Despite advancements in guideline-directed medical therapy (GDMT), including beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs), outcomes remain suboptimal, especially for HF with preserved ejection fraction (HFpEF ≥50%) patients, where disease-modifying treatments are limited. The gene discussed is NR3C2; the disease is hydrops fetalis.