Transcript QT- syndromes - cardiology zagazig university

Q-T Syndromes
By
Mahmoud Shah
Professor of cardiology
Zagazig university
Q-T Syndromes
► Q-T
syndromes can be divided into :
A-Long Q-T Syndrome,
B-Short Q-T Syndrome
► The
upper limit for duration of the
normal QT interval corrected for heart
rate (QTc) is 0.44 second . However,
the normal corrected QT interval may
actually be longer (0.46 second for
men and 0.47 second for women), with
a normal range of plus or minus 15
percent of the mean value.
► Bazet formula
*QTc=QT/square root of R-R interval
► The
nature of the U wave abnormality
and its relationship to long-QT
syndrome is not clear. M cells may be
responsible for the U wave long-QT
syndrome.
► The
probable risk of life-threatening
ventricular arrhythmias developing in
patients with idiopathic long-QT
syndrome is related to the length of the
QTc interval.
►T
wave “humps” in the ECG can
suggest the presence of long-QT
syndrome and may be caused by early
after depolarization. A point score
system has been suggested to aid in
the diagnosis. Unique T wave contours
have been ascribed to specific
genotypes.
Long Q-T syndrome
► ECG
in long Q-T Syndrome will show
the following:
1-Prolonged Q-T interval .
2-Abnormal morphology of T-wave.
3-Torsade de points.
► Torsade
de points is activated by:
1-SNS,
2-Sudden pause.
► LQTS
results in :
-35% of Sudden Cardiac Death in young,
-9% of Sudden infant death syndrome
Congenital LQTS
► The
congenital form is a familial disorder that
can be associated with sensorineural
deafness (Jervell and Lange-Nielsen
syndrome, autosomal recessive) or,
► Normal hearing (Romano-Ward
syndrome, autosomal dominant).
► Most forms of congenital long-QT syndrome
are caused by inherited channelopathies
created by mutations in one or more genes.
Genes involved in LQTS
Variant
LQT1
LQT2
LQT3
LQT4
LQT5
Gene
KCNQ1
KCNH2
SCNSA
ANK2
KCNE1
Protein
Phenotype
IKs
Ikr
INa
Ankyrin B
Iks
Prolonged QT
Prolonged QT
Prolonged QT
Prolonged QT
Prolonged QT
Variant
LQT6
LQT7
Gene
KCNE2
KCNJ2
Protein
Phenotype
Iki
Prolonged QT
IK (Long Q-T and K-sen.preiodic paralysis)
(Anderson Syndrome)
LQT8 (Timothy Synd.) CANAIc
LQT9
CAV3
LQT10
SCN4B
Ca
NaB4
Long QT,ASD,PFO
Prolonged QT
Prolonged QT
► The
familial long QT syndrome is an
uncommon disorder with an estimated
prevalence of 1 in 3,000 to 1 in 5,000 .
► It
is characterized by a prolonged QT
interval (440 milliseconds in male
patient and 460 milliseconds in female
patients) associated with T-wave
abnormalities and a propensity for
polymorphic ventricular arrhythmias
including torsade de pointes.
► Molecular
genetic studies have identified
mutations in the genes encoding ion
channel proteins that control cardiac
repolarization .
► Seven genetic variants have been identified
to date. Most of these mutations result in a
loss or reduction in repolarizing currents.
An exception is LQT3, which results in
delayed inactivation of the sodium channel,
leading to longer duration of depolarizing
currents. The final common pathway
consists of QT prolongation, reduced
repolarization reserve, and a predisposition
to early after depolarizations that may
trigger polymorphic VT.
► Collectively,
these variants account for only
50% to 70% of patients with long QT
syndrome, and mutations in additional genes
remain to be identified. Genotype-phenotype
correlations with respect to clinical course and
prognosis, precipitating factors for arrhythmias,
ECG features, and therapeutic response are
emerging.
► For
example, LQT3 appears to be the most
malignant form, and it is the least responsive to
B-blocker therapy, with symptoms usually
occurring at rest or sleep without obvious
precipitants.
► In
contrast, LQT1 typically presents with
less prolonged QT intervals, a more
favorable long-term prognosis, a strong
association with exercise provocation
(particularly swimming), and an excellent
response to B-blockers
Diagnosis
► The
diagnosis of long QT syndrome
may be straight forward in patients
presenting with a clearly prolonged QT
interval and syncope. A scoring system
for the diagnosis of long QT syndrome,
combining information from the ECG,
clinical history, and family history, was
proposed by Schwartz and associates
to improve the accuracy of diagnosis .
► At
least 10% to 20% of patients with
confirmed mutations may have a
normal QT interval on initial
presentation .Provocative tests such
as epinephrine infusion may be useful
in disclosing occult long QT syndrome,
particularly patients with the LQT1 .
► Genetic
testing may be useful if a
mutation is identified, but it cannot be
used to exclude the diagnosis if testing
reveals no abnormalities.
Diagnostic criteria of congenital
long QT-syndrome
► A-ELECTROCARDIOGRAM:
POINTS
1-QTc >480 ms
3
2-QTc 460-470
2
4-450 (male)
1
5-Torsade de pointes
2
6-T-wave alternans
1
7-Notched T wave in three leads
1
8-Low heart rate for age (less than the second
percentile)
0.5
B-CLINICAL HISTORY:
1-Syncope (exclusive of documented torsade) :
** With stress
2
**Without stress
1
**Congenital deafness
0.5
C-FAMILY HISTORY:
1-Family member with definite long QT
syndrome
1
2- Unexplained sudden death at <30 y in an
immediate family member
0.5
Interpretation
► >4,
►
definite long QT syndrome;
3-4, possible long QT syndrome,
► <1,
low probability of long QT syndrome.
