While substantial data demonstrated that β-blockers, renin–angiotensin–aldosterone system (RAAS) inhibitors, and angiotensin receptor–neprilysin inhibitors (ARNI) significantly improve the prognosis of HF patients with reduced EF (HFrEF), no consistent data reported a prognostic beneficial role of these classes of drugs in HFpEF. This evidence concerns the gene MME and hydrops fetalis.