Preview

Kardiologiia

Advanced search

Biomarkers of Progressive Chronic Heart Failure: The Results of Blood Proteomic Analysis

https://doi.org/10.18087/cardio.2025.12.n3101

Abstract

Aim    To develop of a protein panel to identify patients with progressive chronic heart failure with reduced left ventricular ejection fraction (HFrEF) based on proteomic analysis of blood fractions.
Material and methods    The study included 81 patients with HFrEF associated with postinfarction myocardial scarring or dilated cardiomyopathy. Patients were enrolled both in a stable period (n=48) and with signs of decompensated heart failure (n=33). Proteomic chromatography-mass-spectrometric analysis of blood plasma and extracellular vesicles (EVs) was performed in all patients. The analysis identified proteins differentially represented between groups in each blood compartment. The effectiveness of using individual proteins and integrated protein panels based on these proteins to identify patients with progressive HFrEF was assessed.
Results    Twelve plasma proteins and one BB fraction protein were detected, the concentration of which significantly differed between the groups with and without decompensated HFrEF. Individual protein concentrations demonstrated approximately the same quality indicators in identifying patients with decompensated HF as the classical HF marker, the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). Accordingly, we developed two integrated panels including the concentrations of NT-proBNP and several plasma or BB fraction proteins. The plasma panel included five proteins (APOE, LPA, C7, GPLD1, and TF), and the BB panel included two proteins (APOC4, FGB); the proteins are designated in accordance with their genes in the UniProt database. The plasma protein panel demonstrated the highest efficiency in identifying patients with decompensated HF, with a sensitivity of 78.8% and a specificity of 87.5%.
Conclusion    The study resulted in the development of a plasma protein panel that can identify patients with progressive chronic HFrEF. This panel is more effective than previously described or currently used biomarkers. However, further research is needed to implement this protein panel into clinical practice.

About the Authors

A. S. Anisimova
Davydovsky Municipal Clinical Hospital
Russian Federation

cardiologist of I.V. Davydovsky Moscow City Clinical Hospital, Moscow Department of Healthcare

Moscow, Russia



I. A. Molodtsov
Davydovsky Municipal Clinical Hospital
Russian Federation

analyst of I.V. Davydovsky Moscow City Clinical Hospital, Moscow Department of Healthcare

Moscow, Russia



A. S. Kononikhin
Skolkovo Institute of Science and Technologies
Russian Federation

Senior Research Scientist, Skolkovo Institute of Science and Technology,

Moscow, Russia



E. L. Kordzaya
Davydovsky Municipal Clinical Hospital
Russian Federation

cardiologist of I.V. Davydovsky Moscow City Clinical Hospital, Moscow Department of Healthcare

Moscow, Russia



A. E. Bugrova
Skolkovo Institute of Science and Technologies; Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences
Russian Federation

Senior Research Scientist, Emanuel Institute of Biochemical Physics, Russian Academy of Science

Moscow, Russia



E. V. Maryukhnich
Davydovsky Municipal Clinical Hospital
Russian Federation

junior researcher of Research Department in I.V. Davydovsky Moscow City Clinical Hospital, Moscow Department of Healthcare

Moscow, Russia



M. I. Indeykina
Skolkovo Institute of Science and Technologies; Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences
Russian Federation

staff scientist, Emanuel Institute of Biochemical Physics, Russian Academy of Science

Moscow, Russia



A. V. Tvorogova
Davydovsky Municipal Clinical Hospital
Russian Federation

junior researcher of Research Department in I.V. Davydovsky Moscow City Clinical Hospital, Moscow Department of Healthcare

Moscow, Russia



E. N. Nikolaev
Skolkovo Institute of Science and Technologies
Russian Federation

corresponding member of the Russian Academy of Sciences, Head of Laboratory of mass-spectrometry

Moscow, Russia



E. Yu. Vasilieva
Davydovsky Municipal Clinical Hospital; Russian University of Medicine
Russian Federation

president of I.V. Davydovsky Moscow City Clinical Hospital, Moscow Department of Healthcare, Russian Federation; professor, head of Laboratory of atherothrombosis in Russian University of Medicine

Moscow, Russia

 



