Challenge and Impact of Quinidine Access in Sudden Death Syndromes

Malhi, Navraj; Cheung, Christopher C.; Deif, Bishoy; Roberts, Jason D.; Gula, Lorne J.; Green, Martin S.; Pang, B.; Sultan, Omar; Konieczny, Kaja M.; Angaran, Paul; Dorian, Paul; Lashevsky, Ilan; Healey, Jeff S.; Alak, Aiman; Tadros, Rafik; Andorin, Antoine; Steinberg, Christian; Ayala‐Paredes, Felix; Simpson, Christopher S.; Atallah, Joseph; Krahn, Andrew D.

doi:10.1016/j.jacep.2018.10.007

Cited by 28 publications

(24 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Given the lower risk of arrhythmias in women (2 vs. 5% within 5 years of diagnosis), women are less likely to require an ICD (20 vs. 34%) ( 47 ). Quinidine has been effective in preventing arrhythmias in symptomatic patients with BrS ( 61 , 62 ), and should be considered in BrS patients with recurrent syncope or VT/VF, atrial fibrillation or in those who are reluctant to undergo ICD implantation ( 42 ). Instead of, studies have demonstrated that elimination of arrhythmogenic electrophysiological substrate in the RVOT epicardium by radiofrequency ablation results in ECG normalization and VT/VF non-inducibility ( 58 ), and reduced recurrent VT/VF episodes ( 63 ), suggesting that substrate-based radiofrequency ablation might be useful in selected patients with BrS, particularly those with multiple episodes of VT/VF.…”

Section: Brugada Syndromementioning

confidence: 99%

Sex-related differences in incidence, phenotype and risk of sudden cardiac death in inherited arrhythmia syndromes

Asatryan

Barth

2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Inherited Arrhythmia Syndromes (IAS) including long QT and Brugada Syndrome, are characterized by life-threatening arrhythmias in the absence of apparent structural heart disease and are caused by pathogenic variants in genes encoding cardiac ion channels or associated proteins. Studies of large pedigrees of families affected by IAS have demonstrated incomplete penetrance and variable expressivity. Biological sex is one of several factors that have been recognized to modulate disease severity in IAS. There is a growing body of evidence linking sex hormones to the susceptibility to arrhythmias, yet, many sex-specific disease aspects remain underrecognized as female sex and women with IAS are underinvestigated and findings from male-predominant cohorts are often generalized to both sexes with minimal to no consideration of relevant sex-associated differences in prevalence, disease manifestations and outcome. In this review, we highlight current knowledge of sex-related biological differences in normal cardiac electrophysiology and sex-associated factors that influence IAS phenotypes.

show abstract

Section: Brugada Syndromementioning

confidence: 99%

Sex-related differences in incidence, phenotype and risk of sudden cardiac death in inherited arrhythmia syndromes

Asatryan

Barth

2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…It reduces the frequency of impulse generation by prolonging spontaneous diastolic depolarization and elevates the threshold potential of action potentials. Oral quinidine is recommended for patients with ICD due to BrS, ERS, or IVF, while it decreases the number of ICD shocks and it also improves ICD-free survival (Malhi et al, 2019).…”

