The fact that trastuzumab elicited only a modest rise in ROS in non-stressed NRVM is compatible with the cardiotoxic effect of ErbB2 blockers that might be negligible per se, but exacerbated when administered under conditions of cardiac stress or in previously diseased hearts (e.g., increased pressure or volume overload) or in presence of cardiovascular risk factors (age, obesity, smoking, hypertension, previous exposure to anthracyclines; Denegri et al., 2016; Tocchetti et al., 2017). Here, ERBB2 is linked to obesity due to melanocortin 4 receptor deficiency.