Pacing of Left Bundle Branch Area and Atroventricular Node ablatIon in Patients With Symptomatic Atrial Fibrillation (PALLIATE-AF)

This study aimed to compare the clinical outcomes of left bundle branch area pacing combined with atrioventricular node ablation and pharmacologic treatment optimized according to guidelines in patients with symptomatic atrial fibrillation refractory or intolerant to drug therapy or catheter ablation.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation (AF)
• Intervention / Treatment: Procedure: Pacemaker implantation with Left bundle branch area pacing (LBBAP); Procedure: Atrioventricular node ablation (AVNA); Drug: Pharmacologic therapy optimized for Atrial Fibrillation management

Detailed Description

• Multicenter, randomized, open-label clinical trial
• Randomization 1:1 fashion A randomly permuted-block randomization list was generated by computer at a central location and was stratified by center.

• Study duration:

  1. 6 months (for primary outcome)
  2. 24 months (for secondary outcomes)
• Study subjects number: 50 patients (25 patients per group)

• Procedures

  • Atrioventricular node ablation after successful left bundle branch area pacing at the same procedure time.
  • Left bundle branch area pacing will be performed in all patients (using lumenless or stylet-driven lead, on the operator's discretion)
  • Atrioventricular node ablation will be performed using the quadripolar 7-Fr 3.5-mm tip ablation catheter and the use of 8.5-F sheath (SR0 or SL1, St. Jude Medical Inc., St. Paul, MN, USA) depending on the operator's experience, and if not stable or failed, a deflectable sheath (Agilis, Abbott Electrophysiology, Menlo Park, CA, USA) will be used. Repeated ablation procedures will be recommended during follow-up if regression of atrioventricular block has occurred.
  • Immediately after implant, devices were programmed to achieve the shortest QRS duration. Unipolar pacing was initially used to determine left bundle branch capture.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eue-keun Choi, M.D. Ph.D; Phone Number: 82-2-2072-0688; Email: choiek417@gmail.com

Study Locations

• Korea, Republic of
  • Jongno-gu
    • Seoul, Jongno-gu, Korea, Republic of, 03080
      • Recruiting
      • Seoul National University Hospital
      • Contact: Eue-Keun Choi, M.D. Ph.D.; Phone Number: 82-10-4147-7196; Email: choiek417@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion:

Patients who meet all of the following inclusion criteria 1)-6).

1. Permanent atrial fibrillation
2. Age ≥ 65 years
3. Refractory or intolerant to antiarrhythmic drugs, rate control medications, or catheter ablation
4. New York Heart Association (NYHA) functional class II- IV
5. LVEF > 40% (within the past 3 months)

6. Patients with at least one of the following:

   1. HF hospitalization (defined as HF as the major reason for hospitalization or treatment for HF lasting ≥12 hours and including treatment with intravenous (IV) diuretics at a healthcare facility) within 12 months
   2. Elevated NT-proBNP (>900 pg/ml) in the 30 days prior to enrollment

Exclusion:

Patients who meet at least one of the following exclusion criteria 1)-11).

1. Asymptomatic atrial fibrillation
2. Life expectancy to < 12 months.
3. Primary moderate to severe valvular disease (except for functional mitral valve regurgitation or tricuspid valve regurgitation)
4. Mechanical tricuspid valve replacement
5. Severe chronic kidney disease (estimated Glomerular Filtration Rate ≤ 15 ml/1,73 m2 or receiving renal replacement treatment including hemodialysis or peritoneal dialysis)
6. Obstructive hypertrophic cardiomyopathy
7. Infiltrative cardiomyopathy (amyloidosis, sarcoidosis, Fabry disease, others)
8. Acute coronary syndrome or coronary revascularization (CABG or PCI) <3 months
9. Severe primary pulmonary disease such as cor pulmonale, irreversible lung disease requiring inhalers, oxygen supplementation
10. Pacemaker/ICD/CRT treatment ongoing, or current pacemaker indication
11. Simultaneous participation in a different randomized clinical trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LBBAP+AVNA arm; Left bundle branch area pacing combined with atrioventricular node ablation.	Procedure: Pacemaker implantation with Left bundle branch area pacing (LBBAP); Left bundle branch pacing is a novel pacing modality that can bypass the pathological or disease-vulnerable region in the cardiac conduction system, to provide physiological pacing modality for patients. The procedure involves the implantation of a permanent pacemaker with a pacing lead positioned at the left bundle branch area to achieve physiological conduction system pacing. LBBAP-Pacemaker device and leads should be implanted according to the physician's standard practice.; Procedure: Atrioventricular node ablation (AVNA); Atrioventricular node ablation uses heat energy, called radiofrequency energy, to destroy the area between the upper and lower heart chambers. This area is called the atrioventricular node.
Sham Comparator: Control arm; Pharmacologic treatment optimized according to guidelines in patients with permanent atrial fibrillation refractory or intolerant to drug therapy or catheter ablation.	Drug: Pharmacologic therapy optimized for Atrial Fibrillation management; Pharmacologic therapy includes rate control with beta-blockers (e.g., bisoprolol), calcium channel blockers (e.g., diltiazem), or antiarrhythmic drugs (e.g., flecainide, propafenone, dronedarone, amiodarone) along with anticoagulation therapy (e.g., apixaban) as per current clinical guidelines (e.g., ESC 2024 or ACC/AHA/HRS 2023) in patients with permanent atrial fibrillation refractory or intolerant to drug therapy or catheter ablation. Treatment is tailored based on patient tolerance and clinical efficacy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in NT-proBNP concentration (pg/ml) from baseline to 6-month follow-up	6 months after intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NT-proBNP concentration (pg/ml) at 12, and 24 months		12 months and 24 months after intervention.
Change in health-related quality of life measured by 36-item short form survey (SF-36) questionnaire at 6, 12, 24 months	The SF-36 is a 36-item questionnaire that measures health-related quality of life across eight domains, including physical functioning, bodily pain, and mental health. Scores range from 0 to 100, with higher scores indicating better health-related quality of life.	6, 12 and 24 months after intervention.
Change in health-related quality of life measured by EuroQol 5-Dimension Questionnaire (EQ-5D) at 6, 12, 24 months	The EuroQol 5-Dimension Questionnaire (EQ-5D) evaluates health-related quality of life using a descriptive system with five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores are derived as an index value (range: -0.594 to 1) The value attached to an EQ-5D profile according to a set of weights that reflect, on average, people's preferences about how good or bad the state is. Values are anchored at 1 (full health) and 0 (a state as bad as being dead) as required by their use in economic evaluation. Values less than 0 represent health states regarded as worse than a state that is as bad as being dead. An EQ-5D value is also sometimes known as an 'index', 'score' or 'utility'	6, 12 and 24 months after intervention.
Change in left ventricular ejection fraction (LV-EF, %) at 6, 12, and 24 months		6, 12 and 24 months after intervention
Change in left ventricular end-diastolic diameter (LVEDD, mm) at 6, 12, and 24 months		6, 12 and 24 months after intervention.
Change in left ventricular end systolic diameter (LVESD, mm) at 6, 12, and 24 months		6, 12 and 24 months after intervention.
Change in New York Heart Association (NYHA) functional class at 6, 12, and 24 months	The NYHA functional classification system assesses the severity of heart failure symptoms on a scale from Class I (best) to Class IV (worst). Changes in functional class will be evaluated at 6, 12, and 24 months after the intervention to determine the impact on patients' physical activity and symptom burden.	6, 12 and 24 months after intervention.
Change in 6 min walk test at 6, 12, and 24 months		6, 12, and 24 months after intervention
Change in cognitive function measured by Montreal Cognitive Assessment (MoCA) score at 6, 12, and 24 months	The Montreal Cognitive Assessment (MoCA) is a widely used cognitive screening tool that assesses various cognitive domains, including memory, attention, language, visuospatial skills, and executive function. The MoCA score ranges from 0 to 30, with higher scores indicating better cognitive function. A score of 26 or above is generally considered normal, while lower scores suggest cognitive impairment. Changes in MoCA scores will be evaluated at 6, 12, and 24 months post-intervention.	6, 12 and 24 months after intervention.
Procedure-related complications (tamponade, device infection, re-intervention, pneumothorax, vascular complications, others)		24 months after intervention.
The all-cause mortality at 24 months	Death from any cause during the 24-month follow-up period.	24 months after intervention.
Worsening Heart Failure (HF) at 24 Months	*Worsening HF with or without hospitalization: symptoms, signs, imaging, and analytical criteria that require unplanned medical attention with an increase of diuretic use, intravenous diuretic therapy	24 months after intervention.
Composite Outcome: Mortality and worsening heart failure (HF) at 24 months	Participants meeting at least one of the criteria: (a) all-cause mortality, (b) worsening heart failure.	24 months after intervention.

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 3, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Actual): November 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: atrial fibrillation; left bundle branch area pacing; Atrioventricular node ablation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: PALLIATE-AF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes