Pacemaker Testing for Bundle-Branch Block

(FOCUS-Right Trial)

Overseen By Melissa Sears

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Commonwealth University

Disqualifiers: Chronotropic incompetence, Heart block, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this prospective single center clinical trial is to evaluate the safety and feasibility of performing simultaneous exercise stress cardiac magnetic resonance (CPET-CMR) and cardiopulmonary exercise testing in patients with pre-existing left bundle branch area pacemakers (LBBAP) programmed to an atrial sensing mode. Measurements of right ventricular, left ventricular function, and exercise capacity will be obtained at various LBBAP programming parameters at rest and during low intensity exercise. The main aims of the study are: * Demonstrate the safety and feasibility of performing CPET-CMR in patients with pre-existing LBBAP programmed to P-synchronous ventricular pacing mode. * Generate preliminary data evaluating differences in RV function, LV function, and exercise capacity during various pacemaker programming settings.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to consult with the trial coordinators for specific guidance.

What data supports the idea that Pacemaker Testing for Bundle-Branch Block is an effective treatment?

The available research shows that Left Bundle Branch Area Pacing (LBBAP) is effective in treating Bundle-Branch Block. One study found that LBBAP helps maintain fast electrical signals in the heart, which is important for proper heart function. Another study highlighted that LBBAP can prevent heart problems that might occur with other types of pacemakers over time. Additionally, LBBAP was shown to improve heart function in patients with heart failure when compared to another treatment called biventricular pacing. This suggests that LBBAP is a promising option for people with heart issues related to Bundle-Branch Block. ^{1 2 3 4 5}

What safety data exists for pacemaker treatment in bundle-branch block?

The safety of Left Bundle Branch Area Pacing (LBBAP) has been evaluated in various studies. It is considered effective and safe, particularly in patients with congenital heart disease, although data is limited. The MELOS study, a large multicenter international collaboration, evaluated the outcomes of LBBAP, indicating its promise as a new pacing method. However, long-term safety data, especially beyond one year post-implantation, is not well described. Comparisons with traditional cardiac resynchronization therapy (CRT) in heart failure patients with left bundle branch block also suggest LBBAP's efficacy and safety. ^{5 6 7 8 9}

Is Left Bundle Branch Area Pacemaker (LBBAP) a promising treatment for Bundle-Branch Block?

Yes, Left Bundle Branch Area Pacemaker (LBBAP) is a promising treatment for Bundle-Branch Block. It helps the heart's electrical system work better by keeping the heart's natural rhythm and improving how the heart's ventricles activate. This can lead to better heart function and potentially improved health outcomes for patients. ^{1 7 10 11 12}

Research Team

Ajay Pillai

Principal Investigator

Virginia Commonwealth University

Eligibility Criteria

This trial is for patients with a specific heart condition called left bundle branch block who already have pacemakers. They should be able to undergo exercise tests and cardiac imaging safely. People with conditions that make these procedures risky cannot participate.

Inclusion Criteria

Presence of dual chamber LBBAP implantation

Presence of anodal capture with bipolar pacing configuration as determined at pacing implant.

Exclusion Criteria

Known history of chronotropic incompetence

High degree or complete heart block

Inability to undergo MRI or exercise utilizing supine bicycle at target work-load

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Assessment 1 (No Ventricular Pacing) will be performed with no ventricular pacing to assess baseline right and left ventricular function at rest and during exercise.

1 day

1 visit (in-person)

Non-selective or Selective Left Bundle Branch Area Pacing

Phase 2 will assess right and left ventricular function at rest and during exercise with non-selective or selective left bundle branch area pacing.

1 day

1 visit (in-person)

Left Bundle Branch Area Pacing with Anodal Capture

Phase 3 will assess right and left ventricular function at rest and during exercise with left bundle branch area pacing with anodal capture.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Left Bundle Branch Area Pacemaker (LBBAP)

Trial Overview The FOCUS-Right study is testing how different settings on a patient's pacemaker affect their heart function and ability to exercise. It involves checking the pacemaker, doing an ECG, exercising while inside an MRI machine, and monitoring the pacemaker continuously.

Participant Groups

Group I: No Ventricular Pacing (NVP) Experimental Treatment 3 Interventions

Assessment 1 (No Ventricular Pacing) will be performed with no ventricular pacing to assess baseline right and left ventricular function at rest and during exercise.

Group II: Left Bundle Branch Area Pacing with Anodal Capture (aLBBAP) Experimental Treatment 3 Interventions

Phase 3 (Left Bundle Branch Area Pacing with Anodal Capture or aLBBAP) will assess right and left ventricular function at rest and during exercise with left bundle branch area pacing with anodal capture.

