br Study limitations Although the number of
Study limitations Although the number of CPVT patients enrolled in the present study was small, we documented clearly discernible effects of flecainide on CPVT during exercise testing. The dose of flecainide was adjusted to increase it to the maximum tolerable dose without monitoring serum concentrations. We studied the effects of flecainide in combination with conventional therapy in patients whose arrhythmias were uncontrolled on treatment with conventional therapy. The effect of flecainide was evaluated by exercise testing, as was done in previous studies, and the reproducibility of the effects of flecainide during exercise testing has been reported [7,15]. However, variability in exercise test results cannot be completely ignored and exercise testing may not accurately predict the occurrence of fatal arrhythmic events . Exercise testing prior to the initiation of conventional therapy was not performed for 2 patients whose severe arrhythmic events were easily induced. The aim of this study was to compare the efficacy of conventional therapy and the addition of flecainide on exercise-induced ventricular arrhythmias.
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Introduction Ventricular fibrillation (VF) is the most malignant arrhythmia that causes sudden cardiac death. VF, which occurs in apparently healthy individuals without structural Wnt-C59 cost diseases, is regarded as an idiopathic or primary electrical disease. Among patients with idiopathic VF (IVF), an increased prevalence of early repolarization (ER) was observed, which was considered as a benign electrocardiographic (ECG) finding in the past . Recently, the concept of J-wave syndrome (JWS), including the ER and Brugada (Br) syndromes, has emerged . The mutation KCNJ8-S422L was first identified as the cause of ER syndrome in a 14-year-old Caucasian girl with VF. An ECG showed a prominent ER pattern in the inferolateral leads . KCNJ8 encodes an inward rectifier potassium 6.1 protein (Kir6.1), which is a subunit of cardiac ATP-sensitive K (KATP) channels. The succeeding cases of the mutation were found in five men and two women with ER or Br syndrome [4,5]. However, whether KCNJ8 mutations are present among the Asian population remains to be known. Therefore, the present study aimed to investigate the prevalence of KCNJ8 gene mutation in Japanese patients with JWS or IVF.
Discussion We found no KCNJ8 mutations in our 230 Japanese JWS and/or IVF probands from unrelated families. JWS and Br syndromes are regarded as primary electrical disorders causing VF that occur in individuals without structural heart disease. Antzelevitch and Yan  proposed the concept of JWS, in which the fundamental mechanism of the J-point elevation is caused by an increased transient outward current (Ito) due to a decrease in sodium or calcium current or an increase in potassium current. Irrespective of ECG subtypes such as the ER, Br, or Br–ER pattern, increased Ito seems to play a central role in generating life-threatening events in patients with JWS . A KCNJ8 mutation, S422L, was identified in 6 probands and 1 family member with JWS [3–5]. The probands consisted of 4 Br syndrome and 2 ER patients. Functional analyses showed that this hotspot mutation increased the activity of cardiac ATP-sensitive K current (IK-ATP), which resulted in the AP notch accentuation in collaboration with epicardial Ito, and then caused a larger J-wave and/or ST-segment elevation on the patients\' ECGs. In our cohort, however, we failed to identify a KCNJ8 mutation. This finding may be related to the difference in ethnicities between Asian and Western countries. Recently, 2 novel KCNJ8 mutations, E322del and V346I, were reported in cases of sudden infant death syndrome . In the functional analysis, both mutations displayed a decrease in IK-ATP, which was opposite to the effect of S422L mutation on IK-ATP[4,5]. Therefore, JWS and sudden infant death syndrome seemed to have different underlying mechanisms, though having the same culprit gene, KCNJ8.