Aim a-Defensins are part of the innate immune system. Low-grade inflammation seems to play a crucial role in development and progression of chronic heart failure (CHF). The aims of the present study were to compare plasma levels of a-defensins in CHF patients and healthy controls and to examine the predictive ability of a-defensins, alone and combined with N-terminal pro brain natriuretic peptide (NT-proBNP), with respect to all-cause mortality. METHODS AND RESULTS: In a prospective observational study lasting 2.6 years we examined the prognostic value of plasma a-defensins with respect to mortality in 194 CHF patients, and compared plasma levels with those of 98 age-matched healthy controls. a-Defensin levels were twice as high among CHF patients in New York Heart Association (NYHA) functional class III-IV than in patients in NYHA class I-II and healthy controls (P = 0.001). The absolute increase in risk of mortality for patients with a-defensin levels in the upper tertile vs. the lowest tertile was 30% (P = 0.002). After adjusting for potential confounders including NT-proBNP, plasma a-defensins remained independently associated with an increased risk of all-cause mortality (hazard ratio 1.65, 95% confidence interval 1.19-2.28, P = 0.002) per 1 standard deviation increment in Ln (natural logarithm)-transformed a-defensin values. The combination of high a-defensins and NT-proBNP levels provided incremental prognostic information independent of well-known prognostic biomarkers in heart failure. CONCLUSION: Plasma a-defensins appear to have prognostic information regarding mortality among patients with CHF and seem to provide incremental information to established clinical risk markers.