Background : Extracellular matrix remodeling is thought to play an important role in the progression of heart failure (HF). Matrix metalloproteinases-2 (MMPs) havebeen demonstrated to influence left ventricular properties and serve as targets of potential anti-remodeling agents. Osteopontin, a glycoprotein that can be detected in plasma, was found to be up regulated in several animal models of cardiac failure and may thus represent a new biomarker that facilitates risk stratification in patients with heart failure.Aim: We therefore tested whether osteopontin and MMP-2 plasma levels are elevated in patients with chronic heart failure and whether they are related to the severity of (CHF) speculating it may assume prognostic value.Subjects and Methods: We analyzed osteopontin and matrix metalloproteinase-2 plasma levels using sandwich ELISA technique in fifty one patients suffering from chronic heart failure (group C). Seventeen with asymptomatic left ventricular systolic dysfunction (group B) (E.F=40%-55%) were enrolled in this study.Sixteen age and sex matched healthy controls(group A) (E.F>55%) were also included in the present study.Results: We found that osteopontin plasma levels were significantly elevated in patients with heart failure as compared with healthy control subjects (72.0±20 versus 25.4±5.3 ng/mL, P=0.001), irrespective of heart failure origin (ischemic, valvular and idiopathic).Also, metalloproteinase-2 plasma levels were significantly elevated in patients with heart failure as compared with healthy control subjects (416.6 versus 194 ng/mL, P=0.001), irrespective of heart failure origin (ischemic, valvular and idiopathic).Furthermore, osteopontin and metalloproteinase-2 levels were higher in patients with moderate to severe heart failure than in patients with no or mild symptoms. For OPN (76.8±17 and 95.2±11.9 ng/mL for New York Heart Association class III/IV respectively, versus 53.4±7.7 ng/mL for class I/II, P<0.0001), and for MMP-2 (420±110 and 502±100 ng/mL for New York Heart Association class III/IV respectively, versus 361±59 ng/mL for class II,P<0.0001).Conclusion: Our findings suggest that osteopontin and matrix metalloproteinase-2 plasma levels are directly related toseverity of chronic heart failure.