Global Sensitivity Analysis of Ventricular Myocyte Model-Derived Metrics for Proarrhythmic Risk Assessment.

ABSTRACT: Multiscale computational models of the heart are being extensively investigated for improved assessment of drug-induced torsades de pointes (TdP) risk, a fatal side effect of many drugs. Model-derived metrics such as action potential duration and net charge carried by ionic currents (qNet) have been proposed as potential candidates for TdP risk stratification after being tested on small datasets. Unlike purely statistical approaches, model-derived metrics are thought to provide mechanism-based classification. In particular, qNet has been recently proposed as a surrogate metric for early afterdepolarizations (EADs), which are known to be cellular triggers of TdP. Analysis of critical model components and of the ion channels that have major impact on model-derived metrics can lead to improve

SUBMITTER: Parikh J 

PROVIDER: S-EPMC6797832 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature