Cyclic adenosine monophosphate (cAMP) plays a major role in normal and pathologic signaling in the heart. Phosphodiesterase 4 (PDE4) is a major PDE degrading cAMP in the heart. There are inconsistencies concerning the roles of the PDE4 isoforms 4B and 4D in regulation of cardiac function. Cardiac PDE4B overexpression is beneficial in remodeling and heart failure (HF), however, the effect of PDE4D and PDE4 inhibitor in HF remains unclear. We generated global and conditional cardiac-specific heter...