Long QT Syndrome: A Case Report, Genomics, and Clinical Implications

Long QT syndrome (LQTS) is a hereditary disorder in which the majority of affected individuals present with QT prolongation on electrocardiograms (ECGs), arising from delayed ventricular repolarization. This commonly arrhythmia-associated genetic syndrome can lead to sudden cardiac death (SCD) and increased propensity for arrythmogenic syncope. The authors describe the case of a young patient who presented with episodes of syncope, prolonged QTc interval on ECG, and family history of SCD. He subsequently received an ICD for protection against SCD based on his prior clinical history. The article discusses the clinical manifestations, electrocardiographic (ECG) findings, management of LQTS, and role of the clinician in testing, teaching, and counseling the affected patients and families.

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Paediatric/young versus adult patients with long QT syndrome

Open Heart ◽

10.1136/openhrt-2021-001671 ◽

2021 ◽

Vol 8 (2) ◽

pp. e001671

Author(s):

Sharen Lee ◽

Jiandong Zhou ◽

Kamalan Jeevaratnam ◽

Wing Tak Wong ◽

Ian Chi Kei Wong ◽

...

Keyword(s):

Long Qt Syndrome ◽

Primary Outcome ◽

Population Based ◽

Public Hospitals ◽

Qtc Interval ◽

Onset Age ◽

Long Qt ◽

History Of ◽

Qt Syndrome ◽

Random Survival Forest

IntroductionLong QT syndrome (LQTS) is a less prevalent cardiac ion channelopathy than Brugada syndrome in Asia. The present study compared the outcomes between paediatric/young and adult LQTS patients.MethodsThis was a population-based retrospective cohort study of consecutive patients diagnosed with LQTS attending public hospitals in Hong Kong. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF).ResultsA total of 142 LQTS (mean onset age=27±23 years old) were included. Arrhythmias other than VT/VF (HR 4.67, 95% CI (1.53 to 14.3), p=0.007), initial VT/VF (HR=3.25 (95% CI 1.29 to 8.16), p=0.012) and Schwartz score (HR=1.90 (95% CI 1.11 to 3.26), p=0.020) were predictive of the primary outcome for the overall cohort, while arrhythmias other than VT/VF (HR=5.41 (95% CI 1.36 to 21.4), p=0.016) and Schwartz score (HR=4.67 (95% CI 1.48 to 14.7), p=0.009) were predictive for the adult subgroup (>25 years old; n=58). A random survival forest model identified initial VT/VF, Schwartz score, initial QTc interval, family history of LQTS, initially asymptomatic and arrhythmias other than VT/VF as the most important variables for risk prediction.ConclusionClinical and ECG presentation varies between the paediatric/young and adult LQTS population. Machine learning models achieved more accurate VT/VF prediction.

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The Long QT Syndrome: A Review and Mortality Analysis

Journal of Insurance Medicine ◽

10.17849/insm-45-02-081-087.1 ◽

2015 ◽

Vol 45 (2) ◽

pp. 81-87

Author(s):

Steven J. Rigatti

Keyword(s):

Mortality Risk ◽

Long Qt Syndrome ◽

Interval Length ◽

Qtc Interval ◽

Review Of Literature ◽

Long Qt ◽

Excess Death ◽

History Of ◽

Qt Syndrome ◽

Mortality Analysis

Objective To provide a recent review of literature pertinent to the assessment of life risk for individuals with a history of long QT syndrome (LQTS) and assess the mortality risk of a subset of these patients. Methods Standard comparative mortality techniques were employed to analyze relevant survival curves. Results Mortality risk in LQTS varies by age, sex, QTc interval length, genotype, and history of symptoms. A narrowly-defined subgroup of LQTS patients, those over age 20 with no history of syncope prior to age 20 and a QTc of less than 500ms, have an excess death rate of 0.5 – 2.0 per thousand per year. Conclusions Though the risk of sudden cardiac death in those with a history of long QT syndrome persists, there are subgroups of patients for whom the excess risk is lower than has been reported for this group of patients as a whole.

