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


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Heart and Diabetes Center NRW, Clinic of Thoracic and Cardiovascular Surgery, Erich and Hanna Klessmann-Institute for Cardiovascular Research and Development, Bad Oeynhausen, Germany.
Gülsüm
G
Erkilet
Cenk
C
Özpeker
Dietmar
D
Böthig
Frank
F
Kramer
Daniela
D
Röfe
Birte
B
Bohms
Michiel
M
Morshuis
Jan
J
Gummert
Hendrik
H
Milting
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D005260:Female; D037502:Galectin 3 / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000401:mortality*; D006353:Heart-Assist Devices; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009206:Myocardium / Q000737:chemistry; D057234:Preoperative Period; D012307:Risk Factors
D015415:Biomarkers; D037502:Galectin 3