Recent advancements in the treatment of heart failure with reduced ejection fraction (HFrEF) have significantly improved patient outcomes, with both pharmacological and device-based innovations.1 The ‘four pillars’ of guideline-directed medical therapy (GDMT) sodium-glucose cotransporter-2 inhibitors (SGLT2i), renin-angiotensin-system inhibitors (RASi) or angiotensin receptor neprilysin inhibitors (ARNI), beta-blockers, and mineralocorticoid receptor antagonists (MRA) have been shown to reduce cardiovascular mortality or hospitalization for heart failure (HF) by 64%.2 The gene discussed is NR3C2; the disease is heart failure.