1. Normal Heart VT

2. Syndromes Long QT Short QT Brugada
Catecholaminergic Polymorphic VT-CPVT
Idiopathic VF
Short coupled TdP
Lev-Lenegre Syndrome

3. Channelopathies ECG and the Action Potential

4. Case 1 13 yo girl presents with syncope while swimming QTc ≥500 msec
ß-blocker initiated with no further events
Presents five years later inquiring about stopping medications
Do you stop ß-blocker?
Is an ICD indicated?

5. Long QT Syndrome History
1957
1971
1979
1st LQTS family reported
Romano-Ward Syndrome
25 LQTS cases reported
1st treatment – left stellate ganglionectomy
LQTS registry started
10 LQTS genes identified

6. Long QT Syndrome Overview
Incidence: 1/7,000
Presentation: mean age 8-14 years
Symptoms:
Syncope, palpitations, seizures, sudden death
Syncope in pediatric population should be considered malignant until proven otherwise
Arrhythmia: Torsades des pointes

7. LQT 1 Broad T waves

8. LQT 2 Bifid T waves

9. LQT 3 Prolonged ST segment

10. Long QT Syndrome Diagnosis
ECG definition
QTc > 460 females
QTc > 450 males
Challenges
25 to 50% of LQT 1, 2, & 3 individuals will have QTc ≤ 460 msec
Genetic testing has 3 to 5% false (+) rate
Epinepherine challenge
Useful in evaluating LQT1 (∆QT 30 msec)
Iks response to epinepherine in LQT1 impaired
NPV 93%, PPV 76%, Sens 92%, Spec 86%
Less useful when on beta-blockers

11. LQTS Gene Specific Triggers
Lethal and Non-lethal
CV Events
Schwartz PJ et al. Circulation 103:89-95, 2001

12. Long QT Syndrome High Risk Features
Aborted cardiac arrest
Family history (< 50 y) of cardiac arrest or unexplained syncope
History of “seizures” or congenital deafness
Prolonged QTc ≥500 msec on ECG
Positive genetic test

13. LQTS Risk of Cardiac Event (syncope, cardiac arrest, or sudden death)
QTc ≥ 500 msec: LQT1, LQT2, Male LQT3
Risk 30-50%
QTc ≥ 500 msec: Female LQT3
QTc < 500 msec: Female LQT2/3, Male LQT3
Risk < 30%
QTc < 500 msec: LQT1, Male LQT2

14. LQT Subtypes Type Gene Protein LQT1 KCNQ1 (KVLQT1) Iks 
Hom-JLN / Het-RWS
LQT2
HERG
Ikr 
Het-RWS
LQT3
SCN5A
Na
LQT4
Ankryn B
Lipid bilayer
LQT5
KCNE1 (MinK)
Iks 
LQT6
HERG (MiRP1)
Ikr 
LQT7
KCNJ2
IK1
Andersen’s Syndrome
LQT8
CACNA1C
I Ca 
Timothy Syndrome

15. LQTS Management Options
Lifestyle modification (IB)
Beta-blockers (IB)
Very effective LQT1, Moderate LQT2
Minimal effect LQT3
ICD plus BB
Cardiac arrest (IA)
Syncope / VT (IB)
Prophylactic in LQT2 or LQT3 (IIB)
Left stellate ganglionectomy (IIB)

16. LQT Resources Cardiac Arrhythmias Research & Education (CARE)
Cardiac Arrest Survivors Network (CASN)
International Registry for Drug Induced Arrhythmias

17. Case 1 Review
13 yo girl with syncope during swimming and QTc ≥500 msec
Asymptomatic for 5 y on BB
Swimming…suggests LQT1
High risk subgroup based LQT1 and QTc ≥500 msec
Recommendation
Continue BB given very effective in LQT1
Consider ICD if has arrest, syncope, or VT

18. Case 2 17 yo girl presents with atrial fibrillation
QT 268 msec at HR 69
Mother, age 51, and brother, age 21 with QT intervals of <300 msec also
History, exam, and cardiovascular workup otherwise negative
First reported family
Cardiology 2000;94:99-102

