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

Abstract

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%. 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. 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).