Hepcidin and MELD-XI score as markers of multiple organ failure in patients with heart failure with preserved and reduced ejection fraction

Data on the changes in hepcidin levels in heart failure (HF) patients are contradictory and do not give an answer about its effect on the progression of multiple organ failure. Since the model of end-stage liver disease excluding INR (MELD-XI) reflects the severity of liver and kidney dysfunction, these markers have been suggested to be associated with decompensated HF.

Aim. To assess the MELD-XI score and serum hepcidin levels in patients with decompensated HF with different values of left ventricular ejection fraction (EF).

Material and methods. The study included 68 patients (29 women, 39 men; mean age 72,3±11,7 years) hospitalized due to decompensated HF. Patients were divided into three groups: reduced (HFrEF) (n=20), mid-range (HFmrEF) (n=23), and preserved EF (HFpEF) (n=24)). Upon admission, along with standard diagnostic tests, all patients were examined for hepcidin-25 levels by enzyme-linked immunosorbent assay. MELD-XI score was calculated. Statistical processing was carried out using the software package Statistica 8.0.

Results. Hepcidin levels in the HFrEF group (31,63 ng/ml [22,0; 71,6]) were significantly higher than in the HFmrEF (23,89 ng/ml [21,1; 27,9]) (p<0,05) and HFpEF (26,91 ng/ml [18,6; 31,1]) (p<0,05) groups. In HFpEF, there was a correlation of hepcidin level with body mass index (r=0,47, p<0,05) and chronic obstructive airway diseases (r=0,44, p<0,05). A correlation of hepcidin level with significant cardiac arrhythmias (r=0,61, p<0,05) was revealed in HFmrEF patients. MELD-XI score were significantly increased from 9,44±3,96 for HFpEF and 11,53±3,82 for HFmrEF to 14,3±4,3 for HFrEF (p<0,005). We also revealed correlation of MELD-XI score with hepcidin levels (r=0,3, p<0,05) and EF (r=-0,43, p<0,0003). Patients with a MELD-XI score of >10,4 were more likely to have NYHA class III-IV HF, HFrEF and significantly higher levels of hepcidin (p<0,05 for all) These patients were also more likely to have chronic kidney disease (p<0,05).

Conclusion. Hepcidin level and MELD-XI score in patients with decompensated HF are inversely related to left ventricular EF. There is a direct relationship between hepcidin levels and other clinical parameters: body mass index, the presence of chronic obstructive airway diseases and cardiac arrhythmias.

1. Mareev VY, Fomin IV, Ageev FT, et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiia. 2018;58(6S):8-158. (In Russ.) doi:10.18087/cardio.2475.

2. Ponikowski P, Voors AA, Anker SD, et al. ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-200. doi:10.1093/eurheartj/ehw128.

3. Rich JD, Burns J, Freed BH, et al. Meta‐Analysis Global Group in Chronic (MAGGIC) Heart Failure Risk Score: Validation of a Simple Tool for the Prediction of Morbidity and Mortality in Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2018;7(20):0 09594. doi:10.1161/JAHA.118.009594.

4. Lee DS, Austin PC, Rouleau JL, et al. Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA 2003;290(19):2581-7. doi:10.1001/jama.290.19.2581.

5. Yamada T, Morita T, Furukawa Y, et al. Prognostic value of the combination of cardiac power index and Model of Endstage Liver Disease eXcluding INR (MELD-XI) score in patients admitted for acute decompensated heart failure. JACC. 2018;71;12(2):e0170987. doi:10.1371/journal.pone.0170987.

6. Scholfield M, Schabath MB, Guglin M. Longitudinal trends, hemodynamic profiles, and prognostic value of abnormal liver function tests in patients with acute decompensated heart failure: an analysis of the ESCAPE Trial. J Card Fail. 2014;20(7):476-84. doi:10.1016/j.cardfail.2014.05.001.

7. Yang JA, Kato TS, Shulman BP, et al. Liver dysfunction as a predictor of outcomes in patients with advanced heart failure requiring ventricular assist device support: Use of the Model of End-stage Liver Disease (MELD) and MELD eXcluding INR (MELDXI) scoring system. J Heart Lung Transplant. 2012;31(6):601-10. doi:10.1016/j.healun.2012.02.027.

8. Vela D. Low hepcidin in liver fibrosis and cirrhosis; a tale of progressive disorder and a case for a new biochemical marker. Molecular Medicine. 2018;24:5. doi:10.1186/s10020-018-0008-7.

9. Ruchala P, Nemeth E. The pathophysiology and pharmacology of hepcidin. Trends Pharmacol Sci. 2014;35(3):155-61. doi:10.1016/j.tips.2014.01.004.

10. Wang CY, Babitt JL. Hepcidin regulation in the anemia of inflammation. Curr Opin Hematol. 2016;23(3):189-97. doi:10.1097/MOH.0000000000000236.

11. Vuppalanchi R, Troutt JS, Konrad RJ, et al. Serum hepcidin levels are associated with obesity but not liver disease. Obesity (Silver Spring). 2014;22(3):836-41. doi:10.1002/oby.20403.

12. Divakaran V. Hepcidin in anemia of chronic heart failure Am J Hematol. 2011; 86(1):107-9. doi:10.1002/ajh.21902.

13. Solomakhina NI, Nakhodnova ES, Gitel EP, Belenkov YuN. Hepcidin and its relationship with inflammation in old and older patients with anemia of chronic disease associated with CHF. Kardiologiia. 2018:58(S2):4-11. doi:10.18087/cardio.2457.

14. Ohno Y, Hanawa H, Jiao S, et al. Liver congestion in heart failure contributes to inappropriately increased serum hepcidin despite anemia. J Exp Med. 2015;235:69-79. doi:10.1620/tjem.235.69.

15. Jamali R, Razavizade M, Arj A, Aarabi MH. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease. World J Gastroenterol. 2016;22(21):5096-103. doi:10.3748/wjg.v22.i21.5096.