Lipopolysaccharide responsiveness is an independent predictor of death in patients with chronic heart failure

Background: The origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity. Methods: LPS responsiveness was studied in 122 patients with chronic HF (mean SD: age 67.3 +/- 103 years, 24 female, New York Heart Association class [NYHA] class: 2.5 +/- 0.8, left ventricular ejection fraction [LVEF]: 33.5 +/- 12.5%) and 27 control subjects of similar age (63.7 +/- 7.7 years, p > 0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor-alpha (TNF alpha) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNF alpha secretion). The optimal cut-off value was calculated by receiver-operator characteristic curve (ROC) analysis. Results: A total of 56 patients with chronic HF died from any cause during follow-up. At 24 months, cumulative mortality was 16.4% (95% confidence interval 16.0-16.7%). The delta TNFa value representing the optimal cutoff for the prediction of mortality was 1522 pg/mL (24 months) with a sensitivity of 49.3% (95% confidence interval 37.2-61.4%) and specificity of 81.5% (95% confidence interval 61.9-93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor-responders, 95% confidence interval 0.01-0.67, p < 0.05). Conclusions: LPS responsiveness in patients with chronic HF is an independent predictor of death. (C) 2015 Elsevier Ltd. All rights reserved.