Physiologic Pacing for First-Degree Heart Block

Overseen By Tonya Fambrough, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ascension Health

Disqualifiers: Permanent atrial fibrillation, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if physiologic pacing will improve symptoms and outcomes in patients with symptomatic first-degree heart block (pr interval ≥250ms).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Physiologic Pacing for First-Degree Heart Block?

Research shows that pacing the left bundle branch can improve heart function in patients with heart failure and left bundle branch block, leading to better clinical outcomes. Additionally, His bundle pacing has been effective in improving heart function in patients with atrioventricular block and left bundle branch block, suggesting potential benefits for similar heart conditions. ^{1 2 3 4 5}

Is physiologic pacing safe for humans?

Physiologic pacing methods like His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) are generally considered safe for humans. Studies have shown that these methods are safe and effective alternatives for patients needing heart pacing. ^{6 7 8 9 10}

How is physiologic pacing different from other treatments for first-degree heart block?

Physiologic pacing, including His bundle pacing and left bundle branch pacing, is unique because it mimics the heart's natural electrical pathways, potentially leading to more natural heart function compared to traditional pacemakers that do not engage the heart's conduction system as directly. ^{6 11 12 13 14}

Eligibility Criteria

This trial is for individuals with symptomatic first-degree heart block, which means their hearts have a specific type of electrical delay. Participants must meet certain health criteria to join, but the provided information does not specify these details.

Inclusion Criteria

PR interval ≥250ms

Narrow QRS duration (≤140ms) or prolonged QRS duration with typical Right Bundle Branch Block (RBBB) morphology on 12 lead ECG and sinus rhythm

Ventricular Ejection Fraction (EF) > 50%

Exclusion Criteria

Pregnancy

I have permanent atrial fibrillation.

Contraindication to use of the relevant study device or leads (as per current manuals from manufacturer)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Evaluation

Patients are evaluated for baseline symptoms, exercise capacity, arrhythmia burden, and patient activity

1 week

1 visit (in-person)

Treatment

Patients undergo left bundle pacing and are randomized to DDD-50 vs MVP-50 with a crossover at 3 months

6 months

3 visits (in-person) at baseline, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life, exercise capacity, patient activity, and atrial fibrillation burden

6 months

Treatment Details

Interventions

• Physiologic Pacing

Trial Overview The study is testing whether a special pacing program can help people with this heart condition. It involves implanting a Medtronic pacemaker and setting it to either DDD-50 or AAI-DDD 50 pacing programs to see if symptoms improve.

Participant Groups

Group I: DDD-50 followed by AAI-DDD 50 Experimental Treatment 3 Interventions

Patients will be programmed to DDD-50 first. After 3 months, patients will be programmed to AAI-DDD 50.

Group II: AAI-DDD 50 followed by DDD-50 Experimental Treatment 3 Interventions

Patients will be programmed to AAI-DDD-50 first. After 3 months, patients will be programmed to DDD 50.

Physiologic Pacing is already approved in European Union, United States for the following indications:

Approved in European Union as Physiologic Pacing for:

• Heart failure
• Symptomatic first-degree heart block
• High-grade AV block
• Complete heart block

Approved in United States as Physiologic Pacing for:

• Heart failure
• Symptomatic first-degree heart block
• High-grade AV block
• Complete heart block

Who Is Running the Clinical Trial?

Ascension Health

Lead Sponsor

Trials

28

Recruited

543,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Findings from Research

Three-dimensional (3D) mapping was successfully used to perform left bundle branch area pacing (LBBP) in three patients with various types of heart block, demonstrating its feasibility and effectiveness in complex cases.

The 3D mapping technique not only facilitated the successful implantation of the pacing lead but also allowed for precise assessment of lead depth in the interventricular septum, which can help improve the accuracy and safety of the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left bundle branch pacing utilizing three dimensional mapping. Vijayaraman, P., Panikkath, R., Mascarenhas, V., et al.[2020]

In a study of 74 heart failure patients with left bundle branch block (LBBB), His bundle pacing (HBP) successfully corrected LBBB in 97.3% of cases, demonstrating its efficacy as a pacing therapy.

