Pathophysiology
Clinical meaning
Aldosterone plays a critical pathological role in heart failure beyond its renal sodium-retaining effects. Aldosterone promotes myocardial fibrosis (stimulates collagen synthesis by cardiac fibroblasts), vascular endothelial dysfunction, baroreceptor impairment, potassium and magnesium wasting (increasing arrhythmia risk), and sympathetic nervous system activation. Despite ACEi/ARB therapy, 'aldosterone breakthrough' occurs in up to 40% of patients where aldosterone levels re-elevate through non-ACE pathways. MRAs (spironolactone, eplerenone) block the mineralocorticoid receptor in the heart, vasculature, and kidney, addressing this breakthrough. The RALES trial showed spironolactone reduced mortality by 30% in severe HFrEF (NYHA III-IV). The EMPHASIS-HF trial showed eplerenone reduced cardiovascular death and HF hospitalization in mild HFrEF (NYHA II). Spironolactone is a non-selective MRA that also blocks androgen receptors, causing gynecomastia (10%), breast tenderness, and menstrual irregularities. Eplerenone is selective for the mineralocorticoid receptor without antiandrogen effects but is more expensive. The primary risk with MRAs is hyperkalemia โ potassium must be monitored closely, especially with concurrent RAAS inhibition (ACEi/ARB/ARNI), renal impairment, or potassium supplementation. MRAs should NOT be started if potassium >5.0 mEq/L or creatinine >2.5 mg/dL (men) / >2.0 mg/dL (women)...