Next-generation transcatheter aortic valve implantationCentral MessagePerspective

Objective: Transcatheter aortic valve implantation (TAVI) procedures are increasing rapidly, but the durability of tissue valve and periprocedural complications are not satisfactory. Immune reaction to the galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (α-Gal) and conventional processing protoc...

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Main Authors: Hong-Gook Lim, MD, PhD, Saeromi Jeong, MS, Gi Beom Kim, MD, PhD, Whal Lee, MD, PhD, Kuk Hui Son, MD, PhD, Yong Jin Kim, MD, PhD
Format: Article
Language:English
Published: Elsevier 2020-09-01
Series:JTCVS Open
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666273620300577
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author Hong-Gook Lim, MD, PhD
Saeromi Jeong, MS
Gi Beom Kim, MD, PhD
Whal Lee, MD, PhD
Kuk Hui Son, MD, PhD
Yong Jin Kim, MD, PhD
author_facet Hong-Gook Lim, MD, PhD
Saeromi Jeong, MS
Gi Beom Kim, MD, PhD
Whal Lee, MD, PhD
Kuk Hui Son, MD, PhD
Yong Jin Kim, MD, PhD
author_sort Hong-Gook Lim, MD, PhD
collection DOAJ
description Objective: Transcatheter aortic valve implantation (TAVI) procedures are increasing rapidly, but the durability of tissue valve and periprocedural complications are not satisfactory. Immune reaction to the galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (α-Gal) and conventional processing protocols of cardiac xenografts lead to calcification. Next-generation TAVI needs to be made with α-Gal–free xenografts by multiple anticalcification therapies to avoid immune rejection and enhance durability, and three-dimensional (3D) printing technology to improve the procedural safety. Methods: Porcine pericardia were decellularized and immunologically modified with α-galactosidase. The pericardia were treated by space filler, crosslinked with glutaraldehyde in organic solvent, and detoxified. The sheep-specific nitinol (nickel–titanium memory alloy) wire backbone was made from a 3D-printed model for ovine aortic root. After it passed the fitting test, we manufactured a self-expandable stented valve with the porcine pericardia mounted on the customized nitinol wire–based stent. After in vitro circulation using customized silicone aortic root, we performed TAVI in 9 sheep and obtained hemodynamic, radiological, immunohistopathological, and biochemical results. Results: The valve functioned well, with excellent stent fitting and good coronary flow under in vitro circulation. Sheep were sequentially scheduled to be humanely killed until 238 days after TAVI. Echocardiography and cardiac catheterization demonstrated good hemodynamic status and function of the aortic valve. The xenografts were well preserved without α-Gal immune reaction or calcification based on the immunological, radiographic, microscopic, and biochemical examinations. Conclusions: We proved preclinical safety and efficacy for next-generation α-Gal–free TAVI with multiple anticalcification therapies and 3D-printing technology. A future clinical study is warranted based on these promising preclinical results.
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spelling doaj.art-9a773d451b3540e5befdf436cb448f542022-12-21T23:55:22ZengElsevierJTCVS Open2666-27362020-09-0131424Next-generation transcatheter aortic valve implantationCentral MessagePerspectiveHong-Gook Lim, MD, PhD0Saeromi Jeong, MS1Gi Beom Kim, MD, PhD2Whal Lee, MD, PhD3Kuk Hui Son, MD, PhD4Yong Jin Kim, MD, PhD5Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, KoreaDepartment of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, KoreaDepartment of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, KoreaDepartment of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, KoreaDepartment of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon, KoreaDepartment of Thoracic and Cardiovascular Surgery, Sejong General Hospital, Bucheon, Korea; Address for reprints: Yong Jin Kim, MD, PhD, Department of Thoracic and Cardiovascular Surgery, Sejong General Hospital, 51-7, Hohyeon-ro 489beon-gil, Bucheon-si, Gyeonggi-do 14755, South Korea.Objective: Transcatheter aortic valve implantation (TAVI) procedures are increasing rapidly, but the durability of tissue valve and periprocedural complications are not satisfactory. Immune reaction to the galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (α-Gal) and conventional processing protocols of cardiac xenografts lead to calcification. Next-generation TAVI needs to be made with α-Gal–free xenografts by multiple anticalcification therapies to avoid immune rejection and enhance durability, and three-dimensional (3D) printing technology to improve the procedural safety. Methods: Porcine pericardia were decellularized and immunologically modified with α-galactosidase. The pericardia were treated by space filler, crosslinked with glutaraldehyde in organic solvent, and detoxified. The sheep-specific nitinol (nickel–titanium memory alloy) wire backbone was made from a 3D-printed model for ovine aortic root. After it passed the fitting test, we manufactured a self-expandable stented valve with the porcine pericardia mounted on the customized nitinol wire–based stent. After in vitro circulation using customized silicone aortic root, we performed TAVI in 9 sheep and obtained hemodynamic, radiological, immunohistopathological, and biochemical results. Results: The valve functioned well, with excellent stent fitting and good coronary flow under in vitro circulation. Sheep were sequentially scheduled to be humanely killed until 238 days after TAVI. Echocardiography and cardiac catheterization demonstrated good hemodynamic status and function of the aortic valve. The xenografts were well preserved without α-Gal immune reaction or calcification based on the immunological, radiographic, microscopic, and biochemical examinations. Conclusions: We proved preclinical safety and efficacy for next-generation α-Gal–free TAVI with multiple anticalcification therapies and 3D-printing technology. A future clinical study is warranted based on these promising preclinical results.http://www.sciencedirect.com/science/article/pii/S2666273620300577xenograftheart valvebioprosthesisbioengineeringbiomaterialscalcification
spellingShingle Hong-Gook Lim, MD, PhD
Saeromi Jeong, MS
Gi Beom Kim, MD, PhD
Whal Lee, MD, PhD
Kuk Hui Son, MD, PhD
Yong Jin Kim, MD, PhD
Next-generation transcatheter aortic valve implantationCentral MessagePerspective
JTCVS Open
xenograft
heart valve
bioprosthesis
bioengineering
biomaterials
calcification
title Next-generation transcatheter aortic valve implantationCentral MessagePerspective
title_full Next-generation transcatheter aortic valve implantationCentral MessagePerspective
title_fullStr Next-generation transcatheter aortic valve implantationCentral MessagePerspective
title_full_unstemmed Next-generation transcatheter aortic valve implantationCentral MessagePerspective
title_short Next-generation transcatheter aortic valve implantationCentral MessagePerspective
title_sort next generation transcatheter aortic valve implantationcentral messageperspective
topic xenograft
heart valve
bioprosthesis
bioengineering
biomaterials
calcification
url http://www.sciencedirect.com/science/article/pii/S2666273620300577
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