ArticleFrontiers in physiology2021
Sex Differences in Drug-Induced Arrhythmogenesis.
Article in Frontiers in physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Sex-specific and polygenic effects underlying resting heart rate and associated risk of cardiovascular disease.European journal of preventive cardiology · 2024Pooled it
- Sex Matters: A Comprehensive Comparison of Female and Male Hearts.Frontiers in physiology · 2022Pooled it
- Unveiling sex dimorphism in the healthy cardiac anatomy: Fundamental differences between male and female heart shapes.The Journal of physiology · 2026Article
- Myth, Power and Practice: A Bourdieusian Interpretation of Greentown's Criminal Network.Behavioral sciences (Basel, Switzerland) · 2026Article
- Sex-specific virtual population for the prediction and assessment of arrhythmia risk.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Can in silico models predict drug-induced cardiac risk in vulnerable populations?Toxicology reports · 2026Article
- T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.Circulation research · 2026Article
- Effect of estrogen and testosterone on cardiac electrophysiology and atrial fibrillation.Heart rhythm O2 · 2026Review
- Full-field surrogate modeling of cardiac electrophysiology encoding geometric variability.Computer methods in applied mechanics and engineering · 2026Article
- Developing cardiac biomechanical models beyond the clinic: modeling stressors of daily life.Biomechanics and modeling in mechanobiology · 2025Review
- Heart in a knot: unraveling the impact of the nested tori myofiber architecture on ventricular mechanics.Biomechanics and modeling in mechanobiology · 2025Article
- Sex-specific human electromechanical multiscale in-silico models for virtual therapy evaluation.Journal of molecular and cellular cardiology plus · 2025Article
- Development and Clinical Validation of a Cross-Sex Translator of ECG Drug Responses.JACC. Clinical electrophysiology · 2025Article
- Cardiac digital twins: a tool to investigate the function and treatment of the diabetic heart.Cardiovascular diabetology · 2025Review
- Digital twin for sex-specific identification of class III antiarrhythmic drugs based on in vitro measurements, computer models, and machine learning tools.PLoS computational biology · 2025Article
- Anatomical-electrical coupling of cardiac axes: Definitions and population variability for advancing personalised ECG interpretation.PLoS computational biology · 2025Article
- Computational modelling for improved translation of cardiac inotropic and lusitropic drug effects from rats to humans.Journal of pharmacological and toxicological methods · 2025Article
- Developing cardiac digital twin populations powered by machine learning provides electrophysiological insights in conduction and repolarization.Nature cardiovascular research · 2025Article
- T-World: A highly general computational model of a human ventricular myocyte.bioRxiv : the preprint server for biology · 2025Article
- Predictive Analysis of Non-Cardiac Drug-Induced QTc Interval Prolongation: A Cross-Sectional Study.Clinical pharmacology : advances and applications · 2025Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The electrical activity in the heart varies significantly between men and women and results in a sex-specific response to drugs. Recent evidence suggests that women are more than twice as likely as men to develop drug-induced arrhythmia with potentially fatal consequences. Yet, the sex-specific differences in drug-induced arrhythmogenesis remain poorly understood. Here we integrate multiscale modeling and machine learning to gain mechanistic insight into the sex-specific origin of drug-induced cardiac arrhythmia at differing drug concentrations. To quantify critical drug concentrations in male and female hearts, we identify the most important ion channels that trigger male and female arrhythmogenesis, and create and train a sex-specific multi-fidelity arrhythmogenic risk classifier. Our study reveals that sex differences in ion channel activity, tissue conductivity, and heart dimensions trigger longer QT-intervals in women than in men. We quantify the critical drug concentration for dofetilide, a high risk drug, to be seven times lower for women than for men. Our results emphasize the importance of including sex as an independent biological variable in risk assessment during drug development. Acknowledging and understanding sex differences in drug safety evaluation is critical when developing novel therapeutic treatments on a personalized basis. The general trends of this study have significant implications on the development of safe and efficacious new drugs and the prescription of existing drugs in combination with other drugs.
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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 OpenQuestion graph.