Electrophysiology-Guided Care for Left Bundle Branch Block After TAVI

(COME-TAVI Trial)

Recruiting at 10 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

Trial Summary

What is the purpose of this trial?

The primary hypothesis of the proposed study is that an electrophysiology-based algorithmic approach is superior to standard clinical follow-up with 30-day monitoring in reducing the combined endpoint of syncope, hospitalization, and death in patients in patients with new of left bundle branch block following transcatheter aortic valve implantation (TAVI).

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 data supports the effectiveness of the treatment for left bundle branch block after TAVI?

Research shows that many patients with new left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI) often require a permanent pacemaker (PPM) due to conduction issues. Studies indicate that a significant number of these patients experience relevant ventricular pacing, suggesting that PPM can be effective in managing these conduction disturbances. ^{1 2 3 4 5}

Is the use of a permanent pacemaker after TAVI generally safe?

Studies show that using a permanent pacemaker after TAVI is common and generally safe, though there can be complications. Early pacemaker implantation has been found to be safe and effective, but the timing can vary based on individual needs. ^{3 6 7 8 9}

How is the pacemaker treatment unique for left bundle branch block after TAVI?

The pacemaker treatment for left bundle branch block after TAVI is unique because it involves an electrophysiology-guided approach to determine the need for implantation, which is not standard for all patients. This method uses specific measurements of heart electrical activity to decide if a pacemaker is necessary, potentially leading to more personalized and effective care. ^{4 5 10 11 12}

Research Team

Léna Rivard, MD, MSC

Principal Investigator

Montreal Heart Institute

Eligibility Criteria

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

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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 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 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]

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 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 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]

References

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

Long-term outcomes of new-onset conduction abnormalities following transcatheter aortic valve implantation. [2022]

2. England 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. [2022]

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

Electrophysiological Study-Guided Permanent Pacemaker Implantation in Patients With Conduction Disturbances Following Transcatheter Aortic Valve Implantation. [2021]

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

Outcomes in patients with electrocardiographic left ventricular dyssynchrony following transcatheter aortic valve replacement. [2023]

5. England 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. [2022]

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

Transcatheter aortic valve implantation and requirements of pacing over time. [2013]

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

Pacemaker-Related Complications in Patients Undergoing Transcatheter Aortic Valve Implantation: A Single-Center Experience. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Electrocardiographic and clinical predictors for permanent pacemaker requirement after transcatheter aortic valve implantation: a 10-year single center experience. [2021]

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

Early pacemaker implantation for transcatheter aortic valve implantation is safe and effective. [2022]

10. United States 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. [2023]

11. United States 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. [2020]

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

Transcatheter Heart Valve Selection and Permanent Pacemaker Implantation in Patients With Pre-Existent Right Bundle Branch Block. [2018]