This clinical research study is being conducted in multiple hospitals in Belgium and approximately 519 patients with acute decompensated heart failure are expected to participate. Large-scale research shows that 90% of the physicians treat volume overload with high doses of loop diuretics. However, there is not a lot of scientific data available regarding the optimal doses of these diuretic medications. In addition, it is observed that a lot of people, treated with these drugs, are being readmitted to the hospital due to a new episode of heart failure. The hypothesis of this study is that the volume overload could be better treated when patients receive a combination of different types of diuretics. Additionally, the total dose of the administrated diuretics might be lower this way.

This is a randomized, double blind study with 2 treatment groups. This means that the patients will be randomized to one of the two treatment groups by chance. Patients randomized to the first group will receive standard treatment with high doses of intravenous loop diuretics and a placebo. Patients randomized to the other treatment group will receive a combination of the same doses of loop diuretics and an additional diuretic, acetazolamide (Diamox®). All diuretics will be administered intravenously. It is expected that the patients of the treatment group with the combination therapy will have a faster reduction of their fluid overload. In consequence the treatment duration and total dose of diuretics administered will be shorter. Acetazolamide (Diamox®) is a diuretic that acts at a different location in the kidney compared to the loop diuretics. This mutual reinforcement will probably reduce the total dose and duration of the diuretics.

The study will start during the hospitalization and will last around 3 months.

Inclusion Criteria:

• Signed written informed consent must be obtained before any study assessment is performed
• Male or female patients 18 years of age or older
• An elective or emergency hospital admission with clinical diagnosis of decompensated HF with at least one clinical sign of volume overload (e.g. oedema (score 2 or more), ascites confirmed by echography or pleural effusion confirmed by chest X-ray or echography)
• Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide or an equivalent dose for at least 1 month before hospital admission (Conversion: 1 mg bumetanide = 40 mg furosemide = 20 mg torsemide)
• Plasma NT-proBNP levels >1000 ng/mL or BNP levels >250 ng/mL at the time of screening.
• 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 in addition to a troponin rise above the 99th percentile and/or electrocardiographic changes 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 of admission
• Expected use of intravenous inotropes, vasopressors or nitroprusside during the study. 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 study inclusion
• Treatment with acetazolamide during the index hospitalization and prior to randomization
• Exposure to nephrotoxic agents (i.e. contrast dye) anticipated within the next 3 days
• Use of any non-protocol defined diuretic agent with the exception of mineralocorticoid receptor antagonists. Thiazides, metolazone, indapamide and amiloride should be stopped upon study inclusion. If patient is taking a combination drug including a thiazide-type diuretic, the thiazide-type diuretic should be stopped
• Current use of sodium-glucose transporter-2 inhibitors
• Subjects who are pregnant or breastfeeding

Adverse events were collected from collection of ICF up until 3 months follow-up (3 months after intervention).

1. Nearly all patients were white
2. Patients had a history of chronic heart failure and had been receiving long-term outpatient treatment with at least 40 mg of furosemide equivalent.
3. Patients in the two trial groups received similar loop diuretics.
4. The congestion score focused on the presence of edema in the lower limb, pleural effusion, and ascites - reflective of mainly extracellular volume overload
5. The trial design excluded use of SGLT2 inhibitors