Evidence mapPaperPMID 30328645Full record

ArticleEuropean journal of heart failure2018

Empagliflozin directly improves diastolic function in human heart failure.

Steffen Pabel, Stefan Wagner, Hannah Bollenberg, Philipp Bengel, Árpád Kovács, Christian Schach, Petros Tirilomis, Julian Mustroph, André Renner, Jan Gummert and 8 more

2 registry-linked trialsOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in European journal of heart failure, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 119 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 5 pooled it
15.1field-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.

NCT06249932 phase4recruitingstarted 2024, after this paper: background citation

The Safety and Efficacy of Empagliflozin in Patients with End-stage Renal Disease and Heart Failure with Reduced Ejection Fraction - a Randomized Controlled Trial

Ran2024Enrolled95Registered outcomes33Posted comparisons0ConditionsEnd Stage Renal Disease on Dialysis, Heart Failure With Reduced Ejection FractionArmsempagliflozin 25 mg, Placebo
Open the trial in the graph
NCT06249945 phase4recruitingstarted 2024, after this paper: background citation

The Safety and Efficacy of Empagliflozin in Patients With End-stage Renal Disease and Heart Failure With Preserved Ejection Fraction - a Randomized Controlled Trial

Ran2024Enrolled150Registered outcomes27Posted comparisons0ConditionsEnd Stage Renal Disease on Dialysis, Heart Failure With Preserved Ejection FractionArmsempagliflozin 25 mg, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

119 citing papers in PubMed, 5 syntheses or guidelines pooled it, 214 citations in OpenAlex.

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  4. Highlights in heart failure.ESC heart failure · 2019
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  6. Safety and Short-Term Effects of Empagliflozin in Patients with Heart Failure and End-Stage Renal Disease.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026
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59 more citing papers are in PubMed but not listed here.

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

18 authors at 6 institutions in 1 country.

Steffen PabelDepartment of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
Stefan WagnerDepartment of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
Hannah BollenbergClinic for Cardiology & Pneumology, Georg-August University Goettingen, and German Center for Cardiovascular Research (DZHK), partner site Goettingen, Germany.
Philipp BengelClinic for Cardiology & Pneumology, Georg-August University Goettingen, and German Center for Cardiovascular Research (DZHK), partner site Goettingen, Germany.
Árpád KovácsDepartment of Systems Physiology, Ruhr University Bochum, Bochum, Germany.
Christian SchachDepartment of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
Petros TirilomisClinic for Cardiology & Pneumology, Georg-August University Goettingen, and German Center for Cardiovascular Research (DZHK), partner site Goettingen, Germany.
Julian MustrophDepartment of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
André RennerDepartment of Thoracic, Cardiac and Vascular Surgery (Heart and Diabetes Center), North Rhine Westphalia, Bad Oeynhausen, Germany.
Jan GummertDepartment of Thoracic, Cardiac and Vascular Surgery (Heart and Diabetes Center), North Rhine Westphalia, Bad Oeynhausen, Germany.
Thomas FischerClinic for Cardiology & Pneumology, Georg-August University Goettingen, and German Center for Cardiovascular Research (DZHK), partner site Goettingen, Germany.
Sophie Van LinthoutDepartment of Internal Medicine and Cardiology, Charité University Medicine Berlin, Berlin-Brandenburg Center for Regenerative Therapies and German Center for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany.
Carsten TschöpeDepartment of Internal Medicine and Cardiology, Charité University Medicine Berlin, Berlin-Brandenburg Center for Regenerative Therapies and German Center for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany.
Katrin Streckfuss-BömekeClinic for Cardiology & Pneumology, Georg-August University Goettingen, and German Center for Cardiovascular Research (DZHK), partner site Goettingen, Germany.
Gerd HasenfussClinic for Cardiology & Pneumology, Georg-August University Goettingen, and German Center for Cardiovascular Research (DZHK), partner site Goettingen, Germany.
Lars S MaierDepartment of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
Nazha HamdaniDepartment of Systems Physiology, Ruhr University Bochum, Bochum, Germany.
Samuel SossallaDepartment of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
German Centre for Cardiovascular Research · DEUniversity Hospital Regensburg · DEHeart and Diabetes Center North Rhine-Westphalia · DEUniversity Hospitals of the Ruhr-University of Bochum · DEUniversity of Regensburg · DEBerlin-Brandenburger Centrum für Regenerative Therapien · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsEmpagliflozin, a clinically used oral antidiabetic drug that inhibits the sodium-dependent glucose co-transporter 2, has recently been evaluated for its cardiovascular safety. Surprisingly, empagliflozin reduced mortality and hospitalization for heart failure (HF) compared to placebo. However, the underlying mechanisms remain unclear. Therefore, our study aims to investigate whether empagliflozin may cause direct pleiotropic effects on the myocardium. METHODS AND

resultsIn order to assess possible direct myocardial effects of empagliflozin, we performed contractility experiments with in toto-isolated human systolic end-stage HF ventricular trabeculae. Empagliflozin significantly reduced diastolic tension, whereas systolic force was not changed. These results were confirmed in murine myocardium from diabetic and non-diabetic mice, suggesting independent effects from diabetic conditions. In human HF cardiomyocytes, empagliflozin did not influence calcium transient amplitude or diastolic calcium level. The mechanisms underlying the improved diastolic function were further elucidated by studying myocardial fibres from patients and rats with diastolic HF (HF with preserved ejection fraction, HFpEF). Empagliflozin beneficially reduced myofilament passive stiffness by enhancing phosphorylation levels of myofilament regulatory proteins. Intravenous injection of empagliflozin in anaesthetized HFpEF rats significantly improved diastolic function measured by echocardiography, while systolic contractility was unaffected.

conclusionEmpagliflozin causes direct pleiotropic effects on the myocardium by improving diastolic stiffness and hence diastolic function. These effects were independent of diabetic conditions. Since pharmacological therapy of diastolic dysfunction and HF is an unmet need, our results provide a rationale for new translational studies and might also contribute to the understanding of the EMPA-REG OUTCOME trial.

Indexed as

AnimalsBenzhydryl CompoundsBiopsyDiastoleDisease Models, AnimalEchocardiographyFemaleGlucosidesHeart FailureHeart VentriclesHumansMaleMiceMiddle AgedMyocardial ContractionMyocardiumBenzhydryl CompoundsempagliflozinGlucosidesSodium-Glucose Transporter 2 InhibitorsContractilityDiastolic dysfunctionEmpagliflozinHeart failure

Identifiers

PMID30328645
OpenAlexW2897621296

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.