AC5 transgenic mice with knockout of the Epac1 gene had decreased cardiac dysfunction and were less susceptible to pacing-induced atrial fibrillation after chronic isoproterenol infusion compared to controls while evincing less cardiac apoptosis and fibrosis than the AC5 transgenics, suggesting that Epac1 mediates the deleterious effects of AC5 overexpression on cardiac function and rhythmogenesis (Cai et al., 2016). This evidence concerns the gene RAPGEF3 and atrial fibrillation.