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

## TL;DR

This study shows that SERPINA3 levels decrease after chemotherapy in most cancer patients, but remain high in those who develop moderate heart damage.

## Contribution

The study reveals dynamic changes in SERPINA3 levels and their association with cardiac dysfunction severity after chemotherapy.

## Key findings

- SERPINA3 levels decreased overall after chemotherapy, especially in patients without heart damage.
- Patients with moderate heart dysfunction showed no reduction in SERPINA3 levels.
- SERPINA3 levels at three months correlated with NT-proBNP, a marker of heart stress.

## Abstract

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.

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.

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.

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.

Overview of study protocol CTRCD development and SERPINA3 evolution in the study population. Created using Biorender.

The online version contains supplementary material available at 10.1186/s40959-025-00324-7.