By using a highly translatable large-animal model, this work shows that cumulative exposure to anthracycline results in an irreversible damage to the
heart microcirculation. The microcirculation injury is observed even before overt left ventricular cardiac systolic dysfunction (surrogate for overt cardiotoxicity) is present. Cardiac microcirculation damage is associated with poor clinical outcome in general, and thus the present findings might partially explain the high incidence of cardiovascular adverse outcomes in cancer survivors even in the absence of overt cardiotoxicity.