Article in Circulation. Arrhythmia and electrophysiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
0numbers the graph read from it
0cells of the map it votes in
2citing 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.
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
27 authors.
Simon Libak Haugaard *Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark (S.L.H., M.J.S., S.T.K., J.N.S., H.C., C.H.-I., S.D.N., R. Buhl).ORCID 0000-0003-1787-134X
Mélodie J Schneider *Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark (S.L.H., M.J.S., S.T.K., J.N.S., H.C., C.H.-I., S.D.N., R. Buhl).ORCID 0000-0001-8739-8223
Sofie Troest KjeldsenDepartment of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark (S.L.H., M.J.S., S.T.K., J.N.S., H.C., C.H.-I., S.D.N., R. Buhl).ORCID 0000-0001-9828-5494
Stefan Michael SattlerCardiac Physiology Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences (S.M.S., A.S., C.H., T.J., S.D.N.), University of Copenhagen, Denmark.ORCID 0000-0003-3558-8329
Joakim Armstrong BastrupVascular Biology Group, Department of Biomedical Sciences (J.A.B., T.A.J.), University of Copenhagen, Denmark.ORCID 0000-0002-4292-5234
Arnela SaljicCardiac Physiology Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences (S.M.S., A.S., C.H., T.J., S.D.N.), University of Copenhagen, Denmark.ORCID 0000-0001-8910-0902
Jesper Bratz BirkAugust Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science (J.B.B., R.K., J.F.P.W.), University of Copenhagen, Denmark.ORCID 0000-0001-9775-4789
Caroline HansenCardiac Physiology Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences (S.M.S., A.S., C.H., T.J., S.D.N.), University of Copenhagen, Denmark.ORCID 0009-0005-7609-3308
Josefine Natalie SynnestvedtDepartment of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark (S.L.H., M.J.S., S.T.K., J.N.S., H.C., C.H.-I., S.D.N., R. Buhl).ORCID 0009-0004-0313-575X
Arne van HunnikDepartment of Physiology, Maastricht University, the Netherlands (A.v.H.).ORCID 0000-0003-3089-540X
Vladimír SobotaIHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, France (V.S.).ORCID 0000-0003-2285-5619
Helena CarstensenDepartment of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark (S.L.H., M.J.S., S.T.K., J.N.S., H.C., C.H.-I., S.D.N., R. Buhl).ORCID 0000-0001-8952-9637
Charlotte Hopster-IversenDepartment of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark (S.L.H., M.J.S., S.T.K., J.N.S., H.C., C.H.-I., S.D.N., R. Buhl).ORCID 0000-0003-3606-2484
Colin C SchwarzwaldClinic for Equine Internal Medicine, Vetsuisse Faculty, University of Zurich, Switzerland (C.C.S.).ORCID 0000-0002-6095-5402
Ali AltintaşNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences (A.A., R. Barrès), University of Copenhagen, Denmark.ORCID 0000-0002-8932-0160
Romain BarrèsNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences (A.A., R. Barrès), University of Copenhagen, Denmark.ORCID 0000-0002-0158-519X
Thomas Andrew JeppsVascular Biology Group, Department of Biomedical Sciences (J.A.B., T.A.J.), University of Copenhagen, Denmark.ORCID 0000-0002-9903-714X
Steen LarsenDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences (S.L.), University of Copenhagen, Denmark.ORCID 0000-0002-5170-4337
Rasmus KjøbstedAugust Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science (J.B.B., R.K., J.F.P.W.), University of Copenhagen, Denmark.ORCID 0000-0002-0628-4994
Jørgen F P WojtaszewskiAugust Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science (J.B.B., R.K., J.F.P.W.), University of Copenhagen, Denmark.ORCID 0000-0001-8185-3408
Kate M HerumResearch and Early Development, Novo Nordisk A/S, Maaloev, Denmark (K.M.H.).ORCID 0000-0001-6617-6613
Thomas JespersenCardiac Physiology Laboratory, Department of Biomedical Sciences, Faculty of Health and Medical Sciences (S.M.S., A.S., C.H., T.J., S.D.N.), University of Copenhagen, Denmark.ORCID 0000-0001-6575-360X
Stanley NattelDepartment of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, Canada (S.N.).ORCID 0000-0002-5565-3311
Sarah Dalgas Nissen *Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark (S.L.H., M.J.S., S.T.K., J.N.S., H.C., C.H.-I., S.D.N., R. Buhl).ORCID 0000-0001-8598-7147
Rikke Buhl *Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark (S.L.H., M.J.S., S.T.K., J.N.S., H.C., C.H.-I., S.D.N., R. Buhl).ORCID 0000-0002-8201-0186
Funding
No grant is acknowledged in the PubMed record.
6 · The paper itself
Abstract
backgroundHorses are one of the few animals that spontaneously develop atrial fibrillation (AF), making them a powerful model for studying AF mechanisms and treatment effects. Despite the initial effectiveness of treatment in horses and humans, AF-induced atrial remodeling compromises its long-term success. Observational studies have suggested that metformin may reduce the risk of AF, but its effects on progressive AF-induced atrial remodeling have yet to be evaluated in a high-fidelity large animal model.
methodsHere, we used a longitudinal horse model of tachypacing-induced self-sustained AF to characterize the electrical, molecular, and metabolic atrial changes over 4 months of disease, with and without metformin treatment (30 mg/kg orally, twice daily; initiated before AF induction, N=24 horses). Electrophysiological and multiomic approaches were combined with histology, echocardiography, biochemical, and mitochondrial analyses to evaluate disease progression and treatment response.
resultsThe horse model replicated critical aspects of AF-induced atrial remodeling observed in Humans, including electrical and structural changes. Despite upregulation of metabolic genes and proteins in AF, no significant ultrastructural mitochondrial changes were detected. Metformin plasma trough levels confirmed stable therapeutic exposure. Metformin-treated horses were protected against early AF stabilization and sustained a less complex AF substrate in the right atrium after 4 months of disease. These protective effects were associated with increased right atrial activity of the metabolic regulator, AMPK (AMP-activated protein kinase), changes in metabolic pathways, and modulation of ion-channel gene expression.
conclusionsMetformin treatment conferred protection against early AF stabilization and selectively attenuated right atrial substrate complexity in a translationally relevant preclinical model. These findings support metformin as a lead molecule for AF prevention, warranting further mechanistic and clinical studies.
Indexed as
Anti-Arrhythmia AgentsAtrial FibrillationAtrial RemodelingHeart AtriaHeart RateMetforminAction PotentialsAMP-Activated Protein KinasesAnimalsDisease Models, AnimalHorsesMaleAMP-Activated Protein KinasesAnti-Arrhythmia AgentsMetforminanimalatrial remodelingelectrophysiologyhorsesmetforminmodels
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.
Metformin Protects Against Persistent Atrial Fibrillation in an Equine Model. · full record | OpenQuestion