Conduction System Pacing Versus Biventricular Pacing After Atrioventricular Node Ablation

Study Overview
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Brief Summary
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Atrioventricular node ablation (AVNA) with biventricular (BiV) pacemaker implantation is a feasible treatment option in patients with symptomatic refractory atrial fibrillation and heart failure. However, conduction system pacing (CSP) modalities, including His bundle pacing and left bundle branch pacing, could offer advantages over BiV pacing by providing more physiological activation. The randomized, interventional, multicentric study will explore whether CSP is non-inferior to BiV pacing in echocardiographic and clinical outcomes in heart failure (EF <50%) patients with symptomatic AF and narrow QRS scheduled for AVNA.

Detailed Description
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Atrio-ventricular node ablation (AVNA) with subsequent permanent pacemaker implantation provides definite rate control and represents an alternative therapeutic approach in patients with symptomatic atrial fibrillation (AF) and rapid ventricular rate, refractory to optimal medical treatment or catheter ablation. However, optimal pacing modality remains unclear. Previous studies have demonstrated that biventricular (BiV) pacing followed by AVNA resulted in significant reduction in mortality, heart failure (HF) hospitalizations, significant improvement in symptoms and left ventricular (LV) remodeling. Although, its benefit was much less transparent in patients with narrow QRS and LV impairment, as it still causes abnormal cardiac activation with potential worsening of electrical dyssynchrony. To avoid the detrimental effects of BiV pacing a new concept, conduction system pacing (CSP), including His bundle Pacing (HBP) and left bundle branch pacing (LBBP), was proposed as a potential alternative. Both CSP modalities offer advantages over BiV pacing by providing more physiological activation, avoiding cardiac dyssynchrony and left ventricular dysfunction. Moreover, LBBP showed some advantages over HBP. Since the lead is implanted in the region of the left bundle, which has an adequate distance from the AVNA site, this modality could minimize the risk of increase in capture threshold after AVNA. Additionally, the pacing parameters of LBBP were stable in long-term follow-up studies precluding the need for back-up pacing. Therefore compared to HBP and BiV pacing, LBBP may offer a more feasible physiologic pacing option to be adopted into clinical practice. Some observational studies have already shown positive outcomes of HBP and LBBP in symptomatic AF patients who underwent AVNA with the favorable clinical and echocardiographic improvement compared to BIV pacing, especially in HF patients with narrow baseline QRS and reduced ejection fraction (EF<50%). However, prospective randomized study evaluating the value of CSP as an alternative approach to BiV pacing in combination with AVNA is lacking. The purpose of this study is to compare the effects of CSP and conventional BiV pacing on echocardiographic and clinical outcomes in HF patients with symptomatic AF and narrow QRS scheduled for AVNA. In this multicentric study, 82 patients will be randomized into one of two arms: a BiV pacing arm with BiV pacemaker implantation + AVNA or CSP arm with the implantation of a CSP device + AVNA. In patients randomized in CSP group, LBBP will be the preferred pacing technique. If LBBP will be unobtainable, HBP implantation will be attempted. In both arms additional defibrillator backup will be implanted at the discretion of the physician according to the ESC guidelines. In short-term analysis after 6 months, echocardiographic, laboratory and symptomatic parameters will be evaluated. Long-term analysis to assess HF hospitalization, cardiovascular mortality and pacing parameters will be performed after at least 24 months of follow-up. Investigators hypothesize that CSP could represent a feasible and safe alternative to BiV pacing in terms of clinical and echocardiographic outcomes.

Official Title
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CONDUCTion System Pacing Versus Biventricular Pacing After Atrioventricular Node Ablation in Heart Failure Patients With Symptomatic Atrial Fibrillation and Narrow QRS (CONDUCT-AF Trial)

Conditions
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Heart Failure, Tachycardia-induced Cardiomyopathy, Atrial Fibrillation

Intervention / Treatment
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* Device: Biventricular pacemaker implantation
* Device: Conduction system pacing device implantation
* Procedure: AV node ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic permanent atrial fibrillation, refractory to drug therapy or failed catheter ablation Left ventricular ejection fraction <50% Narrow intrinsic QRS ≤ 120 ms NT-proBNP > 600 ng/L Patient has provided written informed consent Age between 18 years and 85 years Exclusion Criteria: Pre-existing permanent pacemaker, implantable cardioverter-defibrillator or cardiac resynchronization device. Patients who had devices implanted that had <5% of paced beats (i.e., backup pacing) can be enrolled. Life expectancy less than 12 months Severe concomitant non-cardiac disease Pregnancy Recent (<3 months) myocardial infarction, percutaneous or surgical myocardial revascularization Significant heart valve disease (severe insufficiency or stenosis) Contraindication for oral anticoagulation Mechanical tricuspid valve replacement Unwillingness to participate or lack of availability for follow-up

