Depending on the recent findings with sodium-glucose cotransporter 2 (SGLT2) inhibitors’ effect on modulating NHE1 and NCX activities, improving Na+ and Ca2+ handling, and preventing cardiac remodeling while maintaining ATP content [16,113,155], decreasing intracellular Na+ and Ca2+ overload in heart failure might be considered an alternative approach. The gene discussed is SLC5A2; the disease is heart failure.