It was confirmed by using the highly selective β1-blocker CGP-20712A, the PKA inhibitor PKI, and the highly selective Epac activator 8-pCPT, that continuous stimulation of the β1-AR can be mediated through the Epac-mediated Ca2+/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) signaling pathway, which downregulates slow current rectifier potassium current density, delays myocardial repolarization, and increases the risk of arrhythmia [166] (Fig. 6). The gene discussed is ADRB1; the disease is cardiac arrhythmia.