Left Atrial Appendage Closure With the New WATCHMAN FLX Pro Device: Interview With Andrea Natale, MD, FACC

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EP LAB DIGEST. 2023;23(11):12-13.

In September 2023, Boston Scientific, the manufacturer of the WATCHMAN FLX Left Atrial Appendage Closure (LAAC) device, received approval from the FDA for its latest WATCHMAN FLX Pro LAAC device. Designed to further advance the procedural performance and safety of the WATCHMAN technology, which is indicated to reduce stroke risk in patients with non-valvular atrial fibrillation (NVAF) who need an alternative to oral anticoagulation (OAC) therapy, the device now features a thromboresistant polymer coating, visualization markers, and a broader size matrix to treat a wider range of patients.

In this interview, we speak with Andrea Natale, MD, FACC, FESC, FHRS, Executive Medical Director of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin, Texas, and Clinical Associate Professor of Medicine at Metro Health Medical Center, Case Western Reserve University School of Medicine, in Cleveland, Ohio. 

Can you briefly describe why and how LAAC is performed? 

Atrial fibrillation (AFib or AF) is the most common type of rhythm disorder of the heart seen in the clinical practice, and it is estimated that about 12 million people in the United States will have AFib by 2030.¹ AFib can lead to a number of heart-related complications, and it can also increase a person’s risk for stroke fivefold.² When patients are in AFib, blood flow becomes stagnant, which can cause clots to form, especially in the LAA. The LAA can be visualized as a pouch with an uneven surface and significant trabeculation, or small, rod-like bundles of muscle fibers. Stroke-causing clots from AFib almost always start in the LAA. Thus, it was determined that the best strategy would be to close the LAA with a device to reduce the risk of clot formation in that location. Prior to LAAC therapy, the only option for patients was OAC medication, which carries bleeding risks that compound over years. 

The earlier and highly successful WATCHMAN technology, the WATCHMAN FLX device, is a device implanted in the LAA during a one-time minimally invasive procedure.³ Using a standard percutaneous technique, a guidewire and vessel dilator are inserted into the femoral vein. After the access sheath is advanced over the guidewire into the LA and then navigated into the distal portion of the LAA over a catheter, the WATCHMAN FLX device is deployed. Then, heart tissue grows over the device and the LAA is permanently sealed. Patients remain on an OAC or dual antiplatelet therapy (DAPT) for at least 45 days.⁴ 

What are the short-term and long-term outcomes patients today can expect after receiving a WATCHMAN device? 

In a real-world study of over 66,000 patients who received a WATCHMAN FLX device, the implant success rate was 98%. Reinforcing the strong safety profile seen in clinical trials, a low 0.49% of patients experienced an adverse event related to the procedure either within the first week or during their hospital stay, whichever was longer.⁵

In the first 45 days post procedure, the all-cause death rate was 0.84%. Strokes occurred in 0.32% of patients, systemic embolism in 0.01%, and pericardial effusion in 0.5%. At one year, 1.2% of patients had experienced an ischemic stroke and 1.6% of patients experienced a stroke of any kind. 

With the unique design enhancements made to the new WATCHMAN FLX Pro device, we expect to see continued positive outcomes with the potential for additional benefits for physicians and their patients. 

Given its recent FDA approval, how might the WATCHMAN FLX Pro device affect the LAAC procedure and outcomes?

Built on the proven safety profile of the WATCHMAN FLX device, the new WATCHMAN FLX Pro device is designed to enhance the healing process and optimize the therapy for a wider range of patients. Even though the risk of device-associated thrombus formation is very low with the WATCHMAN FLX device, it is still possible in rare instances, especially in the setting of non-compliance to oral anticoagulation.⁶ The WATCHMAN FLX Pro device features a thromboresistant polymer coating (PVDF-HFP) called HEMOCOAT that is designed to reduce the risk and incidence of device-related thrombus (DRT) and enable better endothelization.

This coating is designed to alter the first stage of the body’s natural healing response post procedure, leading to 3 key benefits that help control the healing process: less platelet activation, less inflammation, and less thrombus formation. Notably, the coating has a history of safe use on permanently implantable, blood-contacting cardiac medical devices.

The WATCHMAN FLX Pro device also has features such as radiopaque markers and a larger size option (40 mm), both of which can help reduce the risk of leaks. Think about the device and LAA as concentric spheres. We have to stretch that tissue in order to eliminate space between the device and the wall of the appendage to avoid any leaks. The radiopaque markers on the WATCHMAN FLX Pro make the process of deployment easier and help position the device more accurately. Additionally, because not all patients have the same size appendage, having a 40-mm size option expands the number of patients that are potential candidates for this technology. A larger appendage tends to be more prevalent in East-Asian populations,⁷ but even in other populations, we do see patients where the WATCHMAN FLX device’s 35-mm size is too small. 

How do you define the healing process post LAAC and how is the WATCHMAN FLX Pro coating designed to improve the healing process?

What we expect is an endothelization process over several months where the body covers the surface of the implant with the lining of the heart. What we have seen in preclinical testing for the WATCHMAN FLX Pro device is that while some thrombus formation may still occur with the previous-generation WATCHMAN FLX device, there is less of this phenomenon with the coated WATCHMAN FLX Pro technology, and the healing is more homogeneous and faster. These preclinical outcomes are all signs that the risk of thrombus formation might be reduced with this new LAAC device.

Is the WATCHMAN FLX device currently coupled with post-procedural medications to help promote healing or prevent complications post procedure? 

