His-Bundle vs Biventricular Pacing for Heart Failure

(HIS-CRT Trial)

Recruiting at 2 trial locations

Overseen By Mary Brown

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Rochester

Disqualifiers: LBBB, IVCD, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two methods to assist individuals with heart failure and right bundle branch block (RBBB), a condition where the heart's electrical signals are delayed. The study compares His-bundle pacing (His-CRT), which directly targets the heart's natural electrical pathways, with the more common biventricular pacing (BIV-CRT) that uses three leads to enhance heart function. Suitable candidates are those experiencing significant heart failure symptoms despite taking heart medications and have RBBB. This trial offers a chance to try a new treatment approach. As an unphased trial, it provides a unique opportunity to explore innovative treatments that could improve heart conditions.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should be on optimal medical therapy for heart failure according to current guidelines, which suggests you may need to continue your existing heart failure medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both His-bundle pacing (His-CRT) and biventricular pacing (BIV-CRT) are generally safe for people with heart failure.

For BIV-CRT, studies indicate it can reduce the risk of death and the need for hospital visits due to heart failure. Although complications can occur, they are uncommon. Its widespread use supports its safety.

His-CRT has also demonstrated good results. It improves heart function in people with a specific heart rhythm problem called right bundle branch block (RBBB). Reports suggest it is safe and well-tolerated.

Both treatments have been studied in patients similar to those who might join this trial. They are considered safe options, with evidence supporting their use in treating heart failure. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because His-bundle pacing (His-CRT) and biventricular pacing (BIV-CRT) offer unique approaches to managing heart failure. Unlike traditional pacemakers, His-CRT targets the heart's natural conduction system, potentially improving electrical efficiency and coordination. BIV-CRT, on the other hand, uses three leads to resynchronize the heart's ventricles, which can enhance heart function and patient quality of life. These methods could offer more tailored and effective solutions for heart failure patients, providing alternatives to existing pacemaker technologies.

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

This trial will compare two treatments for heart failure: biventricular pacing (BiV-CRT) and His-bundle pacing (His-CRT). Studies have shown that BiV-CRT can improve outcomes for people with heart failure by lowering the risk of death and reducing hospital visits. This treatment helps the heart pump better in patients with a specific electrical issue, known as a wide QRS interval. Research suggests that BiV-CRT works best when the pacing exceeds 92%.

Meanwhile, research also shows that His-CRT is effective for heart resynchronization therapy. It shortens the QRS duration and improves the heart's pumping ability, measured by the left ventricular ejection fraction (LVEF), in heart failure patients. His-CRT can be a good option for those who don't respond well to BiV-CRT. Participants in this trial will receive either BiV-CRT or His-CRT to evaluate their effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Roderick Tung, MD

Principal Investigator

University of Arizona

Valentina Kutyifa, MD, PhD

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for heart failure patients with right bundle branch block who meet specific criteria: they have certain levels of heart function and symptoms, are at least 18 years old, and follow optimal medical therapy. It's not for those with left bundle branch block, other ECG issues, or a life expectancy under one year.

Inclusion Criteria

My heart function is severely reduced, and I have a specific heart rhythm pattern.

I am receiving the best current treatment for heart failure.

My heart function is severely reduced, with specific heart rhythm characteristics.

Exclusion Criteria

I am willing and able to follow the study's requirements.

You are not expected to live for more than 12 months.

Pregnancy or planned pregnancy during duration of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive His-bundle pacing enhanced cardiac resynchronization therapy (His-CRT) or cardiac resynchronization therapy (BIV-CRT)

6 months

Follow-up

Participants are monitored for changes in left ventricular ejection fraction, ECG biomarkers, NT-proBNP levels, and echocardiography biomarkers

18 months

What Are the Treatments Tested in This Trial?

Interventions

• BIV-CRT
• His-CRT

Trial Overview The study compares two types of pacemaker implantations in heart failure patients: His-bundle pacing (His-CRT) versus traditional cardiac resynchronization therapy (BIV-CRT). The goal is to see which method works better for correcting the heartbeat.

How Is the Trial Designed?

Group I: BIV-CRT implantation Active Control 1 Intervention

BIV-CRT implantation includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular lead, and an epicardial left ventricular lead implanted in a branch of the coronary sinus.

Group II: His-CRT implantation Active Control 1 Intervention

His-CRT implantation includes implantation of three leads, an endocardial right atrial lead, an endocardial right ventricular lead, and an endocardial His-bundle pacing leads directly pacing the intrinsic conduction system.

BIV-CRT is already approved in European Union, United States for the following indications:

Approved in European Union as Biventricular Pacing for:

• Heart failure with reduced ejection fraction (LVEF ≤35%) and left bundle branch block (LBBB)
• Heart failure with reduced ejection fraction (LVEF ≤35%) and wide QRS

Approved in United States as Biventricular Pacing for:

• Heart failure with reduced ejection fraction (LVEF ≤35%) and left bundle branch block (LBBB)
• Heart failure with reduced ejection fraction (LVEF ≤35%) and wide QRS

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

In the His-SYNC pilot trial involving 41 patients, His bundle pacing (His-CRT) showed significantly greater QRS narrowing compared to biventricular pacing (BiV-CRT), indicating better electrical resynchronization.

