Evidence map›Paper›PMID 30999996›Full record

ArticleJournal of the American College of Cardiology2019

Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics.

Carlos G Santos-Gallego, Juan Antonio Requena-Ibanez, Rodolfo San Antonio, Kiyotake Ishikawa, Shin Watanabe, Belen Picatoste, Eduardo Flores, Alvaro Garcia-Ropero, Javier Sanz, Roger J Hajjar and 2 more

4 registry-linked trialsAbstract read
PubMed Publisher
In one paragraph

Article in Journal of the American College of Cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT04183868. Cited by 358 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
358citing papers in PubMed, 13 pooled it
51.6field-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.

NCT04183868 phase4completed

Comparative Effects of Empagliflozin Versus Glimepiride After 26-weeks of Treatment Add on Metformin on Myocardial Metabolic Rate of Glucose Estimated Through 18FDG-PET in Patients With Type 2 Diabetes

Ran2016Enrolled26Registered outcomes10Posted comparisons0ConditionsCardiovascular Risk Factor, Type 2 DiabetesArmsempagliflozin 10 mg, Glimepiride 2 mg
PMID 24929430PMID 24463454PMID 26378978PMID 29496507PMID 758126PMID 8366922PMID 8883708PMID 9673301PMID 9742976PMID 25271206PMID 23404920PMID 22357182other papers from this trial
Open the trial in the graph
NCT05335629 nacompletedstarted 2022, after this paper: background citation

Evaluation of the Effect of Dapagliflozin on Cardiac Remodeling in Post Myocardial Infarction Patients

Ran2022Enrolled54Registered outcomes2Posted comparisons0ConditionsDiabetes Mellitus, Type 2, Myocardial Infarction, Myocardial Remodeling, VentricularArmsDapagliflozin 10mg Tab
PMID 27521518PMID 32067179PMID 32578850PMID 32626540PMID 31607208PMID 30710997PMID 30416379PMID 29922732PMID 29285671PMID 10491084PMID 12460879PMID 15110792other papers from this trial
Open the trial in the graph
NCT06510894 recruitingnot on this mapstarted 2024, after this paper: background citation

Diagnostic Utility of SGLT1/2 Inhibition to Facilitate Myocardial Glucose Suppression During Evaluation of Cardiac Inflammation on FDG-PET

TypeobservationalSponsorUniversity of PennsylvaniaRan2024 to 2027Enrolled40ConditionsCardiac SarcoidosisArmsSotagliflozin
NCT07070765 narecruitingnot on this mapstarted 2025, after this paper: background citation

Sodium-glucose Transporter Type 2 Inhibition in Anthracycline-related Cardiotoxicity - SPRINT

TypeinterventionalSponsorUniversity of AberdeenRan2025 to 2028Enrolled70ConditionsBreast CancerArmsSodium-glucose transport-2 (SGLT-2) inhibitors, Standard medical treatment
3 · Its place in the literature

Who cites it

358 citing papers in PubMed, 13 syntheses or guidelines pooled it, 641 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Carlos G Santos-GallegoAtheroThrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: carlos.santos-gallego@mssm.edu.
Juan Antonio Requena-IbanezAtheroThrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Cardiology Department, University Hospital of Ciudad Real, Ciudad Real, Spain.
Rodolfo San AntonioAtheroThrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Cardiology Department, Hospital Clinic de Barcelona, Barcelona, Spain.
Kiyotake IshikawaCardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Shin WatanabeCardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Belen PicatosteBiochemistry Department, Weill Cornell Medical College, New York, New York.
Eduardo FloresAtheroThrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Cardiology Department, Hospital Clinic de Barcelona, Barcelona, Spain.
Alvaro Garcia-RoperoAtheroThrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Javier SanzCardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Roger J HajjarCardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Valentin FusterCardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Juan J BadimonAtheroThrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: juan.badimon@mssm.edu.
Cardiovascular Institute of the South · USIcahn School of Medicine at Mount Sinai · USMount Sinai Hospital · USCornell University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEmpagliflozin cardiac benefits in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial cannot be explained exclusively by its antihyperglycemic activity.

objectivesThe hypothesis was that empagliflozin's cardiac benefits are mediated by switching myocardial fuel metabolism away from glucose toward ketone bodies (KB), which improves myocardial energy production.

methodsHeart failure was induced in nondiabetic pigs (n = 14) by 2-h balloon occlusion of the proximal left anterior descending artery. Animals were randomized to empagliflozin or placebo for 2 months. Animals were evaluated with cardiac magnetic resonance imaging and 3-dimensional echocardiography. Myocardial metabolite consumption was analyzed by simultaneous blood sampling from coronary artery and coronary sinus. Myocardial samples were obtained for molecular evaluation. Nonmyocardial infarction animals served as comparison.

resultsDespite similar initial ischemic myocardial injury in both groups, the empagliflozin group showed amelioration of adverse remodeling at 2 months (lower left ventricular [LV] mass, reduced LV dilatation, less LV sphericity) versus the control group. LV systolic function (LV ejection fraction and echocardiography-derived strains) was improved, as was neurohormonal activation. Compared with nonmyocardial infarction, control animals increased myocardial glucose consumption mainly through anaerobic glycolysis while reducing utilization of free fatty acid (FFA) and branched-chain amino acid (BCAA). Empagliflozin-treated pigs did not consume glucose (reduction in myocardial glucose uptake, and glucose-related enzymes) but instead switched toward utilization of KB, FFA, and BCAA (increased myocardial uptake of these 3 metabolites, and enhanced expression/activity of the enzymes implicated in the metabolism of KB/FFA/BCAA). Empagliflozin increased myocardial ATP content and enhanced myocardial work efficiency.

conclusionsEmpagliflozin ameliorates adverse cardiac remodeling and heart failure in a nondiabetic porcine model. Empagliflozin switches myocardial fuel utilization away from glucose toward KB, FFA, and BCAA, thereby improving myocardial energetics, enhancing LV systolic function, and ameliorating adverse LV remodeling.

Indexed as

Analysis of VarianceAnimalsBenzhydryl CompoundsDiabetes MellitusDisease Models, AnimalEchocardiography, Three-DimensionalGlucosidesHeart FailureHeart Function TestsRandom AllocationReference ValuesSodium-Glucose Transporter 2 InhibitorsStatistics, NonparametricStroke VolumeSwineTreatment OutcomeBenzhydryl CompoundsempagliflozinGlucosidesSodium-Glucose Transporter 2 Inhibitorsanimal modelscardiac remodelingdiabetesheart failuremyocardial metabolismSGLT2 inhibition

Identifiers

PMID30999996
OpenAlexW2936593438

What Socratic holds

Textmetadata
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 Socratic graph.