PDE9A is the most selective cGMP-hydrolysing PDE of the superfamily.29 In 2015, a study performed in mice demonstrated a role in a model of cardiac pressure-overload, with both global genetic deletion and treatment with a selective PDE9 inhibitor reducing hypertrophy and fibrosis while improving cardiac function.29 The study established a close linkage of PDE9A with the regulation of cGMP generated by NP (rather than nitric oxide) signalling.29 In a recent study in mice, the PDE9 inhibitor CRD-733 improved HF characteristics; human trials in HF using CRD-733 are now underway.133. The gene discussed is ALDH7A1; the disease is hydrops fetalis.