Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in
patients with heart failure and preserved ejection fraction (from the D-HART
pilot study).
Author(s): Van Tassell BW(1), Arena R(2), Biondi-Zoccai G(3), McNair Canada J(1), Oddi C(1),
Abouzaki NA(1), Jahangiri A(1), Falcao RA(1), Kontos MC(1), Shah KB(1), Voelkel
NF(1), Dinarello CA(4), Abbate A(5).
Affiliation(s): Author information:
(1)Virginia Commonwealth University Pauley Heart Center and Victoria Johnson
Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
(2)Department of Physical Therapy, University of Illinois at Chicago, Chicago,
Illinois.
(3)Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University,
Latina, Italy.
(4)Department of Medicine, University of Colorado School of Medicine, Aurora,
Colorado.
(5)Virginia Commonwealth University Pauley Heart Center and Victoria Johnson
Research Laboratories, Virginia Commonwealth University, Richmond, Virginia.
Electronic address: aabbate@mcvh-vcu.edu.
Publication date & source: 2014, Am J Cardiol. , 113(2):321-7
Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome of
exercise intolerance due to impaired myocardial relaxation and/or increased
stiffness. Patients with HFpEF often show signs of chronic systemic inflammation,
and experimental studies have shown that interleukin-1 (IL-1), a key
proinflammatory cytokine, impairs myocardial relaxation. The aim of the present
study was to determine the effects of IL-1 blockade with anakinra on aerobic
exercise capacity in patients with HFpEF and plasma C-reactive protein (CRP)
>2 mg/L (reflecting increased IL-1 activity). A total of 12 patients were
enrolled in a double-blind, randomized, placebo-controlled, crossover trial and
assigned 1:1 to receive 1 of the 2 treatments (anakinra 100 mg or placebo) for
14 days and an additional 14 days of the alternate treatment (placebo or
anakinra). The cardiopulmonary exercise test was performed at baseline, after the
first 14 days, and after the second 14 days of treatment. The placebo-corrected
interval change in peak oxygen consumption was chosen as the primary end point.
All 12 patients enrolled in the present study and receiving treatment completed
both phases and experienced no major adverse events. Anakinra led to a
statistically significant improvement in peak oxygen consumption (+1.2 ml/kg/min,
p = 0.009) and a significant reduction in plasma CRP levels (-74%, p = 0.006).
The reduction in CRP levels correlated with the improvement in peak oxygen
consumption (R = -0.60, p = 0.002). Three patients (25%) had mild and
self-limiting injection site reactions. In conclusion, IL-1 blockade
with anakinra for 14 days significantly reduced the systemic inflammatory
response and improved the aerobic exercise capacity of patients with HFpEF and
elevated plasma CRP levels.
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