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Biventricular pacing + AV node ablation<br>Implantation of biventricular pacemaker with or without defibrillator lead placement followed by AV node ablation. Optimal guidelines-based heart failure treatment. | Device: Biventricular pacemaker implantation<br>* Implantation of permanent pacemaker with biventricular stimulation with or without defibrillator lead placement using standard techniques. The right ventricle lead will be positioned in the RV apex or septum, while the left ventricle lead will be delivered to the most appropriate coronary sinus tributary, preferably posterolateral or lateral vein.<br>Procedure: AV node ablation<br>* Atrioventricular node ablation (AVNA) will be performed following pacemaker implantation (preferably during the same hospitalization). After femoral vein access will be obtained, the ablation catheter will be positioned to the presumed area of the AV node in the mid-septum under fluoroscopy. The location will be optimized according to the intracardiac electrograms. Ablation will be performed in a temperature-controlled mode. Successful AVNA will be recognized with an abrupt drop of heart rate to 40 bpm and will continue for 60 seconds thereafter.<br>|
| Experimental: Conduction system pacing + AV node ablation<br>Implantation of permanent pacemaker with conduction system pacing (preferably left bundle branch) with or without defibrillator lead placement followed by AV node ablation. Optimal guidelines-based heart failure treatment. | Device: Conduction system pacing device implantation<br>* Left bundle branch pacing (LBBP) will be the preferred pacing technique. In brief, after localizing the His bundle area the LBBP lead will be positioned approximately 1-1.5 cm distal to the His bundle position in the right ventricular septum. Before screwing the lead deep into the interventricular septum, the suitable position will be confirmed by fluoroscopic signs and adequate paced QSR morphology. Given that the pacing parameters with LBBP are typically low and stable, backup RV lead will not be mandatory. If LBBP will be unobtainable, His bundle pacing (HBP) implantation will be attempted. His bundle potential mapping will be performed with the use of the electrophysiological system and under fluoroscopic guidance. Distal HB potential with a large ventricular signal and a small atrial signal will be targeted before the pacing lead will be screwed into position. Backup RV lead will be mandatory for all patients receiving HBP devices.<br>Procedure: AV node ablation<br>* Atrioventricular node ablation (AVNA) will be performed following pacemaker implantation (preferably during the same hospitalization). After femoral vein access will be obtained, the ablation catheter will be positioned to the presumed area of the AV node in the mid-septum under fluoroscopy. The location will be optimized according to the intracardiac electrograms. Ablation will be performed in a temperature-controlled mode. Successful AVNA will be recognized with an abrupt drop of heart rate to 40 bpm and will continue for 60 seconds thereafter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular ejection fraction. | Simpson's method assessed with echo. | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the first occurrence of heart failure hospitalization or cardiovascular death. | An episode of heart failure that requires unplanned medical attention with increase of diuretic dose / intravenous diuretic therapy or death due to cardiovascular causes. | at least 24 months | 
| Time to the first occurrence of heart failure hospitalization. | An episode of heart failure that requires unplanned medical attention with increase of diuretic dose or intravenous diuretic therapy. | at least 24 months | 
| Time to cardiovascular death. | Death due to cardiovascular causes. | at least 24 months | 
| Number of heart failure hospitalizations. | Episodes of heart failure that require unplanned medical attention with increase of diuretic dose or intravenous diuretic therapy. | at least 24 months | 
| Change in LV end-diastolic and end-systolic volumes. | Assessed by echo. | baseline and 6 months | 
| Change in clinical parameters | Quality of life measured by New York Heart Association (NYHA) classification. | baseline and 6 months | 
| Change in clinical parameters | Quality of life measured by Kansas City Cardiomyopathy Questionnaire (KCCQ). | baseline and 6 months | 
| Improvement in clinical parameters | Quality of life measured by European Heart Rhythm Association score of atrial fibrillation (EHRA AF). | baseline and 6 months | 
| Change in 6-Minute walk test. | Standard measurement. | baseline and 6 months | 
| Laboratory parameters. | NT-proB-type Natriuretic Peptide (BNP) | baseline and 6 months | 
| Procedural-related characteristics. | Total procedure and fluoroscopy time. | peri-procedural | 
| Procedure-associated adverse events. | Lead dislocations, device infection, bleeding, pneumotorax, etc. | peri-procedural, 30 days after the procedure | 
| Need for procedural reintervention. | Unplanned reintervention due to lead dysfunction or dislocation, device infection etc. | at least 24 months | 
| ECG parameters. | QRS duration and morphology. | before and after the procedure | 
| Pacing parameters. | Capture threshold measurement. | peri-procedural, at least 24 months | 
| Number of detected sustained VT/VF. | Detected sustained ventricular tachycardia or ventricular fibrillation on pacemaker telemetry. | at least 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Atrial fibrillation, Conduction system pacing, His bundle pacing, Left bundle branch pacing, Biventricular pacing, Atrioventricular node ablation