Group III: Non-selective or Selective Left Bundle Branch Area Pacing (nsLBBAP) Active Control 3 Interventions

Phase 2 (non-selective or selective Left Bundle Branch Area Pacing or ns/sLBBAP) will assess right and left ventricular function at rest and during exercise with non-selective or selective left bundle branch area pacing

Left Bundle Branch Area Pacemaker (LBBAP) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cardiac Pacemaker for:

• Heart block
• Bradycardia
• Cardiac arrhythmias

Approved in European Union as Cardiac Pacemaker for:

• Heart block
• Bradycardia
• Cardiac arrhythmias
• Heart failure

Approved in Canada as Cardiac Pacemaker for:

• Heart block
• Bradycardia
• Cardiac arrhythmias

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Findings from Research

In a study of 58 patients undergoing left bundle branch area pacing (LBBAP), the procedure was successful in 97% of cases, leading to significant improvements in left ventricular ejection fraction (LVEF) from 52.9% to 56.9% after 3 months (p=0.004).

LBBAP also resulted in marked reductions in both intraventricular and interventricular dyssynchrony, indicating that this pacing method promotes faster and more synchronized biventricular contractions, regardless of the patients' initial heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early effects of left bundle branch area pacing on ventricular activation by speckle tracking echocardiography. Dell'Era, G., Ghiglieno, C., Degiovanni, A., et al.[2023]

In a study of 151 patients with symptomatic bradycardia who received left bundle branch area pacing (LBBAP), none developed pacing-induced cardiomyopathy (PICM), indicating that LBBAP is a safe option for patients with preserved left ventricular ejection fraction (LVEF).

For patients with a baseline LVEF below 50%, LBBAP significantly improved heart function, with LVEF increasing from 41.4% to 45.6% and global longitudinal strain (GLS) improving from 12.9% to 15.5% over a median follow-up of 23 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left bundle branch area pacing prevents pacing induced cardiomyopathy in long-term observation. Bednarek, A., Kiełbasa, G., Moskal, P., et al.[2023]

Left bundle branch area pacing (LBBAP) is a safe and effective method for correcting complete left bundle branch block (CLBBB) in heart failure patients, with no complications reported in the study of 10 patients.

LBBAP showed superior outcomes compared to biventricular pacing (BIVP), with a higher response rate (100% vs. 63.33%) and greater improvement in electrical synchrony, as indicated by a significantly larger decrease in QRS duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of left bundle branch area pacing compared with biventricular pacing in patients with heart failure: A matched case-control study. Wang, Y., Gu, K., Qian, Z., et al.[2021]

In a study of 50 bradycardia patients receiving left bundle branch area pacing (LBBAP), the lead tip location significantly influenced left ventricular activation time (LVAT), with shorter LVAT observed when the lead tip was within 2 mm of the left ventricular blood pool.

Paced QRS duration (QRSd) remained consistent across different lead tip locations, indicating that LBBAP can achieve physiological pacing characteristics regardless of the precise lead placement within the interventricular septum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computed tomography imaging-identified location and electrocardiographic characteristics of left bundle branch area pacing in bradycardia patients. Chen, K., Liu, X., Hou, X., et al.[2022]

Left bundle branch area pacing (LBBAP) is a safe and effective long-term pacing method for patients with bradycardia, showing stable pacing thresholds and no procedure-related complications over 12 months in a study of 65 patients.

Patients with pre-existing left bundle branch block experienced the most significant improvement, with a 24 ms narrowing of the paced QRS duration, indicating enhanced cardiac function with LBBAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durability of left bundle branch area pacing. Mehta, NA., Saqi, B., Sabzwari, SRA., et al.[2022]

Left bundle branch area pacing (LBBAP) is both feasible and safe for patients with congenital heart disease (CHD), achieving acute success in all 13 CHD patients studied, similar to the 96% success rate in non-CHD patients.

Procedural times and lead parameters were comparable between CHD and non-CHD patients, indicating that LBBAP can be effectively performed in patients with complex heart anatomies without significant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left bundle branch area pacing in congenital heart disease. O'Connor, M., Riad, O., Shi, R., et al.[2023]

A new method for selective left bundle branch pacing (LBBP) using continuous low output (2 V / 0.5 ms) was evaluated in 28 patients, showing a high rate of successful left bundle branch capture during the procedure.

