WITHDRAWal of heart failure directed therapies in recovered Atrial Fibrillation mediated cardiomyopathy- the WITHDRAW-AF study

INTERVENTION: This is a randomised controlled study comparing staged withdrawal versus continuation of heart failure pharmacotherapy in patients with rhythm controlled atrial fibrillation (AF) and recovered cardiomyopathy. Patients undergoing staged withdrawal will first withdraw from a heart failure (HF) specific beta blocker with the option to replace with an antiarrhythmic agent (such as sotalol, amiodarone or flecainide) at the time of enrolment at Cardiologist discretion with an ECG performed at baseline and during initiation of antiarrhythmic therapy to monitor QTc intervals. Antiarrhythmic dose will be decided at the physician’s discretion. At subsequent visits, mineralocorticoid receptor antagonists (MRAs) will be weaned, followed by angiotension receptor antagonists (ACE) inhibitors, angiotensin receptor blockers (ARBs) or angiotensin receptor blocker/neprilysin inhibitor (Eg. Entresto) combinations. Diuretics can be ceased if the patient is taking the equivalent or less than frusemide 40mg daily or spironolactone 25mg daily. Participants taking 25% or less of the maximum recommended dose of ACE inhibitor or ARB can be discontinued; higher doses will be weaned by 50% every 2 weeks. The withdrawal stage involves weaning neurohormonal agents at fortnightly intervals over an 8 week period. There will be no 'wash out' period between treatment intervals. Initial withdrawal will occur at enrolment, with reduction or cessation of diuretics (depending on dose) and changing beta blocker to anti‐arrhythmic agent as appropriate. Participants will then be followed up at 3, 6, 9 and 12 months. Additional clinical reviews can be arranged based on clinical need. This phased withdrawal method is adapted from the recent TRED‐HF study. Patients in the control CONDITION: atrial fibrillation;heart failure; ; atrial fibrillation ; heart failure Cardiovascular ‐ Other cardiovascular diseases PRIMARY OUTCOME: The primary endpoint is equivalence of phased withdrawal compared to continued medical therapy, defined as maintenance of LVEF >50% on cardiac MRI at 6 and 12 months in both study groups. This allows for inter‐observer variability between imaging of <10% as recognised previously. [6 and 12 months post randomisation] SECONDARY OUTCOME: AF burden, as determined by Smart phone monitoring, implantable loop recorder or device interrogation.[12 months post randomisation] Arrhythmia recurrence (AF or AT): defined as AF or AT lasting >30 seconds as detected on Smart phone monitoring, implantable loop recorder or device interrogation. ; [12 months post randomisation] Change from baseline of heart failure / quality of life as measured by SF‐36 and Minnesota Living with Heart Failure Questionnaire (MLHFQ).[6 and 12 months post randomisation] Change from baseline of LVEF from baseline to follow up on cardiac MRI ; ; [6 and 12 months post randomisation] Change from baseline of NYHA class ; ; [6 and 12 months post randomisation] Change from baseline to follow up in cardiac biomarkers serum BNP or NTproBNP (depending on local assay)[6 and 12 months post randomisation] Change from baseline to follow up in functional capacity/exercise time (as measured by 6‐minute walk test and exercise stress test)[6 and 12 months post randomisation] Change in cardiac chamber dimensions as determined by cardiac MRI[6 and 12 months post randomisation] Change in diffuse fibrosis as determined by T1 mapping[6 and 12 months post randomisation] Composite of overall mortality, cardiovascular mortality and unplanned heart failure hospitalisation ascertained from clinic reviews and electronic medical records.[6 and 12 months post randomisation] INCLUSION CRITERIA: ‐ Age>18 years ‐ AF mediated cardiomyopathy Previous LVEF <40% in the setting of AF with recovery to >50% within 6 months after restoration of sinus rhythm (with anti‐arrhythmic medications, electrical cardioversion, catheter ablation or any combination of these) ‐ NYHA class I ‐ Currently on pharmacological anti‐heart failure therapy including at least 2 of: ‐ ACE inhibitor or Angiotensin receptor antagonist ‐ Diuretic (excluding MRA) ‐ Cardiac specific beta blocker ‐ Mineralocorticoid receptor antagonist ‐ Entresto (Sacubitril/Valsartan) ‐ No recurrence of AF with previous 6 months ‐ No heart failure related admissions with last 6 months ‐ Cardiac MRI demonstrating ‐ LVEF >/=50% ‐ The absence of ventricular late gadolinium enhancement ‐ Indexed LVEDV less than 10% upper limit of normal ‐ Able to consent ‐ Willing to adhere to follow up requirements <