Plasma biomarkers of myocardial fibrosis and remodeling in terminal heart failure patients supported by mechanical circulatory support devices.
BACKGROUND
In this study we analyzed putative biomarkers for myocardial remodeling in plasma from 55 endstage heart failure patients with the need for mechanical circulatory support (MCS). We compared our data to 40 healthy controls and examined if MCS by either ventricular assist devices or total artificial hearts has an impact on plasma concentrations of remodeling biomarkers.


RESULTS
Plasma biomarkers were analysed pre and 30 days post implantation of a MCS device using commercially available enzyme linked immunosorbent assays (ELISA). We observed that the plasma concentrations of remodeling biomarkers: tissue inhibitor of metalloproteinase 1 (TIMP1), tenascin C (TNC), galectin 3 (LGALS3), osteopontin (OPN) and of neurohumoral biomarker brain natriuretic peptide (BNP), are significantly elevated in patients with terminal heart failure compared to healthy controls. We did not find elevated plasma concentrations for matrix metalloproteinase 2 (MMP2) and procollagen I C-terminal peptide (PCIP). However, only BNP plasma levels were reduced by MCS, whereas the concentrations of remodeling biomarkers remained elevated or even increased further 30 days after MCS. LGALS3 plasma concentrations at device implantation were significantly higher in patients who did not survive MCS due to multi organ failure (MOF).


CONCLUSIONS
Our findings indicate that mechanical unloading in endstage heart failure is not reflected by a rapid reduction of remodeling plasma biomarkers.
Milting
Hendrik
H
Herz- und Diabeteszentrum NRW, Erich und Hanna Klessmann Institut für Kardiovaskuläre Forschung und Entwicklung, Bad Oeynhausen, Germany. hmilting@hdz-nrw.de
Ellinghaus
Peter
P
Seewald
Michael
M
Cakar
Hamdin
H
Bohms
Birte
B
Kassner
Astrid
A
Körfer
Reiner
R
Klein
Martina
M
Krahn
Thomas
T
Kruska
Lothar
L
El Banayosy
Aly
A
Kramer
Frank
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004719:Endomyocardial Fibrosis / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D037502:Galectin 3 / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology* / Q000601:surgery; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D053495:Osteopontin / Q000097:blood; D012720:Severity of Illness Index; D019063:Tenascin / Q000097:blood; D020257:Ventricular Remodeling
D015415:Biomarkers; D037502:Galectin 3; D019063:Tenascin; D053495:Osteopontin; D020097:Natriuretic Peptide, Brain; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1