In this study, we could demonstrate that both BNP and Sac/Val exert beneficial effects on human atrial myocardium and that NEP expression in progressing HF with reduced EF is downregulated as part of an adaptive mechanism, and our data suggest that the favorable effects of Sac/Val are partly due to the increased concentration of NPs in the myocardium and that these effects are already achieved in therapeutic clinical doses. Here, NPPB is linked to hydrops fetalis.