Expanding biomarker strategies in advanced heart failure: the emerging role of CA-125
P Bernardes, S Goncalves, J Quintal, T Duarte, M Madeira, A Sousa, C Ferreira, S Senhorinho, D Ferreira, A Soares, D Campos, M Tomaz, C Pohle, F SeixoAbstract
Introduction
Carbohydrate antigen 125 (CA-125), a glycoprotein traditionally used as a tumor marker, has recently emerged as a promising biomarker of systemic congestion in heart failure (HF). However, its prognostic and predictive value in advanced HF remains insufficiently characterized.
Purpose
To assess the relationship between CA-125, congestion burden, and clinical outcomes in advanced HF, and to determine whether CA-125 adds information beyond NT-proBNP.
Methods
We conducted a retrospective observational study including 94 outpatients with advanced HF followed at our multidisciplinary HF unit between September 2020 and October 2025. Routine CA-125 measurement was introduced in April 2025 and was available for 60 pts who were alive and under follow-up at that time. Clinical data, biomarker levels, HF hospitalizations, urgent HF visits, and mortality were analysed. Advanced HF was defined according to the 2018 Heart Failure Association (HFA) of the European Society of Cardiology (ESC) position statement.
Results
The subgroup with CA-125 measurements comprised 60 patients (mean age 71 ± 13.6 years; 65% male). Mean follow-up was 19.0 ± 9.5 months, and 90% were in NYHA class III–IV. Comorbidities were common: hypertension (70%), diabetes mellitus (47%), chronic kidney disease (42%), and obesity (37%). Ischaemic cardiomyopathy accounted for 48% of cases. Median CA-125 was 65 U/mL (IQR 16–143) and median NT-proBNP 5174 pg/mL (IQR 2085–15 565). CA-125 correlated with HF hospitalizations (p = 0.045), urgent HF visits (p = 0.032), and NT-proBNP (Spearman ρ = 0.419, p < 0.001). The correlation with NT-proBNP was stronger in patients with right or biventricular HF (ρ = 0.554, p = 0.003) than in those with left-sided HF (ρ = 0.305, p = 0.084). No significant association with mortality was observed (p = 0.466). In multivariable Poisson regression, CA-125 independently predicted the number of HF decompensations (IRR 1.003, 95% CI 1.002–1.004, p < 0.001), meaning that each 100 U/mL increase in CA-125 corresponded to an approximately 35% higher rate of HF decompensations.
Conclusions
In this cohort of advanced HF, elevated CA-125 was strongly associated with congestion burden and decompensation frequency. Its correlation with NT-proBNP—particularly in right/biventricular HF—supports a complementary role in congestion assessment. CA-125 is a simple, inexpensive biomarker providing additive prognostic information when interpreted alongside NT-proBNP.For image description, please refer to the figure legend and surrounding text.