RAPGEF4 and cardiac hypertrophy: While pharmacological inhibition of Epac1 reduces cardiac hypertrophy, fibrosis, inflammation and dysfunction induced by chronic stimulation of β-ARs [113], Epac activators such as 8-pCPT-2′-O-Me-cAMP and its esterified derivative have been shown to promote cardiac hypertrophy and fibrosis [114,115,116].