title: TWEAK and NT-proBNP levels predict exercise capacity in hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, myocyte disarray and increased interstitial fibrosis. The tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a cell surface cytokine with biological activities including stimulation of cell growth, induction of inflammatory cytokines and stimulation of apoptosis. There are controversial data about the potential role of TWEAK in different cardiovascular pathologies. NT-proBNP is an established biomarker of myocardial wall stress, associated with poor functional class in HCM. We hypothesized that effort capacity in patients with HCM could be related to serum levels of these biomarkers.
  
  
  METHODS
  We included 40 haemodynamic stable HCM patients and 53 healthy controls with similar sex and age. We studied exercise capacity by maximal oxygen consumption in a limited treadmill exercise test. TWEAK and NT-proBNP were assayed by ELISA method and automated Elecsys® platform, respectively. We obtained 46 samples of myocardial tissues by septal myectomy in patients with HCM and evaluated myocardial fibrosis, immunoreaction with TWEAK antibody and apoptosis with TUNEL assay.
  
  
  RESULTS
  We found raised TWEAK and NT-proBNP serum levels in patients when compared with control levels (both P < 0.001). In a multivariate analysis, TWEAK and NT-proBNP levels, as well as sex, remained independently associated with the effort capacity (all P < 0.05). We found an association between immunoreaction degree and the degree of myocardial fibrosis (P = 0.021), as well as apoptosis (P = 0.002) in the tissue samples from patients undergoing septal myectomy.
  
  
  CONCLUSIONS
  TWEAK and NT-proBNP levels are biomarkers of disease severity independently associated with the effort capacity in patients with HCM.
authors.affiliation: Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Murcia, Spain; Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Hernández-Romero
authors.forename: Eva
authors.initials: E
authors.lastname: Jover
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Martínez
authors.forename: José M
authors.initials: JM
authors.lastname: Andreu-Cayuelas
authors.forename: Esteban
authors.initials: E
authors.lastname: Orenes-Piñero
authors.forename: Ana I
authors.initials: AI
authors.lastname: Romero-Aniorte
authors.forename: Teresa
authors.initials: T
authors.lastname: Casas
authors.forename: Sergio
authors.initials: S
authors.lastname: Cánovas
authors.forename: José A
authors.initials: JA
authors.lastname: Montero-Argudo
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdés
authors.forename: Gonzalo
authors.initials: G
authors.lastname: de la Morena
authors.forename: Francisco
authors.initials: F
authors.lastname: Marín
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000503:physiopathology*; D016022:Case-Control Studies; D000074049:Cytokine TWEAK; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011446:Prospective Studies; D012372:ROC Curve; D048069:Tumor Necrosis Factors / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D000074049:Cytokine TWEAK; D010446:Peptide Fragments; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Effort capacity; NT-proBNP; TWEAK; hypertrophic cardiomyopathy; myocardial fibrosis