We have recently demonstrated that acute ex vivo incubation of right atrial appendages isolated from overweight, nondiabetic patients with all-spectrum HF undergoing cardiac surgery, with either EMPA or DAPA at clinical relevant concentrations, decreased the expression of the mitochondrial enzyme monoamine oxidase (MAO) and alleviated oxidative stress elicited by the ex vivo exposure to angiotensin II (Ang II) and high glucose, as a novel “off-target” cardiac class effect of SGLT2i. The gene discussed is AGT; the disease is hydrops fetalis.