The Substrate of Sudden Death in Long-QT Syndrome is localized in the Epicardium

ABSTRACT Despite significant advances in the prevention of cardiovascular diseases, sudden cardiac death (SCD) persists as a major public health problem. Among young and apparently healthy individuals, Long-QT syndrome (LQTS) represents a leading progenitor of SCD owing to fatal ventricular arrhythmia. Scientific understanding of this association has grown in recent years, and the mortality rate after LQTS diagnosis has significantly decreased. However, despite medical treatment advances, life-threatening ventricular arrhythmias still occur. Until now, no research has established the degree to which this inherited condition arises from an underlying arrhythmogenic electroanatomical substrate. Here, we present direct evidence showing that LQTS patients who survive spontaneous malignant arrhythmias harbor structural electrophysiological abnormalities localized in the epicardium of the right ventricle. We further show that the elimination of these abnormalities by means of catheter ablation successfully suppresses malignant arrhythmias, offering a new approach for the effective treatment of LQTS patients.