Prophylactic Pulmonary Vein Isolation During Atrial Flutter Ablation

Official title

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

Overview

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.

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.

Interventions

• Device Catheter ablation
  CTI ablation; pulmonary vein isolation (PVI)

Primary outcome measures

• Composite endpoint [Time frame: Up to 4 years]

Secondary outcome measures (4)

• Quality of life before and after ablation [Time frame: 12 months and baseline]
• Procedural complications [Time frame: 1 month]
• Number of subjects with Incident atrial fibrillation [Time frame: At 6, 12 and 24 months]
• Atrial Fibrillation Severity Scale (AFSS) (Scored 0-35, with higher scores worse quality of life) [Time frame: 12 months and baseline]

Eligibility criteria

Inclusion criteria

• Age ≥ 55 years on date of consent
• 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
• Left atrial diameter ≥ 4.5 cm within 12 calendar months prior to or on consent date by transthoracic echocardiography
• No identifiable AF on any prior ECG within past 1 year
• CHA2DS2 -VASc ≥ 2

Exclusion criteria

• Inability to undergo or AFL or AF catheter ablation (e.g., presence of a left atrial thrombus)
• AFL or AF due to reversible cause e.g. hyperthyroid state
• Contraindication to systemic anticoagulation
• Prior surgical or percutaneous cardiac ablation procedure any time in the past
• Prior AFL ablation (e.g. CTI) or PVI ablation any time in the past
• LV ejection fraction < 35%
• Paroxysmal, persistent or longstanding persistent AF
• Presence of NYHA Class IV congestive heart failure
• 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
• Enzyme-positive myocardial infarction within the past 3 calendar months prior to consent
• Severe aortic or mitral valvular heart disease eligible for percutaneous or surgical repair/replacement procedures
• 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
• Any medical condition likely to limit survival to < 1 year
• Renal failure requiring dialysis at time of consent
• Pregnancy
• History of non-compliance to medical therapy
• Participation in other clinical trials (observational/lead registries are allowed) without approval from the DCC
• Inability or unwillingness to provide informed consent
• Resides at such a distance from the enrolling site so travel to follow-up visits would be unusually difficult
• Does not anticipate residing in the vicinity of the enrolling site for the duration of the trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

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. PMID 24832767

Identifiers

NCT: NCT07649603 · 2114335

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