Do cytokines enable risk stratification to be improved in NYHA functional class III patients? Comparison with other potential predictors of prognosis.

AIMS: Elevated plasma levels of proinflammatory cytokines have been reported in patients with congestive heart failure. The purpose of this study was to assess whether cytokines improve risk stratification in a homogeneous group of NYHA class III patients with a left ventricular ejection fraction <40%. METHODS AND RESULTS: Plasma concentrations of big endothelin, tumour necrosis factor alpha, interleukins -1, -6, -10 and -12, sCD14 and GM-CSF were measured by ELISA in 91 NYHA III patients [mean (SD) age: 55 (10) years, 69% male, 34% coronary artery disease, 66% dilated cardiomyopathy] with a left ventricular ejection fraction and a peak oxygen uptake (peak VO2) of 19 (9)% and 12.1 (3.6) ml x min(-1) x kg(-1), respectively. During follow-up [22 (13) months], 31 patients (34%) died due to cardiovascular causes. In non-survivors, interleukin-6 was twice as high as in survivors [12.8 (16.9) pg x ml(-1)vs 5.6(5.3) pg x ml(-1), P<0.003], whereas plasma concentrations of the other cytokines showed no significant differences. Concerning long-term survival (> or =1 year), multivariate Cox regression analysis revealed an independent prognostic power for interleukin-6, which was further improved by combining with left ventricular ejection fraction and peak VO2, while for short-term survival (up to 6 months) interleukin-6 did not allow risk stratification. CONCLUSION: In NYHA class III patients, plasma concentrations of interleukin-6 are predictive of long-term survival. However, its value may be limited for clinical decision-making for cardiac transplantation (short-term survival).