Circulating growth differentiation factor-15 correlates with myocardial fibrosis in patients with non-ischaemic dilated cardiomyopathy and decreases rapidly after left ventricular assist device support

Sjoukje I. Lok*, Bjorn Winkens, Roel Goldschmeding, Ankie J. P. van Geffen, Fay M. A. Nous, Joyce van Kuik, Petra van der Weide, Corinne Klopping, J. Hans Kirkels, Jaap R. Lahpor, Pieter A. Doevendans, Nicolaas de Jonge, Roel A. de Weger

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and is emerging as a biomarker of cardiac remodelling. Left ventricular assist devices (LVADs) provide unloading of the left ventricle, resulting in partial reverse remodelling. Our aim was to study GDF-15 in patients with a non-ischaemic dilated cardiomyopathy (DCM) during LVAD support. We analysed circulating GDF-15 in 30 patients before and 1, 3, and 6 months after LVAD implantation and before heart transplantation or explantation. In addition, mRNA and protein expression of GDF-15 were evaluated in myocardial tissue obtained prior to and after LVAD support. Circulating GDF-15 was significantly higher before LVAD implantation as compared with healthy controls (P 0.001). After 1 month of mechanical support, GDF-15 levels were significantly decreased compared with pre-implantation levels (P 0.001) and remained stable thereafter. Circulating GDF-15 was significantly correlated with kidney function and the severity of myocardial fibrosis. Interestingly, GDF-15 mRNA and protein expression in the myocardium were hardly detectable. High circulating levels of GDF-15 in patients with end-stage non-ischaemic DCM correlate with myocardial fibrosis and kidney function and decline strongly after 1 month of mechanical unloading, remaining stable thereafter. However, cardiac mRNA and protein expression of GDF-15 are very low, suggesting that the heart is not an important source of GDF-15 production in these patients.
Original languageEnglish
Pages (from-to)1249-1256
JournalEuropean journal of heart failure
Volume14
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • GDF-15
  • LVAD
  • Heart failure
  • DCM
  • Remodelling
  • Fibrosis

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