Brugada Syndrome and Long QT Syndrome are cardiac conditions that can cause abnormal heart rhythms and sudden cardiac death. For Brugada Syndrome, the key aspects of diagnosis, risk stratification, and management discussed include identifying type 1 ECG patterns, assessing risk based on exercise stress tests and signal-averaged ECGs, and treating high-risk patients with medications like quinidine or catheter ablation. For Long QT Syndrome, diagnosis involves measuring the corrected QT interval on ECG, risk stratification considers specific genetic mutations and history of syncope, and management relies on beta blockers and ICDs for high-risk patients. Both conditions require careful medical management to reduce risks of life-threatening arrhythmias.

1. EBM Presentation:
Brugada Syndrome and
LQTS
27 Feb 2015
Koh Choong Hou
Supervisor: ColinYeo

2. Scope
• Brugada Syndrome
• Diagnosis
• Risk Stratification
• Management
• Long QT Syndrome
• Diagnosis
• Risk Stratification
• Management

6. Brugada Syndrome
Brugada P, Brugada J. A distinct clinical and electrocardiographic syndrome: right bundle branch block, persistent ST segment elevation with normal QT
interval and sudden cardiac death (abstr) PACE. 1991;14:746.

10. • Type 1 is diagnostic of Brugada syndrome and is characterized by a coved ST-segment
elevation >/=2 mm (0.2 mV) followed by a negative T wave. Brugada syndrome is
definitively diagnosed when a type 1 ST-segment elevation is observed in 1 right precordial
lead (V1 to V3) in the presence or absence of a sodium channel– blocking agent, and in
conjunction with one of the following: documented ventricular fibrillation (VF),
polymorphic ventricular tachycardia (VT), a family history of sudden cardiac death at <45
years old, coved-type ECGs in family members, inducibility of VT with programmed
electrical stimulation, syncope, or nocturnal agonal respiration.
• Confounding factors for ECG abnormality or syncope should be excluded:
1. Atypical RBBB, LVH, early repolarization, acute pericarditis, AMI, pulmonary embolism,
Prinzmetal angina, dissecting aortic aneurysm, various central and autonomic nervous system
abnormalities, Duchenne muscular dystrophy, thiamin deficiency, hyperkalemia, hypercalcemia,
ARVC, pectus excavatum, hypothermia, and mechanical compression of RVOT as occurs in
mediastinal tumor or hemopericardium
Diagnosis of BrS
Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference. Heart Rhythm 2005;2:429–440.

11. BrS Supporting Features
• Attenuation of ST-segment elevation at peak of exercise stress test followed by its
appearance during recovery phase.
• Presence of AF
• Fragmented QRS
• ST-T alternans, spontaneous LBBBVPBs during prolonged ECG monitoring
• V-ERP < 200ms during EPS, and HV interval > 60ms
• Signal average ECG: late potentials
• 1st degree AVB, left axis deviation
• Absence of structural heart disease including myocardial ischaemia
Morita H, Kusano KF, Miura D, et al. Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. Circulation
2008;118:1697–1704.

12. Risk stratification: Augmented ST-Elevation During Recovery From Exercise
Makimoto H, Nakagawa E, Takaki H, et al. Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada
syndrome. J Am Coll Cardiol 2010;56:1576–1584.

13. Augmented ST-Elevation During Recovery From Exercise

14. Risk stratification: SAECG late potentials
Ikeda T, Sakurada H, Sakabe K, et al. Assessment of noninvasive markers in identifying patients at risk in the Brugada syndrome: insight into risk stratification. J
Am Coll Cardiol 2001;37:1628–1634.

15. Risk Stratification: spont type 1 ECG +/- syncope
Priori SG, Napolitano C, Gasparini M, et al. Natural history of
Brugada syndrome: insights for risk stratification and management.
Circulation 2002;105: 1342–1347.

16. Risk stratification: QRS-fragmentation vsVT/VF inducibility
Priori SG, Gasparini M, Napolitano C, et al. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive
valuE) registry. J Am Coll Cardiol 2012;59:37–45.

17. Management of BrS
• Pharmacological
Options
1. Quinidine
2. Isoprenaline
• RFA

18. ICDs not indicated in asymptomatic low risk group
Mizusawa Y, Wilde AA. Brugada syndrome. Circ Arrhythm Electrophysiol 2012;5:606–616.

19. Kaplan–Meier curve of inappropriate shock depending on the period of implantation.
Sacher F et al. Circulation. 2013;128:1739-1747
Copyright © American Heart Association, Inc. All rights reserved.

20. BrS Pharmacological Rx
• BrS pathophysiological basis: gain of function of Ito or Ik , or loss of function
of INa or ICa
• Isoprenaline, which increases the L-type calcium current, has proven to be
useful for treatment of electrical storm in BrS (but controlled data on its
therapeutic role is not available)
• Quinidine, a class IA anti arrhythmic with Ito or IKr blocking effects, shown
to preventVF induction and suppress spontaneous ventricular arrhythmias
in a clinical setting. Currently used for:
1. Pts with ICD and multiple shocks
2. ICD contraindicated
3. Rx of supra ventricular arrhythmias
Maury P, Hocini M, Haissaguerre M. Electrical storms in Brugada syndrome: review of pharmacologic and ablative therapeutic options. Indian Pacing
Electro- physiol J 2005;5:25–34.
Marquez MF, Bonny A, Hernandez-Castillo E, et al. Long-term efficacy of low doses of quinidine on malignant arrhythmias in Brugada syndrome with
an implantable cardioverter-defibrillator: a case series and literature review. Heart Rhythm 2012;9:1995–2000.

