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

Eur J Heart Fail. 2012 Nov;14(11):1249-56. doi: 10.1093/eurjhf/hfs120. Epub 2012 Jul 26.


Aims: 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.

Methods and results: 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.

Conclusions: 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.

MeSH terms

  • Adult
  • Cardiomyopathy, Dilated / blood
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / therapy*
  • Cytokines / blood
  • Female
  • Fibrosis / blood*
  • Fibrosis / pathology
  • Growth Differentiation Factor 15 / blood*
  • Health Status Indicators
  • Heart Ventricles / pathology*
  • Heart-Assist Devices*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Program Evaluation
  • Risk Assessment
  • Statistics, Nonparametric
  • Time Factors
  • Ventricular Dysfunction, Left / therapy*
  • Ventricular Remodeling


  • Cytokines
  • Growth Differentiation Factor 15