Patients are usually kept on a blood thinner for about 45 days post procedure, then moved to DAPT (typically aspirin and clopidogrel) for up to 6 months, and then to low-dose aspirin alone. A consequence of post-implant drug therapy used to mitigate thrombus and allow device healing is bleeding risk. As such, a more hemocompatible LAAC device like the WATCHMAN FLX Pro could serve as a groundbreaking innovation by enabling faster, more controlled healing and a less aggressive post-implant drug therapy, thus presenting another opportunity to reduce a risk that can potentially negatively impact a patient’s outcome. 

Is the WATCHMAN FLX Pro coating drug-eluting? 

No, it is not drug-eluting. The inert HEMOCOAT coating is permanent, and it is designed to reduce inflammation and favor endothelization, both of which we have seen in the preclinical testing.

Are there any drawbacks or limitations unique to the WATCHMAN FLX Pro device? 

We have not seen any issues in preclinical studies that would raise concern. As clinicians and scientists, we are cautiously optimistic. The preclinical testing has been done in a model that tends to have more thrombus formation and more aggressive inflammation than what is typically seen in humans. We need experience in patients, but what we have seen in the preclinical studies is reassuring. 

Can you share more about the preclinical studies of the WATCHMAN FLX Pro device?

I have worked with a group of physicians to compare the WATCHMAN FLX and WATCHMAN FLX Pro implants in an in vivo model where we used serial imaging to evaluate what happened to the surface, and afterward, reviewed the histology. The WATCHMAN FLX Pro device with the HEMOCOAT coating showed less thrombus formation in vivo and resulted in a smoother healing process. We also looked at the process of platelet activation and coagulation activation in an in vitro model that also demonstrated lower levels of inflammation and platelet activation. 

Preclinical data presented at Heart Rhythm 2023, the Society’s 44th annual meeting, built upon previously presented evidence demonstrating that the thromboresistant coating on the WATCHMAN FLX Pro device may further reduce the risk of DRT and result in faster and more uniform tissue coverage on the device at 45 days post implant.

As also recently published in JACC: Clinical Electrophysiology,⁸ canines implanted with WATCHMAN FLX Pro exhibited significantly less device-related thrombus at 45 days than those implanted with the WATCHMAN FLX device. In vitro experiments showed significantly greater albumin adsorption and significantly less platelet adhesion, as well. 

What is next in the clinical pipeline for the WATCHMAN FLX Pro device? Any post-market studies? 

To start, Boston Scientific began the WATCHMAN FLX Pro CT pilot study in early 2023. This prospective, single-center premarket study at Aarhus University Hospital is using multiple imaging modalities to assess post-procedural tissue coverage around the device and the relationship, if any, to the risk of stroke. The trial is anticipated to be completed in the second half of 2024, and we look forward to seeing the outcomes.

The company is also initiating enrollment in the post-market HEAL-LAA study,⁹ which will follow outcomes of approximately 1000 patients with NVAF who receive the WATCHMAN FLX Pro device.

Aside from this study, the plan is to do a post-approval study where patients will be randomized to different antithrombotic post-implant regimens. Compared to the standard of care, which is DAPT, study regimens will be simplified to either start with single antiplatelet therapy alone (low-dose aspirin or a P2Y12 inhibitor) or a half dose of a blood thinner for 3 months. Through this work, we expect to be able to simplify post-implant medical management for patients. 

This article is sponsored by Boston Scientific. Andrea Natale is a consultant for Boston Scientific and was not paid for his participation in this article. 

Please visit watchman.com/implanter for complete warnings, precautions, and instructions for use. 

References

1. Atrial Fibrillation. US Centers for Disease Control and Prevention. Published October 14, 2022. Accessed July 26, 2023. https://www.cdc.gov/heartdisease/atrial_fibrillation.htm

2. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):e199-267. doi:10.1161/CIR.0000000000000041

3. WATCHMAN clinical evidence for physicians. Boston Scientific. Accessed July 26, 2023. https://www.watchman.com/en-us-hcp/clinical-evidence.html

4. About the procedure. Watchman. Boston Scientific. Accessed July 26, 2023. https://www.watchman.com/en-us-hcp/about-the-procedure.html?utm_source=Google&utm_campaign=9970634782&utm_term=watchman%20procedure&utm_medium=cpc&utm_content=101024345256&gclid=CjwKCAjwvdajBhBEEiwAeMh1U0VoAKRycfZNo4h4KQD1bsnlih3QmajGVeaFP-mcVzSXXmhjaKZqbRoCRswQAvD_BwE 

5. SURPASS 1 year results. Watchman. Boston Scientific. Accessed July 26, 2023. https://www.watchman.com/en-us-implanter/clinical-evidence/surpass-one-year-results.html

6. Dhaduk N, Vainrib AF, Bamira D, et al. Device-associated thrombus with Watchman FLX left atrial appendage closure device: a report of two cases. CASE (Phila). 2023;7(6):226-232. doi:10.1016/j.case.2023.01.010

7. Phillips K, Santoso T, Sanders P, et al. Left atrial appendage closure with WATCHMAN in Asian patients: 2 year outcomes from the WASP registry. Int J Cardiol Heart Vasc. 2019;23:100358. doi:10.1016/j.ijcha.2019.100358

8. Saliba WI, Kawai K, Sato Y, et al. Enhanced thromboresistance and endothelialization of a novel fluoropolymer-coated left atrial appendage closure device. JACC: Clin Electrophysiol. 2023;9(8 Pt 2):1555-1567. doi:10.1016/j.jacep.2023.04.013

9. HEAL-LAA clinical trial. ClinicalTrials.gov. Accessed October 5, 2023. https://tinyurl.com/2amvf84r