Dynamics of SERPINA3 in response to anthracycline treatment and cardiovascular dysfunction.

IF 3.2 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardio-oncology Pub Date : 2025-03-14 DOI:10.1186/s40959-025-00324-7

Hanne M Boen, Lobke L Pype, Konstantinos Papadimitriou, Sevilay Altintas, Laure-Anne Teuwen, Sébastien Anguille, Kirsten Saevels, Anke Verlinden, Leen Delrue, Ward A Heggermont, Matthias Bosman, Pieter-Jan Guns, Hein Heidbuchel, Caroline M Van De Heyning, Emeline M Van Craenenbroeck, Constantijn Franssen

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Abstract

Background: SERPINA3 recently emerged as potential prognostic biomarker in heart failure. In a population of cancer survivors with cancer therapy-related cardiac dysfunction (CTRCD) circulating SERPINA3 was elevated compared to age-matched controls. We aimed to assess the longitudinal dynamics of circulating SERPINA3 levels in patients with cancer treated with anthracycline chemotherapy (AnC) and its relation to CTRCD.

Methods: In this single centre cohort study, 55 patients with cancer scheduled for AnC were prospectively enrolled. Cardiac evaluation (echocardiography, high-sensitive cardiac troponin I and NT-proBNP) was performed and SERPINA3 levels in plasma were assessed at 4 timepoints: before chemotherapy, directly after the end of chemotherapy, three months and twelve months after the end of chemotherapy.

Results: Forty-two out of 55 patients (76.4%) developed CTRCD within 1 year after end of treatment. CTRCD was mild in 32 and moderate in 10 patients, defined as a change in cardiac biomarkers or GLS and LVEF decline < 50% respectively. Overall, median SERPINA3 levels decreased from baseline to three months after AnC (215.7 [62.0-984.0] to 176.9 [94.7-678.0] µg/ml, p = 0.031). This decrease was most prominent in patients without CTRCD (30.8% decrease, p = 0.007), followed by mild CTRCD (9.0% decrease, p = 0.022), while patients with moderate CTRCD did not show a reduction in SERPINA3 (5.1% increase, p = 0.987). SERPINA3 values at three months after AnC were positively correlated with NT-proBNP (r = 0.47, p = 0.002). Several malignancy, treatment and patient characteristics were associated with higher SERPINA3 values.

Conclusion: Circulating SERPINA3 levels show dynamic changes in a population of patients with cancer, with an overall decrease following AnC. However, in patients that developed moderate CTRCD, SERPINA3 levels remained elevated. The potential of SERPINA3 dynamics as a biomarker for CTRCD, deserves validation in larger cohorts.

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