Left Bundle Branch Pacing vs Right Ventricular Pacing on AHRE Burden in Patients With Preserved LVEF

Official title

Comparison of Left Bundle Branch Pacing Versus Conventional Right Ventricular Pacing on AHRE Burden in Patients With Preserved Left Ventricular Ejection Fraction and High Ventricular Pacing Dependency (LBBP-AHRE Trial): A Randomized Study

Overview

This prospective, randomized controlled trial aims to evaluate the effect of left bundle branch pacing (LBBP) compared with conventional right ventricular (RV) pacing on the cumulative duration (total time) of atrial high-rate episodes (AHREs) in patients with preserved left ventricular ejection fraction (LVEF) who are expected to require frequent ventricular pacing. Atrial High-Rate Episodes (AHREs) are defined as episodes of atrial tachyarrhythmia that are automatically recorded by device diagnostics and detected by implanted cardiac devices. These episodes usually have an atrial rate ≥170 beats per minute and a duration ≥6 minutes. AHREs are linked to a higher risk of thromboembolic events and clinical atrial fibrillation (AF), and they may indicate subclinical AF or other atrial tachyarrhythmias. Chronic RV pacing has been linked to mechanical and electrical dyssynchrony, which may encourage atrial remodeling and the development of AF. LBBP provides a more physiological ventricular activation and may reduce atrial tachyarrhythmia time (AHRE time). Patients with LVEF \>50% and atrioventricular (AV) conduction disorders requiring a dual-chamber pacemaker will be randomized to either conventional RV septal pacing or LBBP.

Detailed description

This prospective, randomized controlled trial aims to evaluate the effect of left bundle branch pacing (LBBP) compared with conventional right ventricular (RV) pacing on the cumulative duration (total time) of atrial high-rate episodes (AHREs) in patients with preserved left ventricular ejection fraction (LVEF) who are expected to require frequent ventricular pacing.

Atrial High-Rate Episodes (AHREs) are defined as episodes of atrial tachyarrhythmia that are automatically recorded by device diagnostics and detected by implanted cardiac devices. These episodes usually have an atrial rate ≥170 beats per minute and a duration ≥6 minutes. AHREs are linked to a higher risk of thromboembolic events and clinical atrial fibrillation (AF), and they may indicate subclinical AF or other atrial tachyarrhythmias.

Device Algorithm Specificity: AHREs will be validated by reviewing the stored atrial electrograms (EGMs) for a random sample of at least 20% of detected episodes to confirm atrial origin, exclude oversensing, and differentiate atrial tachycardia from atrial fibrillation-like episodes. Device model-specific detection thresholds, including refractory oversensing behavior, atrial blanking periods, and sensitivity parameters, will be documented and standardized across participants where possible.

Chronic RV pacing has been linked to mechanical and electrical dyssynchrony, which may encourage atrial remodeling and the development of AF. LBBP provides a more physiological ventricular activation and may reduce atrial tachyarrhythmia time (AHRE time).

LBBP produces a narrower paced QRS, shorter left ventricular activation time, and more synchronous ventricular contraction compared with RV pacing. These electrophysiologic differences may reduce atrial stretch, left atrial pressure, and atrial substrate remodeling, which are mechanisms believed to lower AHRE burden.

Patients with LVEF \>50% and atrioventricular (AV) conduction disorders requiring a dual-chamber pacemaker will be randomized to either conventional RV septal pacing or LBBP.

Interventions

• Device Right Ventricular Pacing
  Implantation of a dual-chamber pacemaker with the ventricular lead placed in the RV septum. At follow-up, the ventricular pacing percentage and pacing configuration will be noted. All devices used in this study are commercially available in the European Union and carry a valid CE mark.
• Device Left Bundle Branch Pacing
  Implantation of a dual-chamber pacemaker with the ventricular lead placed at the left bundle branch area. Physiological pacing will be programmed into the devices and, at follow-up, the percentage of spontaneous pacing will be noted. All devices used in this study are commercially available in the European Union and carry a valid CE mark.