21. RFA in BrS
Nademanee K, Veerakul G, Chandanamattha P, et al. Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation
over the anterior right ventricular outflow tract epicardium. Circulation 2011;123:1270–1279.
A delayed effect of epicardial ablation
on the ECG pattern.
Left lateral view of the right ventricular
outflow tract (RVOT) displays the
difference in ventricular electrograms
between the endocardial (ENDO) and
epicardial (EPI) site of the anterior
RVOT.

24. Long QT Syndrome
Curran ME, Splawski I, Timothy KW, et al. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 1995;80:795–803.
Wang Q, Shen J, Splawski I, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995;80:805–811.
Schwartz PJ, Periti M, Malliani A. The long Q-T syndrome. Am Heart J 1975;89: 378-90.
Moss AJ, Schwartz PJ, Crampton RS, Locati E, Carleen E. The long QT syn- drome: a prospective international study. Circulation 1985;71:17-21.

27. Diagnosis of LQTS
Diagnosis of LQTS is still based on measurement of QT internal corrected for HR (QTc) using
Bazett’s formula. Need to exclude secondary causes of QTc prolongation (drugs, electrolyte
imbalances etc)

28. Schwartz Score
Text
QTc calculated by Bazett’s formula. Resting HR < 2nd percentile for age. Definite LQTS if score more than 3.
Schwartz PJ, Moss AJ, Vincent GM, et al. Diagnostic criteria for the long QT syndrome. An update. Circulation 1993;88:782–784.

30. Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: do we need a scoring system?
Nynke Hofman , Arthur A.M. Wilde , Stefan Kääb , Irene M. van Langen , Michael W.T. Tanck , Marcel M.A.M. Mannens , Martin Hinterseer , Britt-Maria
Beckmann , Hanno L. Tan. Eur Heart Journal Nov 2006.

31. Risk stratification
• Specific genetic variants: Jervell Lange-Nielsen syndrome,Timothy
syndrome (LQT8)
• Mutations in loops of LQT1
• LQT1 mutations with dominant negative ion current effects
• Mutations in pore region of LQT2
Schwartz PJ, Spazzolini C, Crotti L, et al. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation
2006;113:783–790.
Splawski I, Timothy KW, Sharpe LM, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell
2004;119:19–31.
Barsheshet A, Goldenberg I, O-Uchi J, et al. Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for
mutation-specific response to beta-blocker therapy in type 1 long-QT syndrome. Circulation 2012;125:1988–1996.
Migdalovich D, Moss AJ, Lopes CM, et al. Mutation and gender-specific risk in type 2 long QT syndrome: implications for risk stratification for life-
threatening cardiac events in patients with long QT syndrome. Heart Rhythm 2011;8: 1537–1543.
Moss AJ, Zareba W, Kaufman ES, et al. Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-
go- related gene potassium channel. Circulation 2002;105:794–799.

32. Risk stratification: QTc duration > 500ms
Priori SG, Schwartz PJ, Napolitano C, et al. Risk stratification in the long-QT syndrome. N Engl J Med 2003;348:1866–1874.

33. Risk stratification: Syncope / childhood SCA
Priori SG, Napolitano C, Schwartz PJ, et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA
2004;292:1341–1344.

34. Management of LQTS
• Lifestyle modifications: avoidance of strenuous exercise, esp
swimming, without supervision in LQT1 puts
• Reduction in exposure to abrupt loud noises in LQT2
• Avoidance of all QT-prolonging drugs
• Beta blockers
• ICD implantation
• Left cardiac sympathetic denervation
• Class I antiarrhythmics (mexiletine, flecainide)
. Zipes DP, Camm AJ, Borggrefe M, et al. 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. Circulation
2006;114: e385–e484.

35. Beta blockers in LQTS
Priori SG, Napolitano C, Schwartz PJ, et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA
2004;292:1341–1344.
Schwartz PJ, Spazzolini C, Crotti L. All LQT3 patients need an ICD: true or false? Heart Rhythm 2009;6:113–120.
J Am Coll Cardiol. 2014;64(13):1352-1358. doi:10.1016/j.jacc.2014.05.068

36. ICD therapy in LQTS: arrhythmic events
despite BBs
Jons C, Moss AJ, Goldenberg I, et al. Risk of fatal arrhythmic events in long QT syndrome patients after syncope. J Am Coll Cardiol 2010;55:783–788.

37. Schwartz PJ, Spazzolini C, Priori SG, et al. Who are the long-QT syndrome patients who receive an implantable cardioverter-defibrillator and what
happens to them?: data from the European Long-QT Syndrome Implantable Cardioverter- Defibrillator (LQTS ICD) Registry. Circulation 2010;122:1272–
1282.

39. Schwartz PJ, Priori SG, Cerrone M, et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT
syndrome. Circulation 2004;109:1826–1833.

41. A word on ICDs and an “incurable” disease