Brugada syndrome risk factors: Difference between revisions

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{{Brugada syndrome}}
{{Brugada syndrome}}
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==Overview==
==Overview==
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>
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>
 
==Agents and Scenarios that Provoke the Brugada EKG Pattern and the Clinical Manifestations of Brugada Syndrome==
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" />
 
===Common Risk Factors===
*A combination of [[glucose]] and [[insulin]]. In Thailand large meals of glutinous sticky carbohydrate rich rice have been associated with sudden cardiac death.<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><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>
**[[Ajmaline]] (a diagnostic test agent)<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>
**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 such as [[propranolol]].<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" />
**[[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" /><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)
**[[Heat stroke]]<ref name="pmid19497490">{{cite journal| author=Lacunza J, San Román I, Moreno S, García-Molina E, Gimeno J, Valdés M| title=Heat stroke, an unusual trigger of Brugada electrocardiogram. | journal=Am J Emerg Med | year= 2009 | volume= 27 | issue= 5 | pages= 634.e1-3 | pmid=19497490 | doi=10.1016/j.ajem.2008.09.036 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19497490  }} </ref>
**[[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" />
**[[Lithium]]. Administration of [[Lithium]] can result in EKG manifestations of the Brugada syndrome. <ref name=":0">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 name=":1">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 name=":2">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" /> <ref name="pmid8609322" />(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" /><ref name=":3">''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" />
**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" /><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" /> (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" /><ref name="pmid11204086" />
*:*[[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" /><ref name="pmid15175062" /><ref name="pmid2397572" />
**
 
===Less Common Risk Factors ===
 
* Less common risk factors in the development of [disease name] include:
**[Risk factor 1]
**[Risk factor 2]
**[Risk factor 3]
 
==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.
 
===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>


==Risk Factors: Agents and Scenarios that Provoke the Brugada Syndrome Pattern==
===Male Gender===
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>:
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>
*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>
*[[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>
*[[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>
*[[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> 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.
*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.
*[[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
* Shaving due to [[vagal stimulation]]
*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>
*[[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>


==Risk Statification<ref name="pmid11901046">{{cite journal| author=Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U et al.| title=Natural history of Brugada syndrome: insights for risk stratification and management. | journal=Circulation | year= 2002 | volume= 105 | issue= 11 | pages= 1342-7 | pmid=11901046 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11901046  }} </ref><ref name="pmid12655161">{{cite journal| author=Morita H, Takenaka-Morita S, Fukushima-Kusano K, Kobayashi M, Nagase S, Kakishita M et al.| title=Risk stratification for asymptomatic patients with Brugada syndrome. | journal=Circ J | year= 2003 | volume= 67 | issue= 4 | pages= 312-6 | pmid=12655161 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12655161  }} </ref>==
===Family History===
* Patients with [[syncope]] and an abnormal Type 1 ECG are at higher risk
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>
* Asymptomatic patients at risk can be identified
** Presence of spontaneous Type 1 [[ST-segment elevation]]
** Characteristics of the S wave
** Presence of late potentials
** Inducibility of [[VT]]/[[VF]] using PES is controversial as a risk factor. 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.


==References==
===Symptoms===
{{reflist|2}}
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.


[[Category:Cardiology]]
===Genetic Testing===
[[Category:Electrophysiology]]
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>


==References==
{{Reflist|2}}
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[[CME Category::Cardiology]]
[[Category:Electrophysiology]]
[[Category:Cardiology]]
[[Category:Channelopathy]]
[[Category:Genetic disorders]]
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Latest revision as of 18:01, 25 November 2019

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

Overview

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]

Agents and Scenarios that Provoke the Brugada EKG Pattern and the Clinical Manifestations of Brugada Syndrome

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):[1]

Common Risk Factors

Less Common Risk Factors

  • Less common risk factors in the development of [disease name] include:
    • [Risk factor 1]
    • [Risk factor 2]
    • [Risk factor 3]

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:[40]

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.[41] Some groups have advocated that programmed electrical stimulation (PES) be performed to induce ventricular fibrillation for risk assessment in Brugada patients [42][43] Other groups have not reproduced the predictive value of these tests,[44][45] 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.[46]

Male Gender

Male gender is associate with the 5.5 fold increased risk of sudden cardiac death.[47]

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.[48]

Symptoms

In another study, Brugada has reported that the symptoms of the patient may aid in risk stratification:[49]

  • 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 does not identify patients at high risk of sudden cardiac death and does not aid in risk stratification.[1]

