Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support

Sjoukje I. Lok; Fay M. A. Nous; Joyce van Kuik; Petra van der Weide; Bjorn Winkens; Hans Kemperman; Andre Huisman; Jaap R Lahpor; Roel A. de Weger; Nicolaas de Jonge

doi:10.1093/ejcts/ezu539

Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support

Sjoukje I. Lok^*, Fay M. A. Nous, Joyce van Kuik, Petra van der Weide, Bjorn Winkens, Hans Kemperman, Andre Huisman, Jaap R Lahpor, Roel A. de Weger, Nicolaas de Jonge

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVES: During support with a left ventricular assist device (LVAD), partial reverse remodelling takes place in which fibrosis plays an important role. In this study, we analysed the histological changes and expression of fibrotic markers in patients with advanced heart failure (HF) during continuous-flow LVAD (cf-LVAD) support.

METHODS: In 25 patients, myocardial tissue at the time of LVAD implantation (pre-LVAD) was compared with tissue from the explanted left ventricle (post-LVAD). Interstitial fibrosis and cardiomyocyte size were analysed pre-and post-LVAD. Plasma was obtained from all patients before and during LVAD support. Plasma levels, cardiac mRNA and protein expression of brain natriuretic peptide (BNP), galectin-3 (Gal-3), connective tissue growth factor (CTGF), osteopontin (OPN) and transforming growth factor beta-1 were determined.

RESULTS: Fibrosis increased during cf-LVAD unloading (P <0.05). Cardiomyocytes elongated (P <0.05), whereas cross-sectional area did not change. BNP, Gal-3, CTGF and OPN were significantly elevated pre-LVAD in comparison with controls. BNP decreased significantly after 1 month of cf-LVAD support (P <0.001) to near-normal levels. Pro-fibrotic markers remained elevated in comparison with controls.

CONCLUSIONS: cf-LVAD support is associated with lengthening of cardiomyocytes, without alterations in diameter size. Remarkably, myocardial fibrosis increased as well as circulating pro-fibrotic markers. Whether the morphological changes are a direct effect of reduced pulsatility during cf-LVAD support or due to HF progression requires further investigation.

Original language	English
Pages (from-to)	407-415
Number of pages	9
Journal	European Journal of Cardio-thoracic Surgery
Volume	48
Issue number	3
DOIs	https://doi.org/10.1093/ejcts/ezu539 https://doi.org/10.1093/ejcts/ezu539
Publication status	Published - Sept 2015

Keywords

Adult
Biomarkers
Connective Tissue Growth Factor
Female
Fibrosis
Galectin 3
Heart Failure
Heart-Assist Devices
Humans
Male
Middle Aged
Myocardium
Myocytes, Cardiac
Natriuretic Peptide, Brain
Osteopontin
Transforming Growth Factor beta
Ventricular Remodeling
Journal Article

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Lok, S. I., Nous, F. M. A., van Kuik, J., van der Weide, P., Winkens, B., Kemperman, H., Huisman, A., Lahpor, J. R., de Weger, R. A., & de Jonge, N. (2015). Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support. European Journal of Cardio-thoracic Surgery, 48(3), 407-415. https://doi.org/10.1093/ejcts/ezu539, https://doi.org/10.1093/ejcts/ezu539

@article{5c7ed5a8a1764af8abd19d569d277310,

title = "Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support",

abstract = "OBJECTIVES: During support with a left ventricular assist device (LVAD), partial reverse remodelling takes place in which fibrosis plays an important role. In this study, we analysed the histological changes and expression of fibrotic markers in patients with advanced heart failure (HF) during continuous-flow LVAD (cf-LVAD) support.METHODS: In 25 patients, myocardial tissue at the time of LVAD implantation (pre-LVAD) was compared with tissue from the explanted left ventricle (post-LVAD). Interstitial fibrosis and cardiomyocyte size were analysed pre-and post-LVAD. Plasma was obtained from all patients before and during LVAD support. Plasma levels, cardiac mRNA and protein expression of brain natriuretic peptide (BNP), galectin-3 (Gal-3), connective tissue growth factor (CTGF), osteopontin (OPN) and transforming growth factor beta-1 were determined.RESULTS: Fibrosis increased during cf-LVAD unloading (P <0.05). Cardiomyocytes elongated (P <0.05), whereas cross-sectional area did not change. BNP, Gal-3, CTGF and OPN were significantly elevated pre-LVAD in comparison with controls. BNP decreased significantly after 1 month of cf-LVAD support (P <0.001) to near-normal levels. Pro-fibrotic markers remained elevated in comparison with controls.CONCLUSIONS: cf-LVAD support is associated with lengthening of cardiomyocytes, without alterations in diameter size. Remarkably, myocardial fibrosis increased as well as circulating pro-fibrotic markers. Whether the morphological changes are a direct effect of reduced pulsatility during cf-LVAD support or due to HF progression requires further investigation.",

keywords = "Adult, Biomarkers, Connective Tissue Growth Factor, Female, Fibrosis, Galectin 3, Heart Failure, Heart-Assist Devices, Humans, Male, Middle Aged, Myocardium, Myocytes, Cardiac, Natriuretic Peptide, Brain, Osteopontin, Transforming Growth Factor beta, Ventricular Remodeling, Journal Article",

