No abstract

No abstract

No abstract

DT was not performed in a third of ICD implants, usually due to a perceived lack of need or relative contraindication.

782J -wave syndromes refer to a spectrum of ECG observations characterized by early ST-segment takeoff from the terminal QRS or J-point.1,2 The associated QRS segment may demonstrate terminal slurring, representing a J wave concealed within the QRS complex, or present a more distinctly visible notch representing a J wave. Brugada syndrome is the most well-characterized J-wave syndrome, both in terms of clinical and genetic features. Alternative patterns of J-wave syndromes have long been recognized, commonly involving the inferolateral ECG leads and until recent years were considered a benign ECG pattern. 3-8 Clinical Perspective on p 789In 2008, Haïssaguerre and colleagues 9 challenged the concept that inferolateral patterns of J-wave syndromes are a benign entity, reporting a higher prevalence of inferolateral J waves in previously well individuals experiencing a sudden cardiac arrest. Further data corroborated the observation that inferolateral J-wave ECG patterns are prevalent in 20% to 30% of survivors of unexplained cardiac arrest, which is considerably higher than that found in healthy controls. 10,11The electrophysiological mechanism underlying the manifestation of J waves on the ECG has been elegantly demonstrated using ventricular wedge preparations and has been shown to be the result of transmural dispersion of the early repolarizing current, the transient outward current (I to ), which Background-J-wave ECG patterns are associated with an increased risk of sudden arrhythmic death, and experimental evidence supports a transient outward current (I to )-mediated mechanism of J-wave formation. This study aimed to determine the frequency of genetic mutations in genes encoding the I to in patients with J waves on ECG. Methods and Results-Comprehensive mutational analysis was performed on I to -encoding KCNA4, KCND2, and KCND3 genes, as well as the previously described J-wave-associated KCNJ8 gene, in 51 unrelated patients with ECG evidence defining a J-wave syndrome. Only patients with a resuscitated cardiac arrest or type 1 Brugada ECG pattern were included for analysis. A rare genetic mutation of the KCND2 gene, p.D612N, was identified in a single patient. Co-expression of mutant and wild-type KCND2 with KChIP2 in HEK293 cells demonstrated a gain-of-function phenotype, including an increase in peak I to density of 48% (P<0.05) in the heterozygous state. Using computer modeling, this increase in I to resulted in loss of the epicardial action potential dome, predicting an increased ventricular transmural I to gradient. The previously described KCNJ8-S422L mutation was not identified in this cohort of patients with ECG evidence of J-wave syndrome. Conclusions-These findings are the first to implicate the KCND2 gene as a novel cause of J-wave syndrome associated with sudden cardiac arrest. However, genetic defects in I to -encoding genes seem to be an uncommon cause of sudden cardiac arrest in patients with apparent J-wave syndromes. (Circ Cardiovasc Genet. 2014;7:782-789.)