Elevated circulating levels of serum tumor necrosis factor-alpha in patients with hemodynamically significant pressure and volume overload

OBJECTIVES We sought to determine whether serum tumor necrosis factor-alpha (TNF-alpha) levels are elevated in patients with hemodynamically significa nt pressure and volume overload. BACKGROUND It has been previously shown that TNF-alpha messenger ribonuclei c acid (mRNA) and protein are rapidly expressed in the hearts of animal mod els subjected to abrupt hemodynamic overloading. The clinical significance of these experimental findings has not been tested in pathophysiologically relevant clinical models in human subjects. METHODS We prospectively measured serum TNF-alpha levels and serum TNF rece ptor 1 and 2 levels in 21 patients with severe aortic stenosis (AS), in 26 patients with 3+ to 4+ mitral regurgitation (MR) and in normal age- and gen der-matched control subjects. Patients with AS and MR were either in New Yo rk Heart Association (NYHA) functional class I or II and had no significant coronary disease. We compared the cytokine levels among the groups using a nalysis of variance. We related cytokine levels to the severity of AS using simple regression analysis. RESULTS Serum TNF-alpha levels in patients with AS (2.1 +/- 1.6 pg/ml, n = 21) and MR (1.3 +/- 0.7 pg/ml, n = 26) were significantly higher than those in the control subjects (0.7 1 0.2 pg/ml, n = 28). Serum TNF receptor 1 an d 2 levels were also higher in patients with AS and MR than in control subj ects. Cytokine levels were higher in patients in NYHA class II than in thos e in class I. In patients with a normal ejection fraction (>50%, n = 16), t here was a mild positive correlation (r = 0.56, p = 0.025) between serum TN F-alpha levels and the mean gradient across the aortic valve. CONCLUSIONS This study demonstrates that serum TNF-alpha is elevated in pat ients with chronic hemodynamic overloading and early cardiac decompensation . Furthermore, these findings suggest not only that peripheral TNF-alpha le vels correlate with the severity of the hemodynamic pressure overload, but also that peripheral TNF-alpha and TNF receptor levels increase in direct r elation to deteriorating NYHA functional class. (C) 2000 by the American Co llege of Cardiology.