Recent clinical trials evaluating innovative heart failure medications have shown that three drug classes (mineralocorticoid receptor antagonists [MRAs], angiotensin receptor-neprilysin inhibitors [ARNIs], and sodium/glucose cotransporter 2 [SGLT2] inhibitors) reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF) beyond the conventional therapy consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and β blockers [237,238]. This evidence concerns the gene NR3C2 and heart failure.