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==Overview==
==Overview==
The '''Brugada syndrome''' is a genetic disease that is characterized by abnormal [[electrocardiogram]] (EKG) findings and an increased risk of [[sudden cardiac death]] in young adults, and occasionally in children and infants.
Brugada syndrome is a genetic disease that is characterized by abnormal [[electrocardiogram]] (EKG) findings and an increased risk of [[sudden cardiac death]] in young adults, and occasionally in children and infants. Brugada syndrome is a condition that causes a disruption of the heart's normal rhythm. Specifically, this disorder can lead to uncoordinated electrical activity in the heart's lower chambers ([[ventricles]]), an abnormality called [[ventricular arrhythmia]]. If untreated, the irregular heartbeats can cause [[fainting]] ([[syncope]]), [[seizures]], [[difficulty breathing]], or [[sudden death]]. These complications typically occur when an affected person is resting or asleep.
 
==Historical Perspective ==
The Brugada brothers were the first to describe the syndrome's characteristic EKG recordings and associate them with sudden death.
 
Before this association, the syndrome's characteristic EKG findings were often mistaken for a [[right ventricular myocardial infarction]]. In 1953 a publication by Oscher and Wolf mentioned that despite being mistaken for right ventricular myocardial infarction, the syndrome's characteristic EKG recordings were not associated with myocardial ischemia.<ref name="pmid13104407">{{cite journal |author=OSHER HL, WOLFF L |title=Electrocardiographic pattern simulating acute myocardial injury |journal=[[The American Journal of the Medical Sciences]] |volume=226 |issue=5 |pages=541–5 |year=1953 |month=November |pmid=13104407 |doi= |url= |issn= |accessdate=2012-10-13}}</ref>
 
Although the EKG recordings of Brugada syndrome were first reported<ref>Martini B, Nava A, Thiene G, Buja GF, Canciani B, Scognamiglio R, Daliento L, Dalla Volta S. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J 1989 Dec;118(6):1203-9 PMID 2589161</ref> among survivors of cardiac arrest in 1989, it was not until 1992  that the Brugada brothers<ref>Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol. 1992 Nov 15;20(6):1391-6. PMID 1309182</ref> recognized it as a distinct clinical entity that causes [[sudden cardiac death]] by triggering [[ventricular fibrillation]].


==Historical Perspective==
Brugada syndorme  was potentially first seen on [[EKG]] in survivors of cardiac arrest in 1989, but it was not until 1992 that the Brugada brothers recognized it as a distinct clinical entity which could cause [[sudden death]] by [[ventricular fibrillation]].
==Classification==
There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes.  Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as [[ajmaline]] and [[flecainide]].
==Pathophysiology==
==Pathophysiology==
Approximately 20% of the cases of Brugada syndrome have been shown to be associated with mutation(s) in the [[gene]] that encodes for the [[sodium]] [[ion channel]] in the [[cell (biology)|cell]] [[cell membrane|membrane]]s of the muscle cells of the heart ([[myocyte]]s). The gene, named [[SCN5A]], is located on the short arm of the third [[chromosome]] (3p21). Loss-of-function mutations in this gene lead to a loss of the action potential dome of some epicardial areas of the right ventricle. This results in transmural and epicardial dispersion of repolarization.  Over 160 mutations in the SCN5A gene have been discovered to date, each having varying mechanisms and effects on function, thereby explaining the varying degrees of penetration and expression of this disorder. <ref name="pmid16972995">{{cite journal |author=Napolitano C, Priori SG |title=Brugada syndrome |journal=Orphanet journal of rare diseases |volume=1 |issue= |pages=35 |year=2006 |pmid=16972995 |doi=10.1186/1750-1172-1-35}}</ref>
Approximately 20% of persons with Brugada syndome have a mutation in the gene [[SCN5A]]. This gene encodes for the sodium ion channel. The mutation is inherited in an [[autosomal dominant]] pattern, and is more commonly seen in males. Brugada syndrome has also been shown to result from defects in a calcium channel.
 
==Differentiating Brugada syndrome from other Diseases==
==Differentiating Brugada Syndrome from other Diseases==
Brugada syndrome should be differentiated from other cardiac disorders, electrolyte disturbances, and drug intoxication syndromes. The condition which most similarly presents to Brugada syndrome is [[arrhythmogenic right ventricular dysplasia]], as they both cause [[sudden cardiac death]] in children. Brugada syndrome can be differentiated from [[arrhythmogenic right ventricular dysplasia]] by the genetic counterpart of [[SCN5A]], the lack of structural abnormalities within the heart, the association with [[polymorphic ventricular tachycardia]] during sleep, and [[EKG]] changes that are enhanced by vagotonic agents.
Abnormalities that can lead to ST-segment elevation in the right precordial leads include the following:<ref name="pmid14687250">{{cite journal |author=Takehara N, Makita N, Kawabe J, Sato N, Kawamura Y, Kitabatake A, Kikuchi K |title=A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill |journal=[[Journal of Internal Medicine]] |volume=255 |issue=1 |pages=137–42 |year=2004 |month=January |pmid=14687250 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-6820&date=2004&volume=255&issue=1&spage=137 |issn= |accessdate=2012-10-13}}</ref>
 
* [[myocardial ischemia|Acute myocardial ischemia]] or [[Acute myocardial infarction|infarction]]
* [[Acute myocarditis]]
* [[Acute pericarditis]]
* [[Acute pulmonary thromboemboli]]
* [[Arrhythmogenic right ventricular dysplasia]] / [[Arrhythmogenic right ventricular dysplasia|cardiomyopathy]] ([[Arrhythmogenic right ventricular dysplasia|ARVD/C]])<ref>Corrado  D,  Nava  A,  Buja  G,  Martini  B,  Fasoli  G,  Oselladore  L,  Turrini  P,  Thiene  G.  Familial cardiomyopathy  underlies syndrome of right bundle branch block, ST segment elevation and sudden death. J Am Coll Cardiol.  1996;  27:  443–448.</ref><ref> Corrado  D,  Basso  C,  Buja  G,  Nava  A,  Rossi  L,  Thiene  G.  Right bundle branch block, right precordial ST-segment elevation, and sudden death in young people. Circulation.  2001;  103:  710–717.</ref>
 
* [[Cardioversion]]. Brugada-like ECG changes can be observed briefly after direct-current cardioversion.  It is currently unclear if this is a sign that the patient is a gene carrier for Brugada syndrome.<ref name="pmid10758932">{{cite journal |author=Kok LC, Mitchell MA, Haines DE, Mounsey JP, DiMarco JP |title=Transient ST elevation after transthoracic cardioversion in patients with hemodynamically unstable ventricular tachyarrhythmia |journal=[[The American Journal of Cardiology]] |volume=85 |issue=7 |pages=878–81, A9 |year=2000 |month=April |pmid=10758932 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914999008863 |issn= |accessdate=2012-10-14}}</ref><ref name="pmid12929296">{{cite journal |author=Gurevitz O, Glikson M |title=Cardiac resynchronization therapy: a new frontier in the management of heart failure |journal=[[The Israel Medical Association Journal : IMAJ]] |volume=5 |issue=8 |pages=571–5 |year=2003 |month=August |pmid=12929296 |doi= |url= |issn= |accessdate=2012-10-14}}</ref><ref name="pmid12418739">{{cite journal |author=Gurevitz O, Lipchenca I, Yaacoby E, Segal E, Perel A, Eldar M, Glikson M |title=ST-segment deviation following implantable cardioverter defibrillator shocks: incidence, timing, and clinical significance |journal=[[Pacing and Clinical Electrophysiology : PACE]] |volume=25 |issue=10 |pages=1429–32 |year=2002 |month=October |pmid=12418739 |doi= |url= |issn= |accessdate=2012-10-14}}</ref>
* [[Cocaine intoxication]]
* [[Coronary spasm]]
* [[Dissecting aortic aneurysm]]<ref>
Myers  GB.  Other QRS-T patterns that may be mistaken for myocardial infarction; IV. Alterations in blood potassium; myocardial ischemia; subepicardial myocarditis; distortion associated with arrhythmias. Circulation.  1950;  2:  75–93.</ref>
 
* [[Duchenne muscular dystrophy]]<ref>''Perloff JK, Henze E, Schelbert HR. Alterations in regional myocardial metabolism, perfusion, and wall motion in Duchenne muscular dystrophy studied by radionuclide imaging. Circulation''. '' 1984; 69: 33–42.''</ref>
* [[Early repolarization]]
* [[Friedreich ataxia]]
* [[Heterocyclic antidepressant overdose]]
* [[Hypercalcemia]]<ref name="pmid6475795">{{cite journal |author=Douglas PS, Carmichael KA, Palevsky PM |title=Extreme hypercalcemia and electrocardiographic changes |journal=[[The American Journal of Cardiology]] |volume=54 |issue=6 |pages=674–5 |year=1984 |month=September |pmid=6475795 |doi= |url= |issn= |accessdate=2012-10-13}}</ref><ref name="pmid6475794">{{cite journal |author=Sridharan MR, Horan LG |title=Electrocardiographic J wave of hypercalcemia |journal=[[The American Journal of Cardiology]] |volume=54 |issue=6 |pages=672–3 |year=1984 |month=September |pmid=6475794 |doi= |url= |issn= |accessdate=2012-10-13}}</ref>
* [[Hyperkalemia]]<ref>Myers  GB.  Other QRS-T patterns that may be mistaken for myocardial infarction; IV. Alterations in blood potassium; myocardial ischemia; subepicardial myocarditis; distortion associated with arrhythmias. Circulation. 1950;  2:  75–93.</ref><ref>Merrill  JP,  Levine  HD, Somerville  W,  Smith  S.  Clinical recognition and treatment of acute potassium intoxication.        Ann Intern Med.  1950;  33:  797–830.</ref><ref name="pmid12413761">{{cite journal |author=Ortega-Carnicer J, Benezet J, Ruiz-Lorenzo F, Alcázar R |title=Transient Brugada-type electrocardiographic abnormalities in renal failure reversed by dialysis |journal=[[Resuscitation]] |volume=55 |issue=2 |pages=215–9 |year=2002 |month=November |pmid=12413761 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0300957202002101 |issn= |accessdate=2012-10-13}}</ref>
* [[Hypothermia]], can cause an [[Osborn wave]] on the ECG which can sometimes resemble Brugada syndrome<ref> <div>'' Osborn JJ. Experimental hypothermia; respiratory and blood pH changes in relation to cardiac function. Am J Physiol''. '' 1953; 175: 389–398.''</div> </ref><ref name="pmid12693512">{{cite journal |author=Noda T, Shimizu W, Tanaka K, Chayama K |title=Prominent J wave and ST segment elevation: serial electrocardiographic changes in accidental hypothermia |journal=[[Journal of Cardiovascular Electrophysiology]] |volume=14 |issue=2 |pages=223 |year=2003 |month=February |pmid=12693512 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1045-3873&date=2003&volume=14&issue=2&spage=223 |issn= |accessdate=2012-10-13}}</ref>
* [[Left ventricular hypertrophy]]
* [[Pectus excavatum]]<ref> <div>'' Kataoka H. Electrocardiographic patterns of the Brugada syndrome in right ventricular infarction/ischemia. Am J Cardiol''. '' 2000; 86: 1056.''</div></ref>
* [[Prinzmetal's angina]]<ref name="pmid14645641">{{cite journal |author=Wang K, Asinger RW, Marriott HJ |title=ST-segment elevation in conditions other than acute myocardial infarction |journal=[[The New England Journal of Medicine]] |volume=349 |issue=22 |pages=2128–35 |year=2003 |month=November |pmid=14645641 |doi=10.1056/NEJMra022580 |url=http://www.nejm.org/doi/abs/10.1056/NEJMra022580?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |issn= |accessdate=2012-10-13}}</ref>
* [[Right ventricular outflow tract obstruction|Mediastinal tumor compressing the right ventricular outflow tract]] ([[RVOT]])
* [[RBBB|Right]] or [[left bundle-branch block]] (atypical)
* [[Right ventricular infarction]]
* [[Right ventricular ischemia]]
* [[Right ventricular outflow tract]] compression due to a [[mediastinal tumor]]<ref name="pmid10461308">{{cite journal |author=Tarín N, Farré J, Rubio JM, Tuñón J, Castro-Dorticós J |title=Brugada-like electrocardiographic pattern in a patient with a mediastinal tumor |journal=[[Pacing and Clinical Electrophysiology : PACE]] |volume=22 |issue=8 |pages=1264–6 |year=1999 |month=August |pmid=10461308 |doi= |url= |issn= |accessdate=2012-10-13}}</ref>or [[hemopericardium]]<ref>''Tomcsanyi J, Simor T, Papp L. Images in cardiology. Haemopericardium and Brugada-like ECG pattern in rheumatoid arthritis. Heart''. '' 2002; 87: 234.''</ref>
* [[Thiamine deficiency]]<ref name="pmid7197132">{{cite journal |author=Read DH, Harrington DD |title=Experimentally induced thiamine deficiency in beagle dogs: clinical observations |journal=[[American Journal of Veterinary Research]] |volume=42 |issue=6 |pages=984–91 |year=1981 |month=June |pmid=7197132 |doi= |url= |issn= |accessdate=2012-10-13}}</ref>
* Various central and autonomic nervous system abnormalities
* [[Other conditions that can lead to ST-segment elevation in the right precordial leads]]
* [[Early repolarization syndrome]]
* Other normal variants (particularly in males)
 
