Ankyrin-2 variants associated with idiopathic ventricular fibrillation storm in patients with intermittent early repolarization pattern

Introduction Early repolarization (ER) is a common electrocardiographic finding and is diagnosed by the presence of a J-wave amplitude of Z0.1 mV in Z2 contiguous inferior or lateral leads of a standard 12-lead electrocardiogram (ECG), which is manifested as QRS slurring or notching. The ER pattern is observed in 1%–13% of cases in the general population and is mainly thought to be benign. However, Haïssaguerre et al have underlined the potential malignant role of an ER pattern in idiopathic ventricular fibrillation (VF) patients. Of 206 idiopathic VF cases and 412 controls, ER pattern was more frequently present in patients with idiopathic VF than in those in the control group (31% vs 5%). In addition, a population-based study from Finland including 10.864 middle-aged people found an ER pattern in 630 individuals leading to an increased risk of cardiac death. An ER pattern on the ECG in patients resuscitated from VF is called early repolarization syndrome (ErS). So far, variants in several ion-channel genes have been associated with ErS. Variants in KCNJ8 are associated with a gain of function with an increased outward potassium current, and variants in the subunits of the cardiac L-type calcium channel (CACNA1C, CACNB2, CACNA2D1) lead to a reduced inward calcium current. Finally, a variant in SCN5A causes a loss of function of the sodium channel, which leads to decreased inward sodium current.