Usefulness of Serum Biomarkers of Endothelial Glycocalyx Damage in Prognosis of Decompensated Patients with Heart Failure with Reduced Ejection Fraction

The surface layer of endothelium contains the endothelial glycocalyx (eGC), consisting of proteoglycan polymers. Syndecan-1, heparan sulfate, and hyaluronic acid are major constituents of eGC, and their increasing detection in serum represents active degradation of eGC. Serum was obtained from patients with no heart failure (non-HF) and with HF with reduced ejection fraction (HFrEF) of <40%, either stable chronic HF (CHF) or acute decompensated HF (ADHF). Syndecan-1, heparan sulfate, and hyaluronic acid were measured for comparisons in the groups, adjusting for clinical and laboratory values. In our study cohort, 51 non-HF, 66 ADHF, and 72 patients with CHF were enrolled. Between ADHF and CHF, left ventricular (LV) mass index, LV ejection fraction, and pulmonary capillary wedge pressure did not differ. Patients with ADHF had significantly higher levels of eGC constituents compared with CHF and non-HF. During follow-up, 21 patients with HF died, and the mortality rate was higher in patients with higher serum syndecan-1 or heparan sulfate (log-rank p = 0.007 and 0.016, respectively). In multivariate analysis, a doubling of serum heparan sulfate concentration amounted to a 31.5% increase in all-cause mortality (hazard ratio = 1.315, confidence interval = 1.012-1.709, p = 0.040). In conclusion, serum biomarkers of eGC were elevated in ADHF (but not in CHF) in patients with HFrEF, suggesting the potential roles of eGC degradation and endothelial dysfunction in HF decompensation. Only elevated heparin sulfate was associated with higher all-cause mortality after adjusting for traditional risk variables in patients with HFrEF.