Title
Reappraising myocardial fibrosis in severe aortic stenosis: An invasive and non-invasive study in 133 patients
Date Issued
21 February 2018
Access level
open access
Resource Type
journal article
Author(s)
Treibel T.A.
López B.
González A.
Schofield R.S.
Ravassa S.
Fontana M.
White S.K.
Disalvo C.
Roberts N.
Ashworth M.T.
Díez J.
Moon J.C.
United Kingdom
Publisher(s)
Oxford University Press
Abstract
Aims To investigate myocardial fibrosis (MF) in a large series of severe aortic stenosis (AS) patients using invasive biopsy and non-invasive imaging. Methods and results One hundred thirty-three patients with severe, symptomatic AS accepted for surgical aortic valve replacement underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) quantification. Intra-operative left ventricular (LV) biopsies were performed by needle or scalpel, yielding tissue with (n = 53) and without endocardium (n = 80), and compared with 10 controls. Myocardial fibrosis occurred in three patterns: (i) thickened endocardium with a fibrotic layer; (ii) microscopic scars, with a subendomyocardial predominance; and (iii) diffuse interstitial fibrosis. Collagen volume fraction (CVF) was elevated (P < 0.001) compared with controls, and higher (P < 0.001) in endocardium-containing samples with a decreasing CVF gradient from the subendocardium (P = 0.001). Late gadolinium enhancement correlated with CVF (P < 0.001) but not ECV. Both LGE and ECV correlated independently (P < 0.001) with N-terminal pro-brain natriuretic peptide and high-sensitivity-troponin T. High ECV was also associated with worse LV remodelling, left ventricular ejection fraction and functional capacity. Combining high ECV and LGE better identified patients with more adverse LV remodelling, blood biomarkers and histological parameters, and worse functional capacity than each parameter alone. Conclusion Myocardial fibrosis in severe AS is complex, but three main patterns exist: endocardial fibrosis, microscars (mainly in the subendomyocardium), and diffuse interstitial fibrosis. Neither histological CVF nor the CMR parameters ECV and LGE capture fibrosis in its totality. A combined, multi-parametric approach with ECV and LGE allows best stratification of AS patients according to the response of the myocardial collagen matrix.
Start page
699
End page
709
Volume
39
Issue
8
Language
English
OCDE Knowledge area
Sistema cardiaco, Sistema cardiovascular Radiología, Medicina nuclear, Imágenes médicas
Scopus EID
2-s2.0-85042599386
PubMed ID
Source
European Heart Journal
ISSN of the container
0195668X
Sponsor(s)
This report is independent research arising from a Doctoral Fellowship supported by the National Institute for Health Research (NIHR-DRF DRF-2013-06-102 to T.A.T.). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. J.C.M. is directly and indirectly supported by the University College London Hospitals NIHR Biomedical Research Centre and Biomedical Research Unit at Barts Hospital, respectively. This project was funded by the Carlos III Institute of Health, Spanish Ministry of Economy, Industry and Competitiveness (CIBERCV CB16/11/00483; RD12/0042/0009; and PI15/ 01909 co-financed by FEDER funds) and the European Commission (FP7 programme: HOMAGE project 2012-305507 and FIBRO-TARGETS project 2013-602904).
Sources of information: Directorio de Producción Científica Scopus