title: Neurohormonal activation and exercise tolerance in patients supported with a continuous-flow left ventricular assist device.
abstract: BACKGROUND
  Neurohormones play a key role in regulating hemodynamics in heart failure (HF) both at rest and during exercise. In contrast, little is known about the importance of neurohormonal regulation for exercise capacity in continuous-flow left ventricular assist device (CF-LVAD) patients. The aim of this study was to assess the relation between neurohormonal activation patterns in CF-LVAD patients and exercise capacity.
  
  
  METHODS
  Plasma concentrations of the C-terminal portion of pro-arginine vasopressin precursor (copeptin), pro-adrenomedullin (proADM), pro-B-type (proBNP) and pro-atrial (proANP) natriuretic peptides were measured in 25 CF-LVAD patients (HeartMate II) in the morning prior to maximal cardiopulmonary exercise testing determining peak oxygen uptake (peak VO2). Quality of life (QOL) was determined by questionnaires.
  
  
  RESULTS
  Peak VO2 was severely reduced averaging 13.0±5.3ml/kg/min and exhibited strong negative correlations with copeptin, r=-0.61 (p=0.001) and proADM, r=-0.56 (p=0.005). Additionally comparing patients with peak VO2<14 vs≥14ml/kg/min demonstrated significant differences in copeptin and proADM concentrations, 2.8±0.8 vs 2.1±0.7pmol/l (p=0.03) and 1.0±0.5 vs 0.7±0.2nmol/l (p=0.01), respectively. In contrast natriuretic peptides were not associated with maximal exercise capacity. Lower QOL correlated with increasing proBNP.
  
  
  CONCLUSIONS
  Resting plasma levels of proADM and copeptin are significantly correlated with peak VO2 in CF-LVAD patients. Future studies should address if interventions to lower the levels of these markers are associated with restoration of exercise tolerance.
authors.affiliation: Department of Cardiology, The Heart Center, University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: metteholmejung@dadlnet.dk.
authors.forename: Mette Holme
authors.initials: MH
authors.lastname: Jung
authors.affiliation: Department of Clinical Biochemistry, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Goetze
authors.affiliation: Department of Cardiology, The Heart Center, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Soeren
authors.initials: S
authors.lastname: Boesgaard
authors.affiliation: Department of Cardiology, The Heart Center, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Finn
authors.initials: F
authors.lastname: Gustafsson
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005080:Exercise Test / Q000379:methods; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology / Q000628:therapy; D006353:Heart-Assist Devices; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood*; D011788:Quality of Life; D013223:Statistics as Topic; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; D009479:Neuropeptides; D010446:Peptide Fragments; C094997:adrenotensin; C048197:copeptins; D053607:Adrenomedullin
keywords: Advanced heart failure; Biomarkers; Exercise intolerance; Left ventricular assist device; Neurohormonal activation; Quality of life