Clinical importance of urine sodium and chloride excretion in acute heart failure- a prespecified sub-analysis of the PUSH-AHF trial
L Cosic, L Zonneveld, I E Beldhuis, D J Van Veldhuisen, P Van Der Meer, A A Voors, K Damman, J M Ter MaatenAbstract
Background and objective
In acute decompensated heart failure (ADHF), urine sodium is a promising prognostic marker and target to guide decongestive therapy. This study investigates the value and trajectory of urine sodium as well as chloride excretion during natriuresis-guided therapy.
Methods and results
In this pre-specified sub-analysis of the PUSH-AHF trial, 278 patients with available 24-hour natriuresis were divided into tertiles of natriuresis. Patients in the highest tertile had the highest 48- and 72-hour natriuresis and diuresis compared with patients in the middle and lowest tertile (p-trend for all <0.05). Higher 24-hour natriuresis was associated with allocation to the natriuresis-guided therapy arm, lower age, higher diastolic blood pressure and higher spot urine sodium 2-hours after first diuretic administration. 2-h spot urine sodium was the strongest predictor of 24-h natriuresis (β = 0.42; p<0.001), independent of treatment allocation. 24-hour natriuresis correlated strongly with 24-hour urinary chloride excretion (r > 0.97 in both randomization groups; p<0.001). Urinary chloride excretion was significantly higher at 24-, 48- and 72-hours in patients with natriuresis-guided therapy compared to patients with standard of care (p-value for all <0.05). Each 50 mmol increase in 24-hour natriuresis and urinary chloride excretion corresponded to a lower risk of the combined endpoint of all-cause mortality and HF rehospitalization with a hazard ratio of 0.88 (95% CI: 0.82-0.95; p<0.001) and 0.88 (95% CI: 0.82-0.94; p<0.001), respectively.
Conclusion
Spot urinary sodium at 2 hours after loop diuretic initiation is a robust predictor of 24-hour natriuresis, independently of treatment allocation to natriuresis-guided therapy. 24-hour natriuresis and 24-hour urinary chloride excretion strongly correlate and are both robust predictors of clinical outcomes.For image description, please refer to the figure legend and surrounding text.