Inflammatory biomarkers and effect of exercise on functional capacity in patients with heart failure: Insights from a randomized clinical trial

Abstract

Background In patients with heart failure, inflammation has been associated with worse functional capacity, but it is uncertain whether it could affect their response to exercise training. We evaluated whether inflammatory biomarkers are related to differential effect of exercise on the peak oxygen uptake (V˙O₂) among patients with heart failure. Design Open, parallel group, randomized controlled trial. Methods Patients with heart failure and ejection fraction ≤0.4 were randomized into exercise training or control for 12 weeks. Patients were classified according to: 1) inflammatory biomarkers blood levels, defined as 'low' if both interleukin-6 and tumor necrosis factor-alpha blood levels were below median, and 'high' otherwise; and 2) galectin-3 blood levels, which also reflect pro-fibrotic processes. Results Forty-four participants (50 ± 7 years old, 55% men, 25% ischemic) were allocated to exercise training ( n = 28) or control ( n = 16). Exercise significantly improved peak V˙O₂ among participants with 'low' inflammatory biomarkers (3.5 ± 0.9 vs. -0.7 ± 1.1 ml/kg per min, p = 0.006), as compared with control, but not among those with 'high' inflammatory biomarkers (0.4 ± 0.6 vs. -0.2 ± 0.7 ml/kg per min, p = 0.54, p for interaction = 0.009). Similarly, exercise improved peak V˙O₂ among participants with below median (2.4 ± 0.8 vs. -0.3 ± 0.9 ml/kg per min, p = 0.032), but not among those with above median galectin-3 blood levels (0.3 ± 0.7 vs. -0.7 ± 1.0 ml/kg per min, p = 0.41, p for interaction = 0.053). Conclusion In patients with heart failure, levels of biomarkers that reflect pro-inflammatory and pro-fibrotic processes were associated with differential effect of exercise on functional capacity. Further studies should evaluate whether exercise training can improve clinical outcomes in patients with heart failure and low levels of these biomarkers.

Trial registration: ClinicalTrials.gov NCT02448147.

Keywords: Heart failure; exercise; exercise tolerance; inflammation.