Abstract 3091: The Clinical and Electrocardiographic Phenotype of Unrelated Patients with Genotype-Negative Long QT Syndrome

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Malek M El Yaman ◽  
David J Tester ◽  
Argelia Medeiros Domingo ◽  
Carla M Haglund ◽  
Michael J Ackerman
Keyword(s):  
Cardiac Arrest ◽  
Genetic Testing ◽  
Family History ◽  
Long Qt Syndrome ◽  
Susceptibility Genes ◽  
Long Qt ◽  
Diagnostic Score ◽  
Minor Genes ◽  
History Of ◽  
Qt Syndrome

Long QT syndrome (LQTS) is a heterogeneous group of channelopathies characterized by increased risk of potentially lethal ventricular arrhythmias. LQT1, LQT2, and LQT3 comprise 95% of genetically proven cases and exhibit a number of established genotype-phenotype correlations. The study aimed at examining the phenotypes of genotype-negative LQTS, accounting for ~25% of LQTS cases. An IRB-approved retrospective analysis was conducted on 56 patients (39 female, 25 ± 17 years) who, after genetic testing either in our sudden death genomics laboratory or with the commercially available Familion test, were negative for mutations in the 3 principal LQTS-susceptibility genes ( KCNQ1, KCNH2, and SCN5A), and the minor genes underlying LQT5 and LQT6. All had been diagnosed with LQTS, with a clinical diagnostic score of ≥ 3.5 or QTc ≥ 480 ms. The mean diagnostic score was 4.4 (95% CI 4.2 – 4.7); mean QTc was 525 ms (95% CI 508 – 543 ms). Two-thirds were symptomatic (syncope, cardiac arrest, and/or seizures) with exercise-triggered events in 10 (26%). Twenty-one (38%) had a family history of sudden cardiac arrest. ECG showed a T wave pattern suggestive of LQT1 in 32%, LQT2 in 43%, and LQT3 in 18%. In those with exercise-induced symptoms, the ECG was LQT2-like in 50% and LQT1-like in 30%. One patient had post-partum syncope with an LQT2-like ECG. None had an auditory trigger, but 3 patients, all with an LQT2-like ECG, had a family history of auditory-triggered events. One-third of the patients had received an ICD, 58% as secondary prevention. Over 2/3 were on beta-blockers. Among the 45 patients so far tested for mutations in minor LQTS-susceptibility genes, 2 had LQTS-causing mutations in ANKB (LQT4), 1 in SCN4B (LQT10), 1 in AKAP9 (LQT11) and 2 in SNTA1 (LQT12). Genotype-negative patients with a firm LQTS diagnosis show marked phenotypic heterogeneity, suggesting multiple underlying pathogenic pathways. Only a few patients have LQTS-causing mutations in minor genes after complete LQT1–12 genetic testing. Classifying genotype negative patients into LQT1-, LQT2-, or LQT3-like profiles may guide the discovery of novel genes encoding channel interacting proteins corresponding to those specific signaling pathways.

scholarly journals Prevalence and Spectrum of Large Deletions or Duplications in the Major Long QT Syndrome-Susceptibility Genes and Implications for Long QT Syndrome Genetic Testing

2010 ◽  
Vol 106 (8) ◽  
pp. 1124-1128 ◽  
Author(s):  
David J. Tester ◽  
Amber J. Benton ◽  
Laura Train ◽  
Barbara Deal ◽  
Linnea M. Baudhuin ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Long Qt Syndrome ◽  
Susceptibility Genes ◽  
Long Qt ◽  
Large Deletions ◽  
Qt Syndrome

scholarly journals Genetic variants associated with inherited cardiovascular disorders among 13,131 asymptomatic older adults of European descent

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Paul Lacaze ◽  
Robert Sebra ◽  
Moeen Riaz ◽  
Jodie Ingles ◽  
Jane Tiller ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Genetic Testing ◽  
Long Qt Syndrome ◽  
Polymorphic Ventricular Tachycardia ◽  
Prior History ◽  
Cardiovascular Disorders ◽  
Long Qt ◽  
History Of ◽  
Qt Syndrome

