The goal of this clinical study is to find out which treatment works best for people with persistent atrial fibrillation (a type of irregular heartbeat). Researchers are comparing two types of heart ablation procedures:

• An anterior mitral line ablation (a treatment at the front part of the heart)
• A posterior mitral line ablation (at the back of the heart), sometimes with an extra step using a small vein called the Vein of Marshall

The main questions the study aims to answer are:

• Which approach works better at fixing the heart rhythm?
• Which approach is safer (less complications)?

People who take part in this study will:

• Undergo an ablation procedure as part of their standard care
• Attend follow-up visits at 1, 3, and 6 months
• Have tests like ECGs, heart ultrasound (echocardiogram), blood tests, heart rhythm monitors (Holter), and a heart CT scan

The MIVANT trial aims to compare two different strategies for treating patients with persistent atrial fibrillation (AF) using catheter ablation techniques. AF is a common heart rhythm disorder, and in persistent forms, it often does not respond adequately to pulmonary vein isolation (PVI) alone. For this reason, many patients require additional ablation lines in the left atrium to reduce arrhythmia recurrence and improve long-term rhythm control.

One such ablation strategy involves creating a linear lesion across the mitral isthmus-a region between the mitral valve and the pulmonary veins. There are two main anatomical approaches to target this area:

• The anterior mitral line, which connects the right superior pulmonary vein to the mitral annulus
• The posterior mitral line, which connects the left inferior pulmonary vein to the mitral annulus

The posterior line is technically more challenging because of the complex anatomy, proximity to blood vessels, and epicardial electrical pathways that can bypass endocardial lesions. However, this difficulty can be addressed by a technique known as Vein of Marshall (VOM) ethanol infusion. The VOM is a small vein near the mitral isthmus that contains nerve fibers and muscle bundles involved in atrial arrhythmias. Infusing ethanol into this vein can help create more effective and lasting ablation lines by reaching areas that standard catheter ablation cannot.

The MIVANT study will enroll 146 adult patients with persistent atrial fibrillation who are already scheduled to receive additional ablation beyond PVI. Patients will be randomized in a 1:1 ratio to undergo either:

• A posterior mitral line ablation, with or without ethanol infusion into the Vein of Marshall, depending on anatomical feasibility
• An anterior mitral line ablation without ethanol infusion

All procedures will be performed under general anesthesia or conscious sedation, using state-of-the-art mapping and ablation tools. Standardized ablation parameters will be followed to ensure consistency and quality across sites.

The main objective of this study is to determine whether the posterior approach-with possible VOM infusion-leads to a higher success rate of procedural bidirectional block across the mitral line, compared to the anterior approach.

Secondary objectives include assessing:

• Safety outcomes such as bleeding, stroke, or coronary artery injury
• Efficiency of the procedure, including total time, fluoroscopy exposure, and number of lesions needed
• Recurrence of atrial arrhythmias at 6 months
• Patient quality of life
• Hospitalizations related to cardiovascular events

Participants will attend follow-up visits at 1, 3, and 6 months, during which they will undergo tests such as ECGs, echocardiography, Holter monitoring, CT coronary angiography, and blood tests.

This study is expected to last a total of 24 months, with 18 months allocated for patient recruitment and a minimum of 6 months follow-up per participant. The study is coordinated by AZ Sint-Jan Brugge AV in Belgium, with possible collaboration from other high-volume centers in France and Switzerland.

The findings of the MIVANT study will help clarify whether posterior mitral isthmus ablation-with the aid of Vein of Marshall ethanolisation-is a more effective and equally safe alternative to the anterior approach in the treatment of persistent atrial fibrillation.

Inclusion Criteria:

• Patients between the ages of 18 and 80 years, diagnosed with symptomatic persistent AF with clinical indication for left atrial ablation with a mitral isthmus line. Pulmonary vein will be isolated in all patients before starting the mitral isthmus line (during a previous or the same procedure)

Exclusion Criteria:

• Previous mitral line or any other left atrial ablation beyond pulmonary vein isolation
• Left atrial (LA) thrombus. LA thrombus can be determined by preprocedural imaging: CT, transesophageal echocardiography or MRI.
• LA diameter greater than 60 mm on long axis parasternal view, or left atrial volume more than 250 cc.
• Left ventricular ejection fraction <25%.
• Cardiac surgery within the previous 90 days.
• Expecting cardiac transplantation or other cardiac surgery within 180 days.
• Percutaneous transluminal coronary angioplasty/stenting or myocardial infarction within the previous 30 days.
• Documented history of a thromboembolic event within the previous 60 days.
• Diagnosed atrial myxoma.
• Significant restrictive, constrictive, or chronic obstructive pulmonary disease with chronic symptoms.
• Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment
• Women who are pregnant or who plan to become pregnant during the study.
• Acute illness or active infection at time of index procedure
• Renal insufficiency
• Unstable angina.
• History of blood clotting or bleeding abnormalities.
• Contraindication to anticoagulation.
• Life expectancy less than 1 year.
• Uncontrolled heart failure.
• Presence of a condition that precludes vascular access.
• International normalised ratio (INR) greater than 4 within 24 hours of procedure - for patients taking warfarin.
• Unwilling or unable to provide informed consent.