scholarly journals Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation

2021 ◽  
Vol 22 (15) ◽  
pp. 8090
Author(s):  
Daniela Baracaldo-Santamaría ◽  
Kevin Llinás-Caballero ◽  
Julián Miguel Corso-Ramirez ◽  
Carlos Martín Restrepo ◽  
Camilo Alberto Dominguez-Dominguez ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Molecular Mechanisms ◽  
Torsade De Pointes ◽  
Individual Variability ◽  
Long Qt ◽  
Drug Induced ◽  
Qt Interval Prolongation ◽  
Qt Syndrome ◽  
The Many

Long QT syndromes can be either acquired or congenital. Drugs are one of the many etiologies that may induce acquired long QT syndrome. In fact, many drugs frequently used in the clinical setting are a known risk factor for a prolonged QT interval, thus increasing the chances of developing torsade de pointes. The molecular mechanisms involved in the prolongation of the QT interval are common to most medications. However, there is considerable inter-individual variability in drug response, thus making the application of personalized medicine a relevant aspect in long QT syndrome, in order to evaluate the risk of every individual from a pharmacogenetic standpoint.

A Síndrome do QT Longo Associada ao uso de Citalopram e Escitalopram / The Long QT Syndrome Associated to Citalopram and Escitalopram

1970 ◽  
Vol 6 (2) ◽  
pp. 73-82
Author(s):  
Filipe Santos Falani ◽  
Vinícius Nasser de Carvalho ◽  
Túlio Torres Vargas
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Second Generation ◽  
Long Qt ◽  
Drug Induced ◽  
Electrocardiographic Monitoring ◽  
System A ◽  
Qt Interval Prolongation ◽  
Qt Syndrome ◽  
Low Prevalence

Objetivo: Revisar a literatura em relação à associação do prolongamento do intervalo QT no eletrocardiograma e o uso de citalopram e escitalopram, antidepressivos de segunda geração de largo consumo em escala mundial. Materiais e Métodos: Revisão da literatura em bases de dados Scielo e Medline. Desenvolvimento: citalopram e escitalopram são antidepressivos conhecidos como indutores de QT Longo dose-induzida, e os riscos-benefícios devem ser avaliados antes de seu uso. O citalopram é o inibidor seletivo da recaptação da serotonina mais prescrito no mundo, enquanto o escitalopram é amplamente usado nas doenças depressivas maiores. O escitalopram é também amplamente prescrito devido seus efeitos colaterais leves e transitórios. A Síndrome do QT Longo ocorre devido uma alteração no sistema elétrico cardíaco. Uma duração do intervalo QT maior que 450ms em homens e 460ms em mulheres deve ser considerada anômala, com etiologia específica. Entretanto, arritmias cardíacas ocorrem mais frequentemente quando o QT é maior que 500ms. O principal mecanismo do QT Longo induzido por drogas é a inibição do canal de potássio hERG, particularmente naqueles pacientes com a variante polimórfica. Conclusão: Apesar da pequena prevalência de prolongamento do intervalo QT induzido em usuários de antidepressivos de segunda geração, dado seu amplo uso pela população, é necessária uma maior preocupação em relação à monitorização eletrocardiográfica, principalmente quando estiverem presentes fatores de risco ou sinais de overdose.Palavras-chave: Associação, Síndrome do QT Longo, Citalopram.ABSTRACTObjective: To review the literature regarding the association of QT prolongation on electrocardiogram and the use of citalopram and escitalopram, the second generation of wide consumption worldwide antidepressants. Materials and Methods: Literature review in Scielo and Medline databases. Development: Citalopram and escitalopram are antidepressants known as Long QT-inducing dose-induced, and the benefit-risk should be evaluated before use. Citalopram is the selective inhibitor of serotonin reuptake most widely prescribed in the world as escitalopram is widely used in major depressive disorder. Escitalopram is also widely prescribed because of its mild and transient side effects. The Long QT syndrome occurs because of a change in the cardiac electrical system. A duration of the QT interval greater than 450ms in men and 460ms in women should be considered anomalous, with specific etiology. However, cardiac arrhythmias occur more frequently when QT is greater than 500ms. The primary mechanism of drug-induced long QT is the inhibition of the hERG potassium channel, particularly in those patients with the polymorphic variant. Conclusion: Despite the low prevalence of QT interval prolongation induced in second-generation antidepressant users, given its wide use by the population, a greater concern for electrocardiographic monitoring is required, especially when there are risk factors or signs of overdose.Keywords: Association, Long QT Syndrome, Citalopram.

