The tetragenous therapy for HFrEF recommended in the 2022 AHA/ACC/HFSA heart failure guidelines, includes angiotensin receptor-neprilysin inhibitor (ARNI), β-blockers, sodium-glucose cotransporter-2 inhibitors (SGLT2), mineralocorticoid receptor antagonist (MRA) and other drugs (24). Here, NR3C2 is linked to heart failure.