Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment

Key interventions are:

• Assessment of UNa in spot urine samples after every bolus administration of loop diuretics with continuation of intravenous diuretics until resolution of clinical signs of fluid overload AND UNa <80 mmol/L
• Dosing of loop diuretic bolus according to estimated glomerular filtration rate (eGFR)
• Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia (>145 mmol/L) or metabolic acidosis (bicarbonate <22 mmol/L)
• Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia (>145 mmol/L)
• Switch to full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa <80 mmol/L and persistent clinical signs of fluid overload
• Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during diuretic therapy with intravenous diuretics

Inclusion criteria

• At least 18 y/o and able to provide informed consent
• Hospital admission (anticipated stay >24 h after randomisation) with diagnosis of acute heart failure according to the treating physician
• At least one of the following three signs of volume overload:

• bilateral oedema 2+, indicating clear pitting
• ascites that is amenable for drainage, confirmed by echography (no obligation to perform abdominal echocardiography, but necessary when presence of ascites is used as an entry criterion for the study)
• uni- or bilateral pleural effusions that are amenable for drainage, confirmed by chest X-ray or lung ultrasound (no obligation to perform chest X-ray, but necessary when presence of pleural effusions is used as an entry criterion for the study)
• Plasma NTproBNP level >1,000 ng/L

Exclusion criteria

• No possibility to collect reliable urine spot samples after diuretic administration
• Administration of any diuretic within 6 h before randomisation, except for a mineralocorticoid receptor antagonist or sodium glucose co-transporter-2 inhibitor as part of the patient's maintenance treatment for heart failure. Patients can still be included after withholding these diuretics for 6 h, after which randomisation can be performed if they qualify all other criteria.
• Severe kidney dysfunction, defined as an eGFR <15 mL/min/1.73m² calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and/or previous, current, or planned future renal replacement therapy
• Systolic blood pressure <90 mmHg, mean arterial pressure <65 mmHg, or need for inotropes/vasopressor therapy at randomisation
• Any acute coronary syndrome within 30 days prior to enrolment, defined as typical chest pain with a troponin rise above the 99th percentile of normal and/or electrocardiographic changes suggestive of cardiac ischemia
• History of heart or kidney transplantation
• History of mechanical circulatory support
• Known obstructive hypertrophic cardiomyopathy, congenital heart disease, acute mechanical cause of acute heart failure (e.g., papillary muscular rupture), acute myocarditis, or constrictive pericarditis according to the treating physician
• Pregnant or breastfeeding woman
• Concomitant participation in another interventional study