P5447Prognostic significance of carboxy-terminal telopeptide (ICTP) and Caspase-3 in patients with non-ischemic dilated cardiomyopathy
Abstract Background Non-ischemic dilated cardiomyopathy (niDCM) is a common debilitating disease leading to heart failure and poor prognosis. Therefore, a reliable diagnosis of niDCM and search of prognostic biomarkers is a task of paramount importance preventing final destruction of myocardium and improving the outcomes of the disease. The aim of the study was to evaluate the prognostic value of carboxy-terminal telopeptide (ICTP), a marker of myocardial collagen I degradation, and Caspase-3, a marker of apoptosis, in serum and endomyocardium biopsies (EMBs) of patients with niDCM. Methods 34 consecutive patients (male 25 (78%); 43.83±12.17 years) with niDCM (average of left ventricle (LV) end-diastolic diameter 6.94±0.78 cm, LV ejection fraction 24.97±6.93%, mean pulmonary capillary wedge pressure 32.9±8.7 mmHg) were enrolled in the study. The levels of ICTP and Caspase-3 in patients' serum and EMBs were measured by ELISA. After a follow-up period of 5 years, 18 patients (53%) have reached the primary composite end-point of heart failure: 6 patients (17.6%) died, 6 patients (17.6%) had heart transplantation and 6 patients (17.6%) underwent left ventricle assist device implantation. Results Univariate Cox proportional hazard model and ROC curve analysis identified levels of ICTP and Caspase-3 in serum as predictors of composite end-point (Table 1). However, the levels of ICTP and Caspase-3 in EMBs had no prognostic value. The cut-off values of serum biomarkers for prediction of the outcome were 13.43 pg/mg protein (sensitivity 67%; specificity 81%) for ICTP and 10.21 pg/mg protein (sensitivity 53%; specificity 87%) for Caspase-3. Univariate Cox regression analysis revealed that patients with higher levels of ICTP and Caspase-3 than cut-off values in serum had higher risk of reaching the composite end-point compared to the patients with lower cut-off values (HR 4.4 (95% CI: 1.6–12.1) and 3.15 (95% CI: 1.2–8.29), respectively). Kaplan-Meier survival analysis demonstrated that patients with serum Caspase-3 and ICTP levels above cut-off values had significantly worse outcome (p=0.01 and p=0.002, respectively). Table 1 Biomarkers (pg/mg protein) Mean ± SD HR (95% CI) p-value AUC (95% CI) ICTP in serum 15.26±10.59 1.052 (1.013–1.093) 0.009 0.71 (0.53–0.89) ICTP in EMB 132±295 0.999 (0.998–1.001) 0.56 0.45 (0.28–0.61) Caspase-3 in serum 7.78±9.86 1.047 (1.002–1.093) 0.04 0.69 (0.51–0.87) Caspase-3 in EMB 283±282 1 (0.998–1.002) 0.92 0.50 (0.28–0.72) Conclusion The findings show that increased serum levels of Caspase-3 and ICTP are significantly associated with poor outcome in patients with niDCM. Acknowledgement/Funding the Research Council of Lithuania (Grants nos. MIP-086/2012 and MIP-011/2014), the European Union, EU-FP7, SARCOSI Project (no. 291834)