Individualized corrected QT interval is superior to QT interval corrected using the Bazett formula in predicting mutation carriage in families with long QT syndrome

Background: Long-QT syndrome (LQTS) is characterized by a prolonged heart rate–corrected QT interval (QTc). Genome-wide association studies identified common genetic variants that collectively explain ≈8% to 10% of QTc variation in the general population. Methods: Overall, 423 patients with LQT1, LQT2, or LQT3 were genotyped for 61 QTc-associated genetic variants used in a prototype QTc–polygenic risk score (QTc-PRS). A weighted QTc-PRS (range, 0–154.8 ms) was calculated for each patient, and the FHS (Framingham Heart Study) population-based reference cohort (n=853). Results: The average QTc-PRS in LQTS was 88.0±7.2 and explained only ≈2.0% of the QTc variability. The QTc-PRS in LQTS probands (n=137; 89.3±6.8) was significantly greater than both FHS controls (87.2±7.4, difference-in-means±SE: 2.1±0.7, P <0.002) and LQTS genotype-positive family members (87.5±7.4, difference-in-mean, 1.8±.7, P <0.009). There was no difference in QTc-PRS between symptomatic (n=156, 88.6±7.3) and asymptomatic patients (n=267; 87.7±7.2, difference-in-mean, 0.9±0.7, P=0.15). LQTS patients with a QTc≥480 ms (n=120) had a significantly higher QTc-PRS (89.3±6.7) than patients with a QTc<480 ms (n=303, 87.6±7.4, difference-in-mean, 1.7±0.8, P <0.05). There was no difference in QTc-PRS or QTc between genotypes. Conclusions: The QTc-PRS explained <2% of the QTc variability in our LQT1, LQT2, and LQT3 cohort, contributing 5× less to their QTc value than in the general population. This prototype QTc-PRS does not distinguish/predict the clinical outcomes of individuals with LQTS.

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Instability of ventricular repolarization in long QT syndrome: Is the corrected QT interval sufficient for risk assessment?

Heart Rhythm ◽

10.1016/j.hrthm.2013.05.022 ◽

2013 ◽

Vol 10 (8) ◽

pp. 1176-1177

Author(s):

Ilan Goldenberg ◽

Alon Barsheshet

Keyword(s):

Risk Assessment ◽

Long Qt Syndrome ◽

Qt Interval ◽

Ventricular Repolarization ◽

Long Qt ◽

Corrected Qt Interval ◽

Qt Syndrome

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Age-Gender Influence on the Rate-Corrected QT Interval and the QT-Heart Rate Relation in Families With Genotypically Characterized Long QT Syndrome

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(96)00454-8 ◽

1997 ◽

Vol 29 (1) ◽

pp. 93-99 ◽

Cited By ~ 118

Author(s):

Michael H Lehmann ◽

Katherine W Timothy ◽

Debra Frankovich ◽

Barbara S Fromm ◽

Mark Keating ◽

...

Keyword(s):

Heart Rate ◽

Long Qt Syndrome ◽

Qt Interval ◽

Long Qt ◽

Corrected Qt Interval ◽

Gender Influence ◽

Qt Syndrome ◽

Rate Relation

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Long QT syndrome in children: the value of the rate corrected QT interval in children who present with fainting

Journal of Medical Screening ◽

10.1136/jms.8.4.178 ◽

2001 ◽

Vol 8 (4) ◽

pp. 178-182 ◽

Cited By ~ 5

Author(s):

W.C. Allan ◽

K. Timothy ◽

G.M. Vincent ◽

G.E. Palomaki ◽

L.M. Neveux ◽

...

Keyword(s):

Long Qt Syndrome ◽

False Positive ◽

Qt Interval ◽

False Positives ◽

Long Qt ◽

Corrected Qt Interval ◽

History Of ◽

Qt Syndrome

OBJECTIVE:A strategy was evaluated for identifying a proportion of children with long QT syndrome (LQTS) using the rate corrected QT interval (QTc) to systematically evaluate children who faint. METHODS:QTc measurements and rates of fainting for the present analysis are available from families with KVLQT1, HERG, or SCN5A genotypes. QTc distributions in affected and unaffected children were documented and detection and false positive rates were modelled. RESULTS:The mean QTc (SD) in 117 affected children was 0.484 seconds (0.031), and 0.420 seconds (0.021) among 133 unaffected children. At a cut off of 0.49 seconds, QTc measurement will identify 42.5% of affected and 0.1% of unaffected persons with a history of fainting who are alive at the time of testing. Assumptions include a prevalence of 1:5000 for LQTS, 2% mortality with the first arrhythmia, and a rate of fainting of 50% in affected children and 7% in unaffected children. Given these variables, a QTc cut off of 0.49 seconds detects 42 of 200 affected, along with 70 unaffected children out of a population of 1 million. If QTc ≥0.49 seconds is found in either parent of children with a QTc of 0.44 through 0.48 seconds, another 21 affected and 25 unaffected children will be identified. CONCLUSION:Systematically performing QTc measurements as part of the evaluation of children who faint might optimally identify about one third of patients with LQTS with few false positives and thereby offer an opportunity to prevent some sudden deaths.

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Comparison of Corrected QT Interval as Measured on Electroencephalography Versus 12-Lead Electrocardiography in Children With a History of Syncope

Journal of Child Neurology ◽

10.1177/0883073811408421 ◽

2011 ◽

Vol 26 (11) ◽

pp. 1401-1404

Author(s):

Shavonne L. Massey ◽

Marshall S. Wise ◽

Nandini Madan ◽

Karen Carvalho ◽

Divya Khurana ◽

...

Keyword(s):

Retrospective Study ◽

Long Qt Syndrome ◽

Qt Interval ◽

Neurological Manifestations ◽

Long Qt ◽

Corrected Qt Interval ◽

History Of ◽

Qt Syndrome

Long QT syndrome can present with neurological manifestations, including syncope and seizure-like activity. These patients often receive an initial neurologic evaluation, including electroencephalography (EEG). Our previous retrospective study suggested an increased prevalence of prolonged corrected QT interval (QTc) measured during the EEG of patients with syncope. The aim of the current study is to assess the accuracy of the EEG QTc reading compared with the nonsimultaneous 12-lead electrocardiography (ECG) in children with syncope. Abnormal QTc was defined as ≥450 ms in boys, ≥460 ms in girls. Forty-two children were included. There was no significant correlation between QTc readings in the EEG and ECG. EEG failed to identify 2 children with prolonged QTc in the ECG and overestimated the QTc in 3 children with normal QTc in the ECG. This study suggests that interpretation of the QTc segment during an EEG is limited. Further studies with simultaneous EEG and 12-lead ECG are warranted.

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