Multifocal ectopic Purkinje-related premature contractions: a new SCN5A-related cardiac channelopathy.
J Am Coll Cardiol
; 60(2): 144-56, 2012 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-22766342
ABSTRACT
OBJECTIVES:
The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease.BACKGROUND:
Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias.METHODS:
Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified.RESULTS:
Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine.CONCLUSIONS:
A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ramos Subendocárdicos
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Canales de Sodio
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Complejos Prematuros Ventriculares
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Infant
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Male
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Middle aged
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Newborn
Idioma:
En
Revista:
J Am Coll Cardiol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia