Understanding ECG Features in ARVD, Long QT Long QT and Brugada Syndrome Kazufumi Nakamura, MD., PhD. Kazufumi Nakamura, MD., PhD. D t t f Department of Cardiovascular Medicine, Okayama University Okayama University
Understanding ECG Features in ARVD, Long QTLong QT
and Brugada Syndromeg y
Kazufumi Nakamura, MD., PhD.Kazufumi Nakamura, MD., PhD.
D t t fDepartment of Cardiovascular Medicine,
Okayama UniversityOkayama University
ARVD (ARVC)
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is adysplasia/cardiomyopathy (ARVD/C) is a progressive disease of predominantly th i ht t i l h t i d bthe right ventricle, characterized by ventricular tachycardia that can lead to sudden cardiac death in children and young adults.y g
epsilon wave LBBB type VT
RV dilatation
RV
LVLA
AoV1 V5
LA
ECG i ARVDECG in ARVD
ECG in sinus rhythmECG in sinus rhythm
1) Prolonged QRS duration ≥ 110 msec 1) Prolonged QRS duration ≥ 110 msec in leads V1-V3.
2) Epsilon wave.3) T wave inversion in right precordial 3) T wave inversion in right precordial
leads.4) Low-voltage QRS amplitude.
ARVD (ARVC)ECG in sinus rhythm 1) QRS in V1 ≥ 110 msec
**
2) epsilon wave
*
*
* 3) T wave inversion
ECG i ARVDECG in ARVD
ECG in sinus rhythmECG in sinus rhythm
1) Prolonged QRS duration ≥ 110 msec 1) Prolonged QRS duration ≥ 110 msec in leads V1-V3.
2) Epsilon wave.3) T wave inversion in right precordial 3) T wave inversion in right precordial
leads.4) Low-voltage QRS amplitude.
ECG in ARVD
ECG in sinus rhythm1) Prolonged QRS duration ≥ 110 msec in
leads V1-V3leads V1 V3.Prolonged QRS duration ≥ 110 msec in lead V1 was reported to carry a sensitivity of 55%V1 was reported to carry a sensitivity of 55% and a specificity of 100% in a series of patients whose initial manifestation waspatients whose initial manifestation was sustained ventricular tachycardia.Generally QRS duration is more prolonged inGenerally, QRS duration is more prolonged in lead V1 compared to that in leads I and V6. Complete or incomplete right bundle branchComplete or incomplete right bundle branch block is also a common finding.
ECG i ARVDECG in ARVD
ECG in sinus rhythmECG in sinus rhythm
1) Prolonged QRS duration ≥ 110 msec 1) Prolonged QRS duration ≥ 110 msec in leads V1-V3.
2) Epsilon wave.3) T wave inversion in right precordial 3) T wave inversion in right precordial
leads.4) Low-voltage QRS amplitude.
ECG in ARVD
ECG in sinus rhythm
2) Epsilon wave.
Epsilon wave, an abnormal p ,deflection resulting from delayed right ventricular activation is noticedright ventricular activation is noticed at the end of the QRS complex in
t 30% f ti tup to 30% of patients.
ECG i ARVDECG in ARVD
ECG in sinus rhythmECG in sinus rhythm
1) Prolonged QRS duration ≥ 110 msec 1) Prolonged QRS duration ≥ 110 msec in leads V1-V3.
2) Epsilon wave.3) T wave inversion in right precordial 3) T wave inversion in right precordial
leads.4) Low-voltage QRS amplitude.
ECG in ARVD
ECG in sinus rhythm
3) T wave inversion in right precordial leads.
T wave inversion in right precordial leads is frequently seen in aboutleads is frequently seen in about 60% of patients with T wave abnormalities in leads V1 to V3 andabnormalities in leads V1 to V3 and remains the most suggestive
findicator of ARVD.
ECG i ARVDECG in ARVD
ECG in sinus rhythmECG in sinus rhythm
1) Prolonged QRS duration ≥ 110 msec 1) Prolonged QRS duration ≥ 110 msec in lead V1-V3.
