Endothelial dysfunction and glycocalyx shedding in heart failure: insights from patients receiving cardiac resynchronisation therapy

Chukwudiebube N Ajaero, Nathan E K Procter, Yuliy Y Chirkov, Tamila Heresztyn, Margaret A Arstall, Andrew D McGavigan, Michael P Frenneaux, John D Horowitz

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Abstract

To determine (a) whether chronic heart failure with reduced ejection fraction (HFrEF) is associated with increased glycocalyx shedding; (b) whether glycocalyx shedding in HFrEF with left ventricular dyssynchrony is related to inflammation, endothelial dysfunction and/or redox stress and is ameliorated by cardiac resynchronisation therapy. Glycocalyx shedding has been reported to be increased in heart failure and is a marker of increased mortality. Its role in dyssynchronous systolic heart failure and the effects of cardiac resynchronisation therapy (CRT) are largely unknown. Twenty-six patients with dyssynchronous HFrEF were evaluated before and 6 months after CRT insertion. Echocardiographic septal to posterior wall delay (SPWD) assessed intra-ventricular mechanical dyssynchrony, and quality of life, integrity of nitric oxide (NO) signalling, inflammatory and redox-related biomarkers were measured. Glycocalyx shedding was quantitated via plasma levels of the glycocalyx component, syndecan-1. Syndecan-1 levels pre-CRT were inversely correlated with LVEF (r = - 0.45, p = 0.02) and directly with SPWD (r = 0.44, p = 0.02), QOL (r = 0.39, p = 0.04), plasma NT-proBNP (r = 0.43, p = 0.02), and the inflammatory marker, symmetric dimethylarginine (SDMA) (r = 0.54, p = 0.003). On multivariate analysis, syndecan-1 levels were predicted by SPWD and SDMA (β = 0.42, p = 0.009 and β = 0.54, p = 0.001, respectively). No significant correlation was found between syndecan-1 levels and other markers of endothelial dysfunction/inflammatory activation. Following CRT there was no significant change in syndecan-1 levels. In patients with dyssynchronous HFrEF, markers of glycocalyx shedding are associated with the magnitude of mechanical dyssynchrony and elevation of SDMA levels and inversely with LVEF. However, CRT does not reverse this process.

Original languageEnglish
Pages (from-to)197-206
Number of pages10
JournalHeart and Vessels
Volume35
Issue number2
Early online date27 Aug 2019
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Cardiac failure
  • Endothelial function
  • Glycocalyx shedding
  • Resynchronization therapy
  • Symmetric dimethylarginine
  • MORTALITY
  • SYNDECAN-1
  • MECHANISM
  • BARRIER
  • RENAL-FUNCTION
  • SYMMETRIC DIMETHYLARGININE
  • RESYNCHRONIZATION THERAPY
  • IMPROVEMENT
  • LEUKOCYTE ADHESION
  • ASSOCIATION

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