A. A. Komissarov
Davydovsky Municipal Clinical Hospital; Russian University of Medicine
Russian Federation

researcher of Laboratory of atherothrombosis in Russian University of Medicine, Moscow, Russian Federation; leading researcher of Research Department in I.V. Davydovsky Moscow City Clinical Hospital

Moscow, Russia

 



References

1. Ran J, Zhou P, Wang J, Zhao X, Huang Y, Zhou Q et al. Global, regional, and national burden of heart failure and its underlying causes, 1990–2021: results from the global burden of disease study 2021. Biomarker Research. 2025;13(1):16. DOI: 10.1186/s40364-025-00728-8

2. Polyakov D.S., Fomin I.V., Belenkov Yu.N., Mareev V.Yu., Ageev F.T., Artemjeva E.G. et al. Chronic heart failure in the Russian Federation: what has changed over 20 years of follow-up? Results of the EPOCHCHF study. Kardiologiia. 2021;61(4):4–14. DOI: 10.18087/cardio.2021.4.n1628

3. Mamas MA, Sperrin M, Watson MC, Coutts A, Wilde K, Burton C et al. Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. European Journal of Heart Failure. 2017;19(9):1095–104. DOI: 10.1002/ejhf.822

4. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. New England Journal of Medicine. 2019;381(21):1995–2008. DOI: 10.1056/NEJMoa1911303

5. McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR et al. Angiotensin–niprilysin Inhibition versus enalapril in heart failure. New England Journal of Medicine. 2014;371(11):993–1004. DOI: 10.1056/NEJMoa1409077

6. Sapp JL, Sivakumaran S, Redpath CJ, Khan H, Parkash R, Exner DV et al. Long-Term Outcomes of Resynchronization–Defibrillation for Heart Failure. New England Journal of Medicine. 2024;390(3):212–20. DOI: 10.1056/NEJMoa2304542

7. Huusko J, Tuominen S, Studer R, Corda S, Proudfoot C, Lassenius M et al. Recurrent hospitalizations are associated with increased mortality across the ejection fraction range in heart failure. ESC Heart Failure. 2020;7(5):2406–17. DOI: 10.1002/ehf2.12792

8. Lupón J, Gavidia-Bovadilla G, Ferrer E, de Antonio M, Perera-Lluna A, López-Ayerbe J et al. Dynamic Trajectories of Left Ventricular Ejection Fraction in Heart Failure. Journal of the American College of Cardiology. 2018;72(6):591–601. DOI: 10.1016/j.jacc.2018.05.042

9. Mehra MR, Nayak A, Desai AS. Life-Prolonging Benefits of LVAD Therapy in Advanced Heart Failure: A Clinician’s Action And Communication Aid. JACC: Heart Failure. 2023;11(8):1011–7. DOI: 10.1016/j.jchf.2023.05.013

10. Hsich E, Singh TP, Cherikh WS, Harhay MO, Hayes D, Perch M et al. The International thoracic organ transplant registry of the international society for heart and lung transplantation: Thirty-ninth adult heart transplantation report—2022; focus on transplant for restrictive heart disease. The Journal of Heart and Lung Transplantation. 2022;41(10):1366–75. DOI: 10.1016/j.healun.2022.07.018

11. Masson S, Anand I, Favero C, Barlera S, Vago T, Bertocchi F et al. Serial Measurement of Cardiac Troponin T Using a Highly Sensitive Assay in Patients With Chronic Heart Failure: Data From 2 Large Randomized Clinical Trials. Circulation. 2012;125(2):280–8. DOI: 10.1161/CIRCULATIONAHA.111.044149

12. Meijers WC, Januzzi JL, deFilippi C, Adourian AS, Shah SJ, Van Veldhuisen DJ et al. Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure: A pooled analysis of 3 clinical trials. American Heart Journal. 2014;167(6):853-860.e4. DOI: 10.1016/j.ahj.2014.02.011

13. van Vark LC, Lesman-Leegte I, Baart SJ, Postmus D, Pinto YM, Orsel JG et al. Prognostic Value of Serial ST2 Measurements in Patients With Acute Heart Failure. Journal of the American College of Cardiology. 2017;70(19):2378–88. DOI: 10.1016/j.jacc.2017.09.026