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1970–2020: 50 years of research on the long QT syndrome—from almost zero knowledge to precision medicine

European Heart Journal ◽

10.1093/eurheartj/ehaa769 ◽

2020 ◽

Author(s):

Peter J Schwartz

Keyword(s):

Long Qt Syndrome ◽

Clinical History ◽

Modifier Genes ◽

Phenotype Correlation ◽

Long Qt ◽

Medical Entity ◽

History Of ◽

Qt Syndrome ◽

Novel Therapeutic Strategies ◽

Do So

Abstract To those of us involved in clinical research it seldom happens to begin working on a rather obscure disease, still largely unexplored, and to follow its ripening into a medical entity of large interest to clinicians and basic scientists alike, and moreover to do so for exactly 50 years. This is what has been my privilege in the relentless pursuit of the intriguing disease known as the long QT syndrome (LQTS). This essay begins with the encounter with my first patient affected by LQTS when just a handful of cardiologists had seen similar cases and continues with the series of efforts, some sound some amateurish, which eventually led—together with many brilliant partners and associates—to describe and understand the natural history of the disease and the most effective therapies. It then touches on how our International Registry for LQTS, with its well-documented family trees, constituted the necessary springboard for the major genetic discoveries of the 1990s. From the explosion of genetic data, my own interest focused first on the intriguing genotype–phenotype correlation and then on ‘modifier genes’, in the attempt of understanding why family members with the same disease-causing mutation could have an opposite clinical history. And from there on to iPS-derived cardiomyocytes, used to unravelling the specific mechanisms of action of modifier genes and to exploring novel therapeutic strategies. This long, and highly rewarding, journey continues because the fascination and the attraction of the unknown are irresistible.

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Elucidating the role of Cavin1 in drug-induced long QT syndrome (diLQTS)

Archives of Cardiovascular Diseases Supplements ◽

10.1016/j.acvdsp.2021.04.195 ◽

2021 ◽

Vol 13 (2) ◽

pp. 228-229

Author(s):

Z. Al Sayed ◽

C. Pereira ◽

C. Jouve ◽

J. Hulot

Keyword(s):

Long Qt Syndrome ◽

Long Qt ◽

Drug Induced ◽

Qt Syndrome

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Computational Analysis of Coronary Blood Flow: The Role of Asynchronous Pacing and Arrhythmias

Mathematics ◽

10.3390/math8081205 ◽

2020 ◽

Vol 8 (8) ◽

pp. 1205

Author(s):

Timur Gamilov ◽

Philipp Kopylov ◽

Maria Serova ◽

Roman Syunyaev ◽

Andrey Pikunov ◽

...

Keyword(s):

Heart Rate ◽

Blood Flow ◽

Coronary Blood Flow ◽

Long Qt Syndrome ◽

Premature Ventricular Contraction ◽

Cardiac Pacing ◽

Long Qt ◽

Computational Evaluation ◽

Qt Syndrome

In this work we present a one-dimensional (1D) mathematical model of the coronary circulation and use it to study the effects of arrhythmias on coronary blood flow (CBF). Hydrodynamical models are rarely used to study arrhythmias’ effects on CBF. Our model accounts for action potential duration, which updates the length of systole depending on the heart rate. It also includes dependency of stroke volume on heart rate, which is based on clinical data. We apply the new methodology to the computational evaluation of CBF during interventricular asynchrony due to cardiac pacing and some types of arrhythmias including tachycardia, bradycardia, long QT syndrome and premature ventricular contraction (bigeminy, trigeminy, quadrigeminy). We find that CBF can be significantly affected by arrhythmias. CBF at rest (60 bpm) is 26% lower in LCA and 22% lower in RCA for long QT syndrome. During bigeminy, trigeminy and quadrigeminy, respectively, CBF decreases by 28%, 19% and 14% with respect to a healthy case.

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Paediatric/young versus adult patients with long QT syndrome or catecholaminergic polymorphic ventricular tachycardia

10.1101/2021.01.04.21249214 ◽

2021 ◽

Author(s):

Sharen Lee ◽

Jiandong Zhou ◽

Kamalan Jeevaratnam ◽

Wing Tak Wong ◽

Ian Chi Kei Wong ◽

...

Keyword(s):

Ventricular Tachycardia ◽

Long Qt Syndrome ◽

Primary Outcome ◽

Public Hospitals ◽

Adult Patients ◽

Polymorphic Ventricular Tachycardia ◽

Qtc Interval ◽

Long Qt ◽

Old Patients ◽

Qt Syndrome

AbstractIntroductionLong QT syndrome (LQTS) and catecholaminergic ventricular tachycardia (CPVT) are less prevalent cardiac ion channelopathies than Brugada syndrome in Asia. The present study compared paediatric/young and adult patients with these conditions.MethodsThis was a territory-wide retrospective cohort study of consecutive patients diagnosed with LQTS and CPVT attending public hospitals in Hong Kong. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF).ResultsA total of 142 LQTS (mean onset age= 27±23 years old) and 16 CPVT (mean presentation age=11±4 years old) patients were included. For LQTS, arrhythmias other than VT/VF (HR=4.67, 95% confidence interval=[1.53-14.3], p=0.007), initial VT/VF (HR=3.25 [1.29-8.16], p=0.012) and Schwartz score (HR=1.90 [1.11-3.26], p=0.020) were predictive of the primary outcome for the overall cohort, whilst arrhythmias other than VT/VF (HR=5.41 [1.36-21.4], p=0.016) and Schwartz score (HR=4.67 [1.48-14.7], p=0.009) were predictive for the adult subgroup (>25 years old; n=58). All CPVT patients presented before the age of 25 but no significant predictors of VT/VF were identified. A random survival forest model identified initial VT/VF, Schwartz score, initial QTc interval, family history of LQTS, initially asymptomatic, and arrhythmias other than VT/VF as the most important variables for risk prediction in LQTS, and initial VT/VF/sudden cardiac death, palpitations, QTc, initially symptomatic and heart rate in CPVT.ConclusionClinical and ECG presentation vary between the pediatric/young and adult LQTS population. All CPVT patients presented before the age of 25. Machine learning models achieved more accurate VT/VF prediction.

