Arrhythmia phenotype during fetal life suggests long-QT syndrome genotype: risk stratification of perinatal long-QT syndrome. Circ Arrhythm Electrophysiol 2013 Oct;6(5):946-51
Date
09/03/2013Pubmed ID
23995044Pubmed Central ID
PMC4151528DOI
10.1161/CIRCEP.113.000618Scopus ID
2-s2.0-84891539029 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
BACKGROUND: Fetal arrhythmias characteristic of long QT syndrome (LQTS) include torsades de pointes (TdP) and/or 2° atrioventricular block, but sinus bradycardia, defined as fetal heart rate<3% for gestational age, is most common. We hypothesized that prenatal rhythm phenotype might predict LQTS genotype and facilitate improved risk stratification and management.
METHOD AND RESULTS: Records of subjects exhibiting fetal LQTS arrhythmias were reviewed. Fetal echocardiograms, neonatal ECG, and genetic testing were evaluated. We studied 43 subjects exhibiting fetal LQTS arrhythmias: TdP±2° atrioventricular block (group 1, n=7), isolated 2° atrioventricular block (group 2, n=4), and sinus bradycardia (group 3, n=32). Mutations in known LQTS genes were found in 95% of subjects tested. SCN5A mutations occurred in 71% of group 1, whereas 91% of subjects with KCNQ1 mutations were in group 3. Small numbers of subjects with KCNH2 mutations (n=4) were scattered in all 3 groups. Age at presentation did not differ among groups, and most subjects (n=42) were live-born with gestational ages of 37.5±2.8 weeks (mean±SD). However, those with TdP were typically delivered earlier. Prenatal treatment in group 1 terminated (n=2) or improved (n=4) TdP. The neonatal heart rate-corrected QT interval (mean±SE) of group 1 (664.7±24.9) was longer than neonatal heart rate-corrected QT interval in both group 2 (491.2±27.6; P=0.004) and group 3 (483.1±13.7; P<0.001). Despite medical and pacemaker therapy, postnatal cardiac arrest (n=4) or sudden death (n=1) was common among subjects with fetal/neonatal TdP.
CONCLUSIONS: Rhythm phenotypes of fetal LQTS have genotype-suggestive features that, along with heart rate-corrected QT interval duration, may risk stratify perinatal management.
Author List
Cuneo BF, Etheridge SP, Horigome H, Sallee D, Moon-Grady A, Weng HY, Ackerman MJ, Benson DWMESH terms used to index this publication - Major topics in bold
Atrioventricular BlockBradycardia
ERG1 Potassium Channel
Echocardiography
Electrocardiography
Ether-A-Go-Go Potassium Channels
Female
Genetic Testing
Genotype
Heart Rate
Humans
Infant, Newborn
KCNQ1 Potassium Channel
Long QT Syndrome
Mutation
NAV1.5 Voltage-Gated Sodium Channel
Phenotype
Pregnancy
Pregnancy Outcome
Prenatal Diagnosis
Risk Assessment