Comparison of the furosemide dose titration in the first day of treatment for decompensated chronic heart failure using urine output or urine sodium concentration monitoring

Aim. To compare the efficacy and safety of furosemide dose titration during the first 24 hours of treatment for decompensated heart failure (HF) with fluid retention, based on either urine volume or spot urinary sodium concentration.
Material and methods. This prospective, randomised, open-label, single-center study included 110 patients with decompensated HF, signs of fluid retention, and regular furosemide use. The initial intravenous furosemide dose was twice the outpatient dose. In the first group (n=55), efficacy was assessed by 6-hour urine output: if ≥100 mL/h, the same dose was repeated after 12 hours; if response was insufficient, the dose was doubled every 6 hours until the target urine volume was achieved. In the second group (n=55), the 2-hour spot urinary sodium concentration was used: if ≥50 mmol/L, the same dose was repeated after 12 hours; if <50 mmol/L, the dose was doubled every 6 hours until target natriuresis was reached. After 24 hours, if urine output was <3.5 L with persistent congestion, the last furosemide dose was repeated as a bolus twice daily with the addition of acetazolamide 500 mg/day for 3 days. If the response remained insufficient after 48 hours, hydrochlorothiazide 25 mg/day was added without changing the furosemide dose. For urine output between 3.5 and 5 L, the furosemide dose was unchanged; for output >5 L with signs of congestion, the dose was halved. Once congestion resolved, patients were switched to oral furosemide.
Results. Mean patient age was 74±9.2 years; male proportion was 52.7%. The median intravenous furosemide dose in the first 24 hours was 160 mg in the urine sodiumguided group versus 80 mg in the urine volumeguided group (p<0.001). At 72 hours, the urine sodiumguided group showed greater congestion relief (median fluid overload score 4 vs. 6, p<0.001), lower body weight (median 83 vs. 88 kg, p=0.024), and less dyspnea (VAS 4 vs. 7; Likert 2 vs. 3; p<0.001 for both). Hospital stay was shorter by 2 days in the sodiumguided group (9±1.6 vs. 11±2.6 days, p<0.001), and persistent congestion at discharge was less frequent (7.3% vs. 20%, p<0.001). The composite of allcause death or HF rehospitalization at 3 months was lower in the urine sodiumguided group (21.8% vs. 36.4%, p=0.02). No significant betweengroup differences were observed in inhospital complication rates.
Conclusion. In patients hospitalised with decompensated HF, furosemide dose titration during the first 24 hours based on urinary sodium concentration (compared to the urine volumebased approach) was associated with the use of higher doses, leading to greater weight loss, better congestion relief, an

1. McDonagh TA, Metra M, Adamo M, et al.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-726. DOI:10.1093/eurheartj/ehab368. Erratum in: Eur Heart J. 2021;42(48):4901. DOI:10.1093/eurheartj/ehab670.

2. Felker GM, Lee KL, Bull DA, et al.; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797-805. DOI:10.1056/NEJMoa1005419.

3. Bart BA, Goldsmith SR, Lee KL et al.; Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012;367(24):2296-304. DOI:10.1056/NEJMoa1210357.

4. Butler J, Anstrom KJ, Felker GM, et al.; National Heart Lung and Blood Institute Heart Failure Clinical Research Network. Efficacy and safety of spironolactone in acute heart failure: the ATHENA-HF randomized clinical trial. JAMA Cardiol. 2017;2(9):950-8. DOI:10.1001/jamacardio.2017.2198.

5. Verbrugge FH, Martens P, Dauw J, et al. Natriuretic response to acetazolamide in patients with acute heart failure and volume overload. J Am Coll Cardiol. 2023;81(20):2013-24. DOI:10.1016/j.jacc.2023.03.400.

6. Mullens W, Dauw J, Martens P, et al. Acetazolamide in Decompensated Heart Failure with Volume Overload trial (ADVOR): baseline characteristics. Eur J Heart Fail. 2022;24(9):1601-10. DOI:10.1002/ejhf.2587.

7. Heidenreich PA, Bozkurt B, Aguilar D, et al.; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-1032. DOI:10.1161/CIR.0000000000001063. Erratum in: Circulation. 2022;145(18):e1033. DOI:10.1161/CIR.0000000000001073. Erratum in: Circulation. 2022;146(13):e185. DOI:10.1161/CIR.0000000000001097. Erratum in: Circulation. 2023;147(14):e674. DOI:10.1161/CIR.0000000000001142.

8. Dauw J, Lelonek M, Zegri-Reiriz I, et al. Rationale and Design of the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure Study. ESC Heart Fail. 2021;8(6):4685-92. DOI:10.1002/ehf2.13666.

9. Ter Maaten JM, Beldhuis IE, van der Meer P, et al. Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial. Nat Med. 2023;29(10):2625-32. DOI:10.1038/s41591-023-02532-z.