title: 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).
abstract: 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.
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Benjamin Wallace
authors.initials: BW
authors.lastname: Van Tassell
authors.forename: Ross
authors.initials: R
authors.lastname: Arena
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Justin McNair
authors.initials: JM
authors.lastname: Canada
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Oddi
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Nayef Antar
authors.initials: NA
authors.lastname: Abouzaki
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Arehzo
authors.initials: A
authors.lastname: Jahangiri
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Raquel Appa
authors.initials: RA
authors.lastname: Falcao
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Michael Christopher
authors.initials: MC
authors.lastname: Kontos
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Keyur Bharat
authors.initials: KB
authors.lastname: Shah
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Norbert Felix
authors.initials: NF
authors.lastname: Voelkel
authors.forename: Charles Anthony
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, VA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013318:Stroke Volume / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1