Transcript Long QT Syndrome

Long QT Syndrome
Teresa Menendez Hood M.D.
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
 1:7000 births
 In the US it causes ~ 5% of the SCD/year
 Symptoms include syncope or SCD usually with
physical activity or emotional stress
LQTS:Facts
 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.
LQTS:Facts
 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.
LQTS:Facts
 Syncope often misdiagnosed as vasovagal or
epilepsy
 Family history is important-ask about deafness
and SCD <30 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
LQTS:Facts
 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
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 (<1% of all
LQTS);needs to be homozygous and involves K
consduction in the cilia of the ear
 RW-common,hearing is normal,auto D
LQTS:Facts
 With treatment, can lower the mortality from
10% at 10 years to <1%
 BB prevent symptoms is 70% of patients
 ICD’s are indicated for those who have not
responded to BB
 TdP:Acutely 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
LQTS: The EKG
Measure the QT corrected via the Bazett’s
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
LQTS: Calculating the QTc
 Bazett: 1920 QTc=QT/square root of the RR
 Corrects QT for the heart rate-there is normally
an inverse relation…as one goes up/the other
goes down and vice versa
 Abnormal if QTc in males >470 ms and females
of > 480 ms
 Borderline prolonged QTc 450-470 ms
 Average QTc for someone with the LQTS is 490
ms
LQTS: Nomogram

LQTS:Genetics
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….
LQTS: Genetics
type/gene/chromosome/comment
 LQT1; KCNQ1 (KvLQT1); 11 Trigger: Stress
;Iks;associated 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 ;Ina…8% of known LQTS
 LQT4 ?????
LQTS:Genetics
type/gene/chromosome/comment
LQT5 ; KCNE1 ; 21 ; Associated to the
JLN;Iks
LQT6 ; KCNE2-MiRP1 ; 21 ; Triggers:
certain drugs, exercise;Ikr
LQT7 ; KCNJ2 ; 17 ; Associated to the
Andersen syndrome (periodic
paralysis and skeletal developmental
abnormalities)
Diagnostic Criteria for LQTS
 1. EKG findings
–
QTc
•
•
•
>480
460-470
450 (male)
3
2
1
Diagnostic Criteria for LQTS
Torsdade De Pointes
T-wave alternans
Notched T wave in 3 leads
Low heart rate for age
2
1
1
0.5
Diagnostic Criteria for LQTS
Clinical History
– Syncope
with stress
–
without stress
– Congenital deafness
2
1
0.5
Diagnostic Criteria for LQTS
Family history
– Definite LQTS
– Unexplained SCD in immediate family
member that is less than 30 years of age
1
0.5
Diagnostic Criteria for LQTS
<1 points low probability
2-3 points intermediate probability
 >4 points high probability
Risk stratification in the LQTS
Those at highest risk (>50%) of having a
cardiac event are those with QTc at rest of
>500 msec and females
Those at lowest risk are those with QTc <
500 msed and males
Those with LQT3 have less events, but
when they occur..they are more lethal
El FIN