Heart failure phenotypes determine NT-proBNP levels in haemodialysis patients independent of volaemia

Abstract Background Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is as a widely recognised diagnostic biomarker in heart failure. In haemodialysis patients, its clinical interpretation is confounded by impaired renal clearance and fluctating volaemia. Purpose To evaluate the association between NT-proBNP and heart failure phenotypes (HFrEF/HFmrEF, HFpEF), as well as to explore its association with bioimpedance-derived hydration status, interdialytic weight gain, echocardiographic parameters, and inferior vena cava (IVC) measurements. Methods In our cohort of haemodialysis patients, we recorded age, NT-proBNP, CA125, bioimpedance spectroscopy overhydration (overhydration status in litres (OH) and in percentage of extracellular water (%ECW)), pre- and post-dialysis weight, and derived interdialytic weight gain. Echocardiographic parameters included LVOT VTI, E/A, E/E’ and atrial size. IVC diameter and collapsibility were assessed. Group differences were tested with Mann–Whitney; IVC categories with Kruskal–Wallis and Cuzick trend; correlations with Spearman. Age-adjusted and multivariable median regression included heart failure phenotype(s), age, interdialytic weight gain, OH, IVC measures, E/E’ and atrial size. Results We included 57 patients, 75% of them had heart failure; 15 (26%) had HFrEF/HFmrEF, and 28% had HFpEF. Patients without heart failure were younger (60±4 vs 72±2 years, p=0.0045). In comparison to patients without heart failure, NT-proBNP was higher in HFrEF/HFmrEF (1.782 (IQR 1.274–4.022) vs 16.149 (IQR 7.472–35.000) ng/L; p<0.000), and HFpEF patients (1.782 (IQR 1.274–4.022) vs 6.130 (IQR 3.543–13.734) ng/L; p<0.000). In age-adjusted median regression, any heart failure phenotype remained independently associated with higher NT-proBNP (+5.739 ng/L; 95%CI 1.503–9.975; p=0.009). IVC collapsibility categories were not associated with NT-proBNP (Kruskal–Wallis p=0.240) and there was no significant trend across ordered categories (Cuzick p=0.109). NT-proBNP correlated most with E/E’ (ρ=0.551, p<0.000), and also with %ECW (ρ=0.373, p=0.006) and CA125 (ρ=0.329, p=0.01). In multivariable median regression, E/E’ remained independently associated with NT-proBNP (+849 ng/L per 1-unit increase; 95%CI 335–1.364; p=0.002); while heart failure phenotype, bioimpedance-derived measures, interdialytic weight gain, IVC diameter and collapsibility were not significant predictors. Conclusions In haemodialysis patients, NT-proBNP is markedly higher in in patients with heart failure, regardless of the phenotype. NT-proBNP relates more closely to filling pressure surrogates (E/E’) and bioimpedance %ECW overhydration, supporting a predominantly haemodynamic/cardiac signal beyond simple interdialytic weight gain or hypervolemia.