Abstract 8837: Markers of Extracellular Matrix Turnover and the Development of Right Ventricular Failure After Ventricular Assist Device Implantation in Patients with Advanced Heart Failure
Background. The development of right ventricular failure (RVF) is one of major causes of morbidity and mortality of patients following LVAD placement. The cardiac extracellular matrix (ECM) is a dynamic and metabolically active collagenous network that responds to mechanical strain.
Hypothesis. We assessed the hypothesis that there would be an association between ECM turnover and development of RVF after LVAD implantation in patients with advanced heart failure (HF).
Methods. Circulating levels of osteopontin (OPN), metalloproteinases (MMP)-2 and -9 and tissue inhibitor of MMP (TIMP)-1 and -4 were measured in 61 patients at the time of LVAD implantation and explantation. Serum ECM markers were also measured in 10 normal control subjects. RVF was defined as the need for right ventricular assist device, nitric oxide inhalation>48 hours and/or inotropic support >14 days or re-starting after 14 days.
Results. All ECM markers were elevated in patients with HF compared to controls (all p<0.05). 23 patients (37.7%) developed RVF on LVAD support. All ECM markers decreased on LVAD support in patients without RVF (all p<0.05), but serum MMP-2, TIMP-1 and -4 and OPN remained elevated in patients with RVF. Post-LVAD OPN and TIMP-1 was higher in patients with RVH than those without RVF (316.4±84.6 vs. 202.4±69.1 ng/mL, p<0.01, 210.7±62.4 vs. 164.3±45.2, p<0.01, respectively). Multivariate analysis showed right ventricular stroke work index (RVSWI) [odds ratio (OR) 0.41, 95%confidence interval (CI) 0.207-0.670, p<0.01], pre-LVAD circulating BNP (OR 1.02, 95%CI 1.00-1.04, p<0.05) and OPN (OR 1.32, 95%CI, 1.01-1.61, p<0.05) were significantly associated with RVF. OPN correlated inversely with RVSWI (r=-0.44, p<0.001). OPN levels of >260 ng/mL could discriminate patients developing RVF from those without RVF (83% sensitivity and 82% specificity).
Conclusions. Elevated levels of OPN before LVAD placement are associated with the development of RVF. Persistent elevation of circulating ECM markers after LVAD implantation characterizes patients who develop RVF. These novel biomarkers would have a potential role in the pathogenesis of RVF development in patients undergoing LVAD implantation.
- © 2011 by American Heart Association, Inc.