VExUS and biomarkers in decompensated chronic heart failure: what congestion phenotype are we measuring?

Background Heart failure represents a major healthcare burden in which accurate assessment of congestion is essential to guide treatment. The Venous Excess Ultrasound (VExUS) score has emerged as a bedside tool for evaluating systemic venous congestion; however, it remains unclear whether it primarily reflects intravascular or extravascular congestion. Biomarkers such as NT-proBNP and CA-125 may provide complementary characterisation of these phenotypes. Purpose To determine whether VExUS correlates more strongly with the intravascular congestion biomarker NT-proBNP or the extravascular congestion biomarker CA-125 in patients with chronic heart failure with reduced ejection fraction presenting with acute decompensation. Methods We conducted an observational study including 54 patients with chronic heart failure with reduced ejection fraction admitted for acute decompensation. All patients underwent comprehensive VExUS assessment and simultaneous measurement of CA-125 and NT-proBNP. Associations between biomarkers and VExUS parameters were analysed using Spearman’s correlation and multivariable linear regression, with logarithmic transformation of NT-proBNP and CA-125 to approximate a normal distribution. Results CA-125 showed a moderate correlation with VExUS score (rho = 0.46, p < 0.001), with significant differences across congestion grades (H = 14.12, p = 0.0027) and acceptable discrimination for severe congestion (AUC = 0.79; cut-off 49 U/mL; sensitivity 66.7%, specificity 87.9%). NT-proBNP demonstrated a stronger correlation (rho = 0.70, p < 0.000001) and superior discrimination (AUC = 0.95; cut-off 4681 pg/mL; sensitivity 85.7%, specificity 93.9%). The AUC of NT-proBNP was significantly greater than that of CA-125 (p = 0.004). In multivariable analysis, NT-proBNP remained independently associated with VExUS (β = 0.000073, p = 0.000033), whereas CA-125 lost statistical significance (p = 0.351; R² = 0.389). Conclusions VExUS severity correlates predominantly with NT-proBNP rather than CA-125, suggesting that it mainly reflects the haemodynamic intravascular component of congestion. CA-125 shows a complementary association but does not independently predict VExUS severity. These findings suggest that VExUS primarily reflects intravascular congestion and could contribute to guiding decongestive therapy in patients with chronic heart failure with reduced ejection fraction presenting with acute decompensation.