Electrophysiology-Guided Care for Left Bundle Branch Block After TAVI

(COME-TAVI Trial)

Recruiting at 12 trial locations

Overseen By Léna Rivard, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Montreal Heart Institute

Disqualifiers: Prior pacemaker, Pre-existing RBBB, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 72

Duration: 30 days

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a pacemaker, guided by an electrophysiology-based approach, can better prevent fainting, hospital visits, and death in individuals with a new heart rhythm issue (left bundle branch block) following a heart valve procedure (TAVI). One group may receive a pacemaker after an electrical study, while the other group will undergo heart monitoring for 30 days. The trial seeks participants with a persistent new-onset left bundle branch block after their TAVI procedure. As an unphased trial, it offers participants the opportunity to contribute to innovative research that could enhance future heart care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this electrophysiology-based approach is safe for patients with left bundle branch block after TAVI?

Research has shown that pacemaker implants are generally safe and well-tolerated. In one study, 97% of patients received a pacemaker without major issues during the procedure. Another study found that patients with a specific type of pacemaker, called left bundle branch area pacing, experienced good results over two years.

While specific studies on the safety of transcutaneous cardiac monitors are lacking, this type of heart monitoring is non-invasive. It involves wearing a device on the skin to track heart rhythms and is considered low-risk.

Overall, both treatments are considered safe, with more substantial evidence supporting the use of pacemakers. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative ways to manage Left Bundle Branch Block (LBBB) after Transcatheter Aortic Valve Implantation (TAVI). In one approach, electrophysiology (EP) studies guide the decision to implant a pacemaker, offering a more tailored intervention by assessing electrical conduction issues directly. This method could prevent unnecessary pacemaker implants, reducing risks and improving patient outcomes. The trial also examines the effectiveness of extended ECG monitoring, which could enhance detection of electrical problems early on, potentially leading to more precise and less invasive management of LBBB compared to the current standard of care.

What evidence suggests that this trial's treatments could be effective for left bundle branch block after TAVI?

This trial will compare two approaches for managing left bundle branch block (LBBB) after TAVI. One group of participants will receive a pacemaker implant if an electrophysiological (EP) study detects a specific electrical slowdown. Studies have shown that a pacemaker can improve heart function in patients with LBBB after TAVI, enhancing heart pumping ability within six months and reducing hospital visits for heart failure in the long term.

Another group in this trial will use a transcutaneous cardiac monitor for continuous monitoring. Research shows that this method can detect heart rhythm issues after the valve procedure, helping identify patients who might need additional treatment and allowing for quick action if problems arise. Both the pacemaker and the heart monitor aim to address heart rhythm issues after TAVI, leading to better health outcomes for patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Léna Rivard, MD, MSC

Principal Investigator

Montreal Heart Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've recently had a TAVI procedure and developed a new left bundle branch block (LBBB) by the second day after surgery. It's not open to those with prior pacemakers, defibrillators, or pre-existing LBBB/RBBB, nor those already meeting criteria for pacemaker implantation.

Inclusion Criteria

You have a specific type of heart block that developed after a heart valve procedure.

Informed consent to participate

Exclusion Criteria

Prior pacemaker or implantable cardioverter-defibrillator

I am recommended to get a pacemaker based on guidelines.

You have a pre-existing condition called right bundle branch block or left bundle branch block.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either an electrophysiology-based algorithmic approach or standard clinical follow-up with transcutaneous cardiac monitoring

30 days

Minimum of 72-hour ECG monitoring in hospital

Follow-up

Participants are monitored for cardiovascular hospitalizations, syncope, and death after TAVI

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Pacemaker implant
• Transcutaneous cardiac monitor

Trial Overview

The study aims to see if an electrophysiology-guided approach using algorithms can better prevent fainting spells, hospital visits, or death compared to standard clinical monitoring in patients with new LBBB post-TAVI. Participants will either receive regular follow-ups or be monitored with a transcutaneous cardiac device.

