PDE5A and hydrops fetalis: The main findings of the present study investigating the impact of chronic PDE5 inhibition on cardiac function and structure in HF are threefold: i) PDE5 inhibition improves indices of cardiac contractility and restores systolic calcium and catecholamine responsiveness; ii) t-tubule density is reduced in HF and fully restored to control levels by PDE5 inhibition and, iii) changes in expression of the putative t-tubule regulator AmpII are correlated with changes in t-tubule density and AmpII drives de novo tubule formation in ventricular myocytes.