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Abstract: 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. [ABSTRACT FROM AUTHOR]

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate ( GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy-refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter-regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction-although not by conventional GFR measurements-is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function. [ABSTRACT FROM AUTHOR]