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Pediatric Cardiology Oct 2019Long QT syndrome (LQTS) is an inherited primary arrhythmia syndrome that may present with malignant arrhythmia and, rarely, risk of sudden death. The clinical symptoms... (Review)
Review
Long QT syndrome (LQTS) is an inherited primary arrhythmia syndrome that may present with malignant arrhythmia and, rarely, risk of sudden death. The clinical symptoms include palpitations, syncope, and anoxic seizures secondary to ventricular arrhythmia, classically torsade de pointes. This predisposition to malignant arrhythmia is from a cardiac ion channelopathy that results in delayed repolarization of the cardiomyocyte action potential. The QT interval on the surface electrocardiogram is a summation of the individual cellular ventricular action potential durations, and hence is a surrogate marker of the abnormal cellular membrane repolarization. Severely affected phenotypes administered current standard of care therapies may not be fully protected from the occurrence of cardiac arrhythmias. There are 17 different subtypes of LQTS associated with monogenic mutations of 15 autosomal dominant genes. It is now possible to model the various LQTS phenotypes through the generation of patient-specific induced pluripotent stem cell-derived cardiomyocytes. RNA interference can silence or suppress the expression of mutant genes. Thus, RNA interference can be a potential therapeutic intervention that may be employed in LQTS to knock out mutant mRNAs which code for the defective proteins. CRISPR/Cas9 is a genome editing technology that offers great potential in elucidating gene function and a potential therapeutic strategy for monogenic disease. Further studies are required to determine whether CRISPR/Cas9 can be employed as an efficacious and safe rescue of the LQTS phenotype. Current progress has raised opportunities to generate in vitro human cardiomyocyte models for drug screening and to explore gene therapy through genome editing.
Topics: Electrocardiography; Heart Ventricles; Humans; Induced Pluripotent Stem Cells; Long QT Syndrome; Mutation; Myocytes, Cardiac
PubMed: 31440766
DOI: 10.1007/s00246-019-02151-x -
Circulation. Arrhythmia and... Aug 2012
Review
Topics: Adrenergic beta-Antagonists; Animals; DNA Mutational Analysis; Defibrillators, Implantable; Electric Countershock; Genetic Predisposition to Disease; Genetic Testing; Genetic Therapy; Humans; Long QT Syndrome; Mutation; Phenotype; Prevalence; Sympathectomy
PubMed: 22895603
DOI: 10.1161/CIRCEP.111.962019 -
Current Problems in Cardiology Mar 2019Long QT syndrome (LQT) represents a heterogeneous family of cardiac electrophysiologic disorders characterized by QT prolongation and T-wave abnormalities on the... (Review)
Review
Long QT syndrome (LQT) represents a heterogeneous family of cardiac electrophysiologic disorders characterized by QT prolongation and T-wave abnormalities on the electrocardiogram. It is commonly associated with syncope, however, sudden cardiac death can occur due to torsades de pointes. LQT is a clinical diagnosis and should be suspected in individuals on the basis of clinical presentation, family history and ECG characteristics. Management is focused on the prevention of syncope and ultimately sudden death. Complete cessation of symptoms is the goal. Life-style modification, beta blockers and ICD implantation are the most important therapeutic modalities in proper management of patients with LQT. Awareness should be raised regarding possible circumstances that could increase the risk of QT prolongation. Advanced age, hypokalemia, a history of heart failure, and structural heart disease are often mentioned in this context. Prudent consideration is needed before making a decision to recommend an ICD implantation in a young, active patient. Medical and/or device therapy still represent important therapeutic modalities in the management of patients with LQT with careful clinical judgement for the substrate of patients who will benefit. Insights from benchside to bedside have facilitated progress toward better therapeutic strategies, there also remains a need for tailoring management toward individuals in a mechanism-specific manner to optimize care. In addition, continued progress toward fundamental understanding of mechanisms of ion channel function and drug-channel interaction will guide the development of more effective, mechanism-based molecular agents in the treatment of LQT.
Topics: Death, Sudden, Cardiac; Disease Management; Electrophysiologic Techniques, Cardiac; Humans; Long QT Syndrome
PubMed: 29784533
DOI: 10.1016/j.cpcardiol.2018.04.002 -
Internal Medicine Journal Dec 2021Congenital long QT syndrome (LQTS) is a familial cardiac ion channelopathy first described over 60 years ago. It is characterised by prolonged ventricular... (Review)
Review
Congenital long QT syndrome (LQTS) is a familial cardiac ion channelopathy first described over 60 years ago. It is characterised by prolonged ventricular repolarisation (long QT on electrocardiography), ventricular arrhythmias and associated syncope or sudden cardiac death. As the most closely studied cardiac channelopathy, over the decades we have gained a deep appreciation of the complex genetic model of LQTS. Variability in genetic expression and incomplete penetrance leads to a heterogeneous phenotype that can be challenging to classify clinically. In recent times, progress has been made in diagnostic method, risk stratification and treatment options. This review has been written as a guide for the general cardiologist to understand the basic pathophysiology, diagnosis and management priorities for the most encountered LQTS subtypes: LQT1, LQT2 and LQT3.
Topics: Arrhythmias, Cardiac; Death, Sudden, Cardiac; Electrocardiography; Humans; Long QT Syndrome; Phenotype
PubMed: 34151491
DOI: 10.1111/imj.15437 -
Cardiology in Review 2011Acquired and hereditary long-QT syndromes are important causes of sudden cardiac death. Both categories are characterized by abnormally prolonged cardiac repolarization... (Review)
Review
Acquired and hereditary long-QT syndromes are important causes of sudden cardiac death. Both categories are characterized by abnormally prolonged cardiac repolarization arising from a complex interaction between genetic and environmental factors. This produces a potentially dangerous substrate for polymorphic ventricular tachycardia and sudden cardiac death. In this review, the pathophysiologic, diagnostic, and prognostic features of long-QT syndromes, as well as recommendations regarding therapy, are reviewed.
Topics: Action Potentials; Death, Sudden, Cardiac; Electrocardiography; Humans; Long QT Syndrome; Prognosis; Torsades de Pointes
PubMed: 21808164
DOI: 10.1097/CRD.0b013e3182203504 -
Heart Disease and Stroke : a Journal... 1992
Review
Topics: Clinical Protocols; Electrocardiography; Humans; Long QT Syndrome
PubMed: 1344123
DOI: No ID Found -
JAMA
Review
Topics: Adrenergic beta-Antagonists; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Genotype; Humans; Long QT Syndrome; Pacemaker, Artificial; Sympathectomy; Syncope
PubMed: 12709446
DOI: 10.1001/jama.289.16.2041 -
Europace : European Pacing,... Apr 2022Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of...
AIMS
Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of life-threatening arrhythmias (LAE) for patients with LQTS, based on the genotype (long QT syndrome Type 1, long QT syndrome Type 2, and long QT syndrome Type 3) and the duration of the QTc interval. We sought to externally validate a novel risk score model (1-2-3-LQTS-Risk model) in a geographically diverse cohort from the USA and to evaluate its performance and assess potential clinical implication of this novel model.
METHODS AND RESULTS
The prognostic model (1-2-3-LQTS-Risk model) was derived using data from a prospective, single-centre longitudinal cohort study published in 2018 (discovery cohort) and was validated using an independent cohort of 1689 patients enrolled in the International LQTS Registry (Rochester NY, USA). The validation study revealed a C-index of 0.69 [95% confidence interval (CI): 0.61-0.77] in the validation cohort, when compared with C-index of 0.79 (95% CI: 0.70-0.88) in the discovery cohort. Adopting a 5-year risk ≥5%, as suggested by the ROC curve analysis as the most balanced threshold for implantable cardioverter-defibrillator (ICD) implantation, would result in a number needed to treat (NNT) of nine (NNT = 9; 95% CI: 6.3-13.6).
CONCLUSION
The 1-2-3-LQTS-Risk model, the first validated 5-year risk score model for patients with LQTS, can be used to aid clinicians to identify patients at the highest risk of LAE who could benefit most from an ICD implant and avoid unnecessary implants.
Topics: Arrhythmias, Cardiac; Death, Sudden, Cardiac; Electrocardiography; Humans; Long QT Syndrome; Longitudinal Studies; Prospective Studies; Risk Factors
PubMed: 34505884
DOI: 10.1093/europace/euab238 -
European Heart Journal Oct 2021
Topics: Artificial Intelligence; Electrocardiography; Humans; Long QT Syndrome
PubMed: 34508622
DOI: 10.1093/eurheartj/ehab611 -
Annals of Noninvasive Electrocardiology... Nov 2017Since its initial description by Jervell and Lange-Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. A... (Review)
Review
Since its initial description by Jervell and Lange-Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. A prolonged QT interval in the surface electrocardiogram is the sine qua non of the LQTS and is a surrogate measure of the ventricular action potential duration (APD). Congenital as well as acquired alterations in certain cardiac ion channels can affect their currents in such a way as to increase the APD and hence the QT interval. The inhomogeneous lengthening of the APD across the ventricular wall results in dispersion of APD. This together with the tendency of prolonged APD to be associated with oscillations at the plateau level, termed early afterdepolarizations (EADs), provides the substrate of ventricular tachyarrhythmia associated with LQTS, usually referred to as torsade de pointes (TdP) VT. This review will discuss the genetic, molecular, and phenotype characteristics of congenital LQTS as well as current management strategies and future directions in the field.
Topics: Adrenergic beta-Antagonists; Electrocardiography; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 28670758
DOI: 10.1111/anec.12481