Long-term follow-up (median 37.1 months) showed significant improvements in heart function, with left ventricular ejection fraction increasing from 32.4% to 55.9% and New York Heart Association class improving from 2.73 to 1.03, indicating better clinical outcomes for patients receiving permanent HBP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block. Huang, W., Su, L., Wu, S., et al.[2019]

Pacing the left bundle branch (LBB) beyond the conduction block can effectively restore the His-Purkinje conduction system in patients with heart failure and left bundle branch block (LBBB), using a low output of just 0.5 volts.

After one year of follow-up, the patient experienced significant clinical improvement and better echocardiographic measurements, highlighting the potential of this novel pacing strategy for treating heart failure patients with bundle branch block.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Huang, W., Su, L., Wu, S., et al.[2023]

His bundle pacing is an innovative cardiac pacing technique that can help patients with atrioventricular block and those with left bundle branch block and cardiomyopathy.

In a reported case, a patient who did not respond to cardiac resynchronization therapy showed significant clinical improvement and enhanced cardiac function after receiving permanent His bundle pacing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

His bundle pacing after failure of cardiac resynchronization therapy: a case study. Koščová, K., Chovanec, M., Petrů, J., et al.[2021]

In a study involving 20 patients with permanent atrial fibrillation, left bundle branch pacing (LBBP) was found to significantly widen the QRS duration compared to intrinsic conduction, while his bundle pacing (HBP) did not show this effect, indicating a difference in electrical conduction between the two methods.

Both LBBP and HBP achieved similar levels of left ventricular mechanical synchrony, but LBBP resulted in less interventricular synchrony, suggesting that while both techniques are effective, LBBP may introduce some delays in right ventricular activation that need further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of synchronization between left bundle branch and his bundle pacing in atrial fibrillation patients: An intra-patient-controlled study. Sheng, X., Pan, YW., Yu, C., et al.[2022]

His bundle pacing (HBP) is currently regarded as the most physiologic method for cardiac pacing, but it has notable disadvantages including high pacing thresholds and challenging implantation procedures.

Left bundle branch pacing (LBBP) is proposed as a potentially superior alternative to HBP, as it directly engages the His-Purkinje system, but more large-scale randomized clinical trials are needed to confirm its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent approaches to His-Purkinje system pacing. Cheng, LT., Zhang, JM., Wang, ZF., et al.[2020]

Left bundle branch area pacing (LBBAP) is a safe and effective method for patients requiring ventricular pacing, showing no complications during implantation and stable pacing parameters over an average follow-up of 9.2 months.

Patients receiving LBBAP exhibited a right bundle branch block (RBBB) morphology on ECG with significantly shorter QRS duration and stimulus to peak left ventricular activation time compared to those paced at the right ventricular septum, indicating improved electrical activation of the heart.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Implantation of Left Bundle Branch Area Pacing in Patients with and without Bundle Branch Block. Chen, TP., Shi, XJ., Lu, DY., et al.[2021]

Left bundle branch area pacing (LBBaP) showed a higher implant success rate compared to His bundle pacing (HBP), with a relative risk of 1.24 based on a meta-analysis of 10 studies involving 1596 patients.

LBBaP was associated with lower pacing thresholds, shorter procedure times, and a reduced risk of all-cause mortality and heart failure hospitalization compared to HBP, indicating it may be a more effective initial pacing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of left bundle branch area pacing compared to His bundle pacing as a primary pacing strategy: Systematic review and meta-analysis. Abdin, A., Werner, C., Burri, H., et al.[2023]

In a study of 46 patients requiring pacemakers, both His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) demonstrated high procedural success rates of 96%, with HBP achieving success in 91% of cases and LBBAP in all cases, indicating their feasibility and safety.

