Download Sudden Death In the Structurally Normal Heart

Normal Heart VT
Syndromes
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Long QT
Short QT
Brugada
Catecholaminergic Polymorphic VT-CPVT
Idiopathic VF
Short coupled TdP
Lev-Lenegre Syndrome
Channelopathies
ECG and the Action Potential
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?
Long QT Syndrome
History
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1957
1963-1964
1958-1970
1971
• 1979
• 1991-2007
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1st LQTS family reported
Romano-Ward Syndrome
25 LQTS cases reported
1st treatment – left stellate
ganglionectomy
• LQTS registry started
• 10 LQTS genes identified
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
LQT 1
Broad T waves
LQT 2
Bifid T waves
LQT 3
Prolonged ST segment
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
LQTS
Gene Specific Triggers
70
68
60
55
51
Lethal and Non-lethal
CV Events
50
40
30
28
20
10
34
27
15
Exercise
Emotion
Sleep
18
4
0
LQT1
LQT2
LQT3
Schwartz PJ et al. Circulation 103:89-95, 2001
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
LQTS
Risk of Cardiac Event
(syncope, cardiac arrest, or sudden death)
• Risk > 50%
– 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
LQT Subtypes
Type
Gene
Protein
LQT1
KCNQ1 (KVLQT1)
Iks 
Hom-JLN / Het-RWS
LQT2
HERG
Ikr 
Het-RWS
LQT3
SCN5A
Na
Het-RWS
LQT4
Ankryn B
Lipid bilayer
Het-RWS
LQT5
KCNE1 (MinK)
Iks 
Hom-JLN / Het-RWS
LQT6
HERG (MiRP1)
Ikr 
LQT7
KCNJ2
IK1
Andersen’s Syndrome
LQT8
CACNA1C
I Ca 
Timothy Syndrome
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)
LQT
Resources
• Cardiac Arrhythmias Research &
Education (CARE)
– www.longqt.org
• Cardiac Arrest Survivors Network (CASN)
– www.casn-network.org
• International Registry for Drug Induced
Arrhythmias
– www.qtdrugs.com
Case 1 Review
• 13 yo girl with syncope during swimming and
QTc ≥500 msec
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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
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
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)
sQT
LQT2
IK1
KCNJ2
sQT
LQT7 –
Andersen’s
Syndrome
Short QT
ECG Characteristics
• QT < 300msec
• No significant QT change
with HR ∆s
• Short ST segment with
tall, narrow peaked Twaves in V1-V6
• Reentrant arrhythmias
• Other clues
– Lone AF, VF
– Family Hx of SCD
Short QT
• EP testing
– 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)
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
Case 3
• 39y man c/o cp, palpitations, and presyncope
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PMH: none
SH: married, carpenter, occasional beer
FH: (-) sudden death, arrhythmias, premature CVD
Normal cardiac markers, echo
Brugada Syndrome
Overview
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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)
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)
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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
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
Brugada Syndrome
• Other conduction
abnormalities
– QT prolongation
(R > L precordial)
• Prolonged action
potential duration in RV
epicardium
– P, PR, & QRS
• PR prolongation
associated with Hispurkinje delay
• Utility of EP study
– Controversial
– 6-9% of healthy
individuals of induced
VF at EPS
– Brugada, +EPS
associated w/ 8x risk
Brugada Consensus
Conference
Spontaneous Type 1 ECG
Spontaneous
Type 1 ECG
Symptomatic
Aborted SCD
ICD (I)
Asymptomatic
Syncope
Seizure
NAR
Family Hx
positive
Famil Hx
negative
Extracardiac
Cause
absent
Extracardiac
Cause
present
EPS (IIA)
positive
EPS (IIA)
negative
EPS (IIA)
positive
EPS (IIA)
negative
ICD (I)
Close f/u
ICD (IIA)
Close f/u
ICD (IIA)
Close f/u
Brugada Consensus
Conference
Sodium Channel Blocker Induced Type 1 ECG
Spontaneous
Type 1 ECG
Symptomatic
Aborted SCD
ICD (I)
Asymptomatic
Syncope
Seizure
NAR
Family Hx
positive
Famil Hx
negative
Extracardiac
Cause
absent
Extracardiac
Cause
present
EPS (IIA)
positive
EPS (IIA)
negative
EPS (IIA)
positive
EPS (IIA)
negative
ICD (I)
Close f/u
ICD (IIA)
Close f/u
ICD (IIA)
Close f/u
Case 3 Review
• 39y man c/o cp, palpitations, and presyncope
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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
Case 4
• 16 yo girl suddenly arrests running into store
• History of exertional palpitations and syncope
• Successful resuscitation by bystander nurse
Catecholaminergic Polymorphic Ventricular
Tachycardia (CPVT)
• Clinical Features
– Direct correlation with adrenergic stimulation
(physical/emotional)
• Threshold heart rate 120-130 bpm
• Abnormal automaticity or triggered activity
– Bidirectional VT
– Symptom onset in childhood
– Genetic mutations – Ryanodine / Calsequestrin
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
CPVT
Management
• Anti-adrenergic treatment
– Beta blockers are the mainstay of treatment
• ICDs
– B-blockers not always effective
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
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
Arrhythmogenic Right Ventricular
Cardiomyopathy - ARVC
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
ARVC
• Diffuse fibrosis of the RV
wall with preservation of
normal LV tissue
– Fibrous tissue appears
white
– Normal cardiac tissue
appears black
–
www.geneticheartdisease.org
• Ventriculogram
demonstrating fibrofatty
infiltration
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Indik JH et al. Indian Pacing Electrophys J.
2003:3:148
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.
ARVC
High Risk Features
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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
Case 5 Review
• Diagnosis
– 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
• Idiopathic Ventricular Fibrillation
– 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
Idiopathic Ventricular Fibrillation
Lev-Lenegre Syndrome
• Progressive Cardiac Conduction Defect
– 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
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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;6:409-444
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
HCM - ECG
HCM – Echo
www.hcmny.org
HCM vs. Athletic Heart
• HCM
– 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
Thank You
Questions?