What Is the Best Age for Diagnostic Prediction of Pediatric Long-QT Syndrome With a Borderline QT Interval?

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 10, No. 4What Is the Best Age for Diagnostic Prediction of Pediatric Long-QT Syndrome With a Borderline QT Interval? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBWhat Is the Best Age for Diagnostic Prediction of Pediatric Long-QT Syndrome With a Borderline QT Interval? Aya Miyazaki, MD and Hiraku Doi, MD Aya MiyazakiAya Miyazaki From the Department of Pediatrics (A.M., H.D.) and Congenital Heart Disease Center (H.D.), Tenri Hospital, Nara, Japan. and Hiraku DoiHiraku Doi From the Department of Pediatrics (A.M., H.D.) and Congenital Heart Disease Center (H.D.), Tenri Hospital, Nara, Japan. Originally published29 Mar 2017https://doi.org/10.1161/CIRCEP.117.005119Circulation: Arrhythmia and Electrophysiology. 2017;10:e005119ECGs for long-QT syndrome (LQTS) with borderline long-QT intervals can be troublesome because of the absence of a gold standard diagnostic criterion. The approach to diagnose children with borderline long-QT intervals is undefined, and there is no clarity on whether they should be followed up. There is concern that timely diagnosis and treatment may not be achieved for children with true LQTS who are at risk of sudden death. In the international LQTS registry study, the 5-year cumulative probability of aborted cardiac arrest or sudden cardiac death in children and adolescents with a QTc of <500 ms with and without a history of syncope was reported to be 11% and 1%, respectively.1See Article by Vink et alIn Japan, there is a nationwide school-based ECG screening program for heart diseases for all first, seventh, and 10th graders (ages 6–7, 12–13, and 15–16 years, respectively).2,3 In this program, the detection range for a long-QT interval is a QTc of ≥450 ms at a heart rate of <75 beats per minute and ≥500 ms at a heart rate of ≥75 beats per minute. Moreover, age- and sex-specific criteria are evaluated using Fridericia formula.4 With this system, the probability of diagnosing LQTS was reported to be 1:3298 (0.3/1000) in first graders and 1:1080 (0.93/1000) in seventh graders, based on criteria of the Heart Rhythm Society, European Heart Rhythm Association, and Asia Pacific Heart Rhythm Society expert consensus statement.2,5 Details of the criteria specified in the Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society expert consensus statement indicate that patients with an LQTS risk score of ≥3.5 points and a QTc of ≥500 ms can be diagnosed with asymptomatic LQTs.5 Patients with QTc of 480 to 499 ms can be diagnosed only when they have a history of syncope. How can we predict true LQTS in children with QTc of 480 to 499 ms but without unexpected syncope and in those with QTc of <480 ms with or without syncope?The evaluation of 59 school children (ages 5–18 years) showed the difficulty in detecting LQTS among patients with borderline long-QT intervals.6 The mean QTc of these children with borderline long-QT intervals (400≤QTc<500 ms) was 471±18 ms, and 90% were asymptomatic at diagnosis, when they initially presented hospitals at the median age of 12.4 years (5.3–18 years). Patients were classified into 3 groups according to the LQTS score7 at initial presentation: low probability of LQTS group (n=10), intermediate probability group (n=29), and high probability group (n=20). Syncope, but neither aborted cardiac arrest nor sudden cardiac death, occurred in 2 patients during follow-up (6±3.4 years) with LQTS scores of ≥4.5 points. Genetic testing was positive in 92%, 57%, and 67% of patients with high, intermediate, and low probabilities of LQTS, respectively. Furthermore, QTc at rest and at recovery point after exercise stress test dramatically changed at the last follow-up. Consequently, the probability of LQTS changed in half of the patients. Among 31 female patients, 6 (19%) showed higher probability of LQTS at the last follow-up than that at the initial presentation, and 11 (35%) showed lower probability. Among 17 male patients, only 1 (6%) showed higher probability at the last follow-up than at initial presentation and 6 (35%) showed lower probability.The LQTS score varies with age because the QTc interval changes with age. The rate of probability of diagnosing LQTS was >3× higher in seventh graders (age, 12–13 years) than in first graders (age, 6–7 years).2 For detection of true LQTS among children with borderline long-QT intervals, it is possible that the age at evaluation is an important factor.Vink et al8 showed that trend curves of the QTc interval from birth to adolescence in type 1 (LQT1) and type 2 (LQT2) varies with sex.8 The mean QT of 224 subjects in their study was only 451±39 ms, lower than the score in the above-mentioned study6; 95% had no symptoms at the presentation with a median age of 8 years (3–14 years). Eleven patients (5%) showed cardiac events during follow-up. And then, they presented that the age range of 12 to 14 years was an important transitional period where differences between males and females for both genotypes were seen. Both LQT1 and LQT2 males showed significant QTc interval, shortening after the onset of puberty, whereas age had lesser influence in LQT1 and LQT2 females than in males. Interestingly, the trend curves of the QTc interval for Dutch healthy controls intersected with those of LQT1 and LQT2 males, which overlapped at the age range 17 to 20 years. This indicates that the QTc intervals of healthy controls were higher than those of LQT1 and LQT2 patients during 17 to 20 years.In boys, the period immediately before the onset of puberty, at age ≈10 years, might be the best time to predict LQTS with borderline long-QT intervals, and in girls, at the onset of puberty, at the age of 12 to 14 years. This assumption was supported by the fact that in a Japanese school-based ECG screening program, the probability of diagnosing LQTS in seventh graders (age, 12–13 years) was higher than that in first graders (age, 6–7 years).2 Unfortunately, 88% of the patients in the study by Vink et al8 were administered β-blockers during follow-up. If we could evaluate the natural trends of QTc in LQTS without medication, we would gain more detailed information on the differences in QTc intervals between healthy controls and patients with LQTS.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Aya Miyazaki, MD, Department of Pediatrics, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632–8552, Japan. E-mail [email protected]References1. 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Effect of age and sex on the QTc interval in children and adolescents with type 1 and 2 long-QT syndrome.Circ Arrhythm Electrophysiol. 2017; 10:e004645. doi: 10.1161/CIRCEP.116.004645.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Popa-Fotea N, Cojocaru C, Scafa-Udriste A, Micheu M and Dorobantu M (2020) The Multifaced Perspectives of Genetic Testing in Pediatric Cardiomyopathies and Channelopathies, Journal of Clinical Medicine, 10.3390/jcm9072111, 9:7, (2111) April 2017Vol 10, Issue 4 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.117.005119PMID: 28356308 Originally publishedMarch 29, 2017 Keywordsdeath, sudden, cardiacelectrocardiographypediatriclong QT syndromeheart rateEditorialsPDF download Advertisement SubjectsArrhythmiasElectrocardiology (ECG)