Sjoukje I Lok1, Fay M A Nous2, Joyce van Kuik2, Petra van der Weide2, Bjorn Winkens3, Hans Kemperman4, Andre Huisman2, Jaap R Lahpor5, Roel A de Weger2, Nicolaas de Jonge6. 1. Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands s.lok@umcutrecht.nl. 2. Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands. 3. Department of Methodology and Statistics, University of Maastricht, Maastricht, Netherlands. 4. Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, Netherlands. 5. Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, Netherlands. 6. Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.
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 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.
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 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: Jerzy Pacholewicz; Michał Zakliczyński; Jerzy Nożyński; Paweł Nadziakiewicz; Michał Zembala; Marian Zembala Journal: Kardiochir Torakochirurgia Pol Date: 2019-06-28
Authors: Sabine Ameling; Gourav Bhardwaj; Elke Hammer; Daniel Beug; Leif Steil; Yvonne Reinke; Kerstin Weitmann; Markus Grube; Christiane Trimpert; Karin Klingel; Reinhard Kandolf; Wolfgang Hoffmann; Matthias Nauck; Marcus Dörr; Klaus Empen; Stephan B Felix; Uwe Völker Journal: Basic Res Cardiol Date: 2016-07-13 Impact factor: 17.165