Endovascular shedding markers in patients with heart failure with reduced ejection fraction: Results from a single-center exploratory study

Background: Endothelial glycocalyx degradation has been associated with multiple pathophysiological processes in cardiovascular disease. Aims: To explore the role of glycocalyx shedding markers in pathophysiology of HFrEF. Methods: In 123 HFrEF patients, the concentration, prognostic value, and association of glycocalyx shedding markers with other disease processes were investigated. Results: Median HA levels and syndecan-1 levels in HFrEF patients were, respectively, 29.4 (10.7;61.6) ng/mL and 48.5 (33.6;80.8) ng/mL. Overall, HA-levels were significantly higher in HFrEF patients compared to healthy subjects, but only 31% of HFrEF patients had HA-levels above the cutoff of normal. There was no significant difference among HFrEF patients and healthy subjects regarding syndecan-1 levels. HFrEF patients with elevated HA-levels had a significantly worse outcome (log rank = 0.01) which remained significant after correction for established risk factors (HR 2.53 (1.13-5.69); P = .024). There was no significant relation between levels of shedding markers and neurohumoral activation (PRA, serum aldosterone, NT-proBNP), myocardial injury (HS-trop), inflammation (CRP), or other baseline characteristics. Conclusions: The glycocalyx shedding marker HA is significantly elevated in a subgroup of HFrEF patients and an independent predictor for worse clinical outcome. Glycocalyx shedding might be an additional factor in the pathophysiology of HF which warrants further investigation. P.N., F.V., P.M. and W.M. are researchers for the Limburg Clinical Research Program (LCRP) UHasselt - ZOL - Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. P.M. is supported by a doctoral fellowship by the Research Foundation-Flanders (FWO grant-number: 1127917N)