14. Hartmann F, Packer M, Coats AJS, Fowler MB, Krum H, Mohacsi P et al. Prognostic Impact of Plasma N-Terminal Pro–Brain Natriuretic Peptide in Severe Chronic Congestive Heart Failure: A Substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Trial. Circulation. 2004;110(13):1780–6. DOI: 10.1161/01.CIR.0000143059.68996.A7

15. Kitteringham NR, Jenkins RE, Lane CS, Elliott VL, Park BK. Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2009;877(13):1229–39. DOI: 10.1016/j.jchromb.2008.11.013

16. Bhardwaj M, Weigl K, Tikk K, Holland-Letz T, Schrotz-King P, Borchers CH et al. Multiplex quantitation of 270 plasma protein markers to identify a signature for early detection of colorectal cancer. European Journal of Cancer. 2020;127:30–40. DOI: 10.1016/j.ejca.2019.11.021

17. Anwar MA, Keshteli AH, Yang H, Wang W, Li X, Messier HM et al. Blood-Based Multiomics-Guided Detection of a Precancerous Pancreatic Tumor. OMICS: A Journal of Integrative Biology. 2024;28(4):182–92. DOI: 10.1089/omi.2023.0278

18. Bugrova AE, Strelnikova PA, Kononikhin AS, Zakharova NV, Diyachkova EO, Brzhozovskiy AG et al. Targeted MRM-analysis of plasma proteins in frozen whole blood samples from patients with COVID-19: a retrospective study. Clinical Chemistry and Laboratory Medicine. 2025;63(2):448–57. DOI: 10.1515/cclm-2024-0800

19. Kumar MA, Baba SK, Sadida HQ, Marzooqi SAl, Jerobin J, Altemani FH et al. Extracellular vesicles as tools and targets in therapy for diseases. Signal Transduction and Targeted Therapy. 2024;9(1):27. DOI: 10.1038/s41392-024-01735-1

20. Galyavich A.S., Tereshchenko S.N., Uskach T.M., Ageev F.T., Aronov D.M., Arutyunov G.P. et al. 2024 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2024;29(11):251–349. DOI: 10.15829/1560-4071-2024-6162

21. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2021;42(36):3599–726. DOI: 10.1093/eurheartj/ehab368

22. Korobkov DN, Molodtsov IA, Kononikhin AS, Bugrova AE, Indeykina MI, Brzhozovskiy AG et al. Multiplexed Quantitation of Plasma Proteins by Targeted Mass Spectrometry for Early Diagnosis of Pancreatic Ductal Adenocarcinoma. International Journal of Molecular Sciences. 2025;26(18):9219. DOI: 10.3390/ijms26189219

23. Curtis JP, Sokol SI, Wang Y, Rathore SS, Ko DT, Jadbabaie F et al. The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure. Journal of the American College of Cardiology. 2003;42(4):736–42. DOI: 10.1016/S0735-1097(03)00789-7

24. Lourenço P, Cunha FM, Ferreira‐Coimbra J, Barroso I, Guimarães J, Bettencourt P. Dynamics of growth differentiation factor 15 in acute heart failure. ESC Heart Failure. 2021;8(4):2527–34. DOI: 10.1002/ehf2.13377

25. Vergaro G, Gentile F, Aimo A, Januzzi JL, Richards AM, Lam CSP et al. Circulating levels and prognostic cut‐offs of sST2, hs‐cTnT, and NT‐proBNP in women vs. men with chronic heart failure. ESC Heart Failure. 2022;9(4):2084–95. DOI: 10.1002/ehf2.13883

26. Koller L, Stojkovic S, Richter B, Sulzgruber P, Potolidis C, Liebhart F et al. Soluble Urokinase-Type Plasminogen Activator Receptor Improves Risk Prediction in Patients With Chronic Heart Failure. JACC: Heart Failure. 2017;5(4):268–77. DOI: 10.1016/j.jchf.2016.12.008

27. Pan Y, Li D, Ma J, Shan L, Wei M. NT-proBNP test with improved accuracy for the diagnosis of chronic heart failure. Medicine. 2017;96(51):e9181. DOI: 10.1097/MD.0000000000009181

