It is thought that the suppression of NHE1 by SGLT2i reduces cardiac, injury, hypertrophy and fibrosis as well as reduce in the risk of cardiovascular death and hospitalization for heart failure [40, 41], and AMPK might also mediate indirect SGLT2i–NHE interactions in the heart [44], whereas the suppression of NHE3, which is increased in HF, leads to the inhibition of proximal tubular reabsorption of sodium and thereby decreasing intravascular volume and cardiac wall stress [40, 41, 45]. This evidence concerns the gene SLC9A3 and heart failure.