Evidence map›Paper›PMID 40464107›Full record

ArticleEuropean journal of heart failure2025

Mechanical unloading is accompanied by reverse metabolic remodelling in the failing heart: Identification of a novel citraconate-mediated pathway.

David M Kaye, Xiao Suo Wang, Yen Chin Koay, Mengbo Li, Bailey McIntosh, Yann Huey Ng, Michael Rahman, Yiyang Cao, Francine Z Marques, Cassandra Malecki and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of heart failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Ceramide as a Biomarker for HFpEF in Women: Menopause, Aging, and Pregnancy.International journal of molecular sciences · 2025
    Review
  3. Metabolic Reprogramming in Heart Failure: From Energy Starvation to Therapeutic Targets.Current treatment options in cardiovascular medicine · 2025
    Review
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

16 authors.

David M KayeHeart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Xiao Suo WangCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Yen Chin KoayCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Mengbo LiCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Bailey McIntoshCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Yann Huey NgCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Michael RahmanCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Yiyang CaoCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Francine Z MarquesHeart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Cassandra MaleckiCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Shane NanayakkaraHeart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Justin MarianiHeart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Bing WangHeart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Sean LalCardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
Giovanni Guglielmi *Cardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.
John F O'Sullivan *Cardiometabolic-Medicine Laboratory, The University of Sydney, Camperdown, NSW, Australia.

Funding

National Health and Medical Research Council 1159721
6 · The paper itself

Abstract

aimsAlthough functional recovery of the failing heart with left ventricular assist device (LVAD) unloading can occur, the underpinning mechanism is unclear. We aimed to characterize the effect of myocardial biochemical effect of LVAD support in vivo and in vitro. METHODS AND

resultsWe performed targeted metabolomics and lipidomics on transcardiac (arterial and coronary sinus) blood samples collected from healthy volunteers (n = 13), patients with end-stage heart failure with reduced ejection fraction (HFrEF, n = 20), and LVAD-supported HFrEF patients (n = 18). Complementary biochemical studies in myocardial tissue samples from healthy donor, HFrEF and LVAD patients, and cardiomyoblasts were performed. Myocardial uptake of intermediates in purine, nucleotide, and tricarboxylic acid (TCA) cycle pathways was depressed in HFrEF patients, with recovery in LVAD patients. Glucose uptake was suppressed in HFrEF but restored in LVAD. Metabolite changes suggestive of impaired fatty acid oxidation were present in HFrEF but not in LVAD. We found that the metabolite citraconate was significantly released by HFrEF hearts compared to controls and this was corroborated, in separate patients, by increased levels of citraconate in HFrEF myocardium but not in LVAD. Whilst citraconate increased succinate deydrogenase (SDH) activity in cardiomyoblasts, its isomer itaconate suppressed SDH activity. SDH activity was maintained in HFrEF myocardium but was diminished in LVAD myocardium.

conclusionsWe report, for the first time, the in-vivo biochemical effects of LVAD unloading in the human heart. Our data identify citraconate as a potentially important regulator of the TCA cycle in the failing heart.

Indexed as

Heart-Assist DevicesHeart FailureMyocardiumSuccinatesVentricular RemodelingAdultCitric Acid CycleFemaleHumansLipidomicsMaleMetabolomicsMiddle AgedStroke VolumeSuccinatesHFrEFLipidomicsLVADMetabolomicsMyocardial metabolismRemodelling

Identifiers

PMID40464107
PMCPMC12370577

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.