title: Gremlin-1 identifies fibrosis and predicts adverse outcome in patients with heart failure undergoing endomyocardial biopsy.
abstract: BACKGROUND
  Gremlin-1 (Grem1), an antagonist of bone morphogenetic proteins, is involved in fibrotic tissue formation in kidney and lung. The impact of myocardial Grem1 expression is unknown. We investigated the prognostic value of Grem1 expression in 214 consecutive patients with nonischemic heart failure (HF) undergoing endomyocardial biopsy.
  
  
  METHODS
  In all patients, the following risk factors were assessed: Grem1 expression (semiquantitative score scheme ranging from 1 to 4), presence of inflammatory markers, detection of viral genome, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association functional class (NYHA), troponin I, and B-type natriuretic peptide. Degree of myocardial fibrosis was defined as an index. Study end point was a combination of all-cause death and HF-related rehospitalization within 3 years of follow-up.
  
  
  RESULTS
  Grem1 expression significantly correlated with the degree of myocardial fibrosis (correlation coefficient r = 0.619; P < .0001). Patients with the highest Grem1 expression (score 4) showed the most severely impaired LVEF and highest LVEDD (P < .0001 and P = .030, respectively, for comparison of semiquantitative scores). During follow-up, 33 patients (15.4%) reached the study end point. Grem1 expression and NYHA ≥II were independent predictors of the end point (Grem1: hazard ratio [HR] 7.5, 95% confidence interval [CI] 1.8-32.2; P = .006; NYHA ≥II: HR 2.0, 95% CI 1.0-4.1; P = .048).
  
  
  CONCLUSIONS
  Grem1 correlates with the degree of myocardial fibrosis and left ventricular dysfunction and is an independent predictor of adverse outcome in patients with nonischemic HF.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Karin A L
authors.initials: KA
authors.lastname: Mueller
authors.forename: Elli
authors.initials: E
authors.lastname: Tavlaki
authors.forename: Martina
authors.initials: M
authors.lastname: Schneider
authors.forename: Rezo
authors.initials: R
authors.lastname: Jorbenadze
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Iris I
authors.initials: II
authors.lastname: Mueller
authors.forename: Christine S
authors.initials: CS
authors.lastname: Zuern
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D004699:Endocardium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins
keywords: Gremlin-1, heart failure