Prospective Elimination Of Distal Coronary Sinus-Left Atrial Connections for Atrial Fibrillation Ablation Trial

NCT03646643 | Completed Results DMC

• 1 other identifier: 829990
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people in the US and around the world. Over the last 20 years, catheter based AF ablation has been widely adopted offering improved symptom control for many patients worldwide. However, long-term success rates remain suboptimal. Prior work indicates that distal connections between coronary sinus musculature and the left atrium exist and provide a substrate for single or multiple reentry beats as a trigger for atrial fibrillation. In this trial, the investigators will examine the efficacy of elimination of distal connection(s) between coronary sinus and left atrial musculature for suppression of recurrent atrial arrhythmias.

Conditions

Atrial Fibrillation; Arrhythmias, Cardiac

Keywords

Atrial fibrillation; Coronary sinus-left atrium connection; Ablation

Outcome Measures

Primary Outcomes (1)

• Recurrence Rate of Atrial Arrhythmias

  The primary endpoint of the study is recurrence rate of atrial arrhythmia following ablation. The primary endpoint will be assessed using survival statistical models measuring time to failure among the two study arms. Failure is defined as a non-self-terminating bout of atrial fibrillation, atrial flutter, or atrial tachycardia \>30 seconds in duration following the 90-day post-ablation blanking period. If no AF occurs during the study period, censoring will occur at 180±45 days post-ablation.

  Time to atrial arrhythmia recurrence will be recorded as time to the first ECG or monitor that shows atrial arrhythmia recurrence between the end of the blanking period (90 days post ablation) and the end of the study (180±45 days post ablation).

Study Arms (2)

PVI, non-PV triggers

ACTIVE COMPARATOR

Interventions: Atrial fibrillation ablation, including conventional pulmonary vein isolation (PVI) and non-PV triggers ablation.

Procedure: Standard Atrial fibrillation ablation

PVI, non-PV triggers & CS-LA connection

ACTIVE COMPARATOR

Interventions: Atrial fibrillation ablation, including conventional pulmonary vein isolation (PVI) and non-PV triggers ablation in addition to coronary sinus-left atrium connection elimination. Distal coronary sinus pacing will be utilized to localize the earliest connection (aside from septal) from the coronary sinus to the left atrial musculature. Once localized, focal radiofrequency lesions will be applied at the discretion of the investigator until distal coronary sinus to left atrial connections are eliminated.

Procedure: Standard Atrial fibrillation ablation; Procedure: Coronary sinus to left atrium connection elimination

Interventions

Standard Atrial fibrillation ablation PROCEDURE

The AF ablation procedures should follow the sequence below: Diagnostic catheter placement Electrophysiology study; Transseptal puncture; Left atrial electro-anatomical mapping is required prior to an ablation procedure. Post ablation pacing procedure(s) and/or infusion of cardiac medications to localize triggers/ assess and localize pulmonary vein reconnections (e.g., Adenosine, Isoproterenol 2-20 mcg/min). Study procedure requirements are outlined below: Isolation of all pulmonary veins and Non-pulmonary vein trigger ablation for all patients. Linear ablation lines are only required to treat documented macro-reentry atrial tachycardias and limited to the following targets only: LA roof line, mitral valve isthmus line, LA floor line, right atrial carvotricuspid isthmus linear ablation.

Also known as: Pulmonary vein isolation, Non-PV triggers ablation

PVI, non-PV triggers; PVI, non-PV triggers & CS-LA connection

Coronary sinus to left atrium connection elimination PROCEDURE

Distal coronary sinus pacing will be utilized to localize distal connections between the main coronary sinus body and the left atrium. Focal lesions will be applied to early left atrial activation sites, until no distal coronary sinus to left atrial connections are electrically manifest. If vein of marshall connections to the left atrium are present, differential pacing will be utilized to prove the lack of distal coronary sinus to left atrium connections.

PVI, non-PV triggers & CS-LA connection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with paroxysmal or persistent atrial fibrillation; AND Undergoing first AF ablation; AND Age ≥ 18 years.

You may not qualify if:

• Previous left atrial ablation; Women currently pregnant; Mental or physical inability to take part in the study; Known terminally ill patients.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (5)

• Kim MH, Lin J, Kreilick C, Foltz Boklage SH. Total costs and atrial fibrillation ablation success or failure in Medicare-aged patients in the United States. Adv Ther. 2010 Sep;27(9):600-12. doi: 10.1007/s12325-010-0060-3. Epub 2010 Aug 9.

