Association between Venous Excess Ultrasound (VExUS) Score and Serum CA-125 Levels in Patients with Heart Failure and Left Ventricular Systolic Dysfunction: A Prospective Pilot Study
Asociación entre la puntuación de ultrasonido de exceso venoso (VExUS) y los niveles séricos de CA-125 en pacientes con insuficiencia cardíaca y disfunción sistólica del ventrículo izquierdo: un estudio piloto prospectivo
Louis Fernando Robles-Fernandes, Gabriela Rodríguez-Guzmán, Genaro Hiram Mendoza-Zavala, Eduardo Almeida-Gutierrez, Karina Lupercio-Mora, Diana Romero-Zertuche, Rosalba Carolina García-Méndez, Jesús Salgado-Campos, Amor Yanira Cazares-Avendaño, Juan Betuel Ivey-Miranda
Abstract
Introduction: Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Accurate assessment of congestion is fundamental in patients with worsening HF, yet physical examination and chest radiography may underestimate its severity. Carbohydrate antigen 125 (CA-125) has emerged as a biomarker associated with congestion severity and prognosis in HF. However, its relationship with ultrasound-defined systemic venous congestion using the Venous Excess Ultrasound (VExUS) score has not been evaluated.
Material and methods: We conducted a prospective, cross-sectional, single-center pilot study including ambulatory patients with previously diagnosed chronic HF with reduced ejection fraction and with clinical suspicion of worsening heart failure. At inclusion, blood samples were obtained for CA-125 measurement and transthoracic echocardiography with VExUS assessment was performed during the same visit, prior to treatment adjustment. The primary objective was to determine the association between VExUS score and CA-125 levels.
Results: Fifty-four patients were included. A moderate positive correlation was observed between VExUS grade and CA-125 (Spearman ρ=0.46, p<0.001). In multivariable analysis adjusting for age, ejection fraction and serum creatinine, VExUS grade remained independently associated with CA-125 (β = 0.387, p = 0.001).
Discussion: In patients with HF and left ventricular systolic dysfunction, CA-125 levels correlate with ultrasound-defined systemic venous congestion. CA-125 may represent an accessible biomarker reflecting congestion severity in ambulatory clinical settings.
Keywords
Resumen
Introducción: La insuficiencia cardíaca (IC) sigue siendo una de las principales causas de morbilidad y mortalidad a nivel mundial. La evaluación precisa de la congestión es fundamental en pacientes con IC progresiva; sin embargo, la exploración física y la radiografía de tórax pueden subestimar su gravedad. El antígeno carbohidrato 125 (CA-125) ha surgido como un biomarcador asociado a la gravedad de la congestión y al pronóstico en la IC. No obstante, su relación con la congestión venosa sistémica definida por ecografía mediante la puntuación de exceso venoso por ultrasonido (VExUS) no se ha evaluado.
Material y métodos: Realizamos un estudio piloto prospectivo, transversal y unicéntrico que incluyó pacientes ambulatorios con IC crónica previamente diagnosticada, con fracción de eyección reducida y con sospecha clínica de empeoramiento de la insuficiencia cardíaca. Al inicio del estudio, se obtuvieron muestras de sangre para la medición de CA-125 y se realizó una ecocardiografía transtorácica con evaluación VExUS durante la misma visita, antes del ajuste del tratamiento. El objetivo principal fue determinar la asociación entre la puntuación VExUS y los niveles de CA-125.
Resultados: Se incluyeron cincuenta y cuatro pacientes. Se observó una correlación positiva moderada entre el grado VExUS y el CA-125 (Spearman ρ=0,46, p<0,001). En el análisis multivariante, ajustando por edad, fracción de eyección y creatinina sérica, el grado VExUS se mantuvo asociado de forma independiente con el CA-125 (β = 0,387, p = 0,001).
Discusión: En pacientes con insuficiencia cardíaca y disfunción sistólica del ventrículo izquierdo, los niveles de CA-125 se correlacionan con la congestión venosa sistémica definida por ecografía. El CA-125 podría representar un biomarcador accesible que refleje la gravedad de la congestión en entornos clínicos ambulatorios.
Palabras clave
References
1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-726. doi: 10.1093/eurheartj/ehab368.
2. Olofsson M, Lindmark K, Stålhammar J, Törnblom M, Lundberg A, Wikström G, et al. Characteristics and management of very elderly patients with heart failure: a retrospective, population cohort study. ESC Heart Fail. 2023;10(1):295-302. doi: 10.1002/ehf2.14191.
3. Ruiz-García A, Serrano-Cumplido A, Escobar-Cervantes C, Arranz-Martínez E, Turégano-Yedro M, Pallarés-Carratalá V. Heart Failure Prevalence Rates and Its Association with Other Cardiovascular Diseases and Chronic Kidney Disease: SIMETAP-HF Study. J Clin Med. 2023;12(15):4924. doi: 10.3390/jcm12154924.
4. Kumric M, Kurir TT, Bozic J, Slujo AB, Glavas D, Miric D, et al. Pathophysiology of Congestion in Heart Failure: A Contemporary Review. Card Fail Rev. 2024;10:e13. doi: 10.15420/cfr.2024.07.
5. Magaña-Serrano JA, Rosas-Peralta M, Candanosa-Arias C, Valencia-Sánchez S, Garrido-Garduño M, Arriaga-Nava R, et al. [Heart failure with preserved ejection fraction (HFPEF). Impact of change in the paradigm of isolated diastolic dysfunction]. Gac Med Mex. 2015;151(5):635-47.
6. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421. doi: 10.1016/j.jacc.2021.12.012.
7. Magaña-Serrano JA, Argüero-Sánchez R. [Chronic complications in cardiac transplantation. Clinical implications and future strategies]. Rev Invest Clin. 2005;57(2):338-43.
8. Mallick A, Januzzi JL Jr. Biomarkers in acute heart failure. Rev Esp Cardiol (Engl Ed). 2015;68(6):514-25. doi: 10.1016/j.rec.2015.02.009.
9. Fu S, Ping P, Zhu Q, Ye P, Luo L. Brain Natriuretic Peptide and Its Biochemical, Analytical, and Clinical Issues in Heart Failure: A Narrative Review. Front Physiol. 2018;9:692. doi: 10.3389/fphys.2018.00692.
10. Kaya H, Kurt R, Beton O, Zorlu A, Yucel H, Gunes H, et al. Cancer Antigen 125 is Associated with Length of Stay in Patients with Acute Heart Failure. Tex Heart Inst J. 2017;44(1):22-8. doi: 10.14503/THIJ-15-5626.
11. Llàcer P, Bayés-Genís A, Núñez J. Carbohydrate antigen 125 in heart failure. New era in the monitoring and control of treatment. Med Clin (Barc). 2019;152(7):266-73. doi: 10.1016/j.medcli.2018.08.020.
12. Li KHC, Gong M, Li G, Baranchuk A, Liu T, Wong MCS, et al. Cancer antigen-125 and outcomes in acute heart failure: a systematic review and meta-analysis. Heart Asia. 2018;10(2):e011044. doi: 10.1136/heartasia-2018-011044.
13. Soler M, Miñana G, Santas E, Núñez E, de la Espriella R, Valero E, et al. CA125 outperforms NT-proBNP in acute heart failure with severe tricuspid regurgitation. Int J Cardiol. 2020;308:54-9. doi: 10.1016/j.ijcard.2020.03.027.
14. Llàcer P, Gallardo MÁ, Palau P, Moreno MC, Castillo C, Fernández C, et al. Comparison between CA125 and NT-proBNP for evaluating congestion in acute heart failure. Med Clin (Barc). 2021;156(12):589-94. doi: 10.1016/j.medcli.2020.05.063.
15. Frigy A, Belényi B, Kirchmaier Á, Fekete N, Szabó IA. Elevated CA-125 as Humoral Biomarker of Congestive Heart Failure: Illustrative Cases and a Short Review of Literature. Case Rep Cardiol. 2020;2020:1642914. doi: 10.1155/2020/1642914.
16. Núñez J, de la Espriella R, Miñana G, Santas E, Llácer P, Núñez E, et al. Antigen carbohydrate 125 as a biomarker in heart failure: a narrative review. Eur J Heart Fail. 2021;23(9):1445-57. doi: 10.1002/ejhf.2295.
17. Campos-Sáenz de Santamaría A, Albines Fiestas ZS, Crespo-Aznarez S, Esterellas-Sánchez LK, Sánchez-Marteles M, Garcés-Horna V, et al. VExUS
Protocol Along Cardiorenal Syndrome: An Updated Review. J Clin Med. 2025;14(4):1334. doi: 10.3390/jcm14041334.
18. Núñez J, de la Espriella R, Rossignol P, Voors AA, Mullens W, Metra M, et al. Congestion in heart failure: a circulating biomarker-based perspective. A review from the Biomarkers Working Group of the Heart Failure Association, European Society of Cardiology. Eur J Heart Fail. 2022;24(10):1751-66. doi: 10.1002/ejhf.2664.
19. Beaubien-Souligny W, Rola P, Haycock K, Bouchard J, Lamarche Y, Spiegel R, et al. Quantifying systemic congestion with Point-Of-Care ultrasound: development of the venous excess ultrasound grading system. Ultrasound J. 2020;12(1):16. doi: 10.1186/s13089-020-00163-w.
20. Núñez J, Núñez E, Consuegra L, Sanchis J, Bodí V, Martínez-Brotons A, et al. Carbohydrate antigen 125: an emerging prognostic risk factor in acute heart failure? Heart. 2007;93(6):716-21. doi: 10.1136/hrt.2006.096016.
21. Feng R, Zhang Z, Fan Q. Carbohydrate antigen 125 in congestive heart failure: ready for clinical application? Front Oncol. 2023;13:1161723. doi: 10.3389/fonc.2023.1161723.
22. Rola P, Miralles-Aguiar F, Argaiz E, Beaubien-Souligny W, Haycock K, Karimov T, et al. Clinical applications of the venous excess ultrasound (VExUS) score: conceptual review and case series. Ultrasound J. 2021;13(1):32. doi: 10.1186/s13089-021-00232-8.
23. Argaiz ER, Romero-Gonzalez G, Rola P, Spiegel R, Haycock KH, Koratala A. Bedside Ultrasound in the Management of Cardiorenal Syndromes: An Updated Review. Cardiorenal Med. 2023;13(1):372-84. doi: 10.1159/000534976.
24. Núñez J, Llàcer P, Bertomeu-González V, Bosch MJ, Merlos P, García-Blas S, et al. Carbohydrate Antigen-125-Guided Therapy in Acute Heart Failure: CHANCE-HF: A Randomized Study. JACC Heart Fail. 2016;4(11):833-43. doi: 10.1016/j.jchf.2016.06.007.
25. Núñez J, Núñez E, Bayés-Genís A, Fonarow GC, Miñana G, Bodí V, et al. Long-term serial kinetics of N-terminal pro B-type natriuretic peptide and carbohydrate antigen 125 for mortality risk prediction following acute heart failure. Eur Heart J Acute Cardiovasc Care. 2017;6(8):685-96. doi: 10.1177/2048872616649757.
Submitted date:
02/28/2026
Reviewed date:
04/09/2026
Accepted date:
04/23/2026
Publication date:
04/23/2026
