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. 2023 May 23;81(20):2013-2024.
doi: 10.1016/j.jacc.2023.03.400.

Natriuretic Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload

Frederik H Verbrugge  1 , Pieter Martens  2 , Jeroen Dauw  3 , Petra Nijst  4 , Evelyne Meekers  3 , Silvio Nunes Augusto Jr  5 , Jozine M Ter Maaten  6 , Kevin Damman  6 , Gerasimos Filippatos  7 , Johan Lassus  8 , Alexandre Mebazaa  9 , Frank Ruschitzka  10 , Matthias Dupont  4 , Wilfried Mullens  3
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Free article

Natriuretic Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload

Frederik H Verbrugge et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Acetazolamide facilitates decongestion in acute decompensated heart failure (ADHF).

Objectives: This study sought to investigate the effect of acetazolamide on natriuresis in ADHF and its relationship with outcomes.

Methods: Patients from the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial with complete data on urine output and urine sodium concentration (UNa) were analyzed. Predictors of natriuresis and its relationship with the main trial endpoints were evaluated.

Results: This analysis included 462 of 519 patients (89%) from the ADVOR trial. During 2 days after randomization, UNa was 92 ± 25 mmol/L on average, and total natriuresis was 425 ± 234 mmol. Allocation to acetazolamide strongly and independently predicted natriuresis with a 16 mmol/L (19%) increase in UNa and 115 mmol (32%) greater total natriuresis. Higher systolic blood pressure, better renal function, higher serum sodium levels, and male sex also independently predicted both a higher UNa and greater total natriuresis. A stronger natriuretic response was associated with faster and more complete relief of signs of volume overload, and this effect was already significant on the first morning of assessment (P = 0.022). A significant interaction was observed between the effect of allocation to acetazolamide and UNa on decongestion (P = 0.007). Stronger natriuresis with better decongestion translated into a shorter hospital stay (P < 0.001). After multivariable adjustments, every 10 mmol/L UNa increase was independently associated with a lower risk of all-cause death or heart failure readmission (HR: 0.92; 95% CI: 0.85-0.99).

Conclusions: Increased natriuresis is strongly related to successful decongestion with acetazolamide in ADHF. UNa may be an attractive measure of effective decongestion for future trials. (Acetazolamide in Decompensated Heart Failure with Volume Overload [ADVOR]; NCT03505788).

Keywords: acetazolamide; cardiorenal syndrome; diuretic agents; heart failure; natriuresis; prognosis.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the Belgian Health Care Knowledge Center under the KCE Trials Program (KCE 17001). Dr Damman has received speaker fees from AstraZeneca, Abbott, and Boehringer Ingelheim. Dr Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, was made directly to the University of Zurich); the Department of Cardiology, University Hospital of Zurich/University of Zurich has received research, educational, and/or travel grants from Abbott, Amgen, AstraZeneca, Bayer, Berlin Heart, B Braun, Biosense Webster, Biosensors Europe, Biotronik, Bristol Myers Squibb, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Corteria, Daiichi-Sankyo, Diatools, Edwards Lifesciences, Guidant Europe NV (Boston Scientific), Hamilton Health Sciences, Kaneka Corporation, Kantar, Labormedizinisches Zentrum, Medtronic, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Roche Diagnostics, Sahajanand IN, Sanofi, Sarstedt, Servier, SIS Medical, SSS International Clinical Research, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus, and ZOLL (grants that have not affected his personal remuneration). All other others have reported that they have no relationships relevant to the contents of this paper to disclose.

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