Predicting Torsade de Pointes in Acquired Long QT Syndrome: Optimal Identification of Critical QT Interval Prolongation

Cardiology ◽  
2012 ◽  
Vol 122 (1) ◽  
pp. 3-11 ◽  
Author(s):  
John Chiladakis ◽  
Andreas Kalogeropoulos ◽  
Fani Zagkli ◽  
Nikolaos Koutsogiannis ◽  
Konstantinos Chouchoulis ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Torsade De Pointes ◽  
Interval Prolongation ◽  
Long Qt ◽  
Acquired Long Qt Syndrome ◽  
Qt Interval Prolongation ◽  
Qt Syndrome

scholarly journals Long QT in stunned myocardium: unrecognised cause of acquired long QT syndrome

2014 ◽  
Vol 83 (3) ◽  
pp. 250-254
Author(s):  
Jerzy Sacha
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Ventricular Tachyarrhythmia ◽  
Torsade De Pointes ◽  
Stunned Myocardium ◽  
Long Qt ◽  
Wave Inversion ◽  
Qt Interval Prolongation ◽  
Evolutionary Changes ◽  
Qt Syndrome

Long QT syndrome (LQTS) is a heart disorder characterized by a prolongation of the QT interval on ECG and a predisposition to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest or sudden cardiac death. This condition may be inherited or induced by external factors such as drugs, electrolyte imbalances and some acquired cardiac diseases. The review addresses LQTS caused by acute cardiac illnesses which are associated with a large amount of stunned myocardium, i.e. the reperfused myocardial infarction and the group of stress-related cardiomyopathies. In these cases, specific ECG evolutionary changes may be observed, i.e. dynamic deep T-wave inversion and QT interval prolongation which predispose to fatal polymorphic ventricular tachyarrhythmia, i.e. torsade de pointes. However, lethal arrhythmias are relatively rare in these instances and probably concern patients with an underlying predisposition to LQTS. The pathological mechanisms of both repolarization abnormalities and ventricular arrhythmias as well as the practical approach how to interpret electrocardiographic changes and identify high risk patients are discussed in this review.

scholarly journals Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: A systematic review

2020 ◽  
Author(s):  
Veronique Michaud ◽  
Pamela Dow ◽  
Sweilem B. Al Rihani ◽  
Malavika Deodhar ◽  
Meghan Arwood ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Adverse Event Reporting System ◽  
Torsade De Pointes ◽  
World Health ◽  
Delayed Rectifier ◽  
Long Qt ◽  
Drug Induced ◽  
Repurposed Drugs ◽  
Qt Syndrome

ABSTRACTBackgroundThe World Health Organization first declared SARS-CoV-2 (COVID-19) a pandemic on March 11, 2020. There are currently no vaccines or therapeutic agents proven efficacious to treat COVID-19. So, whether existing approved drugs could be repurposed and used off-label for the treatment of novel COVID-19 disease is being explored.MethodsA thorough literature search was performed to gather information on the pharmacological properties and toxicity of 6 drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, remdesivir) proposed to be repurposed to treat COVID-19. Researchers emphasized affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Risk of drug-induced Long QT Syndrome (LQTS) for these drugs was quantified by comparing six indices used to assess such risk and by querying the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System database with specific key words. Data are also provided to compare the level of risk for drug-induced LQTS by these drugs to 23 other, well-recognized, torsadogenic compounds.ResultsEstimators of LQTS risk levels indicated a very-high or high risk for all COVID-19 repurposed drugs except for azithromycin, although cases of TdP have been reported following the administration of this drug. There was an excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and the 23 torsadogenic compounds.ConclusionThe risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed as such monitoring is possible for hospitalized patients or by the use of biodevices for outpatients initiated on these drugs.

scholarly journals Drug-induced long qt syndrome

2020 ◽  
Vol 27 (3) ◽  
pp. 42-52
Author(s):  
G. A. Golovina ◽  
K. V. Zaphiraki ◽  
E. D. Kosmacheva
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Diagnosis And Treatment ◽  
Fatal Complication ◽  
Long Qt ◽  
Drug Induced ◽  
Long Qt Interval ◽  
Qt Syndrome

In this review drug-induced long QT interval syndrome is described. The authors discuss approaches for the prevention, diagnosis, and treatment of this potentially fatal complication.

scholarly journals Transient Long QT Development in a Patient with Takotsubo Cardiomyopathy

2016 ◽  
Vol 2 (2) ◽  
pp. 81-84
Author(s):  
Dániel Czuriga ◽  
Andrea Szegedi ◽  
Ferenc Győry ◽  
Attila Szilágyi ◽  
Sándor Sipka ◽  
...  
Keyword(s):  
Takotsubo Cardiomyopathy ◽  
Long Qt Syndrome ◽  
Qt Interval ◽  
Ventricular Arrhythmias ◽  
Interval Prolongation ◽  
Long Qt ◽  
Electrolyte Disturbances ◽  
Acquired Long Qt Syndrome ◽  
Qt Interval Prolongation ◽  
Qt Syndrome

