Altered serum levels of neprilysin in heart failure patients with reduced ejection fraction

OBJECTIVE: In addition to the recent success of neprilysin inhibition in treatment of heart failure, elevated soluble neprilysin (sNEP) in circulation has been suggested to be a prognostic biomarker in heart failure with a reduced ejection fraction (HFrEF). However, the diagnostic performance of sNEP is nebulous and its levels in HFrEF have not been compared with controls. For the purpose of this study, we determined the role of sNEP levels as a biomarker in routine ambulatory care of HFrEF patients, when compared to the control subjects. METHODS: Ambulant patients with chronic HFrEF (n = 18) were included. Apparently healthy volunteers - hospital physicians (n = 9) were included as the controls. Besides standard diagnostic tools (echocardiographic examination and laboratory biochemical diagnostic tests including NT-proBNP assessment), we analysed serum levels of neprilysin with a commercially available human soluble neprilysin ultrasensitive ELISA kit (Aviscera Bioscience, USA). RESULTS: Concentrations of sNEP were significantly reduced in HFrEF patients (average ± S.E.M.=1038 ± 464 pg/ml) when compared to the controls (1947 ± 613 pg/ml; p < 0.05). Two of eighteen HFrEF samples were below, while two of ten control samples were above the detection limit of the immunoassay. We documented a lack of significant correlation between sNEP and left ventricular ejection fraction (LVEF) and other echocardiographic features as well as NT-proBNP. However, sNEP significantly negatively correlated to serum natrium levels (Spearman r = ‒0.6112, p < 0.05) and to systolic blood pressure (Spearman r = ‒0.4746, p < 0.05) in HFrEF. CONCLUSION: Levels of sNEP were significantly reduced in HFrEF, when compared to the controls, with absent correlations to relevant HF-related features (e.g. LVEF). These findings might contribute to clarification of the diagnostic value of sNEP in HF (Tab. 2, Fig. 2, Ref. 30)