One of the factors suggested to be involved in the progression from cardiac hypertrophy to heart failure is a decline in fatty acid oxidation that may cause a deficit in ATP production and consequent contractile dysfunction.48,49 Augmentation of fatty acid oxidation has been associated with preserving ATP production and ameliorating the effects of pressure-overload-induced failure.50–52 Our studies of pressure-overload hypertrophy in NOX4 gene-modified mice support this notion. This evidence concerns the gene NOX4 and heart failure.