Pragmatic Urinary Sodium-based Treatment algoritHm in Acute Heart Failure (PUSH-AHF)

Administration of loop diuretics to achieve decongestion is the current cornerstone of therapy for acute heart failure. Unfortunately, there is a lack of evidence of how to guide diuretic treatment. Recently, urinary sodium, as a response measure of diuretic response, has been proposed as a target for therapy. The hypothesis of this study is that natriuresis guided therapy in patients with acute heart failure will improve diuretic response, decongestion, and reduce length of hospital stay, as well as heart failure rehospitalisations.

Objective: To assess the effect of natriuresis guided therapy in acute heart failure to improve diuretic response, decongestion, and clinical outcomes Study design: Randomised, controlled, open label study Study population: 310 patients admitted with the primary diagnosis of acute heart failure requiring intravenous loop diuretics. Intervention: natriuresis guided treatment versus standard of care Main study parameters/endpoints: Co-primary outcome: total natriuresis after 24 hours, and first occurrence of all-cause mortality or heart failure rehospitalisation at 6 months Secondary outcomes: 48- and 72-hours natriuresis, length of hospital stay, percentage change in NT-proBNP at 48 and 72 hours. Safety endpoint: doubling of serum creatinine at 24 or 48 hours, worsening heart failure.

Patients with insufficient decongestive response based on natriuresis (in the active arm) will be eligible for treatment adjustments according to the natriuresis guided treatment algorithm.

The first component of the co-primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 hours after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L).

48-hour natriuresis will be assessed by collecting urine for a second period of 24 hours after the first 24-hour urine collection according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L).

72-hour natriuresis will be assessed by collecting urine for a third period of 24 hours after the second 24-hour urine collection according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L).

The first safety endpoint is defined as number of patients with a doubling of serum creatinine at 24 hours compared with baseline serum creatinine.

The second safety endpoint is defined as the number of patients with a doubling of serum creatinine at 48 hours compared with baseline serum creatinine.

The third safety endpoint is defined as the number of patients with worsening heart failure during hospitalization.

Inclusion Criteria: Male or female ≥ 18 years of age Primary diagnosis of acute /decompensated heart failure as assessed by treating physician a. Acute Heart failure can be de novo or exacerbation of known heart failure and diagnosis is based on criteria in the ESC HF guidelines Requirement of intravenous diuretic use Exclusion Criteria: Dyspnoea primarily due to non-cardiac causes Patients with severe renal impairment receiving dialysis or requiring ultrafiltration Inability to follow instructions Any other medical conditions that may put the patient at risk or influence study results in the investigator's opinion, or that the investigator deems unsuitable for the study