Catheter Ablation Versus Medical Rate Control for Atrial Fibrillation in Patients With Heart Failure

Study Overview
=================
Brief Summary
-----------------
It is still uncertain what the best treatment is for patients who have both atrial fibrillation (AF) and heart failure. The aim of the study is to help identify the optimal treatment for patients with these two significant medical conditions. This will be performed by comparing two alternative strategies for AF management: catheter ablation (to restore normal rhythm) and medical therapy (to control heart rate, but not aiming ro restore normal rhythm). After random assignment, the effect of each strategy will be assessed by looking for changes in exercise capacity, symptoms, heart pump function, and quality of life during 12 months of follow-up.

Detailed Description
-----------------
Currently available evidence suggests that occurrence of AF in patients with heart failure (HF) leads to a decline in exercise tolerance, worsened quality of life, increased hospitalisation, and in many studies an increase in mortality. These may be explained by the haemodynamic effects of AF i.e. reduction in functional cardiac output due to inappropriate heart rates, irregularity, and loss of atrial contraction, plus the risk of thromboembolism. Evidence from large clinical studies has shown that patients with heart failure fare better if sinus rhythm can be restored, but on the contrary a 'rhythm control' strategy (as intention to treat) of cardioversion or antiarrhythmic drugs to achieve sinus rhythm has not been shown to be superior to the strategy of rate control. These apparently contradictory findings might be explained by the poor efficacy and side effects associated with current rhythm control strategies, or could reflect that AF is merely a passive marker of underlying disease severity. However, many studies would point to the former, and it might be hypothesised that the theoretical benefits of sinus rhythm could be seen for real in clinical practice if a superior rhythm-control strategy was used. Catheter ablation, a relatively new treatment for atrial fibrillation, has been shown to be feasible in a non-randomised heart failure patient cohort, with markers suggesting improvement of cardiac function. This prospective clinical trial will enrol HF patients on optimal therapy, with documented persistent AF, and compare the strategies of catheter-ablation and medical rate control in a 1:1 randomised fashion.

Official Title
-----------------
A Randomised Trial to Assess Catheter Ablation Versus Rate-Control in the Management of Persistent Atrial Fibrillation in Chronic Heart Failure

Conditions
-----------------
Atrial Fibrillation, Heart Failure

Intervention / Treatment
-----------------
* Drug: Medication to control ventricular rate in AF
* Procedure: Catheter Ablation for Persistent Atrial Fibrillation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Age ≥ 18 years, < 80years NYHA II-IV symptoms Impairment of left ventricular systolic function (left ventricular ejection fraction estimated as ≤ 35% by radionuclide ventriculography) Documented AF lasting for at least 7 days (persistent or permanent AF) Exclusion criteria: CRT or ICD device implanted in the previous 6 months AV nodal ablation within previous 3 months Prior AV nodal ablation or complete heart block with a single chamber pacemaker Contraindication to anticoagulation Persistent thrombus in the left atrium despite anticoagulation Active malignancy Cerebrovascular accident within the previous 6 months Reversible causes of AF including thyroid disorders, alcohol, recent surgery Reversible causes of heart failure including acute myocarditis or alcohol Cardiac events including myocardial infarction (MI), percutaneous coronary intervention (PCI), valve or coronary bypass surgery within the previous 3 months Prior AF ablation procedure Previous heart transplant, or on urgent heart transplant waiting list Severe neuro-muscular disease Creatinine clearance <30 ml/min Serum bilirubin >50 micromol/L Active participation in another research study Unable to understand and comply with protocol or give written informed consent Body mass index >35 (kg/m2)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rate control<br>Strategy of 'rate-control': acceptance of atrial fibrillation, and dose-adjusted drug therapy as needed to control ventricular rate. | Drug: Medication to control ventricular rate in AF<br>* Standard pharmacologic rate control. Current therapy will be adjusted to achieve rate-control targets of <80bpm and <110bpm on exercise (6 minute walk). Where necessary, additional medication will be given as per standard practice (digoxin or beta-blocker). Typical does: Digoxin 62.5-250mcg o.d. ; Bisoprolol 1.25-20mg o.d.; Carvedilol 3.125-50mg b.d. ; Nebivolol 1.25-10mg o.d.<br>|
| Active Comparator: Catheter Ablation<br>Strategy of 'rhythm control' by catheter ablation: patients will undergo catheter ablation with the intention of restoring sinus rhythm. | Procedure: Catheter Ablation for Persistent Atrial Fibrillation<br>* Radiofrequency catheter ablation, which may include pulmonary vein isolation, atrial substrate modification, and/or linear ablation.<br>* Other names: LA maze;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak oxygen consumption at cardiopulmonary exercise test |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular ejection fraction |  | 12 months | 
| Quality of Life score |  | 3, 6 and 12 months | 
| 6 minute walk distance |  | 3, 6 and 12 months | 
| Level of plasma neurohormones (including BNP) |  | 3, 6 and 12 months | 
| Freedom from AF |  | 3, 6 and 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atrial Fibrillation, Heart Failure, Heart Rate Control, Catheter Ablation