Evolution of CA 125 and NT-proBNP in stable patients with Fontan circulation: longitudinal analysis with sex perspective.

BACKGROUND: Monitoring heart failure in patients with Fontan circulation (FC) remains challenging due to the unique hemodynamic features of this physiology. Conventional heart failure biomarkers are not well validated in this population. We evaluated longitudinal changes in CA125 and NT-proBNP in clinically stable FC patients, with particular attention to sex-based differences. METHODS: We performed a retrospective longitudinal study including clinically stable FC outpatients with ≥2 biomarker measurements separated by ≥ 2 months. Temporal trends of CA125 and NT-proBNP were analyzed using repeated measurements and stratified by sex. RESULTS: Sixty-six outpatients were included, with a median of five determinations per patient. The extracardiac conduit was the most frequent Fontan type (72.7%). Baseline CA125 was 22.73 ± 46.26 U/mL and demonstrated a significant upward trend over time (+1.63 U/mL/year; p = 0.008). Baseline NT-proBNP was 165.13 ± 161.62 pg/mL, with a non-significant increase during follow-up (+3.5 pg/mL/year; p = 0.163). Baseline CA125 levels did not differ between sexes. During follow-up, CA125 remained stable in men (0.63 U/mL/year; p = 0.419) but increased significantly in women (2.75 U/mL/year; p < 0.001). NT-proBNP showed no significant sex differences either at baseline or longitudinally. CONCLUSIONS: In clinically stable patients with Fontan circulation, CA125 levels increased significantly over time, particularly in women, whereas NT-proBNP levels remained largely stable. Serial biomarker assessment may provide complementary information for long-term clinical monitoring in this population.