Prognostic value of fibrosis-related markers in dilated cardiomyopathy: A link between osteopontin and cardiovascular events.

INTRODUCTION

Serum markers of fibrosis provide an insight into extracellular matrix (ECM) fibrosis in heart failure (HF) and dilated cardiomyopathy (DCM). However, their role as predictors of cardiovascular (CV) events in DCM is poorly understood.

METHODS

This is an observational, prospective cohort study. 70 DCM patients (48±12.1years, ejection fraction - EF 24.4±7.4) were recruited. Markers of collagen type I and III synthesis - procollagen type I and III carboxy- and amino-terminal peptides (PICP, PIIICP, PINP, PIIINP), fibrosis controlling factors - ostepontin (OPN), transforming growth factor (TGF1-β) and connective tissue growth factor (CTGF), and matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor (TIMP-1), were measured in serum. All patients underwent endomyocardial biopsy. The end-point was combined with CV death and urgent HF hospitalization. Patients were divided into two groups: those who did (group 1, n=45) and did not reach (group 2, n=25) an end-point.

RESULTS

Over a 12-month period of observation, 6 CV deaths and 19 HF hospitalizations occurred. Qualitative and quantitative measures of ECM fibrosis were similar in both groups. The levels of all of the markers of collagen synthesis, TGF1-β, MMP-9 and TIMP-1 were similar, however, OPN, CTGF and MMP-2 were significantly lower in group 1.

CONCLUSIONS

Invasively-determined fibrosis levels were not related with CV outcomes in DCM. Out of the 11 markers of fibrosis under study, only OPN was found to be related to CV outcomes. OPN is not only the pivotal protein controlling fibrosis, but may also serve as a biomarker associated with prognosis.