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

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 (VO2) 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 (507 years old, 55% men, 25% ischemic) were allocated to exercise training (n=28) or control (n=16). Exercise significantly improved peak VO2 among participants with low' inflammatory biomarkers (3.5 +/- 0.9 vs. -0.7 +/- 1.1ml/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 +/- 0.7ml/kg per min, p=0.54, p for interaction=0.009). Similarly, exercise improved peak VO2 among participants with below median (2.4 +/- 0.8 vs. -0.3 +/- 0.9ml/kg per min, p=0.032), but not among those with above median galectin-3 blood levels (0.3 +/- 0.7 vs. -0.7 +/- 1.0ml/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.