Plasma cytokine parameters and mortality in patients with chronic heart failure

Background - Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-α (TNF-α), soluble TNF receptor 1 and 2 (sTNF-R1/sTNF-R2), interleukin-6 (IL-6), and soluble CD14 receptors (sCD14) in CHF patients. Methods and Results - In 152 CHF patients (age 61±1 years, New York Heart Association [NYHA] class 2.6±0.1, peak VO₂ 17.3±0.6 mL·kg^-1·min^-1, mean±SEM) plasma concentrations of immune variables were prospectively assessed. During a mean follow-up of 34 months (> 12 months in all patients), 62 patients (41%) died. Cumulative mortality was 28% at 24 months. In univariate analyses, increased total and trimeric TNF-α, sTNF-R1, and sTNF-R2 (all P≤0.0001), sCD14 (P=0.0007), and IL-6 (P=0.005) predicted 24-month mortality. With multivariate analysis and receiver operating characteristics, sTNF-R1 emerged among all cytokine parameters as the strongest and most accurate prognosticator in this CHF population, regardless of follow-up duration and independently of NYHA class, peak VO₂, VE/VCO₂ slope, left ventricular ejection fraction, and wasting (P