Abstract 15762: Interleukin-1 Blockade Improves Cardiopulmonary Exercise Performance In Patients With Systolic Heart Failure
Background. Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1 (IL-1) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects. We hypothesized that IL-1 blockade would improve exercise performance in patients with systolic HF and evidence of elevated inflammatory activity.
Methods. We conducted a single-arm, open-label, pilot study (NCT01300650) of IL-1 blockade in HF patients (NYHA functional class II - III) with documented LVEF<40% and high sensitivity C-reactive protein (hsCRP) <2 mg/L. Six HF patients underwent a modified ramp cardiopulmonary exercise protocol at baseline and upon completion of 2 weeks treatment with daily subcutaneous injection of recombinant human IL-1 receptor antagonist (anakinra [Kineret®] 100 mg). The primary end point was peak VO2 at maximal exercise - an independent predictor of HF morality/hospitalization. HF symptoms were evaluated by the Duke Activity Status Index (DASI) questionnaire.
Results. All patients experienced numerical improvements in peak VO2 and exercise time. Mean peak VO2 increased from 12.95±1.03 to 16.25±1.01 mL/kg/min (+3.25 mL/kg/min, P<0.01) and mean exercise time increased from 5.02±0.96 to 6.67±1.00 minutes (+1.65 minutes, P=0.020). This improvement was accompanied by a significant reduction in mean hsCRP (7.97±2.07 [baseline] to 1.38±0.41 [2 weeks], P=0.028) and a trend towards improvement in HF symptoms as measured by DASI (17.80±3.42 [baseline] to 28.48±2.47 [2 weeks], P=0.08).
Conclusions. IL-1 blockade with anakinra was associated with a significant improvement in peak VO2 in patients with systolic HF and elevated hsCRP. IL-1 blockade may represent a potential treatment modality to improve exercise capacity HF patients.
- © 2011 by American Heart Association, Inc.