RAPGEF4 and heart failure: Furthermore, studies aiming at direct pharmacologic activation of Epac using the cAMP analogue 8-CPT (8-pCPT-2’-O-Me-cAMP), that discriminates between PKA and Epac in vitro [24], have incriminated Epac in cardiac hypertrophy and heart failure [25, 26], in addition to protecting from IR-induced kidney injury [27].