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; 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

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, Aloke V. Finn

Cardiovascular Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1555-1567
Number of pages	13
Journal	JACC: Clinical Electrophysiology
Volume	9
Issue number	8
DOIs	https://doi.org/10.1016/j.jacep.2023.04.013
State	Published - Aug 2023

Keywords

WATCHMAN FLX
device-related thromboembolism
fluoropolymer-coated WATCHMAN FLX
left atrial appendage closure

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1016/j.jacep.2023.04.013

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Saliba, W. I., Kawai, K., Sato, Y., Kopesky, E., Cheng, Q., Ghosh, S. K. B., Herbst, T. J., Kawakami, R., Konishi, T., Virmani, R., Jaber, W. A., Gibson, D. N., Shah, M., Natale, A., Gibson, M., Holmes, D. R., & Finn, A. V. (2023). Enhanced Thromboresistance and Endothelialization of a Novel Fluoropolymer-Coated Left Atrial Appendage Closure Device. JACC: Clinical Electrophysiology, 9(8), 1555-1567. https://doi.org/10.1016/j.jacep.2023.04.013

Saliba, WI, Kawai, K, Sato, Y, Kopesky, E, Cheng, Q, Ghosh, SKB, Herbst, TJ, Kawakami, R, Konishi, T, Virmani, R, Jaber, WA, Gibson, DN, Shah, M, Natale, A, Gibson, M, Holmes, DR & Finn, AV 2023, 'Enhanced Thromboresistance and Endothelialization of a Novel Fluoropolymer-Coated Left Atrial Appendage Closure Device', JACC: Clinical Electrophysiology, vol. 9, no. 8, pp. 1555-1567. https://doi.org/10.1016/j.jacep.2023.04.013

@article{0ed18737db8041feab1853aea8602003,

title = "Enhanced Thromboresistance and Endothelialization of a Novel Fluoropolymer-Coated Left Atrial Appendage Closure Device",

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",

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

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

doi = "10.1016/j.jacep.2023.04.013",

language = "English (US)",

volume = "9",

pages = "1555--1567",

journal = "JACC: Clinical Electrophysiology",

issn = "2405-500X",

publisher = "Elsevier USA",

number = "8",

}

TY - JOUR

T1 - Enhanced Thromboresistance and Endothelialization of a Novel Fluoropolymer-Coated Left Atrial Appendage Closure Device

AU - Saliba, Walid I.

AU - Kawai, Kenji

AU - Sato, Yu

AU - Kopesky, Edward

AU - Cheng, Qi

AU - Ghosh, Saikat Kumar B.

AU - Herbst, Thomas J.

AU - Kawakami, Rika

AU - Konishi, Takao

AU - Virmani, Renu

AU - Jaber, Wael A.

AU - Gibson, Douglas N.

AU - Shah, Manish

AU - Natale, Andrea

AU - Gibson, Michael

AU - Holmes, David R.

AU - Finn, Aloke V.

PY - 2023/8

Y1 - 2023/8

N2 - 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.

AB - 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.

KW - WATCHMAN FLX

KW - device-related thromboembolism

KW - fluoropolymer-coated WATCHMAN FLX

KW - left atrial appendage closure

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SN - 2405-500X

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

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