Natriuresis-guided diuretic protocol in acute HF increases natriuresis at day 1

Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF)

News - May 23, 2023

Presented at ESC Heart Failure 2023 by Jeroen Dauw (Ghent, Belgium)

Introduction and methods

The 2021 guidelines for the management of heart failure recommend urine sodium-guided diuretic use in patients with acute heart failure. The protocol in the guidelines was based on a position statement from the HFA with expert consensus, but has not been prospectively evaluated.

Therefore, the ENACT-HF trial -a prospective, multicenter, open-label, non-randomized, pragmatic trial- was performed, in which standard of care was compared to a standardized diuretic protocol. There were 2 sequential phases of recruitment: phase 1 with each center’s standard of care, and phase 2 with the standardized diuretic protocol. 401 Patients were recruited in 29 centers in 18 countries (254 in the standard of care group and 147 in the protocol group). Patients who were admitted with acute heart failure, had at least one sigh of volume overload, had maintenance daily loop diuretic use of ≥40 mg furosemide for ≥1 month, and NT-proBNP >1000 pg/mL or BNP >250 pg/mL were included.

The standardized diuretic protocol was as follows: after inclusion, patients were given twice the oral home dose as IV bolus; after 2 hours, spot urine samples were taken and after 6 hours the diuretic response was evaluated. If urine sodium<50 mmol/L or urine output <100 mL/h, then diuretic dose had to be doubled (to a max of 200 mg of furosemide- if that was reached thiazide had to be added). If criteria of urine sodium and urine output were met, same dose of diuretic was repeated. After the two boluses on day 1, urine output was evaluated again in the morning of day 2. If urine output <3 L then the loop diuretic dose had to be doubled again (otherwise continue current dose). After 2 days, the protocol stopped.

The primary endpoint was natriuresis after day 1.

Main results

  • Mean natriuresis was 174 mmol in the standard of care arm and 282 in the protocol arm (+64% change; mean ratio: 1.64, 95%CI: 1.37-1.95, P<0.001).
  • The effect was consistent across predefined subgroups.
  • In the protocol arm, mean natriuresis (mean ratio: 1.52, 95%CI:1.31-1.76, P<0.001) and diuresis (mean ratio: 1.33, 95%CI: 1.21-1.47, P<0.001) at day 2 were higher compared with standard of care.
  • There was no difference in weight loss and congestion score between the 2 groups.
  • Hospital duration was 7.0 days in the standard of care group and 5.8 days in the protocol group (mean ratio: 0.87, 95%CI: 0.77-0.99, P=0.036).
  • The protocol was safe; no difference in renal endpoints or incidence of hypokalemia or hypotension between groups.


The pragmatic ENACT-HF study showed that a natriuresis-guided protocol when compared to standard of care in patients admitted with acute HF was associated with an increase in natriuresis at day 1. The protocol was safe and feasible in a variety of health care settings.

- Our coverage of ESC Heart Failure 2023 is based on the information provided during the congress –

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