ECG T-Wave Patterns in Genetically Distinct Forms of the Hereditary Long QT Syndrome

Moss, Arthur J.; Zaręba, Wojciech; Benhorin, Jesaia; Locati, Emanuela H.; Hall, William J.; Robinson, Jennifer L.; Schwartz, Peter J.; Towbin, Jeffrey A.; Vincent, G; Lehmann, Michael H.; Keating, Mark T.; MacCluer, Jean W.; Timothy, Katherine W.

doi:10.1161/01.cir.92.10.2929

Cited by 546 publications

(275 citation statements)

References 16 publications

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“…An experienced cardiologist should be able to guess with reasonable accuracy the genotype of his or her patients on the basis of clinical history, of the circumstances associated with the cardiac events [27], and sometimes according to the T-wave morphology on the electrocardiogram [28,29], but confirmation must be sought from the molecular laboratory.…”

Section: Patients Of Known Genotypementioning

confidence: 99%

The congenital long QT syndromes from genotype to phenotype: clinical implications

Schwartz

2005

Journal of Internal Medicine

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The long QT syndrome (LQTS) is a genetic disorder responsible for many sudden deaths before age 20. The identification of several LQTS genes, all encoding cardiac ion channels, has had a major impact on the management strategy for both patients and family members. Genotype-guided therapy allows more effective individually tailored therapy. Therapeutic options, including b-blockers, left cardiac sympathetic denervation, and implantable defibrillators are discussed for patients of known and of unknown genotype. The recent identification of modifier genes which amplify the effect of an LQTS mutation may change the approach to risk stratification.

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Section: Patients Of Known Genotypementioning

confidence: 99%

The congenital long QT syndromes from genotype to phenotype: clinical implications

Schwartz

2005

Journal of Internal Medicine

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210

125

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“…Genotype specific ECG features-Genotype specific ST-T wave morphology was first reported by Moss et al (1995) who highlighted the difference in the shapes of T waves of the ECG among the three most common genotypes. Broad-based prolongation of the T waves is more commonly observed in LQT1, whereas low-amplitude T waves with a notched or bifurcated configuration are seen more frequently in LQT2.…”

Section: 22mentioning

confidence: 99%

Pharmacological approach to the treatment of long and short QT syndromes

Patel

Antzelevitch

2008

Pharmacology & Therapeutics

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Inherited channelopathies have received increasing attention in recent years. The past decade has witnessed impressive progress in our understanding of the molecular and cellular basis of arrhythmogenesis associated with inherited channelopathies. An imbalance in ionic forces induced by these channelopathies affects the duration of ventricular repolarization and amplifies the intrinsic electrical heterogeneity of the myocardium, creating an arrhythmogenic milieu. Today, many of the channelopathies have been linked to mutations in specific genes encoding either components of ion channels or membrane or regulatory proteins. Many of the channelopathies are genetically heterogeneous with a variable degree of expression of the disease. Defining the molecular basis of channelopathies can have a profound impact on patient management, particularly in cases in which genotype-specific pharmacotherapy is available.The long QT syndrome (LQTS) is one of the first identified and most studied channelopathies where abnormal prolongation of ventricular repolarization predisposes an individual to life threatening ventricular arrhythmia called Torsade de Pointes. On the other hand of the spectrum, molecular defects favoring premature repolarization lead to Short QT syndrome (SQTS), a recently described inherited channelopathy. Both of these channelopathies are associated with a high risk of sudden cardiac death due to malignant ventricular arrhythmia. Whereas pharmacological therapy is first line treatment for LQTS, defibrillators are considered as primary treatment for SQTS. This review provides a comprehensive review of the molecular genetics, clinical features, genotype-phenotype correlations and genotype-specific approach to pharmacotherapy of these two mirror-image channelopathies, SQTS and LQTS.

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“…Like in other LQT syndromes, the abnormal prolongation of ventricular repolarization is associated with a susceptibility to a specific polymorphic ventricular tachycardia called torsades de pointes and ventricular fibrillation, leading to syncope and sudden death. Clinically, LQT3 is characterized by an increased duration of the ST segment with a late appearance of the T-wave (Moss, 2002). Bradycardia and pauses occurring at rest, and more particularly during sleep, are often at the origin of the arrhythmias.…”

Section: Models For the Lqt3 Syndromementioning

confidence: 99%

Mouse models of SCN5A-related cardiac arrhythmias

Charpentier

Bourgé

Mérot

2008

Progress in Biophysics and Molecular Biology

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Mutations of SCN5A gene, which encodes the α-subunit of the voltage-gated Na channel Na V 1.5, underlie hereditary cardiac arrhythmic syndromes such as the type 3 long QT syndrome, cardiac conduction diseases, the Brugada syndrome, the sick sinus syndrome, a trial standstill, and numerous overlap syndromes. Patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases. However, they could not clarify how SCN5A mutations can be responsible for such a large spectrum of diseases, for the late age of onset or the progressiveness of some of these diseases and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological mechanisms of cardiac SCN5A-related arrhythmic syndromes and several mouse models have been established. This review presents the results obtained on these models that, for most of them, recapitulate the clinical phenotypes of the patients. This includes two models knocked out for Nav1.5 β1 and β3 auxiliary subunits that are also discussed. Despite their own limitations that we point out, the mouse models still appear as powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the secondary cellular consequences of SCN5A mutations such as the expression remodeling of other genes. This points out the potential role of these genes in the overall human phenotype. Finally, they constitute useful tools for addressing the role of genetic and environmental modifiers on cardiac electrical activity.

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ECG T-Wave Patterns in Genetically Distinct Forms of the Hereditary Long QT Syndrome

Cited by 546 publications

References 16 publications

The congenital long QT syndromes from genotype to phenotype: clinical implications

The congenital long QT syndromes from genotype to phenotype: clinical implications

Pharmacological approach to the treatment of long and short QT syndromes

Mouse models of SCN5A-related cardiac arrhythmias

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