HAND1 and chronic obstructive pulmonary disease: This may lead to an increased degree of metabolic flexibility, as evidenced by the fact that the phenotype of cardiac Hand1 up-regulating neonates is more severe than that of αMHC-Cre::VHL(fl/fl) neonates, which are born with relatively normal cardiac morphology and die with cardiac arrhythmia by the second postnatal week [41].