Section: Cpc Levelmentioning

confidence: 99%

Handling of Ventricular Fibrillation in the Emergency Setting

et al. 2020

View full text Add to dashboard Cite

Ventricular fibrillation (VF) and sudden cardiac death (SCD) are predominantly caused by channelopathies and cardiomyopathies in youngsters and coronary heart disease in the elderly. Temporary factors, e.g., electrolyte imbalance, drug interactions, and substance abuses may play an additive role in arrhythmogenesis. Ectopic automaticity, triggered activity, and reentry mechanisms are known as important electrophysiological substrates for VF determining the antiarrhythmic therapies at the same time. Emergency need for electrical cardioversion is supported by the fact that every minute without defibrillation decreases survival rates by approximately 7%-10%. Thus, early defibrillation is an essential part of antiarrhythmic emergency management. Drug therapy has its relevance rather in the prevention of sudden cardiac death, where early recognition and treatment of the underlying disease has significant importance. Cardioprotective and antiarrhythmic effects of beta blockers in patients predisposed to sudden cardiac death were highlighted in numerous studies, hence nowadays these drugs are considered to be the cornerstones of the prevention and treatment of life-threatening ventricular arrhythmias. Nevertheless, other medical therapies have not been proven to be useful in the prevention of VF. Although amiodarone has shown positive results occasionally, this was not demonstrated to be consistent. Furthermore, the potential proarrhythmic effects of drugs may also limit their applicability. Based on these unfavorable observations we highlight the importance of arrhythmia prevention, where echocardiography, electrocardiography and laboratory testing play a significant role even in the emergency setting. In the following we provide a summary on the latest developments on cardiopulmonary resuscitation, and the evaluation and preventive treatment possibilities of patients with increased susceptibility to VF and SCD.

show abstract

“…Meanwhile, quinidine also blocks potassium channels in phase 3. Recent studies reported that quinidine-induced QT prolongation increased the risk of fatal arrhythmia (18). Hence, further investigation of drug safety is warranted before the prescription of lifetime drug use.…”

Section: Cardiac Safety Evaluation Of Quinidine Using Brs-cmsmentioning

confidence: 99%

Comparative Analysis of Genetic Variations in the Nav1.5 Sodium Channel Subunits that Underlie Brugada Syndrome Using Patient-Specific iPSC-CMs

Zhu

Wang

Cui

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Brugada syndrome (BrS) is an autosomal dominant disorder that causes a high predisposition to sudden cardiac death. Several genes have been reported to be associated with BrS. Considering that the heterogeneity in clinical manifestations may result from genetic variations, the application of patient-specific induced pluripotent stem (iPS) cell-derived cardiomyocytes (CMs) may help to reveal cell phenotype characteristics resulting from different genetic backgrounds. The present study was to compare the structural and electrophysiological characteristics of sodium channel subunits with different genetic variations and evaluate the safety of quinidine for use with BrS patient-specific iPSC-derived cardiomyocytes.Methods: Two BrS patient-specific iPS cell lines were constructed that carried missense mutations in SCN5A and SCN1B. One iPS cell line from a healthy volunteer was used as a control. The differentiated cardiomyocytes from the three groups were evaluated by flow cytometry, immunofluorescence staining, electron microscopy, as well as calcium transient and patch clamp analyses to assess different pathological phenotypes. Finally, we evaluated the drug responses to varying concentrations of quinidine by measuring the action potential.Results: Compared to the control group, BrS-CMs showed a significant reduction in sodium current, prolonged action potential duration and varying degrees of decreased Vmax, but no structural difference was observed. After applying different concentrations of quinidine, the disease-specific groups and the control group had a downward trend in maximal upstroke velocity, resting membrane potential and action potential amplitude, and exhibited prolonged action potential duration without increasing incidence of arrhythmic events.Conclusion: Both patient-specific iPSC-CMs recapitulated the BrS phenotype at the cellular level. Although the SCN5A variation led to a markedly lower sodium current than what was observed with the SCN1B variation, their responses to quinidine were quite similar. The present study provides an advantageous platform for exploring disease mechanisms and evaluating drug safety in vitro.

show abstract

Challenge and Impact of Quinidine Access in Sudden Death Syndromes

Cited by 28 publications

References 16 publications

Sex-related differences in incidence, phenotype and risk of sudden cardiac death in inherited arrhythmia syndromes

Sex-related differences in incidence, phenotype and risk of sudden cardiac death in inherited arrhythmia syndromes

Handling of Ventricular Fibrillation in the Emergency Setting

Comparative Analysis of Genetic Variations in the Nav1.5 Sodium Channel Subunits that Underlie Brugada Syndrome Using Patient-Specific iPSC-CMs

Contact Info

Product

Resources

About