Dynamics of SERPINA3 in response to anthracycline treatment and cardiovascular dysfunction

Figures

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  Fig. 1. Overview of patients with criteria for the diagnosis of CTRCD. Moderate CTRCD was defined as a decline in LVEF to 40–49%. Mild CTRCD was defined as a rise in biomarkers from baseline (hs-cTnI > 45 ng/l and/or NT-proBNP > 125 pg/ml) and/or a rise in GLS with more than 15% from baseline. CTRCD: Cancer therapy related cardiac dysfunction, LVEF: left ventricular ejection fraction, hs-cTnI: highly sensitive cardiac troponin I; GLS: global longitudinal strain; NT-proBNP: NT-pro brain natriuretic peptide. Created with Lucidchart

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  Fig. 2. Evolution of echocardiographic and circulating biomarkers during AnC and after chemotherapy. Figure A-D depict the combined results of the whole study population (n = 55). Figure E, F show the results according to CTRCD group. A A significant decline in LVEF over time is seen in up until 12 months after therapy B A significant rise in GLS is seen over time. C An early peak directly after AnC in hs-cTnI is followed by a decline at 12 months. D Three months after AnC, NT-proBNP is significantly higher in patients. E A significantly greater decline is present in patients with moderate CTRCD compared to mild and no CTRCD. F GLS increases in all CTRCD groups without returning to baseline values. G An early peak in hs-cTnI directly after AnC is followed by a subsequent decline at 12 months and is higher in mild and moderate CTRCD. F Three months after AnC, NT-proBNP is significantly higher in patients with moderate CTRCD compared to no CTRCD. For hs-cTnI and NT-proBNP statistics was performed on logarithmic transformations. CTRCD: Cancer therapy related cardiac dysfunction, LVEF: left ventricular ejection fraction, hs-cTnI: highly sensitive cardiac troponin I; GLS: global longitudinal…

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  Fig. 3. Evolution of SERPINA3 during and after AnC. A Evolution of SERPINA3 in the total cohort. SERPINA3 show a dynamic change over time, with return to baseline levels after 12 months. B Evolution of SERPINA3 according to CTRCD group. A significant decrease is observed (V1-V3) in patients without and with mild CTRCD, while levels remained unaltered in the moderate CTRCD group. C Evolution of SERPINA3 according to presence of a clinically significant decrease in LVEF during follow-up. Only patients with preserved LVEF showed a clinically significant decrease in SERPINA3. CTRCD: cancer therapy related cardiac dysfunction, LVEF: left ventricular ejection fraction. *P < 0.05, **p < 0.01

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  Fig. 4. ROC curves for moderate CTRCD (LVEF 40–49%). A SERPINA3 has the highest AUC at V2 compared to NT-proBNP and hs-cTnI. B SERPINA3 has the highest AUC at V3 compared to NT-proBNP and hs-cTnI. CTRCD: Cancer therapy related cardiac dysfunction, LVEF: left ventricular ejection fraction, hs-cTnI: highly sensitive cardiac troponin I; NT-proBNP: NT-pro brain natriuretic peptide

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  Fig. 5. SERPINA3 according to patient characteristics and malignancy. A SERPINA3 values are higher in male than females. B SERPINA3 values are lower in breast cancer patients compared to leukaemia or lymphoma patients. C SERPINA3 values are lower in HER2 negative compared to HER2 positive breast cancer patients. D SERPINA3 values in patients treated with doxorubicin declines over time, but increased if patients were treated with Daunorubicin. E SERPINA3 values were lower in patients treated with radiotherapy compared to patients who did not receive radiotherapy. HER2: human epidermal growth factor receptor 2; RT: Radiotherapy