His Bundle vs Biventricular Pacing for Heart Failure

Recruiting at 72 trial locations

Overseen By Merin Thomas

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must be taking: Heart failure therapy

Disqualifiers: Pregnancy, Coronary disease, Myocardial infarction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

2136 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two pacing methods to improve life for people with heart failure. Researchers compare traditional biventricular pacing (Cardiac Resynchronization Therapy, or CRT) with a newer method called His or Left Bundle Branch Pacing to determine which better enhances quality of life and reduces hospital visits. The trial seeks participants with heart failure, a low ejection fraction (a measure of heart pumping efficiency), and specific heart rhythm issues. Those with heart failure already on medication may find this trial suitable. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could enhance future heart failure treatments.

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

The trial protocol does not specify if you need to stop your current medications. However, it mentions that participants should be on heart failure guideline-directed medical therapy, so you may need to continue those medications.

What prior data suggests that these pacing techniques are safe for heart failure patients?

Research has shown that both His/Left Bundle Branch Pacing (His/LBBP) and Biventricular Pacing (BiVP) are generally well-tolerated treatments for heart failure. BiVP, used for many years, has reduced hospital visits and death rates related to heart failure. Studies confirm its safety and effectiveness in improving heart function.

For His/LBBP, research suggests this method is also safe, offering benefits such as better heart function and fewer complications. Although these treatments are applied differently, both have demonstrated positive safety records with relatively low rates of side effects.

In conclusion, studies have confirmed the safety of both treatments, providing reassurance about their tolerability and effectiveness in managing heart failure. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about His/Left Bundle Branch Pacing (His/LBBP) and Biventricular Pacing (BiVP) for heart failure because of their unique approaches to improving heart function. Unlike the standard biventricular pacing, His/LBBP directly targets the heart's natural conduction system, potentially offering more efficient and synchronized heartbeats. On the other hand, BiVP remains a reliable option with a proven track record of effectively managing heart failure by coordinating the contraction of both ventricles. These treatments offer promising alternatives to standard heart failure therapies, aiming for improved heart function and patient outcomes.

What evidence suggests that this trial's treatments could be effective for heart failure?

This trial will compare Biventricular Pacing (BiVP) and His/Left Bundle Branch Pacing (His/LBBP) for heart failure. Research has shown that biventricular pacing, also known as cardiac resynchronization therapy (CRT), improves heart function and reduces hospital visits for heart failure patients. Studies have found that patients live longer with effective CRT. For His bundle and left bundle branch pacing (His/LBBP), research suggests these methods align better with the heart's natural electrical signals, potentially enhancing heart function and quality of life. Recent studies have shown positive results for patients with severe electrical issues in the heart using these methods. Both treatments hold promise for managing heart failure, with evidence supporting their ability to improve patient outcomes. ^{1 5 6 7 8}

Who Is on the Research Team?

Mihail Chelu, MD

Principal Investigator

Baylor College of Medicine

Kenneth Ellenbogen, MD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with heart failure and left ventricular dysfunction (LVEF≤50%), who are on standard heart failure meds, have a wide QRS (≥130 ms), or need/already have >40% right ventricular pacing. It's not for those with short life expectancy, certain preexisting conditions, recent heart attacks or procedures, reversible cardiomyopathies, severe valve disease, or women who are pregnant.

Inclusion Criteria

Your heart's pumping ability is less than 50% within the past 6 months.

My heart failure treatment follows the latest guidelines.

Your heart's electrical activity is slower than normal, or you have a device that helps your heart beat and it's used a lot.

Exclusion Criteria

I had a heart attack confirmed by tests in the last 3 months.

I am not pregnant, breastfeeding, nor planning to become pregnant during the trial.

I have Chagas disease, cardiac sarcoidosis, or amyloidosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either His/Left bundle branch pacing or biventricular pacing, with device implantation and monitoring

12 months

Regular visits for device monitoring and adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of heart failure hospitalization and mortality

5.5 years

Annual visits for outcome assessment

What Are the Treatments Tested in This Trial?

Interventions

• BiVP
• His/LBBP

Trial Overview The study compares His bundle or Left bundle branch pacing against standard biventricular pacing in improving quality of life and reducing hospitalizations and mortality in patients with systolic dysfunction and wide QRS complex. It also assesses the safety regarding device complications like lead dislodgement and infection.

How Is the Trial Designed?

