Computational models in cardiology

SA Niederer, J Lumens, NA Trayanova - Nature reviews cardiology, 2019 - nature.com
The treatment of individual patients in cardiology practice increasingly relies on advanced
imaging, genetic screening and devices. As the amount of imaging and other diagnostic …

Evolution of strategies to improve preclinical cardiac safety testing

G Gintant, PT Sager, N Stockbridge - Nature reviews Drug discovery, 2016 - nature.com
The early and efficient assessment of cardiac safety liabilities is essential to confidently
advance novel drug candidates. This article discusses evolving mechanistically based …

Discovery of asciminib (ABL001), an allosteric inhibitor of the tyrosine kinase activity of BCR-ABL1

J Schoepfer, W Jahnke, G Berellini, S Buonamici… - 2018 - ACS Publications
Chronic myelogenous leukemia (CML) arises from the constitutive activity of the BCR-ABL1
oncoprotein. Tyrosine kinase inhibitors (TKIs) that target the ATP-binding site have …

Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity

E Passini, OJ Britton, HR Lu, J Rohrbacher… - Frontiers in …, 2017 - frontiersin.org
Early prediction of cardiotoxicity is critical for drug development. Current animal models
raise ethical and translational questions, and have limited accuracy in clinical risk prediction …

[HTML][HTML] The immature electrophysiological phenotype of iPSC-CMs still hampers in vitro drug screening: Special focus on IK1

B Goversen, MAG van der Heyden… - Pharmacology & …, 2018 - Elsevier
Preclinical drug screens are not based on human physiology, possibly complicating
predictions on cardiotoxicity. Drug screening can be humanised with in vitro assays using …

Calibration of ionic and cellular cardiac electrophysiology models

DG Whittaker, M Clerx, CL Lei… - … Systems Biology and …, 2020 - Wiley Online Library
Cardiac electrophysiology models are among the most mature and well‐studied
mathematical models of biological systems. This maturity is bringing new challenges as …

Optimization of an In silico Cardiac Cell Model for Proarrhythmia Risk Assessment

S Dutta, KC Chang, KA Beattie, J Sheng… - Frontiers in …, 2017 - frontiersin.org
Drug-induced Torsade-de-Pointes (TdP) has been responsible for the withdrawal of many
drugs from the market and is therefore of major concern to global regulatory agencies and …

Human induced pluripotent stem cell (hiPSC)-derived cells to assess drug cardiotoxicity: opportunities and problems

T Magdy, AJT Schuldt, JC Wu… - Annual review of …, 2018 - annualreviews.org
Billions of US dollars are invested every year by the pharmaceutical industry in drug
development, with the aim of introducing new drugs that are effective and have minimal side …

[HTML][HTML] Uncertainty and variability in models of the cardiac action potential: Can we build trustworthy models?

RH Johnstone, ETY Chang, R Bardenet… - Journal of molecular and …, 2016 - Elsevier
Cardiac electrophysiology models have been developed for over 50 years, and now include
detailed descriptions of individual ion currents and sub-cellular calcium handling. It is …

Modeling the electrophysiological properties of the infarct border zone

C Mendonca Costa, G Plank, CA Rinaldi… - Frontiers in …, 2018 - frontiersin.org
Ventricular arrhythmias (VA) in patients with myocardial infarction (MI) are thought to be
associated with structural and electrophysiological remodeling within the infarct border zone …