{"doi":"10.1002/ejhf.3111","title":"Prognostic Value of Gut Microbe-Generated Metabolite Phenylacetylglutamine in Patients with Heart Failure","abstract":"AIM: Phenylacetylglutamine (PAGln) is a phenylalanine-derived metabolite produced by gut microbiota with mechanistic links to heart failure (HF)-relevant phenotypes. We sought to investigate the prognostic value of PAGln in patients with stable HF. METHODS AND RESULTS: Fasting plasma PAGln levels were measured by stable-isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients with stable HF from two large cohorts. All-cause mortality was assessed at 5-year follow-up in the Cleveland cohort, and HF, hospitalization, or mortality were assessed at 3-year follow-up in the Berlin cohort. Within the Cleveland cohort, median PAGln levels were 4.2 (interquartile range [IQR] 2.4-6.9) μM. Highest quartile of PAGln was associated with 3.09-fold increased mortality risk compared to lowest quartile. Following adjustments for traditional risk factors, as well as race, estimated glomerular filtration rate, amino-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, left ventricular ejection fraction, ischaemic aetiology, and HF drug treatment, elevated PAGln levels remained predictive of 5-year mortality in quartile comparisons (adjusted hazard ratio [HR] [95% confidence interval, CI] for Q4 vs Q1: 1.64 [1.07-2.53]). In the Berlin cohort, a similar distribution of PAGln levels was observed (median 3.2 [IQR 2.0-4.8] μM), and PAGln levels were associated with a 1.92-fold increase in 3-year HF hospitalization or all-cause mortality risk (adjusted HR [95% CI] for Q4 vs Q1: 1.92 [1.02-3.61]). Prognostic value of PAGln appears to be independent of trimethylamine N-oxide levels. CONCLUSION: High levels of PAGln are associated with adverse outcomes independent of traditional cardiac risk factors and cardio-renal risk markers.","journal":"European Journal of Heart Failure","year":2023,"id":322586,"datarank":1.0242862332642386,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.4672504232585923,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.4672504232585923,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":36,"citers_with_citation_signal":22,"citers_with_endowment":22,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00590200"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":108881,"name":"Ina Nemet","orcid":"0000-0002-0657-7121","position":1,"is_corresponding":false},{"id":405031,"name":"Xinmin S. Li","orcid":"0000-0003-4946-4271","position":2,"is_corresponding":false},{"id":108890,"name":"Yuping Wu","orcid":"0000-0002-7892-1876","position":3,"is_corresponding":false},{"id":618087,"name":"Arash Haghikia","orcid":"0000-0002-5646-3237","position":4,"is_corresponding":false},{"id":635085,"name":"Marco Witkowski","orcid":"0000-0002-6952-5038","position":5,"is_corresponding":false},{"id":632779,"name":"Robert Koeth","orcid":"0009-0003-1673-2193","position":6,"is_corresponding":false},{"id":336230,"name":"Ilja Demuth","orcid":"0000-0002-4340-2523","position":7,"is_corresponding":false},{"id":1015837,"name":"Maximilian König","orcid":"0000-0003-4873-5519","position":8,"is_corresponding":false},{"id":1017058,"name":"Elisabeth Steinhagen‐Thiessen","orcid":null,"position":9,"is_corresponding":false},{"id":32285,"name":"Fredrik Bäckhed","orcid":"0000-0002-4871-8818","position":10,"is_corresponding":false},{"id":44570,"name":"Michael A. Fischbach","orcid":"0000-0003-3079-8247","position":11,"is_corresponding":false},{"id":244631,"name":"Arjun Deb","orcid":"0000-0003-0978-2611","position":12,"is_corresponding":false},{"id":253775,"name":"Ulf Landmesser","orcid":"0000-0002-0214-3203","position":13,"is_corresponding":false},{"id":108895,"name":"Stanley L. Hazen","orcid":"0000-0001-7124-6639","position":14,"is_corresponding":false},{"id":30816,"name":"W. H. Wilson Tang","orcid":"0000-0002-8335-735X","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T01:07:42.497873Z","pmid":"38124458","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}