The study found that an abrupt shortening of the stimulus-to-peak left ventricular activation time (S-peak LVAT) during low output pacing was highly sensitive (100%) for predicting effective pacing, indicating this method could enhance the safety and efficacy of LBBP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the shortening of the stimulus-to-peak left ventricular activation time at continuous low output to confirm left bundle branch capture. Zhong, J., Zheng, N., Jiang, L.[2022]

In a large study of 2533 patients across 14 European centers, permanent left bundle branch area pacing (LBBAP) showed a high lead implantation success rate of 92.4% for bradyarrhythmia and 82.2% for heart failure, indicating its feasibility as a primary pacing technique.

The study reported a complication rate of 11.7%, with specific complications from the ventricular transseptal route occurring in 8.3% of patients, suggesting that while LBBAP is promising, safety and success rates in heart failure patients need further improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left bundle branch area pacing outcomes: the multicentre European MELOS study. Jastrzębski, M., Kiełbasa, G., Cano, O., et al.[2022]

Left bundle branch area pacing (LBBaP) is a safe and effective method for resynchronizing heart function in patients with heart failure and left bundle branch block, showing significant improvements in heart function after 12 months.

Compared to traditional cardiac resynchronization therapy (CRT), LBBaP resulted in shorter operation and X-ray exposure times, and it achieved a narrower QRS complex more quickly, indicating better electrical synchronization of the heart.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization performed by LBBaP-CRT in patients with cardiac insufficiency and left bundle branch block. Zu, L., Wang, Z., Hang, F., et al.[2021]

Left bundle branch area pacing (LBBAP) is a safe and feasible technique for cardiac pacing, successfully implanted in 96% of 80 patients, with a significant reduction in lead implantation and fluoroscopy times as experience increased.

LBBAP effectively maintains ventricular electrical synchrony, resulting in narrower QRS durations compared to right ventricular septum pacing (RVSP), indicating its potential for better physiological pacing outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-centre prospective evaluation of left bundle branch area pacemaker implantation characteristics. Heckman, LIB., Luermans, JGLM., Jastrzębski, M., et al.[2022]

In a study of 29 heart failure patients, left bundle branch pacing (LBBP) was found to significantly improve left ventricular activation speed and mechanical synchrony compared to left ventricular septal pacing (LVSP).

After an average follow-up of 17 months, patients in the LBBP group showed a greater improvement in left ventricular ejection fraction (LVEF) of 26% compared to just 6% in the LVSP group, indicating that LBBP is more effective for resynchronization in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resynchronization effects and clinical outcomes during left bundle branch area pacing with and without conduction system capture. Zhang, W., Chen, L., Zhou, X., et al.[2023]

Left bundle branch area pacing (LBBAP) was successfully performed in 82.2% of patients, showing a significant reduction in QRS width, which indicates improved electrical activation of the heart, particularly in patients with left bundle branch block (LBBB).

LBBAP preserved intra-ventricular mechanical synchrony in patients with narrow QRS and right bundle branch block (RBBB), while it improved asynchrony parameters in those with LBBB, suggesting its efficacy in enhancing heart function during routine practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left bundle branch area pacing in patients with baseline narrow, left, or right bundle branch block QRS patterns: insights into electrocardiographic and echocardiographic features. Mirolo, A., Chaumont, C., Auquier, N., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Early effects of left bundle branch area pacing on ventricular activation by speckle tracking echocardiography. [2023]

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

Left bundle branch area pacing prevents pacing induced cardiomyopathy in long-term observation. [2023]

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

The efficacy of left bundle branch area pacing compared with biventricular pacing in patients with heart failure: A matched case-control study. [2021]

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

Computed tomography imaging-identified location and electrocardiographic characteristics of left bundle branch area pacing in bradycardia patients. [2022]

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

Durability of left bundle branch area pacing. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Left bundle branch area pacing in congenital heart disease. [2023]

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

Evaluation of the shortening of the stimulus-to-peak left ventricular activation time at continuous low output to confirm left bundle branch capture. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Left bundle branch area pacing outcomes: the multicentre European MELOS study. [2022]

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

Cardiac resynchronization performed by LBBaP-CRT in patients with cardiac insufficiency and left bundle branch block. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A single-centre prospective evaluation of left bundle branch area pacemaker implantation characteristics. [2022]

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

Resynchronization effects and clinical outcomes during left bundle branch area pacing with and without conduction system capture. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Left bundle branch area pacing in patients with baseline narrow, left, or right bundle branch block QRS patterns: insights into electrocardiographic and echocardiographic features. [2023]