Metabolic pathways associated with right ventricular adaptation to pulmonary hypertension: Three dimensional analysis of cardiac magnetic resonance imaging

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Title: Metabolic pathways associated with right ventricular adaptation to pulmonary hypertension: Three dimensional analysis of cardiac magnetic resonance imaging
Authors: Attard, M
Dawes, T
Simoes Monteiro de Marvao, A
Biffi, C
Shi, W
Wharton, J
Rhodes, C
Ghataorhe, P
Gibbs, J
Howard, L
Rueckert, D
Wilkins, M
O'Regan, D
Item Type: Journal Article
Abstract: Aims We sought to identify metabolic pathways associated with right ventricular (RV) adaptation to pulmonary hypertension (PH). We evaluated candidate metabolites, previously associated with survival in pulmonary arterial hypertension, and used automated image segmentation and parametric mapping to model their relationship to adverse patterns of remodelling and wall stress. Methods and results In 312 PH subjects (47.1% female, mean age 60.8 ± 15.9 years), of which 182 (50.5% female, mean age 58.6 ± 16.8 years) had metabolomics, we modelled the relationship between the RV phenotype, haemodynamic state, and metabolite levels. Atlas-based segmentation and co-registration of cardiac magnetic resonance imaging was used to create a quantitative 3D model of RV geometry and function—including maps of regional wall stress. Increasing mean pulmonary artery pressure was associated with hypertrophy of the basal free wall (β = 0.29) and reduced relative wall thickness (β = −0.38), indicative of eccentric remodelling. Wall stress was an independent predictor of all-cause mortality (hazard ratio = 1.27, P = 0.04). Six metabolites were significantly associated with elevated wall stress (β = 0.28–0.34) including increased levels of tRNA-specific modified nucleosides and fatty acid acylcarnitines, and decreased levels (β = −0.40) of sulfated androgen. Conclusion Using computational image phenotyping, we identify metabolic profiles, reporting on energy metabolism and cellular stress-response, which are associated with adaptive RV mechanisms to PH.
Issue Date: 7-Dec-2018
Date of Acceptance: 27-Oct-2018
URI: http://hdl.handle.net/10044/1/65817
DOI: https://dx.doi.org/10.1093/ehjci/jey175
ISSN: 2047-2412
Publisher: Oxford University Press (OUP)
Journal / Book Title: EHJ Cardiovascular Imaging / European Heart Journal - Cardiovascular Imaging
Copyright Statement: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: British Heart Foundation
GlaxoSmithKline Services Unlimited
Imperial College Healthcare NHS Trust- BRC Funding
British Heart Foundation
Medical Research Council (MRC)
The Academy of Medical Sciences
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
British Heart Foundation
Imperial College Healthcare NHS Trust- BRC Funding
Mason Medical Research Foundation
Funder's Grant Number: RE/08/002/23906
COL011953
RD410
FS/15/59/31839
PO4050673447
nil
RDC04
NH/17/1/32725
RDB02
N/A
Publication Status: Published online
Article Number: jey175
Online Publication Date: 2018-12-07
Appears in Collections:Computing
Clinical Sciences
Imaging Sciences
National Heart and Lung Institute
Molecular Sciences
Department of Medicine
Faculty of Medicine



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