The novel proteomic signature for cardiac allograft vasculopathy

Wei, D. et al. (2022) The novel proteomic signature for cardiac allograft vasculopathy. ESC Heart Failure, 9(2), pp. 1216-1227. (doi: 10.1002/ehf2.13796) (PMID:35005846) (PMCID:PMC8934921)

[img] Text
262666.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.



Aims: Cardiac allograft vasculopathy (CAV) is the major long‐term complication after heart transplantation, leading to mortality and re‐transplantation. As available non‐invasive biomarkers are scarce for CAV screening, we aimed to identify a proteomic signature for CAV. Methods and results: We measured urinary proteome by capillary electrophoresis coupled with mass spectrometry in 217 heart transplantation recipients (mean age: 55.0 ± 14.4 years; women: 23.5%), including 76 (35.0%) patients with CAV diagnosed by coronary angiography. We randomly and evenly grouped participants into the derivation cohort (n = 108, mean age: 56.4 ± 13.8 years; women: 22.2%; CAV: n = 38) and the validation cohort (n = 109, mean age: 56.4 ± 13.8 years; women: 24.8%, CAV: n = 38), stratified by CAV. Using the decision tree‐based machine learning methods (extreme gradient boost), we constructed a proteomic signature for CAV discrimination in the derivation cohort and verified its performance in the validation cohort. The proteomic signature that consisted of 27 peptides yielded areas under the curve of 0.83 [95% confidence interval (CI): 0.75–0.91, P < 0.001] and 0.71 (95% CI: 0.60–0.81, P = 0.001) for CAV discrimination in the derivation and validation cohort, respectively. With the optimized threshold of 0.484, the sensitivity, specificity, and accuracy for CAV differentiation in the validation cohort were 68.4%, 73.2%, and 71.6%, respectively. With adjustment of potential clinical confounders, the signature was significantly associated with CAV [adjusted odds ratio: 1.31 (95% CI: 1.07–1.64) for per 0.1% increment in the predicted probability, P = 0.012]. Diagnostic accuracy significantly improved by adding the signature to the logistic model that already included multiple clinical risk factors, suggested by the integrated discrimination improvement of 9.1% (95% CI: 2.5–15.3, P = 0.005) and net reclassification improvement of 83.3% (95% CI: 46.7–119.5, P < 0.001). Of the 27 peptides, the majority were the fragments of collagen I (44.4%), collagen III (18.5%), collagen II (3.7%), collagen XI (3.7%), mucin‐1 (3.7%), xylosyltransferase 1 (3.7%), and protocadherin‐12 (3.7%). Pathway analysis performed in Reactome Pathway Database revealed that the multiple pathways involved by the signature were related to the pathogenesis of CAV, such as collagen turnover, platelet aggregation and coagulation, cell adhesion, and motility. Conclusions: This pilot study identified and validated a urinary proteomic signature that provided a potential approach for the surveillance of CAV. These proteins might provide insights into CAV pathological processes and call for further investigation into personalized treatment targets.

Item Type:Articles
Additional Information:The European Union (HEALTH-F7-305507 HOMAGE) and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601- uPROPHET) and Internal Funds KU Leuven (STG-18-00379) currently support the Studies Coordinating Centre in Leuven. APPREMED (URL: received a non-binding grant from OMRON Healthcare Co., Ltd., Kyoto, Japan.
Glasgow Author(s) Enlighten ID:Mischak, Professor Harald
Authors: Wei, D., Trenson, S., Van Keer, J. M., Melgarejo, J., Cutsforth, E., Thijs, L., He, T., Latosinska, A., Ciarka, A., Vanassche, T., Van Aelst, L., Janssens, S., Van Cleemput, J., Mischak, H., Staessen, J. A., Verhamme, P., and Zhang, Z.‐Y.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:ESC Heart Failure
ISSN (Online):2055-5822
Published Online:10 January 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in ESC Heart Failure 9(2): 1216-1227
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record