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

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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.

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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

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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.

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Authors and Affiliations

  1. The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South, South Australia, Australia

    Chukwudiebube N. Ajaero & John D. Horowitz

  2. Basil Hetzel Institute, Woodville South, South Australia, Australia

    Chukwudiebube N. Ajaero, Yuliy Y. Chirkov, Tamila Heresztyn & John D. Horowitz

  3. The Lyell McEwin Hospital, Haydown Road, Elizabeth Vale, South Australia, Australia

    Margaret A. Arstall

  4. The Flinders Medical Centre, Flinders University, Flinders Drive, Bedford Park, South Australia, Australia

    Andrew D. McGavigan

  5. Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia

    Chukwudiebube N. Ajaero, Margaret A. Arstall & John D. Horowitz

  6. University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK

    Nathan E. K. Procter & Michael P. Frenneaux

  7. Northern Adelaide Local Health Network, Adelaide, South Australia, Australia

    Margaret A. Arstall

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  1. Chukwudiebube N. Ajaero
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Correspondence to Chukwudiebube N. Ajaero.

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Ajaero, C.N., Procter, N.E.K., Chirkov, Y.Y. et al. Endothelial dysfunction and glycocalyx shedding in heart failure: insights from patients receiving cardiac resynchronisation therapy. Heart Vessels 35, 197–206 (2020). https://doi.org/10.1007/s00380-019-01481-3

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  • DOI: https://doi.org/10.1007/s00380-019-01481-3

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