Phenotypic Features of Heart Failure in Patients with Preserved Left Ventricular Ejection Fraction
https://doi.org/10.18087/cardio.2025.9.n3018
Abstract
Aim Chronic heart failure with preserved left ventricular ejection fraction (CHFpEF) is characterized by high prevalence, clinical heterogeneity, and insufficient understanding of its mechanisms compared to other CHF types. One approach to improving the patient group stratification is the identification of subphenotypes based on clinical and functional data and biomarker assessment. The aim of this study was to identify the clinical, laboratory, and instrumental characteristics of patients with CHFpEF and ischemic heart disease based on left ventricular ejection fraction (LVEF).
Material and methods This study included 145 patients with CHFpEF who were scheduled for coronary artery bypass grafting. Inclusion criteria were NYHA class ≥2 symptomatic heart failure, preserved LVEF ≥50%, and a HFA-PEFF algorithm total score ≥3, which helps diagnose CHFpEF. Patients were divided into a group with LVEF 50-60% (group 1; n=53) and a group with LVEF >60% (group 2; n=92). Before surgery, echocardiography, standard laboratory tests, and measurements of plasma biomarkers (N-terminal pre-brain natriuretic peptide (NT-proBNP), vascular endothelial growth factor (VEGF), heart fatty acid binding protein (H-FABP), interleukin receptor ST2, vascular endothelial cell adhesion molecule (VCAM), plasminogen activator inhibitor type 1 (PAI-1), neuropilin-1 (NRP-1) were performed in all patients.
Conclusion CHFpEF subphenotypes have different clinical and laboratory characteristics. Higher neuropilin-1 concentrations were associated with lower LVEF in CHFpEF.
About the Authors
I. A. MustafinaRussian Federation
Associate Professor, Department of Propaedeutics, Bashkir State Medical University, Candidate of Medical Sciences (PhD).
Ufa, Russia
M. R. Plotnikova
Russian Federation
Head of the Department of Cardiology, Bashkir State Medical University, Candidate of Medical Sciences (PhD)
Ufa, Russia
Yu. N. Belenkov
Russian Federation
Director of the Clinic of Hospital Therapy No. 1, Sechenov University; Head of the Department of Hospital Therapy No. 1, Faculty of General Medicine, Sechenov University; Academician of the Russian Academy of Sciences; Professor, Doctor of Medical Sciences (MD, DSc).
Moscow, Russia
N. V. Khabarova
Russian Federation
Assistant Professor, Department of Hospital Therapy No. 1, Sechenov First Moscow State Medical University (Sechenov University), Candidate of Medical Sciences (PhD).
Moscow, Russia
N. Sh. Zagidullin
Russian Federation
Head of the Department of Propaedeutics of Internal Medicine, Bashkir State Medical University; Director of the Research Institute of Cardiology; Doctor of Medical Sciences (MD, DSc), Professor.
Ufa, Russia
References
1. 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
2. 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
3. Larina V.N., Lunev V.I. Phenotyping of outpatients with heart failure with preserved ejection fraction and poor prognosis. Russian Journal of Cardiology. 2024;29(3):105–12. DOI: 10.15829/1560-4071-2024-5759
4. Gu J, Ke J, Wang Y, Wang C, Zhang J. Characteristics, prognosis, and treatment response in HFpEF patients with high vs. normal ejection fraction. Frontiers in Cardiovascular Medicine. 2022;9:944441. DOI: 10.3389/fcvm.2022.944441
5. Kozhevnikova MV, Belenkov YN, Shestakova KM, Ageev AA, Markin PA, Kakotkina AV et al. Metabolomic profiling in heart failure as a new tool for diagnosis and phenotyping. Scientific Reports. 2025;15(1):11849. DOI: 10.1038/s41598-025-95553-2
6. Mustafina I, Elkholey K, Fudim M, Stavrakis S. The impact of atrial fibrillation on clinical outcomes in heart failure with mid-range and preserved ejection fraction patients. Heart Rhythm. 2024;21(11):2110– 7. DOI: 10.1016/j.hrthm.2024.05.039
7. Rosch S, Kresoja K-P, Besler C, Fengler K, Schöber AR, von Roeder M et al. Characteristics of Heart Failure With Preserved Ejection Fraction Across the Range of Left Ventricular Ejection Fraction. Circulation. 2022;146(7):506–18. DOI: 10.1161/CIRCULATIONAHA.122.059280
