AV Junction Ablation or Optimal Medical Treatment in PatiEnts With Cardiac Resynchronization Therapy and Permanent Atrial Fibrillation

Study Overview
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Brief Summary
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A study comparing atrioventricular junction ablation (AVJA) versus continued optimum medical rate control in patients with cardiac resynchronization therapy (CRT) and atrial fibrillation (AF) with suboptimal heart rate control on optimum medication.

Detailed Description
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Patients fulfilling the enrolment criteria will be randomly (randomization with variable blocks of 4, 6, and 8 patients) allocated to intervention and control groups in a 1:1 ratio. AVJA will be done in patients belonging to the intervention group without undue delay after the randomization. The procedure will be repeated in case of recovery of AV nodal conduction during the trial. CRT device will be programmed to a base rate of 70 bpm, hysteresis switched off, and rate response functions activated unless not tolerated by the patient. The triggered mode will be encouraged. All patients will be regularly followed in outpatient clinics. Cross-over to the AVJA study arm will be considered and performed at any time during the trial at the discretion of the operators. This may particularly concern patients with clinical deterioration in terms of functional status, quality of life, systolic left ventricular function, and/or repeated hospitalization, and in whom biventricular pacing (BiVP%) <<100% could be suspected as a significant underlying factor.

Official Title
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AV Junction Ablation or Optimal Medical Treatment in PatiEnts With Cardiac Resynchronization Therapy and Permanent Atrial Fibrillation

Conditions
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Recurrent Atrial Fibrillation, Persistent Atrial Fibrillation

Intervention / Treatment
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* Procedure: Atrioventricular junction ablation in patients with cardiac resynchronization therapy (CRT)
* Drug: Optimal medication treatment in patients with cardiac resynchronization therapy (CRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment with CRT using either a biventricular pacemaker/defibrillator or conduction system pacemaker (>6 months) Diagnosis of AF and classified as: permanent AF or recurrent persistent AF, requiring emergency visits and/or hospitalizations (at least one in recent year) Optimized HF medical treatment and rate control medication BiVP% + ventricular premature complex (VPC%) <99% and >85% during the minimum period of 1 month while already on optimum medical therapy (applicable only for patients with permanent AF) Age >18 and <85 years Signed informed consent Exclusion Criteria: myocardial infarction (MI) or coronary artery bypass graft (CABG) <3 months Technical failure of the CRT system Intentional preference for spontaneous AV conduction Expected survival <1 year Other significant comorbidities and/or conditions that interfere with the proper conduction of the trial Dementia as assessed by mini-mental test (<23 points)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Interventional Model Description: Patients fulfilling the enrolment criteria will be randomly (randomization with variable blocks of 4, 6, and 8 patients) allocated to intervention and control groups in a 1:1 ratio.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atrioventricular junction ablation (AVJA) in patients with cardiac resynchronization therapy (CRT)<br>Patients with cardiac resynchronization therapy (CRT) randomized in this arm will undergo atrioventricular junction ablation. | Procedure: Atrioventricular junction ablation in patients with cardiac resynchronization therapy (CRT)<br>* Ablation of the atrioventricular (AV) node is a procedure used to disrupt or break the electrical connection between the upper heart chambers (the atria) and the lower heart chambers (the ventricles).<br>|
| Active Comparator: Optimal medication treatment in patients with cardiac resynchronization therapy (CRT)<br>Patients with cardiac resynchronization therapy (CRT) randomized in this arm will receive optimal medication treatment. | Drug: Optimal medication treatment in patients with cardiac resynchronization therapy (CRT)<br>* Optimal medication therapy according to the prescription of the physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 36-Item Quality of Life (QoL) | QoL will be assessed using the 36-Item Quality of Life Questionnaire. QoL will be evaluated at 12, 24 and 36 months as a sum of points that are assigned to individual outcome measures, specifically to their change compared to the baseline. To score the SF-36, scales are standardized to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales. | 3 years | 
| Minnesota Living with Heart Failure Questionnaire (MLHFQ) | MLHFQ values will be recorded and evaluated at 12, 24 and 36 months. The questionnaire is comprised of 21 questions around several physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. The patient marks a 0 (zero) to 5 (five) scale to indicate the extent to which each itemized adversity of heart failure has prevented the patient from living as they wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses. | 3 years | 
| Dose of loop diuretics | Change in the dose of loop diuretics will be observed and recorded. This parameter will be evaluated at 12, 24 and 36 months as an increase or decrease of the dose compared to the baseline. | 3 years | 
| NYHA classification | Changes in the New York Heart Association classification (NYHA) will be observed. The NYHA classification values will be evaluated at 12, 24 and 36 months. The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity; the limitations/symptoms are in regards to normal breathing and varying degrees in shortness of breath and or angina pain. | 3 years | 
| Heart failure (HF) events | The number of HF events will be observed. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause death | Patient deaths from all causes will be observed, recorded and analysed. | 3 years | 
| Death from cardiovascular diseases (CV death) | Incidents of CV death will be observed, recorded and analysed. | 3 years | 
| Combined heart failure (HF) death and HF hospitalization | Incidents of combined heart failure (HF) death and HF hospitalization will be observed, recorded and analysed. | 3 years | 
| Time-averaged proportional change in NT-pro-Brain Natriuretic Peptide (NT-pro-BNP) | The time-averaged proportional change in NT-pro-BNP will be observed, recorded and analysed. | 3 years | 
| Days in the hospital because of heart failure (HF) | The number of days in the hospital because of heart failure (HF) will be recorded. | 3 years | 
| Time-averaged change in the NYHA class | The time-averaged change in the NYHA class will be observed, recorded and analysed. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atrial fibrillation, atrioventricular junction ablation, biventricular pacing, heart rate control, cardiac resynchronization therapy