Serum tenascin-C level as a potential predictive marker of quantitative myocardial fibrosis in dilated cardiomyopathy

INTRODUCTION: The extent of myocardial fibrosis in dilated cardiomyopathy (DCM) patients is an important predictor of prognosis and response to therapy. Although endomyocardial biopsy (EMB) is the gold standart technique in the diagnosis of myocardial fibrosis, due to limitation in the number of biopsy materials and heterogeneity, it has limited significance in detection of global fibrosis and also it is an invasive procedure. Cardiac magnetic resonance imaging (CMR) does not contain these limitations and can evaluate all segments of myocardium, particularly in assessing quantitative myocardial fibrosis. Tenascin-C (TN-C) glycoprotein was shown to be a marker of ongoing fibrosis in myocardium in trials of DCM patients. It was also detected in EMB specimens of DCM patients. However, there are limited number of studies with limited number of patients assessing the association of TN-C with myocardial fibrosis. Moreover, none of these studies evaluated the myocardial fibrosis by CMR, a technique to detect accurate and quantitative myocardial fibrosis. In the basis of these data, we planned this study to detect if serum TN-C levels can be used as a potential marker in predicting quantitative myocardial fibrosis in DCM patients. METHODS: 30 DCM patients followed in our DCM clinic were included in our study. Serum TN-C levels were measured by ELISA technique. Additionally, we performed CMR and echocardiography procedures and routine blood biochemical measures at the same day. CMR images were evaluated by an experienced radiologist in terms of quantitative myocardial fibrosis. In this manner, the association of serum levels of TN-C, that is a biomarker of ongoing fibrosis in myocardium, and the extent of myocardial fibrosis detected by CMR was evaluated in DCM patients. All data were evaluated relatively using appropriate statistical analysis. RESULTS: In our study, the mean level of serum TN-C was 12.61 ± 8.31 ng/mL; lower than the levels in the literature. Also, the mean quantitative myocardial fibrosis level detected by CMR was 19.9 ± 23.8 %, that was higher than the levels in the literature. As a result of these data, we observed no correlation between the serum TN-C levels and quantitative myocardial fibrosis by CMR in our 30 DCM patients (r=0,018, p=0,925). Also, there was a significant negative correlation between serum levels of TN-C and LVEF (r=-0,474, p=0,008), FS (r=-0,480, p=0,007), beta blocker therapy (serum TN-C in patients with therapy 14.37 ng/mL, without therapy 25.67 ng/mL, p=0.035) and CK levels (r=-0,428, p=0,021); whereas a significant positive correlation was detected between serum levels of TN-C and SPAP (r=0,509, p=0,004), MR (r=0,585, p=0,001), TR (r=0,414, p=0,023), NYHA functional level (r=0,406, p=0,026), pro-BNP levels (r=0,666, p<0,001), LVDD (the mean serum TN-C level in patients with LVDD was higher: 17.73 ng/mL/11.05 ng/mL, p=0.05), troponin levels (r=0,462, p=0,015), LDL (r=0,522 p=0,004) and blood urea (r=0,531, p=0,003). Finally, quantitative myocardial fibrosis was shown to have a significant negative correlation with vitamin D (r=-0,468, p=0,016) and significant positive correlation with LVDD (18,08% in patients with LVDD and 10,35% in patients without LVDD, p=0.022). CONCLUSION: In DCM patients, no relationship was detected between serum TN-C and quantitative myocardial fibrosis detected by CMR. This result may be explanied as TN-C plays role in ongoing fibrotic and active inflammatory myocardial tissue, not in chronic fibrotic myocardial tissue. Another explanation is that TN-C may be released to circulation not directly from myocardium, but from hepatic or pulmonary tissue secondary to inflammatory process in myocardium. We also detected that serum TN-C is correlated with prognostic factors of DCM. Thus, TN-C can predict severe heart failure and worse prognosis. At this point, it should be discussed how TN-C is related with worse cardiovascular prognosis; since no correlation was detected with myocardial fibrosis. A possible explanation is that even TN-C is not associated with total amount of myocardial fibrosis, it may be associated with only ongoing fibrosis amount. Also, since it may be synthesized in liver and lung secondary to myocardial inflammation, it may be associated with worse prognosis by means of secondary pulmonary hypertension or other pulmonary and hepatic complications. However, we should underline the fact that serum TN-C levels in our study were much lower than those in the literature. In this manner, one should keep in mind that in stable DCM patients under optimal medical therapy, serum TN-C may be in normal ranges even in severe heart failure with worse prognostic factors. This is the first study to investigate the correlation of TN-C with the amount of myocardial fibrosis. We expect this study to contribute to literature in this issue. However, further studies with larger populations are needed in order to evaluate this relationship accurately. KEY WORDS: Dilated cardiomyopathy, Tenascin-C, Cardiac MRI, myocardial fibrosis, predictor.