HMGCS2 is a critical mitochondrial enzyme that catalyses the rate-limiting step in ketogenesis and may affect the heart’s ability to efficiently manage metabolic stress.46,47 Additionally, cardiac proteomics of Rbm20 KO rats revealed the up-regulation of Ankrd1, which promotes hypertrophic gene expression,48,49 and the down-regulation of FHL2, a negative regulator of cardiac hypertrophy.46,50 The combined effect of increased Ankrd1 and decreased FHL2 expression could contribute to the development of hypertrophic remodelling. This evidence concerns the gene HMGCS2 and cardiac hypertrophy.