Natriuresis-guided therapy in acute heart failure: rationale and design of the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) trial

Abstract

Aims: Insufficient diuretic response frequently occurs in patients admitted for acute heart failure (HF) and is associated with worse clinical outcomes. Recent studies have shown that measuring natriuresis early after hospital admission could reliably identify patients with a poor diuretic response during hospitalization who might require enhanced diuretic treatment. This study will test the hypothesis that natriuresis-guided therapy in patients with acute HF improves natriuresis and clinical outcomes.

Methods: The Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) is a pragmatic, single-centre, randomized, controlled, open-label study, aiming to recruit 310 acute HF patients requiring treatment with intravenous loop diuretics. Patients will be randomized to natriuresis-guided therapy or standard of care. Natriuresis will be determined at set time points after initiation of intravenous loop diuretics, and treatment will be adjusted based on the urinary sodium levels in the natriuresis-guided group using a pre-specified stepwise approach of increasing doses of loop diuretics and the initiation of combination diuretic therapy. The co-primary endpoint is 24-h urinary sodium excretion after start of loop diuretic therapy and a combined endpoint of all-cause mortality or first HF rehospitalization at 6 months. Secondary endpoints include 48- and 72-h sodium excretion, length of hospital stay, and percentage change in N-terminal pro brain natriuretic peptide at 48 and 72 h.

Conclusion: The PUSH-AHF study will investigate whether natriuresis-guided therapy, using a pre-specified stepwise diuretic treatment approach, improves natriuresis and clinical outcomes in patients with acute HF.

Figure 1

In patients with acute heart failure, loop diuretics are the first and only recommended choice of treatment aimed at relieving congestion by increasing diuresis and natriuresis. Actively assessing natriuresis and using this to optimize diuretic treatment could improve decongestion and clinical outcomes. This figure was created with images adapted from Servier Medical Art licensed under a Creative Commons Attribution 3.0.

Figure 2

Overview of the PUSH‐AHF study protocol. HF, heart failure; iv, intravenous; LD, loop diuretic; NT‐proBNP, N‐terminal pro brain natriuretic peptide.

Figure 3

(A) PUSH‐AHF treatment protocol in the natriuresis‐guided arm during the first 24 h (0–24 h after randomization). (B) PUSH‐AHF treatment protocol in the natriuresis‐guided arm during the second 24 h (24–48 h after randomization). eGFR, estimated glomerular filtration rate; HCT, hydrochlorothiazide; LD, loop diuretic; SGLT2‐i, sodium–glucose co‐transporter inhibitor.

Figure 4

PRECIS‐2 wheel diagram for the PUSH‐AHF study.PRECIS‐2, Pragmatic Explanatory Continuum Indicator Summary 2; PUSH‐AHF, Pragmatic Urinary Sodium‐based treatment algoritHm in Acute Heart Failure.