Abstract QT interval prolongation on the electrocardiogram is considered a precursory sign for imminent, potentially lethal ventricular arrhythmias. Beside the inherited condition of long QT syndrome, numerous drugs, certain electrolyte disturbances and early transmural ischemia have been identified to induce reversible prolongation of the QT interval, collectively called as acquired long QT syndrome. Herein we describe a case of a patient with transient QT prolongation and Takotsubo cardiomyopathy, a rather infrequent cause of long QT development. Serial changes of the repolarization pattern were documented to demonstrate progression and resolution of the abnormal QT interval.

Video-Assisted Modified Left Sympathectomy for Long-QT Syndrome

2000 ◽  
Vol 8 (1) ◽  
pp. 52-53 ◽  
Author(s):  
Guo Xing Weng ◽  
Hang Ding ◽  
Juan Qi ◽  
Chun Xuan Xu
Keyword(s):  
Ventricular Tachycardia ◽  
Long Qt Syndrome ◽  
Qt Interval ◽  
Torsade De Pointes ◽  
Horner’S Syndrome ◽  
Horner's Syndrome ◽  
Long Qt ◽  
Video Assisted ◽  
Qt Syndrome

A 22-year-old female suffering from idiopathic long-QT syndrome complicated by frequent syncope, torsade-de-pointes-type ventricular tachycardia, and asthma, was successfully treated by video-assisted extensive left second and third thoracic sympathetic ganglionectomy, instead of left stellate and first thoracic ganglio-nectomy, to avoid postoperative Horner's syndrome. The QT interval was significantly shortened from 0.6 to 0.43 seconds four days after the surgery. It remained at 0.43 seconds during a 3-month follow-up with no recurrence of tachycardia or syncope.

scholarly journals Ranolazine as an Alternative Therapy to Flecainide for SCN5A V411M Long QT Syndrome Type 3 Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Jordi Cano ◽  
Esther Zorio ◽  
Andrea Mazzanti ◽  
Miguel Ángel Arnau ◽  
Beatriz Trenor ◽  
...  
Keyword(s):  
Clinical Data ◽  
Long Qt Syndrome ◽  
Qt Interval ◽  
Sodium Current ◽  
Long Qt ◽  
One Dimensional ◽  
Qt Interval Prolongation ◽  
Number Of Patients ◽  
Qt Syndrome ◽  
Type 3

The prolongation of the QT interval represents the main feature of the long QT syndrome (LQTS), a life-threatening genetic disease. The heterozygous SCN5A V411M mutation of the human sodium channel leads to a LQTS type 3 with severe proarrhythmic effects due to an increase in the late component of the sodium current (INaL). The two sodium blockers flecainide and ranolazine are equally recommended by the current 2015 ESC guidelines to treat patients with LQTS type 3 and persistently prolonged QT intervals. However, awareness of pro-arrhythmic effects of flecainide in LQTS type 3 patients arose upon the study of the SCN5A E1784K mutation. Regarding SCN5A V411M individuals, flecainide showed good results albeit in a reduced number of patients and no evidence supporting the use of ranolazine has ever been released. Therefore, we ought to compare the effect of ranolazine and flecainide in a SCN5A V411M model using an in-silico modeling and simulation approach. We collected clinical data of four patients. Then, we fitted four Markovian models of the human sodium current (INa) to experimental and clinical data. Two of them correspond to the wild type and the heterozygous SCN5A V411M scenarios, and the other two mimic the effects of flecainide and ranolazine on INa. Next, we inserted them into three isolated cell action potential (AP) models for endocardial, midmyocardial and epicardial cells and in a one-dimensional tissue model. The SCN5A V411M mutation produced a 15.9% APD90 prolongation in the isolated endocardial cell model, which corresponded to a 14.3% of the QT interval prolongation in a one-dimensional strand model, in keeping with clinical observations. Although with different underlying mechanisms, flecainide and ranolazine partially countered this prolongation at the isolated endocardial model by reducing the APD90 by 8.7 and 4.3%, and the QT interval by 7.2 and 3.2%, respectively. While flecainide specifically targeted the mutation-induced increase in peak INaL, ranolazine reduced it during the entire AP. Our simulations also suggest that ranolazine could prevent early afterdepolarizations triggered by the SCN5A V411M mutation during bradycardia, as flecainide. We conclude that ranolazine could be used to treat SCN5A V411M patients, specifically when flecainide is contraindicated.

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