Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR)

Inclusion Criteria:

• Signed written informed consent must be obtained before any study assessment isperformed

• Male or female patients 18 years of age or older

• An elective or emergency hospital admission with clinical diagnosis of decompensatedHF with at least one clinical sign of volume overload (e.g. oedema (score 2 ormore), ascites confirmed by echography or pleural effusion confirmed by chest X-rayor echography)

• Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanideor an equivalent dose for at least 1 month before hospital admission (Conversion: 1mg bumetanide = 40 mg furosemide = 20 mg torsemide)

• Plasma NT-proBNP levels >1000 ng/mL or BNP levels >250 ng/mL at the time ofscreening.

• Assessed LVEF by any imaging technique; i.e. echocardiography, catheterization,nuclear scan or magnetic resonance imaging within 12 months of inclusion

Exclusion Criteria:

• Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain inaddition to a troponin rise above the 99th percentile and/or electrocardiographicchanges suggestive of cardiac ischemia

• History of congenital heart disease requiring surgical correction

• History of a cardiac transplantation and/or ventricular assist device

• Systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg at the moment ofadmission

• Expected use of intravenous inotropes, vasopressors or nitroprusside during thestudy. Use of nitrates is allowed only if the patient's systolic blood pressure is >140 mmHg

• Estimated glomerular filtration rate <20 mL/min/1.73m² at screening

• Use of renal replacement therapy or ultrafiltration at any time before studyinclusion

• Treatment with acetazolamide during the index hospitalization and prior torandomization

• Exposure to nephrotoxic agents (i.e. contrast dye) anticipated within the next 3days

• Use of any non-protocol defined diuretic agent with the exception ofmineralocorticoid receptor antagonists. Thiazides, metolazone, indapamide andamiloride should be stopped upon study inclusion. If patient is taking a combinationdrug including a thiazide-type diuretic, the thiazide-type diuretic should bestopped

• Current use of sodium-glucose transporter-2 inhibitors

• Subjects who are pregnant or breastfeeding