2) Epsilon wave.3) T wave inversion in right precordial 3) T wave inversion in right precordial
leads.4) Low-voltage QRS amplitude.
ECG in ARVD
ECG in sinus rhythm
4) Low-voltage QRS amplitude4) Low voltage QRS amplitude.
Low voltage QRS amplitudeLow-voltage QRS amplitude indicates a widespread
di lmyocardial process.
ARVD (ARVC) -severe case-ECG in sinus rhythm 1) QRS in V1 ≥ 110 msec
* *
2) epsilon wave
*4) low-voltage
** 3) T wave inversion
ECG i ARVDECG in ARVD
Signal averaged ECGSignal-averaged ECG
Abnormal signal averaged ECGs are oftenAbnormal signal-averaged ECGs are often found in patients with ARVD.Th fib f l h i i fThe fibrofatty replacement characteristic of ARVD interrupts the electrical continuity of p ymyocardial fibers, which accounts for conduction delay.conduction delay.Signal-averaged ECG have a sensitivity of 57% and a specificity of 95%57% and a specificity of 95%.
ECG in ARVDSignal-averaged ECG
Late potentials
ECG i ARVDECG in ARVD
ECG of arrhythmiasECG of arrhythmias
Left bundle branch block (LBBB) type ventricular tachycardiaventricular tachycardia.
F t t i l t t lFrequent ventricular extrasystole(more than 1000/24 hours)
ARVD (ARVC)ARVD (ARVC)
Ventricular premature contraction: VPCVentricular premature contraction: VPC
**LBBB type
*
ARVD (ARVC)ARVD (ARVC)ventricular tachycardia: VT
LBBB type
ARVDDiagnostic Criteria-Diagnostic Criteria-
I Global and/or regional dysfunction and structural alterationsMAJOR
Severe dilatation and reduction of right ventricular ejection fraction with no (or only mild) LV impairment2 major criteria
orLocalised right ventricular aneurysms (akinetic or dyskinetic areas with diastolic bulging)Severe segmental dilatation of the right ventricle
MINORMild global right ventricular dilatation and/or ejection fraction reduction with normal left ventricleMild segmental dilatation of the right ventricle
or1 major +
2 minor criteriaor
Regional right ventricular hypokinesiaII Tissue characterisation ofwalls
MAJORFibrofatty replacement of myocardium on endomyocardial biopsy
III Repolarisation abnormalities
4 minor criteria
MINORInverted T waves in right precordial leads (V2 and V3)(people aged more than 12 yr; in absence of right bundle branch block)
IV Depolarisation/conduction abnormalitiesMAJOR
E il l li d l ti ( 1 10 ) f th QRS l i i ht di l l d (V1 V3)Epsilon waves or localised prolongation (> 1 10 ms) of the QRS complex in right precordial leads (V1-V3)MINOR
Late potentials (signal averaged ECG)V Arrhythmias
MINORL ft b dl b h bl k t t i l t h diLeft bundle branch block type ventricular tachycardia(sustained and non-sustained) (ECG, Holter, exercise testing).Frequent ventricular extrasystoles (more than 1000/24 h) (Holter)
VI Family historyMAJOR
Familial disease confirmed at necropsy or surgery M K t lFamilial disease confirmed at necropsy or surgeryMINOR
Familial history of premature sudden death (<35 yr) due to suspected right ventricular dysplasia.Familial history (clinical diagnosis based on present criteria)
McKenna et al.Br Heart J.1994;71:215-218.
CaseA 47-year-old female
ECG Clinical VT1 Clinical VT2
A 47 year old female
ⅠⅠ V 1
V 11) QRS in V1 ≥ 110 ms
2) il*
ⅡⅡ V 2
V 22) epsilon wave
3) T wave inversion*
Ⅲ Ⅲ
V 3
V 3
*
)
4) low-voltage
aVRV 4V 4 aVR
4) low voltage
aVF
aVL V 5V 5aVL
aVF V 6V 6
LBBB type
UCGSignal averaged ECG
RV dilatation
g g E
Late potentials
RV
LVLA
Ao
LA
RV
LV
LQTS
The long QT syndrome (LQTS) is characterized by a prolonged QT interval in the electrocardiogram (ECG), p g g ( ),syncope, and sudden cardiac death due to ventricular tachyarrhythmias, typically torsades de pointes. Two major h t i i t h b i i ll d ib d O iphenotypic variants have been originally described. One is
autosomal dominant (Romano Ward syndrome) and the other is rare autosomal recessive (Jervell and Lange-other is rare autosomal recessive (Jervell and Lange-Nielsen syndrome) also presenting with sensorineural deafness. Sporadic LQTS patients have also been p pclinically described.
