title: Markers of extracellular matrix turnover and the development of right ventricular failure after ventricular assist device implantation in patients with advanced heart failure.
abstract: BACKGROUND
  Cardiac extracellular matrix (ECM) is a dynamic and metabolically active collagenous network that responds to mechanical strain. The association between ECM turnover and right ventricular failure (RVF) development after left ventricular assist device (LVAD) implantation in patients with advanced heart failure (HF) was investigated.
  
  
  METHODS
  Circulating levels of osteopontin, metalloproteinases (MMP)-2 and MPP-9, and tissue inhibitor of MMP (TIMP)-1 and TIMP-4 were measured in 61 patients at LVAD implantation and explantation and in 10 control subjects. RVF was defined as the need for RVAD, nitric oxide inhalation > 48 hours and/or inotropic support > 14 days.
  
  
  RESULTS
  All ECM markers were elevated in patients with HF compared with controls (all p < 0.05). RVF developed in 23 patients (37.7%) on LVAD support. All ECM markers decreased on LVAD support in patients without RVF (all p < 0.05), but serum MMP-2, TIMP-1, TIMP-4, and osteopontin remained elevated in RVF patients. Multivariate analysis identified that right ventricular stroke work index (RVSWI), circulating B-type natriuretic peptide, and osteopontin were associated with RVF (all p < 0.05). Osteopontin correlated inversely with RVSWI (r = -0.44, p < 0.001). Osteopontin levels > 260 ng/ml discriminate patients who develop RVF from those without RVF (sensitivity, 83%; specificity, 82%).
  
  
  CONCLUSIONS
  Marked elevation of osteopontin levels before LVAD placement is associated with RVF development. Persistent elevation of circulating ECM markers after LVAD implantation characterizes patients who develop RVF. These novel biomarkers would have a potential role in the prediction of RVF development in patients undergoing LVAD implantation.
authors.affiliation: Department of Medicine, Division of Cardiology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Tomoko S
authors.initials: TS
authors.lastname: Kato
authors.forename: Aalap
authors.initials: A
authors.lastname: Chokshi
authors.forename: Parvati
authors.initials: P
authors.lastname: Singh
authors.forename: Tuba
authors.initials: T
authors.lastname: Khawaja
authors.forename: Shinichi
authors.initials: S
authors.lastname: Iwata
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Akashi
authors.forename: Faisal
authors.initials: F
authors.lastname: Cheema
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yang
authors.forename: Hiroo
authors.initials: H
authors.lastname: Takayama
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Naka
authors.forename: Maryjane
authors.initials: M
authors.lastname: Farr
authors.forename: Donna
authors.initials: D
authors.lastname: Mancini
authors.forename: P Christian
authors.initials: PC
authors.lastname: Schulze
mesh_terms: D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood; D018497:Ventricular Dysfunction, Right / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D015415:Biomarkers; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4