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

血栓形成 血栓 医学 白蛋白 血小板 抗血栓 体内 纤维蛋白 生物医学工程 内科学 核医学 免疫学 生物 生物技术
作者
Walid I. Saliba,Kenji Kawai,Yu Sato,Edward Kopesky,Qi Cheng,Saikat Ghosh,Thomáš Herbst,Rika Kawakami,Takao Konishi,Renu Virmani,Wael A. Jaber,Douglas Gibson,Manish H. Shah,Andrea Natale,Michael Gibson,David R. Holmes,Aloke V. Finn
出处
期刊:JACC: Clinical Electrophysiology [Elsevier]
卷期号:9 (8): 1555-1567 被引量:25
标识
DOI:10.1016/j.jacep.2023.04.013
摘要

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.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).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).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.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.

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