19. Short QT Syndrome 1999 – Dr. P. Bjerregaard
Ion Current
Gene
Gain of Function
Loss of Function
IKs
KvLQT1
sQT
LQT1
JLN/RWS
IKr
HERG2 (KCNH2)
LQT2
IK1
KCNJ2
LQT7 – Andersen’s Syndrome

20. Short QT ECG Characteristics
QT < 300msec
No significant QT change with HR ∆s
Short ST segment with tall, narrow peaked T-waves in V1-V6
Reentrant arrhythmias
Other clues
Lone AF, VF
Family Hx of SCD

21. Short QT EP testing Management
Short atrial and ventricular refractory periods
Management
Pharmacological (small studies)
Only hydroquinidine effective in increasing QT
Fleicanide, sotalol, ibutilide ineffective
ICD experience (limited)
T wave oversensing/inappropriate shocks
Device selection (St.Jude – delay/decay)

22. Case 2 Review
17 yo girl with AF and short QT. Mother and brother with short QT.
Treated with quinidine
For atrial fibrillation suppression
QT prolongation via K+ channel blockade
Long-term follow-up unavailable

23. Case 3 39y man c/o cp, palpitations, and presyncope PMH: none
SH: married, carpenter, occasional beer
FH: (-) sudden death, arrhythmias, premature CVD
Normal cardiac markers, echo

24. Brugada Syndrome Overview
Identified 1992
Age spectrum - 2d to 84y
Mean age sudden death 40 ± 15y
Men > 5x risk of arrhythmic events
Prevalence
5/10,000 - overall
#2 cause of death SE Asian men <40y
Dynamic but characteristic ECG changes
1 in 5 have Na channel mutation (SCN5A)

25. Brugada Syndrome Definition
Type 1 pattern ECG in V1-V3 plus 1 of following:
Pharm conversion to Type 1 from Type 2/3 ECG
Na channel blocker (procainamide, fleicanide, ajmaline)
Documented VF/polymorphic VT
Family history of SCD < 45y
Inducible VT at EP study
Syncope
Nocturnal agonal respirations
ECG pattern only = Brugada pattern ECG but not Brugada Syndrome
Exclude other heart conditions

26. Brugada pattern ECG ST elevation V1-V3
Type 1 (DIAGNOSTIC)
Coved ST elevation ≥ 2mm with negative T wave
sensitivity by moving V2/V3 from 4th to 2nd/3rd intercostal space
Type 2
Saddleback ST elevation ≥ 2mm w/ ST trough ≥ 1mm
Positive/biphasic T wave
Type 3
Coved/saddle ST elevation ≥ 2mm w/ ST trough < 1mm
Also reported in inferior leads and left precordial leads
Some individuals also had SCN5A mutation

27. Brugada Syndrome Other conduction abnormalities Utility of EP study
QT prolongation (R > L precordial)
Prolonged action potential duration in RV epicardium
P, PR, & QRS
PR prolongation associated with His-purkinje delay
Utility of EP study
Controversial
6-9% of healthy individuals of induced VF at EPS
Brugada, +EPS associated w/ 8x risk

28. Brugada Consensus Conference Spontaneous Type 1 ECG

29. Brugada Consensus Conference Sodium Channel Blocker Induced Type 1 ECG

30. Case 3 Review 39y man c/o cp, palpitations, and presyncope
Spontaneous type 1 ECG
“Asymptomatic”
Negative family hx
EP study (IIA indication)
Sustained VT with DES at 500 from RVA
No supraventricular arrhythmias induced
Normal AV node and His-Purkinje function
ICD was implanted (IIA indication)
Asymptomatic without events at 32 mo f/u
** Most events occur at night - autonomic role?
Other tx options: ablation, quinidine

31. Case 4 16 yo girl suddenly arrests running into store
History of exertional palpitations and syncope
Successful resuscitation by bystander nurse

32. Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
Clinical Features
Direct correlation with adrenergic stimulation (physical/emotional)
Threshold heart rate bpm
Abnormal automaticity or triggered activity
Bidirectional VT
Symptom onset in childhood
Genetic mutations – Ryanodine / Calsequestrin

33. CPVT Genetic Mutations
Calsequestrin (CASQ2)
Autosomal Recessive
Calcium storage protein w/in lumen of sarcoplasmic reticulum
Cardiac Ryanodine Receptor (RyR2)
Autosomal Dominant
Regulates Ca++ from sarcoplasmic reticulum
Delayed after-depolarizations
Associated with ARVC
RYR1 - malignant hyperthermia syndrome

