Myocardial Proinflammatory Cytokine Expression and Left Ventricular Remodeling in Patients With Chronic Mitral Regurgitation

BACKGROUND: In an animal model, stretch was shown to induce myocardial tumor necrosis factor-alpha (TNF-alpha) expression. The purposes of this study were to determine whether the left ventricular (LV) volume overload that occurs in patients with chronic mitral regurgitation (MR) can induce myocardial and systemic TNF-alpha expression and whether there is a relationship between TNF-alpha expression and LV remodeling. METHODS AND RESULTS: Plasma TNF-alpha and its receptors were measured before mitral valve (MV) repair surgery in 26 MR patients and 23+/-12 months after MV repair surgery in 9 MR patients. Myocardial mRNA copies of TNF-alpha were determined in 11 MR and 10 donor hearts using quantitative RT-PCR. Compared with 15 control subjects, pre-MV repair plasma TNF-alpha (3.59+/-1.81 versus 2.03+/-1.02 pg/mL, P<0.005) and its receptor levels were elevated in MR patients. Myocardial TNF-alpha mRNA copies (corrected for beta-actin mRNA expression) in MR patients and donor hearts were 38.96+/-42.74x10(6) and 0.88+/-0.75x10(6), respectively (P=0.01). After MV surgery, there was a decrease in the plasma levels of TNF-alpha (2.79+/-1.14 versus 3.51+/-1.34 pg/mL, P=0.02) and its receptors. There was a correlation between myocardial TNF-alpha expression and preoperative LV end-diastolic and end-systolic volumes. Moreover, there was an inverse correlation between myocardial TNF-alpha expression and regression in LV end-diastolic (r=-0.76, P=0.007) and end-systolic (r=-0.73, P=0.01) volumes after MV surgery. CONCLUSIONS: TNF-alpha is expressed in the myocardium and plasma of MR patients. Correction of the LV volume overload with MV surgery results in reversal of TNF-alpha expression. There is a relationship between TNF-alpha expression and parameters of LV remodeling, suggesting that TNF-alpha may play a role in the pathogenesis of the LV remodeling that occurs in MR.