A practical natriuresis-guided diuretic approach in patients with acute heart failure significantly increases 24-hour natriuresis without impacting all-cause mortality or heart failure rehospitalization, in accordance with late breaking research presented in a Hot Line session today at ESC Congress 2023.

The PUSH-AHF trial provides the primary randomized evidence supporting the natriuresis-guided treatment approach advised within the ESC heart failure guidelines.”

Dr. Jozine ter Maaten, Principal Investigator, University Medical Centre Groningen

Hospitalization for acute heart failure is predominantly attributable to signs and symptoms of congestion, reminiscent of breathlessness, edema and fatigue. The first goal is to eliminate the surplus fluid, and the principal treatment for that is loop diuretic therapy. Nevertheless, a lot of patients have an insufficient response to diuretics, which is related to residual congestion and an increased risk of mortality and heart failure rehospitalization. In current practice, it’s difficult to adequately and reliably monitor response to diuretics. Surrogate measures reminiscent of weight reduction and net fluid output are typically used, but these are sometimes unreliable and require waiting not less than 24 hours after the beginning of diuretics for the primary assessment. ESC guidelines recommend early and repeated assessment of spot urinary sodium in patients with acute heart failure to guide diuretic treatment, but so far there are limited, non-randomized data showing the usefulness of this approach.

The PUSH-AHF trial investigated the effectiveness of natriuresis-guided diuretic therapy on natriuresis and clinical outcomes in patients with acute heart failure and provides the primary randomized data on this proposed personalized treatment approach. Adult patients presenting with acute heart failure requiring treatment with intravenous loop diuretics were enrolled. The inclusion and exclusion criteria were intentionally broad to enroll a up to date, representative, all-comer acute heart failure population.

Patients were randomized in a 1:1 ratio to natriuresis-guided diuretic therapy or standard of care using electronic health records. Within the natriuresis-guided group, spot urinary sodium was determined at 2, 6, 12, 18, 24 and 36 hours after starting intravenous loop diuretics. Diuretic therapy was consequently intensified using a prespecified stepwise approach if response was insufficient (spot urinary sodium below 70 mmol and/or diuresis below 150 ml/hour). Physicians were blinded to urinary sodium levels in the usual of care arm to forestall cross-over between treatment arms.

The study had two primary endpoints and p<0.025 for every was considered statistically significant: 1) 24-hour natriuresis, and a couple of) a combined endpoint of time to all-cause mortality or heart failure rehospitalization at 180 days.

A complete of 310 patients were enrolled from the University Medical Centre Groningen, the Netherlands. The median age of the patients was 74 years and 45% were women. Natriuresis in the course of the first 24 hours was significantly higher within the natriuresis-guided versus standard-of-care group (409±178 vs. 345±202 mmol, respectively; p=0.0061). The combined endpoint of time to all-cause mortality or first heart failure rehospitalization at 180 days occurred in 46 patients (31%) within the natriuresis-guided group and in 50 patients (31%) within the standard-of-care group with no significant difference between groups (hazard ratio: 0.92; 95% confidence interval 0.62-1.38; p=0.6980).

Regarding secondary endpoints, natriuresis guided therapy resulted in increased 48-hour natriuresis (653±249 vs. 575±290 mmol; p=0.0241), 24-hour diuresis (3,900 [interquartile range (IQR) 3,200-4,945] vs. 3,330 [IQR 2,510-4,500] mL; p=0.0053), in addition to 48-hour diuresis (6,655 [IQR 5,401-7,824] vs. 5915 [IQR 4,600-7,400] mL; p=0.0140). The length of hospital stay was not significantly different within the natriuresis-guided group (6 [IQR 5-9] days) versus the usual of care group (7 [IQR 5-10 days]; p=0.1436).

Natriuresis-guided therapy had an identical safety profile to straightforward of care and there was no difference in prespecified renal safety endpoints or worsening renal function.

Dr. ter Maaten said: “The outcomes confirm the hypothesis that early, repeated assessment of urinary sodium and subsequent adjustments to diuretic treatment lead to higher response. Although 180-day clinical consequence was not affected on this relatively small sample size, the strategy was secure and didn’t lead to significant renal or electrolyte perturbations compared with standard of care. Clinicians should consider natriuresis guided diuretic therapy as a primary step to a personalised treatment approach in patients with acute heart failure to enhance decongestion.”

Source:

European Society of Cardiology (ESC)