In light of these studies, ketones have been hypothesized to be a “thrifty-fuel” (9), with increases in ketone availability (either directly by ketone infusion or indirectly through SGLT2 inhibition) being demonstrated to reduce pathologic cardiac remodeling and improve systolic function in murine, canine, and swine models of heart failure (15, 20, 21). This evidence concerns the gene SLC5A2 and heart failure.