The true CV benefit with SGLT2-inhibition could be benchmarked against the only other novel therapy shown to reduce mortality in a well-treated HF population—the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan, which works by augmenting the natriuretic peptide system and simultaneously inhibiting the renin–angiotensin–aldosterone system [33]. The gene discussed is REN; the disease is hydrops fetalis.