It can be speculated that while activation of AMPK by post-translational modifications could be an acute response to energy deficiency or increase in workload, in the long term as in hypertrophy or heart failure, energy deficiency induces transcriptional up-regulation of AMPK subunits leading to an increase in the active form of the enzyme despite maintained phosphorylation ratio. This evidence concerns the gene PRKAA2 and heart failure.