Atrial Fibrillation (AF), Atrioventricular Block, Pacemaker Therapy, Preserved Ejection Fraction
Conditions
Keywords
Left bundle branch pacing, Cardiac electrophysiology, Right ventricular pacing, AHRE burden, Preserved ejection fraction, Heart Failure, Quality of life, Pacing-induced cardiomyopathy (PICM)
Brief summary
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
DEVICERight 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.
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.
Sponsors
University Hospital of Patras
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
The primary hypothesis of the study is that left bundle branch pacing is superior to right ventricular pacing with respect to atrial high-rate episode (AHRE) burden, defined as the cumulative duration of all device-detected AHREs with individual episode duration \>6 minutes from implantation to 24 months (atrial rate threshold ≥170 bpm). Because cumulative AHRE time is expected to be highly right-skewed with a substantial proportion of zero values, the primary endpoint will be analyzed using a prespecified two-part hurdle modeling approach, with the transformed continuous component defined as Y = ln(1 + cumulative AHRE minutes). For sample size determination, a pragmatic design-stage approximation was used based on a two-sample comparison of means on the transformed scale Y. This approach was selected because internal pilot data were available for Y and because closed-form sample size procedures for two-part hurdle models require specification of distributional parameters for both the z
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total cumulative AHRE time for device-detected episodes lasting >6 minutes | From pacemaker implantation (or randomization) to 24 months (primary endpoint) | Sum of the durations of all device-detected AHREs with individual episode duration \>6 minutes (atrial rate threshold per device diagnostics, typically ≥170 bpm), expressed as total time (minutes/hours). Total analyzable monitoring time will be defined as the interval from implantation to the last successful device interrogation/remote transmission, excluding periods of missing device data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total cumulative time in AHRE episodes with individual episode duration 0 to 6 minutes. | 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. | From pacemaker implantation (or randomization) to 24 months | — |
| Total cumulative time in AHRE episodes with individual episode duration 6 hours to 24 hours. | From pacemaker implantation (or randomization) to 24 months | — |
| Total cumulative time in AHRE episodes with individual episode duration >24 hours. | From pacemaker implantation (or randomization) to 24 months | — |
| Time to event - for AHRE episodes > 6 min | 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). | From pacemaker implantation (or randomization) to 24 months | — |
| Time to first clinically documented atrial fibrillation. | From pacemaker implantation (or randomization) to 24 months | — |
| Development of permanent atrial fibrillation. | From pacemaker implantation (or randomization) to 24 months | Atrial fibrillation (AF) will be evaluated using routine interrogation of implanted pacemakers, which provide device-recorded atrial arrhythmia data, including AF burden and episode duration. Permanent atrial fibrillation will be defined according to the ESC Guidelines for Atrial Fibrillation and will require a consensus decision between the treating physician and the patient that the arrhythmia is ongoing. This consensus will also include an agreement to pursue a rate-control strategy with no further attempts to restore or maintain sinus rhythm. |
| Time to progression to permanent atrial fibrillation. | 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). | From pacemaker implantation (or randomization) to 24 months | — |
| All-cause mortality. | From pacemaker implantation (or randomization) to 24 months | — |
| Hospitalization due to AF | From pacemaker implantation (or randomization) to 24 months | — |
| Hospitalization due to HF | From pacemaker implantation (or randomization) to 24 months | — |
| Need for cardioversion. | From pacemaker implantation (or randomization) to 24 months | — |
| Development of pacing-induced cardiomyopathy (PICM) | From pacemaker implantation (or randomization) to 24 months | Defined as a drop in LVEF of at least 10 percentage points resulting in LVEF \<50%, or a relative reduction in global longitudinal strain of at least 15% |
| Changes in biomarkers associated with myocardial stress, inflammation, or injury | At baseline and at 12 and 24 months, where available. | NT-proBNP, hsCRP, and troponin |
| Changes in structured echocardiographic parameters | At baseline and at 12 and 24 months, where available. | Including left atrial strain, left atrial volume index, interventricular mechanical delay, left ventricular mechanical delay, and global longitudinal strain, in participants with available echocardiographic studies from centers able to perform these measurements. |
| Quality-of-life change assessed using a validated questionnaire during follow-up. | At baseline and at 3,6,12,18 and 24 months | Minnesota living with heart-failure questionnaire |
Countries
Greece
Contacts
CONTACTGEORGIOS LEVENTOPOULOS
CONTACTPeriklis Davlouros
Outcome results
None listed