Simvastatin decreases myocardial tumor necrosis factor alpha 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 alpha (TNF-alpha) expression; TNF-alpha 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-alpha 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-alpha 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-alpha 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-alpha expression. This decrease did not translate into a difference in the markers of hypertrophy. However, decreased myocardial TNF-alpha may be a marker of a general statin-mediated decrease in inflammation in the transplanted heart that leads to improved graft and patient survival.