Cryoballoon/Radiofrequency/Pulsed Field Ablation of Atrial Fibrillation Versus Medical Treatment for Heart

Prior treatment

• Previous atrioventricular (AV) nodal ablation.
• Previous pulmonary vein isolation (PVI) or surgical ablation.
• Currently participating in another randomised controlled trial of another drug or medical device.

Other illness

• Recent (\<90 days) (type 1 spontaneous) myocardial infarction (type 2 myocardial infarctions are not an exclusion criterion), percutaneous coronary intervention, coronary artery bypass grafting, cardiac resynchronisation therapy or stroke.
• Severe aortic or pulmonary valve disease.
• Active illness (other than HF) likely to result in death within 2 years.
• Known allergy to contrast.
• Other conditions that may prevent subjects from adhering to the trial protocol, in the opinion of the investigator.

Other

• Long standing (\>3 year) persistent or permanent AF.
• Severe primary or secondary mitral valve regurgitation.
• People who are pregnant or planning to become pregnant during the trial.
• People who are breastfeeding.
• Contraindication for PVI.

• Patients aged ≥18 years.
• Patient is willing and able to give informed consent for participation.
• Able and willing to comply with all study requirements, including ability to participate in study for 12 months.
• Willing to allow their General Practitioner (GP) to be notified of participation in the study.
• Patient with one of the following AF categories and at least one episode of AF documented (by any means eg ECG, Holter, Cardiac Implantable Electronic Device (CIED) interrogation or any other means):
  • Paroxysmal AF defined as spontaneous self-terminating AF lasted \> 6 hours and \<7 days.
  • Persistent AF as defined by at least one episode of AF \>7 days but not \>3 years (since 1st documentation)
• Optimal tolerated medical therapy for HF (including ACE-I (or ARB or ARNi), beta-blocker, SGLT2 inhibitor and mineralocorticoid receptor antagonist (MRA) and cardiac resynchronisation therapy (CRT) where indicated \& tolerated) for at least 6 weeks (according to the most contemporary European Society of Cardiology (ESC) HF guidelines). Maximal doses of these drugs are not mandated.
• New York Heart Association Classification (NYHA) class II to III
• LVEF \<50% (Cardiac imaging report of LVEF\<50% within 1 year (by echocardiography, cardiac magnetic resonance imaging or nuclear cardiology assessment)) AND after optimisation of medical therapy (see previous definition). Note - a LVEF of \<50% must be documented by any cardiac imaging performed after optimisation of medical therapy. Documentation of other baseline echocardiographic parameters (eg LA volume, E/E' etc can be obtained from any echocardiogram within 2.5 years). This allows a handheld or echocardiogram focused on LVEF assessment.
  • For those with LVEF 41-49% and without ongoing atrial fibrillation/flutter, N-terminal pro B-type natriuretic peptide (NT-proBNP) of ≥300pg/mL is required within 12 months prior to randomisation.
  • For those with LVEF 41-49% and with ongoing atrial fibrillation/flutter, NTproBNP of ≥600pg/mL is required within 12 months prior randomisation.
  • For those with LVEF ≤40%, NTproBNP is not required