Background-An increasing number of observations in patients with end-stage heart failure suggest that chronic ventricular unloading by mechanical circulatory support may lead to recovery of cardiac function. Tumor necrosis factor-␣ (TNF-␣) is a proinflammatory cytokine capable of producing pulmonary edema, dilated cardiomyopathy, and death. TNF-␣ is produced in the myocardium in response to volume overload; however, the effects of normalizing ventricular loading conditions on myocardial TNF-␣ expression are not known. We hypothesize that chronic ventricular unloading by the placement of a left ventricular assist device (LVAD) may eliminate the stress responsible for persistent TNF-␣ expression in human failing myocardium. Methods and Results-Myocardial tissue was obtained from normal hearts and from paired samples of 8 patients with nonischemic end-stage cardiomyopathy at the time of LVAD implantation and removal. Tissue sections were stained for TNF-␣, and quantitative analysis of the stained area was performed. We found that TNF-␣ content decreased significantly after LVAD support. Furthermore, the magnitude of the changes did not correlate with the length of LVAD support, although greater reductions in myocardial TNF-␣ content were found in patients who were successfully weaned off the LVAD who did not require transplantation. Conclusions-These data show for the first time that chronic mechanical circulatory assistance decreases TNF-␣ content in failing myocardium; furthermore, we suggest that the magnitude of the change may predict which patients will recover cardiac function.
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