28. Han C, Yang J, Sun J, Qin G. Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications. Pharmacology & Therapeutics. 2022;233:108025. DOI: 10.1016/j.pharmthera.2021.108025

29. Fu S, Zhang Y, Li Y, Luo L, Zhao Y, Yao Y. Extracellular vesicles in cardiovascular diseases. Cell Death Discovery. 2020;6(1):68. DOI: 10.1038/s41420-020-00305-y

30. Zhen K, Wei X, Zhi Z, Shang S, Zhang S, Xu Y et al. Circulating Extracellular Vesicles from Heart Failure Patients Inhibit Human Cardiomyocyte Activities. Journal of Cardiovascular Translational Research. 2025;18(6):1566–83. DOI: 10.1007/s12265-024-10571-1

31. Peng W, Liu J, Chen G, Zheng M, Zhang L, Li A et al. The correlation between ApoE gene polymorphism and non-ischemic chronic heart failure. International Journal of Clinical and Experimental Medicine. 2017;10(12):16809–14

32. Liehn EA, Department of Cardiology, Angiology and Intensive Care, Medical Faculty, University Hospital Aachen, Aachen, Germany, Victor Babes National Institute of Pathology, Bucharest, Romania, Lupan A-M, Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania, Diaconu R et al. Heart function assessment during aging in apolipoprotein E knock-out mice. Discoveries. 2021;9(3):e136. DOI: 10.15190/d.2021.15

33. Singh S, Baars DP, Aggarwal K, Desai R, Singh D, Pinto-Sietsma S-J. Association between lipoprotein (a) and risk of heart failure: A systematic review and meta-analysis of Mendelian randomization studies. Current Problems in Cardiology. 2024;49(4):102439. DOI: 10.1016/j.cpcardiol.2024.102439

34. Mehta A, Shapiro MD. Apolipoproteins in vascular biology and atherosclerotic disease. Nature Reviews Cardiology. 2022;19(3):168–79. DOI: 10.1038/s41569-021-00613-5

35. Kuku KO, Shearer JJ, Hashemian M, Oyetoro R, Park H, Dulek B et al. Development and Validation of a Protein Risk Score for Mortality in Heart Failure: A Community Cohort Study. Annals of Internal Medicine. 2024;177(1):39–49. DOI: 10.7326/M23-2328

36. Tonry C, Linden K, Collier P, Ledwidge M, McDonald K, Collins BC et al. Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy. Biomedicines. 2024;12(8):1712. DOI: 10.3390/biomedicines12081712

37. Yu W, Guo Z, Liang H, Ma D, Lin C, Li Z et al. GPLD1 Attenuates Heart Failure via Dual-Membrane Localization to Inhibit uPAR. Circulation Research. 2025;137(5):e124–43. DOI: 10.1161/CIRCRESAHA.124.325623

38. Santulli G, Xie W, Reiken SR, Marks AR. Mitochondrial calcium overload is a key determinant in heart failure. Proceedings of the National Academy of Sciences. 2015;112(36):11389–94. DOI: 10.1073/pnas.1513047112

39. Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart. Cell Reports. 2015;13(3):533–45. DOI: 10.1016/j.celrep.2015.09.023

40. Masini G, Graham FJ, Pellicori P, Cleland JGF, Cuthbert JJ, Kazmi S et al. Criteria for Iron Deficiency in Patients With Heart Failure. Journal of the American College of Cardiology. 2022;79(4):341–51. DOI: 10.1016/j.jacc.2021.11.039


Review

For citations:


Anisimova A.S., Molodtsov I.A., Kononikhin A.S., Kordzaya E.L., Bugrova A.E., Maryukhnich E.V., Indeykina M.I., Tvorogova A.V., Nikolaev E.N., Vasilieva E.Yu., Komissarov A.A. Biomarkers of Progressive Chronic Heart Failure: The Results of Blood Proteomic Analysis. Kardiologiia. 2025;65(12):28-38. (In Russ.) https://doi.org/10.18087/cardio.2025.12.n3101

Views: 82

JATS XML


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 0022-9040 (Print)
ISSN 2412-5660 (Online)