Measurement of the QT Interval of an ECG
QT
Bazett’s formula
The end of T wave
Lepeschkin E,Surawicz B. Circulation. 1952;6:378-388.
-Criteria for diagnosis of LQTS-
1993 LQTS Diagnostic Criteria
Points
ECG findings
A. QTc1/2 3
1/2 460-470 msec1/2 2
450 msec1/2 (in males) 1
B. Torsade de pointes 2
C T l 1≤1 point, low probability
C. T-wave alternans 1
D. Notched T wave in three leads 1
E. Low heart rate for age 0.5
Clini l hi t r
of LQTS
2 to 3 points, intermediate probability of LQTSClinical history
A. Syncope
With stress 2
Without stress 1
probability of LQTS
≥4 points, high probability of LQTS
Without stress 1
B. Congenital deafness 0.5
Family history
A Family members with definete LQTS 1
Schwartz et al. Circulation.A. Family members with definete LQTS 1
B. Unexplained sudden cardiac death below age 30
among immediate family members 0.5
1993;88:782-4
LQTSLQTSDisease Gene Ion channelR W d dRomano-Ward syndrome LQT1 KCNQ1 (KVLQT1) IKs
LQT2 KCNH2 (HERG) IKr LQT2 KCNH2 (HERG) IKr LQT3 SCN5A INa LQT4 ANK2 (ankyrin B) Na-K ATPase LQT5 KCNE1 (minK) IKs LQT6 KCNE2 (MiRP) IKr
LQT9 CAV3 (caveolin-3) I LQT9 CAV3 (caveolin-3) INa LQT10 SCN4B INaJavell & Lange-Nielsen syndrome JLN1 KCNQ1 IKs JLN2 KCNE1 IKsAndersen Tawil syndrome(LQT7) KCNJ2 I (Ki 2 1)Andersen-Tawil syndrome (LQT7) KCNJ2 IK1 (Kir2.1)Timothy Syndrome (LQT8) CACNA1c ICa-L
ECG recordings in three patients with LQTS
LQT3 LQT2 LQT1
late-onset T waves early onset of broad-based T waves
low-amplitude T waves
Moss AJ. et al. Circulation 1995;92:2929-2934
LQT ECG type
• LQT1 Broad-based T waveLQT1 Broad based T wave
• LQT2 Low-amplitude bifid T waveLQT2 Low amplitude bifid T wave
• LQT3 Late-onset T waveLQT3 Late onset T wave
• ATS Manifest U waveATS Manifest U wave
LQT1KCNQ1 V254M
B d b d T
KCNQ1, V254M
Broad-based T wave
Late-onset normal-appearing T-wave
LQT2KCNH2 G47C
Low-amplitude bifid T waveKCNH2, G47C
p
LQT3SCN5A E1784K
L t t T
SCN5A, E1784K
Late-onset T wave
Andersen-Tawil syndrome
M if t UKCNJ2, T75M
Manifest U wave
Torsades de pointesTorsades de pointes
short long short
ECG showed marked QT prolongation, T-wave alternans, and episodes of Torsades de pointes.
Nakamura et al. J Am Coll Cardiol. 2007;50:1808-9
Exercise a) Control b) Post exercise
I
IILQT1 II
III
LQT1
II
12
39
6Auditory stimulus LQT2
TdP
Brugada SyndromeBrugada SyndromeBrugada syndrome is
I
II
V1
V2
Brugada syndrome is a clinical entity characterized by ST-
III V3
ysegment elevation in right precordial leads (V1 V3) d i d
aVL
aVR V4
V5
(V1-V3) and episodes of ventricular tachyarrhythmia in the
aVF V6
tachyarrhythmia in the absence of structural heart disease.
V2
Brugada Syndrome : Clinical characteristicsBrugada Syndrome : Clinical characteristics
1. Male predominant (M:F>20:1)2. The incidence of Brugada syndrome is higher in Asian
countries.countries.3. Cardiac sudden death due to VF often occurs at night.
a 4% of all sudden deaths (SD)a.4% of all sudden deaths (SD)b.20-50% of SD in patients with structurally normal hearts
A f il hi t f l i d dd d th i tc. A family history of unexplained sudden death is present in approximately 20% of cases.
4. Mutation of the SCN5A gene, the gene encoding the sodium channel, accounts for about 20% of Brugada syndrome cases.
ST segment abnormalities in lead V1 to V3
J point ≥ 2 mm ≥ 2 mm ≥ 2 mm
Type 1 Type 2 Type 3
T wave
ST-T configuration
ST segment (terminal portion)
negative
coved type
gradually descending
positive or biphasic
saddleback
elevated ≥ 1 mm
positive
saddleback
elevated < 1 mm
Wilde et al. Circulation 2002:106;2514
Diagnostic CriteriaDiagnostic Criteria
Brugada syndrome is definitively diagnosed:
Type 1 ECG > 1 right precordial lead (V1-3)
Brugada syndrome is definitively diagnosed:
yp g p ( )with or without Na+ channel blocker
+• Ventricular fibrillation• Polymorphic ventricular tachycardia
+
• Polymorphic ventricular tachycardia• Family history of sudden cardiac death (<45 y.o.)• Coved-type ECGs in family member• Inducibility of VT with programmed electrical stimulation• Syncope• Nocturnal agonal respirationNocturnal agonal respiration
Heart Rhythm 2005 Consensus Report
Dynamic changes of ST segment
May ’96 June ’96 July ’96Jan ’9171 y.o. Male
May 96 June 96 July 96Jan 91(VF attack)
V1
V2
V3
Sodium channel blockers amplify or unmaskSodium channel blockers amplify or unmask ST segment elevation
Control Na channel blocker(pilsicainide)
V1 0.12ST level
0.30ST level
1.65
V2 0.70
(mV) (mV)
39 y.o. Male
PVC and initiation of VF PVC and initiation of VF V and initiation of VF V and initiation of VF in Brugada syndromein Brugada syndrome
II
II
aVRaVL
III
aVL
aVFV1V1
V3V2
V4V5
V3
V5
V6
Genotype
Type Locus onChromosome Gene Protein Affected
CurrentEffect on
channel functionIncidence
(%)
BS1 3p21 SCN5A Nav1.5 INa Loss of function 20
BS2 3p24 GPD1-L GPD1-L protein INa Loss of function
BS3 12p13.3 CACNA1C Cav1.2 ICa-L Loss of function
BS4 10p12.33 CACNB2b Cav ICa-L Loss of function
BS5 19q13.1 SCN1B Nav INa Loss of function
BS6 11q13-14 KCNE3 MiRP2 It Gain of functionBS6 11q13 14 KCNE3 MiRP2 Ito Gain of function
SCN5A Mutation (-) SCN5A Mutation (+)( ) ( )51 y.o. Male, VF(+) 33 y.o. Male, VF(+)
V1V1
V2V2
V3
Genotype and Phenotype relationship
66±13ms 48±9ms209±51ms 163±24ms 66±13ms 48±9ms209±51ms 163±24ms
Wilde et al. JACC 2002;40:350
<A k l d t >
Daiji Miura
<Acknowledgments>
Daiji Miura, Satoshi Nagase, Hiroshi Morita, Kengo F KusanoKengo F Kusano,Tohru Ohe
Department of Cardiovascular Medicine, Okayama University, p , y y,Okayama, Japan
Mamoru Ouchida, Kenji Shimizu,Department of Molecular Genetics, Okayama University, Okayama, Japan
Thank you for your attention.御清聴ありがとうございました。