Mechanical circulatory support
Plasma Biomarkers of Myocardial Fibrosis and Remodeling in Terminal Heart Failure Patients Supported by Mechanical Circulatory Support Devices

https://doi.org/10.1016/j.healun.2008.02.018Get rights and content

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.

Methods & 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.

Section snippets

Patient Population

We analyzed plasma samples of 40 blood donors and 55 patients with deteriorating HF and need for MCS. Forty of the MCS patients were supported by a VAD and 15 by a TAH. Left ventricular end-diastolic diameter (LVEDD) and ejection fraction (EF), respectively, at the time of MCS device implantation were as follows (mean ± SD): VAD patients, 72.5 ± 9.4 mm and 26.2 ± 11.1%; and TAH patients, 65 ± 11.3 mm and 23.5 ± 17.9%. See Table 1 for abbreviations and detailed clinical data. TAH implantation

B-type Natriuretic Peptide

Natriuretic peptide BNP is released by the myocardium upon mechanical stress.11 In control samples from blood donors we observed a plasma concentration (mean ± SD) of 17.4 ± 14.6 pg/ml. At the time of VAD or TAH implantation we detected levels of 1,663 ± 1,627 pg/ml and 2,151 ± 2,431 pg/ml, respectively. Mechanical unloading of the heart or removal of the failing ventricles reduced plasma concentrations to 438.6 ± 501.4 pg/ml in VAD patients and to 311.8 ± 259.1 pg/ml in TAH recipients (Figure 1

Discussion

Impaired myocardial collagen turnover is associated with cardiac remodeling and HF. Structural reshaping of the myocardium is mainly controlled by the activity of MMPs and TIMPs. The failing heart displays an increased expression of MMP-2, TIMP1 and TIMP4 on mRNA and protein level.21, 22, 23 In addition, it has been found that plasma concentrations of MMP-2 and TIMP1 are correlated with the severity of HF, as defined by the classication of the New York Heart Association (NYHA),13, 24, 25 and

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    The first two authors (H.M. and P.E.) contributed equally to this work.

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