Cardiac Injury Due to Anthracycline in Paediatric Oncological Patients

Anthracycline chemotherapy (AC) can cause dose-related cardiomyocyte injury and death, possibly leading to left ventricular dysfunction. The most commonly accepted pathophysiological mechanism of anthracycline-induced cardiotoxicity is the oxidative stress hypothesis, which suggests that the generation of reactive oxygen species and lipid peroxidation of the cell membrane damage cardiomyocytes. However, there is considerable variability among patients in their susceptibility to anthracyclines: while many tolerate standard-dose anthracyclines without long-term complications, treatment-related cardiotoxicity may occur as early as after the first dose in other patients.

An increase in cancer survival, along with better awareness of the possible late effects of cardiotoxicity, has led to growing recognition of the need for surveillance of anthracycline-treated cancer survivors to prevent the development of heart failure.

Strategies for screening and detection of cardiotoxicity include cardiac imaging \[echocardiography, nuclear imaging, cardiac magnetic resonance (CMR)\] and biomarkers (troponin, natriuretic peptides).

The echocardiographic clinical standards for measuring left ventricular (LV) systolic function are LV ejection fraction (LVEF) and global longitudinal strain (GLS) with the latter as a more sensitive parameter to detect mild systolic dysfunction. There is abundant documentation that left ventricular ejection fraction (LVEF) is useful to guide clinical decisions, and emerging data show the clinical value of measuring global longitudinal strain (GLS). In the past, a study investigated the role of conventional- and speckle-tracking echocardiography in a cohort of asymptomatic children after anthracycline therapy, showing that impaired left ventricular myocardial deformation and mechanical dyssynchrony may exist after anthracycline therapy despite having normal left ventricular shortening fractions.

However, both left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) depend on left ventricular (LV) afterload and do not provide information regarding the ventricle's efficiency. Recently, the use of non-invasive myocardial work (MW) was proposed to measure left ventricular systolic function in a way that incorporates afterload and has the potential to quantify left ventricular (LV) energy waste.

Noninvasive myocardial work (MW) is a robust and reproducible index of left ventricular (LV) systolic performance. It correlates with myocardial metabolism and shows less afterload dependency than left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS).

Different studies have shown the potential role of myocardial work (MW) in predicting the response to cardiac resynchronisation therapy (CRT) in patients with heart failure and reduced ejection fraction (HFrEF). However, the role of myocardial work (MW) in cancer paediatric patients has not yet been fully investigated.

• Sensitivity of change in myocardial work values 1 month after first Anthracycline chemotherapy treatment combined with Troponin-I hs and NT-proBNP biomarkers in predicting a decrease of the ejection fraction at 12 months [Time frame: 12 months after first Anthracycline chemotherapy treatment]
• Sensitivity of change in myocardial work values 6 months after first Anthracycline chemotherapy treatment combined with Troponin-I hs and NT-proBNP biomarkers in predicting a decrease of the ejection fraction at 12 months [Time frame: 12 months after first Anthracycline chemotherapy treatment]