Marshall Ethanolization, Pulmonary Vein Isolation and Line Completion for Ablation of Persistent Atrial Fibrillation

In ablation strategy for persistent Atrial Fibrillation (PsAF), ablation limited to Pulmonary Vein (PV) isolation is the most straightforward approach but the result give only 50% of arrhythmia free follow-up. Substrate modification strategies have failed to demonstrate their superiority with variable reported success rate. The Marshall network is a highly arrhythmogenic structure that has not been incorporated in current ablation strategies. The investigators sought to investigate a new ablation strategy that target systematically the vein of Marshall by ethanol infusion. This step is integrated in a new ablation strategy consisting in a global anatomical substrate based ablation including PV isolation and left atrial linear ablation (Marshall-Plan).

Atrial fibrillation (AF) characterized by a fast and anarchic electrical activation of the atria, results in uncoordinated and inefficient atrial contractions that increases the risks of heart failure and strokes. Besides being a major source of morbidity and mortality, AF is one of the most common heart condition and its prevalence increases with age. Radiofrequency catheter ablation of AF has become one of the treatment of choice in AF resistant to conventional antiarrhythmic drugs. For paroxysmal AF, the ablation strategy is clear and consists in complete pulmonary veins isolation (PVI). However, if this strategy works well in paroxysmal AF, the recurrences rate remains high in persistent AF. Beyond PVI, the ablation strategy that has prevailed over the past two decades remains controversial: the left atrium partition using linear lesions ("cox-maze" strategy); the mapping of the left atrium in AF to identify and localize the arrhythmia sources. Both methods have, besides favoring atrial flutters, failed to demonstrated superiority compared to PVI alone (as showed by the clinical trial STAR AF 2). The investigators aims to test a new method of ablation for patients suffering from persistent AF in order to decrease post ablation recurrence. They propose a strategy targeting the native structures facilitating reentries including the ligament of Marshall (LOM), an embryological remnant. Indeed, two studies have demonstrated that LOM could be the source of focal activities, the substrate of reentries and a strong parasympathetic modulator. For these reasons, LOM may represent a major target in AF treatment besides PV isolation. To date, ablation techniques do not ensure the complete destruction of the Marshall's musculature and parasympathetic ganglia that surround it, largely isolated by a sheath of adipose tissue. To overcome this technical limitation, LOM elimination can be achieved by alcohol injection into the vein of Marshall. This innovative approach will then consist in 3 consecutive steps: 1) the destruction of Marshall bundles by ethanol infusion followed by the ablation of the distal and proximal muscular ramification (coronary sinus and ridge); 2) the standard PV isolation; 3) the linear lesions: the mitral, the roof and of the cavo-tricuspid isthmus, main causes of recurrence in atrial flutter.

Eligibility Criteria:
Inclusion Criteria:

* Age \> 18 years of both genders
* Suitable candidate for catheter and ablation of atrial fibrillation defined as: history of symptomatic persistent atrial fibrillation in the past year documented by ECG,
* Patient affiliated or beneficiary of social security scheme,
* Free, informed and written consent signed by the participant and the principal investigator (at least at the inclusion date and before all exams required for the clinical research),
* Effective contraception for women of childbearing potential.

Exclusion Criteria:

* Prior left atrial heart ablation procedure,
* Documented left atrial thrombus or another abnormality which precludes catheter introduction,
* Contraindication to anticoagulation therapy (heparin, warfarin, or novel oral anticoagulant (NOAC)),
* Contraindication to iodinated contrast products (history of major immediate reaction, thyrotoxicosis),
* Ethanol hypersensitivity,
* Unstable angina or ongoing myocardial ischemia,
* Myocardial infarction within 3 months prior to inclusion,
* Congenital heart disease, where the underlying abnormality increases the ablation risk,
* Severe bleeding, clotting or thrombotic disorder,
* Hypertrophic cardiomyopathy defined by a left ventricular septum thickness \> 1.5 cm,
* Pregnant, parturient or nursing women,
* Person unable to give informed consent,
* Patient detained by judicial or administrative order, patient under legal protection (guardianship, curators, safeguarding justice).