Abstract 2636: Age-Related Triggers for Life-Threatning Arrhythmia in the Genotyped Long QT Syndrome

OBJECTIVES We aimed to examine whether triggers for cardiac events are different depending on the age in genotyped and symptomatic long QT syndrome (LQTS) patients. BACKGROUND Patients with LQTS become symptomatic in adolescence, but some at age ≥20 y/o. It remains unknown whether clinical features of these symptomatic LQTS patients differ depending on the onset of age. METHODS Study cohort consisted of consecutive 108 symptomatic LQTS patients (34 males and 74 females from 88 families) who were identified to carry the following genotypes; LQT1 (n = 48), LQT2 (n = 52), LQT3 (n = 8). They were divided into 2 groups according to the age of their first onset of symptoms (low age <20 y/o, n = 75, average age = 10 y/o, and high age ≥20 y/o, n = 33, average age = 43 y/o), and triggers of their cardiac events (ventricular tachycardia, syncope or cardiac arrest) were analyzed. We divided the triggers into 3 categories: adrenergically-mediated factors; exercise, emotional stress, loud noise and arousal, vagally-mediated factors; rest/sleep, and secondary factors; drugs, hypokalemia, and bradycardia. RESULTS Percentage of patients with family history was significantly higher in the low age group (68% vs. 39%; p = 0.005), and prevalence of females and probands were significantly higher in the high age group (60% vs. 88%; p = 0.004, 75% vs. 97%; p = 0.006, respectively). There were no significant differences in both QTc intervals (523 ± 7 ms vs. 505 ± 10; p = 0.15) and Schwartz scores (6.3 ± 0.2 vs. 5.6 ± 0.3; p = 0.06) between the 2 groups. In the low age group, 76% of the cardiac events were initiated by adrenergically-mediated factors, and 20% were vagally mediated, but none was triggered by secondary factors. In contrast, in the high age group, 48% of the cardiac events were triggered by secondary factors, 12% adrenergically-mediated, and 18% vagally-mediated factors. The prevalence of secondary factors were as follows; 0/75 [0%] in low age vs. 16/33 [48%] in high age; p < 0.001. About the subdivision of secondary triggers on the genotype, hypokalemia was only observed in LQT1, drugs mainly in LQT2, and bradycardia only in LQT2. CONCLUSION Arrhythmic triggers in LQTS differ depending on the age of the patients, stressing the importance of age-related therapy for genotyped LQTS patients.

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Abstract 16509: Young Long QT Syndrome Patients With KCNH2 Mutations Have Late Onset but Severe Symptoms

Circulation ◽

10.1161/circ.130.suppl_2.16509 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Junichi Ozawa ◽

Seiko Ohno ◽

Hideki Itoh ◽

Takeru Makiyama ◽

Minoru Horie

Keyword(s):

Long Qt Syndrome ◽

Age Of Onset ◽

Late Onset ◽

Torsades De Pointes ◽

Preventive Therapy ◽

Cardiac Events ◽

Long Qt ◽

Mutation Carriers ◽

Age Related ◽

Qt Syndrome

Introduction: The long QT syndrome (LQTS) is one of the causes of sudden cardiac death in children. Although the risk factors for cardiac events depending on the genotype have been reported, age-related difference in phenotype remains unknown. Objectives: We aimed to clarify the age-and genotype-related clinical features in the young LQTS cohort (form 1 to 20y.o.). Methods and Results: This study comprised 101 symptomatic LQTS patients that were genotyped (male n=36, mean age 10.6±4.3). We excluded patients with multiple mutations. Fifty patients carried heterozygous mutations in KCNQ1, 48 in KCNH2 and 3 in SCN5A. LQTS-related cardiac events were classified into 3 categories; syncope, documented Torsades de pointes (TdP) and cardio-pulmonary arrest (CPA). Ninety patients experienced syncope, 7 were documented TdP and 4 suffered CPA. Figure shows a frequency histogram for the ages of first event in each genotype. The mean age of the onset in KCNH2 mutation carriers were significantly older (12.2±4.6y.o.) than those in KCNQ1 (9.2±3.5y.o., p<0.001). The numbers and mean ages of the patients suffered CPA were 1 in KCNQ1 (12y.o.), 2 in KCNH2 (10.5±3.5y.o.) and 1 in SCN5A (6y.o.). TdP was significantly more frequently documented in the patients with KCNH2 mutations (n=6, 13.7±3.3y.o.) than those with KCNQ1 mutations (n=1, 9y.o., p=0.029). Conclusion: In the young LQTS patients, therefore, KCNH2 mutation carriers showed a severer phenotype than those of KCNQ1, though their age of onset was older. These finding helped us to choose more appropriate preventive therapy depend on the age of onset and genotype.

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Faculty Opinions recommendation of Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717984108.793473300 ◽

2013 ◽

Author(s):

Robert Sheldon ◽

Tarek Hatoum

Keyword(s):

Long Qt Syndrome ◽

Cardiac Events ◽

Long Qt ◽

Life Threatening ◽

Qt Syndrome

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Who Is at Risk for Cardiac Events in Young Patients With Long QT Syndrome?

