PDE9A and hydrops fetalis: Lee et al. (2015) revealed that PDE9A is upregulated in the failing human heart and inhibits NP- rather than NO-dependent cGMP signaling. Inhibition of PDE9A was subsequently shown to protect the myocardium from neurohormonal and hemodynamic stress. Interestingly, oral PDE9A inhibitors are available and well tolerated in humans (Schwam et al., 2014; Moschetti et al., 2016; Brown et al., 2019) and might constitute a future approach to HF treatment.