Usefulness of the Klotho protein, FGF-23 and GDF-15 in assessment of the new onset Acute Heart Failure
Authors: Plonka J , Wojcicki K , Chruscicki D , Olejnik A , Klus A , Wezyk-Wylegala N , Rzepiela L , Dabrowska K , Gawrylak-Dryja E , Bil-Lula I , Gierlotka M 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, University of Opole, Poland.

Background
Acute heart failure (AHF) is a life-threatening multifaceted clinical condition requiring intensive and expensive treatment. Earlier studies highlighted the difference in characteristics and prognosis of new onset AHF (NO- AHF) and acute decompensated heart failure (ADHF). Protein Klotho and FGF23 could be attractive tools in the evaluation of patients with AHF. GDF-15 is a recognized marker of the risk of death and complications, including bleeding in many cardiovascular diseases.

Aim
The aim of the study was to compare selected biomarkers (Protein Klotho, FGF-23, GDF-15) with clinical characteristics and 12-month outcomes of patients with NO-AHF and ADHF.

Methods
As part of the prospective Acute Heart Failure Registry (OP-AHF), data from 112 patients hospitalized in Intensive Cardiac Care Unit (ICCU) were collected from June 2019. Inclusion criteria were: hospitalization for AHF and the use of at least one of: intravenous diuretics, catecholamines or mechanical circulatory support. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were than follow-up for one year.

Results
Patients with NO-AHF constituted 46% of the study group (52 out of 112) and compared to patients with ADHF they were more often aged under 65 years (44% vs. 30%, p=0.12), better educated (25% vs. 8%, p=0.03), less frequently with diabetes (31% vs. 43%, p=0.17), hypertension (58% vs. 83%, p=0.03), and prior myocardial infarction (19% vs. 45%, p=0.004). In both groups there were more men (69% vs. 80%,p=0.19) and ischemic etiology of heart failure were more frequent (33% vs. 51%, p=0.42) in NO-AHF and ADHF, respectively. Left ventricular ejection fraction (LVEF) was insignificantly higher in patients with NO-AHF on admission (30% vs. 26%, p=0.6) and at discharge (35% vs. 30%, p=0.27).Only patient with NO-AHF improved LVEF at the 12- month follow–up (50% vs. 35%, p=0,003).It was no signifcant differences between median value of Klotho protein in both groups at admission, discharge and 30–day follow up visit. We observed significant reduction in FGF-23 and GDF-16 at tree time points (Table 1). 12-month mortality in patients with NO-AHF was insignificantly lower (17% vs. 28% in ADHF HR=1,7 (95% Cl=0.25-1.18)),also after correction for age, sex and ,LVEF- 20% vs. 25%, respectively, p=0.58; HR=1,26 (0.3-1.8). In the Cox multivariate model, the risk of death was presented as hazard ratio (HR) and was highest for GDF-15 in both groups (Table2).

Conclusion
Patients with the NO- AHF have different clinical profile than patients with acute decompensated heart failure with a tendency to lower 12-month mortality. There were no significant differences in the median value of Klotho protein in both groups. Reduction of the FGF-23 during hospitalization can serve as a marker of AHF compensation, thus FGF-23 could be a valuable tool for assessing response to treatment. GDF-15 seems to be the strongest predictor of death in both groups of AHF.