Abstract 18278: The Prognostic Value Of WFDC2, a New Biomarker for Heart Failure

Abstract

Aim s: Identification of plasma biomarkers that help to stratify heart failure (HF) patients may help to improve treatment. We investigated the prognostic value of WAP four-disulfide core domain protein 2 (WFDC2, also termed HE4), a biomarker not previously described in HF. Methods: Data of 567 patients participating in the Coordinating study evaluating outcomes of Advising and Counselling in Heart failure (COACH) study were analysed. Patients had been hospitalized for HF and were followed for 18 months. Several plasma biomarker levels were determined using an ELISA platform. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization. Results: Mean age was 71±11 years, 62% were males, mean LVEF was 33±14%, and mean eGFR was 54±20 mL/minute. WFDC2 was identified as a biomarker that showed strong correlation with HF severity, according to NYHA functional class and BNP levels ( P < 0.001). WFDC2 also showed a strong positive correlation with GDF15 ( P <0.001). In addition, WFDC2 levels correlated with kidney function (BUN, creatinine, and eGFR; all P <0.001). Cox regression analysis revealed that a doubling of WFDC2 levels was associated with a hazard ratio (HR) of 1.73 (1.53-1.95) for the primary outcome ( P <0.001). After correction for age, gender, BNP and eGFR the HR was 1.46 (1.23-1.72) ( P <0.001) and after additional adjustment for GDF15 the HR lowered to 1.30 (1.07-1.59) ( P =0.009). The AUC in the ROC curve analysis increased from 0.7123 to 0.7375 when WFDC2 was included to the clinical model ( P =0.068). The IDI and NRI metrics for reclassification showed highly significant improvements when WFDC2 was added to the clinical model (NRI=0.12, P <0.001) and this remained significant after inclusion of BNP to this model. Conclusion: WFDC2 plasma levels are correlated with markers of HF severity, show prognostic value, and improve risk assessment in HF.