While there is consensus that activation of the CaMKII-HDAC4-MEF2 pathway causes the adverse left ventricular remodeling and heart failure that is associated with TAC-induced LVH (Ling et al., 2009; Kreusser et al., 2014), it has been less clear to some that this pathway induces the hypertrophy per se. This evidence concerns the gene HDAC4 and heart failure.