Tumour necrosis factor alpha as a predictor of impaired peak leg blood flow in patients with chronic heart failure

Tumour necrosis factor alpha (TNFα) is increased in patients with cardiac cachexia, a condition associated with reduced peripheral blood flow both at rest and after interventions causing vasodilation. By contrast, in patients with chronic heart failure (CHF), higher TNF levels are associated with a greater capacity for vasodilation in the arm. To clarify the relationship between peripheral blood flow and TNF in CHF, we studied the relation between TNFα and blood flow in the leg (plethysmography, post maximal exercise and 5 min ischaemia) in 34 patients (age 63 ± 2 years, ejection fraction 29 ± 3%, peak VO₂ 16.6 ± 1.1 ml/kg/min, mean ± SEM). Peak leg blood flow correlated significantly with total TNFα (r = -0.68, p <0.0001), peak VO₂ (r = 0.54), and soluble TNF receptors 1 (r = -0.56) and 2 (r = -0.52, all p <0.002). TNFα, soluble TNF receptors 1 and 2 and aldosterone correlated with peak blood flow independently of age, ejection fraction, peak VO₂ and functional NYHA class. TNFα was the only parameter that showed strong correlations for peak blood flow in all clinically relevant subgroups (severe vs. mild, ischaemic vs. dilated, cachectic vs. non-cachectic patients). This study shows a close and inverse relationship between peak leg blood flow and the plasma concentration of TNFα, suggesting a pathophysiological role for TNFα in reducing peak peripheral blood flow in CHF.