Surgical Ablation of AF Efficacy Trial

Study Overview
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Brief Summary
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SAFE is an international multicentre RCT of concomitant surgical atrial fibrillation (AF) ablation in patients with paroxysmal or persistent AF undergoing cardiac surgery.

Detailed Description
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Atrial fibrillation (AF) affects more than 1% of the general population and is an important risk factor for stroke. AF prevalence increases with age, occurring in 10 to 15% of patients older than 80 years of age, which is important with the aging population. Of patients undergoing cardiac surgery, 10.8% have a history of AF. AF is believed to cause the left atrium to dilate and lose its transport function. AF significantly increases the risk of ischemic stroke of cardioembolic origin, but is also associated with heart failure and impairs quality of life. Although the causal relationship between the 2 clinical entities has not been fully elucidated, AF is believed to cause heart failure via several mechanisms. Ablation of AF is the application of scars to the atrial tissue to disrupt faulty electrical signals that cause the arrhythmia. If surgical ablation of AF yields a benefit similar to catheter-based AF ablation, thousands of people undergoing cardiac surgery could benefit from this procedure each year. SAFE will be a landmark trial in cardiac surgery, definitely establishing surgical AF ablation's impact on cardiovascular outcomes. Cardiac surgery is the optimal setting to establish whether maintenance of sinus rhythm through AF ablation yields clinical benefit, and is a setting where sham-control is possible. This will not only provide evidence for the cardiac surgical patients but will bolster the evidence for ablation (catheter or stand-alone surgical) in other AF patients. The intervention under investigation is concomitant surgical AF ablation which is compared to no surgical AF ablation. The primary outcome is hospital readmissions with heart failure during 4 years of follow-up. This study will enroll 2000 patients from 50 centres, globally. Patients will be followed at hospital discharge, 4 to 6 weeks after surgery, 6 months after surgery, and then at 6-month intervals until the final follow-up visit, for a median follow-up for 4 years.

Official Title
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Surgical Ablation of AF Efficacy Trial

Conditions
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Atrial Fibrillation, Heart Failure

Intervention / Treatment
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* Procedure: Surgical Atrial Fibrillation Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; Undergoing a clinically indicated cardiac surgical procedure: CABG, AVR, ascending aorta replacement, or combinations thereof; Documented history of paroxysmal or persistent AF Provide informed consent Exclusion Criteria: Dominant atrial arrhythmia is atrial flutter; Documented left atrial diameter ≥ 6 cm; Previous cardiac surgery requiring opening of the pericardium; Patients undergoing any of the following procedures: Heart transplant Complex congenital heart surgery Sole indication for surgery is ventricular assist device insertion Mitral valve repair or replacement Tricuspid valve repair or replacement Patient resides in a long-term care facility

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Each patient will be assigned in a blinded fashion to one of two groups (atrial fibrillation ablation or no atrial fibrillation ablation) in a 1:1 ratio.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgical Atrial Fibrillation Ablation Group<br>Surgeon will perform left atrial ablation during patient's cardiac surgery procedure. | Procedure: Surgical Atrial Fibrillation Ablation<br>* Surgeon will preform surgical atrial fibrillation ablation using either cryoablation or bipolar radiofrequency clamps including 2 layers of atrium or vein, a minimum of 2 burns per clamping with at least 3 lines in the ablation group. Cavo-tricuspid isthmus and mitral lines will be allowed.<br>|
| No Intervention: No Surgical Atrial Fibrillation Ablation Group<br>Surgeon will not perform left atrial ablation during the patient's cardiac surgery procedure. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of hospital readmissions for heart failure over duration of follow-up | Total number of hospital readmissions for heart failure. | Common termination point for trial (median follow-up of 4 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Ischemic stroke or systemic arterial embolism events over duration of follow up | Number of Ischemic stroke or systemic arterial embolism events over duration of follow up | Common termination point for trial (median follow-up of 4 years) | 
| Length of ICU stay | Length of ICU stay, including readmissions, from study intervention surgery to hospital discharge, including readmissions | From the date of study intervention surgery completion to the date of index hospital discharge, assessed up to the common termination point for trial (median follow-up of 4 years) | 
| Length of hospital stay | Length of hospital stay | From the date of study intervention surgery completion to the date of index hospital discharge, assessed up to the common termination point for trial (median follow-up of 4 years) | 
| Freedom from recurrence of atrial tachyarrhythmia | Freedom from recurrence of atrial tachyarrhythmia | 1 year post-operatively | 
| Number of days free from admission to healthcare facility or presentation to the emergency department for heart failure | Number of days free admission to healthcare facility or presentation to the emergency department for heart failure | Common termination point for trial (median follow-up of 4 years) | 
| All-cause mortality | All-cause mortality | Common termination point for trial (median follow-up of 4 years) | 
| Cardiovascular mortality | Cardiovascular mortality | Common termination point for trial (median follow-up of 4 years) | 
| Antiarrhythmic drug use | Antiarrhythmic drug use | Beyond 6 weeks until common termination point for trial (median follow-up of 4 years) | 
| Number of patients undergoing atrial fibrillation ablation | Number of patients undergoing atrial fibrillation ablation | 90 days post- study surgery until common termination point for trial (median follow-up of 4 years) | 
| Quality of Life - atrial fibrillation specific | Atrial fibrillation specific quality of life as assessed by the Atrial Fibrillation Effect on QualiTy of Life questionnaire (AFEQT) which is 20 questions using a 7 point Likert scale where a higher score means a worse outcome. | At 1 year, and at common termination point for trial (median follow-up of 4 years) | 
| Quality of Life - heart failure specific | Heart failure specific quality of life assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) which is a 12 questions using Likert scales where a higher score is a better outcome. | At 1 year, and at common termination point for trial (median follow-up of 4 years) | 
| Quality of Life - General | Quality of life- general as assessed by the European quality of life index version 5D (EQ-5D-5L) which consists of a descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. | At 1 year, and at common termination point for trial (median follow-up of 4 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgical Ablation, Cardiac Surgery