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The biomarker plasma galectin-3 in advanced heart failure and survival with mechanical circulatory support devices

by: Gülsüm Erkilet, Cenk Özpeker, Dietmar Böthig, Frank Kramer, Daniela Röfe, Birte Bohms, Michiel Morshuis, Jan Gummert, Hendrik Milting
The Journal of Heart and Lung Transplantation, Vol. 32, No. 2. (February 2013), pp. 221-230, doi:10.1016/j.healun.2012.11.011  Key: citeulike:12046511

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Abstract

During screening of heart transplantation (HTx) candidates supported by ventricular assist devices (VADs) for plasma biomarkers we found that galectin-3 (Gal-3) was increased pre-operatively in patients who later died during VAD support. Therefore, we analyzed the predictive value of plasma Gal-3 in the context of other potential clinical risk factors for death on device (DOD) in a cohort of 175 VAD patients. We analyzed numerous clinical factors and plasma Gal-3 levels of 175 VAD patients before device implantation. Eighty VAD patients were successfully bridged to HTx (BTT, 45.7%), 80 (45.7%) died on VAD, 2 recovered on device (BTR, 1.1%) and 13 (7.4%) were still on device. Uni- and multivariate analyses were performed to assess the importance of Gal-3 with respect to other clinical factors. Myocardial gene expression of Gal-3 was investigated in apex samples by RT-PCR (n = 30) and Western blotting (n = 45). Plasma Gal-3 levels were higher in VAD patients than in controls (16.6±9.3 vs 9.5±3.9 ng/ml, p < 0.0001). Cox regression showed several clinical factors and type of VAD as independent outcome predictors, but Gal-3 was not among them. Using the regression equation we grouped patients according to their factor constellation for prediction of survival on VAD. We propose a calculation method for VAD survival prediction. Gal-3 mRNA and protein were detectable in failing myocardium, but did not correlate with its plasma concentration. Galectin-3 levels are associated with severe heart failure but do not provide sufficient discrimination for prediction of outcomes after VAD implantation. Importantly, we were unable to confirm myocardial tissue as a primary source for the observed plasma elevations of Gal-3.


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