Endomyocardial expression of SDF-1 predicts mortality in patients with suspected myocarditis

Clin Res Cardiol. 2015 Dec;104(12):1033-43. doi: 10.1007/s00392-015-0871-y. Epub 2015 May 26.

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.

Methods and 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.

Keywords: Biomarker; Cardiomyopathy; Endomyocardial biopsy; Myocarditis; SDF-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Chemokine CXCL12 / metabolism*
  • Female
  • Fibrosis
  • Follow-Up Studies
  • Humans
  • Inflammation / diagnosis*
  • Inflammation / mortality
  • Inflammation / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocarditis / diagnosis*
  • Myocarditis / mortality
  • Myocarditis / pathology
  • Myocardium / pathology*
  • Prospective Studies
  • Risk
  • Severity of Illness Index

Substances

  • Chemokine CXCL12