Primary outcome measures

• Total cumulative AHRE time for device-detected episodes lasting >6 minutes [Time frame: From pacemaker implantation (or randomization) to 24 months (primary endpoint)]

Secondary outcome measures (12)

• Total cumulative time in AHRE episodes with individual episode duration 0 to 6 minutes. [Time frame: From pacemaker implantation (or randomization) to 24 months (primary endpoint)]
• Total cumulative time in AHRE episodes with individual episode duration 6 minutes to 6 hours. [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Total cumulative time in AHRE episodes with individual episode duration 6 hours to 24 hours. [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Total cumulative time in AHRE episodes with individual episode duration >24 hours. [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Time to event - for AHRE episodes > 6 min [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Incidence of progression to clinically documented atrial fibrillation (paroxysmal or persistent, symptomatic or asymptomatic, confirmed by ECG, Holter, or wearable monitoring). [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Time to first clinically documented atrial fibrillation. [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Development of permanent atrial fibrillation. [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Time to progression to permanent atrial fibrillation. [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Device- or procedure-related complications (e.g., cardiac perforation, pericardial tamponade, pneumothorax, hemothorax, infection requiring antibiotics or system removal, generator or lead malfunction, hematoma). [Time frame: From pacemaker implantation (or randomization) to 24 months]
• All-cause mortality. [Time frame: From pacemaker implantation (or randomization) to 24 months]
• Hospitalization due to AF [Time frame: From pacemaker implantation (or randomization) to 24 months]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Scheduled implantation of a dual-chamber pacemaker for:

Permanent complete heart block Permanent second-degree AV block (Mobitz II or Mobitz I)

• Documented preserved LVEF (≥50%)
• Sinus rhythm at baseline
• Ability to provide written informed consent

Exclusion criteria

• History of paroxysmal, persistent, or permanent atrial fibrillation
• Previous atrial fibrillation ablation (catheter-based or surgical)
• LVEF < 50%
• Sinus node disease
• Transient AV block requiring pacemaker implantation
• Significant structural or valvular heart disease
• Requirement for pacemaker system upgrade during the study period
• Requirement for antiarrhythmic therapy for causes other than atrial fibrillation
• Existing pacemaker or other cardiac device requiring modification for study participation
• Enrollment in another clinical trial that could interfere with study endpoints or pacing parameters
• Contraindication to LBBP or associated lead implantation procedure
• Life expectancy < 12 months
• Any condition judged by the investigator to compromise participation or the integrity of study data

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Greece · 1 center

• University General Hospital of Patras — Pátrai

Publications

• Becher N, Metzner A, Toennis T, Kirchhof P, Schnabel RB. Atrial fibrillation burden: a new outcome predictor and therapeutic target. Eur Heart J. 2024 Aug 16;45(31):2824-2838. doi: 10.1093/eurheartj/ehae373. PMID 38953776
• Jansson V, Bergfeldt L, Schwieler J, Kenneback G, Rubulis A, Jensen SM, Raatikainen P, Sciaraffia E, Blomstrom-Lundqvist C. Atrial fibrillation burden, episode duration and frequency in relation to quality of life in patients with implantable cardiac monitor. Int J Cardiol Heart Vasc. 2021 May 11;34:100791. doi: 10.1016/j.ijcha.2021.100791. eCollection 2021 Jun. PMID 34036145
• Rosner GF, Reiffel JA, Hickey K. The Concept of "Burden" in Atrial Fibrillation. J Atr Fibrillation. 2012 Feb 2;4(5):400. doi: 10.4022/jafib.400. eCollection 2012 Feb-Mar. PMID 28496712
• Boriani G, Tartaglia E, Trapanese P, Tritto F, Gerra L, Bonini N, Vitolo M, Imberti JF, Mei DA. Subclinical atrial fibrillation/atrial high-rate episodes: what significance and decision-making? Eur Heart J Suppl. 2025 Feb 19;27(Suppl 1):i162-i166. doi: 10.1093/eurheartjsupp/suae088. eCollection 2025 Feb. PMID 39980773
• Simu G, Rosu R, Cismaru G, Puiu M, Gusetu G, Minciuna I, Istratoaie S, Tomoaia R, Zdrenghea D, Pop D. Atrial high-rate episodes: a comprehensive review. Cardiovasc J Afr. 2021 Mar-Apr 23;32(2):102-107. doi: 10.5830/CVJA-2020-052. Epub 2021 Jan 15. PMID 33496721
• AlTurki A, Essebag V. Atrial Fibrillation Burden: Impact on Stroke Risk and Beyond. Medicina (Kaunas). 2024 Mar 26;60(4):536. doi: 10.3390/medicina60040536. PMID 38674182

Identifiers

NCT: NCT07250529 · UHP-LBBP-AHRE-2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