author = "Lok, {Sjoukje I.} and Nous, {Fay M. A.} and {van Kuik}, Joyce and {van der Weide}, Petra and Bjorn Winkens and Hans Kemperman and Andre Huisman and Lahpor, {Jaap R} and {de Weger}, {Roel A.} and {de Jonge}, Nicolaas",

year = "2015",

month = sep,

doi = "10.1093/ejcts/ezu539",

language = "English",

volume = "48",

pages = "407--415",

journal = "European Journal of Cardio-thoracic Surgery",

issn = "1010-7940",

publisher = "Elsevier",

number = "3",

}

Lok, SI, Nous, FMA, van Kuik, J, van der Weide, P, Winkens, B, Kemperman, H, Huisman, A, Lahpor, JR, de Weger, RA & de Jonge, N 2015, 'Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support', European Journal of Cardio-thoracic Surgery, vol. 48, no. 3, pp. 407-415. https://doi.org/10.1093/ejcts/ezu539, https://doi.org/10.1093/ejcts/ezu539

TY - JOUR

T1 - Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support

AU - Lok, Sjoukje I.

AU - Nous, Fay M. A.

AU - van Kuik, Joyce

AU - van der Weide, Petra

AU - Winkens, Bjorn

AU - Kemperman, Hans

AU - Huisman, Andre

AU - Lahpor, Jaap R

AU - de Weger, Roel A.

AU - de Jonge, Nicolaas

PY - 2015/9

Y1 - 2015/9

N2 - OBJECTIVES: During support with a left ventricular assist device (LVAD), partial reverse remodelling takes place in which fibrosis plays an important role. In this study, we analysed the histological changes and expression of fibrotic markers in patients with advanced heart failure (HF) during continuous-flow LVAD (cf-LVAD) support.METHODS: In 25 patients, myocardial tissue at the time of LVAD implantation (pre-LVAD) was compared with tissue from the explanted left ventricle (post-LVAD). Interstitial fibrosis and cardiomyocyte size were analysed pre-and post-LVAD. Plasma was obtained from all patients before and during LVAD support. Plasma levels, cardiac mRNA and protein expression of brain natriuretic peptide (BNP), galectin-3 (Gal-3), connective tissue growth factor (CTGF), osteopontin (OPN) and transforming growth factor beta-1 were determined.RESULTS: Fibrosis increased during cf-LVAD unloading (P <0.05). Cardiomyocytes elongated (P <0.05), whereas cross-sectional area did not change. BNP, Gal-3, CTGF and OPN were significantly elevated pre-LVAD in comparison with controls. BNP decreased significantly after 1 month of cf-LVAD support (P <0.001) to near-normal levels. Pro-fibrotic markers remained elevated in comparison with controls.CONCLUSIONS: cf-LVAD support is associated with lengthening of cardiomyocytes, without alterations in diameter size. Remarkably, myocardial fibrosis increased as well as circulating pro-fibrotic markers. Whether the morphological changes are a direct effect of reduced pulsatility during cf-LVAD support or due to HF progression requires further investigation.

AB - OBJECTIVES: During support with a left ventricular assist device (LVAD), partial reverse remodelling takes place in which fibrosis plays an important role. In this study, we analysed the histological changes and expression of fibrotic markers in patients with advanced heart failure (HF) during continuous-flow LVAD (cf-LVAD) support.METHODS: In 25 patients, myocardial tissue at the time of LVAD implantation (pre-LVAD) was compared with tissue from the explanted left ventricle (post-LVAD). Interstitial fibrosis and cardiomyocyte size were analysed pre-and post-LVAD. Plasma was obtained from all patients before and during LVAD support. Plasma levels, cardiac mRNA and protein expression of brain natriuretic peptide (BNP), galectin-3 (Gal-3), connective tissue growth factor (CTGF), osteopontin (OPN) and transforming growth factor beta-1 were determined.RESULTS: Fibrosis increased during cf-LVAD unloading (P <0.05). Cardiomyocytes elongated (P <0.05), whereas cross-sectional area did not change. BNP, Gal-3, CTGF and OPN were significantly elevated pre-LVAD in comparison with controls. BNP decreased significantly after 1 month of cf-LVAD support (P <0.001) to near-normal levels. Pro-fibrotic markers remained elevated in comparison with controls.CONCLUSIONS: cf-LVAD support is associated with lengthening of cardiomyocytes, without alterations in diameter size. Remarkably, myocardial fibrosis increased as well as circulating pro-fibrotic markers. Whether the morphological changes are a direct effect of reduced pulsatility during cf-LVAD support or due to HF progression requires further investigation.

KW - Adult

KW - Biomarkers

KW - Connective Tissue Growth Factor

KW - Female

KW - Fibrosis

KW - Galectin 3

KW - Heart Failure

KW - Heart-Assist Devices

KW - Humans

KW - Male

KW - Middle Aged

KW - Myocardium

KW - Myocytes, Cardiac

KW - Natriuretic Peptide, Brain

KW - Osteopontin

KW - Transforming Growth Factor beta

KW - Ventricular Remodeling

KW - Journal Article

U2 - 10.1093/ejcts/ezu539

DO - 10.1093/ejcts/ezu539

M3 - Article

C2 - 25609773

SN - 1010-7940

VL - 48

SP - 407

EP - 415

JO - European Journal of Cardio-thoracic Surgery

JF - European Journal of Cardio-thoracic Surgery

IS - 3

ER -

Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support

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Keywords

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