shugangzhang / lqt1

Code for our paper "Multiscale virtual heart reveals the mechanism of KCNQ1-linked long QT syndrome and the therapeutic potential of gene therapy"

LQT1

This repository contains codes for our paper "Multiscale virtual heart reveals the mechanism of KCNQ1-linked long QT syndrome and the therapeutic potential of gene therapy".

Brief Introduction

Long QT syndrome (LQTS) is a highly dangerous cardiac disorder that can lead to life-threatening arrhythmias such as Torsades de Pointes (TdP). However, knowledge regarding its underlying pathogenesis remains extremely insufficient due to the natural complexity arises from the multiple biological levels involved in LQTS. We conceive this study to answer two basic questions:

1. How does a molecular-level change finally evolve into an organ-level event?
2. How does the lethal arrhythmia occur spontaneously in LQT patients?

It is difficult to answer these two questions by leveraging conventional experimental means. In contrast, in this study, we develop a multiscale virtual heart that ranges from subcellular level to three-dimensional (3D) organ level, by which we are able to conduct in silico experiments to reveal how the gene mutation finally evolves into “electrical storms” in the heart. Several key factors, such as the β-adrenergic stimulation and the “MCELL island”, are analyzed thoroughly in this study. Besides, an advanced gene therapy that may provide useful treatments is also investigated.

Simulation results

Development of ventricular arrhythmias in LQT1 patients:

Movie_S3_withISO_BCL500.mp4

Please refer to our paper fore more details: "Multiscale virtual heart reveals the mechanism of KCNQ1-linked long QT syndrome and the therapeutic potential of gene therapy"