• Haoran Wei, Junfang Wu, Huiqing Wang, Jin Huang, Chenze Li, Yuxuan Zhang, Yaonan Song, Zhitong Zhou, Yang Sun, Lei Xiao, Liyuan Peng, Chen Chen, Chunxia Zhao, and Dao Wen Wang.
• Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
• J. Intern. Med. 2023 Oct 1; 294 (4): 515530515-530.

BackgroundPhenylacetylglutamine (PAGln)-a newly discovered microbial metabolite produced by phenylalanine metabolism-is reportedly associated with cardiovascular events via adrenergic receptors. Nonetheless, its association with cardiovascular outcomes in heart failure (HF) patients remains unknown.ObjectivesThis study aimed to prospectively investigate the prognostic value of PAGln for HF.MethodsPlasma PAGln levels were quantified by liquid chromatography-tandem mass spectrometry. We first assessed the association between plasma PAGln levels and the incidence of adverse cardiovascular events in 3152 HF patients (including HF with preserved and reduced ejection fraction) over a median follow-up period of 2 years. The primary endpoint was the composite of cardiovascular death or heart transplantation. We then assessed the prognostic role of PAGln in addition to the classic biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP). The correlation between PAGln levels and β-blocker use was also investigated.ResultsIn total, 520 cardiovascular deaths or heart transplantations occurred in the HF cohort. Elevated PAGln levels were independently associated with a higher risk of the primary endpoint in a dose-response manner, regardless of HF subtype. Concurrent assessment of PAGln and NT-proBNP levels enhanced risk stratification among HF patients. PAGln further showed prognostic value at low NT-proBNP levels. Additionally, the interaction effects between PAGln and β-blocker use were not significant.ConclusionsPlasma PAGln levels are an independent predictor of an increased risk of adverse cardiovascular events in HF. Our work could provide joint and complementary prognostic value to NT-proBNP levels in HF patients.© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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