Effect of Empirical Left Atrial Appendage Isolation on Long-term Procedure Outcome in Patients With Persistent or Long-standing Persistent Atrial Fibrillation Undergoing Catheter Ablation (BELIEF)

The purpose of this prospective randomized study is to assess whether empirical Left Atrial Appendage (LAA) isolation along with the standard approach of pulmonary vein isolation (PVI) and ablation of extra-pulmonary triggers is superior to the standard approach alone in enhancing the long-term success rate of catheter ablation in persistent or long-standing persistent atrial fibrillation (AF) patients.

Study Overview

• Status: Completed
• Conditions: Persistent Atrial Fibrillation
• Intervention / Treatment: Procedure: RFCA of PV and extra-PV triggers; Procedure: LAA isolation along with the conventional ablation strategy

Detailed Description

Persistent (PeAF) and long-standing persistent (LSP) AF are defined as sustained AFs extending beyond seven days and one year respectively (1). Hypertensive, ischemic, valvular and other structural heart diseases most commonly underlie these arrhythmias (2) and the resulting abnormal atrial substrate is believed to be the major contributor toward perpetuation of AF in these non-paroxysmal categories. Several studies have demonstrated that pulmonary vein isolation (PVI) by radiofrequency catheter ablation (RFCA) though successfully restores sinus rhythm in most patients with paroxysmal AF; it has limited success in these sustained arrhythmias (3). Presence of potential trigger-generating areas in the left and right atrium besides pulmonary veins, with reported incidence from 3.2% to 47% (4), can be held responsible for this limited success. These areas include superior vena cava, ligament of Marshall, crista terminalis, coronary sinus, left atrial (LA) posterior wall and LA appendage (3). Therefore, in order to enhance the procedural-success rate, various hybrid measures have emerged to target the PV as well as extra-PV areas that have the ability to initiate or maintain AF. Several previous studies have demonstrated the prevalence of LAA firing in patients with recurrence of AF/AT (atrial tachycardia) after catheter ablation of AF (4). Embryologically, LAA is the remnant of primitive LA, which is formed by the adsorption of primordial PV and their branches during 4th week of embryonic development. Therefore, it is logical to suggest that LAA may initiate AF like pulmonary veins. In an earlier study conducted by our group on 987 AF patients, LAA firing was revealed to be the source of AF in 27% of patients and 93% of those patients were arrhythmia free 6 months after LAA isolation (4).

Our study aims to compare the procedure outcome for two different ablation strategies; 1) standard approach of pulmonary vein isolation extended to the posterior wall down to the coronary sinus and to the left side of the interatrial septum along with isolation of superior vena cava and ablation of complex fractionated atrial electrograms (CFAE) in the atria and coronary sinus, 2) standard approach plus LAA isolation.

Hypothesis: LAA isolation combined with standard ablation procedure enhances the procedural success rate in non-paroxysmal AF patients undergoing catheter ablation.

• Study Type: Interventional
• Enrollment (Anticipated): 156
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Cardiac Arrhythmia Research Foundation
    • Austin, Texas, United States, 78705
      • St. David's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-75 years
2. History of PeAF or LSP AF refractory to antiarrhythmic drugs
3. Willing and ability to understand and sign an informed consent

Exclusion Criteria:

1. Reversible causes of AF (hyperthyroidism)
2. Left atrial thrombus
3. Moderate to severe valvular heart disease
4. Contraindication for anticoagulation
5. Life expectancy < 12 months
6. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ablation of PV and extra-PV triggers; Conventional approach which includes pulmonary vein isolation (PVI) and ablation of extra-pulmonary triggers	Procedure: RFCA of PV and extra-PV triggers; PVAI and isolation of extra PV triggers
Active Comparator: LAA isolation along with the conventional ablation strategy	Procedure: LAA isolation along with the conventional ablation strategy; PVAI + isolation of extra PV triggers + LAA isolation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from AF/ATs	Freedom from AF/ATs, defined as no episodes of AF/AT without AADs lasting >30 seconds at follow-up	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe adverse events due to cardiac cause	Severe adverse events (hospital admissions or death due to a cardiac cause)	12 months

Collaborators and Investigators

• Sponsor: Texas Cardiac Arrhythmia Research Foundation

Publications and helpful links

General Publications

• Di Biase L, Burkhardt JD, Mohanty P, Mohanty S, Sanchez JE, Trivedi C, Gunes M, Gokoglan Y, Gianni C, Horton RP, Themistoclakis S, Gallinghouse GJ, Bailey S, Zagrodzky JD, Hongo RH, Beheiry S, Santangeli P, Casella M, Dello Russo A, Al-Ahmad A, Hranitzky P, Lakkireddy D, Tondo C, Natale A. Left Atrial Appendage Isolation in Patients With Longstanding Persistent AF Undergoing Catheter Ablation: BELIEF Trial. J Am Coll Cardiol. 2016 Nov 1;68(18):1929-1940. doi: 10.1016/j.jacc.2016.07.770.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: May 26, 2011
• First Submitted That Met QC Criteria: May 27, 2011
• First Posted (Estimate): May 30, 2011

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Long-standing persistent atrial fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: TCAI_BELIEF