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Purpose: Elevated carbohydrate antigen 125 (CA125) predicts adverse outcome after transcatheter aortic valve implantation (TAVI). While known underlying pathophysiological mechanisms of elevated CA125 include serosal effusions and inflammatory stimuli, clinical determinants associated with elevated CA125 in patients referred for TAVI remain unknown. Therefore, we investigated clinical, laboratory and echocardiographic determinants of elevated CA125 in patients with severe aortic valve stenosis referred for TAVI. Methods: This study includes 650 patients with severe aortic stenosis referred for TAVI. Baseline CA125 was determined by an immunoassay and dichotomized (elevated versus normal) based on the manufacturer cutoff value (>35 U/mL). Results: CA125 elevation was present in 28% (181/650). Patients with elevated CA125 had an overall worse clinical profile and were more symptomatic with a higher rate of NYHA class III/IV (80% versus 58%; p < 0.001). In a multivariate analysis, independent predictors of elevated CA125 were New York Heart Association (NYHA) class, baseline hemoglobin, C-reactive protein (CRP), left ventricular ejection fraction and severe tricuspid regurgitation. Conclusion: Elevated CA125 levels in patients referred for TAVI summarize a subset of patients with an overall worse clinical profile who are more symptomatic. [ABSTRACT FROM AUTHOR]