Osteopontin and galectin-3 predict the risk of ventricular tachycardia and fibrillation in heart failure patients with implantable defibrillators

J Cardiovasc Electrophysiol. 2014 Jun;25(6):609-16. doi: 10.1111/jce.12364. Epub 2014 Jan 30.

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.

Keywords: Galectin-3; ICD; biomarkers; heart failure; osteopontin; sudden death.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Proteins
  • Defibrillators, Implantable / adverse effects*
  • Female
  • Follow-Up Studies
  • Galectin 3 / blood*
  • Galectins
  • Heart Failure / blood*
  • Heart Failure / diagnosis
  • Humans
  • Male
  • Middle Aged
  • Osteopontin / blood*
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Tachycardia, Ventricular / blood*
  • Tachycardia, Ventricular / diagnosis
  • Ventricular Fibrillation / blood
  • Ventricular Fibrillation / diagnosis*

Substances

  • Biomarkers
  • Blood Proteins
  • Galectin 3
  • Galectins
  • LGALS3 protein, human
  • Osteopontin