Mutation location effect on severity of phenotype during exercise testing in type 1 long-QT syndrome: impact of transmembrane and C-loop location.
J Cardiovasc Electrophysiol
; 24(9): 1015-20, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23691991
ABSTRACT
BACKGROUND:
Targeted mutation site-specific differences have correlated C-loop missense mutations with worse outcomes and increased benefit of beta-blockers in LQT1. This observation has implicated the C-loop region as being mechanistically important in the altered response to sympathetic stimulation known to put patients with LQT1 at risk of syncope and sudden cardiac death.OBJECTIVE:
The objective of this study was to determine if there is mutation site-specific response to sympathetic stimulation and beta-blockers using exercise testing.METHODS:
This study is a retrospective review of LQT1 patients undergoing exercise testing at 3 academic referral centers.RESULTS:
A total of 123 patients (age 28 ± 17 years, 59 male) were studied including 34 patients (28%) with C-loop mutations. There were no significant differences in supine, standing, peak exercise and 1-minute recovery QTc duration between patients with C-loop mutations and patients with alternate mutation sites. In 37 patients that underwent testing on and off beta-blockers, beta-blocker use was associated with a significant reduction in supine, standing and peak exercise QTc. This difference was not seen in the small group of patients (7/37) with C-loop mutations. There was no difference in QTc at 1 and 4 minutes into recovery.CONCLUSIONS:
Genetically confirmed LQT1 patients in this study cohort with C-loop mutations did not demonstrate the expected increase in QTc in response to exercise, or resultant response to beta-blocker. The apparent increased risk of cardiac events associated with C-loop mutation sites and the marked benefit received from beta-blocker therapy are not reflected by exercise-mediated effects on QTc in this study population.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Mutação de Sentido Incorreto
/
Síndrome de Romano-Ward
/
Canal de Potássio KCNQ1
/
Teste de Esforço
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article