Zlog-NT-proBNP as a Diagnostic and Prognostic Biomarker in Patients with Total Cavopulmonary Connection

All articles of this category (opens in new window) Background: Patients with Fontan circulation remain at risk for long-term complications and adverse outcomes. Reliable biomarkers are needed to support clinical surveillance. The age-adjusted zlog-NT-proBNP enables standardized interpretation across the pediatric-to-adult spectrum and may capture functional status, hemodynamics, and prognosis. Methods: All patients with total cavopulmonary connection (TCPC) who had NT-proBNP measured during outpatient visits or hospital admissions between January 1, 2011, and December 31, 2023, were identified. Because of the strong age dependency of NT-proBNP concentrations, absolute values were transformed into age-adjusted zlog values (“zlog-NT-proBNP”). Comprehensive clinical, laboratory, imaging, and functional data were obtained at the time of measurement, and associations with zlog-NT-proBNP were analyzed. Survival status was determined during longitudinal follow-up. Results: Among 299 TCPC patients (median age: 11.6 years, 62.5% male), median zlog-NT-proBNP was 1.49 (IQR: 0.79–2.22). Higher levels were independently associated with impaired systemic ventricular function ( β = 0.33, p < 0.001) and higher NYHA class ( β = 0.21, p < 0.001). Additional determinants included systemic right ventricular morphology ( β = 0.16, p < 0.001), aortic regurgitation ( β = 0.14, p = 0.004), and later age at Fontan completion ( β = 0.19, p < 0.001). Patients with decompensation ( n = 23; mean 2.39 vs. 1.51, p < 0.001) or acute rhythm disturbances requiring treatment ( n = 14; mean 3.04 vs. 1.51, p < 0.001) had significantly higher zlog-NT-proBNP. In exercise testing ( n = 114), zlog-NT-proBNP inversely correlated with peak VO 2 ( r = −0.36, p < 0.001). In patients who underwent catheterization ( n = 96), zlog-NT-proBNP correlated with mean pulmonary artery pressure ( r = 0.24, p = 0.025) and atrial pressure ( r = 0.32, p = 0.015). During a median follow-up of 3.7 years, 14 patients (4.7%) died. Zlog-NT-proBNP independently predicted mortality (HR: 1.92 [95% CI: 1.40–2.63], p < 0.001; AUC: 0.75). For clinical application, levels < 1.7 (sensitivity: 79%, NPV: 97%) may serve as a rule-out cutoff, while levels ≥ 2.7 (specificity: 89%, PPV: 18%) could serve as a rule-in threshold for identifying high-risk patients. Conclusion: Zlog-NT-proBNP is an age-independent biomarker that reflects functional status and Fontan pathway loading in TCPC patients. Elevated values indicate systemic ventricular dysfunction, relevant aortic regurgitation, impaired exercise capacity, increased Fontan pressures, and are associated with higher mortality. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany