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A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography

Lookup NU author(s): Dr Chris Kotanidis

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. Background Coronary inflammation induces dynamic changes in the balance between water and lipid content in perivascular adipose tissue (PVAT), as captured by perivascular Fat Attenuation Index (FAI) in standard coronary CT angiography (CCTA). However, inflammation is not the only process involved in atherogenesis and we hypothesized that additional radiomic signatures of adverse fibrotic and microvascular PVAT remodelling, may further improve cardiac risk prediction. Methods and results: We present a new artificial intelligence-powered method to predict cardiac risk by analysing the radiomic profile of coronary PVAT, developed and validated in patient cohorts acquired in three different studies. In Study 1, adipose tissue biopsies were obtained from 167 patients undergoing cardiac surgery, and the expression of genes representing inflammation, fibrosis and vascularity was linked with the radiomic features extracted from tissue CT images. Adipose tissue wavelet-transformed mean attenuation (captured by FAI) was the most sensitive radiomic feature in describing tissue inflammation (TNFA expression), while features of radiomic texture were related to adipose tissue fibrosis (COL1A1 expression) and vascularity (CD31 expression). In Study 2, we analysed 1391 coronary PVAT radiomic features in 101 patients who experienced major adverse cardiac events (MACE) within 5 years of having a CCTA and 101 matched controls, training and validating a machine learning (random forest) algorithm (fat radiomic profile, FRP) to discriminate cases from controls (C-statistic 0.77 [95%CI: 0.62-0.93] in the external validation set). The coronary FRP signature was then tested in 1575 consecutive eligible participants in the SCOTHEART trial, where it significantly improved MACE prediction beyond traditional risk stratification that included risk factors, coronary calcium score, coronary stenosis, and high-risk plaque features on CCTA (D[C-statistic] = 0.126, P < 0.001). In Study 3, FRP was significantly higher in 44 patients presenting with acute myocardial infarction compared with 44 matched controls, but unlike FAI, remained unchanged 6 months after the index event, confirming that FRP detects persistent PVAT changes not captured by FAI. Conclusion: The CCTA-based radiomic profiling of coronary artery PVAT detects perivascular structural remodelling associated with coronary artery disease, beyond inflammation. A new artificial intelligence (AI)-powered imaging biomarker (FRP) leads to a striking improvement of cardiac risk prediction over and above the current state-of-the-art.


Publication metadata

Author(s): Oikonomou EK, Williams MC, Kotanidis CP, Desai MY, Marwan M, Antonopoulos AS, Thomas KE, Thomas S, Akoumianakis I, Fan LM, Kesavan S, Herdman L, Alashi A, Centeno EH, Lyasheva M, Griffin BP, Flamm SD, Shirodaria C, Sabharwal N, Kelion A, Dweck MR, Van Beek EJR, Deanfield J, Hopewell JC, Neubauer S, Channon KM, Achenbach S, Newby DE, Antoniades C

Publication type: Article

Publication status: Published

Journal: European Heart Journal

Year: 2019

Volume: 40

Issue: 43

Pages: 3529-3543

Print publication date: 14/11/2019

Online publication date: 03/09/2019

Acceptance date: 06/08/2019

Date deposited: 21/12/2022

ISSN (print): 0195-668X

ISSN (electronic): 1522-9645

Publisher: Oxford University Press

URL: https://doi.org/10.1093/eurheartj/ehz592

DOI: 10.1093/eurheartj/ehz592

PubMed id: 31504423


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Funding

Funder referenceFunder name
CH/09/002
CH/16/1/32013
Edinburgh and Lothians Health Foundation Trust
CZH/4/588
FS/14/55/30806
Heart Diseases Research Fund
FS/16/15/32047
National Institute for Health Research Oxford Biomedical Research Centre
RE/13/3/30183
TG/16/3/32687

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