Cardiac Injury Due to Anthracycline in Paediatric Oncological Patients

The study investigates the role of echocardiography and of serum biomarkers (NT-proBNP, cardiac Troponin-I) in predicting cardiac injury in a cohort of paediatric oncological patients treated with Anthracycline chemotherapy.

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).

As far as we are, 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 LVEF is useful to guide clinical decisions, and emerging data shows the clinical value of measuring 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 LVEF and GLS depend on 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 LV systolic function in a way that incorporates afterload and has the potential to quantify LV energy waste.

Noninvasive MW is a robust and reproducible index of LV systolic performance. It correlates with myocardial metabolism and shows less afterload dependency than LVEF and GLS.

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

Eligibility Criteria:
Inclusion Criteria:

* Paediatric oncological patients 0-18 years
* Planned start of anthracycline therapy
* Normal left ventricular systolic function according to International Guidelines before the treatment with AC

Exclusion Criteria:

* Previous anthracycline treatment, bone marrow transplantation or chest radiation
* Pre-anthracycline treatment echocardiographic evidence of:
* More than mild pericardial effusion
* More than mild mitral regurgitation
* Poor echocardiographic acoustic window