While HBP patients had higher capture thresholds and lower R-wave amplitudes during implantation, both pacing methods showed stable pacing thresholds at three months, with a low re-intervention rate of 6.5% for HBP, suggesting both techniques are effective long-term options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

His bundle pacing and left bundle branch area pacing: Feasibility and safety. Saleiro, C., Sousa, PA., Nogueira, C., et al.[2023]

In a study of 359 patients with AV block who received permanent pacemakers, left bundle branch area pacing (LBBAP) showed similar clinical outcomes to his bundle pacing (HBP) regarding the risk of death and heart failure hospitalization.

Both pacing methods resulted in comparable paced QRS durations and did not show significant differences in the primary composite outcome of death or heart failure hospitalization, suggesting that LBBAP is a safe alternative to HBP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of left bundle branch area pacing compared to His bundle pacing. Vijayaraman, P., Rajakumar, C., Naperkowski, AM., et al.[2022]

Direct His bundle pacing is a highly physiological method for pacing the ventricles, preserving the natural His-Purkinje conduction system, which is crucial for effective heart function.

This technique may be particularly beneficial for patients with a damaged intrinsic conduction system, offering a promising alternative to traditional pacing methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

His bundle pacing: Initial experience and lessons learned. Deshmukh, A., Deshmukh, P.[2018]

Recent advancements in cardiac pacing techniques, particularly His bundle pacing and left bundle branch pacing, have significantly improved the understanding and application of conduction system pacing.

The review highlights the rapid evolution of knowledge regarding the anatomy and physiology of the conduction system, which is crucial for optimizing pacing strategies in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Conduction System Pacing: A Comprehensive Update. Vijayaraman, P., Chelu, MG., Curila, K., et al.[2023]

In a case of symptomatic intermittent AV block with alternating bundle branch block, conduction system pacing was used as a more physiological alternative to traditional pacing methods.

Left bundle branch pacing successfully restored stable atrioventricular synchrony and produced a paced QRS complex that closely resembled the patient's native rhythm, suggesting it may be an effective treatment option for similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left bundle branch pacing in alternating bundle branch block. Benezet-Mazuecos, J., Baranchuk, A., Lozano, Á., et al.[2023]

In a study of 338 patients, left bundle branch pacing (LBBP) demonstrated significantly better device performance compared to His-bundle pacing (HBP), with 79% of LBBP patients achieving optimal performance versus only 34% for HBP.

LBBP was associated with lower pacing thresholds and higher R-wave amplitudes, and it resulted in fewer heart failure hospitalizations or deaths (9% vs 24% for HBP), suggesting it may offer improved clinical outcomes and should be preferred for cardiac pacing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Pacing Performance and Clinical Outcomes Between Left Bundle Branch and His Bundle Pacing. Tan, ESJ., Soh, R., Boey, E., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Left bundle branch pacing utilizing three dimensional mapping. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block. [2019]

3. England pubmed.ncbi.nlm.nih.gov

A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. [2023]

4. England pubmed.ncbi.nlm.nih.gov

His bundle pacing after failure of cardiac resynchronization therapy: a case study. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Comparison of synchronization between left bundle branch and his bundle pacing in atrial fibrillation patients: An intra-patient-controlled study. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Recent approaches to His-Purkinje system pacing. [2020]

7. Pakistan pubmed.ncbi.nlm.nih.gov

The Implantation of Left Bundle Branch Area Pacing in Patients with and without Bundle Branch Block. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Outcomes of left bundle branch area pacing compared to His bundle pacing as a primary pacing strategy: Systematic review and meta-analysis. [2023]

9. Portugal pubmed.ncbi.nlm.nih.gov

His bundle pacing and left bundle branch area pacing: Feasibility and safety. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical outcomes of left bundle branch area pacing compared to His bundle pacing. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

His bundle pacing: Initial experience and lessons learned. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Cardiac Conduction System Pacing: A Comprehensive Update. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Left bundle branch pacing in alternating bundle branch block. [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Comparison of Pacing Performance and Clinical Outcomes Between Left Bundle Branch and His Bundle Pacing. [2023]