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

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

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

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.

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. However, long-term success rates fhave been reported to be as low as 50% and 20% for paroxysmal and persistent AF, respectively. To achieve permanent arrhythmia suppression, repeated ablation procedures are often needed. Prior work indicates that distal connections between coronary sinus musculature and the left atrium provide a substrate for single or multiple reentry beats as a trigger for atrial fibrillation. In this prospective randomized trial the investigators will define the efficacy of elimination of distal connections between coronary sinus and left atrial musculature for suppression of recurrent atrial arrhythmias. Patients will be randomly assigned to standard of care ablation (pulmonary vein isolation and non pulmonary vein trigger ablations) alone, or standard of care ablation augmented by distal coronary sinus to left atrial connection elimination.

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.

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.

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

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.

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.

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.

The primary endpoint of the study is time to the recurrence 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 days post-ablation.

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

AF burden will be compared among study groups as a secondary outcome variable. AF burden will be measured from the 30 day monitors.

Follow-up 6 months after ablation. A 30-day event monitor will be used for the 1st and 6th month after ablation to detect the burden of atrial arrhythmias.

Inclusion Criteria: Patients with paroxysmal or persistent atrial fibrillation; AND Undergoing first AF ablation; AND Age ≥ 18 years. Exclusion Criteria: Previous left atrial ablation; Women currently pregnant; Mental or physical inability to take part in the study; Known terminally ill patients.

Information about study subjects will be kept confidential and managed according to the requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed subject authorization informing the subject of the following: What protected health information (PHI) will be collected from subjects in this study Who will have access to that information and why Who will use or disclose that information The rights of a research subject to revoke their authorization for use of their PHI. In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains the ability to use all information collected prior to the revocation of subject authorization. For subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study period.

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.

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