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Korean J Physiol Pharmacol 2019; 23(5): 295-303

Published online September 1, 2019 https://doi.org/10.4196/kjpp.2019.23.5.295

Copyright © The Korean Journal of Physiology & Pharmacology.

Clinical and pharmacological application of multiscale multiphysics heart simulator, UT-Heart

Jun-ichi Okada1,2,*, Takumi Washio1,2, Seiryo Sugiura1, and Toshiaki Hisada1

1UT-Heart Inc., Tokyo 154-0003, 2Future Center Initiative, The University of Tokyo, Chiba 277-0871, Japan

Correspondence to:*Jun-ichi Okada, E-mail: okada@sml.k.u-tokyo.ac.jp

Received: July 10, 2019; Revised: August 2, 2019; Accepted: August 6, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A heart simulator, UT-Heart, is a finite element model of the human heart that can reproduce all the fundamental activities of the working heart, including propagation of excitation, contraction, and relaxation and generation of blood pressure and blood flow, based on the molecular aspects of the cardiac electrophysiology and excitation-contraction coupling. In this paper, we present a brief review of the practical use of UT-Heart. As an example, we focus on its application for predicting the effect of cardiac resynchronization therapy (CRT) and evaluating the proarrhythmic risk of drugs. Patient-specific, multiscale heart simulation successfully predicted the response to CRT by reproducing the complex pathophysiology of the heart. A proarrhythmic risk assessment system combining in vitro channel assays and in silico simulation of cardiac electrophysiology using UT-Heart successfully predicted drug-induced arrhythmogenic risk. The assessment system was found to be reliable and efficient. We also developed a comprehensive hazard map on the various combinations of ion channel inhibitors. This in silico electrocardiogram database (now freely available at http://ut-heart.com/) can facilitate proarrhythmic risk assessment without the need to perform computationally expensive heart simulation. Based on these results, we conclude that the heart simulator, UT-Heart, could be a useful tool in clinical medicine and drug discovery.

Keywords: Cardiac resynchronization therapy, Cardiotoxicity, Computer simulation, Drug evaluation, preclinical, Models, cardiovascular