Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial

Figures

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  Fig. 1. Patient flow diagram. Created with BioRender.com.

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  Fig. 2. The urinary sodium and diuresis-based treatment protocol in PUSH-AHF. Schematic of the treatment protocol, showing that loop diuretics were administered twice daily (in black), at 12 h intervals. At the timepoints at which natriuresis and diuresis was assessed, in the case of an insufficient response as determined by predetermined cutoffs (box 1), treatment was intensified according to the treatment algorithm (box 2). First step was the administration of an additional dose of loop diuretics (double the previous dose to a maximum of 5 mg of bumetanide). If an additional, increased dose of loop diuretic was administered, the maintenance dose (the twice-daily administered loop diuretic dose) was further increased to a level that was double the previous dose, to a maximum of 5 mg bumetanide. If response continued to be insufficient despite two consecutive maximum doses of loop diuretic, combination diuretic therapy was started. First choice for combination diuretic therapy was the addition of hydrochlorothiazide; however, if a patient for instance already used combination diuretic therapy with hydrochlorothiazide before admission or response remained insufficient after addition of…

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  Fig. 3. Natriuresis, diuresis and the combined endpoint of all-cause mortality and HF rehospitalization according to randomization group. a, Natriuresis at 24 and 48 h after start of loop diuretic (LD) treatment. Mean ± 95% CI. Student’s t-test. b, Kaplan–Meier plot for the combined primary endpoint of all-cause mortality and HF rehospitalization at 180 days. Cox regression. c, Diuresis at 24 and 48 h after start of LD treatment. Mean ± 95% CI. Student’s t-test.

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  Extended Data Fig. 1. Intensification of treatment during the first 36 hours in the natriuresis guided group. Abbreviations: HCT: hydrochlorothiazide; SLGT2i: Sodium Glucose co-Transporter 2 inhibitor.

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  Extended Data Fig. 2. Spot urinary sodium values during the first 36 hours in the natriuresis guided group. Median with interquartile ranges, whiskers and outliers.

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  Extended Data Fig. 3. Subgroup analyses 24- hour natriuresis. Hazard ratio with 95% Confidence Intervals. Abbreviations: eGFR: estimated Glomerular Filtration Rate; HF: Heart Failure; NT-proBNP: N Terminal-pro Blood Natriuretic Peptide; SLGT2i: Sodium Glucose co-Transporter 2 inhibitor. Linear regression analysis with the inclusion of an interaction term.

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  Extended Data Fig. 4. Subgroup analyses combined endpoint of all-cause mortality and heart failure rehospitalization at 180 days. Hazard ratio with 95% Confidence Intervals. Abbreviations: eGFR: estimated Glomerular Filtration Rate; HF: Heart Failure; NT-proBNP: N Terminal-pro Blood Natriuretic Peptide; SLGT2i: Sodium Glucose co-Transporter 2 inhibitor. Cox regression analysis with the inclusion of an interaction term.

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  Extended Data Fig. 5. Kaplan Meier plot for heart failure rehospitalization at 180 days. Abbreviations: CI: Confidence Interval; HF: Heart Failure; HR: Hazard Ratio. Cox regression.

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  Extended Data Fig. 6. Kaplan Meier plot for all-cause mortality at 180 days. Abbreviations: CI: Confidence Interval; HR: Hazard Ratio. Cox regression.

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  Extended Data Fig. 7. Natriuresis according to treatment group up to 72 hours. Mean ± 95% Confidence Interval. Students T-test.

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  Extended Data Fig. 8. Diuresis according to treatment group up to 72 hours. Mean ± 95% Confidence Interval. Students T-test.