Evidence map›Paper›PMID 36524472›Full record

Trial reportCirculation. Heart failure2023

Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure.

Kymberleigh A Romano, Ina Nemet, Prasenjit Prasad Saha, Arash Haghikia, Xinmin S Li, Maradumane L Mohan, Beth Lovano, Laurie Castel, Marco Witkowski, Jennifer A Buffa and 14 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation. Heart failure, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00590200 (Molecular Determinants of Coronary Artery Disease), which is not on this map. Cited by 104 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 2 pooled it
21.5field-weighted citation impact, top 1% of its field
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.

NCT00590200 active not recruitingnot on this map

Molecular Determinants of Coronary Artery Disease

TypeobservationalSponsorThe Cleveland ClinicRan2001 to 2030Enrolled9,880ConditionsCardiovascular Diseases
3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.

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44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 9 institutions in 4 countries.

Kymberleigh A RomanoDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).
Ina NemetDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0002-0657-7121
Prasenjit Prasad SahaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0003-4679-2368
Arash HaghikiaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0002-5646-3237
Xinmin S LiDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0003-4946-4271
Maradumane L MohanDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0003-4224-150X
Beth LovanoDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0002-3994-600X
Laurie CastelDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0003-0249-1504
Marco WitkowskiDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0002-6952-5038
Jennifer A BuffaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).
Yu SunDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0002-9819-3263
Lin LiDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0003-1578-9182
Christopher M MengeDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).
Ilja DemuthDepartment of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Charitéplatz, Germany (I.D., M.K., E.S.-T.).ORCID 0000-0002-4340-2523
Maximilian KönigDepartment of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Charitéplatz, Germany (I.D., M.K., E.S.-T.).ORCID 0000-0003-4873-5519
Elisabeth Steinhagen-ThiessenDepartment of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Charitéplatz, Germany (I.D., M.K., E.S.-T.).
Joseph A DiDonatoDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).
Arjun DebDivision of Cardiology and Department of Medicine, David Geffen School of Medicine, University of California Los Angeles (A.D.).
Fredrik BäckhedDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Sweden (F.B.).ORCID 0000-0002-4871-8818
W H Wilson TangDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0002-8335-735X
Sathyamangla Venkata Naga PrasadDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0003-3984-3788
Ulf LandmesserDepartment of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany; German Center for Cardiovascular Research, Partner Site Berlin, Germany; and Berlin Institute of Health, Germany (A.H., U.L.).
David R Van WagonerDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0001-8250-9828
Stanley L HazenDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (K.A.R., I.N., P.P.S., A.H., X.S.L., M.L.M., B.L., L.C., M.W., J.A.B., Y.S., L.L., C.M.M., J.A.D., W.H.W.T., S.V.N.P., D.R.V.W., S.L.H.).ORCID 0000-0001-7124-6639
L-3 Communications (United States) · USMACOM (United States) · USBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DECharité - Universitätsmedizin Berlin · DECleveland Clinic · USAnna Needs Neuroblastoma Answers · USBerlin-Brandenburger Centrum für Regenerative Therapien · DEUniversity of California, Los Angeles · USWallenberg Wood Science Center · SE

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
Diet, Gut Microbiota, and Heart FailureR01HL126827 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2016 to 2019
$3.1M
Role of GPNMB in cardiac remodelingR01HL152176 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2021 to 2024
$2.8M
Targeting cardiac fibroblast-myocyte cross talk to enhance heart function after cardiac injuryR01HL149658 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2020 to 2023
$2.2M
Role of collagen heterogeneity in remodeling of acute and chronic heart scarsR01HL149687 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN, PELLEGRINI, MATTEO · 2020 to 2023
$2.0M
CWRU- Cardiovascular Research Training ProgramT32HL134622 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI JAIN, MUKESH KUMAR, PROWELLER, AARON · 2017 to 2021
$1.9M
NHLBI NIH HHS P01 HL147823NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL126827NHLBI NIH HHS R01 HL149658NHLBI NIH HHS R01 HL149687NHLBI NIH HHS R01 HL152176NHLBI NIH HHS T32 HL134622
6 · The paper itself

Abstract

backgroundThe gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is both associated with atherothrombotic heart disease in humans, and mechanistically linked to cardiovascular disease pathogenesis in animal models via modulation of adrenergic receptor signaling.

methodsHere we examined both clinical and mechanistic relationships between PAGln and heart failure (HF). First, we examined associations among plasma levels of PAGln and HF, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide in 2 independent clinical cohorts of subjects undergoing coronary angiography in tertiary referral centers (an initial discovery US Cohort, n=3256; and a validation European Cohort, n=829). Then, the impact of PAGln on cardiovascular phenotypes relevant to HF in cultured cardiomyoblasts, and in vivo were also examined.

resultsCirculating PAGln levels were dose-dependently associated with HF presence and indices of severity (reduced ventricular ejection fraction, elevated N-terminal pro-B-type natriuretic peptide) independent of traditional risk factors and renal function in both cohorts. Beyond these clinical associations, mechanistic studies showed both PAGln and its murine counterpart, phenylacetylglycine, directly fostered HF-relevant phenotypes, including decreased cardiomyocyte sarcomere contraction, and B-type natriuretic peptide gene expression in both cultured cardiomyoblasts and murine atrial tissue.

conclusionsThe present study reveals the gut microbial metabolite PAGln is clinically and mechanistically linked to HF presence and severity. Modulating the gut microbiome, in general, and PAGln production, in particular, may represent a potential therapeutic target for modulating HF. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT00590200 and URL: https://drks.de/drks_web/; Unique identifier: DRKS00020915.

Indexed as

Gastrointestinal MicrobiomeHeart FailureVentricular Dysfunction, LeftAnimalsGlutamineHumansMiceNatriuretic Peptide, BrainStroke VolumeVentricular Function, LeftGlutamineNatriuretic Peptide, Brainphenylacetylglutaminegut microbiomeheart failuremetabolismphenylacetylglutamine

Identifiers

PMID36524472
PMCPMC9851997
OpenAlexW4312065274

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Read underepoch 390

Registered trials

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.