To determine the histopathologic effect of prolonged (> 30 days) left ventricular unloading on the myocardium, the authors studied myocardial tissue specimens from eight men (mean age, 40.8 years) with end-stage cardiomyopathy (six idiopathic, two ischemic) who were supported with the HeartMate (Thermo Cardiosystems, Inc., Woburn, MA) left ventricular assist device (LVAD) as a bridge to cardiac transplantation. The average length of support was 79.6 days (range, 31-136 days). Before left ventricular support was instituted, transthoracic echocardiography revealed that all patients had significantly dilated left ventricular cavities (average left ventricular diastolic dimension, 7.2 cm). Tissue specimens from the core of the left ventricular apex, which is removed at the time of LVAD implantation, were compared through pathologic examination with specimens from the explanted hearts at the time of cardiac transplantation. Apical core specimens from all patients exhibited extensive areas of attenuated myocardial fibers, combined with wavy patterns in some areas. In these regions, the nuclei of the cardiac myocytes from idiopathic cardiomyopathy specimens were neither pyknotic nor disappearing, as was noted in an infarcted area of a specimen from one patient with ischemic cardiomyopathy. At the time of heart transplantation, myocardial tissue specimens from the explanted hearts had a significant decrease or disappearance of stretched fibers. There was also a slight increase in interstitial replacement fibrosis, as well as an increase in the diameter of the myocardial fibers. These findings appear to correlate with the clinical impression of improved native ventricular function and with radiographic findings and decreased chamber size during prolonged ventricular support.