Transcatheter Aortic Heart Valves: Histological Analysis Providing Insight to Leaflet Thickening and Structural Valve Degeneration.
Aged
Aged, 80 and over
Aortic Valve
/ enzymology
Calcinosis
/ etiology
Device Removal
Endothelial Cells
/ pathology
Female
Fibrosis
Heart Valve Prosthesis
Humans
Male
Matrix Metalloproteinase 1
/ metabolism
Prosthesis Design
Prosthesis Failure
Registries
Retrospective Studies
Thrombosis
/ etiology
Time Factors
Transcatheter Aortic Valve Replacement
/ adverse effects
Treatment Outcome
TAVR
leaflet thrombosis
structural valve degeneration
transcatheter heart valves
Journal
JACC. Cardiovascular imaging
ISSN: 1876-7591
Titre abrégé: JACC Cardiovasc Imaging
Pays: United States
ID NLM: 101467978
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
13
02
2018
revised:
09
05
2018
accepted:
22
06
2018
pubmed:
19
11
2018
medline:
14
1
2020
entrez:
19
11
2018
Statut:
ppublish
Résumé
This study investigated processes causing leaflet thickening and structural valve degeneration (SVD). Although transcatheter aortic valve replacement (TAVR) has changed the treatment of aortic stenosis, concerns remain regarding SVD, potentially related to valve thrombosis and thickening, based on studies using computed tomography (CT). Detailed histological analyses are provided to help attain insights into these processes. Explanted transcatheter heart valves (THVs) were evaluated for thrombosis, fibrosis, and calcification for quantification of leaflet thickness. Immunohistochemical and microscopy approaches were used to investigate SVD-associated mechanisms. THVs (n = 23) were obtained from 22 patients (median 81 years of age; 50% male) from 0 to 2,583 days post TAVR. Maximal leaflet thickness increased relative to implant duration (ρ = 0.427; p = 0.027). THVs explanted after >2 years were thicker than those explanted after <2 years (p = 0.007). All THVs had adherent thrombus on both aortic and ventricular sides, which beyond 60 days was seen in combination with fibrosis and beyond 4 years had calcification. Early thrombus formation (<60 days) occurred despite rapid endothelialization with an abnormal hyperplastic phenotype. Fibrosis was observed in 6 patients on both the aortic and the ventricular THV surfaces, remodeled over time, and was associated with matrix metalloproteinase-1 expression. Five THVs showed overt calcification associated with adherent thrombus and fibrosis. There is a time-dependent degeneration of THVs consisting of thrombus formation, endothelial hyperplasia, fibrosis, tissue remodeling, proteinase expression, and calcification. Future investigation is needed to further understand these mechanisms contributing to leaflet thickening and SVD.
Sections du résumé
OBJECTIVES
This study investigated processes causing leaflet thickening and structural valve degeneration (SVD).
BACKGROUND
Although transcatheter aortic valve replacement (TAVR) has changed the treatment of aortic stenosis, concerns remain regarding SVD, potentially related to valve thrombosis and thickening, based on studies using computed tomography (CT). Detailed histological analyses are provided to help attain insights into these processes.
METHODS
Explanted transcatheter heart valves (THVs) were evaluated for thrombosis, fibrosis, and calcification for quantification of leaflet thickness. Immunohistochemical and microscopy approaches were used to investigate SVD-associated mechanisms.
RESULTS
THVs (n = 23) were obtained from 22 patients (median 81 years of age; 50% male) from 0 to 2,583 days post TAVR. Maximal leaflet thickness increased relative to implant duration (ρ = 0.427; p = 0.027). THVs explanted after >2 years were thicker than those explanted after <2 years (p = 0.007). All THVs had adherent thrombus on both aortic and ventricular sides, which beyond 60 days was seen in combination with fibrosis and beyond 4 years had calcification. Early thrombus formation (<60 days) occurred despite rapid endothelialization with an abnormal hyperplastic phenotype. Fibrosis was observed in 6 patients on both the aortic and the ventricular THV surfaces, remodeled over time, and was associated with matrix metalloproteinase-1 expression. Five THVs showed overt calcification associated with adherent thrombus and fibrosis.
CONCLUSIONS
There is a time-dependent degeneration of THVs consisting of thrombus formation, endothelial hyperplasia, fibrosis, tissue remodeling, proteinase expression, and calcification. Future investigation is needed to further understand these mechanisms contributing to leaflet thickening and SVD.
Identifiants
pubmed: 30448122
pii: S1936-878X(18)30915-X
doi: 10.1016/j.jcmg.2018.06.028
pii:
doi:
Substances chimiques
MMP1 protein, human
EC 3.4.24.7
Matrix Metalloproteinase 1
EC 3.4.24.7
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
135-145Subventions
Organisme : British Heart Foundation
ID : FS/13/77/30488
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/14/78/31020
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/16/10/32375
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT103782AIA
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.