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Oxidative stress is known to play a crucial role in the pathogenesis of heart failure (HF). We investigated whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), a product of oxidative DNA damage, is a clinically useful biomarker of the severity of chronic heart failure (CHF) and oxidative stress levels in failing hearts.We measured 8-OHdG in the serum obtained from the coronary sinus (CS) and aortic root (Ao) in small groups of control subjects and CHF patients. We then measured urinary 8-OHdG and other biomarkers (brain natriuretic peptide, 8-isoplastane, high-sensitivity C-reactive protein, interleukin-6, and tumour necrosis factor-α) in 31 control subjects and 194 patients with CHF [left-ventricular ejection fraction (LVEF): 28.3 ± 8.1%]. Serum 8-OHdG was significantly higher in the CS than the Ao in CHF patients only. Urinary 8-OHdG was also significantly higher in CHF patients than in control subjects, and urinary 8-OHdG became higher as New York Heart Association class increased. Moreover, there was a significant correlation between urinary 8-OHdG and LVEF (r = −0.27), pulmonary capillary wedge pressure (r = 0.31), or left-ventricular end-diastolic volume index (r = 0.22). In contrast, there was poor correlation between the severity of CHF and the other neurohumoral biomarkers.In HF, urinary 8-OHdG seems to reflect the level of oxidative stress and various parameters related to symptomatic status and functional severity of CHF.