Diuretic Resistance Risk and the Efficacy of Natriuresis-Guided Diuretic Therapy in Acute Heart Failure: Post Hoc...

Diuretic resistance (DR) is common in acute decompensated heart failure (ADHF) and is associated with residual congestion and poor prognosis. It remains unknown whether DR affects the beneficial effects of natriuresis-guided therapy.

This study aims to evaluate the efficacy of natriuresis-guided therapy in ADHF patients at risk of DR, as assessed by the BAN-ADHF (blood urea nitrogen, creatinine, natriuretic peptide levels, atrial fibrillation, diastolic blood pressure, hypertension and home diuretic, and heart failure hospitalization) score.

This post hoc analysis of the PUSH-AHF (Pragmatic Urinary Sodium AlgoritHm in Acute Heart Failure) trial stratified patients across DR risk groups using the previously validated BAN-ADHF score (<12: low DR risk; ≥12: high DR risk). The treatment effects of natriuresis-guided therapy vs standard of care were compared across the groups for the dual primary endpoint of 24-hour natriuresis and time to all-cause mortality or HF rehospitalization at 180 days and secondary endpoints.

Among 306 patients, 21% had a high BAN-ADHF score. Patients with high BAN-ADHF scores showed lower 24-hour (294 vs 398 mmol; P < 0.001) and 48-hour natriuresis (514 vs 641 mmol; P = 0.001) and a higher risk of composite endpoint (HR: 3.51 [95% CI: 2.33-5.30]; P < 0.001). Natriuresis-guided therapy increased 24-hour natriuresis regardless of baseline DR risk (P interaction = 0.364). The BAN-ADHF score did not modify the treatment effect on the overall neutral composite clinical outcome (P interaction = 0.391). However, it modified the effect of natriuresis-guided therapy on 48-hour (P interaction = 0.038) and 72-hour natriuresis (P interaction = 0.068), with increased natriuresis observed in patients with high BAN-ADHF scores and natriuresis-guided therapy.

Patients with a high BAN-ADHF score had impaired natriuresis and worse clinical outcomes. Natriuresis-guided therapy improved 24-hour natriuresis consistently across the spectrum of BAN-ADHF scores, with enhanced natriuretic effects at later time points among those with high DR risk. (Pragmatic Urinary Sodium AlgoritHm in Acute Heart Failure [PUSH-AF]; NCT04606927).