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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Marshall Plan arm | Experimental | Patients will undergo (1) the destruction of Marshall bundles by ethanol infusion followed by ablation of the distal coronary sinus bundles, the ridge and the saddle; (2) the standard pulmonary veins sleeves isolation; (3) and finally the ablation of the mitral, the roof, and the cavo-tricuspid isthmus. |
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| Pulmonary vein isolation arm | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Destruction of Marshall bundles | Procedure | Destruction of Marshall bundles by ethanol 96% infusion (2 separate injections of 5ml on 1 minute each) followed by ablation of the distal coronary sinus bundles, the ridge and the saddle. |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence of AF or Atrial Tachycardia (AT) greater than 30 seconds with or without antiarrhythmic medications after a single ablation procedure | Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post ablation, at 2 years with or without antiarrhythmic medications after a single ablation procedure. Recurrences will be identified through transtelephonic electrocardiogram (ECG) monitor with weekly transmitted ECG and at any time in case of symptoms. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence of AF or AT greater than 30 seconds after multiple ablation procedures | Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post procedure, at 2 years after multiple ablation procedures. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms. | 2 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicolas DERVAL, MD | University Hospital, Bordeaux | Principal Investigator |
| Antoine BENARD, MD | University Hospital, Bordeaux | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AZ Sint Jan Brugge | Bruges | 8000 | Belgium | |||
| Clinique Saint Augustin |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41951089 | Derived | Derval N, Tixier R, Duchateau J, Georget A, Albenque JP, Combes S, Massoullie G, Zhao A, Cauchemez B, Knecht S, Duytschaever M, Escande W, Lepillier A, Denis A, Chauvel R, Bortone A, Maury P, Sacristan B, Charton J, Sacher F, Hocini M, Haissaguerre M, Jais P, Benard A, Pambrun T. Marshall-Plan ablation strategy versus pulmonary vein isolation in persistent atrial fibrillation: Clinical trial design. Am Heart J. 2026 Aug;298:107442. doi: 10.1016/j.ahj.2026.107442. Epub 2026 Apr 6. |
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The Marshall Plan is a prospective randomized, parallel-group, multicenter clinical trial of superiority
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| Pulmonary veins isolation | Procedure | Achievement of a wide disconnection of the right and left pulmonary veins. |
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| Linear ablation in the left and right atria | Procedure | Ablation of the mitral, the roof, and the cavo-tricuspid isthmus |
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| Recurrence of AF or AT greater than 30 seconds after a single ablation procedure (1) | Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post procedure, at 2 years, will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms. | 2 years |
| Recurrence of AF greater than 30 seconds after a single ablation procedure (2) | Recurrence rate (percentage) of AF > 30 seconds after the blanking period of 3-months post procedure, at 2 years after a single ablation procedure. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms. | 2 years |
| Recurrence of AF greater than 30 seconds after multiple ablation procedure. | Recurrence rate (percentage) of AF > 30 seconds after the blanking period of 3-months post procedure, at 2 years after a multiple ablation procedure. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms. | 2 years |
| Recurrence of AF or AT greater than 30 seconds without antiarrhythmic medications after a single ablation procedure. | Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post procedure at 2-years without antiarrhythmic medications after a single ablation procedure. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms. | 2 years |
| Recurrence of AF or AT greater than 30 seconds without antiarrhythmic medications after multiple ablation procedure. | Recurrence rate (percentage) of AF or AT > 30 seconds after the blanking period of 3-months post procedure at 2-years without antiarrhythmic medications after multiple ablation procedure. It will be identified through transtelephonic ECG monitor with weekly transmitted ECG and at any time in case of symptoms. | 2 years |
| Proportion of patients under antiarrhythmic medications | Percentage of patients | 2 years |
| Proportion of patients with repeated procedures | Percentage of patients | up to 2 years |
| Incidence of periprocedural complications | Percentage of periprocedural complications : transient ischemic attack or stroke, cardiac tamponade, atrioesophageal fistula, pericarditis, complications at access site (hematoma, arteriovenous fistula, pseudoaneurysm) | 2 years |
| Bordeaux |
| 33074 |
| France |
| Clermont-Ferrand University Hospital | Clermont-Ferrand | 63003 | France |
| Ambroise Paré Hospital | Neuilly-sur-Seine | 92200 | France |
| Les Franciscaines Hospital | Nîmes | 30032 | France |
| Bordeaux University Hospital | Pessac | 33604 | France |
| Centre Cardiologique du Nord | Saint-Denis | 93200 | France |
| Clinique Pasteur | Toulouse | 31076 | France |
| Toulouse University Hospirtal | Toulouse | 31400 | France |
| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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