title: Impact of atrial fibrillation on exercise capacity in heart failure with preserved ejection fraction: a RELAX trial ancillary study.
abstract: BACKGROUND
  Atrial fibrillation (AF) is common among patients with heart failure and preserved ejection fraction (HFpEF), but its clinical profile and impact on exercise capacity remain unclear. RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF) was a multicenter randomized trial testing the impact of sildenafil on peak VO2 in stable outpatients with chronic HFpEF. We sought to compare clinical features and exercise capacity among patients with HFpEF who were in sinus rhythm (SR) or AF.
  
  
  RESULTS
  RELAX enrolled 216 patients with HFpEF, of whom 79 (37%) were in AF, 124 (57%) in SR, and 13 in other rhythms. Participants underwent baseline cardiopulmonary exercise testing, echocardiogram, biomarker assessment, and rhythm status assessment before randomization. Patients with AF were older than those in SR but had similar symptom severity, comorbidities, and renal function. β-blocker use and chronotropic indices were also similar. Despite comparable left ventricular size and mass, AF was associated with worse systolic (lower EF, stroke volume, and cardiac index) and diastolic (shorter deceleration time and larger left atria) function compared with SR. Pulmonary artery systolic pressure was higher in AF. Patients with AF had higher N-terminal pro-B-type natriuretic peptide, aldosterone, endothelin-1, troponin I, and C-telopeptide for type I collagen levels, suggesting more severe neurohumoral activation, myocyte necrosis, and fibrosis. Peak VO2 was lower in AF, even after adjustment for age, sex, and chronotropic response, and VE/VCO2 was higher.
  
  
  CONCLUSIONS
  AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity. These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in patients with HFpEF and AF is warranted.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867.
authors.affiliation: Division of Cardiology, Mayo Clinic, Rochester, MN.
authors.forename: Rosita
authors.initials: R
authors.lastname: Zakeri
authors.forename: Barry A
authors.initials: BA
authors.lastname: Borlaug
authors.forename: Steven E
authors.initials: SE
authors.lastname: McNulty
authors.forename: Selma F
authors.initials: SF
authors.lastname: Mohammed
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.forename: Anita
authors.initials: A
authors.lastname: Deswal
authors.forename: Martin
authors.initials: M
authors.lastname: LeWinter
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
mesh_terms: D000367:Age Factors; D000368:Aged; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015331:Cohort Studies; D015897:Comorbidity; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate
keywords: atrial fibrillation; exercise; heart failure