ArticleMethods in molecular biology (Clifton, N.J.)2024
HPC Framework for Performing in Silico Trials Using a 3D Virtual Human Cardiac Population as Means to Assess Drug-Induced Arrhythmic Risk.
Article in Methods in molecular biology (Clifton, N.J.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Can in silico models predict drug-induced cardiac risk in vulnerable populations?Toxicology reports · 2026Article
- Developing cardiac biomechanical models beyond the clinic: modeling stressors of daily life.Biomechanics and modeling in mechanobiology · 2025Review
- Digital twins in healthcare: a comprehensive review and future directions.Frontiers in digital health · 2025Review
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators.NPJ digital medicine · 2024Article
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Authors and funding
12 authors.
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Abstract
Following the 3 R's principles of animal research-replacement, reduction, and refinement-a high-performance computational framework was produced to generate a platform to perform human cardiac in-silico clinical trials as means to assess the pro-arrhythmic risk after the administrations of one or combination of two potentially arrhythmic drugs. The drugs assessed in this study were hydroxychloroquine and azithromycin. The framework employs electrophysiology simulations on high-resolution three-dimensional, biventricular human heart anatomies including phenotypic variabilities, so as to determine if differential QT-prolongation responds to drugs as observed clinically. These simulations also reproduce sex-specific ionic channel characteristics. The derived changes in the pseudo-electrocardiograms, calcium concentrations, as well as activation patterns within 3D geometries were evaluated for signs of induced arrhythmia. The virtual subjects could be evaluated at two different cycle lengths: at a normal heart rate and at a heart rate associated with stress as means to analyze the proarrhythmic risks after the administrations of hydroxychloroquine and azithromycin. Additionally, a series of experiments performed on reanimated swine hearts utilizing Visible Heart
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