@article {43086,
	title = {Validating the Arrhythmogenic Potential of High-, Intermediate-, and Low-Risk Drugs in a Human-Induced Pluripotent Stem Cell-Derived Cardiac Microphysiological System},
	journal = {ACS Pharmacology \& Translational Science},
	volume = {5},
	year = {2022},
	pages = {652{\textendash}667},
	publisher = {American Chemical Society},
	abstract = {Evaluation of arrhythmogenic drugs is required by regulatory agencies before any new compound can obtain market approval. Despite rigorous review, cardiac disorders remain the second most common cause for safety-related market withdrawal. On the other hand, false-positive preclinical findings prohibit potentially beneficial candidates from moving forward in the development pipeline. Complex\&nbsp;in vitro\&nbsp;models using cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) have been identified as a useful tool that allows for rapid and cost-efficient screening of proarrhythmic drug risk. Currently available hiPSC-CM models employ simple two-dimensional (2D) culture formats with limited structural and functional relevance to the human heart muscle. Here, we present the use of our 3D cardiac microphysiological system (MPS), composed of a hiPSC-derived heart micromuscle, as a platform for arrhythmia risk assessment. We employed two different hiPSC lines and tested seven drugs with known ion channel effects and known clinical risk: dofetilide and bepridil (high risk); amiodarone and terfenadine (intermediate risk); and nifedipine, mexiletine, and lidocaine (low risk). The cardiac MPS successfully predicted drug cardiotoxicity risks based on changes in action potential duration, beat waveform (i.e., shape), and occurrence of proarrhythmic events of healthy patient hiPSC lines in the absence of risk cofactors. We showcase examples where the cardiac MPS outperformed existing hiPSC-CM 2D models.},
	doi = {https://doi.org/10.1021/acsptsci.2c00088},
	url = {https://pubs.acs.org/doi/abs/10.1021/acsptsci.2c00088},
	author = {Charwat, Verena and Charrez, B{\'e}r{\'e}nice and Brian A. {Siemons} and Finsberg, Henrik and Karoline Horgmo {J{\ae}ger} and Andrew G {Edwards} and Huebsch, Nathaniel and Wall, Samuel and Miller, Evan and Tveito, Aslak and Kevin E. {Healy}}
}
@article {27952,
	title = {Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics},
	journal = {Frontiers in Pharmacology},
	volume = {12},
	year = {2021},
	pages = {684252},
	publisher = {Frontiers Media SA},
	doi = {10.3389/fphar.2021.684252},
	url = {doi.org/10.3389/fphar.2021.684252},
	author = {Charrez, B{\'e}r{\'e}nice and Charwat, Verena and Siemons, Brian and Goswami, Ishan and Sakolish, Courtney and Luo, Yu-Syuan and Finsberg, Henrik and Andrew G {Edwards} and Miller, Evan and Rusyn, Ivan and Healy, Kevin}
}
@article {27951,
	title = {In vitro safety {\textquotedblleft}clinical trial{\textquotedblright} of the cardiac liability of drug polytherapy},
	journal = {Clinical and Translational Science},
	volume = {14},
	year = {2021},
	month = {03/2021},
	pages = {1155-1165},
	publisher = {Wiley Online Library},
	doi = {https://doi.org/10.1111/cts.13038},
	url = {https://ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.13038},
	author = {Charrez, B{\'e}r{\'e}nice and Charwat, Verena and Siemons, Brian and Finsberg, Henrik and Miller, Evan and Andrew G {Edwards} and Kevin E. {Healy}}
}
@article {27665,
	title = {In Vitro Safety {\textquotedblleft}Clinical Trial{\textquotedblright} of the Cardiac Liability of Hydroxychloroquine and Azithromycin as COVID19 Polytherapy},
	journal = {Clinical Pharmacology \& Therapeutics},
	year = {2020},
	publisher = { Wiley},
	author = {Charrez, B{\'e}r{\'e}nice and Charwat, Verena and Siemons, Brian and Finsberg, Henrik and Miller, Evan and Andrew G {Edwards} and Kevin E. {Healy}}
}
