Enhanced Thromboresistance and Endothelialization of a Novel Fluoropolymer-Coated Left Atrial Appendage Closure Device

Walid I Saliba; Kenji Kawai; Yu Sato; Edward Kopesky; Qi Cheng; Saikat Kumar B Ghosh; Thomas J Herbst; Rika Kawakami; Takao Konishi; Renu Virmani; Wael A Jaber; Douglas N Gibson; Manish Shah; Andrea Natale; Michael Gibson; David R Holmes Jr; Aloke V Finn

doi:10.1016/j.jacep.2023.04.013

Enhanced Thromboresistance and Endothelialization of a Novel Fluoropolymer-Coated Left Atrial Appendage Closure Device

JACC Clin Electrophysiol. 2023 Aug;9(8 Pt 2):1555-1567. doi: 10.1016/j.jacep.2023.04.013. Epub 2023 May 18.

Authors

Walid I Saliba¹, Kenji Kawai², Yu Sato², Edward Kopesky³, Qi Cheng², Saikat Kumar B Ghosh², Thomas J Herbst³, Rika Kawakami², Takao Konishi², Renu Virmani², Wael A Jaber¹, Douglas N Gibson⁴, Manish Shah⁵, Andrea Natale⁶, Michael Gibson⁷, David R Holmes Jr⁸, Aloke V Finn⁹

Affiliations

¹ Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
² CVPath Institute, Gaithersburg, Maryland, USA.
³ Boston Scientific Corporation, Maple Grove, Minnesota, USA.
⁴ Prebys Cardiovascular Institute, Scripps Clinic, San Diego, California, USA.
⁵ Department of Medicine, MedStar Georgetown Washington Hospital Center, Washington, DC.
⁶ Department of Electrophysiology, Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Internal Medicine, Metro Health Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
⁷ Department of Medicine, Beth Israel Medical Center, Boston, Massachusetts, USA.
⁸ Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁹ CVPath Institute, Gaithersburg, Maryland, USA; University of Maryland, School of Medicine, Baltimore, Maryland, USA. Electronic address: afinn@cvpath.org.

PMID: 37204356
DOI: 10.1016/j.jacep.2023.04.013

Abstract

Background: Device-related thrombus (DRT) after left atrial appendage closure (LAAC) procedures is a rare but potentially serious event. Thrombogenicity and delayed endothelialization play a role in the development of DRT. Fluorinated polymers are known to have thromboresistant properties that may favorably modulate the healing response to an LAAC device.

Objectives: The goal of this study was to compare the thrombogenicity and endothelial coverage (EC) after LAAC between the conventional uncoated WATCHMAN FLX (WM) and a novel fluoropolymer-coated WATCHMAN FLX (FP-WM).

Methods: Canines were randomized for implantation with WM or FP-WM devices and given no postimplant antithrombotic/antiplatelet agents. The presence of DRT was monitored by using transesophageal echocardiography and verified histologically. The biochemical mechanisms associated with coating were assessed by using flow loop experiments to quantify albumin adsorption, platelet adhesion, and porcine implants to quantify EC and the expression of markers of endothelial maturation (ie, vascular endothelial-cadherin/p120-catenin).

Results: Canines implanted with FP-WM exhibited significantly less DRT at 45 days than those implanted with WM (0% vs 50%; P < 0.05). In vitro experiments showed significantly greater albumin adsorption (52.8 [IQR: 41.0-58.3] mm² vs 20.6 [IQR: 17.2-26.6] mm²; P = 0.03) and significantly less platelet adhesion (44.7% [IQR: 27.2%-60.2%] vs 60.9% [IQR: 39.9%-70.1%]; P < 0.01) on FP-WM. Porcine implants showed significantly greater EC by scanning electron microscopy (87.7% [IQR: 83.4%-92.3%] vs 68.2% [IQR: 47.6%-72.8%]; P = 0.03), and higher vascular endothelial-cadherin/p120-catenin expression after 3 months on FP-WM compared with WM.

Conclusions: The FP-WM device showed significantly less thrombus and reduced inflammation in a challenging canine model. Mechanistic studies indicated that the fluoropolymer-coated device binds more albumin, leading to reduced platelet binding, less inflammation, and greater EC.

Keywords: WATCHMAN FLX; device-related thromboembolism; fluoropolymer-coated WATCHMAN FLX; left atrial appendage closure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Atrial Appendage* / diagnostic imaging
Atrial Appendage* / surgery
Atrial Fibrillation*
Dogs
Fluorocarbon Polymers
Inflammation
Prosthesis Design
Swine
Thrombosis* / complications
Treatment Outcome

Substances

Fluorocarbon Polymers