Exploring Neurohormonal Modulation by Acetazolamide in Heart Failure

Background Heart failure (HF) is commonly managed by addressing water and sodium (Na) balance, with arterial circulation playing a major role in influencing renal Na and water excretion. Recently, chloride (Cl) has been recognized as an important factor in HF, associated with volume regulation and its modulation of renin-angiotensin-aldosterone system (RAAS) activity through macula densa signaling, which impacts Na retention and neurohormonal activation. Acetazolamide, a carbonic anhydrase inhibitor, can enhance decongestion in HF by increasing urinary Na and Cl excretion when added to loop diuretics, a mechanism supported by prior studies demonstrating improved urine output and decongestion. Objective This study investigates the neurohormonal effects of acetazolamide in acute HF, focusing on its ability to enhance decongestion, reduce neurohormonal activation (e.g., renin and aldosterone), and modulate RAAS markers. Methods In this prospective, single-center observational study, 80 patients with acute HF were enrolled and divided into two groups: a case group (n=40) receiving acetazolamide with standard therapy and a control group (n=40) on standard therapy alone. Patients were matched based on clinical characteristics to reduce selection bias. Baseline characteristics, neurohormonal profiles, including plasma renin activity (PRA) and aldosterone, electrolyte levels, and clinical outcomes were compared. Results The acetazolamide group exhibited higher urinary Cl excretion (108.9±25.3 mEq/L vs. 79.2±22.7 mEq/L; p<0.001) and reduced PRA and aldosterone levels (1.3±0.4 ng/mL/h and 88±21 pg/mL) compared to controls (1.7±0.6 ng/mL/h and 128±29 pg/mL; p=0.002 and p=0.006, respectively). These reductions in PRA and aldosterone are significant as they correlate with improved volume status and reduced neurohormonal stress, which are critical components in HF management. Improved clinical outcomes included a greater percentage of patients becoming symptom-free within 72 hours (77.5% vs. 52.5%; p=0.018) and shorter hospitalization (5.6±1.4 days vs. 7.1±1.7 days; p=0.028). Conclusion Acetazolamide in addition to standard therapy enhances decongestion and reduces neurohormonal activation in acute HF, suggesting its dual benefit in fluid management and neurohormonal modulation. Further research is needed to confirm these benefits, assess long-term effects, and overcome limitations, including the study's single-center observational design.