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Atrial Fibrillation (AF) and Heart Failure (HF) are colliding global cardiovascular epidemics, individually impairing quality of life and cardiac performance, as well as increasing the risk of hospitalisation and mortality. When AF and HF co-exist, disease progression accelerates and the adverse outcomes are magnified, leading to incrementally higher morbidity, mortality, and healthcare expenditure. The management of AF has been dichotomised into the restoration and maintenance of sinus rhythm ("Rhythm control") or acceptance of AF with control of the ventricular response ("Rate control"). Previous studies suggested that pharmacologic rhythm control and pharmacologic rate control confer similar survival and morbidity outcomes in patients with significant left ventricular dysfunction. Recognising the limitations of pharmacotherapy, more recent studies have examined the utility of catheter ablation procedures, either designed to restore and maintain sinus rhythm (e.g., catheter-based pulmonary vein isolation) or control the ventricular response (e.g., pacemaker implantation in combination with catheter ablation of the atrioventricular junction). Compared to pharmacotherapy, these studies have suggested that catheter ablation may provide sustained improvements in quality of life, decreased hospitalisation and, potentially, improved survival for patients with co-existing AF and HF. However, these studies were performed prior to the modern era of quadruple LV enhancing therapy (beta-blocker, an angiotensin receptor-neprilysin inhibitor, mineralocorticoid receptor antagonist, and an SGLT2 inhibitor). The true impact of catheter-based interventions, and thus the optimal management of AF for patients with co-existing HF is not known. The investigators propose a randomised controlled trial to definitively answer the question regarding the optimal invasive treatment of AF in patients with heart failure with reduced ejection fraction (HFrEF - LVEF ≤ 40%).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Optimal Medical Therapy | Active Comparator | Patients randomised to medical rate control will receive evidence-based beta-blockers (extended-release metoprolol succinate, bisoprolol, carvedilol), titrated to achieve a resting heart rate of <100 bpm during AF, in accordance with contemporary guidelines (Appendix B). In the event of patients not achieving satisfactory symptom or heart rate-control with monotherapy, then these agents may be combined with digoxin (trough target 0.5 and 0.9 ng/ml) or oral amiodarone. |
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| Catheter Ablation with The Goal of Sinus Rhythm Restoration (Pulmonary Vein Isolation) | Active Comparator | Patients randomised to invasive rhythm control will undergo a percutaneous catheter ablation procedure using standardised techniques to achieve pulmonary vein isolation. The procedure will be performed with a combined radiofrequency + pulsed-field ablation energy catheter. Circumferential lesions around the veins will be considered complete when spontaneous, associated PV potentials are no longer recorded by the circular catheter (entrance block) and when exit block (dissociated spontaneous PV ectopy, and/or local PV capture without conduction from the pulmonary vein into the left atrium) has been demonstrated. |
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| Catheter Ablation with The Goal of Ventricular Rate Control and Regularization (AVJ Ablation) | Active Comparator | Patients randomised to catheter ablation of the AV junction will undergo a percutaneous catheter ablation procedure using standardised techniques to achieve complete AV block. Patients randomised to AVJ ablation will receive a cardiac resynchronisation capable device owing to the risk of pacing induced cardiomyopathy (CRT-D if LVEF ≤35%, CRT-P or CSP with an FDA approved conduction system lead if LVEF 36-40%) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pulmonary Vein Isolation | Device | PVI |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite of cardiovascular mortality, stroke, and total number of heart failure events | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of ejection fraction, distance on the 6-minute walk test, and QOL score | 1 year | |
| Time to death from any cause | 5 years | |
| Time to death from cardiovascular cause |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jason Andrade | Contact | 6048755069 | jason.andrade@vch.ca |
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The decision to share IPD will be decided at a later dat by the academic steering committee.
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| Atrioventricular Node Ablation | Procedure | AVJ |
|
| Pharmacological Rate Control | Drug | Rate |
|
| 5 years |
| Number of Participants with unplanned emergency department visit or all-cause hospitalisation | 5 years |
| Number of Participants with unplanned emergency department visit or hospitalisation for heart failure | 5 years |
| Number of Participants with unplanned emergency department visit or hospitalisation for atrial fibrillation or arrhythmia | 5 years |
| Number of Participants with heart failure event | 5 years |
| Change in Quality of Life from baseline | 5 years |
| Number of Participants with ischemic stroke or systemic arterial emboli | 5 years |
| Number of Participants with new onset cognitive dysfunction | 5 years |
| Change in left ventricular function (ejection fraction) | 5 years |
| Time to first appropriate and inappropriate ICD intervention (ATP or ICD shock) | 5 years |
| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| D006333 | Heart Failure |
| D009202 | Cardiomyopathies |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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