==Differentiating Brugada Syndrome from Arrhythmogenic Right Ventricular Dysplasia==
Although both Brugada syndrome and [[Arrhythmogenic Right Ventricular Dysplasia]] are associated with [[sudden cardiac death]] in young patients, the two syndromes are fairly easy to distinguish electrocardiographically and clinically.
===Genetics===
There is only one gene associated with Brugada syndrome, namely the SCN5A gene, and there is no overlap of the genetic abnormalities associated with [[Arrhythmogenic Right Ventricular Dysplasia]].
 
=== Structural Abnormalities of the right Ventricle===
While Brugada syndrome is not associated with structural abnormalities in the right ventricle, [[arrhythmogenic right ventricular dysplasia]] is associated with fibrofatty infiltration.
 
=== Precipitant of Ventricular Arrhythmias===
[[Arrhythmogenic right ventricular dysplasia]] is associated with [[monomorphic ventricular tachycardia]] with a left bundle branch morphology and is precipitated by catecholamines or exercise. In contrast, Brugada syndrome is associated with [[polymorphic ventricular tachycardia]] and occurs predominantly during sleep or rest.
 
=== Response to Pharmacologic Agents===
The EKG abnormalities of Brugada syndrome are enhanced by [[vagotonic]] agents, beta-adrenergic blockers, and sodium channel blockers whereas the EKG changes of [[arrhythmogenic right ventricular dysplasia]] are constant and do not very with vagotonic agents, beta-adrenergic blockers, or sodium channel blockers.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
Insofar as Brugada syndrome is a relatively newly recognized syndrome, its incidence and prevalence continues to increase.  Brugada syndrome is quite common in Southeast Asia where it is endemic, and affects 50 out of every 10,000 individuals.  It is the second leading cause of death after car accidents among young people in these countries.  It has been estimated that Brugada syndrome accounts for 4% of all sudden cardiac deaths and 20% of sudden cardiac deaths among patients with structurally normal hearts.  It is 8-10 times more common in men.
Insofar as Brugada syndrome is a relatively newly recognized syndrome, its [[incidence]] and [[prevalence]] continues to increase.  Brugada syndrome is quite common in Southeast Asia where it is [[endemic]], and affects 500 out of every 100,000 individuals.  It is the second leading cause of death after car accidents among young people in these countries.  It has been estimated that Brugada syndrome accounts for 4% of all sudden cardiac deaths and 20% of [[sudden cardiac death]]s among patients with structurally normal hearts.  It is 8-10 times more common in men.


==Prevalence==
==Risk Factors==
The prevalence of the Brugada syndrome is estimated at 5-50:10,000, largely depending on geographic location.  
The EKG changes of Brugada syndrome can vary over time, depending on the autonomic balance and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the [[ST segment]] elevation, while [[vagal stimulation]] worsens it.  During sleep, there is [[heightened vagal tone]], and the pattern may be exacerbated at that time (as is the risk of [[sudden cardiac death]] at that time).  The administration of class Ia, Ic and III drugs increases the [[ST segment]] elevation, as does [[fever]]. The impact of exercise depends upon when the EKG is obtained: during exercise the [[ST segment]] elevation may decrease but may increase later after exercise when the body temperature has risen.  Similar to [[early repolarization variant]], when the heart rate decreases, the [[ST segment]] elevation increases and when the heart rate increases the [[ST segment]] elevation decreases.  While Brugada syndrome is often associated with polymorphic VT which may be self terminating, in the presence of autonomic imbalance, [[hypokalemia]], fever or exacerbating drugs sustained [[ventricular fibrillation]] and [[sudden cardiac death]] may result.<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-14}}</ref>


==Age==
==Screening==
The average age at the time of initial diagnosis or sudden death is 40 ± 22 years, with the youngest patient diagnosed at 2 days of age and the oldest at 84 years. Brugada syndrome usually becomes apparent in adulthood, although signs and symptoms, including sudden death, can occur any time from early infancy to old age. The mean age of sudden death is approximately 40 years. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than one year. It is characterized by sudden and unexplained death, usually during sleep.  Sudden unexplained nocturnal death syndrome (SUNDS) is a condition characterized by unexpected cardiac arrest in young adults, usually at night during sleep. This condition was originally described in Southeast Asian populations, where it is a major cause of death. Researchers have determined that SUNDS and Brugada syndrome are the same disorder.
Relatives of patients with Brugada syndrome can be screened for the syndrome by obtaining an [[EKG]], although the diagnostic pattern may be concealed.  Genetic testing can also be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-14}}</ref> Unfortunately, despite the association of the Brugada syndrome with the [[SCN5A]] genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis.


==Race==
==Natural History, Complications and Prognosis==
This condition occurs much more frequently in people of Asian ancestry, particularly in Japanese and Southeast Asian populations.  It is the most common cause of sudden death in young men without known underlying cardiac disease in Thailand and Laos<ref>Brugada J, Brugada P, Brugada R. The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome. Europace. 1999 Jul;1(3):156-66. PMID 11225790 </ref>.  In some southeast Asian countries the disease is considered endemic and believed to be the second cause of death among young men (after car accidents). In these countries Brugada syndrome is believed to underly (in part) the 'Sudden Unexpected Death Syndrome' (SUDS). This relation has, however, not been thoroughly investigated and there are almost no epidemiological studies into Brugada syndrome ECGs (apart from Japan). In different Asian countries, different names have been given to SUDS: in the Phillipines it is called ''bangungut'' (to rise and moan in sleep) and in Thailand ''lai tai'' (death during sleep).
Brugada syndrome usually becomes apparent in adulthood, although it may present in infants and children as [[sudden cardiac death]]. The mean age of sudden death in patients with Brugada syndrome is 40 years old. The Brugada patient may develop atrial arrhythmias and abnormalities in atrial conduction, and these abnormalities are associated with inducibility of [[ventricular fibrillation]]. Implantation of a cardiac defibrillator [[AICD]] can improve prognosis for some.


==Gender==
==Diagnosis==
Although Brugada syndrome affects both men and women, the condition appears to be 8 to 10 times more common in men. Researchers suspect that testosterone, a sex hormone present at much higher levels in men, may be responsible for this difference.
===Diagnostic Criteria===
The diagnosis of brugada syndrome is based upon electrocardiographic and clinical criteria. Only the Type I Brugada pattern qualifies as part of the diagnostic criteria for Brugada syndrome. Other rhythm abnormalities and family history are also taken into account when making the diagnosis of Brugada syndrome.


==Risk Factors: Agents and Scenarios that Provoke the Brugada Syndrome Pattern==
===History and Symptoms===
The EKG changes of Brugada syndrome can vary over time, depending on the autonomic balance and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the [[ST segment]] elevation, while [[vagal stimulation]] worsens it.  During sleep, there is [[heightened vagal tone]], and the pattern may be exacerbated at that time (as is the risk of [[sudden cardiac death]] at that time). The administration of class Ia, Ic and III drugs increases the [[ST segment]] elevation, as does [[fever]]. The impact of exercise depends upon when the EKG is obtained: during exercise the [[ST segment]] elevation may decrease but may increase later after exercise when the body temperature has risen.  Similar to [[early repolarization variant]], when the heart rate decreases, the [[ST segment]] elevation increases and when the heart rate increases the [[ST segment]] elevation decreases.  While Brugada syndrome is often associated with polymorphic VT which may be self terminating, in the presence of autonomic imbalance, hypokalemia, fever or exacerbating drugs sustained ventricular fibrillation and sudden cardiac death may result.<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-14}}</ref>
Patients with Brugada syndrome will sometimes have a family history of [[sudden cardiac death]] and a personal history of of arrhythmias. If patients are symptomatic they often have symptoms of [[syncope]], [[seizures]], [[agonal breathing]], difficulty breathing, and patients may even present with [[sudden death]].  These symptoms most often come on either at rest or during sleep.


The electrocardiographic findings of Brugada syndrome are often concealed, but can be unmasked or modulated by a number of drugs and pathophysiological states including (in alphabetical order)<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-13}}</ref>:
===Physical Examination===
*A combination of [[glucose]] and [[insulin]]<ref name="pmid12687840">{{cite journal| author=Nogami A, Nakao M, Kubota S, Sugiyasu A, Doi H, Yokoyama K et al.| title=Enhancement of J-ST-segment elevation by the glucose and insulin test in Brugada syndrome. | journal=Pacing Clin Electrophysiol | year= 2003 | volume= 26 | issue= 1 Pt 2 | pages= 332-7 | pmid=12687840 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12687840  }} </ref>. In Thailand large meals of glutinous sticky carbohydrate rich rice have been associated with sudden cardiac death.<ref name="pmid1681278">{{cite journal |author=Nimmannit S, Malasit P, Chaovakul V, Susaengrat W, Vasuvattakul S, Nilwarangkur S |title=Pathogenesis of sudden unexplained nocturnal death (lai tai) and endemic distal renal tubular acidosis |journal=[[Lancet]] |volume=338 |issue=8772 |pages=930–2 |year=1991 |month=October |pmid=1681278 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0140-6736(91)91786-T |issn= |accessdate=2012-10-14}}</ref>
Insofar as Brugada syndrome is not associated with any structural heart disease, there are generally no abnormalities on physical examination.  [[Vagal maneuvers]] such as [[carotid sinus massage]] may increase vagal tone and may unmask the presence of a Type I Brugada pattern.  In a patient who has experienced recent symptoms such as [[syncope]], it is important to check the temperature in so far as fever may trigger a self terminating or sustained episode of [[ventricular tachycardia]] / [[ventricular fibrillation]]. The presence of fever is also a target of [[antipyretic]] therapy.
*[[Ajmaline]]<ref name="pmid12804924">{{cite journal| author=Rolf S, Bruns HJ, Wichter T, Kirchhof P, Ribbing M, Wasmer K et al.| title=The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and recommended protocol. | journal=Eur Heart J | year= 2003 | volume= 24 | issue= 12 | pages= 1104-12 | pmid=12804924 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12804924 }} </ref> (a diagnostic test agent)
*[[α-adrenergic agonists]]<ref name="pmid8609322">{{cite journal| author=Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S| title=Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. | journal=J Am Coll Cardiol | year= 1996 | volume= 27 | issue= 5 | pages= 1061-70 | pmid=8609322 | doi=10.1016/0735-1097(95)00613-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8609322  }} </ref>
*[[β-adrenergic blockers]]<ref name="pmid10750126">{{cite journal| author=Brugada P, Brugada J, Brugada R| title=Arrhythmia induction by antiarrhythmic drugs. | journal=Pacing Clin Electrophysiol | year= 2000 | volume= 23 | issue= 3 | pages= 291-2 | pmid=10750126 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10750126  }} </ref><ref name="pmid8609322">{{cite journal| author=Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S| title=Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. | journal=J Am Coll Cardiol | year= 1996 | volume= 27 | issue= 5 | pages= 1061-70 | pmid=8609322 | doi=10.1016/0735-1097(95)00613-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8609322  }} </ref> such as [[propranolol]].
*[[Calcium channel blockers]]
:*[[Diltiazem]]
:*[[Nifedipine]]
:*[[Verapamil]]
*[[Carotid sinus massage]]
*[[Cocaine]]<ref name="pmid11590577">{{cite journal| author=Ortega-Carnicer J, Bertos-Polo J, Gutiérrez-Tirado C| title=Aborted sudden death, transient Brugada pattern, and wide QRS dysrrhythmias after massive cocaine ingestion. | journal=J Electrocardiol | year= 2001 | volume= 34 | issue= 4 | pages= 345-9 | pmid=11590577 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11590577  }} </ref><ref name="pmid11204086">{{cite journal| author=Rouleau F, Asfar P, Boulet S, Dube L, Dupuis JM, Alquier P et al.| title=Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome. | journal=J Cardiovasc Electrophysiol | year= 2001 | volume= 12 | issue= 1 | pages= 61-5 | pmid=11204086 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11204086  }} </ref><ref name="pmid10943241">{{cite journal| author=Littmann L, Monroe MH, Svenson RH| title=Brugada-type electrocardiographic pattern induced by cocaine. | journal=Mayo Clin Proc | year= 2000 | volume= 75 | issue= 8 | pages= 845-9 | pmid=10943241 | doi=10.4065/75.8.845 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10943241 }} </ref>
*[[Dimenhydrinate]]
*Family History: In large studies, a family history of [[sudden cardiac death]] among patients with Brugada syndrome does not appear to be a risk factor for [[sudden cardiac death]] in siblings.
*[[Fever]]<ref name="pmid12494608">{{cite journal| author=Antzelevitch C, Brugada R| title=Fever and Brugada syndrome. | journal=Pacing Clin Electrophysiol | year= 2002 | volume= 25 | issue= 11 | pages= 1537-9 | pmid=12494608 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12494608  }} </ref>.<ref name="pmid10816181">{{cite journal| author=González Rebollo JM, Hernández Madrid A, García A, García de Castro A, Mejías A, Moro C| title=[Recurrent ventricular fibrillation during a febrile illness in a patient with the Brugada syndrome]. | journal=Rev Esp Cardiol | year= 2000 | volume= 53 | issue= 5 | pages= 755-7 | pmid=10816181 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10816181  }} </ref><ref name="pmid12049381">{{cite journal| author=Saura D, García-Alberola A, Carrillo P, Pascual D, Martínez-Sánchez J, Valdés M| title=Brugada-like electrocardiographic pattern induced by fever. | journal=Pacing Clin Electrophysiol | year= 2002 | volume= 25 | issue= 5 | pages= 856-9 | pmid=12049381 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12049381  }} </ref><ref name="pmid12494626">{{cite journal| author=Porres JM, Brugada J, Urbistondo V, García F, Reviejo K, Marco P| title=Fever unmasking the Brugada syndrome. | journal=Pacing Clin Electrophysiol | year= 2002 | volume= 25 | issue= 11 | pages= 1646-8 | pmid=12494626 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12494626  }} </ref><ref name="pmid12494630">{{cite journal| author=Kum LC, Fung JW, Sanderson JE| title=Brugada syndrome unmasked by febrile illness. | journal=Pacing Clin Electrophysiol | year= 2002 | volume= 25 | issue= 11 | pages= 1660-1 | pmid=12494630 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12494630  }} </ref> Hot baths and warm climates (such as that in Northeastern Thailand) may be precipitating factors for sudden cardiac death. It is for this reason that [[antipyretic]] agents are recommended to aggressively treat a fever in the patient with Brugada syndrome.
*[[Flecainide]]<ref name="pmid10750126">{{cite journal| author=Brugada P, Brugada J, Brugada R| title=Arrhythmia induction by antiarrhythmic drugs. | journal=Pacing Clin Electrophysiol | year= 2000 | volume= 23 | issue= 3 | pages= 291-2 | pmid=10750126 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10750126  }} </ref><ref name="pmid10090224">{{cite journal| author=Fujiki A, Usui M, Nagasawa H, Mizumaki K, Hayashi H, Inoue H| title=ST segment elevation in the right precordial leads induced with class IC antiarrhythmic drugs: insight into the mechanism of Brugada syndrome. | journal=J Cardiovasc Electrophysiol | year= 1999 | volume= 10 | issue= 2 | pages= 214-8 | pmid=10090224 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10090224  }} </ref><ref name="pmid9835260">{{cite journal| author=Krishnan SC, Josephson ME| title=ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. | journal=J Cardiovasc Electrophysiol | year= 1998 | volume= 9 | issue= 11 | pages= 1167-72 | pmid=9835260 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9835260  }} </ref><ref name="pmid12687841">{{cite journal| author=Gasparini M, Priori SG, Mantica M, Napolitano C, Galimberti P, Ceriotti C et al.| title=Flecainide test in Brugada syndrome: a reproducible but risky tool. | journal=Pacing Clin Electrophysiol | year= 2003 | volume= 26 | issue= 1 Pt 2 | pages= 338-41 | pmid=12687841 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12687841  }} </ref> (a diagnostic test agent)
*[[Hypercalcemia]]<ref name="pmid6475795">{{cite journal| author=Douglas PS, Carmichael KA, Palevsky PM| title=Extreme hypercalcemia and electrocardiographic changes. | journal=Am J Cardiol | year= 1984 | volume= 54 | issue= 6 | pages= 674-5 | pmid=6475795 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6475795  }} </ref><ref name="pmid6475794">{{cite journal| author=Sridharan MR, Horan LG| title=Electrocardiographic J wave of hypercalcemia. | journal=Am J Cardiol | year= 1984 | volume= 54 | issue= 6 | pages= 672-3 | pmid=6475794 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6475794  }} </ref>
*[[Hyperkalemia]]<ref name="pmid15427197">{{cite journal| author=MYERS GB| title=Other QRS-T patterns that may be mistaken for myocardial infarction; IV. alterations in blood potassium; myocardial ischemia; subepicardial myocarditis; distortion associated with arrhythmias. | journal=Circulation | year= 1950 | volume= 2 | issue= 1 | pages= 75-93 | pmid=15427197 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15427197  }} </ref><ref name="pmid14771753">{{cite journal| author=MERRILL JP, LEVINE HD, SOMERVILLE W, SMITH S| title=Clinical recognition and treatment of acute potassium intoxication. | journal=Ann Intern Med | year= 1950 | volume= 33 | issue= 4 | pages= 797-830 | pmid=14771753 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14771753  }} </ref><ref name="pmid12413761">{{cite journal| author=Ortega-Carnicer J, Benezet J, Ruiz-Lorenzo F, Alcázar R| title=Transient Brugada-type electrocardiographic abnormalities in renal failure reversed by dialysis. | journal=Resuscitation | year= 2002 | volume= 55 | issue= 2 | pages= 215-9 | pmid=12413761 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12413761  }} </ref>
*[[Hypokalemia]].<ref name="pmid12520160">{{cite journal| author=Araki T, Konno T, Itoh H, Ino H, Shimizu M| title=Brugada syndrome with ventricular tachycardia and fibrillation related to hypokalemia. | journal=Circ J | year= 2003 | volume= 67 | issue= 1 | pages= 93-5 | pmid=12520160 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12520160  }} </ref> [[Hypokalemia]] in a patient with Brugada syndrome may trigger sustained [[ventricular fibrillation]] and [[sudden cardiac death]].  In northeastern Thailand where potassium deficiency is widespread, there is a higher incidence of [[sudden cardiac death]] than is observed in Bangkok where potassium levels in food are much higher.<ref name="pmid1681278">{{cite journal |author=Nimmannit S, Malasit P, Chaovakul V, Susaengrat W, Vasuvattakul S, Nilwarangkur S |title=Pathogenesis of sudden unexplained nocturnal death (lai tai) and endemic distal renal tubular acidosis |journal=[[Lancet]] |volume=338 |issue=8772 |pages=930–2 |year=1991 |month=October |pmid=1681278 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0140-6736(91)91786-T |issn= |accessdate=2012-10-14}}</ref>
*[[Lithium]]. Administration of [[Lithium]] can result in EKG manifestations of the Brugada syndrome. <ref>Pirotte  MJ,  Mueller  JG,  Poprawski  T.  A case report of Brugada-type  electrocardiographic changes in a patient taking lithium. Am J Emerg Med.  2008;  26:  113.</ref><ref>Wright D, Salehian O. Brugada-Type Electrocardiographic Changes Induced by Long-Term Lithium Use. Circulation, FRCPC2010;122:e418-e419</ref>.  [[Syncope]] and [[sudden cardiac death]] have been observed in these patients.<ref>Laske  C,  Soekadar  SR,  Laszlo  R,  Plewnia  C.  Brugada syndrome in a patient treated with lithium. Am J Psychiatry.  2007;  164:  1440–1441. </ref> The putative role of [[lithium]] has been suggested in so far as withdrawal of [[lithium]] results in either 1) normalization of the ECG or 2) conversion of the Brugada pattern to type 2 or 3. The appearance of Brugada type EKG patterns does not require toxic [[lithium]] levels.
*[[Phenothiazine]]s
:*[[Perphenazine]]
:*[[Cyamemazine]]
*[[Potassium channel openers]] such as [[nicorandil]].
*[[Procainamide]]<ref name="pmid10750126">{{cite journal| author=Brugada P, Brugada J, Brugada R| title=Arrhythmia induction by antiarrhythmic drugs. | journal=Pacing Clin Electrophysiol | year= 2000 | volume= 23 | issue= 3 | pages= 291-2 | pmid=10750126 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10750126  }} </ref> <ref name="pmid8609322">{{cite journal| author=Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S| title=Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. | journal=J Am Coll Cardiol | year= 1996 | volume= 27 | issue= 5 | pages= 1061-70 | pmid=8609322 | doi=10.1016/0735-1097(95)00613-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8609322  }} </ref>(a diagnostic test agent)
*[[Propranolol]] intoxication<ref name="pmid15817098">{{cite journal| author=Aouate P, Clerc J, Viard P, Seoud J| title=Propranolol intoxication revealing a Brugada syndrome. | journal=J Cardiovasc Electrophysiol | year= 2005 | volume= 16 | issue= 3 | pages= 348-51 | pmid=15817098 | doi=10.1046/j.1540-8167.2005.40564.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15817098  }} </ref>
*[[Selective serotonin reuptake inhibitors]]
:*[[Fluoxetine]]
* Shaving due to [[vagal stimulation]]<ref name="pmid9142005">{{cite journal| author=Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T, Isogai R et al.| title=Idiopathic ventricular fibrillation induced with vagal activity in patients without obvious heart disease. | journal=Circulation | year= 1997 | volume= 95 | issue= 9 | pages= 2277-85 | pmid=9142005 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9142005  }} </ref><ref name="pmid15175062">{{cite journal| author=Mizumaki K, Fujiki A, Tsuneda T, Sakabe M, Nishida K, Sugao M et al.| title=Vagal activity modulates spontaneous augmentation of ST elevation in the daily life of patients with Brugada syndrome. | journal=J Cardiovasc Electrophysiol | year= 2004 | volume= 15 | issue= 6 | pages= 667-73 | pmid=15175062 | doi=10.1046/j.1540-8167.2004.03601.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15175062  }} </ref><ref name="pmid2397572">{{cite journal| author=Litovsky SH, Antzelevitch C| title=Differences in the electrophysiological response of canine ventricular subendocardium and subepicardium to acetylcholine and isoproterenol. A direct effect of acetylcholine in ventricular myocardium. | journal=Circ Res | year= 1990 | volume= 67 | issue= 3 | pages= 615-27 | pmid=2397572 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2397572  }} </ref>
*Sleep may exacerbate the electrocardiographic and clinical findings of brugada syndrome due to variations in the balance of sympathetic versus vagal tone, hormonal changes and other metabolic factors.<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-14}}</ref><ref>''Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T, Isogai R, Shoda M, Toyoshima Y, Hosoda S. Idiopathic ventricular fibrillation induced with vagal activity in patients without obvious heart disease. Circulation''. '' 1997; 95: 2277–2285.''</ref><ref name="pmid8174872">{{cite journal |author=Proclemer A, Facchin D, Feruglio GA, Nucifora R |title=[Recurrent ventricular fibrillation, right bundle-branch block and persistent ST segment elevation in V1-V3: a new arrhythmia syndrome? A clinical case report] |language=Italian |journal=[[Giornale Italiano Di Cardiologia]] |volume=23 |issue=12 |pages=1211–8 |year=1993 |month=December |pmid=8174872 |doi= |url= |issn= |accessdate=2012-10-14}}</ref><ref name="pmid15175062">{{cite journal |author=Mizumaki K, Fujiki A, Tsuneda T, Sakabe M, Nishida K, Sugao M, Inoue H |title=Vagal activity modulates spontaneous augmentation of ST elevation in the daily life of patients with Brugada syndrome |journal=[[Journal of Cardiovascular Electrophysiology]] |volume=15 |issue=6 |pages=667–73 |year=2004 |month=June |pmid=15175062 |doi=10.1046/j.1540-8167.2004.03601.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1045-3873&date=2004&volume=15&issue=6&spage=667 |issn= |accessdate=2012-10-14}}</ref>
*[[Sodium channel blockers]]<ref name="pmid10662748">{{cite journal| author=Brugada R, Brugada J, Antzelevitch C, Kirsch GE, Potenza D, Towbin JA et al.| title=Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. | journal=Circulation | year= 2000 | volume= 101 | issue= 5 | pages= 510-5 | pmid=10662748 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10662748  }} </ref><ref name="pmid10750126">{{cite journal| author=Brugada P, Brugada J, Brugada R| title=Arrhythmia induction by antiarrhythmic drugs. | journal=Pacing Clin Electrophysiol | year= 2000 | volume= 23 | issue= 3 | pages= 291-2 | pmid=10750126 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10750126  }} </ref><ref name="pmid11196553">{{cite journal| author=Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N et al.| title=Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. | journal=J Cardiovasc Electrophysiol | year= 2000 | volume= 11 | issue= 12 | pages= 1320-9 | pmid=11196553 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11196553  }} </ref><ref name="pmid9835260">{{cite journal| author=Krishnan SC, Josephson ME| title=ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. | journal=J Cardiovasc Electrophysiol | year= 1998 | volume= 9 | issue= 11 | pages= 1167-72 | pmid=9835260 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9835260  }} </ref> (a diagnostic test agent)
*[[Tetracyclic antidepressants]]<ref name="pmid9193039">{{cite journal| author=Bolognesi R, Tsialtas D, Vasini P, Conti M, Manca C| title=Abnormal ventricular repolarization mimicking myocardial infarction after heterocyclic antidepressant overdose. | journal=Am J Cardiol | year= 1997 | volume= 79 | issue= 2 | pages= 242-5 | pmid=9193039 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9193039  }} </ref>
:*[[Maprotiline]]
*[[Tricyclic antidepressants]]<ref name="pmid12015405">{{cite journal| author=Goldgran-Toledano D, Sideris G, Kevorkian JP| title=Overdose of cyclic antidepressants and the Brugada syndrome. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 20 | pages= 1591-2 | pmid=12015405 | doi=10.1056/NEJM200205163462020 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12015405  }} </ref><ref name="pmid11232630">{{cite journal| author=Tada H, Sticherling C, Oral H, Morady F| title=Brugada syndrome mimicked by tricyclic antidepressant overdose. | journal=J Cardiovasc Electrophysiol | year= 2001 | volume= 12 | issue= 2 | pages= 275 | pmid=11232630 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11232630  }} </ref><ref name="pmid9193039">{{cite journal| author=Bolognesi R, Tsialtas D, Vasini P, Conti M, Manca C| title=Abnormal ventricular repolarization mimicking myocardial infarction after heterocyclic antidepressant overdose. | journal=Am J Cardiol | year= 1997 | volume= 79 | issue= 2 | pages= 242-5 | pmid=9193039 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9193039  }} </ref><ref name="pmid11204086">{{cite journal| author=Rouleau F, Asfar P, Boulet S, Dube L, Dupuis JM, Alquier P et al.| title=Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome. | journal=J Cardiovasc Electrophysiol | year= 2001 | volume= 12 | issue= 1 | pages= 61-5 | pmid=11204086 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11204086  }} </ref>
:*[[Amitriptyline]]
:*[[Nortriptyline]]
:*[[Desipramine]]<ref name="pmid12173907">{{cite journal| author=Babaliaros VC, Hurst JW| title=Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine. | journal=Clin Cardiol | year= 2002 | volume= 25 | issue= 8 | pages= 395-8 | pmid=12173907 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12173907  }} </ref>
:*[[Clomipramine]]
*[[Vagotonic agents]], [[heightened vagal tone]] and [[vagal maneuvers]]<ref name="pmid9142005">{{cite journal| author=Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T, Isogai R et al.| title=Idiopathic ventricular fibrillation induced with vagal activity in patients without obvious heart disease. | journal=Circulation | year= 1997 | volume= 95 | issue= 9 | pages= 2277-85 | pmid=9142005 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9142005  }} </ref><ref name="pmid15175062">{{cite journal| author=Mizumaki K, Fujiki A, Tsuneda T, Sakabe M, Nishida K, Sugao M et al.| title=Vagal activity modulates spontaneous augmentation of ST elevation in the daily life of patients with Brugada syndrome. | journal=J Cardiovasc Electrophysiol | year= 2004 | volume= 15 | issue= 6 | pages= 667-73 | pmid=15175062 | doi=10.1046/j.1540-8167.2004.03601.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15175062  }} </ref><ref name="pmid2397572">{{cite journal| author=Litovsky SH, Antzelevitch C| title=Differences in the electrophysiological response of canine ventricular subendocardium and subepicardium to acetylcholine and isoproterenol. A direct effect of acetylcholine in ventricular myocardium. | journal=Circ Res | year= 1990 | volume= 67 | issue= 3 | pages= 615-27 | pmid=2397572 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2397572  }} </ref>


