Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure

Background: Cardiac resynchronization therapy (CRT) promotes left ventricular (LV) reverse remodelling and affects myocardial collagen turnover in heart failure (HF) patients. Osteopontin (OPN) is a matrix glycoprotein required for the activation of fibroblasts upon TGF-beta 1 stimulation. In humans, plasma OPN and OPN-expressing lymphocytes correlate with the severity of HF. We sought to evaluate whether plasma OPN and TGF-beta 1 reflect LV reverse remodelling following CRT. Methods: Eighteen patients (12 men, mean age 65 +/- 11 years) undergoing CRT were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma OPN and TGF-beta 1. The evaluation was repeated 8.5 +/- 4 months after device implantation. Eight healthy age-and sex-matched subjects served as controls. Results: In HF patients, baseline plasma OPN and TGF-beta 1 were higher as compared to control subjects (OPN: 99 +/- 48 vs 59 +/- 22 ng/ml; p<0.05; TGF-beta 1: 15.9 +/- 8.0 vs 9.3 +/- 5.6 ng/ml; p<0.05). At follow-up, 12 patients responded to CRT and showed LV reverse remodelling, whereas 6 did not. Plasma OPN decreased in CRT responders (108 +/- 47 vs 84 +/- 37 ng/ml; p=0.03) and increased in non-responders (79 +/- 58 vs 115 +/- 63 ng/ml; p<0.01). TGF-beta 1 showed a trend towards reduction in responders (17.5 +/- 8.7 vs 10.2 +/- 8.9 ng/ml; p=0.08) and was unchanged in non-responders. A significant correlation (r=-0.56; p=0.01) was found between relative changes of LVESV and plasma OPN. Conclusions: CRT-induced LV reverse remodelling is reflected by changes in plasma OPN. Circulating OPN may represent a marker of LV dilation/impairment and an indicator of the response to HF therapies promoting LV reverse remodelling. (C) 2010 Elsevier Ireland Ltd. All rights reserved.