Tumour necrosis factor-alpha soluble receptors type I are related to symptoms and left ventricular function in hypertrophic cardiomyopathy.

BACKGROUND: High circulating levels of tumour necrosis factor-alpha (TNF-alpha) and its soluble receptors (sTNFRI, sTNFRII) are involved in the pathogenesis of congestive heart failure due to left ventricular (LV) systolic dysfunction. However, their role in hypertrophic cardiomyopathy (HCM) has not been elucidated. OBJECTIVES: To determine the circulating serum levels of sTNFRI in a wide spectrum of patients with HCM, and to study in detail their relationship with symptom severity and various echocardiographic disease characteristics. PATIENTS AND METHODS: sTNFRI serum levels were measured in 66 patients with HCM and 30 age-matched healthy subjects using enzyme linked immunosorbent assay for serum levels of soluble TNF-a receptor type I at rest and at 1, 3 (sTNFRI-3e) and 6 h after dobutamine stress echocardiography (DSE). RESULTS: sTNFRI-r levels were significantly higher in patients with HCM than in control subjects (2.8+/-0.8 compared with 1.4+/-0.5 ng/mL, P<0.002). In patients with HCM, there was a significant difference in sTNFRI-r levels between mildly (New York Heart Association [NYHA] functional class I and II) and severely (NYHA functional class III and IV) symptomatic patients (1.4+/-0.9 compared with 4.8+/-1.0 ng/mL, p<0.001). Higher sTNFRI-r and sTNFRI-3e levels were found in patients with an LV restrictive filling pattern during DSE compared with sustained abnormal relaxation (p<0.052, p<0.004, respectively), and in patients with reduced compared with normal increments in LV fractional shortening during DSE (p<0.02, p<0.003, respectively). CONCLUSIONS: Significant differences in sTNFRI serum levels between patients with HCM and healthy subjects were shown. In patients with HCM, sTNFRI levels were higher in severely symptomatic patients, and in patients with reduced LV systolic and diastolic reserve during DSE. These data suggest that TNF may be involved in the pathogenesis of HCM.