Prophylactic Pulmonary Vein Isolation During Atrial Flutter Ablation (PREVENT-AF II)

Prophylactic Pulmonary Vein Isolation During Atrial Flutter Ablation: The PREVENT-AF Study II

Pulmonary vein isolation (PVI) via catheter ablation has been successfully employed for years to treat symptomatic atrial fibrillation (AF). Moreover, PVI has not been used as a prophylactic intervention even in groups known to be high-risk for the future development of AF. Preliminary studies, including our pilot PREVENT AF I randomized trial, suggested that prophylactic PVI may be effective at reducing new onset AF and overall AF burden in atrial flutter (AFL) patients.

This is a multicenter single-blind randomized controlled trial, "Prophylactic Pulmonary Vein Isolation During Atrial Flutter Ablation" (PREVENT AF II) to determine if PVI in conjunction with AFL ablation for patients with typical AFL results in a significant reduction in cardiac events and healthcare utilization.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Flutter Typical
• Intervention / Treatment: Device: Catheter ablation

Detailed Description

Atrial flutter (AFL) is a distinct arrhythmic entity with a recognizable ECG phenotype resulting from a well characterized atrial arrhythmia mechanism. Typical AFL results from a single reentrant circuit located in the right atrium. The circuit is large and entirely confined to the right atrium, revolving around the tricuspid annulus. The reentrant circuit rotates in a counterclockwise direction, caudocranial along the interatrial septum and craniocaudal along the right atrial free wall. An area of slow conduction exists in the posterior-inferior aspect of the circuit, with a fully excitable gap. It is believed that most circuits utilize an anatomic or functional obstacle in the posterior right atrium, such as the crista terminalis and inferior vena cava.

AFL is diagnosed in about 200,000 new cases per year in the US. Because of the high- risk of recurrence of typical AFL with medical therapy, catheter ablation of the cavo-tricuspid isthmus has emerged as definitive and first-line treatment for these patients. The AFL ablation procedure is performed in about 47,000 patients per year in the US. However, it has been recognized that in many of these patients, atrial fibrillation (AF) will develop during follow-up.

PVI via catheter ablation has been successfully employed for years to treat symptomatic AF. Moreover, PVI has not been used as a prophylactic intervention even in groups known to be high-risk for the future development of AF. Preliminary studies, including our pilot PREVENT AF I randomized trial, suggested that prophylactic PVI may be effective at reducing new onset AF and overall AF burden in AFL patients. Based on this pilot trial, we propose a multicenter randomized clinical trial enrolling 620 patients with paroxysmal or persistent typical AFL (with no known AF) who have been referred for a catheter ablation procedure based on conventional clinical indications and who will be randomized 1:1 to catheter ablation of the cavo-tricuspid isthmus (CTI) for AFL alone (control group) or catheter ablation of AFL plus complete PVI (experimental group ) with prespecified clinical endpoints. There is a strong premise based on several observational studies and a few small pilot trials that prophylactic PVI in patients undergoing AFL ablation for AFL is associated with a significant reduction in the risk and burden of AF in comparison to AFL ablation performed without concomitant PVI. However, data from these clinical trials are lacking in regard to whether PVI in addition to routine AFL ablation will contribute to a significant reduction in cardiac events and healthcare utilization.

• Study Type: Interventional
• Enrollment (Estimated): 620
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 55 years on date of consent
2. History of typical AFL and plans for a guideline-supported catheter ablation for AFL - including paroxysmal AFL defined as AFL with duration of up to 7 days and persistent AFL as longer than 7 days or if interrupted by cardioversion for clinical reasons and up to 1 year
3. Left atrial diameter ≥ 4.5 cm within 12 calendar months prior to or on consent date by transthoracic echocardiography
4. No identifiable AF on any prior ECG within past 1 year
5. CHA2DS2 -VASc ≥ 2

Exclusion Criteria:

1. Inability to undergo or AFL or AF catheter ablation (e.g., presence of a left atrial thrombus)
2. AFL or AF due to reversible cause e.g. hyperthyroid state
3. Contraindication to systemic anticoagulation
4. Prior surgical or percutaneous cardiac ablation procedure any time in the past
5. Prior AFL ablation (e.g. CTI) or PVI ablation any time in the past
6. LV ejection fraction < 35%
7. Paroxysmal, persistent or longstanding persistent AF
8. Presence of NYHA Class IV congestive heart failure
9. Acute coronary syndrome or coronary artery bypass surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within 3 calendar months prior to consent date
10. Enzyme-positive myocardial infarction within the past 3 calendar months prior to consent
11. Severe aortic or mitral valvular heart disease eligible for percutaneous or surgical repair/replacement procedures
12. Angiographic evidence of coronary disease that requires coronary revascularization and with likelihood of undergoing a CABG or PCI in the next 3 calendar months following consent date
13. Any medical condition likely to limit survival to < 1 year
14. Renal failure requiring dialysis at time of consent
15. Pregnancy
16. History of non-compliance to medical therapy
17. Participation in other clinical trials (observational/lead registries are allowed) without approval from the DCC
18. Inability or unwillingness to provide informed consent
19. Resides at such a distance from the enrolling site so travel to follow-up visits would be unusually difficult
20. Does not anticipate residing in the vicinity of the enrolling site for the duration of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atrial flutter ablation; Radiofrequency or pulsed field catheter ablation from the tricuspid annulus to the inferior vena cava in the cavo-tricuspid isthmus	Device: Catheter ablation; CTI ablation; pulmonary vein isolation (PVI)
Experimental: Atrial flutter ablation + prophylactic pulmonary vein isolation; After completion of the standard atrial flutter ablation, radiofrequency, cryoballoon or pulsed field ablation of the pulmonary veins	Device: Catheter ablation; CTI ablation; pulmonary vein isolation (PVI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite endpoint	Time to cardiovascular hospitalization/emergency room visits, stroke, or death, whichever comes first	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life before and after ablation	Atrial Fibrillation Effect On Quality-Of-Life Questionnaire (AFEQT) (Score 0-100, higher scores indicate better quality of life	12 months and baseline
Procedural complications	Adverse events	1 month
Number of subjects with Incident atrial fibrillation	Obtained by serial 7-day Holters and standard of care ECGs	At 6, 12 and 24 months
Atrial Fibrillation Severity Scale (AFSS) (Scored 0-35, with higher scores worse quality of life)	Quality of life questionnaire	12 months and baseline

Collaborators and Investigators

• Sponsor: University of Rochester

Publications and helpful links

General Publications

• Steinberg JS, Romanov A, Musat D, Preminger M, Bayramova S, Artyomenko S, Shabanov V, Losik D, Karaskov A, Shaw RE, Pokushalov E. Prophylactic pulmonary vein isolation during isthmus ablation for atrial flutter: the PReVENT AF Study I. Heart Rhythm. 2014 Sep;11(9):1567-72. doi: 10.1016/j.hrthm.2014.05.011. Epub 2014 May 12.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2027
• Primary Completion (Estimated): May 1, 2032
• Study Completion (Estimated): May 1, 2032

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Surgical Procedures, Operative; Ablation Techniques; Radiofrequency Ablation; Radiofrequency Therapy; Catheter Ablation
• Other Study ID Numbers: 2114335

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes