Pulmonary Vein Isolation With Versus Without Continued Antiarrhythmic Drugs in Persistent Atrial Fibrillation

Background: In real-life, ADT is often continued after catheter ablation for persistent AF. No study investigated whether ADT continued beyond the blanking period reduces recurrence after a first ablation for persistent AF.

Purpose: The aim of this trial is to investigate whether continued ADT (ADT ON) reduces recurrence of atrial tachyarrhythmia (ATA) in the first year after contact-force guided PVI for persistent AF.

Hypothesis: Continued use of ADT beyond the blanking period reduces recurrence of ATA in the first year after PVI .

Eligibility: Subjects that are planned for catheter ablation for persistent AF.

Inclusion: Symptomatic persistent AF resistant to ongoing or prior ADT (failed ADT). Persistent AF is defined as the presence of any prior AF episode ≥7 days.

Exclusion: Any prior AF episode ≥12 months, any recurrence of AF <3 days after cardioversion.

Echo criteria: advanced valvular heart disease, left atrium (LA) volume >37ml/m2, left ventricle (LV) ejection fraction <35% (except if suspected tachycardiomyopathy), septal diameter >15mm, Life expectancy <1 year, BMI >35.

Trial design: This is a prospective, multi-center, randomized (1:1), open label, blinded endpoint study (PROBE). Eligible subjects who sign the study informed consent form at the time of procedural planning will be randomized into one of two study arms: In the ADT off arm (ADT OFF), ADT will be stopped at 3 months after the first procedure. In the ADT ON arm, ADT will be continued at 3 months until 1 year follow up (FU).

First ablation and blanking: In both arms, catheter ablation will consist of 'CLOSE'-guided PVI only (abl index and interlesion distance). High-density voltage mapping will be performed during sinus rhythm. After ablation, ADT is continued/restarted during the 3-month blanking period (except for amiodarone). During the blanking period cardioversions are allowed. At the 3-month visit, all patients will be cardioverted if ATA is present.

Repeat ablation strategy: In case of recurrence of ATA's after 3 months, a repeat ablation is recommended. Depending on the reconnection status of the pulmonary veins (PV), repeat ablation will consist of either PVI only or a patient-tailored ablation approach (antral isolation, superior vena cava (SVC) isolation, isolation of low voltage, linear lesions). Patients stay on the ADT ON or ADT OFF arm.

Primary Endpoint: Any documented ATA (atrial fibrillation, AF, atrial tachycardia, AT, atrial flutter, AFL) lasting >30s from 3 months through 12 month follow-up after the first procedure.

Secondary Endpoints:

ATA recurrence in patients with early peristent AF (defined as AF ≤3 months) Incidence of repeat ablation Unscheduled visits and hospitalisation ADT or ablation related adverse events QOL and symptoms Outcome after repeat ablation

Sample size: In the ADT OFF group ATA recurrence after a first PVI is expected to be 50%. ADT are expected to reduce ATA recurrence to 30%. Given power of 80% and α of 0.05 up to 200 subjects need be enrolled in this study (20 per center)

Inclusion criteria

• Patient with symptomatic persistent AF, resistant to ongoing or prior ADT (failed ADT) Patients is considered to have persistent AF if the patient has suffered any prior AF episode ≥7 days (ESC 2016 guidelines).
• Before PVI, there was at least one episode of persistent AF in the last year.
• Signed Patient Informed Consent Form.
• Age 18 years or older.
• Able and willing to comply with all follow-up testing and requirements.

Exclusion criteria

• Patients not willing or not suited to take any class IC or III ADT.
• Any prior AF episode ≥12 months, or any recurrence of AF <3 days after cardioversion.
• Presence of structural heart disease on echo criteria:

severe valvular heart disease; LA diameter >50mm; LV ejection fraction <35% (except if suspected tachycardiomyopathy); septal diameter >15mm

• BMI >35
• Recent (<3 months) coronary artery bypass grafting (CABG), myocardial infarction, cerebral vascular accident (CVA), uncontrolled heart failure or angina
• Active illness or systemic infection or sepsis
• AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause
• Awaiting cardiac transplantation or other cardiac surgery
• Documented left atrial thrombus or atrial myxoma on imaging
• History of blood clotting or bleeding abnormalities
• Enrollment in any other study evaluating another device or drug
• Women with childbearing potential
• Life expectancy less than 12 months
• Contraindication for catheter ablation (intramural thrombus, tumor or other abnormality that precludes catheter introduction, contraindication to anticoagulation therapy)