The Genetics and Epigenetics of Ventricular Arrhythmias in Patients Without Structural Heart Disease

Wang, Mengru; Tu, Xin

doi:10.3389/fcvm.2022.891399

Cited by 11 publications

(8 citation statements)

References 194 publications

(177 reference statements)

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“…Approximately 18% of patients with epilepsy die due to SUDEP (8). One of the leading theories behind the pathophysiological mechanisms of SUDEP involves the onset of fatal cardiac arrhythmias (42). This theory is supported by retrospective cohort studies which suggest that patients with epileptic seizures have an increased incidence of abnormal electrocardiogram signs (46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Unmasking of Brugada syndrome by lamotrigine in a patient with pre-existing epilepsy: A case report with review of the literature

Omer

Omer²,

Alyousef³

et al. 2022

Front. Cardiovasc. Med.

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Brugada syndrome is an inherited cardiac channelopathy arising from mutations in voltage-gated cardiac sodium channels. Idiopathic epilepsy portrays a coalescent underlying pathophysiological mechanism pertaining to the premature excitation of neuronal voltage-gated ion channels resulting in the disruption of presynaptic neurons and the unregulated release of excitatory neurotransmitters. The coexistence of epilepsy and Brugada syndrome may be explained by mutations in voltage-gated ion channels, which are coexpressed in cardiac and neural tissue. Moreover, the incidence of sudden unexpected death in epilepsy has been associated with malignant cardiac arrhythmias in the presence of mutations in voltage-gated ion channels. Lamotrigine is an antiepileptic drug that inhibits neuronal voltage-gated sodium channels, thus stabilizing neural impulse propagation and controlling seizure activity in the brain. However, lamotrigine has been shown to inhibit cardiac voltage-gated sodium channels resulting in a potential arrhythmogenic effect and the ability to unmask Brugada syndrome in genetically susceptible individuals. We are reporting a case of a 27-year-old male patient with a background of presumed idiopathic epilepsy who was initiated on lamotrigine therapy resulting in the unmasking of Brugada syndrome and the onset of syncopal episodes. This case provides further evidence for the arrhythmogenic capacity of lamotrigine and highlights the relationship between epilepsy and Brugada syndrome. In this report, we aim to review the current literature regarding the associations between epilepsy and Brugada syndrome and the impact of lamotrigine therapy on such patients.

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Section: Discussionmentioning

confidence: 99%

Unmasking of Brugada syndrome by lamotrigine in a patient with pre-existing epilepsy: A case report with review of the literature

Omer

Omer²,

Alyousef³

et al. 2022

Front. Cardiovasc. Med.

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“…The common genes in IVF are CCR7 and PKN2, SCN5A, KCNQ1 and RYR2 (29,34) in the Asian populations, and CALM1~3, RYR2, TRDN, CACNA1C, SCN5A, KCNE5 in the Caucasian populations. (35) Searching for the cause of unexplained SCD is a great challenge. (32) In the current era, genetic test or molecular autopsy may provide some implications.…”

Section: Discussionmentioning

confidence: 99%

Identification of Genetic Variants in Patients with Idiopathic Ventricular Arrhythmia by Taiwan Arrhythmia Gene Panel Implying Underlying Mechanisms

Chen,

Chang,

Chiu

et al. 2024

Preprint

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Background Sudden cardiac death (SCD) due to idiopathic ventricular tachycardia or ventricular fibrillation is a catastrophic disease. Its genetic basis is heterogeneous and has been rarely addressed in Asia. We aim to find variants in an Asian cohort of idiopathic ventricular arrhythmia (IVA). Methods Nationwide patients with IVA were consecutively recruited. We designed a SCD gene panel (134 genes) to detect variants by next-generation sequencing (NGS) including most of the channelopathy and cardiomyopathy genes. Results A total of 40 IVA patients were included. Thirteen variants with unknown significance (VUS) and 7 pathogenic/likely pathogenic (P/LP) variants were identified in 20 patients (50%). All variants were novel and not found in dbSNP, ExAC and our general population. The identified variants were in genes implicated for long QT or Brugada syndromes (SCN5A, KCNH2, CACNA1C and ANK2), cardiomyopathy (MYH6, DSP and TTN) and catecholaminergic polymorphic ventricular tachycardia (RYR2). Patients with P/LP were younger, and more were women than those with VUS. Conclusions A high yield rate of genetic test was found in the largest NGS cohort of Asian IVA patients. These patients should be vigorously followed up for possible channelopathy or cardiomyopathy with repeated provocative test and myocardial imaging.

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“…Increasing interest in determining genes that are responsible for causing hereditary arrhythmogenesis is emerging (cf. recent state-of-the-art review by Wang and Tu [ 42 ]); numerous mutations of ion channels that configure the cardiac action potential have been determined. Other mutations are also known to reside in gene coding proteins with different biological functions, such as cytoskeletal architecture, calcium handling, sodium transport and cytokine signaling [ 43 , 44 , 45 ].…”

Section: General Principlesmentioning

confidence: 99%

Overview of Cardiac Arrhythmias and Treatment Strategies

Kingma¹,

Simard

Drolet

2023

Pharmaceuticals

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Maintenance of normal cardiac rhythm requires coordinated activity of ion channels and transporters that allow well-ordered propagation of electrical impulses across the myocardium. Disruptions in this orderly process provoke cardiac arrhythmias that may be lethal in some patients. Risk of common acquired arrhythmias is increased markedly when structural heart disease caused by myocardial infarction (due to fibrotic scar formation) or left ventricular dysfunction is present. Genetic polymorphisms influence structure or excitability of the myocardial substrate, which increases vulnerability or risk of arrhythmias in patients. Similarly, genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups within the population that affect specific drug biotransformation reactions. Nonetheless, identification of triggers involved in initiation or maintenance of cardiac arrhythmias remains a major challenge. Herein, we provide an overview of knowledge regarding physiopathology of inherited and acquired cardiac arrhythmias along with a summary of treatments (pharmacologic or non-pharmacologic) used to limit their effect on morbidity and potential mortality. Improved understanding of molecular and cellular aspects of arrhythmogenesis and more epidemiologic studies (for a more accurate portrait of incidence and prevalence) are crucial for development of novel treatments and for management of cardiac arrhythmias and their consequences in patients, as their incidence is increasing worldwide.

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The Genetics and Epigenetics of Ventricular Arrhythmias in Patients Without Structural Heart Disease

Cited by 11 publications

References 194 publications

Unmasking of Brugada syndrome by lamotrigine in a patient with pre-existing epilepsy: A case report with review of the literature

Unmasking of Brugada syndrome by lamotrigine in a patient with pre-existing epilepsy: A case report with review of the literature

Identification of Genetic Variants in Patients with Idiopathic Ventricular Arrhythmia by Taiwan Arrhythmia Gene Panel Implying Underlying Mechanisms

Overview of Cardiac Arrhythmias and Treatment Strategies

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