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。