Molecular Insights into the Short QT Syndrome

Short QT syndrome (SQTS) is a myocardial conduction disorder characterized by a short QT interval on electrocardiogram and predisposition to familial atrial fibrillation and/or sudden cardiac death. Genetic SQTS is primarily caused by one or more cardiac ion channelopathies, in which either impaired depolarization currents or enhanced repolarization currents shorten cardiac action potential duration. Given that QT interval duration is not always predictive of arrhythmia burden and risk of death in SQTS, there is a need to understand the molecular mechanisms of the condition to improve risk prognostication and potential pharmacologic treatment. In the last decade, several computational advances and in vitro preclinical studies have provided insight into the molecular mechanisms underlying congenital SQTS. In this review, we discuss recent findings in SQTS molecular mechanisms and correlate these advances with clinical guidelines for SQTS diagnosis and treatment.