ArticlePLoS computational biology2021
Computational prediction of drug response in short QT syndrome type 1 based on measurements of compound effect in stem cell-derived cardiomyocytes.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- In silico modelling of multi-electrode arrays for enhancing cardiac drug testing on hiPSC-CM heterogeneous tissues.The Journal of physiology · 2026Article
- Determining properties of human-induced pluripotent stem cell-derived cardiomyocytes using spatially resolved electromechanical metrics.The Journal of physiology · 2026Article
- Drug Proarrhythmic Evaluation in a High Throughput Cardiac New Approach Methodology.bioRxiv : the preprint server for biology · 2026Article
- Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.PLoS computational biology · 2024Article
- The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity.International journal of molecular sciences · 2024Review
- The simplified Kirchhoff network model (SKNM): a cell-based reaction-diffusion model of excitable tissue.Scientific reports · 2023Article
- Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings.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 · 2023Article
- Computational analysis of arrhythmogenesis in KCNH2 T618I mutation-associated short QT syndrome and the pharmacological effects of quinidine and sotalol.NPJ systems biology and applications · 2022Article
- Arrhythmogenic influence of mutations in a myocyte-based computational model of the pulmonary vein sleeve.Scientific reports · 2022Article
- Article
- A computational method for identifying an optimal combination of existing drugs to repair the action potentials of SQT1 ventricular myocytes.PLoS computational biology · 2021Article
- Effects of Antiarrhythmic Drugs on hERG Gating in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Short QT (SQT) syndrome is a genetic cardiac disorder characterized by an abbreviated QT interval of the patient's electrocardiogram. The syndrome is associated with increased risk of arrhythmia and sudden cardiac death and can arise from a number of ion channel mutations. Cardiomyocytes derived from induced pluripotent stem cells generated from SQT patients (SQT hiPSC-CMs) provide promising platforms for testing pharmacological treatments directly in human cardiac cells exhibiting mutations specific for the syndrome. However, a difficulty is posed by the relative immaturity of hiPSC-CMs, with the possibility that drug effects observed in SQT hiPSC-CMs could be very different from the corresponding drug effect in vivo. In this paper, we apply a multistep computational procedure for translating measured drug effects from these cells to human QT response. This process first detects drug effects on individual ion channels based on measurements of SQT hiPSC-CMs and then uses these results to estimate the drug effects on ventricular action potentials and QT intervals of adult SQT patients. We find that the procedure is able to identify IC50 values in line with measured values for the four drugs quinidine, ivabradine, ajmaline and mexiletine. In addition, the predicted effect of quinidine on the adult QT interval is in good agreement with measured effects of quinidine for adult patients. Consequently, the computational procedure appears to be a useful tool for helping predicting adult drug responses from pure in vitro measurements of patient derived cell lines.
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