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

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Citation: JACC. Clinical Electrophysiology. 2023 May 07PMID: 37204356Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: IN PROCESS -- NOT YET INDEXED | Year: 2023ISSN:
  • 2405-500X
Name of journal: JACC. Clinical electrophysiologyAbstract: 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.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. Copyright � 2023 The Authors. Published by Elsevier Inc. All rights reserved.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).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).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 [41.0-58.3] mm2 vs 20.6 [17.2-26.6] mm2; P = 0.03) and significantly less platelet adhesion (44.7% [27.2%-60.2%] vs 60.9% [39.9%-70.1%]; P < 0.01) on FP-WM. Porcine implants showed significantly greater EC by scanning electron microscopy (87.7% [83.4%-92.3%] vs 68.2% [47.6%-72.8%]; P = 0.03), and higher vascular endothelial-cadherin/p120-catenin expression after 3 months on FP-WM compared with WM.All authors: Cheng Q, Finn AV, Ghosh SKB, Gibson DN, Gibson M, Herbst TJ, Holmes DR Jr, Jaber WA, Kawai K, Kawakami R, Konishi T, Kopesky E, Natale A, Saliba WI, Sato Y, Shah M, Virmani RFiscal year: FY2023Digital Object Identifier: Date added to catalog: 2023-06-28
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Journal Article MedStar Authors Catalog Article 37204356 Available 37204356

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.

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. Copyright � 2023 The Authors. Published by Elsevier Inc. All rights reserved.

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).

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).

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 [41.0-58.3] mm2 vs 20.6 [17.2-26.6] mm2; P = 0.03) and significantly less platelet adhesion (44.7% [27.2%-60.2%] vs 60.9% [39.9%-70.1%]; P < 0.01) on FP-WM. Porcine implants showed significantly greater EC by scanning electron microscopy (87.7% [83.4%-92.3%] vs 68.2% [47.6%-72.8%]; P = 0.03), and higher vascular endothelial-cadherin/p120-catenin expression after 3 months on FP-WM compared with WM.

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