We found 76 human genes with recently evolved cardiac-enriched expression, such as CMAHP, a hydroxilase involved in sialic acid metabolism that was pseudogenized 2–3 million years ago (Mya)24, and an Alu-derived isoform encoded by the sodium-glucose co-transporter gene SGLT1. We show that evolutionarily young genes and sORFs can be biologically active and show dysregulation in heart failure. This evidence concerns the gene SLC5A1 and heart failure.