Congenital Heart And Pediatric Electrophysiology

Diagnostic accuracy of the 12-lead electrocardiogram in the first 48 hours of life for newborns of a parent with congenital long QT syndrome. Perez Y, Tobert K, Saunders M, Sorensen K, Bos M, Ackerman M. Heart Rhythm. 2022 June; 19(6): 969-974. doi: 10.1016/j.hrthm.2022.01.041.   Take Home Points: This study looked at the accuracy of ECGs in the first 48 hours of life in diagnosing LQTS in neonates born to a parent with LQTS. Using a recommended QTc threshold of ≥ 440 ms, the ECG is 88% sensitive but only 29% specific, resulting in significant overdiagnosis. Confirmatory variant-specific, cascade genetic testing should be initiated before discharge to ensure the most accurate diagnosis in this at-risk population. Commentary by Dr. Roberto G. Gallotti (Seattle, USA), Congenital and Pediatric Cardiac EP section editor   Congenital long QT syndrome (LQTS) affects ~ 1 in 2000 persons, with the majority of LQTS caused by pathogenic variants in KNCQ1, KCNH2, and SCN5A. The pattern of inheritance is typically autosomal dominant, where a single variant is inherited from one of the parents, meaning there is a 50% probability of inheriting a disease-causative variant.   The optimal timing for ECG screening in newborn infants remains contested with differing opinions with regards to when it should occur. This study sought to elucidate the diagnostic accuracy of ECGs obtained in the first 48 hours of life to correctly identify LQTS in neonates born to a genotype-positive parent.   This was a retrospective review that included infants with at least one LQTS genotype-positive parent, ECG performed within the first 48 hours of life, and LQTS genetic testing results available. A total of 74 newborns (36 female [49%]) were included, among whom 23 (46%) had LQT1 (KCNQ1), 15 (30%) had LQT2 (KCNH2), 8 (16%) had LQT3 (SCN5A) and 4 had multiple LQTS-associated pathogenic variants. The remaining 24 (32%) had negative genetic testing for the parent’s LQTS variant.   Among the genotype-positive newborns, the QTc mean was 506 ± 52 ms versus 455 ± 41 ms in the genotype-negative cohort (see distribution table below). The large overlap in QTc values highlights the challenge of making the diagnosis of LQTS by ECG alone in this population.     Analysis using a QTc cutoff of 440, 450, 460 and 470 ms was performed (see below). The most notable finding was that using a standard cutoff of 440 ms (previously validated as the 97.5th percentile in 4-day old newborns), ECG alone to diagnose LQTS had a positive-predictive value of 72% and negative-predictive value of 54%. In other words, among 50 genotype positive newborns, 6 (12%) would have been missed (underdiagnosed; false-negative), and among 24 genotype negative newborns, 17 (71%) would have been wrongly diagnosed with LQTS (overdiagnosed; false positive).     Conclusions The present study demonstrates the challenge of using the ECG alone to diagnose LQTS in a cohort of newborns who have a 50% pretest probability of having a disease-causative genetic variant. The QTc interval varies significantly in the first week of life and regardless of the adopted QTc cutoff, the newborn ECG will have a relatively high sensitivity but low specificity.   The authors highlight the importance of confirmatory variant-specific, cascade genetic testing to ensure the most accurate diagnosis in this at-risk population. They also emphasize that universal ECG screening is not recommended and would only lead to a higher number of misdiagnoses given the low prevalence of disease.   Lastly, the authors propose the below alogithm for the evaluation of newborns suspected for long QT syndrome. In their experienced practice, they allow the newborn to bond with their mother and do no transfer to a monitored unit unless there are other obstetrical or medical indications to do so.