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Efectos de la flecainida en pacientes con nueva mutación SCN5A: terapia específica de la mutación para el síndrome
J Benhorin1, R Taub, M Goldmit
1Department of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel. benhorin@md2.huji.ac.il
Circulation
|April 12, 2000
Resumen
El acetato de flecainida trató eficazmente el síndrome de intervalo QT largo causado por una mutación específica de SCN5A, a diferencia de la lidocaína. Este hallazgo es crucial para el desarrollo de terapias dirigidas para las variantes del síndrome de QT largo.
Área de la Ciencia:
- Cardiología Cardiología.
- Genética La genética.
- Farmacología Farmacología.
Sus antecedentes:
- El síndrome congénito de QT largo puede ser el resultado de mutaciones en el gen del canal de sodio cardíaco (SCN5A).
- Algunas mutaciones de SCN5A responden a los fármacos antiarrítmicos tipo Ib.
- Una nueva mutación de SCN5A (D1790G) sugiere que los bloqueadores de tipo Ib pueden ser ineficaces.
Objetivo del estudio:
- Para evaluar la eficacia del acetato de flecainida, un bloqueador de sodio tipo Ic, en individuos con la mutación D1790G SCN5A.
- Para comparar los efectos del acetato de flecainida y la lidocaína en portadores de la mutación.
Principales métodos:
- Se estudiaron 8 portadores asintomáticos de la mutación SCN5A D1790G y 5 sujetos de control.
- La lidocaína y el acetato de flecainida administrados por vía intravenosa.
- Parámetros del electrocardiograma (ECG) monitoreado, incluidos el QT (c) y la compensación S al intervalo de inicio T.
Principales resultados:
- La lidocaína no mostró ningún efecto significativo en los parámetros del ECG en los dos portadores de la mutación probados.
- El acetato de flecainida acortó significativamente la duración de la repolarización corregida por la frecuencia cardíaca (QT (c) y la compensación de S a T) en los portadores de la mutación, pero no en los controles.
- Flecainide normalizó la dispersión de repolarización y los efectos se mantuvieron durante el tratamiento a largo plazo sin eventos adversos.
Conclusiones:
- Este estudio es el primero en demostrar una respuesta significativa al acetato de flecainida en portadores de la mutación SCN5A que no responden a la lidocaína.
- Estos hallazgos resaltan la importancia de las estrategias terapéuticas específicas de alelos para el síndrome del intervalo QT largo.
- El acetato de flecainida representa una opción terapéutica potencial para los pacientes con esta mutación específica de SCN5A.
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