===Laboratory Findings===
[[Hypokalemia]] and [[hyperkalemia]] can both trigger either sustained or nonsustained episodes of [[ventricular tachycardia]] / [[ventricular fibrillation]] and serum electrolytes should therefore be checked.  Both alcohol and cocaine intoxication can be associated with either sustained or nonsustained episodes of ventricular tachycardia/ventricular fibrillation and a toxicology  screen should be ordered if there is a clinical suspicion. Likewise, tricyclic antidepressants can be associated with exacerbations of the syndrome, and levels of these agents should also be checked if there is a clinical suspicion.


==Natural History==
===Electrocardiogram===
Brugada syndrome usually becomes apparent in adulthood, although signs and symptoms, including sudden death, can occur any time from early infancy to old age. The mean age of sudden death is approximately 40 years. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than one year. It is characterized by sudden and unexplained death, usually during sleep. Sudden unexplained nocturnal death syndrome (SUNDS) is a condition characterized by unexpected cardiac arrest in young adults, usually at night during sleep. This condition was originally described in Southeast Asian populations, where it is a major cause of death. Researchers have determined that SUNDS and Brugada syndrome are the same disorder.
There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes. Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as [[ajmaline]] and [[flecainide]]. Type 1 Brugada syndrome may always be present on the EKG, or it may be elicited by the administration of particular drugs (e.g., Class IC antiarrythmic drugs that blocks sodium channels such as [[ajmaline]], [[flecainide]]) or it may be unmasked by various [[Brugada syndrome risk factors|triggers]] or [[Brugada syndrome risk factors|risk factors]].


