ArticleHeart rhythm O22021
Quantifying arrhythmic long QT effects of hydroxychloroquine and azithromycin with whole-heart optical mapping and simulations.
Article in Heart rhythm O2, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Fast interactive simulations of cardiac electrical activity in anatomically accurate heart structures by compressing sparse uniform cartesian grids.Computer methods and programs in biomedicine · 2024Article
- HPC Framework for Performing in Silico Trials Using a 3D Virtual Human Cardiac Population as Means to Assess Drug-Induced Arrhythmic Risk.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Ephaptic Coupling as a Resolution to the Paradox of Action Potential Wave Speed and Discordant Alternans Spatial Scales in the Heart.Physical review letters · 2023Article
- Fiber Organization Has Little Effect on Electrical Activation Patterns During Focal Arrhythmias in the Left Atrium.IEEE transactions on bio-medical engineering · 2023Article
- Role of ephaptic coupling in discordant alternans domain sizes and action potential propagation in the heart.Physical review. E · 2023Article
- Article
- Robust, Automated Analysis of Electrophysiology in Induced Pluripotent Stem Cell-Derived Micro-Heart Muscle for Drug Toxicity.Tissue engineering. Part C, Methods · 2022Article
- Circle Method for Robust Estimation of Local Conduction Velocity High-Density Maps From Optical Mapping Data: Characterization of Radiofrequency Ablation Sites.Frontiers in physiology · 2022Article
- Methodology for Cross-Talk Elimination in Simultaneous Voltage and Calcium Optical Mapping Measurements With Semasbestic Wavelengths.Frontiers in physiology · 2022Article
- Chloroquine/Hydroxychloroquine Use and Suicide Risk: Hypotheses for Confluent Etiopathogenetic Mechanisms?Behavioral sciences (Basel, Switzerland) · 2021Article
- Interactive 3D Human Heart Simulations on Segmented Human MRI Hearts.Computing in cardiology · 2021Article
- Unimapper: An Online Interactive Analyzer/Visualizer of Optical Mapping Experimental Data.Computing in cardiology · 2021Article
- Not all Long-QTs Are The Same, Proarrhytmic Quantification with Action Potential Triangulation and Alternans.Computing in cardiology · 2021Article
- Fast Posterior Estimation of Cardiac Electrophysiological Model ParametersFrontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn March 2020, hydroxychloroquine (HCQ) alone or combined with azithromycin (AZM) was authorized as a treatment for COVID-19 in many countries. The therapy proved ineffective with long QT and deadly cardiac arrhythmia risks, illustrating challenges to determine the new safety profile of repurposed drugs.
objectiveTo investigate proarrhythmic effects and mechanism of HCQ and AZM (combined and alone) with high doses of HCQ as in the COVID-19 clinical trials.
methodsProarrhythmic effects of HCQ and AZM are quantified using optical mapping with voltage-sensitive dyes in ex vivo Langendorff-perfused guinea pig (GP) hearts and with numerical simulations of a GP Luo-Rudy and a human O'Hara-Virag-Varro-Rudy models, for Epi, Endo, and M cells, in cell and tissue, incorporating the drug's effect on cell membrane ionic currents.
resultsExperimentally, HCQ alone and combined with AZM leads to long QT intervals by prolonging the action potential duration and increased spatial dispersion of action potential (AP) repolarization across the heart, leading to proarrhythmic discordant alternans. AZM alone had a lesser arrhythmic effect with less triangulation of the AP shape. Mathematical cardiac models fail to reproduce most of the arrhythmic effects observed experimentally.
conclusionsDuring public health crises, the risks and benefits of new and repurposed drugs could be better assessed with alternative experimental and computational approaches to identify proarrhythmic mechanisms. Optical mapping is an effective framework suitable to investigate the drug's adverse effects on cardiac cell membrane ionic channels at the cellular level and arrhythmia mechanisms at the tissue and whole-organ level.
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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.