An important harmful side effect of the prolonged support of the left ventricle (LV) with an LV assist device (LVAD) in patients with advanced heart failure (HF) is development of cardiac atrophy. Our first aim was to evaluate if implantation of the four-branch spring expander into LV of the rat will exhibit greater attenuation of unloading-induced cardiac atrophy as compared with the threebranch spring expander. The second aim was to assess if sex-related differences are present in the development of unloading-induced cardiac atrophy in the failing hearts with implanted either threebranch or four-branch spring expander into the LV. Heterotopic heart transplantation in the rat (HTx) served as the model of heart unloading after LVAD implantation. HF was induced by volume overload achieved by creation of the aorto-caval fistula. The degree of cardiac atrophy was assessed as the weight ratio of the heterotopically transplanted heart to the control native heart. We found that enhancement of isovolumic loading by implantation of either type of spring expander into the LV reduced the degree of post-HTx cardiac atrophy in the failing hearts but the four-branch variant was significantly more effective. In addition, we found that there were no sex-related differences in the development of unloading-induced cardiac atrophy or in the attenuation of this process in the failing hearts. We propose that enhancing cardiac work by increasing isovolumic loading via implantation of the spring expander might be a reasonable approach to attenuate the unloading-induced cardiac atrophy in the failing hearts in both sexes.