How Is the Trial Designed?

Group I: EP-based approach/pacemaker implant Experimental Treatment 1 Intervention

Subjects will undergo an EP study prior to hospital discharge and will receive a pacemaker implantation if the HV interval is ≥65 msec. In the case where the electrical slowdown is not confirmed by the electrophysiological study, the participant will not have a pacemaker implantation.

Group II: Compared transcutaneous cardiac monitor Experimental Treatment 1 Intervention

Subjects will undergo a minimum of 72 hour ECG monitoring in hospital and receive transcutaneous monitoring prior to hospital discharge for a duration of 30 days.

Pacemaker implant is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Pacemaker for:

• Symptomatic bradycardia
• High-degree atrioventricular block
• Complete heart block
• Sick sinus syndrome

Approved in United States as Pacemaker for:

• Symptomatic bradycardia
• High-degree atrioventricular block
• Complete heart block
• Sick sinus syndrome

Approved in Canada as Pacemaker for:

• Symptomatic bradycardia
• High-degree atrioventricular block
• Complete heart block
• Sick sinus syndrome

Approved in Japan as Pacemaker for:

• Symptomatic bradycardia
• High-degree atrioventricular block
• Complete heart block
• Sick sinus syndrome

Approved in China as Pacemaker for:

• Symptomatic bradycardia
• High-degree atrioventricular block
• Complete heart block
• Sick sinus syndrome

Approved in Switzerland as Pacemaker for:

• Symptomatic bradycardia
• High-degree atrioventricular block
• Complete heart block
• Sick sinus syndrome

Who Is Running the Clinical Trial?

Montreal Heart Institute

Lead Sponsor

Trials

125

Recruited

85,400+

Published Research Related to This Trial

In a study of 550 patients undergoing transcatheter aortic valve replacement (TAVR), 9.5% developed new or worsening left bundle branch block (LBBB), indicating that this is a common complication after the procedure.

Patients with new or worsening LBBB who were discharged without a permanent pacemaker (PPM) had a significantly higher rate of needing a PPM within one year (15.2%) compared to those without LBBB (4.5%), highlighting the importance of monitoring these patients post-TAVR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of new and persistent left bundle branch block after transcatheter aortic valve replacement on long-term need for pacemaker implantation. Hamandi, M., Tabachnick, D., Lanfear, AT., et al.[2020]

In a study of 2370 patients undergoing transcatheter aortic valve implantation (TAVI), new left bundle branch block (LBBB) was linked to a significantly higher risk of all-cause mortality over 5 years, with an adjusted hazard ratio of 1.41.

Patients who received a new permanent pacemaker (PPM) after TAVI also showed a trend towards increased mortality, although this was not statistically significant, indicating potential risks associated with both new conduction abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of new-onset conduction abnormalities following transcatheter aortic valve implantation. Tomii, D., Okuno, T., Heg, D., et al.[2022]

In a study of 736 patients who underwent transcatheter aortic valve implantation (TAVI), 16.3% required permanent pacemaker (PPM) implantation, with self- and mechanically expandable valves showing a higher risk of PPM compared to balloon-expandable valves (27.5% vs 7.6%).

Major bleeding complications were notably high, occurring in 24.1% of patients, particularly within the first 24 hours post-PPM implantation, highlighting the need for careful management during this critical period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pacemaker-Related Complications in Patients Undergoing Transcatheter Aortic Valve Implantation: A Single-Center Experience. Lanzillo, G., Mangieri, A., Pagnesi, M., et al.[2021]

In a study of 155 patients who developed new-onset left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI), 24% required permanent pacemaker implantation (PPI), primarily due to total atrioventricular block.

