Evidence Hub

Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators

Dominguez-Gomez P, Zingaro A, Baldo-Canut L, Balzotti C, Darpo B, Morton C, Vázquez M, Aguado-Sierra J

NPJ digital medicine, 2024

9 citations

Abstract

In silico trials for drug safety assessment require many high-fidelity 3D cardiac simulations to predict drug-induced QT interval prolongation, which is often computationally prohibitive. To streamline this process, we developed sex-specific emulators for a fast prediction of QT interval, trained on a dataset of 900 simulations. Our results show significant differences between 3D and 0D single-cell models as risk levels increase, underscoring the ability of 3D modeling to capture more complex cardiac responses. The emulators demonstrated an average error of 4% compared to simulations, allowing for efficient global sensitivity analysis and fast replication of in silico clinical trials. This approach enables rapid, multi-dose drug testing on standard hardware, addressing critical industry challenges around trial design, assay variability, and cost-effective safety evaluations. By integrating these emulators into drug development, we can improve preclinical reliability and advance the practical application of digital twins in biomedicine.

Read the paper

Related studies

Go deeper in Evidence Hub

Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.

Open this study Sign up free