title: A randomized pilot trial of remote ischemic preconditioning in heart failure with reduced ejection fraction.
abstract: BACKGROUND
  Remote ischemic preconditioning (RIPC) induced by transient limb ischemia confers multi-organ protection and improves exercise performance in the setting of tissue hypoxia. We aimed to evaluate the effect of RIPC on exercise capacity in heart failure patients.
  
  
  METHODS
  We performed a randomized crossover trial of RIPC (4×5-minutes limb ischemia) compared to sham control in heart failure patients undergoing exercise testing. Patients were randomly allocated to either RIPC or sham prior to exercise, then crossed over and completed the alternate intervention with repeat testing. The primary outcome was peak VO2, RIPC versus sham. A mechanistic substudy was performed using dialysate from study patient blood samples obtained after sham and RIPC. This dialysate was used to test for a protective effect of RIPC in a mouse heart Langendorff model of infarction. Mouse heart infarct size with RIPC or sham dialysate exposure was also compared with historical control data.
  
  
  RESULTS
  Twenty patients completed the study. RIPC was not associated with improvements in peak VO2 (15.6+/-4.2 vs 15.3+/-4.6 mL/kg/min; p = 0.53, sham and RIPC, respectively). In our Langendorff sub-study, infarct size was similar between RIPC and sham dialysate groups from our study patients, but was smaller than expected compared to healthy controls (29.0%, 27.9% [sham, RIPC] vs 51.2% [controls]. We observed less preconditioning among the subgroup of patients with increased exercise performance following RIPC (p<0.04).
  
  
  CONCLUSIONS
  In this pilot study of RIPC in heart failure patients, RIPC was not associated with improvements in exercise capacity overall. However, the degree of effect of RIPC may be inversely related to the degree of baseline preconditioning. These data provide the basis for a larger randomized trial to test the potential benefits of RIPC in patients with heart failure.
  
  
  BACKGROUND
  ClinicalTrials.gov +++++NCT01128790.
authors.affiliation: Division of Cardiology, Peter Munk Cardiac Centre, University of Toronto, Toronto, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McDonald
authors.affiliation: Division of Cardiology, Peter Munk Cardiac Centre, University of Toronto, Toronto, Canada.
authors.forename: Juarez R
authors.initials: JR
authors.lastname: Braga
authors.affiliation: Division of Cardiology, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Cardiology, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.affiliation: Division of Cardiology, Peter Munk Cardiac Centre, University of Toronto, Toronto, Canada.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ross
authors.affiliation: Division of Cardiology, Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Redington
mesh_terms: D016022:Case-Control Studies; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D010865:Pilot Projects; D013318:Stroke Volume