High CA125 levels as a red flag for ATTR cardiac amyloidosis

INTRODUCTION: Recognition of transthyretin cardiac amyloidosis (ATTR-CA) remains challenging. In heart failure, plasmatic carbohydrate antigen 125 (CA125) is an established biomarker, reflecting inflammation and volume overload, common issues in ATTR-CA. Our aim was to evaluate the potential utility of CA125 as a 'rule-in' biomarker for suspected ATTR-CA. METHODS AND RESULTS: This is a retrospective, multicentre, case-control study that included 626 consecutive ambulatory patients (median age 79 years, 74.8% male) from three tertiary centres. All individuals underwent 99mTc-DPD scintigraphy for suspected cardiac amyloidosis and had a CA125 determination available at the time of the evaluation. Following diagnostic workup, 451 (72%) patients were diagnosed with ATTR-CA, while 175 (28%) were ruled out for the disease. Patients with ATTR-CA showed a non-significant trend towards higher CA125 levels (16.2 [10.2-29.7] vs 14 [8-26.3] U/mL, P = .065). A CA125 cut-off of 40 U/mL yielded a positive predictive value of 81.7% (95% confidence interval: 78.6%-84.7%). In a multivariate logistic regression model, CA125 was an independent predictor for the diagnosis of ATTR-CA (odds ratio 2.109; 95% confidence interval: 1.197-3.717; P = .01). Combining CA125 (>40 U/mL) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (>2500 pg/mL) significantly improved the diagnostic accuracy of the model. Patients with both biomarkers above their respective cut-offs had a three-fold higher likelihood of ATTR-CA (odds ratio: 3.38; 1.704-6.719; P < .001). CONCLUSIONS: In ambulatory patients with suspected ATTR-CA, a CA125 > 40 U/mL, particularly when combined with elevated NT-proBNP, supports the clinical suspicion of the disease. High CA125 levels may be useful in ATTR-CA recognition.