Carbohydrate Antigen (CA 125): A Promising New Biomarker in Children and Adults with Fontan Circulation

Background: Long-term outcomes for patients with Fontan circulation are often compromised by a high risk for complications, which significantly limit survival. Risk prediction in these patients is challenging, as conventional scoring systems are validated for patients with biventricular circulation. Early detection of impending complications is decisive for further prognosis. In this study, we sought to analyze the relationship between Carbohydrate Antigen 125 (CA 125) and clinical complications in patients with Fontan circulation.

Methods: Children and adults with Fontan circulation and ambulatory CA 125 measurement between April 2014 and December 2023 were retrospectively identified. Baseline characteristics including findings of the physical examination, functional class, echocardiography, previous cardiac catheterization, and NT-proBNP measurement were obtained at the time of (first) CA 125 measurement. Medical records were reviewed for follow-up. The composite endpoint (Fontan-specific major adverse cardiovascular event, MACE) was defined as either all-cause death, resuscitation, mechanical circulatory support, heart failure hospitalizations, listing for heart transplantation, Fontan-associated liver disease (FALD) or Failing Fontan (protein-losing enteropathy, plastic bronchitis).

Results: A total of 157 patients (median age 14.8 years [IQR, 10.7–25.6], 61.8% males) were identified. The majority had a total cavopulmonary connection (n = 107 with extracardiac conduit, n = 30 with intracardiac lateral tunnel). Median CA 125 level was significantly higher in Fontan patients with edema (p = 0.02), ascites (p < 0.001), and NYHA >I (p = 0.018). There was a trend toward higher CA 125 concentrations in patients with at least moderately impaired systemic ventricular function (p = 0.058) or AV valve regurgitation (p = 0.044). No significant correlations were found between CA 125 and height (p = 0.81), weight (p = 0.26), age (p = 0.19), sex (p = 0.20), systemic ventricular morphology (0.54), or type of Fontan connection (p = 0.73). Over a median follow-up of 5.8 years (IQR, 3.2–7.9), 30 patients reached the composite endpoint. CA 125 level at baseline was a significant predictor of Fontan-specific MACE (HR for log CA 125, 6.7 [95% CI, 2.6–17.0], p < 0.001).

Conclusion: CA 125 levels were significantly elevated in Fontan patients with edema, ascites, and higher NYHA functional class, and were highly associated with Fontan-specific MACE. These data suggest that CA 125 may serve as a valuable biomarker for risk prediction in patients with Fontan circulation.

Publication History

Article published online:
11 February 2025