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

• Published in: European journal of heart failure Vol. 14; no. 11; pp. 1249 - 1256
• Main Authors: Lok, Sjoukje I., Winkens, Bjorn, Goldschmeding, Roel, van Geffen, Ankie J.P., Nous, Fay M.A., van Kuik, Joyce, van der Weide, Petra, Klöpping, Corinne, Kirkels, J. Hans, Lahpor, Jaap R., Doevendans, Pieter A., de Jonge, Nicolaas, de Weger, Roel A.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2012
• Subjects: Adult; Cardiomyopathy, Dilated - blood; Cardiomyopathy, Dilated - pathology; Cardiomyopathy, Dilated - therapy; Cytokines - blood; DCM; Female; Fibrosis; Fibrosis - blood; Fibrosis - pathology; GDF-15; Growth Differentiation Factor 15 - blood; Health Status Indicators; Heart failure; Heart Ventricles - pathology; Heart-Assist Devices; Humans; LVAD; Male; Middle Aged; Prognosis; Program Evaluation; Remodelling; Risk Assessment; Statistics, Nonparametric; Time Factors; Ventricular Dysfunction, Left - therapy; Ventricular Remodeling
• ISSN: 1388-9842; 1879-0844
• DOI: 10.1093/eurjhf/hfs120

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.