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Original article
Available online 14 August 2022
CA125: a new biomarker in patients with Fontan circulation
CA125 como nuevo biomarcador en pacientes con circulación de Fontan
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Francisco Buendía Fuentesa,b,c,
Corresponding author
franciscobuendia@svcardio.org

Corresponding author:
, Pablo Jover Pastora, Miguel Ángel Arnau Vivesa,b, Silvia Lozano Edoa, María Rodríguez Serranoa, Jaime Aguerob, Ana Osa Sáeza,b, Isabel Conde Amield, Victoria Aguilera Sancho-Tellod, Luis Martínez-Dolza,b, Joaquín Rueda Sorianoa,b,c
a Servicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain
b Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain
c Unidad de Cardiopatías Congénitas del Adulto, Hospital Universitario y Politécnico La Fe, Valencia, Spain
d Unidad de Hepatología, Servicio Medicina Digestiva, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Received 14 February 2022. Accepted 17 May 2022
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Abstract
Introduction and objectives

Patients with Fontan circulation (FC) have a high incidence of clinical complications. However, no biomarker is able to accurately stratify risk. The aim of this study was to analyze the relationship between biomarkers and clinical complications, including carbohydrate antigen 125 (CA125) for the first time, and to propose a risk estimation based on a combination of biomarkers.

Methods

Cross-sectional study of patients with FC. The clinical endpoint was the combination of heart failure, atrial arrhythmias, veno-venous fistulae, protein-losing enteropathy, or plastic bronchitis. Demographic, clinical, and laboratory variables were analyzed, including CA125, NT-proBNP, renal and liver function, and red cell distribution width (RDW). We performed univariate and multivariate analyses of the relationship between these variables and the composite endpoint. Cutoff values were calculated by ROC curves.

Results

We included 56 patients (27.4±7.8 years). A total of 34% showed the composite endpoint, with significantly higher CA125 levels (30.1 IU/mL vs 12.6 IU/mL; P=.001). In the multivariate model, the biomarkers related to the endpoint were LnCA125 (OR, 5.1; 95%CI, 1.2-22), RDW (OR, 1.8; 95%CI, 1.1-3.1), and FIB4 (OR, 38, 95%CI, 1.7-855). The cutoff points were CA125 ≥ 20 U/mL, FIB4 ≥ 0.75, and RDW ≥ 14.5%, and the probability of the occurrence of the endpoint was 81% if ≥ 2 biomarkers were elevated.

Conclusions

CA125 elevation is associated with a higher prevalence of complications in patients with Fontan-type circulation. CA125 levels ≥ 20U/mL, FIB4 ≥ 0.75 and RDW ≥ 14.5% identify with a high probability the clinical failure of FC.

Keywords:
Fontan procedure
Antigen CA125
Failing Fontan circulation
Abbreviations:
RDW
CA125
Resumen
Introducción y objetivos

Los pacientes con circulación de Fontan (CF) presentan una gran incidencia de complicaciones y ningún biomarcador estratifica el riesgo. El objetivo es analizar la asociación de biomarcadores con un perfil clínico de disfunción de la CF, incluyendo por primera vez el antígeno carbohidrato 125 (CA125), y proponer una estimación del riesgo basada en la combinación de biomarcadores.

Métodos

Estudio transversal de adultos con CF. Se consideró perfil clínico desfavorable el combinado de insuficiencia cardiaca, arritmias auriculares, fístulas venovenosas, enteropatía pierdeproteínas o bronquitis plástica. Se analizaron variables clínicas y analíticas, incluidos CA125, NT-proBNP, función renal y hepática y amplitud de distribución eritrocitaria (ADE). Se realizó un estudio univariado y multivariado de la relación de dichas complicaciones clínicas y curvas ROC para obtener puntos de corte.

Resultados

Se incluyó a 56 pacientes (media de edad, 27,4±7,8 años). El 34% tenía un perfil clínico desfavorable, con valores de CA125 significativamente mayores (30,1 frente a 12,6 UI/ml; p=0,001). LnCA125 (OR=5,1; IC95%, 1,2-22), ADE (OR=1,8; IC95%, 1,1-3.1) y FIB4 (OR=38; IC95%, 1,7-855) se asociaron con un perfil de disfunción clínica. Los puntos de corte fueron CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5%, y la probabilidad de un perfil clínico desfavorable fue del 81% con 2 o más biomarcadores elevados.

Conclusiones

El aumento de CA125 se asocia con mayor prevalencia de complicaciones en pacientes con CF. Los valores de CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5% identifican con alta probabilidad fracaso clínico de la CF.

Palabras clave:
Paliación tipo Fontan
Antígeno carbohidrato 125
Disfunción de la circulación Fontan

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