Patients with Brugada syndrome frequently develop or are born with supraventricular tachycardias:<ref>Morita  H, Kusano-Fukushima  K,  Nagase  S,  Fujimoto  Y,  Hisamatsu  K,  Fujio  H,  Haraoka  K,  Kobayashi  M,  Morita        ST,  Nakamura  K,  Emori  T,  Matsubara  H,  Hina  K,  Kita  T,  Fukatani  M,  Ohe  T. Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome. J Am Coll Cardiol.  2002;  40:  1437–1444.</ref>
===Chest X Ray===
*[[Supraventricular tachycardia]]: 20% of Brugada patients
Insofar as Brugada syndrome is not associated with structural abnormalities of the heart, there are no associated abnormalities on the chest x-ray.
*[[Atrial fibrillation]]: 10% - 20% of Brugada patients
===Echocardiography or Ultrasound===
*[[Atrioventricular (AV) nodal reentrant tachycardia]]
There is ongoing controversy as to whether there are structural abnormalities among patients with Brugada syndrome. There was one small study of 11 patients with Brugada syndrome that demonstrated a rapid swinging motion shifting towards the right ventricle of the basal segment of the intraventricular septum and early systole in 73% (8/11) of patients with Brugada syndrome.  None of the control patients demonstrated this abnormality.<ref name="pmid18067763">{{cite journal |author=Huang ZR, Chen LL, Li WH, Tang QZ, Huang CX, Xie Q, Wu G, Fan L |title=Interventricular septum motion abnormalities: unexpected echocardiographic changes of Brugada syndrome |journal=[[Chinese Medical Journal]] |volume=120 |issue=21 |pages=1898–901 |year=2007 |month=November |pmid=18067763 |doi= |url=http://www.cmj.org/Periodical/LinkIn.asp?journal=Chinese%20Medical%20Journal&linkintype=pubmed&year=2007&vol=120&issue=21&beginpage=1898 |issn= |accessdate=2012-10-13}}</ref>
*[[Wolff-Parkinson-White syndrome]]<ref name="pmid11584469">{{cite journal |author=Eckardt L, Kirchhof P, Johna R, Haverkamp W, Breithardt G, Borggrefe M |title=Wolff-Parkinson-White syndrome associated with Brugada syndrome |journal=[[Pacing and Clinical Electrophysiology : PACE]] |volume=24 |issue=9 Pt 1 |pages=1423–4 |year=2001 |month=September |pmid=11584469 |doi= |url= |issn= |accessdate=2012-10-13}}</ref>


Disturbances of atrial conduction and sinus node function have also been reported:
===Electrophysiologic Studies===
* Prolonged sinus node recovery time and sinoatrial conduction time <ref name="pmid15118291">{{cite journal |author=Morita H, Fukushima-Kusano K, Nagase S, Miyaji K, Hiramatsu S, Banba K, Nishii N, Watanabe A, Kakishita M, Takenaka-Morita S, Nakamura K, Saito H, Emori T, Ohe T |title=Sinus node function in patients with Brugada-type ECG |journal=[[Circulation Journal : Official Journal of the Japanese Circulation Society]] |volume=68 |issue=5 |pages=473–6 |year=2004 |month=May |pmid=15118291 |doi= |url=http://joi.jlc.jst.go.jp/JST.JSTAGE/circj/68.473?from=PubMed |issn= |accessdate=2012-10-13}}</ref>
*[[Slowed atrial conduction]]<ref name="pmid14687250">{{cite journal |author=Takehara N, Makita N, Kawabe J, Sato N, Kawamura Y, Kitabatake A, Kikuchi K |title=A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill |journal=[[Journal of Internal Medicine]] |volume=255 |issue=1 |pages=137–42 |year=2004 |month=January |pmid=14687250 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-6820&date=2004&volume=255&issue=1&spage=137 |issn= |accessdate=2012-10-13}}</ref>
*[[Atrial standstill]]<ref name="pmid14687250">{{cite journal |author=Takehara N, Makita N, Kawabe J, Sato N, Kawamura Y, Kitabatake A, Kikuchi K |title=A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill |journal=[[Journal of Internal Medicine]] |volume=255 |issue=1 |pages=137–42 |year=2004 |month=January |pmid=14687250 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-6820&date=2004&volume=255&issue=1&spage=137 |issn= |accessdate=2012-10-13}}</ref>
 
The appearance of atrial arrhythmias and impaired atrial conduction are remarkable in so far as these findings are associated with inducibility of ventricular fibrillation.<ref>Eur Heart J (2004) 25;(10): 879-884. doi: 10.1016/j.ehj.2004.01.004</ref>  Indeed those patients who undergo implantation of a defibrillator ([[AICD]]) have twice the incidence of atrial arrhythmias (27% versus 13%)(p<0.05).
 
==Complications==
The following arrhythmias may occur in the patient with Brugada syndrome:
* [[Polymorphic VT]] resembling a rapid [[Torsade de Pointes]] ([[TdP]]) as shown below:
[[File:Torsade in a patient with Brugada syndrome.PNG|center|500px]]
----
* [[Monomorphic VT]] is observed infrequently
* [[VT]]/[[VF]] often terminates spontaneously in patients with the Brugada syndrome which may explain why patients wake up at night after episodes of [[agonal respiration]] caused by the arrhythmia.
 
==Prognosis==
Patients who are symptomatic with unexplained [[syncope]], [[ventricular tachycardia]] or aborted [[sudden cardiac death]] may have a symptom recurrence risk of 2% to 10% per year. In these patients an [[AICD]] implant is advisable.
==Risk Stratification==
In a study of 547 individuals who had confirmed Brugada syndrome who had no prior history of [[cardiac arrest]], Brugada and associates identified the following correlates of future events:<ref> <div>'' Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation''. '' 2003; 108: 3092–3096.''</div></ref>
 
===Inducibility on Electrophysiologic Testing===
Patients who are inducible at the time electrophysiologic study have an eightfold increased risk of aborted [[sudden cardiac death]] compared with those patients who are not inducible.<ref> <div>'' Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation''. '' 2003; 108: 3092–3096.''</div></ref>  Some groups have advocated that programmed electrical stimulation (PES) be performed to induce [[ventricular fibrillation]] for risk assessment in Brugada patients <ref name="pmid11772879">{{cite journal |author=Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P |title=Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3 |journal=[[Circulation]] |volume=105 |issue=1 |pages=73–8 |year=2002 |month=January |pmid=11772879 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11772879 |issn= |accessdate=2012-10-13}}</ref><ref name="pmid12776858">{{cite journal |author=Brugada P, Brugada R, Mont L, Rivero M, Geelen P, Brugada J |title=Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart |journal=[[Journal of Cardiovascular Electrophysiology]] |volume=14 |issue=5 |pages=455–7 |year=2003 |month=May |pmid=12776858 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1045-3873&date=2003&volume=14&issue=5&spage=455 |issn= |accessdate=2012-10-13}}</ref>  Other groups have not reproduced the predictive value of these tests,<ref name="pmid11901046">{{cite journal |author=Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, Ronchetti E, Faggiano G, Nastoli J |title=Natural history of Brugada syndrome: insights for risk stratification and management |journal=[[Circulation]] |volume=105 |issue=11 |pages=1342–7 |year=2002 |month=March |pmid=11901046 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11901046 |issn= |accessdate=2012-10-13}}</ref><ref name="pmid15642768">{{cite journal |author=Eckardt L, Probst V, Smits JP, Bahr ES, Wolpert C, Schimpf R, Wichter T, Boisseau P, Heinecke A, Breithardt G, Borggrefe M, LeMarec H, Böcker D, Wilde AA |title=Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome |journal=[[Circulation]] |volume=111 |issue=3 |pages=257–63 |year=2005 |month=January |pmid=15642768 |doi=10.1161/01.CIR.0000153267.21278.8D |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15642768 |issn= |accessdate=2012-10-13}}</ref> so the value of programmed electrical stimulation (PES) and inducibility remains controversial.
Patients who are inducible at the time electrophysiologic study have an eightfold increased risk of aborted [[sudden cardiac death]] compared with those patients who are not inducible.<ref> <div>'' Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation''. '' 2003; 108: 3092–3096.''</div></ref>  Some groups have advocated that programmed electrical stimulation (PES) be performed to induce [[ventricular fibrillation]] for risk assessment in Brugada patients <ref name="pmid11772879">{{cite journal |author=Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P |title=Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3 |journal=[[Circulation]] |volume=105 |issue=1 |pages=73–8 |year=2002 |month=January |pmid=11772879 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11772879 |issn= |accessdate=2012-10-13}}</ref><ref name="pmid12776858">{{cite journal |author=Brugada P, Brugada R, Mont L, Rivero M, Geelen P, Brugada J |title=Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart |journal=[[Journal of Cardiovascular Electrophysiology]] |volume=14 |issue=5 |pages=455–7 |year=2003 |month=May |pmid=12776858 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1045-3873&date=2003&volume=14&issue=5&spage=455 |issn= |accessdate=2012-10-13}}</ref>  Other groups have not reproduced the predictive value of these tests,<ref name="pmid11901046">{{cite journal |author=Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, Ronchetti E, Faggiano G, Nastoli J |title=Natural history of Brugada syndrome: insights for risk stratification and management |journal=[[Circulation]] |volume=105 |issue=11 |pages=1342–7 |year=2002 |month=March |pmid=11901046 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11901046 |issn= |accessdate=2012-10-13}}</ref><ref name="pmid15642768">{{cite journal |author=Eckardt L, Probst V, Smits JP, Bahr ES, Wolpert C, Schimpf R, Wichter T, Boisseau P, Heinecke A, Breithardt G, Borggrefe M, LeMarec H, Böcker D, Wilde AA |title=Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome |journal=[[Circulation]] |volume=111 |issue=3 |pages=257–63 |year=2005 |month=January |pmid=15642768 |doi=10.1161/01.CIR.0000153267.21278.8D |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15642768 |issn= |accessdate=2012-10-13}}</ref> so the value of programmed electrical stimulation (PES) and inducibility remains controversial.
===Spontaneous Type I Brugada Pattern===
The presence of a spontaneous abnormal Type I pattern of ST segment elevation is associated with a 7.7 fold increased risk of in arrhythmic event during a patient's lifetime compared with those patients who only develop a Type I pattern following sodium blocker infusion.<ref> <div>'' Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation''. '' 2003; 108: 3092–3096.''</div></ref>
===Male Gender===
Male gender is associate with the 5.5 fold increased risk of [[sudden cardiac death]].<ref> <div>'' Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation''. '' 2003; 108: 3092–3096.''</div></ref>
===Family History===
A family history of the disease is not associated with a higher risk of sudden death compared with sporadic occurrence of the disease.<ref> <div>'' Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation''. '' 2003; 108: 3092–3096.''</div></ref>
===Symptoms===
In another study, Brugada has reported that the symptoms of the patient may aid in risk stratification:<ref>Brugada  J,  Brugada  R,  Antzelevitch  C,  Towbin  J,  Nademanee  K,  Brugada  P.  Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation.  2002;  105:  73–78.</ref>
*Brugada syndrome patients who present with aborted [[sudden cardiac death]] are at particularly high risk of recurrence with an incidence of 69% at 54 months of follow-up in the Brugada series.
*Brugada syndrome patients with [[syncope]] and Type 1 ST elevation pattern have a 19% risk of recurrence at 26 months.
*Brugada syndrome patients who are asymptomatic have an 8% risk of cardiac events over the same time period.


