Childhood acute lymphoblastic leukemia (ALL) patients are treated with doxorubicin-based chemotherapy(Singal and Iliskovic, 1998). The long-term association between doxorubicin and cardiotoxicity is a well-known cause of several long-term adverse effects. Indeed, childhood ALL survivors often suffer from impaired left ventricular (LV) contractility, reduced ejection fraction, contractility and diastolic function, high-grade ectopy, late congestive heart failure, and sudden death(2019; Grenier and Lipshultz, 1998, Hudson et al., 2013, Kremer et al., 2001, Lemay et al., 2019). Independently of the received doxorubicin doses, subclinical dysfunctions and cardiac abnormalities have been reported(Armstrong et al., 2012; 2019; Lipshultz et al., 1991, Lipshultz et al., 2005, Ylänen et al., 2013).

Studies have reported that the mechanical properties of the myocardium could be an adequate indicator of the tissue’s viability, in addition to being good predictors of cardiac disease development(Dabiri et al., 2018, Wang et al., 2018, Whitaker et al., 2016). Indeed, myofiber stress and myocardial stiffness are used to identify patients with severe heart failure(Wang et al., 2018). Moreover, a variation in subepicardial and subendocardial contractility can be involved in the development of heart failure with a preserved ejection fraction(Dabiri et al., 2018). This is of interest since adult survivors treated with doxorubicin have been reported to experience late cardiac dysfunction that may begin with congestive heart failure(Hequet et al., 2004, Ness et al., 2011). Cardiac abnormalities are highly dependent on cumulative doxorubicin doses(Armenian et al., 2015, Steinherz et al., 1991). In this sense, cardiac magnetic resonance (CMR) imaging is used to obtain high-quality cardiac functional information and to study childhood ALL survivors’ doxorubicin-related cardiotoxicity(Group, 2013, Shankar et al., 2008, Wassmuth et al., 2001).

Considering the current literature, we propose a new approach using the combination of CMR imaging, cardiopulmonary exercise testing (CPET) and the CircAdapt model to explore hemodynamics and intraventricular mechanisms at rest and during exercise. The use of the CircAdapt model, a lumped-element model, is favored to better understand the complexity of the myocardial mechanisms in childhood ALL survivors. Moreover, it allows live interaction simulations between the myocardium walls and can be used as a non-invasive tool to study hemodynamics and intraventricular mechanisms(Lumens and Delhaas, 2012). The strength of the parameterized numerical CircAdapt model is that it addresses the issue of the high number of unknown variables necessary in the lumped-element model(Arts et al., 2005).

Our study aims to characterize myocardial subtle changes induced by doxorubicin-related cardiotoxicity in childhood ALL survivors. To reach this goal, the mechanical properties of the LV are rigorously studied by using volumes extracted from CMR imaging coupled with data from a CPET and a reverse material identification approach based on the CircAdapt model.