Brugada syndrome and sinus node dysfunction

Hayashi, Hidemori; Sumiyoshi, Masataka; Nakazato, Yuji; Daida, Hiroyuki

doi:10.1002/joa3.12046

Cited by 20 publications

(12 citation statements)

References 53 publications

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“…syndrome and sinus node dysfunction" in the Journal of Arrhythmia as a compilation of our studies concerning BrS and SSS 9) . My first BrS patient encountered during my night shift at Juntendo University Hospital had a documented episode of VF 32 years earlier, and he has been doing well without syncope or an ICD operation since then.…”

Section: Epiloguementioning

confidence: 99%

A Clinical Study Starting from an Encounter with a Patient

Sumiyoshi

2021

Juntendo Medical Journal

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The story of this clinical study began with a patient I encountered as a post-graduate student on night duty at Juntendo University Hospital in 1989. The patient was diagnosed as idiopathic ventricular fibrillation (IVF) with incomplete right bundle branch block and a bizarrely shaped ST segment elevation in V 1-3 . He had a history of sick sinus syndrome (SSS) one year earlier. Three years after that encounter, the Brugada brothers reported eight patients with IVF whose ECG findings were very similar to those of my patient, and this syndrome was later named Brugada syndrome (BrS). It is now known that there are many individuals with BrS in Japan and across Asia, and regrettably the first patient's report was not released in Japan. With the later progress in genomic research it has become apparent that a single gene mutation could be a cause of both BrS and SSS. We have begun a clinical study of the association between BrS and SSS and have published several papers about this issue. My first patient with BrS and SSS has been doing well without syncope for over 30 years.

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Section: Epiloguementioning

confidence: 99%

A Clinical Study Starting from an Encounter with a Patient

Sumiyoshi

2021

Juntendo Medical Journal

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“…A number of SCN5A mutations have been associated with inherited SSS, and interestingly these can be both loss-of-function and gain-of-function mutations. Consequently, the occurrence of SSS has a considerable overlap with BrS ( 24 ) and LQT3 ( 25 , 26 ). Loss-of-function, i.e., a reduction of I Na availability, decreases the speed of the diastolic depolarization phase of SAN cells and thereby pacemaker activity ( 25 ).…”

Section: Cardiac Disorders Associated With Scn5a Mmentioning

confidence: 99%

Disease Modifiers of Inherited SCN5A Channelopathy

Verkerk

Amin

Remme

2018

Front. Cardiovasc. Med.

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To date, a large number of mutations in SCN5A, the gene encoding the pore-forming α-subunit of the primary cardiac Na+ channel (NaV1.5), have been found in patients presenting with a wide range of ECG abnormalities and cardiac syndromes. Although these mutations all affect the same NaV1.5 channel, the associated cardiac syndromes each display distinct phenotypical and biophysical characteristics. Variable disease expressivity has also been reported, where one particular mutation in SCN5A may lead to either one particular symptom, a range of various clinical signs, or no symptoms at all, even within one single family. Additionally, disease severity may vary considerably between patients carrying the same mutation. The exact reasons are unknown, but evidence is increasing that various cardiac and non-cardiac conditions can influence the expressivity and severity of inherited SCN5A channelopathies. In this review, we provide a summary of identified disease entities caused by SCN5A mutations, and give an overview of co-morbidities and other (non)-genetic factors which may modify SCN5A channelopathies. A comprehensive knowledge of these modulatory factors is not only essential for a complete understanding of the diverse clinical phenotypes associated with SCN5A mutations, but also for successful development of effective risk stratification and (alternative) treatment paradigms.

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“…Mutations in SCN5A may also lead to overlapping phenotypes (SCN5A overlap syndromes), where clinical characteristics of LQTS, BrS, and other arrhythmia syndromes (conduction disease, sinus node dysfunction) coexist in a single family or even in a single patient [6,13]. Sinus node dysfunction (SND) is a relatively common observation in both LQTS3 and BrS1 patients [14,15].…”

Section: Aim Of the Studymentioning

confidence: 99%

Mechanism of Sinus Node Dysfunction in Carriers of the E161K Mutation in the SCN5A Gene

Wilders

2018

2018 Computing in Cardiology Conference (CinC)

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Heterozygous carriers of the E161K mutation in the SCN5A gene, which encodes the Na V 1.5 pore-forming αsubunit of the ion channel carrying the cardiac fast sodium current (I Na), show sinus node dysfunction. We assessed the mechanism by which the E161K mutation causes sinus bradycardia and reduces atrial excitability, as well as the potential role of the common H558R polymorphism. To this end, we incorporated reported mutation-induced changes in I Na into the recently developed Fabbri-Severi model of a single human sinoatrial node (SAN) cell. The threshold current of the Courtemanche-Ramirez-Nattel human right atrial cell model was used as a measure of atrial excitability. The E161K/H558 mutation significantly increased the cycle length of the SAN cell, in particular under vagal tone. The mutant component of I Na was effectively zero, thus slowing diastolic depolarization. Highly similar results were obtained with the E161K/R558 mutation. The E161K mutation increased the threshold stimulus current of the atrial cell by a factor of ≈2.2, virtually independent of the H558 or R558 background. We conclude that the E161K mutation underlies the clinically observed sinus node dysfunction. Furthermore, we conclude that the common H558R polymorphism does not significantly alter the effects of the E161K mutation.

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Brugada syndrome and sinus node dysfunction

Cited by 20 publications

References 53 publications

A Clinical Study Starting from an Encounter with a Patient

A Clinical Study Starting from an Encounter with a Patient

Disease Modifiers of Inherited SCN5A Channelopathy

Mechanism of Sinus Node Dysfunction in Carriers of the E161K Mutation in the SCN5A Gene

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