SCN5A mutation is associated with early and frequent recurrence of ventricular fibrillation in patients with Brugada syndrome.
BACKGROUND
Mutations in SCN5A are reportedly linked to Brugada syndrome (BS), but recent observations suggest that they are not necessarily associated with ventricular fibrillation (VF) in BS patients. Therefore, the clinical importance of SCN5A mutations in BS patients was examined in the present study.


RESULTS
The 108 BS patients were examined for SCN5A mutations and various parameters were compared between patients with and without mutations. An implantable cardioverter defibrillator (ICD) was implanted in 49 patients and a predictor of appropriate ICD shock was investigated. The existence of a SCN5A mutation was not associated with initial VF episodes (21.7% vs 20.0%, P=0.373). In the secondary prevention group, appropriate shock-free survival rate was significantly lower in patients with spontaneous type 1 ECG than in those without (41.1% vs 85.7% at 2 years, P=0.014). The appropriate shock-free survival rate was also significantly lower in patients with SCN5A mutations than in those without (28.6% vs 83.3% at 1 year, P=0.040). Appropriate shock was more frequent in patients with SCN5A mutations than in those without (6.6±6.2 vs 1.7±3.0, P=0.007).


CONCLUSIONS
SCN5A mutations are associated with early and frequent VF recurrence, but not with initial VF episodes. This is the first report on the genotype-phenotype interaction and clinical significance of this mutation.
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. nnishii@md.okayama-u.ac.jp
Nobuhiro
N
Nishii
Masahiro
M
Ogawa
Hiroshi
H
Morita
Kazufumi
K
Nakamura
Kimikazu
K
Banba
Daiji
D
Miura
Naoko
N
Kumagai
Akira
A
Matsunaga
Hiroshi
H
Kawamura
Shigemi
S
Urakawa
Kohei
K
Miyaji
Masahiro
M
Nagai
Katsumasa
K
Satoh
Koji
K
Nakagawa
Masamichi
M
Tanaka
Shigeki
S
Hiramatsu
Takeshi
T
Tada
Masato
M
Murakami
Satoshi
S
Nagase
Kunihisa
K
Kohno
Kengo Fukushima
KF
Kusano
Keijiro
K
Saku
Tohru
T
Ohe
Hiroshi
H
Ito
D000328:Adult; D053840:Brugada Syndrome / Q000150:complications / Q000235:genetics / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D017147:Defibrillators, Implantable; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D012008:Recurrence; D012769:Shock / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics*; D015996:Survival Rate; D014693:Ventricular Fibrillation / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000503:physiopathology / Q000628:therapy
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels