Abstract Body (Do not enter title and authors here): BACKGROUND: Chronic heart failure (CHF) is a complex clinical syndrome associated with high morbidity and mortality. Recent studies have explored a potential novel biomarker, carbohydrate antigen 125 (CA 125) to predict prognosis. This systematic review and meta-analysis evaluates the association between CA 125 and CHF prognosis.

OBJECTIVE: To evaluate the use of CA 125 as a prognostic biomarker for clinical outcomes in chronic heart failure.

METHODS: We systematically searched PubMed, Cochrane Library, and Embase from January 2020 to June 2025. We included retrospective and prospective cohort studies that enrolled adult patients with CHF—either with reduced or preserved ejection fraction—and a minimum follow-up duration of 12 months.

RESULTS: Six studies (6 observational cohorts) including a total of 3,093 patients with CHF were included (mean age 71.8 years old, 60.4% male, mean follow-up 20.4 months). All studies evaluated baseline CA 125 levels in relation to clinical outcomes. All studies consistently reported that elevated CA 125 levels were significantly associated with increased all-cause mortality. Hazard ratios ranged from 1.58 to 2.32 across diverse heart failure phenotypes, including HFrEF, HFpEF, and advanced-stage CHF. Across studies, elevated CA 125 levels were consistently associated with a higher risk of first or recurrent CHF-related hospitalizations. Effect estimates included hazard ratios ranging from 1.29 to 1.81 and incidence rate ratios up to 1.62. In the meta-analysis, patients with high CA 125 levels had a significantly increased risk of all-cause mortality. The pooled risk ratio was 3.29 [95% CI, 1.90–5.70] (p < 0.0001), indicating over three times the mortality risk compared to those with low CA 125. Heterogeneity was substantial (I²= 92%), supporting the use of a random-effects model.

CONCLUSION: This systematic review and meta-analysis found that higher CA 125 levels are significantly associated with higher mortality and readmission in patients with CHF, these attributes position it as a highly potential biomarker for risk stratification. Further studies are needed to establish CA 125 as a biomarker in the prognosys of CHF.