The associations between low soluble neprilysin levels and an adverse cardiometabolic and smoking profile in the general population on one hand and the association between high levels and poor outcome [18–20] as well as the beneficial effect of simultaneous neprylisin and angiotensinII inhibition in HF with altered LVEF populations [12] may be explained by different populations and different levels and patterns of neurohormonal activation. The gene discussed is MME; the disease is hydrops fetalis.