Article

Efficacy of an implantable cardioverter-defibrillator in a neonate with LQT3 associated arrhythmias.

Department of Pediatric Cardiology, Erasmus MC-Sophia, 3015 GJ Rotterdam, The Netherlands.
Europace (impact factor: 1.98). 02/2005; 7(1):77-84. DOI:10.1016/j.eupc.2004.09.007
Source: PubMed

ABSTRACT We present a case in which LQTS induced severe prenatal and neonatal arrhythmias. LQT3 was diagnosed (mutation R1623Q). Short-acting beta-blockers were ineffective as well as sotalol and mexiletine in preventing recurrent ventricular arrhythmias. An ICD was implanted at the age of 7 months (weight and length of the infant at implantation 6 kg and 60 cm respectively). Flecainide was prescribed in addition to the ICD implantation. After an appropriate shock the flecainide plasma levels were shown to be subtherapeutic. Readjustment of the flecainide dose resulted in adequate plasma levels. No further shocks occurred during a further 17 months follow-up period. The combination of an active can with a subcutaneous patch proved feasible, and lifesaving shocks occurred at 7 months after implantation.

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    Article: A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic response.
    John R Bankston, Minerva Yue, Wendy Chung, Meghan Spyres, Robert H Pass, Eric Silver, Kevin J Sampson, Robert S Kass
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    ABSTRACT: SCN5A encodes the alpha-subunit (Na(v)1.5) of the principle Na(+) channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS) variant 3 (LQT-3) in adults by disrupting inactivation of the Na(v)1.5 channel. Pharmacological targeting of mutation-altered Na(+) channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS) and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults. Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C) discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na(+) channel blockers flecainide and mexiletine. Our goal was to determine the Na(+) channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na(+) channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C) and a common variant in KCNH2 (K897T). Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na(+) channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically. The results of our study provide further evidence of the grave vulnerability of newborns to Na(+) channel defects and suggest that both genetic background and age are particularly important in developing a mutation-specific therapeutic personalized approach to manage disorders in the young.
    PLoS ONE 02/2007; 2(12):e1258. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

60 cm respectively
 
adequate plasma levels
 
appropriate shock
 
feasible
 
Flecainide
 
flecainide dose
 
flecainide plasma levels
 
implantation 6 kg
 
lifesaving shocks
 
LQTS induced severe prenatal
 
mexiletine
 
neonatal arrhythmias
 
recurrent ventricular arrhythmias
 
shocks
 
Short-acting beta-blockers