Multiparametric risk stratification for inadequate natriuretic response to hypertonic saline supported diuretics in acute decompensated heart failure

Background

In acute decompensated heart failure, hypertonic saline solution combined with high dose loop diuretics is used to enhance decongestion by preserving intravascular volume and improving renal perfusion. However, the natriuretic response remains markedly heterogeneous. Early identification of patients at risk for inadequate response is crucial for timely therapeutic optimization.

Purpose

To evaluate a comprehensive multiparametric risk stratification strategy integrating tubular, hemodynamic and functional markers to predict inadequate natriuretic response to hypertonic saline supported diuretics.

Methods

This prospective observational study included 79 hospitalized patients treated with a standardized protocol of hypertonic saline solution combined with high dose intravenous loop diuretics. Inadequate response was defined as cumulative urinary sodium excretion <105 mEq within 24 hours (final n=77). Clinical characteristics, serum neutrophil gelatinase associated lipocalin and electrolytes, second hour spot urinary sodium, and advanced echocardiographic markers of right heart function and systemic venous congestion including right ventricular outflow tract velocity-time integral, inferior vena cava diameter, estimated right atrial pressure and venous excess ultrasound score were analyzed. Independent predictors were identified using multivariable logistic regression.

Results

Among 77 patients (mean age 70.3±10.8 years, 57% male), 37 (48.1%) demonstrated inadequate natriuretic response. Non-responders exhibited lower baseline serum sodium and chloride (both p<0.001), higher neutrophil gelatinase associated lipocalin levels (p=0.004), larger inferior vena cava diameters (p=0.010), higher right atrial pressure (p<0.001), and lower right ventricular outflow tract velocity-time integral (p=0.012). A second hour spot urinary sodium <70 mEq/L was strongly associated with inadequate response (p<0.001). In multivariable analysis, neutrophil gelatinase associated lipocalin ≥10 ng/mL (OR 4.16, p=0.025), serum sodium <135 mmol/L (OR 6.45, p=0.004), second hour spot urinary sodium <70 mEq/L (OR 14.36, p<0.001), and concomitant lung disease (OR 11.45, p=0.002) independently predicted inadequate response.

Conclusion

In acute decompensated heart failure treated with hypertonic saline supported diuretics, inadequate natriuretic response defines a distinct cardiorenal high-risk phenotype characterized by tubular stress, hyponatremia and severe right-sided venous congestion. Conventional congestion biomarkers alone failed to discriminate responders, whereas early functional sodium handling provided strong independent prognostic discrimination.

A multiparametric strategy integrating tubular injury, right heart hemodynamics and early spot urinary sodium may refine early clinical decision-making and identify patients requiring prompt therapeutic escalation beyond conventional diuretic strategies.Figure1_Integrated_Risk_Model_AHF.pngFig2_Independent_Predictors_FP.png