In the adjacent population of HF with reduced ejection fraction, we previously estimated that comprehensive medical therapy with four therapies (targeting five distinct pathways) with ARNI, β-blocker, MRA and SGLT2i could afford over 6 years of additional event-free survival in a 65-year-old compared with conventional medical therapy (consisting of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and β-blocker)8. The gene discussed is ACE; the disease is hydrops fetalis.