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The European High Performance Computing Joint Undertaking (EuroHPC JU)

Human In-silico Clinical Trials to assess Drug-induced Arrhythmic Risk

Awarded Resources (in core hours)
Vega CPU
System Partition
1 July 2022 - 30 June 2023
Allocation Period

Drug cardiotoxicity is a major health issue due to the need to develop new safe and efficient drugs in a fast manner.

It is also a difficult problem when drugs are repurposed to treat new diseases in emergency situations, as was the case of hydroxychloroquine and azithromycin during the Covid-19 crisis. Currently, quantification of the cardiac safety of any new drug is part of the preclinical stages of the drug development pipeline.

Therefore, it is assessed after a compound is fully developed. About 50% of drugs were called off the market between 1994 and 2006. Regulatory bodies are incorporating in-silico assessment of cardiotoxicity using mathematical models of the cardiomyocyte.

These models provide markers that correlate to the proarrhythmic risk observed clinically, but not to the clinical measurable data. This single cell approach does not consider the complexity of the heart.

This work proposal aims to complete the validation and uncertainty quantification of a novel HPC methodology capable of reproducing the drug-induced arrhythmic risk in a human heart population. The methodology is based on highly detailed finite element models that reproduce the electrophysiological behaviour of the human ventricles observed in a normal human population and considers the gender-specific known differences.