Progression of heart failure (HF) is driven in part by maladaptive responses of cardiac muscle to pathological stress.1 There is growing evidence that stimulation of a signalling pathway within cardiac myocytes, the cyclic GMP (cGMP)–protein kinase-G (PKG) axis, dampens these cardiac stress responses, and its activation can attenuate pathological hypertrophy, protect against ischaemic injury and enhance cell survival.2 One means of potentiating cGMP–PKG is by inhibiting the degradation of cytosolic cGMP by phosphodiesterase-5 (PDE5, figure 1). Here, PRKG1 is linked to hydrops fetalis.