Inherited Kidney Diseases Zehra Eren M.D. Nephrology Department.
Inherited Arrhythmogenic Diseases
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Transcript of 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
Structurally normal heart
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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
Structurally normal heart
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