ICE-Guided Watchman Device Implantation for Atrial Fibrillation

Overseen By Shady Nakhla, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Disqualifiers: Concomitant ablation, Prior incomplete ligation, 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: 1

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is to look at the success of Intracardiac Echocardiography (ICE) in the Watchman procedure. Currently the process is to use a Transesophageal Echocardiography (TEE) to place the Watchman in patients. This study is aiming to show how the ICE is just as effective in placing the device correctly and effectively.

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 ICE-Guided Watchman Device Implantation for Atrial Fibrillation?

Research shows that using the Watchman device for closing the left atrial appendage (a small pouch in the heart) can help prevent strokes in people with atrial fibrillation (a heart rhythm disorder). Studies have found that using intracardiac echocardiography (a type of heart imaging) to guide the implantation of the Watchman device is both safe and effective. ^{1 2 3 4 5}

Is the ICE-guided Watchman device implantation safe for humans?

The Watchman device, used for closing the left atrial appendage to prevent strokes in atrial fibrillation patients, has been shown to be safe in humans, with procedural safety improving significantly over time. Intracardiac echocardiography (ICE) is a feasible method to guide the implantation of the Watchman device, and studies have demonstrated its safety in these procedures. ^{1 2 3 5 6}

How is the ICE-Guided Watchman Device Implantation treatment for atrial fibrillation different from other treatments?

The ICE-Guided Watchman Device Implantation is unique because it uses intracardiac echocardiography (ICE) to guide the placement of a device that closes the left atrial appendage, reducing the risk of stroke in patients with atrial fibrillation. This approach is different from traditional treatments like blood thinners, as it physically prevents blood clots from forming in the heart. ^{7 8 9 10 11}

Research Team

Shady Nakhla, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for patients who qualify for a Watchman heart device implant and aren't part of another clinical study. It's not for those getting an ablation procedure, with prior incomplete left atrial appendage closure, or issues that complicate trans-septal equipment delivery like PFO or ASD closures.

Inclusion Criteria

You are eligible for a Watchman device implant according to standard guidelines and are not currently in another research study.

Exclusion Criteria

You have a condition that would make it hard for the medical equipment to be delivered, such as having a PFO or ASD closure devices in place.

I am undergoing a procedure to destroy abnormal tissue.

I had an incomplete procedure to close off a part of my heart.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Procedure

Intracardiac echocardiography (ICE) guided Watchman device implantation

During the procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the procedure

4 weeks

Treatment Details

Interventions

• Intracardiac Echocardiography (ICE)

Trial Overview The study tests the effectiveness of using Intracardiac Echocardiography (ICE) instead of Transesophageal Echocardiography (TEE) to place the Watchman device in patients with conditions like Atrial Fibrillation.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Intracardiac Echocardiography (ICE)

Intracardiac Echocardiography (ICE) is already approved in European Union, United States for the following indications:

Approved in European Union as Watchman for:

• Reduction of the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation

Approved in United States as Watchman for:

• Reduction of the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores and are recommended for anticoagulation therapy

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Findings from Research

The Watchman FLX device demonstrated a high procedural success rate of 93.4% in left atrial appendage occlusion (LAAO) among 91 patients, with technical success achieved in 99% of cases, indicating its efficacy for a wide range of LAA anatomies.

The use of intracardiac echocardiography (ICE) for guiding the implantation resulted in a low complication rate of 5.5%, with no device-related thrombosis reported, showcasing the safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Watchman FLX Device: First European Experience and Feasibility of Intracardiac Echocardiography to Guide Implantation. Korsholm, K., Samaras, A., Andersen, A., et al.[2021]

The study found that using intracardiac echocardiography (ICE) for 'one-stop' procedures combining radiofrequency catheter ablation and left atrial appendage closure (LAAC) resulted in significantly fewer cases of thrombus formation compared to transesophageal echocardiography (TEE), with only 1.46% in the ICE group versus 11.63% in the TEE group.

ICE-guided procedures also demonstrated advantages in terms of safety and efficiency, including less radiation exposure, shorter procedure times, and fewer postoperative complications compared to TEE, making ICE a preferable option for these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intracardiac vs. transesophageal echocardiography for "one-stop" procedures of combined radiofrequency catheter ablation and left atrial appendage closure with the Watchman device in the treatment of atrial fibrillation. Shang, X., Sun, M., Wang, Z., et al.[2023]

The WATCHMAN™ LAA closure device is an effective mechanical strategy for preventing strokes in patients with atrial fibrillation (AF) by closing off the left atrial appendage, which is a major source of blood clots.

Clinical data from two randomized trials indicate that the safety of the WATCHMAN device has significantly improved over time, making it a viable alternative to traditional anticoagulants that carry bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left atrial appendage occlusion with the WATCHMAN™ for stroke prevention in atrial fibrillation. Price, MJ.[2022]

In a study of 58 patients undergoing WATCHMAN device implantation for atrial fibrillation, incomplete occlusion of the left atrial appendage (LAA) was observed in a significant number of cases, with gaps noted in 27.6% to 34.5% of patients over 12 months.

