Modelling Long QT Syndrome With iPS Cells: Be Still, My Beating Heart …

Abstract

### Modeling the Long QT Syndrome With Induced Pluripotent Stem Cells Itzhaki et al Nature . Published Online 1/16/11. doi:10.1038/nature09747 ### Patient-Specific Induced Pluripotent Stem-Cell Models for Long-QT Syndrome Moretti et al N Engl J Med . 2010;363:1397–1409 Recent publications by Itzhaki et al1 and Moretti et al2 introduce the latest improvement for in vitro disease modelling of cardiac arrhythmias. iPS lines derived from patients with LTQ1 and LTQ2 can be differentiated into cardiomyocytes, showing the disease's characteristic electrophysiologic signature, establishing a convenient and powerful system for studying mechanisms of pathogenesis and testing therapeutic compounds. Long QT syndrome (LQTS) is characterized by prolonged QT interval on a surface electrocardiogram (ECG). Clinically, LQTS presents with sudden arrhythmia, which can lead to fainting or syncope and sudden death, typically in young or otherwise completely healthy individuals.3 The cardiac action potential is the consequence of the concerted function of many ion channels and involves ongoing cycles of depolarization followed by repolarization. In an ECG, the distance between the onset of Q to the end of the T waves (the QT interval) measures the time it takes for the heart to depolarize and repolarize in preparation for the next beat. A longer than normal QT interval can be caused by mutations in more than 10 potassium and sodium channels involved in cardiac electrophysiology. It can also be induced by certain medications, such as cisapride,1 haloperidol, or ziprasidone.4 The diagnosis can be problematic, as up to 2.5% of healthy individuals may show prolonged QT intervals, and up to 15% of mutation carriers may fail to show prolonged QT intervals in an electrocardiogram. A delay in the repolarization of the heart can lead to palpitations typically caused by ventricular arrhythmias, such as torsade de pointes and eventually to fainting or sudden …