Clinical trial NCT05467163: Conduction System Pacing Versus Biventricular Pacing After Atrioventricular Node Ablation
Official title: CONDUCTion System Pacing Versus Biventricular Pacing After Atrioventricular Node Ablation in Heart Failure Patients With Symptomatic Atrial Fibrillation and Narrow QRS (CONDUCT-AF Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Tachycardia-induced Cardiomyopathy
Atrial Fibrillation
Keywords: Heart failure
Atrial fibrillation
Conduction system pacing
His bundle pacing
Left bundle branch pacing
Biventricular pacing
Atrioventricular node ablation
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2022-07-20
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Symptomatic permanent atrial fibrillation, refractory to drug therapy or failed catheter ablation
2. Left ventricular ejection fraction \<50%
3. Narrow intrinsic QRS ≤ 120 ms
4. NT-proBNP \> 600 ng/L
5. Patient has provided written informed consent
6. Age between 18 years and 85 years

Exclusion Criteria:

1. 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.
2. Life expectancy less than 12 months
3. Severe concomitant non-cardiac disease
4. Pregnancy
5. Recent (\<3 months) myocardial infarction, percutaneous or surgical myocardial revascularization
6. Significant heart valve disease (severe insufficiency or stenosis)
7. Contraindication for oral anticoagulation
8. Mechanical tricuspid valve replacement
9. Unwillingness to participate or lack of availability for follow-up

Primary outcomes:
measure: Change in left ventricular ejection fraction.
timeFrame: baseline and 6 months
Secondary outcomes:
measure: Time to the first occurrence of worsening heart failure or cardiovascular death.
timeFrame: at least 24 months
measure: Time to the first occurrence of worsening heart failure.
timeFrame: at least 24 months
measure: Time to cardiovascular death.
timeFrame: at least 24 months
measure: Number of heart failure hospitalizations.
timeFrame: at least 24 months
measure: Change in LV end-diastolic and end-systolic volume index.
timeFrame: baseline and 6 months
measure: Change in clinical parameters
timeFrame: baseline and 6 months
measure: Change in clinical parameters
timeFrame: baseline and 6 months
measure: Improvement in clinical parameters
timeFrame: baseline and 6 months
measure: Change in 6-Minute walk test.
timeFrame: baseline and 6 months
measure: Laboratory parameters.
timeFrame: baseline and 6 months
measure: Procedural-related characteristics.
timeFrame: peri-procedural
measure: Procedure-associated adverse events.
timeFrame: peri-procedural, 30 days after the procedure
measure: Need for procedural reintervention.
timeFrame: at least 24 months
measure: ECG parameters.
timeFrame: before and after the procedure
measure: Pacing parameters.
timeFrame: peri-procedural, at least 24 months
measure: Number of detected sustained VT/VF.
timeFrame: at least 24 months
Other outcomes:
Locations:
city: Graz
country: Austria
facility: University Hospital Graz - Divison of Cardiology
city: Genk
country: Belgium
facility: Hospital Oost-Limburg (Hartzentrum Genk)
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda Hospital - Department of Invasive Electrophysiology
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka
city: Split
country: Croatia
facility: University Hospital of Split
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Budapest
country: Hungary
facility: Central-Hospital of Northern Pest - Military Hospital
city: Braşov
country: Romania
facility: County Clinical emergency hospital of Brasov - Department of Interventional Cardiology
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana - Department of cardiology
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana - Department of cardiovascular surgery
Study officials:
affiliation: UMC Ljubljana
name: Andrej Pernat, MD, PhD
role: STUDY_DIRECTOR
affiliation: UMC Ljubljana
name: David Zizek, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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