Group I: Biventricular Pacing (BiVP) Active Control 1 Intervention

Patients with LVEF≤35% at entry will receive a BiV defibrillator which includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular ICD lead, and and an epicardial left ventricular lead implanted in a branch of the coronary sinus. Patients with LVEF 36-50% at entry will receive BiV pacemaker which includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular pacing lead, and and an epicardial left ventricular lead implanted in a branch of the coronary sinus.

Group II: His/Left Bundle Branch Pacing (His/LBBP) Active Control 1 Intervention

Patients with LVEF≤35% at entry will receive a His/LBB defibrillator which includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular ICD lead, and an endocardial His-bundle or left bundle branch pacing lead directly pacing the intrinsic conduction system. Patients with LVEF 36-50% at entry will receive His/LBB pacemaker which includes implantation of two leads, an endocardial right atrial lead, and an endocardial His-bundle or left bundle branch pacing lead directly pacing the intrinsic conduction system.

BiVP is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Biventricular Pacing for:

• Heart failure with reduced left ventricular ejection fraction (LVEF)
• Wide QRS complex

Approved in United States as Biventricular Pacing for:

• Heart failure with reduced left ventricular ejection fraction (LVEF)
• Wide QRS complex

Approved in Canada as Biventricular Pacing for:

• Heart failure with reduced left ventricular ejection fraction (LVEF)
• Wide QRS complex

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Cleveland Clinic Florida

Collaborator

Trials

16

Recruited

6,800+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Virginia Commonwealth University

Collaborator

Trials

732

Recruited

22,900,000+

Rush University

Collaborator

Trials

46

Recruited

3,294,000+

East Carolina University

Collaborator

Trials

111

Recruited

42,400+

Published Research Related to This Trial

In a study of 137 patients with severe heart failure, left bundle branch pacing (LBBP) and His bundle pacing (HBP) showed similar and significant improvements in left ventricular ejection fraction (LVEF) and symptoms compared to biventricular pacing (BVP), which had lower efficacy.

LBBP was associated with higher R-wave amplitude and lower pacing thresholds than HBP, suggesting it may be a more effective method for cardiac resynchronization therapy (CRT) and warrants further investigation in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Bundle Branch Pacing for Cardiac Resynchronization Therapy: Nonrandomized On-Treatment Comparison With His Bundle Pacing and Biventricular Pacing. Wu, S., Su, L., Vijayaraman, P., et al.[2021]

A meta-analysis of 10 studies involving 1063 heart failure patients showed that left bundle branch pacing (LBBP) significantly reduced heart failure hospitalization rates compared to biventricular pacing (BVP), with a risk ratio of 0.60.

LBBP-CRT also improved other important measures, including left ventricular ejection fraction (LVEF) and pacing thresholds, and resulted in a higher percentage of patients classified as responders and super-responders compared to BVP-CRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left bundle branch pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis. Parlavecchio, A., Vetta, G., Caminiti, R., et al.[2023]

His-bundle pacing (HBP) significantly outperforms biventricular endocardial (BiV-endo) and biventricular epicardial (BiV-epi) pacing in reducing left ventricular activation times and interventricular dyssynchrony in heart failure patients with left bundle branch block, based on computer simulations of 24 heart models.

Left bundle pacing (LBP) also reduces left ventricular activation times but does not improve interventricular dyssynchrony compared to BiV-endo and BiV-epi pacing; however, optimizing the atrioventricular delay during LBP can enhance its effectiveness, making it comparable to HBP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

His-bundle and left bundle pacing with optimized atrioventricular delay achieve superior electrical synchrony over endocardial and epicardial pacing in left bundle branch block patients. Strocchi, M., Lee, AWC., Neic, A., et al.[2021]

In a study of 100 patients with heart failure and left bundle branch block, left bundle branch pacing cardiac resynchronization therapy (LBBP-CRT) showed a higher success rate (98%) compared to optimized biventricular pacing (BVP-aCRT) at 91%, indicating LBBP-CRT is a feasible and effective option.

LBBP-CRT resulted in greater improvements in left ventricular ejection fraction and a higher rate of super-responses at both 6 months and 1 year compared to BVP-aCRT, suggesting it may provide better clinical outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy via left bundle branch pacing vs. optimized biventricular pacing with adaptive algorithm in heart failure with left bundle branch block: a prospective, multi-centre, observational study. Chen, X., Ye, Y., Wang, Z., et al.[2023]

His bundle pacing (HBP) can effectively shorten left ventricular activation times (LVAT) in 87.5% of patients with left bundle branch block (LBBB), with 33.3% achieving complete ventricular resynchronization similar to normal heart patterns.

