Atrioventricular Junction Ablation and Biventricular Pacing for Atrial Fibrillation and Heart Failure

Study Overview
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Brief Summary
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There is evidence of superiority of AV junction ablation strategy over pharmacological therapy only for symptoms of atrial fibrillation, but not for heart failure, hospitalization, morbidity and mortality. Hypothesis of trial is that AV junction ablation is superior to pharmacological therapy as regard hospitalization and mortality

Detailed Description
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Prospective randomized, controlled, investigator-initiated trial which consists of two specific consecutive(overlapped) phases: Morbidity trial (APAF-CRT morbidity). Small size (280 pts), follow-up 24 months. Primary endpoint: combined of mortality due to heartfailure, hospitalization for heart failure or atrial fibrillation or worsening heart failure. Predefined subgroup analysis for patients with ejection fraction ≤35% versus >35% Mortality trial (APAF-CRT mortality). Large size (pts included in morbidity trial plus additional  1500 pts, long-term follow-up (at least 4 years). Primary endpoint: total mortality. Predefined subgroup analysis for patients with ejection fraction ≤35% versus >35%

Official Title
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A Randomized Controlled Trial of Atrioventricular (AV) Junction Ablation and Biventricular Pacing Versus Optimal Pharmacological Therapy in Patients With Permanent Atrial Fibrillation

Conditions
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Permanent Atrial Fibrillation

Intervention / Treatment
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* Procedure: AV junction ablation
* Device: CRT
* Drug: Optimized drug therapy
* Device: ICD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible, each patient must be in the following condition: Permanent atrial fibrillation (>6 months) which has been considered unsuitable for ablation or failed ablation Narrow QRS ≤ 110 ms Severely symptomatic (atrial fibrillation-related symptoms), refractory to drug therapy for rate control At least one hospitalization related to atrial fibrillation and/or heart failure in the previous year (see definition below) Exclusion Criteria: New York Heart Association (NYHA) class IV and systolic blood pressure <80 mmHg despite optimized therapy; severe concomitant non-cardiac disease; need for surgical intervention; myocardial infarction within the previous 3 months; previous implanted devices (PM/ICD/CRT)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug therapy<br>Control Arm: optimized drug therapy (plus implantable defibrillator (ICD) according to guidelines) | Drug: Optimized drug therapy<br>* Optimized drug therapy for heart failure and atrial fibrillation rate control<br>* Other names: Pharmacological therapy;Device: ICD<br>* Implantable defibrillator (in control Group or in association with CRT in study Group) according to guidelines<br>* Other names: Implantable defibrillator;|
| Active Comparator: Device: AV junction ablation & CRT<br>AV junction ablation + CRT (CRT-P or CRT-D according to guidelines) + optimized drug therapy | Procedure: AV junction ablation<br>* AV junction ablation<br>* Other names: AV nodal ablation;Device: CRT<br>* Implantation of device for pacing and cardiac resynchronization therapy (CRT-P or CRT-D according to guidelines)<br>* Other names: Cardiac resynchronization therapy;Drug: Optimized drug therapy<br>* Optimized drug therapy for heart failure and atrial fibrillation rate control<br>* Other names: Pharmacological therapy;Device: ICD<br>* Implantable defibrillator (in control Group or in association with CRT in study Group) according to guidelines<br>* Other names: Implantable defibrillator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined end-point | Morbidity trial end-points Primary end-point: a combined of (1) mortality due to heart failure, (2) hospitalization for heart failure or uncontrolled intolerable atrial fibrillation, or (3) worsening heart failure | Upto 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major clinical events | Morbidity trial end-points Secondary end-points: total mortality, total hospitalizations, hospitalization for heart failure and/or atrial fibrillation and worsening heart failure. | Up to 3 years | 
| Major clinical events | Mortality trial end-points Secondary end-point: cardiovascular mortality and hospitalization for heart failure or uncontrolled intolerable atrial fibrillation | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Implantable defibrillator, Atrial fibrillation, Heart failure, Catheter ablation, Cardiac resynchronization therapy