title: Osteopontin and galectin-3 predict the risk of ventricular tachycardia and fibrillation in heart failure patients with implantable defibrillators.
abstract: BACKGROUND
  Myocardial extracellular matrix remodelling provides electrical heterogeneity entailing ventricular tachycardia/fibrillation (VT/VF) in heart failure (HF) patients. Osteopontin (OPN) and Galectin-3 (Gal-3) are fibrosis markers and may reflect the extension of the arrhythmogenic substrate. We assessed whether plasma OPN and Gal-3 predict the risk of sustained VT/VF in a cohort of HF patients with implantable cardioverter-defibrillator (ICD).
  
  
  METHODS
  A total of 75 HF patients underwent pre-ICD implantation clinical evaluation and assessment of plasma OPN and Gal-3. The primary endpoint was the time to the occurrence of the first sustained VT/VF. Hazard ratios (HR) were derived from Cox proportional-hazards analysis.
  
  
  RESULTS
  Patients with coronary artery disease (CAD) had higher plasma OPN (79.8 ± 44.0 ng/mL vs. 66.0 ± 31.8 ng/mL; P = 0.04). Both Gal-3 (r = -0.38; P = 0.01) and OPN (r = -0.27; p = 0.01) were negatively related to estimated glomerular filtration rate. After 29 ± 17 months, 20 patients (27%) reached the primary endpoint. Patients with VT/VF had higher plasma OPN and Gal-3 (97.4 ± 51.7 ng/mL vs. 65.9 ± 31.3 ng/mL; P = 0.002 and 19.7 ± 8.5 ng/mL vs. 16.2 ± 6.2 ng/mL; P = 0.05). In univariate analysis, OPN (log-OPN, HR: 32.4; 95%CI: 3.9-264.7; P = 0.001) and Gal-3 (HR: 1.05; 95%CI: 1.00-1.11; P = 0.04) predicted sustained VT/VF. In multivariable analysis, both OPN (HR: 41.4; 95%CI: 3.8-441.9; P = 0.002) and Gal-3 (HR: 1.06; 95%CI: 1.00-1.12; P = 0.03) retained their prognostic power after correction for age, sex, history of MI, EF, NYHA class, eGFR, use of ACE-I, and amiodarone.
  
  
  CONCLUSIONS
  Plasma OPN and Gal-3 predict sustained VT/VF in HF patients at high risk for SCD. Larger prospective studies should outline the role of these biomarkers in predicting SCD on top of conventional risk stratification.
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, University Sapienza, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Francia
authors.forename: Carmen
authors.initials: C
authors.lastname: Adduci
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Semprini
authors.forename: Marina
authors.initials: M
authors.lastname: Borro
authors.forename: Agnese
authors.initials: A
authors.lastname: Ricotta
authors.forename: Isabella
authors.initials: I
authors.lastname: Sensini
authors.forename: Daria
authors.initials: D
authors.lastname: Santini
authors.forename: Massimo
authors.initials: M
authors.lastname: Caprinozzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Balla
authors.forename: Maurizio
authors.initials: M
authors.lastname: Simmaco
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins; D017147:Defibrillators, Implantable / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood*; D037161:Galectins; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D017180:Tachycardia, Ventricular / Q000097:blood* / Q000175:diagnosis; D014693:Ventricular Fibrillation / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D053495:Osteopontin
keywords: Galectin-3; ICD; biomarkers; heart failure; osteopontin; sudden death