Most of the epicardium, with the exception of that enveloping the distal outflow tract, is derived from the epicardial primordium (proepicardium), after heart tube looping. Cells derived from the epicardium are the only extra cardiac cells that do not enter the heart tube via its poles. Other epicardial cells arise from the splanchnic mesoderm of the ventral pharynx near the outflow pole forms the epicardium of the outflow tract. By E10.5, the surface of the heart is completely enveloped by epicardium; the aorta becomes encased by the epicardium at E11.5. The epicardium is required for the normal growth and maturation of the myocardium. If it fails to grow over the surface of the myocardium, the embryo dies due to cardiac failure.
Epicardium forms at day 28 of human development and between E9.5
and E11.5 in mouse development.