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The natural history of fetal long QT syndrome

Journal of Electrocardiology ◽

10.1016/j.jelectrocard.2016.07.023 ◽

2016 ◽

Vol 49 (6) ◽

pp. 807-813 ◽

Cited By ~ 11

Author(s):

Bettina F. Cuneo ◽

Janette F. Strasburger ◽

Ronald T. Wakai

Keyword(s):

Natural History ◽

Long Qt Syndrome ◽

Long Qt ◽

History Of ◽

Qt Syndrome

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ECG patterns related to arrhythmias and sudden death: channelopathies, early repolarization, and pre-excitation

ESC CardioMed ◽

10.1093/med/9780198784906.003.0074 ◽

2018 ◽

pp. 382-389

Author(s):

Wojciech Zareba ◽

Pyotr Platonov

Keyword(s):

Sudden Death ◽

Long Qt Syndrome ◽

Ventricular Arrhythmias ◽

Prior History ◽

Long Qt ◽

Early Repolarization ◽

Genes Encoding ◽

History Of ◽

Qt Syndrome ◽

Characteristic Features

Electrocardiogram (ECG) patterns recognized in patients with sudden death without structural abnormalities in the heart have guided cardiology over the last few decades towards a better understanding of the role of cardiac ion channels in physiology and in arrhythmogenicity in rare electrical diseases. The long QT syndrome became the paradigm for evaluating the association between specific ion channel abnormalities caused by mutations in genes encoding predominantly potassium and sodium channels and phenotypic ECG expression. Specific ECG patterns observed in long QT syndrome help in diagnosis and improve prognosis in patients affected by this disorder. Short QT syndrome also is characterized by specific patterns in repolarization morphology that relate to affected potassium current or calcium handling genes. Brugada syndrome and early repolarization syndrome are considered as J-wave syndromes, having some similarities in ECG features but with distinctive patterns associated with classical forms of these disorders. Spontaneous appearance of cove-type Brugada pattern is associated with a worse prognosis. Early repolarization patterns may also indicate prognosis in subjects with a prior history of cardiac arrest or ventricular arrhythmias or a family history of cardiac arrests. Catecholaminergic polymorphic ventricular tachycardia is another channelopathy without characteristic features in standard resting ECG but with characteristic polymorphic ventricular arrhythmias during catecholaminergic challenge (exercise test, stressing situations). Pre-excitation syndromes associated with sudden cardiac death are well recognized and current understanding of these disorders leads to a better therapy.

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Delayed diagnosis of long QT syndrome in a patient with seizures

Hong Kong Journal of Emergency Medicine ◽

10.1177/1024907918754921 ◽

2019 ◽

Vol 26 (3) ◽

pp. 190-193

Author(s):

Seung Yong Shin ◽

Jun Young Hong ◽

Dong Hoon Lee

Keyword(s):

Emergency Department ◽

Long Qt Syndrome ◽

Delayed Diagnosis ◽

Clinical Manifestations ◽

Initial Assessment ◽

Long Qt ◽

Prolonged Qt Interval ◽

Qt Syndrome ◽

Seizure Episode ◽

Diagnostic Work

Introduction: Long QT syndrome accompanied by a seizure episode is often misdiagnosed as primary epilepsy. Although patients with Long QT syndrome who are misdiagnosed and improperly managed are likely to result in fatality, their first clinical manifestations are seizure episodes in many cases. Case presentation: A 17-year-old boy visited the emergency department with poorly controlled seizure during epilepsy treatment was found to have been misdiagnosed with epilepsy when he was 7 years old. His electrocardiography showed a prolonged QT interval. After careful re-evaluation, he was finally diagnosed with Long QT syndrome and recovered without any seizure episodes in the absence of anti-epileptic agents. Discussion and conclusion: Careful initial assessment including repetitive electrocardiography, when abnormal, is required for those who visit the emergency department with a seizure or who show no definite abnormalities in diagnostic work up process.

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