8. Filatova A.Yu., Sobolevskaya M.S., Potekhina A.V., Svirida O.N., Masenko V.P., Kuznetsova T.V. et al. Prognostic value of soluble biomarkers of haemodynamic stress, inflammation and fibrosis in HFpEF: a retrospective cohort study. Russian Cardiology Bulletin. 2024;19(2):47–54. DOI: 10.17116/Cardiobulletin20241902147
9. Zhang Y, Guo X, Chen S, Wang Y, Li J, Sun X et al. Left ventricular geometry characteristics and clinical outcomes in hemodialysis patients with heart failure with preserved ejection fraction. BMC Cardiovascular Disorders. 2024;24(1):327. DOI: 10.1186/s12872-024-03985-x
10. Nakagawa A, Yasumura Y, Yoshida C, Okumura T, Tateishi J, Yoshida J et al. Predictors and Outcomes of Heart Failure With Preserved Ejection Fraction in Patients With a Left Ventricular Ejection Fraction Above or Below 60. Journal of the American Heart Association. 2022;11(15):e025300. DOI: 10.1161/JAHA.122.025300
11. Gorica E, Geiger MA, Di Venanzio L, Atzemian N, Kleeberger JA, Grigorian D et al. Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment. Cardiovascular Diabetology. 2025;24(1):265. DOI: 10.1186/s12933-025-02774-w
12. Tromp J, Khan MAF, Klip IjT, Meyer S, De Boer RA, Jaarsma T et al. Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction. Journal of the American Heart Association. 2017;6(4):e003989. DOI: 10.1161/JAHA.116.003989
13. Pal S, Su Y, Nwadozi E, Claesson-Welsh L, Richards M. Neuropilin-1 controls vascular permeability through juxtacrine regulation of endothelial adherens junctions. Angiogenesis. 2025;28(1):7. DOI: 10.1007/s10456-024-09963-3
14. Han J, Li G, Zhang D, Wang X, Guo X. Predicting Late Recurrence of Atrial Fibrillation After Radiofrequency Ablation in Patients With Atrial Fibrillation: Comparison of C2HEST and HATCH Scores. Frontiers in Cardiovascular Medicine. 2022;9:907817. DOI: 10.3389/fcvm.2022.907817
15. Harada T, Sunaga H, Sorimachi H, Yoshida K, Kato T, Kurosawa K et al. Pathophysiological role of fatty acid‐binding protein 4 in Asian patients with heart failure and preserved ejection fraction. ESC Heart Failure. 2020;7(6):4256–66. DOI: 10.1002/ehf2.13071
16. Yen C-H, Lin J-L, Sung K-T, Su C-H, Huang W-H, Chen Y-Y et al. Association of free fatty acid binding protein with central aortic stiffness, myocardial dysfunction and preserved ejection fraction heart failure. Scientific Reports. 2021;11(1):16501. DOI: 10.1038/s41598-021-95534-1
17. Winter M-P, Kleber ME, Koller L, Sulzgruber P, Scharnagl H, Delgado G et al. Prognostic significance of tPA/PAI-1 complex in patients with heart failure and preserved ejection fraction. Thrombosis and Haemostasis. 2017;117(3):471–8. DOI: 10.1160/TH16-08-0600
18. Serezhina E.K., Obrezan A.G. Myocardial damage and remodelling biomarkers in the diagnosis of heart failure with a preserved ejection fraction. Russian Medical Journal. 2019;3(10–1):23–6.
19. Larina V.N., Lunev V.I., Karpenko D.G., Sidorova V.P. Heart failure with preserved ejection fraction: opportunities in diagnosis and risk stratification in elderly patients. Medical Business. 2021;4:148–54. DOI: 10.24412/2071-5315-2021-12404
20. Grakova E.V., Kop’eva K.V., Gusakova A.M., Smorgon A.V., Maltseva A.N., Mochula A.V. et al. Role of humoral markers in the pathogenesis of heart failure with preserved ejection fraction in patients with non-obstructive coronary artery disease. Russian Journal of Cardiology. 2022;27(10):57–63. DOI: 10.15829/1560-4071-2022-5162
21. Pabel S, Wagner S, Bollenberg H, Bengel P, Kovács Á, Schach C et al. Empagliflozin directly improves diastolic function in human heart failure. European Journal of Heart Failure. 2018;20(12):1690–700. DOI: 10.1002/ejhf.1328
Review
For citations:
Mustafina I.A., Plotnikova M.R., Belenkov Yu.N., Khabarova N.V., Zagidullin N.Sh. Phenotypic Features of Heart Failure in Patients with Preserved Left Ventricular Ejection Fraction. Kardiologiia. 2025;65(9):3-9. (In Russ.) https://doi.org/10.18087/cardio.2025.9.n3018