References

  1. ↑ 1.0 1.1 1.2 1.3 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. ↑ Nogami A, Nakao M, Kubota S, Sugiyasu A, Doi H, Yokoyama K; et al. (2003). "Enhancement of J-ST-segment elevation by the glucose and insulin test in Brugada syndrome". Pacing Clin Electrophysiol. 26 (1 Pt 2): 332–7. PMID 12687840.
  3. ↑ 3.0 3.1 Nimmannit S, Malasit P, Chaovakul V, Susaengrat W, Vasuvattakul S, Nilwarangkur S (1991). "Pathogenesis of sudden unexplained nocturnal death (lai tai) and endemic distal renal tubular acidosis". Lancet. 338 (8772): 930–2. PMID 1681278. Retrieved 2012-10-14. Unknown parameter |month= ignored (help)
  4. ↑ Rolf S, Bruns HJ, Wichter T, Kirchhof P, Ribbing M, Wasmer K; et al. (2003). "The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and recommended protocol". Eur Heart J. 24 (12): 1104–12. PMID 12804924.
  5. ↑ 5.0 5.1 5.2 Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S (1996). "Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome". J Am Coll Cardiol. 27 (5): 1061–70. doi:10.1016/0735-1097(95)00613-3. PMID 8609322.
  6. ↑ 6.0 6.1 6.2 6.3 Brugada P, Brugada J, Brugada R (2000). "Arrhythmia induction by antiarrhythmic drugs". Pacing Clin Electrophysiol. 23 (3): 291–2. PMID 10750126.
  7. ↑ Ortega-Carnicer J, Bertos-Polo J, Gutiérrez-Tirado C (2001). "Aborted sudden death, transient Brugada pattern, and wide QRS dysrrhythmias after massive cocaine ingestion". J Electrocardiol. 34 (4): 345–9. PMID 11590577.
  8. ↑ 8.0 8.1 Rouleau F, Asfar P, Boulet S, Dube L, Dupuis JM, Alquier P; et al. (2001). "Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome". J Cardiovasc Electrophysiol. 12 (1): 61–5. PMID 11204086.
  9. ↑ Littmann L, Monroe MH, Svenson RH (2000). "Brugada-type electrocardiographic pattern induced by cocaine". Mayo Clin Proc. 75 (8): 845–9. doi:10.4065/75.8.845. PMID 10943241.
  10. ↑ Antzelevitch C, Brugada R (2002). "Fever and Brugada syndrome". Pacing Clin Electrophysiol. 25 (11): 1537–9. PMID 12494608.
  11. ↑ González Rebollo JM, Hernández Madrid A, García A, García de Castro A, Mejías A, Moro C (2000). "[Recurrent ventricular fibrillation during a febrile illness in a patient with the Brugada syndrome]". Rev Esp Cardiol. 53 (5): 755–7. PMID 10816181.
  12. ↑ Saura D, García-Alberola A, Carrillo P, Pascual D, Martínez-Sánchez J, Valdés M (2002). "Brugada-like electrocardiographic pattern induced by fever". Pacing Clin Electrophysiol. 25 (5): 856–9. PMID 12049381.
  13. ↑ Porres JM, Brugada J, Urbistondo V, García F, Reviejo K, Marco P (2002). "Fever unmasking the Brugada syndrome". Pacing Clin Electrophysiol. 25 (11): 1646–8. PMID 12494626.
  14. ↑ Kum LC, Fung JW, Sanderson JE (2002). "Brugada syndrome unmasked by febrile illness". Pacing Clin Electrophysiol. 25 (11): 1660–1. PMID 12494630.
  15. ↑ Fujiki A, Usui M, Nagasawa H, Mizumaki K, Hayashi H, Inoue H (1999). "ST segment elevation in the right precordial leads induced with class IC antiarrhythmic drugs: insight into the mechanism of Brugada syndrome". J Cardiovasc Electrophysiol. 10 (2): 214–8. PMID 10090224.
  16. ↑ 16.0 16.1 Krishnan SC, Josephson ME (1998). "ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia". J Cardiovasc Electrophysiol. 9 (11): 1167–72. PMID 9835260.
  17. ↑ Gasparini M, Priori SG, Mantica M, Napolitano C, Galimberti P, Ceriotti C; et al. (2003). "Flecainide test in Brugada syndrome: a reproducible but risky tool". Pacing Clin Electrophysiol. 26 (1 Pt 2): 338–41. PMID 12687841.
  18. ↑ Lacunza J, San Román I, Moreno S, García-Molina E, Gimeno J, Valdés M (2009). "Heat stroke, an unusual trigger of Brugada electrocardiogram". Am J Emerg Med. 27 (5): 634.e1–3. doi:10.1016/j.ajem.2008.09.036. PMID 19497490.
  19. ↑ Douglas PS, Carmichael KA, Palevsky PM (1984). "Extreme hypercalcemia and electrocardiographic changes". Am J Cardiol. 54 (6): 674–5. PMID 6475795.
  20. ↑ Sridharan MR, Horan LG (1984). "Electrocardiographic J wave of hypercalcemia". Am J Cardiol. 54 (6): 672–3. PMID 6475794.
  21. ↑ MYERS GB (1950). "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. 2 (1): 75–93. PMID 15427197.
