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

  • Chukwudiebube N. AjaeroEmail author
  • Nathan E. K. Procter
  • Yuliy Y. Chirkov
  • Tamila Heresztyn
  • Margaret A. Arstall
  • Andrew D. McGavigan
  • Michael P. Frenneaux
  • John D. Horowitz
Original Article

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.

Keywords

Glycocalyx shedding Cardiac failure Resynchronization therapy Endothelial function Symmetric dimethylarginine 

Abbreviations

CRT

Cardiac resynchronisation therapy

SPWD

Septal to posterior wall delay

QOL

Quality of life

LVEF

Left ventricular ejection fraction

NT-proBNP

N-terminal pro-B-type natriuretic peptide

AIX

Augmentation index

NO

Nitric oxide

SDMA

Symmetric dimethylarginine

TXNIP

Thioredoxin interacting protein

Notes

Acknowledgements

The authors wish to thank Jeanette Stansborough and Irene Stafford for helping out with the logistics of the research. Thanks to Matthew Chapman for the echocardiograms.

Compliance with ethical standards

Conflict of interest

The authors declare that there was no conflict of interest.

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Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Chukwudiebube N. Ajaero
    • 1
    • 2
    • 5
    Email author
  • Nathan E. K. Procter
    • 6
  • Yuliy Y. Chirkov
    • 2
  • Tamila Heresztyn
    • 2
  • Margaret A. Arstall
    • 3
    • 5
    • 7
  • Andrew D. McGavigan
    • 4
  • Michael P. Frenneaux
    • 6
  • John D. Horowitz
    • 1
    • 2
    • 5
  1. 1.The Queen Elizabeth HospitalWoodville SouthAustralia
  2. 2.Basil Hetzel InstituteWoodville SouthAustralia
  3. 3.The Lyell McEwin HospitalElizabeth ValeAustralia
  4. 4.The Flinders Medical CentreFlinders UniversityBedford ParkAustralia
  5. 5.Department of MedicineThe University of AdelaideAdelaideAustralia
  6. 6.University of East AngliaNorwichUK
  7. 7.Northern Adelaide Local Health NetworkAdelaideAustralia

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