title: Myocardial fibrosis and pro-fibrotic markers in end-stage heart failure patients during continuous-flow left ventricular assist device support.
abstract: OBJECTIVE
  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 β-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.
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands s.lok@umcutrecht.nl.
authors.forename: Sjoukje I
authors.initials: SI
authors.lastname: Lok
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Fay M A
authors.initials: FM
authors.lastname: Nous
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Joyce
authors.initials: J
authors.lastname: van Kuik
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: van der Weide
authors.affiliation: Department of Methodology and Statistics, University of Maastricht, Maastricht, Netherlands.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Winkens
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Kemperman
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Andre
authors.initials: A
authors.lastname: Huisman
authors.affiliation: Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Jaap R
authors.initials: JR
authors.lastname: Lahpor
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Nicolaas
authors.initials: N
authors.lastname: de Jonge
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D055513:Connective Tissue Growth Factor / Q000097:blood; D005260:Female; D005355:Fibrosis; D037502:Galectin 3 / Q000097:blood; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000601:surgery*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D053495:Osteopontin / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D037502:Galectin 3; D016212:Transforming Growth Factor beta; D053495:Osteopontin; D020097:Natriuretic Peptide, Brain; D055513:Connective Tissue Growth Factor
keywords: Biomarkers; Fibrosis; Heart failure; LVAD; Reverse remodelling