Normal Heart VT

Syndromes

• Long QT

• Short QT

• Brugada

• Catecholaminergic Polymorphic VT-CPVT

• Idiopathic VF

• Short coupled TdP

• Lev-Lenegre Syndrome

ChannelopathiesECG 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 SyndromeHistory

• 1957• 1963-1964• 1958-1970• 1971

• 1979• 1991-2007

• 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 SyndromeOverview

• 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 1Broad T waves

LQT 2Bifid T waves

LQT 3Prolonged ST segment

Long QT SyndromeDiagnosis

• 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

LQTSGene Specific Triggers

68

28

4

15

51

34

18

27

55

0

10

20

30

40

50

60

70

LQT1 LQT2 LQT3

ExerciseEmotionSleep

Schwartz PJ et al. Circulation 103:89-95, 2001

Lethal and Non-lethal CV Events

Long QT SyndromeHigh 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

LQTSRisk 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

LQTSManagement 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)

LQTResources

• 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– 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 Syndrome1999 – 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 QTECG 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

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– PMH: none– SH: married, carpenter, occasional beer– FH: (-) sudden death, arrhythmias, premature CVD– Normal cardiac markers, echo

Brugada SyndromeOverview

• 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 SyndromeDefinition

• 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

Brugada pattern ECGST 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

• Utility of EP study – Controversial– 6-9% of healthy

individuals of induced VF at EPS

– Brugada, +EPS associated w/ 8x risk

• Other conduction abnormalities– QT prolongation

(R > L precordial)• Prolonged action

potential duration in RV epicardium

– P, PR, & QRS• PR prolongation

associated with His-purkinje delay

Brugada Consensus Conference

Spontaneous Type 1 ECG

ICD (I)

Aborted SCD

ICD (I)

ExtracardiacCauseabsent

Close f/u

ExtracardiacCausepresent

SyncopeSeizure

NAR

Symptomatic

ICD (IIA)

EPS (IIA)positive

Close f/u

EPS (IIA)negative

Family Hxpositive

ICD (IIA)

EPS (IIA)positive

Close f/u

EPS (IIA)negative

Famil Hxnegative

Asymptomatic

SpontaneousType 1 ECG

Brugada Consensus Conference

Sodium Channel Blocker Induced Type 1 ECG

ICD (I)

Aborted SCD

ICD (I)

ExtracardiacCauseabsent

Close f/u

ExtracardiacCausepresent

SyncopeSeizure

NAR

Symptomatic

ICD (IIA)

EPS (IIA)positive

Close f/u

EPS (IIA)negative

Family Hxpositive

ICD (IIA)

EPS (IIA)positive

Close f/u

EPS (IIA)negative

Famil Hxnegative

Asymptomatic

SpontaneousType 1 ECG

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

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

CPVTGenetic 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

CPVTManagement

• 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

ARVCIndik 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

– 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

• 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

• 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 – Echowww.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?