===Genetic Testing===
===Genetic Testing===
Genetic testing does not identify patients at high risk of sudden cardiac death and does not aid in risk  stratification.<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-14}}</ref>
Despite the association of the Brugada syndrome with the SCN5A genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis. Genetic testing can be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-14}}</ref>
 
==Symptoms==
The arrhythmias typically occur when an affected person is resting or asleep:
*[[Fainting]]
*[[Syncope]]
*[[Seizures]]
*[[Difficulty breathing]]
*[[Sudden death]]
*[[Agonal breathing]]
 
==EKG Characteristics==
There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes.  Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as [[ajmaline]] and [[flecainide]].  Type 1 Brugada syndrome may always be present on the EKG, or it may be elicited by the administration of particular drugs (e.g., Class IC antiarrythmic drugs that blocks sodium channels such as [[ajmaline]], [[flecainide]]) or it may be unmasked by various [[Brugada syndrome risk factors|triggers]] or [[Brugada syndrome risk factors|risk factors]].
 
Type 1 Brugada pattern is characterized by ST elevations in leadsV<sub>1</sub>-V<sub>3</sub> with a [[right bundle branch block]] ([[RBBB]]). A prolongation of the [[PR interval]] is also frequently seen.  The EKG changes of Brugada syndrome can vary over time, depending on the autonomic balance and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the [[ST segment]] elevation, while vagal stimulation worsens it. The administration of class Ia, Ic and III drugs increases the [[ST segment]] elevation, as does [[fever]]. Exercise decreases [[ST segment]] elevation in some patients but increases it in others (after exercise when the body temperature has risen). The changes in heart rate induced by atrial pacing are accompanied by changes in the degree of [[ST segment]] elevation.  When the heart rate decreases, the [[ST segment]] elevation increases and when the heart rate increases the [[ST segment]] elevation decreases.
 
The three patterns of Brugada syndrome (Type I,II,III) are shown below:
[[File:Brugada type 123.jpg|center|500px]]
 
The table below is from ECGpedia and is adapted from Wilde et al.<ref name="pmid12417552">{{cite journal |author=Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P, Corrado D, Hauer RN, Kass RS, Nademanee K, Priori SG, Towbin JA |title=Proposed diagnostic criteria for the Brugada syndrome: consensus report |journal=[[Circulation]] |volume=106 |issue=19 |pages=2514–9 |year=2002 |month=November |pmid=12417552 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12417552 |issn= |accessdate=2012-10-14}}</ref>
<center>
{| class="wikitable" font-size="90%"
|- style="text-align:center;background-color:#6EB4EB;"
|+'''ST segment abnormalities in the different types of Brugada syndrome'''
|-
!
!Type I
!Type II
!Type III
|-
!J wave amplitude
|>= 2mm
|>= 2mm
|>= 2mm
|-
!T wave
|Negative
|Positive or biphasis
|Positive
|-
!ST-T configuration
|Coved type
|Saddleback
|Saddleback
|-
!ST segment (terminal portion)
|Gradually descending
|Elevated >= 1mm
|Elevated < 1mm
|-
|}
</center>
 
==Diagnostic Criteria for Brugada Syndrome<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-14}}</ref>==
 
Only a Type I Brugada pattern qualifies as one of the required diagnostic criteria of Brugada syndrome.  Type II and Type III EKG patterns do not qualify.  Furthermore, the presence of the Type I Brugada pattern is necessary, but is not sufficient to make the diagnosis of Brugada '''''syndrome'''''.  Other clinical criteria must be met as well.  The diagnosis of Brugada syndrome requires that the criteria below be met:
 
1. The presence of Type 1 ST-segment elevation in more than one right precordial lead (V<sub>1</sub>-V<sub>3</sub>).  Type I Brugada pattern ST elevation must be observed either spontaneously or following the administration of a sodium channel blocking agent.
 
2. One or more of the following criteria must also be met:
:* Family history of [[sudden cardiac death]] ([[SCD]]) (<45 years old)
:* Documented [[ventricular fibrillation]] ([[VF]])
:* [[Polymorphic ventricular tachycardia]]
:* Coved-type ECG changes in family members
:* Inducibility of [[ventricular tachycardia]] ([[VT]]) with programmed electrical stimulation (PES)
 
3. The patient is also diagnosed as having Brugada syndrome when a Type 2 (saddleback pattern) or Type 3 ST-segment elevation is observed in more than one right precordial lead under baseline conditions that can be converted to the diagnostic Type 1 Brugada pattern following administration of a [[sodium channel blocker]].
 
==Type 1 Brugada Pattern==
As shown by the tracing below, the EKG characteristics of Type 1 Brugada syndrome include the following EKG findings in the right precordial leads (V<sub>1</sub>-V<sub>3</sub>):
*a) A broad [[P-wave]] with some [[PR prolongation]]
*b) [[J point]] elevation in the right precordial leads (V<sub>1</sub>-V<sub>3</sub>)
*c) Coved [[ST segment elevation]]
*d) An inverted [[T wave]]
 
[[File:Brugada ecg characteristics.png|center|500px]]
 
Slight [[QT prolongation]] may also be observed, particularly in the right precordial leads.<ref> <div>'' Alings M, Wilde A. “Brugada” syndrome: clinical data and suggested pathophysiological mechanism. Circulation''. '' 1999; 99: 666–673.''</div></ref><ref>''Bezzina C, Veldkamp MW, van Den Berg MP, Postma AV, Rook MB, Viersma JW, Van Langen IM, Tan-Sindhunata G, Bink-Boelkens MT, van Der Hout AH, Mannens MM, Wilde AA. A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res''. '' 1999; 85: 1206–1213.''</ref><ref>''Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Brignole M, Giordano U, Giovannini T, Menozzi C, Bloise R, Crotti L, Terreni L, Schwartz PJ. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: a prospective evaluation of 52 families. Circulation''. '' 2000; 102: 2509–2515.''</ref>
Typically these changes are in the right precordial leads but these EKG  changes can occur in the inferior <ref name="pmid10695469">{{cite journal |author=Kalla H, Yan GX, Marinchak R |title=Ventricular fibrillation in a patient with prominent J (Osborn) waves and ST segment elevation in the inferior electrocardiographic leads: a Brugada syndrome variant? |journal=[[Journal of Cardiovascular Electrophysiology]] |volume=11 |issue=1 |pages=95–8 |year=2000 |month=January |pmid=10695469 |doi= |url= |issn= |accessdate=2012-10-14}}</ref> or left precordial leads<ref name="pmid14661171">{{cite journal |author=Horigome H, Shigeta O, Kuga K, Isobe T, Sakakibara Y, Yamaguchi I, Matsui A |title=Ventricular fibrillation during anesthesia in association with J waves in the left precordial leads in a child with coarctation of the aorta |journal=[[Journal of Electrocardiology]] |volume=36 |issue=4 |pages=339–43 |year=2003 |month=October |pmid=14661171 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0022073603000797 |issn= |accessdate=2012-10-14}}</ref>.  The fact that these cases may represent atypical variants of Brugada syndrome is supported by the observation that these cases were associated with [[SCN5A]] genetic abnormalities.
 
Shown below is an example of the EKG characteristics in Type I Brugada syndrome - a right bundle branch block morphology in leads V<sub>1-3</sub> and ST segment elevation in leads V<sub>1-3</sub>:
 
[[Image:BrugadaS.jpg|center|500px]]
 
==Unmaksing Type 1 Brugada Pattern==
The electrocardiographic findings of Type 1 Brugada syndrome are often concealed, but may be unmasked by placing the leads higher on the chest (i.e. using the "Brugada Leads") or by infusion of a [[sodium channel blockers]].  Infusion of a [[sodium channel blocker]] may also convert a Type II or Type III Brugada pattern to a Type I Brugada pattern to establish a definitive diagnosis of the syndrome.
 
===Unmasking Brugada Syndrome by Positioning the EKG Leads Higher on the Chest Wall: The Brugada Leads===
The electrocardiographic findings of Brugada syndrome can be unmasked by placing the electrocardiographic leads higher on the chest.  The EKG leads should be placed on the second and third intercostal space rather than the fourth intercostal space as shown below.  When the electrodes are placed in this higher position they are called Brugada leads.<ref name="pmid10809492">{{cite journal |author=Shimizu W, Matsuo K, Takagi M, Tanabe Y, Aiba T, Taguchi A, Suyama K, Kurita T, Aihara N, Kamakura S |title=Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome: clinical implication of eighty-seven-lead body surface potential mapping and its application to twelve-lead electrocardiograms |journal=[[Journal of Cardiovascular Electrophysiology]] |volume=11 |issue=4 |pages=396–404 |year=2000 |month=April |pmid=10809492 |doi= |url= |issn= |accessdate=2012-10-14}}</ref><ref>''sukhowong P, Tungsanga K. New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives. Eur Heart J''. '' 2001; 22: 2290–2296.''</ref>
[[Image:Brugada_lead_placement.jpg|center|500px]]
 
===Sodium Channel Blocker Challenge===
====Agents====
Several sodium channel blockers are effective in unmasking Type 1 Brugada syndrome and in converting Type II and III Brugada syndrome to Type I to establish the diagnosis of Brugada syndrome.  These agents include:
* [[Ajmaline]] 1 mg/kg/5 min IV
* [[Flecainide]] 2 mg/kg/10 min IV or 400 mg PO
* [[Procainamide]] 10 mg/kg/10 min IV
* [[Pilsicainide]] 1 mg/kg/10 min IV
 
====When to Terminate the Sodium Channel Blocker Infusion====
The sodium challenge should be terminated when:
# A diagnostic Type 1 Brugada pattern [[ST-segment elevation]] develops
# The [[ST segment elevation]] in Type 2 increases by ≥ 2 mm
# [[Premature ventricular beats]] or other arrhythmias develop
# the [[QRS]] widens to ≥ 130% of baseline
 
====Precautions====
The infusion should be carried out in a highly monitored area equipped to perform resuscitation. In an elderly patient with prolongation of the electrocardiographic intervals, the test is best performed in the electrophysiology laboratory. Exercise caution in the presence of pre-existing conduction abnormalities, or in the presence of QRS prolongation as the infusion may cause [[complete AV block]].  Isoproteronol can be used as an antidote should this complication should occur.
 
==Type II Brugada Pattern==
The Type II Brugada pattern is not diagnostic of Brugada syndrome.  The Type II Brugada pattern is characterized by a "saddleback appearance" to the ST segment.  The ST segment must be elevated greater than 2 mm, and the trough of the ST segment elevation at the bottom of the saddle must be elevated > 1 mm.  The Type II Brugada pattern may alternate with the Type I Brugada pattern at different times in the same patient.
 
In order for a patient with type II Brugada pattern to be diagnosed as having Brugada syndrome, there must be a conversion of the Type II pattern to a Type I pattern with greater than 2 mm of ST segment elevation in the right precordial leads (either spontaneously or following infusion of a sodium channel blocking agent).  In addition to these electrocardiographic changes, the required clinical criteria to establish the diagnosis of Brugada syndrome described above for the Type I Brugada pattern must also be present.
   
