Importantly, NRG-1 exerts a lusitropic effect on isolated cardiac muscle preparations via a NO-dependent mechanism (Lemmens et al., 2004): this requires a functional NO synthase, with preserved NO bioavailability, a condition which can be hampered by the increased oxidative stress in HF (Nediani et al., 2011; Arcaro et al., 2016). Here, NRG1 is linked to hydrops fetalis.