Evidence map›Paper›PMID 38124458›Full record

ArticleEuropean journal of heart failure2024

Prognostic value of gut microbe-generated metabolite phenylacetylglutamine in patients with heart failure.

W H Wilson Tang, Ina Nemet, Xinmin S Li, Yuping Wu, Arash Haghikia, Marco Witkowski, Robert A Koeth, Ilja Demuth, Maximilian König, Elisabeth Steinhagen-Thiessen and 5 more

Abstract read
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Article in European journal of heart failure, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed.

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  14. Gut-heart axis: cardiac remodeling and heart failure in the context of inflammatory bowel disease and dysbiosis.American journal of physiology. Gastrointestinal and liver physiology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

W H Wilson TangCenter for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Ina NemetCenter for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Xinmin S LiCenter for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Yuping WuDepartment of Mathematics and Statistics, Cleveland State University, Cleveland, OH, USA.
Arash HaghikiaDepartment of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Marco WitkowskiCenter for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Robert A KoethCenter for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Ilja DemuthDepartment of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Maximilian KönigBerlin Institute of Health (BIH), Berlin, Germany.
Elisabeth Steinhagen-ThiessenDepartment of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Fredrik BäckhedWallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden.
Michael A FischbachDepartment of Bioengineering and ChEM-H, Stanford University, Stanford, CA, USA.
Arjun DebDivision of Cardiology and Department of Medicine, David Geffen School of Medicine, Los Angeles, CA, USA.
Ulf LandmesserDepartment of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Stanley L HazenCenter for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

Funding

Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic diseaseP01HL147823 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MICHAEL ANDREW FISCHBACH · 2019 to 2026
$17.0M
Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
TMAO and Initiation, Extent, and Clinical Onset of Atherosclerotic CVDR01HL135920 · NHLBI · TUFTS UNIVERSITY BOSTON · PI Stanley L Hazen, DARIUSH MOZAFFARIAN · 2017 to 2026
$8.7M
Gut microbial dietary phenylalanine metabolism and heart failureR01HL167831 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI Stanley L Hazen · 2024 to 2026
$2.4M
NHLBI NIH HHS P01 HL147823NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL135920NHLBI NIH HHS R01 HL167831NIH HHS P01HL147823NIH HHS R01HL103866NIH HHS R01HL167831-01A1
6 · The paper itself

Abstract

aimPhenylacetylglutamine (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

resultsFasting 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.

conclusionHigh levels of PAGln are associated with adverse outcomes independent of traditional cardiac risk factors and cardio-renal risk markers.

Indexed as

Gastrointestinal MicrobiomeHeart FailureBiomarkersChromatography, LiquidGlutamineHumansPrognosisStroke VolumeTandem Mass SpectrometryVentricular Function, LeftBiomarkersGlutaminephenylacetylglutamineHeart failureMicrobiomePhenylacetylglutamineTrimethylamine N‐oxide

Identifiers

PMID38124458
PMCPMC12512454

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.