  22. ↑ MERRILL JP, LEVINE HD, SOMERVILLE W, SMITH S (1950). "Clinical recognition and treatment of acute potassium intoxication". Ann Intern Med. 33 (4): 797–830. PMID 14771753.
  23. ↑ Ortega-Carnicer J, Benezet J, Ruiz-Lorenzo F, Alcázar R (2002). "Transient Brugada-type electrocardiographic abnormalities in renal failure reversed by dialysis". Resuscitation. 55 (2): 215–9. PMID 12413761.
  24. ↑ Araki T, Konno T, Itoh H, Ino H, Shimizu M (2003). "Brugada syndrome with ventricular tachycardia and fibrillation related to hypokalemia". Circ J. 67 (1): 93–5. PMID 12520160.
  25. ↑ 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.
  26. ↑ Wright D, Salehian O. Brugada-Type Electrocardiographic Changes Induced by Long-Term Lithium Use. Circulation, FRCPC2010;122:e418-e419
  27. ↑ Laske C, Soekadar SR, Laszlo R, Plewnia C. Brugada syndrome in a patient treated with lithium. Am J Psychiatry. 2007; 164: 1440–1441.
  28. ↑ Aouate P, Clerc J, Viard P, Seoud J (2005). "Propranolol intoxication revealing a Brugada syndrome". J Cardiovasc Electrophysiol. 16 (3): 348–51. doi:10.1046/j.1540-8167.2005.40564.x. PMID 15817098.
  29. ↑ 29.0 29.1 Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T, Isogai R; et al. (1997). "Idiopathic ventricular fibrillation induced with vagal activity in patients without obvious heart disease". Circulation. 95 (9): 2277–85. PMID 9142005.
  30. ↑ 30.0 30.1 30.2 Mizumaki K, Fujiki A, Tsuneda T, Sakabe M, Nishida K, Sugao M; et al. (2004). "Vagal activity modulates spontaneous augmentation of ST elevation in the daily life of patients with Brugada syndrome". J Cardiovasc Electrophysiol. 15 (6): 667–73. doi:10.1046/j.1540-8167.2004.03601.x. PMID 15175062.
  31. ↑ 31.0 31.1 Litovsky SH, Antzelevitch C (1990). "Differences in the electrophysiological response of canine ventricular subendocardium and subepicardium to acetylcholine and isoproterenol. A direct effect of acetylcholine in ventricular myocardium". Circ Res. 67 (3): 615–27. PMID 2397572.
  32. ↑ 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.
  33. ↑ Proclemer A, Facchin D, Feruglio GA, Nucifora R (1993). "[Recurrent ventricular fibrillation, right bundle-branch block and persistent ST segment elevation in V1-V3: a new arrhythmia syndrome? A clinical case report]". Giornale Italiano Di Cardiologia (in Italian). 23 (12): 1211–8. PMID 8174872. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  34. ↑ Brugada R, Brugada J, Antzelevitch C, Kirsch GE, Potenza D, Towbin JA; et al. (2000). "Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts". Circulation. 101 (5): 510–5. PMID 10662748.
  35. ↑ Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N; et al. (2000). "Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome". J Cardiovasc Electrophysiol. 11 (12): 1320–9. PMID 11196553.
  36. ↑ 36.0 36.1 Bolognesi R, Tsialtas D, Vasini P, Conti M, Manca C (1997). "Abnormal ventricular repolarization mimicking myocardial infarction after heterocyclic antidepressant overdose". Am J Cardiol. 79 (2): 242–5. PMID 9193039.
  37. ↑ Goldgran-Toledano D, Sideris G, Kevorkian JP (2002). "Overdose of cyclic antidepressants and the Brugada syndrome". N Engl J Med. 346 (20): 1591–2. doi:10.1056/NEJM200205163462020. PMID 12015405.
  38. ↑ Tada H, Sticherling C, Oral H, Morady F (2001). "Brugada syndrome mimicked by tricyclic antidepressant overdose". J Cardiovasc Electrophysiol. 12 (2): 275. PMID 11232630.
  39. ↑ Babaliaros VC, Hurst JW (2002). "Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine". Clin Cardiol. 25 (8): 395–8. PMID 12173907.
  40. ↑
    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.
  41. ↑
    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.
  42. ↑ 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)
  43. ↑ 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)
  44. ↑ 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)
  45. ↑ 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)
  46. ↑
    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.
  47. ↑
    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.
  48. ↑
    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.
  49. ↑ 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.

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