title: Endomyocardial expression of SDF-1 predicts mortality in patients with suspected myocarditis.
abstract: BACKGROUND
  Risk stratification in patients with suspected myocarditis is pivotal for optimizing therapy. Stromal cell-derived factor 1 (SDF-1) is an inflammatory chemokine expressed in the inflamed and failing myocardium. Therefore, we aimed to investigate whether endomyocardial expression of SDF-1 identifies high-risk patients with suspected myocarditis.
  
  
  RESULTS
  We prospectively enrolled 174 patients with non-ischemic HF who underwent endomyocardial biopsy for suspected myocarditis. Biopsies were analyzed using established histopathological and immunohistological criteria together with SDF-1 staining. SDF-1 was significantly enhanced in patients with inflammatory cardiomyopathy (65.4 % positive biopsies) as compared to patients with non-inflammatory cardiomyopathy (19.1 %, p < 0.001). SDF-1 expression levels correlated significantly with the degree of myocardial fibrosis (correlation coefficient r = 0.196; p = 0.010) since patients with severe myocardial fibrosis displayed high myocardial SDF-1 expression. During a mean follow-up of 27.5 months, 20 patients (11.5 %) died. The 4-year mortality rate was 26.0 % among the 92 SDF-1-positive patients vs. 9.5 % among the 82 SDF-1-negative patients (p = 0.001). On multivariable analysis which considered clinical (NYHA functional class, left ventricular ejection fraction), laboratory (brain natriuretic peptide, troponin I) and biopsy staining, SDF-1 was the strongest independent predictor of mortality (hazard ratio 6.1; 95 % confidence interval 1.4-27.5; p = 0.018). Subgroup analysis revealed SDF-1 as a predictor of mortality in both patients with inflammatory and non-inflammatory cardiomyopathy.
  
  
  CONCLUSIONS
  Endomyocardial expression of SDF-1 is enhanced in inflammatory cardiomyopathy, positively correlates with myocardial fibrosis and identifies high-risk patients with suspected myocarditis.
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany. christine.zuern@gmx.de.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Zuern
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076, Tuebingen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Walker
authors.affiliation: Department of Molecular Pathology, University of Tuebingen, Liebermeisterstr. 8, 72076, Tuebingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Schaub
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Mueller
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rath
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Tegtmeyer
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.affiliation: Department of Molecular Pathology, University of Tuebingen, Liebermeisterstr. 8, 72076, Tuebingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076, Tuebingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: Department of Molecular Pathology, University of Tuebingen, Liebermeisterstr. 8, 72076, Tuebingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany. meinrad.gawaz@med.uni-tuebingen.de.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.|Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076, Tuebingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009205:Myocarditis / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D011446:Prospective Studies; D012306:Risk; D012720:Severity of Illness Index
chemical_list: D054377:Chemokine CXCL12
keywords: Biomarker; Cardiomyopathy; Endomyocardial biopsy; Myocarditis; SDF-1