Key result
Natriuresis-guided diuretic therapy reduces 180-day death or HF rehospitalization ~49% in men, but not women.
Why the study?
Sex-related differences in response to decongestive therapy in acute heart failure may affect the treatment effect of natriuresis-guided therapy, which requires investigation.
Does natriuresis-guided diuretic therapy improve natriuresis and reduce 180-day HF rehospitalization or all-cause mortality compared to standard of care in men and women with acute heart failure?
RCT (n=310)
Open-label
1:1
No
Does natriuresis-guided diuretic therapy improve natriuresis and reduce 180-day HF rehospitalization or all-cause mortality compared to standard of care in men and women with acute heart failure?
Natriuresis-guided diuretic therapy in acute heart failure significantly improves natriuresis and reduces 180-day mortality or HF rehospitalization in men, but not in women, highlighting important sex-specific differences in response to decongestive strategies.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“So the results of the PUSH AHF, in my opinion, show that we can use urinary sodium as a personalised treatment approach for patient acute heart failure. By using natriuresis-guided therapy, you identify patients that do not respond adequately, and we show that if you increase doses or administer additional dose or even initiate combination diuretic therapy, these patients indeed pee out more sodium, but they also have significantly more diuresis in the first days of hospitalisation. So I think the conclusions of the PUSH AHF are is that we now have a first evidence for personalised treatment therapy and acute heart failure.”
“The PUSH-AHF trial confirmed that UNa+-guided diuretic treatment versus standard of care in acute HF increased total 24 h natriuresis (the first co-primary endpoint of the trial) with 64 mmol, a highly significant result (p = 0.006). Moreover, the difference in natriuresis between both treatment arms increased over time, hinting toward an even greater impact of serial UNa+ assessments.”
May warrant sex-stratified diuretic approaches in acute heart failure; leaves open whether natriuresis-guided therapy benefits women pending dedicated trials.
Aim Natriuresis-guided therapy has been proposed as a personalized approach for decongestion in acute heart failure (HF). Given the evidence of sex-related differences in response to decongestive therapy, we performed a sex-specific analysis on the treatment effect of natriuresis-guided therapy in the PUSH-AHF trial. Methods The PUSH-AHF trial randomized 310 patients (45% women) to natriuresis-guided therapy or standard of care (SOC). The endpoints of PUSH-AHF were compared between men and women. The 24-h natriuretic response was calculated as 24-h natriuresis divided by the total 24-h loop diuretic dose (mg of bumetanide equivalents). Results In men, mean total 24-h natriuresis was greater with natriuresis-guided therapy compared to SOC (443 vs. 354 mmol, p = 0.004), whereas in women, this was similar between the groups (357 vs. 336 mmol, p = 0.533, adjusted p -interaction = 0.276). The median 24-h natriuretic response was lower in women receiving natriuresis-guided therapy (23 vs. 52 mmol urinary sodium/mg bumetanide, p = 0.001) when compared to SOC, whereas in men, there was no significant difference between treatment arms (38 vs. 45 mmol respectively, p = 0.337, adjusted p -interaction = 0.009). Natriuresis-guided therapy was associated with a lower risk of 180-day HF rehospitalization or all-cause mortality in men (adjusted HR 0.51 (95% CI, 0.30–0.86; p = 0.011), but not in women (adjusted HR 1.40 (95% CI, 0.67–2.91; p = 0.368), adjusted p -interaction = 0.026). Conclusion Natriuresis-guided therapy was associated with greater natriuresis and a lower risk of 180-day all-cause mortality or HF rehospitalization in men but not in women. These exploratory sex-specific patterns warrant further investigation and confirmation.
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Qin et al. (2026) conducted an RCT in Acute heart failure (n=310). Natriuresis-guided diuretic therapy vs. Standard of care was evaluated on 180-day heart failure rehospitalization or all-cause mortality in men (adjusted HR 0.51, 95% CI 0.30-0.86, p=0.011). Natriuresis-guided diuretic therapy reduced the risk of 180-day heart failure rehospitalization or all-cause mortality by 49% in men (adjusted HR 0.51), but not in women, compared to standard of care.
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