Ana Rahma Yuniarti, Aroli Marcellinus, Ali Ikhsanul Qauli, Ki Moo Lim
The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative positions in silico simulations as essential tools for cardiac safety assessment. While single-cell simulations reveal ionic perturbations, they under-represent tissue-scale conduction, electrotonic coupling, and spatial heterogeneity that shape organ-level arrhythmogenesis. Investigate whether a multiscale classifier that combines a single-cell biomarker (qNet) with an organ-level metric (simulated QT) improves Torsades de Pointes (TdP) risk stratification over either biomarker alone. Twenty-eight CiPA drugs were simulated at 1–4×Cmax. We derived Avg. qNet from single-cell simulations (2,000 IC50–h samples × 4 concentrations) and Avg. QT from 3D tissue simulations (median parameters). Ordinal Logistic Regression (OLR) models were evaluated under split-sample (12/16) and full-set (28) analyses. Avg. qNet outperformed Avg. QT. Adding Avg. QT to Avg. qNet provided no material gain across AUC, ordinal calibration, likelihood ratios (LR±), and error rates, with only a small improvement for identifying high-risk drugs in the full-set analysis. Within this framework and dataset, ECG-derived QT is insufficient as a standalone predictor of tissue-level arrhythmogenicity; Avg. qNet is a robust primary biomarker, and the multiscale (Avg. qNet + Avg. QT) model offers at most incremental benefit. Multiscale gains will likely require ECG features that capture conduction/dispersion and larger, more diverse cohorts. © Korean Society of Medical and Biological Engineering 2025.
Department of IT Convergence Engineering, Kumoh National Institute of Technology, Gyeongsangbuk, Gumi, South Korea; Department of Computer Engineering, Universitas Pendidikan Indonesia, West Java, Bandung, Indonesia; Faculty of Advanced Technology and Multidiscipline, Department of Engineering, Universitas Airlangga, Surabaya, East Java, Indonesia; Department of Biomedical Engineering, Kumoh National Institute of Technology, Gyeongsangbuk, Gumi, South Korea; Meta Heart Inc, Gyeongsangbuk, Gumi, South Korea
Research at a Glance
Register to unlock
Topics & SDG Alignment
Register to unlock
Collaboration
Register to unlock
Author Profile (Selected)
Register to unlock
References Overview
Register to unlock
Journal & Source
Register to unlock
Metadata & Integrity
Register to unlock