This document discusses long QT syndrome (LQTS), a genetic disorder characterized by a prolonged QT interval on electrocardiogram that can cause dangerous arrhythmias like torsade de pointes. It describes the genetic causes and clinical features of LQTS, including presentations like unexplained syncope. Triggering factors like exercise and emotions are discussed. The pathophysiology involving early and delayed afterdepolarizations is explained. Diagnosis, risk stratification, and management including lifestyle changes, beta blockers, pacemakers, and ICDs are summarized.
3. Fig.3. Acting potential and reltive net ion current in myocardiocyte(Lin et al., 2011)
• Phase 4 resting potential
• Phase 0 Fast Na+ influx via Na+ channel (fase depolarisasi)
• Phase 1 Closed Na+ channel, opened delayed rectifier potassium channel
(fase repolarisasi singkat)
• Phase 2 Opened L-type Ca channel vs K+ efflux
• Phase 3 K+ efflux continues, work of Na+-Ca2+ exchanger, Ca2+-ATP ase,
Na+K+-ATP ase (inaktivasi kanal Ca tipe L, efluks K
4. • In specialized conduction system less negative
resting potential, more rapid phase 0 (kanal ion Na
selalu tertutup)
• Fase 4 : lebih menanjak krn
influks ion Na+ shg lebih tdk
negatif (aliran PM)
• Karena depolarisasi pada sel PM
hanya bergantung pada Ca2+
depolarisasi cenderung terjadi
lebih lambat dengan amplitudo
yang lebih rendah
Fig.4. Acting potential of
pacemaker cell (Lin et al., 2011)
12. Long QT Syndrome
■ Genetic disorder (1:5,000-10,000)
■ ECG evidence: QTc interval prolonged
■ >440 ms in males
■ >450 ms in females
■ Hallmark arrhythmia: Torsade de pointesVT
■ Persistently inward INa in LQT3 and reduced Ikr in LQT2 and Iks in
LQT1
■ Primary presenting symptom:Syncope
■ SCD in children or young adults
13. LQTS: Identification of Risk
■ Most common presenting symptom: unexplained syncope.
■ Syncope on exertion in pediatric patients should be
considered malignant until proven otherwise.
■ History & ECG:
– Onset and offset of syncopal episode
– Siblings, or family members with unexplained syncope or
sudden death
– Family history of “seizures” or congenital deafness
– ProlongedQTc on ECG
18. Pathophysiology
■ EAD (R onT VT)
■ DAD
■ Reentry- TdP
– [HypoK, HypoMg, K blocking
drugs (I, III), bradycardia]
19. EarlyAfter Depolarization(EAD)
■ EAD occurs when large inward current during platue phase occurs
resulting in prolongation of plateau.This provides time for
reactivation of Ical. It is this second phase of reactivation of
inward Ical that produces EAD by depolarizing cell membrane.
■ A delicate balance between depolarizing and repolarizing currents
controls the plateaue phase of theAP
.An increase in inward
current and or decrease in outward current may induce EADs.
■ Example include persistently inward INa in LQT3 and reduced Ikr in
LQT2 and Iks in LQT1
■ Ical is the primary depolarizing factor responsible for EAD
20. Delayed after Depolarizations
■ Delayed after depolarizations (DADs) begin during
phase 4, after repolarization is completed but
before another action potential would normally
occur via the normal conduction systems of the
heart.
■ They are due to elevated
cytosolic calcium concentrations, classically seen
with digoxin toxicity.
■ The overload of the sarcoplasmic reticulum may
cause spontaneous Ca2+ release after
repolarization, causing the released Ca2+ to exit
the cell through the 3Na+/Ca2+-exchanger. This
results in a net depolarizing current.
25. Triggering Events for Syncope orSCD
■ 3 main factors contributing to syncope or SCD
– Exercise (LQT1), especially swimming
– Emotions or emotional stress (LQT2)
– Events occurring during sleep or at rest,
with or without arousal (LQT3)
29. Hereditary varients
■ Jervell and Lange-Nielsen syndrome:
-longQT syndrome, associated with severe, bilateral sensorineural hearing loss
-mutation on KCNQ1 or KCNE1 genes (LQT1- Iks)
-most severe variant of LQTS (autosomal recessive)
- 90% have cardiac event by age 3
-ICD should be seriously considered
■ Romano-ward syndrome :
-LongQT syndrome, not associated with hearing loss
-Mutations in theANK2, KCNE1, KCNE2, KCNH2, KCNQ1, andSCN5A genes can cause
Romano–Ward syndrom
-most common form of LQTS (autosomal dominanat)
30. Hereditary varients
■ Andersen tawil syndrome: LQT7
periodic paralysis, dysmorphic feature, ventricular arrhythmia
mean age 5 years
prolonged terminalT wave, wideTU junction, biphasic and enlargeU wave
■ Timothy syndrome: LQT8
highly lethal arrhythmia disorder, fetal bradycardia, extreme prolongation ofQT,
microscopicT wave alterans, 2:1AV block at birth, syndactyly, dysmorphic feature.
■ Ankyrin B Syndrome: LQT4
33. Management
■ Life style modification
■ blockers in LQTS clinical diagnosis (ecg) [ may be given in patient
with molecular diagnosis alone]
■ PPI in cases with sustained pause dependentVT +/-QT prolongation
■ ICD in survivors of cardiac arrest, may be given in blocker
resistant,
considered in high risk groups [LQT2, LQT3,QT>500ms]
[Left cardiac sympathetic denervation considered for symptomatic
34. Management by Genotype
■ LQT1 and LQT2 benefit the most from ß-blocker therapy
■ The benefit of ß-blocker therapy is less clear in LQT3.
■ ICDs indicated:
– if the patient presents asSCD survivor or aborted cardiac arrest
– if ß-blockers are not effective in preventing cardiac events