Noninvasive electrocardiographic mapping can help identify which patients with LBBB are likely to benefit from HBP, suggesting that HBP may offer better resynchronization compared to biventricular pacing (BVP).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrocardiographic predictors of successful resynchronization of left bundle branch block by His bundle pacing. Arnold, AD., Shun-Shin, MJ., Keene, D., et al.[2022]

Permanent His-bundle pacing (HBP) was successful in 90% of patients (95 out of 106), showing it as a feasible alternative for cardiac resynchronization therapy (CRT) in those who either failed biventricular pacing (BVP) or had indications for CRT.

After an average follow-up of 14 months, patients experienced significant improvements, including a reduction in QRS duration from 157 ms to 117 ms, an increase in left ventricular ejection fraction from 30% to 43%, and a better functional class, indicating that HBP effectively enhances heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Permanent His-bundle pacing as an alternative to biventricular pacing for cardiac resynchronization therapy: A multicenter experience. Sharma, PS., Dandamudi, G., Herweg, B., et al.[2018]

In a study of 21 patients with heart failure and left bundle branch block, left bundle branch pacing (LBBP) showed greater improvements in electrical and mechanical synchrony compared to biventricular pacing (BVP), including a significant reduction in QRS duration and area.

LBBP also resulted in a higher increase in hemodynamic performance, as measured by the maximum rate of left ventricular pressure rise (dP/dtmax), indicating it may be a more effective option for cardiac resynchronization therapy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Bundle Branch Pacing Versus Biventricular Pacing for Acute Cardiac Resynchronization in Patients With Heart Failure. Liang, Y., Wang, J., Gong, X., et al.[2022]

In two patients with end-stage heart failure, upgrading from conventional right ventricular apical and left ventricular pacing (BiVRVA+LV) to His-bundle pacing combined with left ventricular pacing (BiVHB+LV) led to significant improvements in heart failure status.

This suggests that BiVHB+LV pacing may be a more effective option for patients with advanced heart failure and conduction defects, as it addresses issues of dyssynchrony that conventional pacing may not fully correct.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upgrade of cardiac resynchronization therapy by utilizing additional His-bundle pacing in patients with inotrope-dependent end-stage heart failure: a case series. Baba, M., Yoshida, K., Hanaki, Y., et al.[2022]

His-bundle pacing (HBP) is a feasible alternative to biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT), showing equivalent clinical responses in patients with heart failure after 1 year of follow-up.

In a study of 29 patients, 72% showed electrical resynchronization with HBP, indicating that this method may be effective for a broader range of patients with left bundle branch block than previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: A crossover design comparison. Lustgarten, DL., Crespo, EM., Arkhipova-Jenkins, I., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3382419/

Biventricular Pacing (Cardiac Resynchronization Therapy) The Medical Advisory Secretariat concluded that there was evidence of short (6 months) and longer-term (12 months) effectiveness in terms of cardiac function ...

2. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(24)02910-2/fulltext

Ineffective cardiac resynchronization pacing is associated ... In a landmark study, Hayes et al identified that the greatest improvement in survival occurred in patients with CRT pacing exceeding 98% of all ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1071916425001617

Evolving Indications, Challenges and Advances in Cardiac ... Cardiac resynchronization therapy (CRT) via biventricular pacing has markedly improved heart failure outcomes over the past 2 decades.

4. emedicine.medscape.com emedicine.medscape.com/article/1839506-overview

Cardiac Resynchronization Therapy REVERSE showed significant reverse remodeling, MADIT-CRT showed less hospitalization, and RAFT showed significant reduction in mortality in the ...

5. ahajournals.org ahajournals.org/doi/abs/10.1161/circ.128.suppl_22.a11330

Abstract 11330: The Influence of Percent Biventricular ... Results: As shown in Figure 1, BIV pacing ≤ 96% did not improve clinical outcome in patients with CRT-D as compared to those with ICD. Higher BIV pacing ...

6. academic.oup.com academic.oup.com/europace/article/26/Supplement_1/euae102.461/7681256

Clinical and long term safety outcomes of conduction system ... The outcomes were defined as at least one heart failure hospitalization and the complication rates for both arms. Results. Median [IQR] ...

7. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(24)00242-X/fulltext

Comparisons of long-term clinical outcomes with left ... Cardiac resynchronization therapy (CRT) with biventricular pacing (BiVP-CRT) reduces all-cause mortality and heart failure hospitalization (HFH) ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12151867/

Cardiac resynchronization therapy for heart failure In the early 1990s, attempts at treating patients with dilated cardiomyopathy and end-stage heart failure by using right-sided, dual-chamber pacing met with ...