title: Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure.
abstract: BACKGROUND
  Cardiac resynchronization therapy (CRT) promotes left ventricular (LV) reverse remodelling and affects myocardial collagen turnover in heart failure (HF) patients. Osteopontin (OPN) is a matrix glycoprotein required for the activation of fibroblasts upon TGF-β1 stimulation. In humans, plasma OPN and OPN-expressing lymphocytes correlate with the severity of HF. We sought to evaluate whether plasma OPN and TGF-β1 reflect LV reverse remodelling following CRT.
  
  
  METHODS
  Eighteen patients (12 men, mean age 65 ± 11 years) undergoing CRT were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma OPN and TGF-β1. The evaluation was repeated 8.5 ± 4 months after device implantation. Eight healthy age- and sex-matched subjects served as controls.
  
  
  RESULTS
  In HF patients, baseline plasma OPN and TGF-β1 were higher as compared to control subjects (OPN: 99 ± 48 vs 59 ± 22 ng/ml; p<0.05; TGF-β1: 15.9 ± 8.0 vs 9.3 ± 5.6 ng/ml; p<0.05). At follow-up, 12 patients responded to CRT and showed LV reverse remodelling, whereas 6 did not. Plasma OPN decreased in CRT responders (108 ± 47 vs 84 ± 37 ng/ml; p=0.03) and increased in non-responders (79 ± 58 vs 115 ± 63 ng/ml; p<0.01). TGF-β1 showed a trend towards reduction in responders (17.5 ± 8.7 vs 10.2 ± 8.9 ng/ml; p=0.08) and was unchanged in non-responders. A significant correlation (r=-0.56; p=0.01) was found between relative changes of LVESV and plasma OPN.
  
  
  CONCLUSIONS
  CRT-induced LV reverse remodelling is reflected by changes in plasma OPN. Circulating OPN may represent a marker of LV dilation/impairment and an indicator of the response to HF therapies promoting LV reverse remodelling.
authors.affiliation: Cardiology, 2nd Faculty of Medicine, Sapienza University, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Francia
authors.forename: Cristina
authors.initials: C
authors.lastname: Balla
authors.forename: Agnese
authors.initials: A
authors.lastname: Ricotta
authors.forename: Arianna
authors.initials: A
authors.lastname: Uccellini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Frattari
authors.forename: Anna
authors.initials: A
authors.lastname: Modestino
authors.forename: Marina
authors.initials: M
authors.lastname: Borro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Simmaco
authors.forename: Adriano
authors.initials: A
authors.lastname: Salvati
authors.forename: Luciano
authors.initials: L
authors.lastname: De Biase
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D058406:Cardiac Resynchronization Therapy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015415:Biomarkers; D053495:Osteopontin