Although there was a trend towards higher echocardiographic response rates in the His-CRT group, no significant differences in cardiovascular hospitalization or mortality were found, suggesting that while His-CRT may improve electrical function, its impact on clinical outcomes needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial. Upadhyay, GA., Vijayaraman, P., Nayak, HM., et al.[2020]

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]

In a study involving 176 patients with heart failure, left ventricular (LV) pacing was found to be noninferior to biventricular (BiV) pacing in terms of clinical and echocardiographic responses after 6 months, indicating that LV-only stimulation can be as effective as BiV stimulation.

Both pacing methods showed similar improvement rates in heart failure symptoms, with 76.2% of BiV patients and 74.7% of LV patients responding positively, suggesting that LV pacing could be a viable alternative to BiV pacing for patients with specific heart failure characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized double-blind comparison of biventricular versus left ventricular stimulation for cardiac resynchronization therapy: the Biventricular versus Left Univentricular Pacing with ICD Back-up in Heart Failure Patients (B-LEFT HF) trial. Boriani, G., Kranig, W., Donal, E., et al.[2016]

Cardiac resynchronization therapy using conduction system pacing (CSP-CRT), specifically His pacing and left bundle branch pacing, showed higher success rates (73.5% for His-CRT and 91.5% for LBB-CRT) compared to traditional biventricular pacing, indicating better synchronization and effectiveness in patients with reduced left ventricular ejection fraction.

CSP-CRT resulted in significant improvements in heart function, including increased left ventricular ejection fraction and reduced QRS duration, along with lower pacing thresholds and reduced risks of mortality and hospitalizations, suggesting it may be a superior alternative to biventricular CRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of conduction system pacing for cardiac resynchronization therapy: A systematic review and network meta-analysis. Tavolinejad, H., Kazemian, S., Bozorgi, A., et al.[2023]

His bundle pacing (HBP) significantly reduces the Tp-e and Tp-e/QTc repolarization parameters compared to biventricular pacing (CRT) in patients with left ventricular systolic dysfunction, indicating a potential advantage in repolarization stability.

Both pacing methods showed comparable clinical outcomes and left ventricular function after 6 months, but the implications of improved repolarization with HBP on arrhythmic events require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

His-bundle pacing versus cardiac resynchronisation therapy: Effect on ECG parameters of repolarization. Sarkar, R., Subramanian, M., Rangaswamy, VV., et al.[2022]

In a study involving patients with heart failure and left bundle branch block, both His-bundle pacing and conventional biventricular pacing significantly reduced mechanical dyssynchrony after 6 months, with no significant differences between the two methods.

Both pacing techniques also improved global longitudinal strain, indicating enhanced heart function, but again, there were no significant differences in the improvements between the His-CRT and BiV-CRT groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy on resynchronization and longitudinal contractile function comparing His-bundle pacing to conventional biventricular pacing. - A substudy to the His-alternative study. Højgaard, EV., Philbert, BT., Linde, JJ., et al.[2023]

In a study involving 23 patients with heart failure, His bundle pacing significantly shortened left ventricular activation time and improved ventricular resynchronization compared to conventional biventricular pacing, with notable reductions in QRS duration and left ventricular dyssynchrony.

His bundle pacing also resulted in a greater acute hemodynamic response, indicating it may provide better overall heart function than traditional biventricular pacing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

His Resynchronization Versus Biventricular Pacing in Patients With Heart Failure and Left Bundle Branch Block. Arnold, AD., Shun-Shin, MJ., Keene, D., et al.[2021]

Citations

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

Biventricular Pacing (Cardiac Resynchronization Therapy) The goal of treatment with BiV pacing is to improve cardiac output for people in heart failure (HF) with conduction defect on ECG (wide QRS interval)

2. 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) ...

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. jacc.org jacc.org/doi/10.1016/j.jacc.2022.07.019

Left Bundle Branch Pacing for Cardiac Resynchronization LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in heart failure patients with nonischemic cardiomyopathy and LBBB.

5. ahajournals.org ahajournals.org/doi/10.1161/circ.128.suppl_22.A11330

The Influence of Percent Biventricular Pacing on CRT ... Background: Previous studies have found optimal benefit of cardiac resynchronization therapy (CRT) with biventricular (BIV) pacing above 92%.

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. sciencedirect.com sciencedirect.com/science/article/pii/S2405500X25001872

Clinical Response to Resynchronization Therapy ... Nayak, et al. His corrective pacing or biventricular pacing for cardiac resynchronization in heart failure. J Am Coll Cardiol, 74 (1) (2019), pp. 157-159.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5673318/

His Bundle Pacing Or Biventricular Pacing For Cardiac ... Case 2:A 70-year-old man with nonischemic cardiomyopathy and severely reduced LV function, LBBB and class III CHF on optimal medical therapy was referred for ...