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Progress in Biophysics and Molecular... Jul 2016Long QT syndrome (LQTS) is a rare inherited channelopathy caused mainly by different mutations in genes encoding for cardiac K(+) or Na(+) channels, but can also be... (Review)
Review
Long QT syndrome (LQTS) is a rare inherited channelopathy caused mainly by different mutations in genes encoding for cardiac K(+) or Na(+) channels, but can also be caused by commonly used ion-channel-blocking and QT-prolonging drugs, thus affecting a much larger population. To develop novel diagnostic and therapeutic strategies to improve the clinical management of these patients, a thorough understanding of the pathophysiological mechanisms of arrhythmogenesis and potential pharmacological targets is needed. Drug-induced and genetic animal models of various species have been generated and have been instrumental for identifying pro-arrhythmic triggers and important characteristics of the arrhythmogenic substrate in LQTS. However, due to species differences in features of cardiac electrical function, these different models do not entirely recapitulate all aspects of the human disease. In this review, we summarize advantages and shortcomings of different drug-induced and genetically mediated LQTS animal models - focusing on mouse and rabbit models since these represent the most commonly used small animal models for LQTS that can be subjected to genetic manipulation. In particular, we highlight the different aspects of arrhythmogenic mechanisms, pro-arrhythmic triggering factors, anti-arrhythmic agents, and electro-mechanical dysfunction investigated in transgenic LQTS rabbit models and their translational application for the clinical management of LQTS patients in detail. Transgenic LQTS rabbits have been instrumental to increase our understanding of the role of spatial and temporal dispersion of repolarization to provide an arrhythmogenic substrate, genotype-differences in the mechanisms for early afterdepolarization formation and arrhythmia maintenance, mechanisms of hormonal modification of arrhythmogenesis and regional heterogeneities in electro-mechanical dysfunction in LQTS.
Topics: Animals; Animals, Genetically Modified; Disease Models, Animal; Humans; Ion Channels; Long QT Syndrome; Rabbits
PubMed: 27210307
DOI: 10.1016/j.pbiomolbio.2016.05.004 -
Journal of Insurance Medicine (New... 2003A 29-year-old male presented for an evaluation of his risk for having congenital long QT syndrome. Despite being asymptomatic and having a normal QTc interval on the... (Review)
Review
A 29-year-old male presented for an evaluation of his risk for having congenital long QT syndrome. Despite being asymptomatic and having a normal QTc interval on the resting ECG, a suggestive family history was an indication for a thorough cardiac evaluation. A geneticist reviewed this workup and recommended against genetic testing. While up to 10% of affected carriers of a congenital long QT syndrome gene mutation can be asymptomatic with a normal QTc, consideration of all of the clinical factors allowed for further risk stratification. The evaluation of an ECG for the long QT syndrome includes calculating a corrected QT interval for the heart rate and assessing the T-waves for morphology associated with this syndrome.
Topics: Adult; Electrocardiography; Genetic Testing; Heterozygote; Humans; Insurance, Life; Long QT Syndrome; Male; Risk Assessment
PubMed: 14971094
DOI: No ID Found -
The Turkish Journal of Pediatrics 2019Kurnaz E, Savaş Erdeve Ş, Özgür S, Keskin M, Özbudak P, Çetinkaya S, Aycan Z. Congenital long-QT syndrome in type 1 diabetes: a unique association. Turk J Pediatr...
Kurnaz E, Savaş Erdeve Ş, Özgür S, Keskin M, Özbudak P, Çetinkaya S, Aycan Z. Congenital long-QT syndrome in type 1 diabetes: a unique association. Turk J Pediatr 2019; 61: 791-793. In contrast to acquired long QT syndrome (LQTS), congenital LQTS is a relatively rare channelopathy with an incidence of 1/2,500. We describe a patient found to have a prolonged QTc in the setting of newly diagnosed Type 1 DM. To the best of our knowledge, this unique association has not been previously reported. Currently, it is shown that glucose ingestion aggravated cardiac repolarization disturbances in LQT2 patients and prolonged the cardiac repolarization phase in healthy controls. Our case presented to the hospital with syncope after increased glucose level. Therefore, it seems that increased glucose level may have prolonged QTc interval and aggravated cardiac repolarization disturbances in the presented case. By this report, we want to emphasize the importance of hyperglycaemia in congenital LQTS.
Topics: Adolescent; Diabetes Mellitus, Type 1; Electrocardiography; Female; Humans; Long QT Syndrome
PubMed: 32105015
DOI: 10.24953/turkjped.2019.05.022 -
Heart Rhythm Jan 2008
Topics: Death, Sudden, Cardiac; Humans; Long QT Syndrome; Risk Factors; Torsades de Pointes
PubMed: 18065280
DOI: 10.1016/j.hrthm.2007.11.009 -
Annals of Internal Medicine Dec 2002The congenital long QT syndrome is a potentially fatal, inherited cardiac syndrome. Early diagnosis and preventive treatment are instrumental to prevent sudden cardiac... (Review)
Review
BACKGROUND
The congenital long QT syndrome is a potentially fatal, inherited cardiac syndrome. Early diagnosis and preventive treatment are instrumental to prevent sudden cardiac death in patients with the congenital long QT syndrome.
PURPOSE
To review new insights in genetics and cellular electrophysiology, as well as the current understanding of the clinical diagnosis and treatment of the congenital long QT syndrome.
DATA SOURCES
Authors' personal databases and search of PubMed database from 1966 to 2001.
STUDY SELECTION
Experimental and clinical studies on the congenital long QT syndrome.
DATA EXTRACTION
Data from peer-reviewed studies were manually extracted, classified, and summarized.
DATA SYNTHESIS
The congenital long QT syndrome is characterized by abnormally prolonged ventricular repolarization, which predisposes patients to syncope, ventricular arrhythmias, and sudden cardiac death. The recent discovery of mutations in genes encoding ion channels has improved our understanding of the cellular origin of this condition. The congenital long QT syndrome may result from inherited defects in cardiac K+ and Na+ channels, which both result in prolongation of the ventricular action potential. The diagnosis is based on electrocardiographic and clinical criteria. Genetic screening of symptomatic patients or asymptomatic family members may identify patients at risk for life-threatening ventricular arrhythmias. beta-Blocking agents are the mainstay of treatment. Certain patients may also benefit from a pacemaker or implantable cardioverter defibrillator. Recent studies suggest that genotype-specific treatment of the congenital long QT syndrome will be feasible in the near future.
CONCLUSIONS
The congenital long QT syndrome is a potentially life-threatening condition caused by mutations in genes encoding cardiac ion channels. Better understanding of the mechanisms responsible for this condition will guide genotype-specific therapy in the near future.
Topics: Electrocardiography; Electrophysiology; Female; Genotype; Humans; Long QT Syndrome; Male; Mutation; Polymorphism, Genetic; Risk Factors
PubMed: 12484714
DOI: 10.7326/0003-4819-137-12-200212170-00012 -
Annals of Noninvasive Electrocardiology... Jul 2018We report a case of torsades de pointes arrhythmia as the first manifestation of congenital Long QT syndrome in a 77-year-old man with family history of sudden...
We report a case of torsades de pointes arrhythmia as the first manifestation of congenital Long QT syndrome in a 77-year-old man with family history of sudden unexplained death. This case illustrates the importance of vigilant clinical assessment and genetic counseling in families with sudden death in order to identify properly asymptomatic relatives at risk for cardiac events. It also demonstrates that Long QT syndrome can still manifest with potentially fatal arrhythmias late in life in previously asymptomatic elderly patients.
Topics: Aged; Anti-Arrhythmia Agents; Electrocardiography; Humans; Long QT Syndrome; Male; Propranolol; Severity of Illness Index; Time
PubMed: 29194874
DOI: 10.1111/anec.12517 -
European Journal of Pediatrics Jul 2009Congenital long-QT syndrome (LQTS) is a sporadic or familial inherited arrhythmia. It can lead to sudden death by ventricular fibrillation which occurs at any age but... (Review)
Review
INTRODUCTION
Congenital long-QT syndrome (LQTS) is a sporadic or familial inherited arrhythmia. It can lead to sudden death by ventricular fibrillation which occurs at any age but particularly during infancy. Recent studies of postmortem molecular analysis in infants who died of unexplained sudden infant death syndrome (SIDS) showed abnormal mutations to LQTS in 10% to 12%. Current methods of etiologic investigation of sudden infant death syndrome do not allow the diagnosis of LQTS. A targeted anamnesis together with systematic electrocardiograms of first- and second-degree relatives could be an efficient LQTS diagnostic tool. Therefore, we propose to include them in screening procedures for SIDS etiologies.
CONCLUSION
LQTS accounts for a significant number of unexplained SIDS. We suggest adding a systematic familial electrocardiographic screening to the current etiologic investigations in order to track congenital LQTS in relatives.
Topics: Electrocardiography; Family; Genetic Predisposition to Disease; Humans; Infant; Infant, Newborn; Long QT Syndrome; Postmortem Changes; Risk Factors; Sudden Infant Death; Ventricular Fibrillation
PubMed: 19266217
DOI: 10.1007/s00431-009-0951-y -
Tidsskrift For Den Norske Laegeforening... Oct 2006Long QT syndrome is a rare condition. The syndrome is characterised by a prolonged QT-interval corrected for heart rate (QTc). The typical clinical presentation is the... (Review)
Review
BACKGROUND
Long QT syndrome is a rare condition. The syndrome is characterised by a prolonged QT-interval corrected for heart rate (QTc). The typical clinical presentation is the occurrence of syncope or cardiac arrest in young and otherwise healthy individuals. Cardiac events can be precipitated by environmental factors and use of certain drugs. The purpose of the present study is to provide guidelines regarding risk factors that may worsen the syndrome, based on available literature.
MATERIAL AND METHODS
PubMed was searched for all literature in English from 1966 through 2004 on the Long QT syndrome. The articles and their literature references were examined. Additional information was achieved from experienced colleagues and from some key sites on the internet.
RESULTS
The symptoms of the Long QT syndrome are tachycardia, syncope or cardiac arrest, often related to psychological or physical stress in young, usually healthy individuals. The syndrome can be inherited or acquired and is commonly caused by mutations in the potassium channel or by lack of inactivation of the sodium channels. The most common causes of acquired conditions are electrolyte abnormalities, intracranial disease, dietary deficiencies, myocardial infarction, dilated cardiomyopathy, mitral valve prolapse, bradycardia, severe malnutrition among anorexic patients and the use of medication.
INTERPRETATION
It is important to have knowledge about the Long QT Syndrome. The treatment is primarily to remove potential risk factors and medically to give beta-blockers or insert pacemakers or cardiac defibrillators.
Topics: Death, Sudden, Cardiac; Humans; Long QT Syndrome; Practice Guidelines as Topic; Risk Factors
PubMed: 17028631
DOI: No ID Found -
European Heart Journal Aug 2002
Topics: Humans; Long QT Syndrome; Mutation; Sympathetic Nervous System; Torsades de Pointes
PubMed: 12175662
DOI: 10.1053/euhj.2002.3287 -
The American Journal of Emergency... Sep 1992A 21-year-old woman was brought to the emergency department after being found unconscious in a hotel lobby. On presentation, she was awake but confused. The initial... (Review)
Review
A 21-year-old woman was brought to the emergency department after being found unconscious in a hotel lobby. On presentation, she was awake but confused. The initial evaluation revealed no evidence of trauma, metabolic abnormality, drug ingestion, or intracranial process. The only abnormality noted was electrocardiographic, and included a long QT interval as well as occasional atrial and junctional beats within a normal sinus rhythm. While in the department the patient developed tonic-clonic activity and was concurrently noted to have developed ventricular tachycardia. A precordial thump was given with the simultaneous cessation of the arrythmia and the seizure. After definitive electrophysiologic study, the diagnosis of long QT syndrome was made. Treatment consisting of beta blockade and pacemaker insertion prevented further arrythmia or seizure activity. Long QT syndrome should be considered a possible etiology in any patient presenting with new onset seizures, especially in the young.
Topics: Adrenergic beta-Antagonists; Adult; Diagnosis, Differential; Electrocardiography; Female; Humans; Long QT Syndrome; Pacemaker, Artificial; Syncope
PubMed: 1353675
DOI: 10.1016/0735-6757(92)90071-5