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.
