Evidence map›Paper›PMID 40396194›Full record

ArticleEuropean heart journal2025

Empagliflozin enhances metabolic efficiency and improves left ventricular hypertrophy in a hypertrophic cardiomyopathy mouse model.

Tomas Baka, Jarrod Moore, Fuzhong Qin, Salva R Yurista, Aifeng Zhang, Huamei He, Jordan M Chambers, Dominique Croteau, Raghuveera K Goel, Hunter Smith and 13 more

Abstract read
In one paragraph

Article in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Trial
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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

23 authors.

Tomas BakaMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.ORCID 0000-0003-4752-9828
Jarrod MooreCenter for Network Systems Biology, Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
Fuzhong QinMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.ORCID 0000-0002-9534-3617
Salva R YuristaMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.ORCID 0000-0001-9126-739X
Aifeng ZhangMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.
Huamei HePhysiological NMR Core Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jordan M ChambersMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.ORCID 0000-0002-4285-7454
Dominique CroteauMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.ORCID 0000-0001-9274-5314
Raghuveera K GoelCenter for Network Systems Biology, Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.ORCID 0000-0001-7348-3996
Hunter SmithMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.
Miranda C WangDepartment of Biomedical Engineering, Boston University, Boston, MA, USA.ORCID 0000-0002-9534-5276
Christopher S ChenDepartment of Biomedical Engineering, Boston University, Boston, MA, USA.ORCID 0000-0003-2445-8449
Ion A HobaiDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-0567-6873
Martina RombaldovaLaboratory of Metabolism of Bioactive Lipids, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.ORCID 0000-0002-1869-355X
Ondrej KudaLaboratory of Metabolism of Bioactive Lipids, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.ORCID 0000-0001-7034-4536
Jil C TardiffDepartment of Biomedical Engineering, University of Arizona, Tucson, AZ, USA.ORCID 0000-0003-4291-4882
James A BalschiPhysiological NMR Core Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
David R PimentelMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.
Christine E SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6380-1209
Jonathan G SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9082-3566
Andrew EmiliCenter for Network Systems Biology, Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.ORCID 0000-0001-8995-246X
Wilson S ColucciMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.ORCID 0000-0002-0576-9420
Ivan LuptakMyocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, Evans Biomed Research Ctr (room 704B), Boston, MA 02118, USA.ORCID 0000-0001-7498-7694

Funding

Targeting Energetics to Improve Outcomes in Hypertrophic CardiomyopathyR01HL166606 · NHLBI · BOSTON MEDICAL CENTER · PI Ivan Luptak · 2024 to 2026
$2.4M
Targeting Energetics to Improve Outcomes in Hypertrophic CardiomyopathyR56HL157367 · NHLBI · BOSTON MEDICAL CENTER · PI LUPTAK, IVAN · 2022 to 2022
$818k
American Heart AssociationEuropean UnionNational Institute for Research of Metabolic and Cardiovascular DiseasesNational Science Foundation Engineering Research Center on Cellular MetamaterialsNational Science Foundation Graduate Research FellowshipNHLBI NIH HHS R01 HL166606NHLBI NIH HHS R56 HL157367NIH HHS
6 · The paper itself

Abstract

BACKGROUND AND

aimsHypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and impaired metabolic efficiency. This study investigates the therapeutic potential of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin (EMPA) in ameliorating these pathological features in a mouse model carrying the myosin R403Q mutation.

methodsMale mice harbouring the R403Q mutation were treated with EMPA for 16 weeks. Multi-nuclear magnetic resonance spectroscopy (31P, 13C, and 23Na MRS), echocardiography, transcriptomic, proteomic, and phosphoproteomic profiling were utilized to assess metabolic, structural, and functional changes.

resultsEmpagliflozin facilitated the coupling of glycolysis with glucose oxidation and normalized elevated intracellular sodium levels. Treatment resulted in a significant reduction in LVH and myocardial fibrosis as evidenced by echocardiography and histopathology. These structural improvements correlated with enhancements in mitochondrial adenosine triphosphate (ATP) synthesis, fatty acid oxidation, and branched-chain amino acid catabolism. Furthermore, EMPA improved left ventricular diastolic function and contractile reserve, underscored by improved ATP production and reduced energy cost of contraction. Notably, these benefits were linked to down-regulation of the mammalian target of rapamycin signalling pathway and normalization of myocardial substrate metabolic fluxes.

conclusionsEmpagliflozin significantly mitigates structural and metabolic dysfunctions in a mouse model of HCM, underscoring its potential as a therapeutic agent for managing this condition. These findings suggest broader applicability of SGLT2i in cardiovascular diseases, including those due to myocardial-specific mutations, warranting further clinical investigation.

Indexed as

Cardiomyopathy, Hypertrophic, FamilialSodium-Glucose Transporter 2 InhibitorsAnimalsBenzhydryl CompoundsEnergy MetabolismFatty AcidsGlucosidesHeartHeart Failure, DiastolicHypertrophy, Left VentricularMaleMiceMyocardiumBenzhydryl CompoundsempagliflozinFatty AcidsGlucosidesSodium-Glucose Transporter 2 InhibitorsBranched-chain amino acidsCardiac energeticsCardiac metabolismHypertrophic cardiomyopathyMetabolic reprogrammingmTORSGLT2 inhibitionUncoupled glycolysis

Identifiers

PMID40396194
PMCPMC12539926

What Socratic holds

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Registered trials

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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 Socratic graph.