# HLS-Cardiac Safety AI Trained Human Heart and Micro Heart Model

> **NIH NIH R44** · INVIVOSCIENCES, INC. · 2020 · $861,204

## Abstract

HLS17-12. The US FDA is considering to establish a new cardiac safety assessment approach 
defined by a new paradigm called, “Comprehensive in vitro Proarrhythmia Assay (CIPA)”. The
CIPA will 1) assess drug effects on each cardiac ion channel type individually using a high-
throughput assay ion channel assays, 2) compute net effect on repolarization and risks for 
torsade pointes (TdP) using a mathematical model, and 3) confirm the computational prediction by
measuring the drug’s effects on action potentials in induced pluripotent stem cell (iPSC) derived
human cardiac myocytes (CMs). This paradigm shift, if successful, could reduce the cost of 
cardiac safety analyses by replacing or lowering the requirement to perform an expensive ($2-4
million) thorough QT study during clinical trials. Protecting consumers from drug induced 
arrhythmia and sudden deaths is a paramount importance for the regulators and pharmaceutical
companies as well as lowing the cost of drug development.
Many cardiac safety scientists, however, are skeptical about CIPA’s approach since CMs derived
from human iPSCs exhibit a poor excitation-contraction coupling due to their immaturity. In
addition, a proposed CIPA mathematical model was developed to simulate electrophysiology of
human adult CMs, so there is a mismatch between experimental system and computational tool.
To address these concerns, we proposed three specific aims in tw0 phases by following Fast-
Track SBIR processes. Phase I feasibility Aim 1 will measure drug-induced changes in AP and
CaT using human adult heart slices isolated from human donors. Here we will confirm our 
successful handling and analyzing human adult heart slices, which will be based on a recently 
published protocol by our collaborator, Dr. Igor Efimov, at George Washington University. After this
validation, we will move on to perform the following two studies: Aim 2. Compare drug-induced
changes in AP and CaT in NuHearts generated from adult CMs and cardiac fibroblasts from
same human donor hearts; Aim 3. Validate and improve the computational models and train an
artificial intelligence to predict cardiac safety risks of unknow compounds.
After our successful completion proposed projects, we can establish an unprecedented cardiac
safety assessment platform that can predict safety issues using a well-trained AI without doing
any experiments using human heart slices that are rarely accessible for most of the safety 
laboratories or biotech firms.

## Key facts

- **NIH application ID:** 9948757
- **Project number:** 5R44HL139248-03
- **Recipient organization:** INVIVOSCIENCES, INC.
- **Principal Investigator:** Tetsuro Wakatsuki
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $861,204
- **Award type:** 5
- **Project period:** 2019-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948757

## Citation

> US National Institutes of Health, RePORTER application 9948757, HLS-Cardiac Safety AI Trained Human Heart and Micro Heart Model (5R44HL139248-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948757. Licensed CC0.

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