Shown below are examples of the Type II Brugada pattern demonstrating J point elevation, and a "saddle shaped" ST segment:
[[Image:Brugada_syndrome_type2_example1.jpg|center|800px]]
[[Image:Brugada_syndrome_type2_example2.jpg|center|800px]]
 
==Type III Brugada Pattern==
The Type 3 Brugada pattern is associated with either a "saddleback" or a "coved" appearance but the magnitude of ST-segment elevation is <1 mm.
 
In order for a patient with type II Brugada pattern to be diagnosed as having Brugada syndrome, there must be a conversion of the Type II pattern to a Type I pattern with greater than 2 mm of ST segment elevation in the right precordial leads (either spontaneously or following infusion of a sodium channel blocking agent).  In addition to these electrocardiographic changes, the required clinical criteria to establish the diagnosis of Brugada syndrome described above for the Type I Brugada pattern must also be present.
 
A sodium channel blocker infusion can be administered to convert a type III Brugada pattern to a type I Brugada pattern to facilitate the definitive diagnosis of Brugada syndrome, however the conversion of a type III Brugada pattern to a type II Brugada pattern is not considered diagnostic of the Brugada syndrome.<ref name="pmid15898165">{{cite journal |author=Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A |title=Brugada syndrome: report of the second consensus conference |journal=[[Heart Rhythm : the Official Journal of the Heart Rhythm Society]] |volume=2 |issue=4 |pages=429–40 |year=2005 |month=April |pmid=15898165 |doi= |url= |issn= |accessdate=2012-10-14}}</ref>


==Treatment==
==Treatment==
Implantation of a cardiac defibrillator is the only proven method of treatment in Brugada syndrome.
Implantation of a [[cardiac defibrillator]] is the only proven method of treatment in Brugada syndrome.Patients with aborted [[sudden cardiac death]] are at high risk for recurrence and should undergo [[AICD]] implantation, and do not require an electrophysiologic study to assess inducibility.  Patients with symptoms (either [[syncope]], [[seizures]] or nocturnal [[agonal respirations]]) should undergo implantation of a [[defibrillator]] if no other cause of their symptoms can be identified.  Asymptomatic patients should undergo electrophysiologic testing, and if [[VT]] / [[VF]] can be induced, they should undergo implantation of an [[ICD]].  Asymptomatic patients who cannot be induced should followed-up closely.  Patients who are asymptomatic with no family history of Brugada syndrome can be followed-up closely.
Patients with aborted [[sudden cardiac death]] are at high risk for recurrence and should undergo [[AICD]] implantation, and do not require an electrophysiologic study to assess inducibility.  Patients with symptoms (either [[syncope]], [[seizures]] or nocturnal [[agonal respirations]]) should undergo implantation of a [[defibrillator]] if no other cause of their symptoms can be identified.  Asymptomatic patients should undergo electrophysiologic testing, and if [[VT]] / [[VF]] can be induced, they should undergo implantation of an [[ICD]].  Asymptomatic patients who cannot be induced should followed-up closely.  Patients who are asymptomatic with no family history of Brugada syndrome can be followed-up closely.
===Drugs to Avoid===
 
There are certain drugs that should be avoided in patients with Brugada syndrome.  These drugs include [[ajmaline]], [[flecainide]], pilsicainide, [[procainamide]], and [[propafenone]]. These drugs are all sodium blocking [[antiarrhythmic]]s which are either in the IA class or IC class.
The 2005 consensus statement divides patients into two groups:
 
*Higher risk patients with spontaneous Type I Brugada pattern
*A less high risk cohort of patients who require infusion of a sodium channel blocker to induce a Type I Brugada pattern.
 
The management of these two groups of patients will be discussed separately.
 
==Management of Patients with a Spontaneous Type I Brugada Pattern==
Implantation of a cardiac defibrillator should be considered in the following patients:
=== Symptomatic Patients===
*Patients with aborted [[sudden cardiac death]]
*Patients with [[syncope]], [[seizures]] or nocturnal [[agonal respirations]] who have no other identifiable cause for their symptoms
=== Asymptomatic Patients===
*Patients with a family history of [[sudden cardiac death]] that is suspected to be due to Brugada syndrome in whom VT VF can be induced on electrophysiologic testing.
*Patients with no family history of [[sudden cardiac death]] in whom VT VF can be induced on electrophysiologic testing.
 
In essence, if VT VF can be induced on electrophysiologic testing in these patients, a cardiac defibrillator should be implanted.  It is unclear if the same recommendations apply to those patients who require that the electrodes be placed one to two intercostal spaces higher to demonstrate a Brugada type I electrocardiographic pattern.
 
The flowchart below summarizes the recommendations of the 2005 consensus panel.
 
==Management of Patients with a Sodium Channel Induced Type I Brugada Pattern==
Implantation of a cardiac defibrillator should be considered in the following patients:
=== Symptomatic Patients===
*Patients with aborted [[sudden cardiac death]]
*Patients with [[syncope]], [[seizures]] or nocturnal [[agonal respirations]] who have no other identifiable cause for their symptoms
=== Asymptomatic Patients===
*Patients with a family history of [[sudden cardiac death]] that is suspected to be due to Brugada syndrome in whom VT VF can be induced on electrophysiologic testing.
 
The flowchart below summarizes the recommendations of the 2005 consensus panel.
 
==Pharmacotherapy==
Pharmacotherapy alone may not be sufficient to treat Brugada syndrome, but it may be required in regions of the world where ICD implantation is cost prohibitive or in infants.  [[Quinidine]] reduces the number of [[VF]] episodes and corrects spontaneous ECG changes, possibly via inhibiting I</sup>to channels.<ref name="pmid15381640">{{cite journal |author=Belhassen B, Glick A, Viskin S |title=Efficacy of quinidine in high-risk patients with Brugada syndrome |journal=Circulation |volume=110 |issue=13 |pages=1731–7 |year=2004 |pmid=15381640 |doi=10.1161/01.CIR.0000143159.30585.90}}</ref>  No drug has demonstrated long term efficacy in the prevention of [[sudden cardiac death]].
 
===Drugs with Potential Antiarrhythmic Effect===
 
(Alphabetical order generic name)
<font size="-1">
 
{| cellspacing="2" cellpadding="3" border="0"
| '''Generic name'''
| '''Brand name®'''
| '''Class / Clinical use'''
| '''References'''
| '''Recommendation'''
|-
| [http://www.drugbank.ca/drugs/DB01166 Cilostazol]
| e.g.<br />Pletal®
| Phosphodiesterase inhibitor
| [http://www.ncbi.nlm.nih.gov/pubmed/12139296?dopt=Citation Tsuchiya 2002]<br />[http://www.ncbi.nlm.nih.gov/pubmed/16533260?dopt=Citation Abud 2006]<br />[http://www.ncbi.nlm.nih.gov/pubmed/10372225?dopt=Citation Matsui 1999]
| Class IIb
|-
| [http://www.drugbank.ca/drugs/DB01064 Isoproterenol]<br />[http://www.drugbank.ca/drugs/DB01064 Isoprenaline]
| e.g.<br />Isuprel®
| Beta-adrenergic receptor stimulation
| [http://www.ncbi.nlm.nih.gov/pubmed/8609322?dopt=Citation Miyazaki 1996]<br />[http://www.ncbi.nlm.nih.gov/pubmed/11083249?dopt=Citation Suzuki 2000]<br />[http://www.ncbi.nlm.nih.gov/pubmed/16760208?dopt=Citation Watanabe 2006]<br />[http://www.ncbi.nlm.nih.gov/pubmed/17556186?dopt=Citation Ohgo 2007]<br />[http://www.ncbi.nlm.nih.gov/pubmed/16397147?dopt=Citation Ganesan 2006]
| Class I
|-
| [http://www.drugbank.ca/drugs/DB00816 Orciprenaline]
| e.g.<br />Alotec®<br />Metaprel®<br />Novasmasol®
| Beta-adrenergic receptor stimulation
| [http://www.ncbi.nlm.nih.gov/pubmed/19346290?dopt=Citation Kyriazis 2009]
| Class IIa
|-
| [http://www.drugbank.ca/drugs/DB00908 Quinidine]
| e.g.<br />Quinalan®<br />Chinidin®
| Antiarrhythmic Agent
| [http://www.ncbi.nlm.nih.gov/pubmed/11083249?dopt=Citation Suzuki 2000]<br />[http://www.ncbi.nlm.nih.gov/pubmed/11584468?dopt=Citation Alings 2001]<br />[http://www.ncbi.nlm.nih.gov/pubmed/15381640?dopt=Citation Belhassen 2004]<br />[http://www.ncbi.nlm.nih.gov/pubmed/16633076?dopt=Citation Mizusawa 2006]<br />[http://www.ncbi.nlm.nih.gov/pubmed/17404158?dopt=Citation Probst 2007]<br />[http://www.ncbi.nlm.nih.gov/pubmed/17556186?dopt=Citation Ohgo 2007]<br />[http://www.ncbi.nlm.nih.gov/pubmed/10517739?dopt=Citation Yan 1999]
| Class I
|-
|
|
|
|
|
|}
</font>
Recommendation: Class I: convincing evidence/opinion; Class IIa: evidence/opinion less clear; Class IIb: conflicting evidence/opinion; Class III: very little evidence.
 
==Treatment of VT Storm==
VT storm has been successfully treated with Isoproterenol.  The mechanism is thought to be augmenting the cardiac L type channel.
 
==Treatment of Coronary Ischemia==
Patients with risk factors for [[coronary artery disease]] may require an angiogram before ICD implantation.
 
==Treatment of Factors that may Precipitate Brugada Type EKG Changes and Clinical Symptoms==
*Fever in a Brugada syndrome patient should be treated with an antipyretic.
*Brugada syndrome patients should avoid hot tubs, very hot baths or extremely hot climates.
*[[Hypokalemia]], [[hyperkalemia]], and [[hypercalcemia]] should be treated aggressively.
*[[Carbohydrate loading]] should be avoided.
 
== ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (DO NOT EDIT) <ref name="pmid16935995">{{cite journal| author=Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M et al.| title=ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. | journal=Circulation | year= 2006 | volume= 114 | issue= 10 | pages= e385-484 | pmid=16935995 | doi=10.1161/CIRCULATIONAHA.106.178233 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16935995}}</ref> ==
 
=== Recommendations for Brugada Syndrome ===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class I]]
 
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' An ICD is indicated for Brugada syndrome patients with previous cardiac arrest receiving chronic optimal medical therapy and who have reasonable expectation of survival with a good functional status for more than 1 y. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}


{|class="wikitable"
===Drugs to Preferably Avoid===
|-
Drugs which are not contraindicated in Brugada syndrome, but which should be avoided, are [[amiodarone]], [[cibenzoline]], [[disopyramide]], [[lidocaine]], [[propanolol]], and [[verapamil]]. These agents are all antiarrhythmics. Topical lidocaine used for anesthesia is thought to be safe when used in persons with Brugada syndrome.
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIa]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' An ICD is reasonable for Brugada syndrome patients with spontaneous ST-segment elevation in V1, V2, or V3 who have had syncope with or without mutations demonstrated in the SCN5A gene and who have reasonable expectation of survival with a good functional status for more than 1 y. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Clinical monitoring for the development of a spontaneous ST-segment elevation pattern is reasonable for the management of patients with ST-segment elevation induced only with provocative pharmacological challenge with or without symptoms. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' An ICD is reasonable for Brugada syndrome patients with documented VT that has not resulted in cardiac arrest and who have reasonable expectation of survival with a good functional status for more than 1 y. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''4.''' Isoproterenol can be useful to treat an electrical storm in the Brugada syndrome. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIb]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' EP testing may be considered for risk stratification in asymptomatic Brugada syndrome patients with spontaneous ST elevation with or without a mutation in the SCN5A gene. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Quinidine might be reasonable for the treatment of electrical storm in patients with Brugada syndrome.''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}


==References==
==References==
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{{Reflist|2}}
{{WH}}
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[[CME Category::Cardiology]]
[[Category:Electrophysiology]]
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[[Category:Genetic disorders]]
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Latest revision as of 05:51, 15 March 2016

Brugada syndrome Microchapters

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Overview

Historical Perspective

Classification

Pathophysiology

Differentiating Brugada syndrome from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Examples of Type I Brugada Syndrome

Chest X Ray

Echocardiography or Ultrasound

Electrophysiologic Studies

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Treatment

Treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Brugada syndrome is a genetic disease that is characterized by abnormal electrocardiogram (EKG) findings and an increased risk of sudden cardiac death in young adults, and occasionally in children and infants. Brugada syndrome is a condition that causes a disruption of the heart's normal rhythm. Specifically, this disorder can lead to uncoordinated electrical activity in the heart's lower chambers (ventricles), an abnormality called ventricular arrhythmia. If untreated, the irregular heartbeats can cause fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep.

Historical Perspective

Brugada syndorme was potentially first seen on EKG in survivors of cardiac arrest in 1989, but it was not until 1992 that the Brugada brothers recognized it as a distinct clinical entity which could cause sudden death by ventricular fibrillation.

Classification

There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes. Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as ajmaline and flecainide.

Pathophysiology

Approximately 20% of persons with Brugada syndome have a mutation in the gene SCN5A. This gene encodes for the sodium ion channel. The mutation is inherited in an autosomal dominant pattern, and is more commonly seen in males. Brugada syndrome has also been shown to result from defects in a calcium channel.

Differentiating Brugada syndrome from other Diseases

Brugada syndrome should be differentiated from other cardiac disorders, electrolyte disturbances, and drug intoxication syndromes. The condition which most similarly presents to Brugada syndrome is arrhythmogenic right ventricular dysplasia, as they both cause sudden cardiac death in children. Brugada syndrome can be differentiated from arrhythmogenic right ventricular dysplasia by the genetic counterpart of SCN5A, the lack of structural abnormalities within the heart, the association with polymorphic ventricular tachycardia during sleep, and EKG changes that are enhanced by vagotonic agents.

Epidemiology and Demographics

Insofar as Brugada syndrome is a relatively newly recognized syndrome, its incidence and prevalence continues to increase. Brugada syndrome is quite common in Southeast Asia where it is endemic, and affects 500 out of every 100,000 individuals. It is the second leading cause of death after car accidents among young people in these countries. It has been estimated that Brugada syndrome accounts for 4% of all sudden cardiac deaths and 20% of sudden cardiac deaths among patients with structurally normal hearts. It is 8-10 times more common in men.

Risk Factors

The EKG changes of Brugada syndrome can vary over time, depending on the autonomic balance and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the ST segment elevation, while vagal stimulation worsens it. During sleep, there is heightened vagal tone, and the pattern may be exacerbated at that time (as is the risk of sudden cardiac death at that time). The administration of class Ia, Ic and III drugs increases the ST segment elevation, as does fever. The impact of exercise depends upon when the EKG is obtained: during exercise the ST segment elevation may decrease but may increase later after exercise when the body temperature has risen. Similar to early repolarization variant, when the heart rate decreases, the ST segment elevation increases and when the heart rate increases the ST segment elevation decreases. While Brugada syndrome is often associated with polymorphic VT which may be self terminating, in the presence of autonomic imbalance, hypokalemia, fever or exacerbating drugs sustained ventricular fibrillation and sudden cardiac death may result.[1]

Screening

Relatives of patients with Brugada syndrome can be screened for the syndrome by obtaining an EKG, although the diagnostic pattern may be concealed. Genetic testing can also be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.[1] Unfortunately, despite the association of the Brugada syndrome with the SCN5A genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis.

Natural History, Complications and Prognosis

Brugada syndrome usually becomes apparent in adulthood, although it may present in infants and children as sudden cardiac death. The mean age of sudden death in patients with Brugada syndrome is 40 years old. The Brugada patient may develop atrial arrhythmias and abnormalities in atrial conduction, and these abnormalities are associated with inducibility of ventricular fibrillation. Implantation of a cardiac defibrillator AICD can improve prognosis for some.

Diagnosis

Diagnostic Criteria

The diagnosis of brugada syndrome is based upon electrocardiographic and clinical criteria. Only the Type I Brugada pattern qualifies as part of the diagnostic criteria for Brugada syndrome. Other rhythm abnormalities and family history are also taken into account when making the diagnosis of Brugada syndrome.

History and Symptoms

Patients with Brugada syndrome will sometimes have a family history of sudden cardiac death and a personal history of of arrhythmias. If patients are symptomatic they often have symptoms of syncope, seizures, agonal breathing, difficulty breathing, and patients may even present with sudden death. These symptoms most often come on either at rest or during sleep.

Physical Examination

Insofar as Brugada syndrome is not associated with any structural heart disease, there are generally no abnormalities on physical examination. Vagal maneuvers such as carotid sinus massage may increase vagal tone and may unmask the presence of a Type I Brugada pattern. In a patient who has experienced recent symptoms such as syncope, it is important to check the temperature in so far as fever may trigger a self terminating or sustained episode of ventricular tachycardia / ventricular fibrillation. The presence of fever is also a target of antipyretic therapy.

Laboratory Findings

Hypokalemia and hyperkalemia can both trigger either sustained or nonsustained episodes of ventricular tachycardia / ventricular fibrillation and serum electrolytes should therefore be checked. Both alcohol and cocaine intoxication can be associated with either sustained or nonsustained episodes of ventricular tachycardia/ventricular fibrillation and a toxicology screen should be ordered if there is a clinical suspicion. Likewise, tricyclic antidepressants can be associated with exacerbations of the syndrome, and levels of these agents should also be checked if there is a clinical suspicion.

Electrocardiogram

There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes. Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as ajmaline and flecainide. Type 1 Brugada syndrome may always be present on the EKG, or it may be elicited by the administration of particular drugs (e.g., Class IC antiarrythmic drugs that blocks sodium channels such as ajmaline, flecainide) or it may be unmasked by various triggers or risk factors.

Chest X Ray

Insofar as Brugada syndrome is not associated with structural abnormalities of the heart, there are no associated abnormalities on the chest x-ray.

Echocardiography or Ultrasound

There is ongoing controversy as to whether there are structural abnormalities among patients with Brugada syndrome. There was one small study of 11 patients with Brugada syndrome that demonstrated a rapid swinging motion shifting towards the right ventricle of the basal segment of the intraventricular septum and early systole in 73% (8/11) of patients with Brugada syndrome. None of the control patients demonstrated this abnormality.[2]

Electrophysiologic Studies

Patients who are inducible at the time electrophysiologic study have an eightfold increased risk of aborted sudden cardiac death compared with those patients who are not inducible.[3] Some groups have advocated that programmed electrical stimulation (PES) be performed to induce ventricular fibrillation for risk assessment in Brugada patients [4][5] Other groups have not reproduced the predictive value of these tests,[6][7] so the value of programmed electrical stimulation (PES) and inducibility remains controversial.

Genetic Testing

Despite the association of the Brugada syndrome with the SCN5A genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis. Genetic testing can be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.[1]

Treatment

Implantation of a cardiac defibrillator is the only proven method of treatment in Brugada syndrome.Patients with aborted sudden cardiac death are at high risk for recurrence and should undergo AICD implantation, and do not require an electrophysiologic study to assess inducibility. Patients with symptoms (either syncope, seizures or nocturnal agonal respirations) should undergo implantation of a defibrillator if no other cause of their symptoms can be identified. Asymptomatic patients should undergo electrophysiologic testing, and if VT / VF can be induced, they should undergo implantation of an ICD. Asymptomatic patients who cannot be induced should followed-up closely. Patients who are asymptomatic with no family history of Brugada syndrome can be followed-up closely.

Drugs to Avoid

There are certain drugs that should be avoided in patients with Brugada syndrome. These drugs include ajmaline, flecainide, pilsicainide, procainamide, and propafenone. These drugs are all sodium blocking antiarrhythmics which are either in the IA class or IC class.

Drugs to Preferably Avoid

Drugs which are not contraindicated in Brugada syndrome, but which should be avoided, are amiodarone, cibenzoline, disopyramide, lidocaine, propanolol, and verapamil. These agents are all antiarrhythmics. Topical lidocaine used for anesthesia is thought to be safe when used in persons with Brugada syndrome.

References

  1. ↑ 1.0 1.1 1.2 Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde A (2005). "Brugada syndrome: report of the second consensus conference". Heart Rhythm : the Official Journal of the Heart Rhythm Society. 2 (4): 429–40. PMID 15898165. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  2. ↑ Huang ZR, Chen LL, Li WH, Tang QZ, Huang CX, Xie Q, Wu G, Fan L (2007). "Interventricular septum motion abnormalities: unexpected echocardiographic changes of Brugada syndrome". Chinese Medical Journal. 120 (21): 1898–901. PMID 18067763. Retrieved 2012-10-13. Unknown parameter |month= ignored (help)
  3. ↑
    Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation. 2003; 108: 3092–3096.
  4. ↑ Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P (2002). "Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3". Circulation. 105 (1): 73–8. PMID 11772879. Retrieved 2012-10-13. Unknown parameter |month= ignored (help)
  5. ↑ Brugada P, Brugada R, Mont L, Rivero M, Geelen P, Brugada J (2003). "Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart". Journal of Cardiovascular Electrophysiology. 14 (5): 455–7. PMID 12776858. Retrieved 2012-10-13. Unknown parameter |month= ignored (help)
  6. ↑ Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, Ronchetti E, Faggiano G, Nastoli J (2002). "Natural history of Brugada syndrome: insights for risk stratification and management". Circulation. 105 (11): 1342–7. PMID 11901046. Retrieved 2012-10-13. Unknown parameter |month= ignored (help)
  7. ↑ Eckardt L, Probst V, Smits JP, Bahr ES, Wolpert C, Schimpf R, Wichter T, Boisseau P, Heinecke A, Breithardt G, Borggrefe M, LeMarec H, Böcker D, Wilde AA (2005). "Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome". Circulation. 111 (3): 257–63. doi:10.1161/01.CIR.0000153267.21278.8D. PMID 15642768. Retrieved 2012-10-13. Unknown parameter |month= ignored (help)

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