The early promise of istaroxime, which promotes the activity of sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and thereby promotes expulsion of free intracellular ionic calcium through transmembrane sodium/calcium channels appears not to been sustained since the publication of the findings of the HORIZON study [19,20,21] and the results of the CUPID-HF study suggest that gene transfer of the SERCA2 gene is not yet a proven intervention [22]. The gene discussed is ATP2A2; the disease is hydrops fetalis.