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-α (TNF-α) 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-α expression and whether there is a relationship between TNF-α expression and LV remodeling. Methods and Results - Plasma TNF-α 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-α were determined in 11 MR and 10 donor hearts using quantitative RT-PCR. Compared with 15 control subjects, pre-MV repair plasma TNF-α (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-α mRNA copies (corrected for β-actin mRNA expression) in MR patients and donor hearts were 38.96±42.74 × 10⁶ and 0.88±0.75 × 10⁶, respectively (P=0.01). After MV surgery, there was a decrease in the plasma levels of TNF-α (2.79±1.14 versus 3.51±1.34 pg/mL, P=0.02) and its receptors. There was a correlation between myocardial TNF-α expression and preoperative LV end-diastolic and end-systolic volumes. Moreover, there was an inverse correlation between myocardial TNF-a 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-α is expressed in the myocardium and plasma of MR patients. Correction of the LV volume overload with MV surgery results in reversal of TNF-α expression. There is a relationship between TNF-α expression and parameters of LV remodeling, suggesting that TNF-α may play a role in the pathogenesis of the LV remodeling that occurs in MR.