Long QT Syndrome

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Long QT Syndrome

• Teresa Menendez Hood M.D.

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LQTS Facts

• Abnormalities of ion channels that result in
  long QT intervals ( prolongation of phase
  III-time for repolarization) and predispose to
  polymorphous ventricular tachycardia (Torsade de
  Pointe)
• Common cause of sudden death in children and
  young adults
• 17000 births
• In the US it causes 5 of the SCD/year
• Symptoms include syncope or SCD usually with
  physical activity or emotional stress

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LQTSFacts

• Prolonged recovery from electrical excitation
  contributes to increased likelihood of dispersion
  of refractoriness.
• Consequently, the wave of excitation may pursue
  a distinctive pathway around a focal point in
  myocardium (circus reentrant rhythm), leading to
  polymorphous ventricular tachycardia. syncope
  and possibly sudden death.

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LQTSFacts

• QT prolongation in LQTS is due to overload of
  myocardial cells with positively charged ions
  during ventricular repolarization (not enough K
  getting out or too much Na in )
• In LQT1, LQT2, LQT5, and LQT6 types, potassium
  ion channels are blocked or they open with a
  delay or are open for a shorter period than in
  normally functioning channels, leading to
  decreased potassium outward current and prolonged
  repolarization. In LQT3, caused by mutations of
  the SCN5A sodium channel gene, persistent inward
  sodium current contributes to prolonged
  repolarization.

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LQTSFacts

• Syncope often misdiagnosed as vasovagal or
  epilepsy
• Family history is important-ask about deafness
  and SCD lt30 years of age
• 1/3 of patients with LQTS are asymptomatic
• 10 of patients will have a normal QT interval
• Rule out drug induced LQT and other causes of SCD
  in young patients(HCM,Brugada,ARVD)
• Treatment is BB /- ICD

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LQTSFacts

• Gender differences SCD- males-higher risk during
  childhood with mean age 13 of SCD and females
  have higher risk in adulthood with mean age of 20
  of SCD
• Women are twice as likely to be symptomatic and
  develop TdP than their male counterparts (the
  estrogen?)
• Competitive sports should be avoided
• Most episodes result in syncope with only 5
  resulting in SCD
• EP studies are not helpful

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LQTS Facts

• Inherited/Congenital first described in 1957
  with an autosomal dominant type (Romano Ward)
  and an autosomal recessive type (Jervell
  Lange-Nielsen). In the 1990s the genetic
  mutations have been linked to at least 6 genes
  and 2 ion channels.
• JLN-deafness, auto R, rare (lt1 of all
  LQTS)needs to be homozygous and involves K
  consduction in the cilia of the ear
• RW-common,hearing is normal,auto D

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LQTSFacts

• With treatment, can lower the mortality from 10
  at 10 years to lt1
• BB prevent symptoms is 70 of patients
• ICDs are indicated for those who have not
  responded to BB
• TdPAcutely need to treat with defibrillation, IV
  magnesium, consider temporary pacing if
  bradycardic ,and remove offending drugs
• Need to avoid drugs which can further prolong the
  QT-www.qtdrugs.org

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LQTS The EKG

• Measure the QT corrected via the Bazetts formula
  and look for T-wave abnormalities
• Do not rely on the automated QTc from the
  computer read EKG
• T wave abnormalities wide based, double hump,
  T-U complex, low amplitude
• Do an EKG on the parents and siblings
• Take an average of 3 QTc intervals

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LQTS Calculating the QTc

• Bazett 1920 QTcQT/square root of the RR
• Corrects QT for the heart rate-there is normally
  an inverse relationas one goes up/the other goes
  down and vice versa
• Abnormal if QTc in males gt470 ms and females of gt
  480 ms
• Borderline prolonged QTc 450-470 ms
• Average QTc for someone with the LQTS is 490 ms

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LQTS Nomogram

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LQTSGenetics

• Not all is known since 40 of families with LQTS
  have not yet been linked to the known genetic
  causes
• LQT1-LQT7
• All encode for K channels except LQT3 which is
  linked to the Na channel-very good test question.

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LQTS Geneticstype/gene/chromosome/comment

• LQT1 KCNQ1 (KvLQT1) 11 Trigger Stress
  Iksassociated with JLN
• LQT2 KCNH2 (hERG) 7 Trigger Noise Ikr
• LQTS1 and 2 87 of known LQTS
• LQT3 SCN5A 3 Trigger Sleep, rest. Beta
  blocker therapy seems to be the less effective
  Ina8 of known LQTS
• LQT4 ?????

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LQTSGenetics type/gene/chromosome/comment

• LQT5 KCNE1 21 Associated to the JLNIks
• LQT6 KCNE2-MiRP1 21 Triggers certain
  drugs, exerciseIkr
• LQT7 KCNJ2 17 Associated to the Andersen
  syndrome (periodic paralysis and skeletal
  developmental abnormalities)

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Diagnostic Criteria for LQTS

• 1. EKG findings
• QTc
• gt480 3
• 460-470 2
• 450 (male) 1

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Diagnostic Criteria for LQTS

• Torsdade De Pointes 2
• T-wave alternans 1
• Notched T wave in 3 leads 1
• Low heart rate for age 0.5

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Diagnostic Criteria for LQTS

• Clinical History
• Syncope with stress 2
• without stress 1
• Congenital deafness 0.5

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Diagnostic Criteria for LQTS

• Family history
• Definite LQTS
  1
• Unexplained SCD in immediate family member that
  is less than 30 years of age 0.5

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Diagnostic Criteria for LQTS

• lt1 points low probability
• 2-3 points intermediate probability
• gt4 points high probability

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Risk stratification in the LQTS

• Those at highest risk (gt50) of having a cardiac
  event are those with QTc at rest of gt500 msec and
  females
• Those at lowest risk are those with QTc lt 500
  msed and males
• Those with LQT3 have less events, but when they
  occur..they are more lethal

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• El FIN