AbstractGenetic testing is used to optimise the management of inherited cardiovascular disorders that can cause sudden cardiac death. Yet more genotype–phenotype correlation studies from populations not ascertained on clinical symptoms or family history of disease are required to improve understanding of gene penetrance. We performed targeted sequencing of 25 genes used routinely in clinical genetic testing for inherited cardiovascular disorders in a population of 13,131 asymptomatic older individuals (mean age 75 years) enrolled in the ASPREE trial. Participants had no prior history of cardiovascular disease events, dementia or physical disability at enrolment. Variants were classified following ACMG/AMP standards. Sudden and rapid cardiac deaths were clinically adjudicated as ASPREE trial endpoints, and assessed during mean 4.7 years of follow-up. In total, 119 participants had pathogenic/deleterious variants in one of the 25 genes analysed (carrier rate of 1 in 110 or 0.9%). Participants carried variants associated with hypertrophic cardiomyopathy (N = 24), dilated cardiomyopathy (N = 29), arrhythmogenic right-ventricular cardiomyopathy (N = 22), catecholaminergic polymorphic ventricular tachycardia (N = 4), aortopathies (N = 1), and long-QT syndrome (N = 39). Among 119 carriers, two died from presumed sudden/rapid cardiac deaths during follow-up (1.7%); both with pathogenic variants in long-QT syndrome genes (KCNQ1, SCN5A). Among non-carriers, the rate of sudden/rapid cardiac deaths was significantly lower (0.08%, 11/12936, p < 0.001). Variants associated with inherited cardiovascular disorders are found in asymptomatic individuals aged 70 years and older without a history of cardiovascular disease.

Effect of clinical phenotype on yield of long QT syndrome genetic testing

Heart Rhythm ◽  
2005 ◽  
Vol 2 (5) ◽  
pp. S46 ◽  
Author(s):  
David J. Tester ◽  
Melissa L. Will ◽  
Carla M. Haglund ◽  
Michael J. Ackerman
Keyword(s):  
Genetic Testing ◽  
Long Qt Syndrome ◽  
Clinical Phenotype ◽  
Long Qt ◽  
Qt Syndrome

Endocrinopathies mimicking gene negative long QT syndrome

2021 ◽  
pp. 1-3
Author(s):  
Praloy Chakraborty ◽  
Jason D. Roberts ◽  
Michael H. Gollob
Keyword(s):  
Genetic Testing ◽  
Long Qt Syndrome ◽  
Qt Prolongation ◽  
Long Qt ◽  
Ventricular Repolarisation ◽  
Qt Syndrome ◽  
Hormonal Milieu

Abstract Ventricular repolarisation can be influenced by hormonal milieu which may mimic long QT syndrome. We describe a series of patients referred for genetic testing for diagnosed long QT syndrome where a detailed clinical workup demonstrated endocrinopathies as the cause of presumed “gene negative” long QT syndrome and QT prolongation.

scholarly journals Prolonged QTc: "Mind the Gap"

2014 ◽  
Vol 2 (1) ◽  
pp. 44-45
Author(s):  
Ahmad Mursel Anam ◽  
Raihan Rabbani ◽  
Farzana Shumy ◽  
M Mufizul Islam Polash ◽  
M Motiul Islam ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Long Qt Syndrome ◽  
Qt Interval ◽  
Torsades De Pointes ◽  
Junior Doctors ◽  
Long Qt ◽  
Acquired Long Qt Syndrome ◽  
Prolonged Qt Interval ◽  
Prolonged Qt ◽  
Qt Syndrome

