets all of the inclusion criteria, and none of the exclusion criteria, is eligible to participate in this study. All patients will be accounted for and documented, assigning an identification code linked to their names, alternative identification, or contact information.This log will be kept up to date throughout the clinical study by the principal investigator. To ensure subject privacy and confidentiality of data this log must be maintained throughout the clinical study at the clinical site.