  PMID: 20700678 RESULT

• Chauvin M, Shah DC, Haissaguerre M, Marcellin L, Brechenmacher C. The anatomic basis of connections between the coronary sinus musculature and the left atrium in humans. Circulation. 2000 Feb 15;101(6):647-52. doi: 10.1161/01.cir.101.6.647.

  PMID: 10673257 RESULT

• Huang D, Marine JE, Li JB, Zghaib T, Ipek EG, Sinha S, Spragg DD, Ashikaga H, Berger RD, Calkins H, Nazarian S. Association of Rate-Dependent Conduction Block Between Eccentric Coronary Sinus to Left Atrial Connections With Inducible Atrial Fibrillation and Flutter. Circ Arrhythm Electrophysiol. 2017 Jan;10(1):e004637. doi: 10.1161/CIRCEP.116.004637.

  PMID: 28039281 RESULT

• Antz M, Otomo K, Arruda M, Scherlag BJ, Pitha J, Tondo C, Lazzara R, Jackman WM. Electrical conduction between the right atrium and the left atrium via the musculature of the coronary sinus. Circulation. 1998 Oct 27;98(17):1790-5. doi: 10.1161/01.cir.98.17.1790.

  PMID: 9788835 RESULT

• Kuo L, Frankel DS, Lin A, Arkles J, Hyman M, Santangeli P, Marchlinski FE, Nazarian S. PRECAF Randomized Controlled Trial. Circ Arrhythm Electrophysiol. 2021 Jan;14(1):e008993. doi: 10.1161/CIRCEP.120.008993. Epub 2020 Dec 10.

  PMID: 33301361 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

(1) A single-center pilot study with a relatively small sample size; (2) 40% of patients underwent insertable cardiac monitor implantation; (3) Of patients without insertable monitors, 56% had 30-days wearable monitor pre-ablation, during the 1st \& 6th-month after ablation. (4) 44% had follow-up for detection of atrial arrhythmia recurrences based upon symptom or pulse check prompted monitors and ECGs during clinic visits.

Results Point of Contact

• Title: Dr. Saman Nazarian
• Organization: University of Pennsylvania

Saman.Nazarian@pennmedicine.upenn.edu

215-615-5220

Study Officials

• Saman Nazarian, M.D., Ph.D

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Once patients are enrolled in the study, they will be randomized to arm A: PVI + triggers ablation, or arm B: PVI + triggers ablation + coronary sinus-left atrium connection ablation. Patients will be blinded to the randomization scheme.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine, Cardiac Electrophysiology

Model Details: The PRECAF study is designed as a randomized, single-blind, small scale pilot study. Enrolled subjects who satisfy all eligibility criteria will then undergo the ablation procedure. Study randomization will be performed in a 1:1 fashion using the Urn Randomization program (https://health.uconn.edu/community-medicine/programs/health-services-research-unit/project-match/urn-randomization/) while balancing sex and AF type (paroxysmal and non-paroxysmal). The master list of study assignments will be kept by the study coordinator in a password protected and encrypted computer. After the ablation procedure, participants will remain in the study for 6 months. A 30-day event monitor will be used for the first month after ablation. Then, regular clinic visits at 6 weeks and 6 months will be arranged after ablation with 12 lead electrocardiogram check-up. In the last month, a 30-day event monitor will again be utilized to detect atrial arrhythmia recurrence.

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 24, 2018
• Study Start: August 18, 2018
• Primary Completion: November 20, 2019
• Study Completion: September 22, 2021
• Last Updated: November 29, 2024
• Results First Posted: November 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Recruitment will end when 100 participants are enrolled at Penn. Enrolled subjects who satisfy all eligibility criteria will then undergo the ablation procedure. After the study ablation procedure, participants will be part of the study for 6 months after ablation. A 30-day event monitor will be used for the first month after ablation. Then, regular clinic visits at 6 weeks and 6 months will arranged after ablation with 12 lead electrocardiogram check-up. In the last month, a 30- day event monitor will be set to detect the recurrence of atrial arrhythmias. All data are available and stored for 7 years after the end of the study.

Locations

US (1)