In utero diagnosis of long QT syndrome by magnetocardiography.
BACKGROUND
The electrophysiology of long QT syndrome (LQTS) in utero is virtually unstudied. Our goal here was to evaluate the efficacy of fetal magnetocardiography (fMCG) for diagnosis and prognosis of fetuses at risk of LQTS.


RESULTS
We reviewed the pre/postnatal medical records of 30 fetuses referred for fMCG because of a family history of LQTS (n=17); neonatal/childhood sudden cardiac death (n=3), or presentation of prenatal LQTS rhythms (n=12): 2° atrioventricular block, ventricular tachycardia, heart rate < 3(rd) percentile. We evaluated heart rate and reactivity, cardiac time intervals, T-wave characteristics, and initiation/termination of Torsade de Pointes, and compared these with neonatal ECG findings. After birth, subjects were tested for LQTS mutations. Based on accepted clinical criteria, 21 subjects (70%; 9 KCNQ1, 5 KCNH2, 2 SCN5A, 2 other, 3 untested) had LQTS. Using a threshold of corrected QT= 490 ms, fMCG accurately identified LQTS fetuses with 89% (24/27) sensitivity and 89% (8/9) specificity in 36 sessions. Four fetuses (2 KCNH2 and 2 SCN5A), all with corrected QT ≥ 620 ms, had frequent episodes of Torsade de Pointes, which were present 22-79% of the time. Although some episodes initiated with a long-short sequence, most initiations showed QRS aberrancy and a notable lack of pause dependency. T-wave alternans was strongly associated with severe LQTS phenotype.


CONCLUSIONS
Corrected QT prolongation (≥490 ms) assessed by fMCG accurately identified LQTS in utero; extreme corrected QT prolongation (≥620 ms) predicted Torsade de Pointes. FMCG can play a critical role in the diagnosis and management of fetuses at risk of LQTS.
Department of Pediatrics, Children's Hospital of Colorado, University of Colorado School of Medicine, Denver (B.F.C.); Division of Cardiology, Department of Pediatrics, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee (J.F.S.); Department of Medical Physics, University of Wisconsin-Madison, (S.Y., R.T.W.); Department of Child Health, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan (H.H.); Department of Biomedical Engineering, Osaka Electro-Communication University, Osaka, Japan (T.H.); and Central Research Laboratory, Hitachi, Ltd, Tokyo, Japan (A.K.).
Bettina F
BF
Cuneo
Janette F
JF
Strasburger
Suhong
S
Yu
Hitoshi
H
Horigome
Takayoshi
T
Hosono
Akihiko
A
Kandori
Ronald T
RT
Wakai
D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D056726:Genetic Association Studies; D006340:Heart Rate, Fetal; D006801:Humans; D007231:Infant, Newborn; D008012:Lidocaine / Q000627:therapeutic use; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D053798:Magnetocardiography / Q000379:methods*; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012032:Refractory Period, Electrophysiological; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016171:Torsades de Pointes / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine
alternan; arrhythmias, cardiac; fetus; long QT syndrome; magnetocardiography; torsades de pointes