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

This is a pragmatic, multicenter, interventional, parallel-arm, randomized, open-label trial to investigate whether a diuretic regimen, based on serial assessment of sodium concentration (UNa) on spot urine samples after diuretic administration and with low-threshold use of combination diuretic therapy, improves decongestion versus usual care in acute heart failure (AHF), potentially leading to better clinical outcomes.

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

Eligibility Criteria:
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:

  1. bilateral oedema 2+, indicating clear pitting
  2. 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)
  3. 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