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

Atrial Fibrillation Clinical Trial

— MARSHALL-PLAN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04681872
• Other study ID #: CHUBX 2019/55
• Status: Recruiting
• Phase: N/A
• Start date: September 20, 2021
• Est. completion date: September 20, 2024

Study information

• Verified date: February 2022
• Source: University Hospital, Bordeaux
• Contact: Nicolas DERVAL, MD
• Phone: (0)5 57 65 64 71
• Email: nicolas.derval[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 262
• Est. completion date: September 20, 2024
• Est. primary completion date: September 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Procedure:
• Destruction of Marshall bundles
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.
• Pulmonary veins isolation
Achievement of a wide disconnection of the right and left pulmonary veins.
• Linear ablation in the left and right atria
Ablation of the mitral, the roof, and the cavo-tricuspid isthmus

Locations

Country	Name	City	State
Belgium	AZ Sint Jan Brugge	Brugge
France	Clinique Saint Augustin	Bordeaux
France	Clermont-Ferrand University Hospital	Clermont-Ferrand
France	Ambroise Paré Hospital	Neuilly-sur-Seine
France	Les Franciscaines Hospital	Nîmes
France	Bordeaux University Hospital	Pessac
France	Centre Cardiologique du Nord	Saint-Denis
France	Clinique Pasteur	Toulouse
France	Toulouse University Hospirtal	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of patients under antiarrhythmic medications	Percentage of patients	2 years
Secondary	Proportion of patients with repeated procedures	Percentage of patients	up to 2 years
Secondary	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