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The aim of this study was to investigate the long-term prognostic value of pentraxin-3 (PTX3) in patients with chronic heart failure (CHF). 377 patients were prospectively followed up for 3 years to determine cardiac events including cardiac death or rehospitalization for worsening heart failure. The plasma PTX3 levels were significantly higher in CHF patients than in healthy subjects (p < 0.001), and they increased with advancing New York Heart Association (NYHA) Functional Classification (p < 0.001). Plasma PTX3 levels in CHF patients with cardiac events were significantly higher than in event-free patients (p < 0.001). We determined the normal upper limit of plasma PTX3 levels from the mean + 2 SD value of 64 control subjects (3.64 ng/mL). A Kaplan-Meier analysis revealed that patients with increased PTX3 (>3.64 ng/mL) were at a higher risk for cardiac events than those without increased PTX3 (p < 0.01). A multifactorial Cox proportional hazards model showed that increased PTX3 (≥3.64 nglmL) was an independent risk factor for cardiac events in CHF patients (hazard ratio (HR) = 4.224, p < 0.01; 95% CI: 1.130-15.783). Plasma PTX3 levels are a long-term independent predictor of prognosis in patients with CHF. [ABSTRACT FROM AUTHOR]