Evaluation of carbohydrate antigen 125 in heart failure with preserved ejection fraction diagnosis

Current evidence supports the role of circulating carbohydrate antigen 125 (CA125) in risk assessment, disease monitoring and therapeutic guidance in heart failure (HF). However, there is limited data on its diagnostic applicability. This study aimed to assess the diagnostic performance of CA125 in identifying HF with preserved ejection fraction (HFpEF) in an outpatient population. This was a prospective, multicentre study involving 246 consecutive patients with clinically suspected HF. Patients with a left ventricular ejection fraction <50% (n=8) and those with a history of malignancy (n=22) were excluded. The final study cohort comprised 210 patients. The diagnosis of HFpEF was confirmed by a trained cardiologist blinded to the biomarker levels. The mean age of the study cohort was 69.7±15 years, and 69% were women. Median levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and CA125 were 125 pg/mL (IQR: 51-332) and 11 U/mL (IQR: 8-17), respectively. HFpEF was diagnosed in 65 (31%) patients. For HFpEF diagnosis, NT-proBNP and CA125 levels demonstrated comparable areas under the receiver operating characteristic curves 0.765 (95% CI: 0.686 to 0.843) vs 0.715 (95% CI: 0.636 to 0.793), respectively (p=0.323). Optimal cut points were identified as 12.2 U/mL for CA125 (sensitivity: 0.69; specificity: 0.68) and 243 pg/mL for NT-proBNP (sensitivity: 0.65; specificity: 0.83). Elevated CA125 levels (>23 U/mL, 12.4% of the sample) exhibited high specificity (0.97), a positive predictive value of 80.8% and correctly classified 77.1% of cases as HFpEF. Conversely, CA125 levels<9 U/mL were associated with a high negative predictive value (85.7%). In an ambulatory setting, CA125 exhibits acceptable diagnostic performance for identifying HFpEF and may complement NT-proBNP in clinical practice.