We report a case of drug induced torsades de pointes, following acquired long QT syndrome. The patient got admitted for shock with acute abdomen. The initial prolonged QT-interval was missed, and a torsadogenic drug was introduced post-operatively. Patient developed torsades de pointes followed by cardiac arrest. She was managed well and discharged without complications. The clinical manifestations of long QT syndromes, syncope or cardiac arrest, result from torsades de pointes. As syncope or cardiac arrest have more common differential diagnoses, even the symptomatic long QT syndrome are commonly missed or misdiagnosed. In acquired long QT syndrome with no prior suggestive feature, it is not impossible to miss the prolonged QT-interval on the ECG tracing. We share our experience so that the clinicians, especially the junior doctors, will be more alert on checking the QT-interval even in asymptomatic patients. DOI: http://dx.doi.org/10.3329/bccj.v2i1.19970 Bangladesh Crit Care J March 2014; 2 (1): 44-45

scholarly journals Genetic testing for long QT syndrome and the category of cardiac ion channelopathies

PLoS Currents ◽  
2012 ◽  
Vol 4 ◽  
pp. e4f9995f69e6c7 ◽  
Author(s):  
Stephen M. Modell ◽  
David J. Bradley ◽  
Michael H. Lehmann
Keyword(s):  
Genetic Testing ◽  
Long Qt Syndrome ◽  
Long Qt ◽  
Qt Syndrome

scholarly journals Paediatric/young versus adult patients with long QT syndrome

Open Heart ◽  
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.

scholarly journals The natural history of fetal long QT syndrome

2016 ◽  
Vol 49 (6) ◽  
pp. 807-813 ◽  
Author(s):  
Bettina F. Cuneo ◽  
Janette F. Strasburger ◽  
Ronald T. Wakai
Keyword(s):  
Natural History ◽  
Long Qt Syndrome ◽  
Long Qt ◽  
History Of ◽  
Qt Syndrome

Preclinical short QT syndrome models: studying the phenotype and drug-screening

EP Europace ◽  
2021 ◽  
Author(s):  
Xuehui Fan ◽  
Guoqiang Yang ◽  
Jacqueline Kowitz ◽  
Firat Duru ◽  
Ardan M Saguner ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Family History ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Experimental Models ◽  
Short Qt Syndrome ◽  
Pathophysiological Mechanisms ◽  
History Of ◽  
Qt Syndrome ◽  
European Society Of Cardiology

Abstract Cardiovascular diseases are the main cause of sudden cardiac death (SCD) in developed and developing countries. Inherited cardiac channelopathies are linked to 5–10% of SCDs, mainly in the young. Short QT syndrome (SQTS) is a rare inherited channelopathy, which leads to both atrial and ventricular tachyarrhythmias, syncope, and even SCD. International European Society of Cardiology guidelines include as diagnostic criteria: (i) QTc ≤ 340 ms on electrocardiogram, (ii) QTc ≤ 360 ms plus one of the follwing, an affected short QT syndrome pathogenic gene mutation, or family history of SQTS, or aborted cardiac arrest, or family history of cardiac arrest in the young. However, further evaluation of the QTc ranges seems to be required, which might be possible by assembling large short QT cohorts and considering genetic screening of the newly described pathogenic mutations. Since the mechanisms underlying the arrhythmogenesis of SQTS is unclear, optimal therapy for SQTS is still lacking. The disease is rare, unclear genotype–phenotype correlations exist in a bevy of cases and the absence of an international short QT registry limit studies on the pathophysiological mechanisms of arrhythmogenesis and therapy of SQTS. This leads to the necessity of experimental models or platforms for studying SQTS. Here, we focus on reviewing preclinical SQTS models and platforms such as animal models, heterologous expression systems, human-induced pluripotent stem cell-derived cardiomyocyte models and computer models as well as three-dimensional engineered heart tissues. We discuss their usefulness for SQTS studies to examine genotype–phenotype associations, uncover disease mechanisms and test drugs. These models might be helpful for providing novel insights into the exact pathophysiological mechanisms of this channelopathy and may offer opportunities to improve the diagnosis and treatment of patients with SQT syndrome.

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

ESC CardioMed ◽  
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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