Decreased Expression of Tumor Necrosis Factor-α in Failing Human Myocardium After Mechanical Circulatory Support

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Abstract
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-α (TNF-α) is a proinflammatory cytokine capable of producing pulmonary edema, dilated cardiomyopathy, and death. TNF-α is produced in the myocardium in response to volume overload; however, the effects of normalizing ventricular loading conditions on myocardial TNF-α 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-α 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-α, and quantitative analysis of the stained area was performed. We found that TNF-α 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-α 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-α content in failing myocardium; furthermore, we suggest that the magnitude of the change may predict which patients will recover cardiac function.