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AimsTo explore the associations between serum phenylacetylglutamine (PAGln) and chronic heart failure (HF). Methods and resultsTotally 956 subjects were enrolled consecutively from the Department of Cardiovascular Medicine, Ruijin Hospital. Baseline data were obtained from all participants, and 471 stable chronic HF subjects were followed up. Serum PAGln was analysed by liquid chromatography-tandem mass spectrometry. The association between PAGln and basic renal indicators was assessed by simple correlation analysis. Logistic regression analysis was conducted to measure the association between PAGln and HF risk. Event-free survival was determined by Kaplan-Meier curves, and differences in survival were assessed using log-rank tests. Cox proportional hazards analysis was used to assess the prognostic value of PAGln in HF. Serum PAGln levels were increased in patients with chronic HF (3.322 ± 8.220 μM vs. 1.249 ± 1.168 μM, P < 0.001) and were associated with HF after full adjustment [odds ratio (OR), 1.507; 95% confidence interval (CI): 1.213-1.873; P < 0.001]. PAGln levels were correlated with the levels of basic renal indicators. High PAGln levels indicated a high risk of renal dysfunction in HF (OR: 1.853; 95% CI: 1.344-2.556; P < 0.001), and elevated PAGln levels were associated with a high risk of cardiovascular death in patients with chronic HF (HR: 2.049; 95% CI: 1.042-4.029; P = 0.038). Conclusions Elevated PAGln levels are an independent risk factor for HF and are associated with a higher risk of cardiovascular death. High PAGln levels could indicate renal dysfunction in HF patients. PAGln can be a valuable indicator of HF.