Patients who received PPI had a lower mortality rate (11%) compared to those who did not receive PPI (29%), indicating that PPI may improve prognosis in patients with severe cardiac conduction defects after TAVI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe conduction defects requiring permanent pacemaker implantation in patients with a new-onset left bundle branch block after transcatheter aortic valve implantation. Nijenhuis, VJ., Van Dijk, VF., Chaldoupi, SM., et al.[2022]

A study involving 78 TAVI patients showed that an electrophysiological study (EPS)-guided strategy for permanent pacemaker (PPM) implantation is highly effective, with a sensitivity of 100% and a negative predictive value of 100%, allowing safe discharge for many patients without needing a PPM.

The EPS-guided approach also demonstrated good specificity (89.6%) and positive predictive value (81.5%), indicating it can accurately identify patients at risk for high-degree atrioventricular block (HAVB) who do not require immediate PPM implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrophysiological Study-Guided Permanent Pacemaker Implantation in Patients With Conduction Disturbances Following Transcatheter Aortic Valve Implantation. Bourenane, H., Galand, V., Boulmier, D., et al.[2021]

The COME-TAVI trial is investigating two management strategies for patients with new-onset left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI), comparing an electrophysiological study (EPS)-guided approach with a noninvasive 30-day monitoring strategy.

The primary endpoint of the trial focuses on the net clinical benefit, including serious outcomes like sudden cardiac death and the need for pacemaker implantation, with a target of 452 patients to assess the effectiveness of these management strategies over 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Randomized Bayesian Multicenter COME-TAVI Trial in Patients With a New Onset Left Bundle Branch Block. Rivard, L., Nault, I., Krahn, AD., et al.[2023]

In a study of 431 patients undergoing transaortic valve implantation (TAVI), 18% required a permanent pacemaker (PPM), with pre-existing right bundle branch block (RBBB) significantly increasing the risk of PPM implantation by over five times.

The use of a self-expandable prosthesis also raised the risk of needing a PPM by nearly three times, while a history of syncope was linked to late PPM implantation, indicating specific clinical factors that can help identify patients at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrocardiographic and clinical predictors for permanent pacemaker requirement after transcatheter aortic valve implantation: a 10-year single center experience. Errigo, D., Golzio, PG., D'Ascenzo, F., et al.[2021]

In a study of 306 patients with pre-existing right bundle branch block undergoing transcatheter aortic valve replacement, the overall rate of permanent pacemaker implantation was 41%, indicating a significant risk associated with this condition.

Among different valve designs, the Boston Scientific Lotus valve had the highest PPM implantation rate at 75%, while the Edwards Sapien XT and Sapien 3 valves had lower rates of 32% and 34%, respectively, suggesting that valve choice may influence the need for pacemaker support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter Heart Valve Selection and Permanent Pacemaker Implantation in Patients With Pre-Existent Right Bundle Branch Block. van Gils, L., Tchetche, D., Lhermusier, T., et al.[2018]

In a study of 1398 TAVI patients, early permanent pacemaker (PPM) implantation was found to be safe, with only 6 patients experiencing complications out of 105 who required a PPM.

The majority of patients (83%) needed pacing after TAVI, and those who received a PPM had a longer hospital stay compared to those who did not, indicating that while early PPM implantation is effective, it may lead to increased healthcare resource use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early pacemaker implantation for transcatheter aortic valve implantation is safe and effective. Patel, KP., Lim, WY., Pavithran, A., et al.[2022]

In a study of 362 patients who underwent transcatheter aortic valve replacement (TAVR), those who developed left ventricular (LV) dyssynchrony due to high-burden right ventricular pacing or permanent left bundle branch block (LBBB) had a significantly higher risk of all-cause mortality (adjusted hazard ratio of 2.16) and cardiomyopathy (adjusted hazard ratio of 14.80) at one year post-procedure.

