Markers of extracellular matrix turnover and the development of right ventricular failure after ventricular assist device implantation in patients with advanced heart failure

Tomoko S. Kato, Aalap Chokshi, Parvati Singh, Tuba Khawaja, Shinichi Iwata, Shunichi Homma, Hirokazu Akashi, Faisal Cheema, Jonathan Yang, Hiroo Takayama, Yoshifumi Naka, Maryjane Farr, Donna Mancini, P. Christian Schulze

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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. 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. 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%). 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.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume31
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • echocardiography
  • heart failure
  • remodeling
  • transplant
  • ventricular assist device

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Fingerprint

Dive into the research topics of 'Markers of extracellular matrix turnover and the development of right ventricular failure after ventricular assist device implantation in patients with advanced heart failure'. Together they form a unique fingerprint.

Cite this