Evidence map›Paper›PMID 41944014›Full record

ArticleCirculation research2026

T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.

Jakub Tomek, Maxx Holmes, Thomas Bury, Marketa Tomkova, Heeseung Jo, Norbert Nagy, Ambre Bertrand, Alfonso Bueno-Orovio, Michael A Colman, Blanca Rodriguez and 2 more

Abstract readValidation Study
In one paragraph

Article in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Jakub TomekDepartment of Anatomy, Physiology and Genetics (J.T., H.J.), University of Oxford, United Kingdom.ORCID 0000-0002-0157-4386
Maxx HolmesDepartment of Computer Science (M.H., A.B., A.B.-O., B.R.), University of Oxford, United Kingdom.
Thomas BuryDepartment of Physiology, McGill University, Montreal, CA (T.B.).
Marketa TomkovaLudwig Cancer Research (M.T.), University of Oxford, United Kingdom.ORCID 0000-0001-9094-2365
Heeseung JoDepartment of Anatomy, Physiology and Genetics (J.T., H.J.), University of Oxford, United Kingdom.ORCID 0009-0006-5080-2310
Norbert NagyDepartment of Pharmacology and Pharmacotherapy, University of Szeged, Hungary (N.N.).ORCID 0000-0002-4557-8442
Ambre BertrandDepartment of Computer Science (M.H., A.B., A.B.-O., B.R.), University of Oxford, United Kingdom.ORCID 0000-0001-5116-6463
Alfonso Bueno-OrovioDepartment of Computer Science (M.H., A.B., A.B.-O., B.R.), University of Oxford, United Kingdom.ORCID 0000-0002-1634-3601
Michael A ColmanSchool of Biomedical Sciences, University of Leeds, United Kingdom (M.A.C.).ORCID 0000-0003-2817-8508
Blanca RodriguezDepartment of Computer Science (M.H., A.B., A.B.-O., B.R.), University of Oxford, United Kingdom.ORCID 0000-0001-6361-3339
Donald M BersDepartment of Pharmacology, University of California, Davis (J.T., D.M.B.).ORCID 0000-0002-2237-9483
Jordi HeijmanGottfried Schatz Research Center, Division of Medical Physics and Biophysics, Medical University of Graz, Austria (J.H.).ORCID 0000-0002-1418-108X

Funding

Pathophysiological Regulation of Cardiac Myocyte RyR ChannelR01HL092097 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Donald M Bers, Robyn T Rebbeck · 2010 to 2026
$9.3M
NHLBI NIH HHS R01 HL092097
6 · The paper itself

Abstract

backgroundCardiovascular disease is the leading global cause of morbidity and mortality. New technologies are needed to improve mechanistic understanding and inform therapeutic strategies. Human-centric cardiac simulations show great promise; however, existing cellular models can reproduce only a few arrhythmia-driving behaviors and show important discrepancies with experimental data. We aimed to develop a new model overcoming this lack of generality, which markedly limits the predictivity and translational utility of virtual cardiomyocytes.

methodsWe developed T-World, a novel virtual human cardiomyocyte, using data-driven differential equations to describe sex-specific excitation-contraction coupling, mechanical contraction, β-adrenergic signaling, and its effects on cellular targets. The model contains several key innovations, including a new approach to coupling L-type calcium channels and ryanodine receptors, with updated calcium-dependent-inactivation of the former and novel calcium-induced refractoriness and complete reparameterization of the latter. We also redeveloped the sodium-potassium pump and made major improvements to the sodium-calcium exchanger formulation.

resultsT-World shows broad agreement with experimental data on rate-dependent action potential (AP), calcium handling, and contraction properties. Extensively validated on independent data, T-World demonstrates strong predictive performance, for example, in drug-induced AP changes. The model reproduces the effects of sympathetic stimulation, including AP duration shortening and increased calcium-transient amplitude and contractility. Importantly, it recapitulates for the first time all key cellular mechanisms driving life-threatening arrhythmias (early and delayed afterdepolarizations, alternans, and steep S1-S2 restitution), including experimentally observed responses to interventions such as sympathetic activation, SERCA (sarco/endoplasmic reticulum Ca

conclusionsT-World is a highly general and predictive open-source computer model of a human ventricular cardiomyocyte, suitable for multiscale research studies investigating determinants of arrhythmogenesis.

Indexed as

Arrhythmias, CardiacComputer SimulationModels, CardiovascularMyocytes, CardiacAction PotentialsCalcium Channels, L-TypeCalcium SignalingExcitation Contraction CouplingFemaleHumansMaleMyocardial ContractionRyanodine Receptor Calcium Release ChannelSodium-Calcium ExchangerCalcium Channels, L-TypeRyanodine Receptor Calcium Release ChannelSodium-Calcium Exchangeraction potentialsarrhythmias, cardiaccardiovascular diseasesmorbiditymyocytes, cardiac

Identifiers

PMID41944014
PMCPMC13152079

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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 OpenQuestion graph.