Circulation Journal ◽

10.1253/circj.67.1007 ◽

2003 ◽

Vol 67 (12) ◽

pp. 1007-1012 ◽

Cited By ~ 10

Author(s):

Masao Yoshinaga ◽

Masami Nagashima ◽

Toshimitsu Shibata ◽

Ichiro Niimura ◽

Mitsuo Kitada ◽

...

Keyword(s):

At Risk ◽

Long Qt Syndrome ◽

Young Patients ◽

Cardiac Events ◽

Long Qt ◽

Qt Syndrome

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Abstract 4669: Does Long-QT Syndrome Involve the Sinus Node?

Circulation ◽

10.1161/circ.118.suppl_18.s_928-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Vladimir Shusterman ◽

Jan Nemec ◽

Marie Buncova ◽

Bruce Winter ◽

Win-Kuang Shen ◽

...

Keyword(s):

Heart Rate ◽

Long Qt Syndrome ◽

High Frequency ◽

Cardiac Rhythm ◽

Sinus Node ◽

List Type ◽

High Frequency Power ◽

Long Qt ◽

Qt Syndrome ◽

Frequency Power

Background: The hallmark of Long QT Syndrome (LQTS) is a prolongation of the ventricular electrical action potential caused by mutations involving key cardiac ion channels on the surface membrane of ventricular myocytes. Different mutations are associated with specific modes of arrhythmia initiation and distinct changes in cardiac rhythm prior to these events. We hypothesized that some LQTS-causing mutations might involve the sinus node, leading to aberrations in cardiac rhythm. To test this hypothesis, we examined the features of cardiac rhythm in 23 genotyped patients with LQTS and 14 matched controls (C) using Holter ECG data (6hrs). Methods: QRS-complexes were identified using custom software and verified by an experienced ECG reader; series of sinus beats were extracted and gaps in time series were linearly interpolated. The mean, max, and min heart rate (HR), the time (SD, SDNN, SDANN, RMSSD, pNN50) and frequency-domain (Total (TP), Very low (VLF), Low (LF), High (HF) frequency powers, and LF/HF) indices of heart rate variability (HRV) were calculated in each 5-min interval and over the entire recording. The short-long-short irregularity was examined using the novel multiscale rhythmogenetic analysis (MRA), which quantifies changes in the HRV indices during the transition from one time-scale window to another. Results: The maximum heart rate was slower in LQTS than in C (101±13 and 119±19bpm, p=0.001). The high-frequency power (HF) was lower in LQTS than in C (80±76 and 113±58ms 2 , p<0.05). However, the short-term irregularity (quantified by the difference in RMSSD between the 75ms and 2000ms time scales) was 4 times greater in LQTS compared to C (p=0.003). Inclusion or exclusion of two patents who were on β-blockers did not change the results. Conclusions: LQTS is associated with specific changes in cardiac rhythm, including: diminished acceleration capacity, decreased high-frequency power, and enhanced short-long-short irregularity. This suggests that LQTS involves channel modifications in the sinus node, which might contribute to arrhythmogenesis. Rhythm characterization in genetic sub-types of LQTS might improve arrhythmia risk stratification in this heterogeneous patient population.

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The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1–3 According to Individuals’ Gender, Age, and QTc Intervals: A Network Meta-analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2020.579525 ◽

2020 ◽

Vol 11 ◽

Author(s):

Lu Han ◽

Fuxiang Liu ◽

Qing Li ◽

Tao Qing ◽

Zhenyu Zhai ◽

...

Keyword(s):

Long Qt Syndrome ◽

Clinical Evidence ◽

Beta Blockers ◽

Meta Analysis ◽

Cardiac Events ◽

Long Qt ◽

Confounding Variables ◽

Qt Syndrome ◽

The Relationship

Long QT syndrome (LQTS) is an arrhythmic heart disease caused by congenital genetic mutations, and results in increased occurrence rates of polymorphic ventricular tachyarrhythmias and sudden cardiac death (SCD). Clinical evidence from numerous previous studies suggested that beta blockers (BBs), including atenolol, propranolol, metoprolol, and nadolol, exhibit different efficacies for reducing the risk of cardiac events (CEs), such as syncope, arrest cardiac arrest (ACA), and SCD, in patients with LQTS. In this study, we identified relevant studies in MEDLINE, PubMed, embase, and Cochrane databases and performed a meta-analysis to assess the relationship between the rate of CEs and LQTS individuals with confounding variables, including different gender, age, and QTc intervals. Moreover, a network meta-analysis was not only established to evaluate the effectiveness of different BBs, but also to provide the ranked efficacies of BBs treatment for preventing the recurrence of CEs in LQT1 and LQT2 patients. In conclusion, nadolol was recommended as a relatively effective strategy for LQT2 in order to improve the prognosis of patients during a long follow-up period.

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