TY - JOUR
T1 - Markers of extracellular matrix turnover and the development of right ventricular failure after ventricular assist device implantation in patients with advanced heart failure
AU - Kato, Tomoko S.
AU - Chokshi, Aalap
AU - Singh, Parvati
AU - Khawaja, Tuba
AU - Iwata, Shinichi
AU - Homma, Shunichi
AU - Akashi, Hirokazu
AU - Cheema, Faisal
AU - Yang, Jonathan
AU - Takayama, Hiroo
AU - Naka, Yoshifumi
AU - Farr, Maryjane
AU - Mancini, Donna
AU - Schulze, P. Christian
N1 - Funding Information:
This work was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) to Dr Schulze ( K23 HL095742-01 and P30 HL101272-01 ).
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - echocardiography
KW - heart failure
KW - remodeling
KW - transplant
KW - ventricular assist device
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U2 - 10.1016/j.healun.2011.10.007
DO - 10.1016/j.healun.2011.10.007
M3 - Article
C2 - 22071239
AN - SCOPUS:83555164852
SN - 1053-2498
VL - 31
SP - 37
EP - 45
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 1
ER -