In the pivotal PARADIGM-HF trial, sacubitril/valsartan as the first-in-class angiotensin receptor–neprilysin inhibitor (ARNI) was associated with a 20% relative reduction in the risk of cardiovascular (CV) death and heart failure (HF)-related hospitalization (primary endpoint) in adult patients with symptomatic chronic HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] ≤ 40%) compared with angiotensin-converting enzyme inhibitor (ACEi) [1]. This evidence concerns the gene ACE and hydrops fetalis.