Inherited Arrhythmogenic Diseases

8/3/2019 Inherited Arrhythmogenic Diseases

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Dr. Jyothish Vijay


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Introduction Predisposes to arrhythmias and sudden death

Structurally normal heart

Previously considered as Idiopathic VF Cardiac channelopathies


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Long QT Syndrome

Brugada Syndrome

Catecholaminergic Polymorphic VT Short QT Syndrome


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LONG QT SYNDROMES


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Genesis of T wave


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Correlation of action potential with

ECG


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Uncommon genetic disorder (1:5,000 -1:10,000)

ECG evidence: QTc interval prolonged

> 450ms in males> 460ms in females

Hallmark arrhythmia: Torsade de pointes VT

Primary symptom: Syncope

Peak risk of SCD: children and young adults


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Holter in long QT

Torsa de pointes


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Two major phenotypic variants have been

originally described in the early sixties:

Romano Ward syndrome (autosomal dominant ) Jervell -Lange-Nielsen syndrome (rare autosomal

recessive with sensorineural deafness)


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Type of LQTS Chromosomal Locus

MutatedGene

Ion CurrentAffected

LQT1 11p15.5 KVLQT1, orKCNQ1(heterozygotes)

Potassium

(IKs)

LQT2 7q35-36 HERG, KCNH2 Potassium(IKr)

LQT3 3p21-24 SCN5A Sodium (INa)

LQT4 4q25-27 ANK2, ANKB Sodium,potassium andcalcium

LQT5 21q22.1-22.2 KCNE1(heterozygotes)

Potassium(IKs)

LQT6 21q22.1-22.2 MiRP1, KNCE2 Potassium(IKr)


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LQT7 (Anderson

syndrome)

17q23.1-q24.2 KCNJ2 Potassium (IK1)

LQT8 (Timothysyndrome)

12q13.3 CACNA1C Calcium (ICa-Lalpha)

LQT9 3p25.3 CAV3 Sodium (INa)

LQT10 11q23.3 SCN4B Sodium (INa)LQT11 7q21-q22 AKAP9 Potassium (IKs)

LQT12 SNTAI Sodium (INa)

JLN1 11p15.5 KVLQT1, or

KCNQ1(homozygotes)

Potassium (IKs)

JLN2 21q22.1-22.2 KCNE1(homozygotes)

Potassium (IKs)


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Genotype

Phenotype correlation Most common genetic variants

LQT1 45% , LQT2 45% ,LQT3 7%


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TreatmentActivity restriction

Avoid QT prolonging drugs

Beta Blockers Pacemakers

ICD

Left stellate ganglionectomy


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1992 Brugada & Brugada

a very specific ECG

apparent RBBBST elevation in leads V1-V3

Susceptibility to vent tachyarrhythmias



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Ionic basismutation in Sodium channel SCN5A


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ECG pattrerns


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Typical arrhythmia rapid polymorphic VT ,frequently degenerate into VF

Increased propensity to develop AF

Usually manifested 3rd and 4th decade

Male are more affected 8:1

Specific triggers Fever , Tricyclic antidepressant use,cocaine

Cardiac events occur mostly during sleep or at rest


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Intermittent nature of ECG pattern needs provocativedrug testing to unmask concealed forms .

Drugs used Class 1C antiarrhythmic

Ajmaline - 1mg/kg

Flecainide - 2 mg/kg

Procainamide - 15 mg/kg


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Genetics Cardiac sodium channel gene ( SCN5A)

Loss of function Brugada syndrome - BrS1

Gain of function LQT3 BrS2 GPD1-L gene (recently detected )


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Clinical decision making Role of EP for risk sratification is not definite

High risk syncope & spontaneous ECG pattern ICDis indicated

Intermediate risk spontaneous abnormal ECG -strategy ?

Lowest risk negative baseline ECG

No pharmacological treatment .


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Adrenergically induced VT Syncope & SCD


Cardiac events are triggered by exercise or acuteemotion

Baseline ECG normal During graded exercise VPCsNSVT VT

VT can be Bidirectional VT or irregular polymorphicVT

SVT can also occur during exercise


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Genetics

Autosomal Dominant CPVT cardiac ryanodinereceptor mutation

Autsomal recessive CPVT CASQ2 mutation


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a new congenital channelopathy

Short QT interwal below 300 to 320 msec

3 genes are identified K+ current gain of function Propensity to develop atrial and ventricular fast

rhythm

these patients are at risk of sudden death from birth


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ECG


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Exclude secondary causes for short QT

Hyperkalemia

Hypercalcemia

Hyperthermia

Acidosis Digoxin therapy


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Treatment The finding that Quinidine effectively prolongs the

QT interval and ventricular ERP and preventsventricular arrhythmia induction suggests that it may

be considered as a potential therapy for short QTpatients.

Prophylactic ICD


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THANKYOU

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Inherited Arrhythmogenic Diseases