Surgical Ablation of AF Efficacy Trial (SAFE)

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

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 surgical AF ablation which is compared to no surgical AF ablation. The primary outcome is hospital readmissions for heart failure at 4 years. 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.

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.

Blinding to allocation will be maintained for all parties, excluding the operating surgeon and necessary operating room personnel.

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 lines will be allowed.

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)

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)

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

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.

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.

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.

From date of study intervention surgery completion to date of index hospital discharge, assessed up to the common termination point for trial (median follow-up of 4 years)

Economic analysis will be assessed via a questionnaire of health care visits and costs incurred by patients.

Inclusion Criteria: Age ≥ 18 years; Undergoing a clinically indicated cardiac surgical procedure: CABG, AVR, ascending aorta replacement, or combinations thereof; Documented history of paroxysmal (AF episode(s) lasting more that 30 seconds but terminating within 7 days) or persistent AF (AF lasting for more than 7 days but less than one year). Provide informed consent Exclusion Criteria: Dominant atrial arrhythmia is atrial flutter; Documented left atrial diameter ≥ 5.5 cm or left atrial volume ≥100 mL (absolute); Long-standing persistent AF (absence of any sinus rhythm for more than 1 year); Patients undergoing any of the following procedures: Previous cardiac surgery requiring opening of the pericardium 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 Closure of an atrial septal defect (excluding patent foramen ovale) or ventricular septal defect Patient resides in a long-term care facility