Patients with LV dyssynchrony experienced a mean decline in left ventricular ejection fraction (LVEF) of 10.5%, while the control group showed a slight increase in LVEF, highlighting the adverse impact of LV dyssynchrony on heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in patients with electrocardiographic left ventricular dyssynchrony following transcatheter aortic valve replacement. Ananwattanasuk, T., Atreya, AR., Teerawongsakul, P., et al.[2023]

About one-third of patients (33%) required a permanent pacemaker (PPM) after undergoing transcatheter aortic valve implantation (TAVI), indicating a significant need for pacing support in this population.

The presence of a porcelain aorta was identified as a strong predictor of pacemaker dependency, with patients having a much higher likelihood of needing pacing support, highlighting the importance of anatomical considerations in TAVI outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcatheter aortic valve implantation and requirements of pacing over time. Pereira, E., Ferreira, N., Caeiro, D., et al.[2013]

In a study of 61 patients who received a permanent pacemaker (PPM) after transcatheter aortic valve implantation (TAVI) due to new left bundle branch block (LBBB) or atrioventricular block (AVB) I, 59% exhibited significant ventricular pacing rates (≥1%) at a median follow-up of 6.23 months.

Patients with higher ventricular pacing rates had longer QRS durations at the time of PPM implantation and were less likely to have received a balloon-expandable Edwards Sapiens Valve, indicating potential predictors for pacing dependency that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Permanent pacemaker dependency in patients with new left bundle branch block and new first degree atrioventricular block after transcatheter aortic valve implantation. Hartrampf, B., Jochheim, D., Steffen, J., et al.[2022]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S2474870624001532

The Prognostic Relevance of a New Bundle Branch Block ...

NOP-LBBB is associated with higher mortality and heart failure rehospitalization after TAVI, whilst both NOP-LBBB and NOP-RBBB increase the risk of permanent ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35843731/

Effects of Left Bundle Branch Block and Pacemaker ...

Patients with a baseline LVEF ≤50% who received PPI showed an improvement in LVEF at 6 months regardless of the RV pacing burden.

3.

heartrhythmjournal.com

heartrhythmjournal.com/article/S1547-5271(24)03318-6/abstract

Long-term outcomes of left bundle branch area pacing ...

LBBAP improved long-term clinical outcomes compared with RVP in patients undergoing PPMI after TAVI in terms of less HFH and better LVEF ...

4.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.125.015446

Prospective Observational Study on the Accuracy of ...

CONDUCT-TAVI is a prospective observational study of 200 patients undergoing TAVI across 2 centers. Baseline demographic, anatomic and ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6719385/

Rate and Predictors of Permanent Pacemaker Implantation ...

Several previous studies have examined recovery of conduction after TAVI, and their results showed a majority of patients recover conduction during follow-up [ ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8235153/

Impact of Bundle Branch Block on Permanent Pacemaker ...

Current data about the clinical impact of bundle branch block on post-TAVI PPI remain controversial [9,10]. Left bundle branch block (LBBB) occurs in 5 to 65% ...

7.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCEP.120.008874

Pros and Cons of Left Bundle Branch Pacing | Circulation

A total of 57 of 59 patients underwent successful LBBP (success rate 97%). The average follow-up duration was 6.2±5 months. The implanted ...

8.

heartrhythmjournal.com

heartrhythmjournal.com/article/S1547-5271%2825%2902378-1/fulltext

First-in-human study of a leadless pacemaker system for ...

The primary safety endpoint was freedom from serious device adverse events (SADEs) within 1 month of the implant procedure. The primary ...

9.

academic.oup.com

academic.oup.com/europace/article/27/8/euaf181/8242754

Two-year outcomes of left bundle branch area pacing versus ...

Left bundle branch area pacing significantly lowered the 2-year composite of CV death and HFH compared to RVP in patients aged <65 years old.

10.

sciencedirect.com

sciencedirect.com/science/article/pii/S1547527124028716

Safety and performance of conduction system pacing

The purpose of this study was to characterize the safety and performance of HBP and LBBAP among patients enrolled in the Medtronic product surveillance ...