Clinically, McMurray et al. (18) demonstrated in the PARADIGM-HF trial that the angiotensin receptor–neprilysin inhibitor (ARNI) LCZ696 not only inhibited RAAS activity but also enhanced natriuretic peptide system function, synergistically improving cardiac load and neurohormonal imbalance, and producing greater reductions in cardiovascular mortality and HF rehospitalization compared with the ACE inhibitor enalapril. This evidence concerns the gene MME and hydrops fetalis.