RAPGEF4 and hydrops fetalis: Activation of CaMKII is in turn attributable to increased cytosolic Ca and cyclic adenosine monophosphate(cAMP)/exchange protein directly activated by cyclic AMP 2 (cAMP/EPAC2) signaling43 as well as elevated levels of reactive oxygen species (ROS) in the setting of chronic sympathetic overstimulation during HF development.44, 45