Arrhythmia phenotype during fetal life suggests long-QT syndrome genotype: risk stratification of perinatal long-QT syndrome.

Background Fetal arrhythmias characteristic of long QT syndrome (LQTS) include torsades de pointes (TdP) and/or 2 degrees 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: TdP2 degrees atrioventricular block (group 1, n=7), isolated 2 degrees 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.