Myocardial work derived from myocardial stiffness and strain in childhood cancer survivors treated with high-dose anthracycline chemotherapy

Background Myocardial function assessment in childhood cancer survivors (CCS) is challenging as conventional measurements do not accurately reflect myocardial performance. Non-invasive calculation of myocardial work (MW) derived from myocardial stiffness (MS) and strain offers clinically relevant advantages, providing insights into the heart's energetic demands. Purpose We aimed to compare MW in CCS who received a cumulative anthracycline (AC) dose ≥250 mg/m² and had been off therapy ≥5 years, with age-matched healthy volunteers (HV). Shear wave elastography and MW were measured to predict which patients are most likely to develop subclinical cardiac abnormalities before the onset of overt AC-induced cardiac dysfunction. Methods Cross-sectional single-centre study. We included 20 CCS (median age at study: 16 years [IQR 15;17]), median AC cumulative dose 367 mg/m2 [IQR 300;435], diagnosed with either solid tumours (n=11) or blood malignancies (n=9), and 20 age-matched HVs. The study population underwent clinical assessment with full conventional echocardiography and shear wave elastography on the same day. Myocardial strain, wall thickness, and MS were assessed in the basal antero-septal segment of the interventricular septum throughout the entire cardiac cycle. From combined stiffness and strain measurements, we derived contributive work, reflecting the segmental contribution to left ventricular pump function, and one-beat segmental work, representing the effective mechanical energy generated by the antero-basal interventricular septum during systole. Results Strain values did not differ between the two study groups and were within the normal range. Peak systolic MS was lower in CCS compared to HV (28.3±4.79 KPa vs 40.4±5.02 KPa, p <0.001), while mean diastolic MS was significantly higher in CCS (14.59±5.02 KPa vs 8.85±1.81 KPa, p <0.001) (Figure 1). Both contributive work and one-beat segmental work were significantly lower in CCS (7.8 ±9.4 J/mm and 38.9±22 kPa%, respectively) compared to healthy controls (26.9±26uJ/mm and 61.8±27 kPa%, respectively), p=0.02. The stiffness-strain loop area was higher in HV compared to cancer patients (221.38 ± 237.23 KPa% vs 75.73±100.19 KPa% respectively, p=0.01) (Figure 2), as well as the stress-strain loop area (peak stress 6.64 ±1.72 KPa vs 3.39±1.63 KPa respectively, p=0.001). Conclusion In this cohort of high-risk long-term CCS, MW was significantly impaired despite preserved left ventricular ejection fraction and normal global longitudinal strain. This integrated approach represents a feasible methodological innovation, linking altered tissue biomechanics to functional consequences. Myocardial work analysis may provide incremental value for the early identification of AC-related cardiotoxicity, supporting more refined and risk-adapted cardiovascular surveillance in long-term pediatric cardiooncology follow-up.Figure 1.MS, Peak systolic dataFigure 2.