Two recent large randomized clinical trials have demonstrated the benefits of SGLT2 inhibitors [62,133] compared to a placebo in patients with HFpEF and NYHA HF classes II to IV symptoms, structural heart disease (left atrial enlargement or left ventricular hypertrophy), recent HF hospitalization, elevated BNP levels, and an EF greater than 40% [134]. This evidence concerns the gene NPPB and hydrops fetalis.