The ENACT-HF study investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure (AHF) and signs of volume overload. The study compared the standard of care with a protocol that used urinary sodium to guide diuretic therapy. A total of 401 patients from 29 centers in 18 countries were enrolled. The protocol arm showed significantly higher natriuresis (282 mmol vs. 174 mmol after 1 day) and diuresis (5776 mL vs. 4381 mL after 2 days) compared to the standard of care arm. The protocol also resulted in a shorter length of stay (5.8 days vs. 7.0 days). In-hospital mortality was low and similar between the two groups. The study found that the protocol was feasible, safe, and effective in improving diuretic response and reducing hospital stay. The results support the use of urinary sodium to guide decongestion in AHF and suggest that a standardized natriuresis-guided protocol may be beneficial in various healthcare settings. The study also highlights the need for further research on the long-term effects of natriuresis-guided decongestion in AHF.The ENACT-HF study investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure (AHF) and signs of volume overload. The study compared the standard of care with a protocol that used urinary sodium to guide diuretic therapy. A total of 401 patients from 29 centers in 18 countries were enrolled. The protocol arm showed significantly higher natriuresis (282 mmol vs. 174 mmol after 1 day) and diuresis (5776 mL vs. 4381 mL after 2 days) compared to the standard of care arm. The protocol also resulted in a shorter length of stay (5.8 days vs. 7.0 days). In-hospital mortality was low and similar between the two groups. The study found that the protocol was feasible, safe, and effective in improving diuretic response and reducing hospital stay. The results support the use of urinary sodium to guide decongestion in AHF and suggest that a standardized natriuresis-guided protocol may be beneficial in various healthcare settings. The study also highlights the need for further research on the long-term effects of natriuresis-guided decongestion in AHF.