The study found that these gaps often persisted and could increase in size over time, raising concerns about the potential risk of thromboembolic events, as evidenced by two patients who experienced complications after discontinuing anticoagulation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraprocedural and long-term incomplete occlusion of the left atrial appendage following placement of the WATCHMAN device: a single center experience. Bai, R., Horton, RP., DI Biase, L., et al.[2016]

In a study of 27 patients with atrial fibrillation, transcatheter left atrial appendage closure using intracardiac echocardiography (ICE) guidance was found to be safe, with no major procedural complications reported.

The procedure was successful in all patients, with a 14.8% rate of minor complications, primarily access site hematomas, and confirmed effective closure of the left atrial appendage at 45 days post-implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Atrial Appendage Closure Under Intracardiac Echocardiographic Guidance: Feasibility and Comparison With Transesophageal Echocardiography. Matsuo, Y., Neuzil, P., Petru, J., et al.[2018]

Transcatheter left atrial appendage (LAA) closure using devices like the Watchman has shown promising results in significantly reducing stroke risk in patients with atrial fibrillation, offering a potential alternative to traditional oral anticoagulants.

The Watchman device trials indicate that its efficacy in preventing strokes is comparable to that of warfarin, highlighting its effectiveness and supporting the concept of LAA closure as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Atrial Appendage Closure with Transcatheter-Delivered Devices. Whisenant, B., Weiss, P.[2019]

In a study involving 2-day-old mice, the application of the ICE protease inhibitor YVAD-CHO to lesioned facial nerves resulted in a 32% reduction in apoptotic motoneurones, suggesting that ICE proteases play a role in nerve injury-induced cell death.

The findings indicate that targeting ICE or ICE-like proteases could be a potential strategy to delay motoneurone death following nerve injury, highlighting a possible therapeutic approach for nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute application of an interleukin-1 beta-converting enzyme-specific inhibitor delays axotomy-induced motoneurone death. de Bilbao, F., Dubois-Dauphin, M.[2019]

The study highlights the role of the interleukin-1 beta converting enzyme (ICE) and its family members in neuronal death, suggesting that while ICE itself is not expressed in neurons, its homologs may mediate apoptosis and programmed cell death.

Given the involvement of ICE family members in neurodegenerative diseases, targeting these proteases with antagonists could offer neuroprotective benefits, potentially leading to new therapeutic strategies for conditions with apoptotic components.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Watch for ICE in neurodegeneration. Vasilakos, J., Shivers, B.[2006]

Gamma-irradiation effectively induces apoptosis in human retinoblastoma cell lines (WERI-Rb-1 and Y79) in a dose-dependent manner, with a significant increase in the levels of interleukin-1beta-converting enzyme (ICE) observed after treatment.

Inhibition of ICE using a specific tetrapeptide inhibitor (Ac-YVAD-CMK) reduced gamma-irradiation-induced apoptosis, while overexpression of ICE alone was sufficient to trigger apoptosis, indicating its crucial role in the process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of interleukin-1beta-converting enzyme in apoptosis of irradiated retinoblastomas. Kondo, Y., Liu, J., Haqqi, T., et al.[2015]

Peptide inhibitors of the ICE protease family can prevent programmed cell death in motoneurons both in vitro and in vivo, suggesting a protective role against cell death due to trophic factor deprivation.

The study provides evidence that ICE or similar proteases are crucial in regulating not only motoneuron death but also the developmental cell death of interdigital cells, highlighting their importance in both neural and developmental processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vivo and in vitro. Milligan, CE., Prevette, D., Yaginuma, H., et al.[2019]

The interleukin-1 beta converting enzyme (ICE) is involved in programmed cell death in vertebrates, similar to its role in the nematode C. elegans, suggesting a conserved mechanism across species.

Microinjecting the crmA gene from cowpox virus into chicken neurons can inhibit ICE activity and prevent cell death caused by nerve growth factor deprivation, highlighting a potential therapeutic approach to protect neurons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of vertebrate neuronal death by the crmA gene. Gagliardini, V., Fernandez, PA., Lee, RK., et al.[2019]

References

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

The Watchman FLX Device: First European Experience and Feasibility of Intracardiac Echocardiography to Guide Implantation. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of intracardiac vs. transesophageal echocardiography for "one-stop" procedures of combined radiofrequency catheter ablation and left atrial appendage closure with the Watchman device in the treatment of atrial fibrillation. [2023]

3. Singapore pubmed.ncbi.nlm.nih.gov

Left atrial appendage occlusion with the WATCHMAN™ for stroke prevention in atrial fibrillation. [2022]

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

Intraprocedural and long-term incomplete occlusion of the left atrial appendage following placement of the WATCHMAN device: a single center experience. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Left Atrial Appendage Closure Under Intracardiac Echocardiographic Guidance: Feasibility and Comparison With Transesophageal Echocardiography. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Left Atrial Appendage Closure with Transcatheter-Delivered Devices. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Acute application of an interleukin-1 beta-converting enzyme-specific inhibitor delays axotomy-induced motoneurone death. [2019]

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

Watch for ICE in neurodegeneration. [2006]

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

Involvement of interleukin-1beta-converting enzyme in apoptosis of irradiated retinoblastomas. [2015]

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

Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vivo and in vitro. [2019]

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

Prevention of vertebrate neuronal death by the crmA gene. [2019]