Rhythm Control - Catheter Ablation With or Without Anti-arrhythmic Drug Control of Maintaining Sinus Rhythm Versus Rate Control With Medical Therapy and/or Atrio-ventricular Junction Ablation and Pacemaker Treatment for Atrial Fibrillation

Substudy_ In a subset of patients, following informed consent, additional data collection will include annual NT-proBNP/BNP measurements, Echocardiogram baseline and annually and 14 Day ECG Continuous Monitoring at six month intervals.

Updated June 2024:

Additional analysis will be completed using the winratio analysis for the hierarchical primary outcome of:

• All-cause mortality (time to event)
• Heart Failure Events (number of events per year) defined as an admission to a healthcare facility for > 24 hours or clinically significant worsening heart failure leading to an intervention (defined as treatment in an emergency department, a same-day access clinic, or an infusion centre) or unscheduled visits to a healthcare provider for administration of an intravenous diuretic as accepted by FDA, and an increase in chronic heart failure therapy
• Minnesota Living with Heart Failure Questionnaire (change from baseline to 12-month)
• Six Minute Hall Walk Test (change from baseline to 12-month)

Inclusion criteria

• Patients with one of the following AF categories and at least one ECG documentation of AF

• High burden Paroxysmal defined as ≥ 4 episodes of AF in the last 6 months, and at least one episode > 6 hours (and no episode requiring cardioversion and no episode > 7 days)
• Persistent AF (1) defined as ≥ 4 episodes of AF in the last 6 months, and at least one episode > 6 hours, and at least one AF episode less than 7 days but requires cardioversion. No AF episodes are > 7 days
• Persistent AF (2) as defined by at least one episode of AF > 7 days but not > 1 year
• Long term persistent AF defined as an AF episode, at least one year in length and no episodes > 3 years
• Optimal therapy for heart failure of at least 6 weeks (according to 2009 ACCF/AHA class 1 recommendations).
• HF with NYHA class II or III symptoms with either impaired LV function (LVEF ≤ 45%) as determined by EF assessment within the previous 12 months or preserved LV function (LVEF > 45%) determined by by EF assessment within the previous 12 months
• NT-pro BNP measures:

A) Patient has been hospitalized for Heart Failure* in the past 9 months, has been discharged AND:

i- Is presently in Normal Sinus Rhythm and NT-pro BNP is ≥ 400 pg/mL

ii- Is presently in Atrial Fibrillation and NT-pro BNP is ≥ 600 pg/mL

OR

B) Patient has had no hospitalization for Heart Failure in the past 9 months AND:

i- Has had paroxysmal Atrial Fibrillation, is presently in Normal Sinus Rhythm and NT-proBNP is ≥ 600 pg/mL

ii- Is presently in Atrial Fibrillation and NT-proBNP is ≥ 900 pg/mL

*Heart Failure Admission is defined as admission to hospital > 24 hours and received treatment for Heart failure

• Suitable candidate for catheter ablation or rate control therapy for the treatment of AF
• Age ≥18

Exclusion criteria

• Have an LA dimension > 55 mm as determined by an echocardiography within the previous year
• Had an acute coronary syndrome or coronary artery bypass surgery within 12 weeks
• Have rheumatic heart disease, severe aortic or mitral valvular heart disease using the AHA/ACC guidelines
• Have congenital heart disease including previous ASD repair, persistent left superior vena cava
• Had prior surgical or percutaneous AF ablation procedure or atrioventricular nodal (AVN) ablation
• Have a medical condition likely to limit survival to < 1 year
• Have New York Heart Association (NYHA) class IV heart failure symptoms
• Have contraindication to systematic anticoagulation
• Have renal failure requiring dialysis
• AF due to reversible cause e.g. hyperthyroid state
• Are pregnant
• Are included in other clinical trials that will affect the objectives of this study
• Have a history of non-compliance to medical therapy
• Are unable or unwilling to provide informed consent