# A biophysical modeling approach for understanding arrhythmia mechanisms arising from remuscularization of the infarcted ventricles.

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2020 · $44,535

## Abstract

Project Summary
Persistent muscle deficiency following myocardial infarction (MI), attributable to the fact that the adult human
heart is one of the least regenerative organs, contributes to heart failure (HF) progression and its growing
prevalence worldwide. To-date, cardiology practice has been limited to managing HF progression and palliative.
Direct remuscularization, or the transplantation of cardiomyocytes, seeks to address post-MI muscle deficiency
by replacing lost or damaged heart muscle. Graft-induced ventricular tachycardias (VTs) remain a critical
concern, however. In several preclinical large animal studies, graft-induced VTs were widespread a week after
treatment; while most VTs revolved by 3 weeks, VT persisted in some animals. Why and how such high rates of
acute VT transiently occur in vivo while some persist remains a mystery. To explore this, I will implement a
recently developed modeling framework that can accurately represent the early process of electromechanical
engraftment and incorporate morphological and membrane kinetic differences between PSC-CMs and host
ventricular cardiomyocytes. I will test a novel hypothesis that graft-induced VTs are driven by a focal mechanism
during early engraftment but driven by a reentrant mechanism later on. To explore this, I will study how targeted
remuscularization with PSC-CMs alters the dynamics of VT and VT burden in whole, 3D models of the post-MI
ventricles. If cardiac arrhythmias can be addressed, targeted direct remuscularization holds the potential to
prevent the onset of HF but also treat post-MI reentrant VT.

## Key facts

- **NIH application ID:** 9991031
- **Project number:** 1F31HL152525-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Joseph Yu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $44,535
- **Award type:** 1
- **Project period:** 2020-06-01 → 2021-05-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991031

## Citation

> US National Institutes of Health, RePORTER application 9991031, A biophysical modeling approach for understanding arrhythmia mechanisms arising from remuscularization of the infarcted ventricles. (1F31HL152525-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9991031. Licensed CC0.

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