Simvastatin decreases myocardial tumor necrosis factor α content in heart transplant recipients

Background Statins improve patient survival and decrease rejection episodes in heart transplant recipients. We studied the effects of simvastatin treatment on myocardial tumor necrosis factor α (TNF-α) expression; TNF-α is a potent pro-inflammatory cytokine associated with hypertrophy and fibrosis in heart transplant recipients. Methods We randomized 10 consecutive heart transplant recipients to receive either 20 mg/day simvastatin (n = 5) or placebo (n = 5) for 6 months after cardiac transplantation. Routine surveillance endomyocardial biopsy specimens were obtained from all patients. We analyzed tissues for myocardial TNF-α content, total collagen content, and myocyte size using semiquantitative immunohistochemistry. Results Myocyte size and total collagen content of placebo and simvastatin groups did not show a statistically significant difference at any biopsy time point. Myocardium TNF-α content (% tissue area stained) at 1 week after transplantation was similar in the simvastatin and placebo groups. At the 24^th week after transplantation, when compared with Week 1 values, we found a significant decrease in myocardium TNF-α content in the simvastatin group (15.0% ± 2.3% vs 5.8% ± 2.4%, p = 0.02) that was not observed in the placebo group (15.0% ± 1.5% vs 12.0% ± 2.6%, p = not significant). Conclusion Simvastatin treatment in heart transplant recipients decreased myocardium TNF-α expression. This decrease did not translate into a difference in the markers of hypertrophy. However, decreased myocardial TNF-α may be a marker of a general statin-mediated decrease in inflammation in the transplanted heart that leads to improved graft and patient survival.