Comparative analysis of the cardiotoxicity induced by doxorubicin and epirubicin and exploratory investigations of clinical parameters indicating the cardiotoxicity in healthy dogs

Cardiotoxicity of doxorubicin (DOX) and epirubicin (EPI) has not been thoroughly compared in dogs. Fractional shortening (FS) is considered insufficient for detecting early myocardial damage induced by these drugs. This study aimed to compare the cardiotoxicity between EPI and DOX and to investigate parameters associated with histopathological findings induced by these drugs. Eight healthy beagles were randomly divided into two groups and administered either DOX or EPI until development of anthracycline-induced cardiac dysfunction (AICD), defined as consecutive FS below 30%, or until reaching a cumulative dose of 300 mg/m². After the final evaluation, the dogs were euthanized, and cardiac tissues were histopathologically evaluated. One dog in the EPI group developed AICD after six administrations (cumulative dose of 168 mg/m²), whereas no other dogs did. The number of vacuolated myocardial cells was significantly higher in the DOX group than in the EPI group. In the DOX group, but not in the EPI group, longitudinal strain (A4C-LS) and tissue motion mitral annulus displacement (A4C-TMAD) from the left apical four-chamber view, global longitudinal strain, myocardial performance index and velocity-time integral from left ventricle, mitral annular plane systolic excursion, and high-sensitivity cardiac troponin I showed significant changes after treatment. Furthermore, A4C-LS and A4C-TMAD were correlated with the extent of myocardial collagen fibers. These results suggest that EPI induces less severe myocardial injury than DOX, although individual variability in drug sensitivity exists. Echocardiographic parameters such as A4C-LS and A4C-TMAD may serve as sensitive markers for early myocardial injury.