34. CPVT Management Anti-adrenergic treatment ICDs
Beta blockers are the mainstay of treatment
ICDs
B-blockers not always effective

35. Case 4 Review
16 yo with history of palpitations and syncope who collapses in store
Arrested 3 times en route to hospital
ICD implanted and atenolol started
3 ICD revision procedures
2 lead dislodgements resulting in inappropriate ICD therapies

36. Case 5 24 yo man with recurrent syncope Signs and symptoms
Recent decrease in exercise tolerance
Lower extremity edema
Mild elevation in liver transaminases
Family hx + for sudden death – paternal uncle
Telemetry strip below

37. Arrhythmogenic Right Ventricular Cardiomyopathy - ARVC

38. ARVC Indik JH et al. Indian Pacing Electrophys J. 2003:3:148
Top picture:
Fibro-fatty replacement of the myocardium
Thin and enlarged RV wall.
Bottom picture:
Trichrome stain
Areas of mature fibrosis (F) and adipose tissue (A) within the epicardial (Epi) and mid-myocardial zones

39. ARVC
Diffuse fibrosis of the RV wall with preservation of normal LV tissue
Fibrous tissue appears white
Normal cardiac tissue appears black
Ventriculogram demonstrating fibrofatty infiltration
Indik JH et al. Indian Pacing Electrophys J :3:148

40. ARVC Signal-Averaged ECG -SAECG (below left):
Characteristic high-frequency low-amplitude late-potential
SAECG averages multiple QRS complexes that are then digitalized and filtered and further processed with spectral analysis to eliminate noise.
Late-potentials represent areas of delayed activation due to slowed conduction from either regions of scar or fibrosis  electrical substrate that initiates and perpetuates ventricular tachycardia.

41. ARVC High Risk Features
Younger patients
Recurrent syncope
History of cardiac arrest or sustained VT
Clinical signs of RV failure or LV involvement
Patients with or having a family member with the high risk ARVD gene (ARVD2)
Increase in QRS dispersion ≥ 40 msec
QRS dispersion = max measured QRS minus min measured QRS
Naxos disease

42. Case 5 Review Diagnosis Risk Management
Rhythm strip and ECG notable for epsilon waves and T wave inversion in right precordial leads
Risk
High risk features present – young age, recurrent syncope, signs of RV failure, family history of sudden cardiac arrest
Management
ICD implantation

43. Idiopathic Ventricular Fibrillation Short-coupled Torsades des Pointes
Sodium channel mutation
Short-coupled Torsades des Pointes
Normal QT interval with coupling interval of 1st ectopic beat < 300 msec
Prognosis poor with unproven tx (BB or CCB); ablation?
Lev-Lenegre Syndrome
Progressive cardiac conduction defect associated with bradyarrhythmias although tachyarrhythmias may also occur
Sodium channel defect

44. Idiopathic Ventricular Fibrillation

45. Lev-Lenegre Syndrome Progressive Cardiac Conduction Defect Very rare
Acquired complete heart block
Idiopathic fibrosis and calcification of cardiac conduction system
Very rare
Sodium channel mutations (subtype-SCN 5A)
Often result in bradyarrhythmias although tachyarrhythmias may also result
Lev M. Anatomic basis for atrioventricular block. Am J Med 1964;37:742-8.
Lenegre J. Etiology and pathology of bilateral bundle branch block in relation to complete heart block. Prog Cardiovasc Dis 1964;6:

46. Hypertrophic Cardiomyopathy
#1 cause of SCA in athletes
> 1/3 of deaths
Often associated with physical activity
60% high school age
>90% males
Genetic disorder left ventricular hypertrophy
First symptom often sudden death

47. HCM - ECG

48. HCM – Echo

49. HCM vs. Athletic Heart HCM Athletic Heart Septum > 15mm
Assymetrical (septum:posterior wall thickness > 1.5:1)
Occasional family history
No change with deconditioning
Athletic Heart
Septum < 15mm
Symmetrical thickening
No family history
Resolves with deconditioning – 3 mo

50. Thank You
Questions?