Editing Brugada syndrome (section)

== Mechanisms ==
[[File:Wavebreak and re-entry as a mechanism of arrhythmias.png|thumb|upright=1.3|Adjacent regions of cardiac tissue with differing refractory periods can lead to a normally smooth wavefront of depolarisation undergoing wavebreak leading to re-entrant arrhythmias]]
The abnormal heart rhythms seen in those with Brugada syndrome are typically dangerous arrhythmias such as ventricular fibrillation or polymorphic ventricular tachycardia, but those with BrS are also more likely to experience rapid heart rates due to less dangerous arrhythmias such as [[AV nodal reentrant tachycardia|AV nodal re-entrant tachycardia]]<ref>{{cite journal|vauthors=Hasdemir C, Payzin S, Kocabas U, Sahin H, Yildirim N, Alp A, Aydin M, Pfeiffer R, Burashnikov E, Wu Y, Antzelevitch C|date=July 2015|title=High prevalence of concealed Brugada syndrome in patients with atrioventricular nodal reentrant tachycardia|journal=Heart Rhythm|volume=12|issue=7|pages=1584–94|doi=10.1016/j.hrthm.2015.03.015|pmid=25998140}}</ref> and abnormally slow heart rhythms such as [[Sick sinus syndrome|sinus node dysfunction]].<ref>{{cite journal|vauthors=Letsas KP, Korantzopoulos P, Efremidis M, Weber R, Lioni L, Bakosis G, Vassilikos VP, Deftereos S, Sideris A, Arentz T|date=March 2013|title=Sinus node disease in subjects with type 1 ECG pattern of Brugada syndrome|journal=Journal of Cardiology|volume=61|issue=3|pages=227–31|doi=10.1016/j.jjcc.2012.12.006|pmid=23403368|doi-access=free}}</ref> There are several mechanisms by which the genetic mutations causing this condition might produce these arrhythmias.<ref name="Wilde_2010">{{cite journal | vauthors = Wilde AA, Postema PG, Di Diego JM, Viskin S, Morita H, Fish JM, Antzelevitch C | title = The pathophysiological mechanism underlying Brugada syndrome: depolarization versus repolarization | journal = Journal of Molecular and Cellular Cardiology | volume = 49 | issue = 4 | pages = 543–53 | date = October 2010 | pmid = 20659475 | pmc = 2932806 | doi = 10.1016/j.yjmcc.2010.07.012 }}</ref>

Some argue that the main reason these arrhythmias arise is due to abnormally slow electrical conduction in areas of the heart, specifically the [[Ventricle (heart)|right ventricle]].  The genetic variants associated with BrS support the concept as SCN5A, the gene most commonly associated with the condition, along with SCN10A, SCN1B, SCN2B and SCN3B, all directly affect the sodium current ''I''<sub>Na</sub>. The sodium current is a major contributor to the characteristic flow of electrical charge across the membrane of heart muscle cells that occurs with each heartbeat known as the [[Cardiac action potential|action potential]].  ''I''<sub>Na</sub> causes the initial rapid upstroke of the action potential (phase 0), and decreasing the early peak current, as occurs in BrS-associated genetic variants, leads to slowing of the electrical conduction through the heart muscle.<ref name="Ant2013" /> This slow conduction allows 'short circuits' to form, blocking the waves of electrical activity in some areas while allowing the waves to pass in others in a phenomenon known as wavebreak.  Given the right circumstances, this wavebreak can allow the waves of electricity to perform a U-turn within the muscle, travelling in the reverse direction before beginning to rapidly circle around a point, referred to as re-entry, and causing an abnormal heart rhythm.<ref name="Ant2013" /> Those who support this view (known as the depolarisation hypothesis) argue that conduction slowing may explain why arrhythmias in those with Brugada syndrome tend to occur in middle age, when other factors such as scarring or fibrosis that accompany old age have exacerbated the tendency to conduction slowing caused by the genetic mutation.<ref name="Wilde_2010" />

Others suggest that the main cause of arrhythmias is a difference in the electrical properties between the inside ([[endocardium]]) and outside ([[Pericardium|epicardium]]) of the heart (known as the repolarisation hypothesis).<ref name="Ant2013" /> The shape of the action potential differs between the epicardium and the endocardium. The action potential in cells from the epicardium shows a prominent notch after the initial spike due to a transient outward current. This notch is far less evident in cells from the endocardium, and the difference between the endocardium and epicardium are most clearly seen in the right ventricle. In those with Brugada syndrome, these differences are increased, creating a brief period within each cardiac cycle when current flows from the endocardium to the epicardium creating the characteristic ECG pattern.  The differences in electrical properties between the epi- and endocardium are described as a 'transmural dispersion of repolarisation" which if large enough can lead to electrical impulses becoming blocked in some regions but not others.  Once again, this wavebreak can allow the waves of electricity which usually travel in only one direction to instead begin circling around a point as a re-entrant circuit, causing an arrhythmia.<ref name="Ant2013" />

A further factor promoting arrhythmias in Brugada syndrome is changes to the structure of the heart.<ref name="Wilde_2010" /> Whilst the heart of those with Brugada syndrome may look normal, scarring or fibrosis is often seen in particular regions of the heart, specifically the right ventricular outflow tract.  As Brugada syndrome can be caused by mutation in many different genes, it is possible that different mechanisms may be responsible for the arrhythmias seen in different patients.<ref name="Wilde_2010" />