Aquired long QT-Syndrome
► The
acquired form has a long-QT interval
caused by various drugs, such as quinidine,
procainamide, N-acetylprocainamide,
sotalol, amiodarone, disopyramide,
phenothiazines, tricyclic antidepressants,
erythromycin, pentamidine, some
antimalarials, cisapride, and probucol;
electrolyte abnormalities, such as
hypokalemia and hypomagnesemia;
► The
effects of a liquid protein diet and
starvation; central nervous system lesions;
significant bradyarrhythmias; cardiac
ganglionitis; and mitral valve prolapse.
► In
some cases, the acquired long-QT
syndrome may be a form of the inherited
form, resulting from polymorphism in some
of the same genes responsible for the
acquired syndrome, which becomes manifest
when a person takes a drug impairing
repolarization.
Management of LQTS
Class I:
1-Life style modification (level of evidence B)
2-Beta blockers (level of evidence B)
3-ICD and Beta blockers in:
a)Previous cardiac arrest,
b)Previous syncope,
c)Family history of sudden cardiac death.
Class IIa:
1-Beta blockers decrease incidence of SCD in
molecular LQTS and normal QT interval
(level of evidence B).
2-ICD and BB decreses incidence of SCD in
LQTS patients with syncope and /or VT.A
Class IIb:
1-Left cardiac sympathetic denervation in:
a)LQTS and syncope,TDP, or, Cardiac arrest
while receiving BB .
(level of evidence B)
2-ICD and BB as a prophylaxis of SCD for
patients with high risk of cardiac arrest
(LQT2,LQT3,QTc more than 500 msec).
(level of evidence B)
► Beta-blockers
are effective especially
in LQT1 .
► Combined incidence of resuscitated CA
and SCD:
*1% in LQT1,
*7% in LQT2,
*14% in LQT3
*Increased risk of CA , SCD in :
a)Young less than (40 years),
b)Asymptomic,
c)Untreated.
*All LQTS are treated ,except:
a)Borderline QTc,
b)LQT1 male more than 25-30 years.
*All symptomatic patients must be
treated.
*Recurrent syncope despite BB:
a)Left cardiac sympathetic denervation
(LCSD),
b)Prophylactic ICD.
► Predictors
of failure of BB in LQTS:
1-LQT2,LQT3 genotypes,
2-QTc more than 500msec,
3-First syncope less than 7 years,
*All require ICD as primary prevention
► Indications
of permenant pacemaker:
*Infrequently used today,
*Only in selected LQTS and AV.block ,or
sinus block or pause-dependant
tachycardia ,
*Adjunt to BB or ICD.
**LQT3 :
*Caused by increased late INa,
*Na-channel blockers (mexelitine) induce
short Q-T in LQT3,not LQT2.
► Mexiletine
and BB are effective in
infants with prolonged QT and major
arrhythmias.
*Triggers of cardiac events:
-LQT1 :increased risk with physical or
emotional stress.
-LQT3 :Increased risk at rest or during
sleep (80%), 5% only during exercise
► LQT2:
increased risk during:
a)Arousla or emotions (37%),
b)Sleep ,rest (63%),
c)Not at all during exercise.
*99% of cardiac events during
swimming LQT1.
*80% of events during arousal LQT2.
**Symptomatic LQTS :
LQT1 :4% SCD / CA ,
LQT2 :4% SCD / CA ,
LQT3 :17% SCD /CA.
*Natural history and risk stratification:
-Lower cummulative event-free survival
in LQT2 vs LQT1 and LQT3 vs LQT1,
*Gender :
-no influence among LQT1,
- Females are at higher risk in LQT2,
-Males are at a higher risk in LQT3,
*Silent mutation carriers (genetically
affected patients with normal QTinterval:
-More in LQT1(36%) than in LQT2
(19%) ,LQT3 (10%).
1-Higher risk (SCD / CA /Syncope):
-50% risk ,
-QTc more than 500msec,
-LQT1, LQT2, male LQT3.
2-Intermediate risk:
-30-50% risk,
-QTc less than 500msec,
-Female LQT2,
-Male LQT3,
-QTc 500 in female with LQT3.
3-Low risk:
-Risk less than 30%,
-QTc less than 500 msec,
-Male LQT2,
-LQT1
ECG in long QT-syndrome
ECG of a patient with long Q-T (0,54 s) due to
hypokalemia caused by excessive diuretic therapy.
Long Q-T syndrome progressed
to TDP
TDP
Short QT-Syndrome
A heritable cardiac ion channel disorder
associated with a high risk of recurrent
syncope, polymorphic VT, and sudden
death
has been identified recently in several
families.
Diagnosis
► ECG
shows:
• Q-T interval more than 300msec,
• Distinct T-wave shape,
• Absent ST-segment.
► Clinical :
-Silent mutation carriers rather
prevelant in LQT6 not present in SQTS.
-It is due to impaired Q-T adaptation to
increased heart rate.
-Q-T measured at heart rate less than 80
bpm.
-It is difficult to identify SQTS in infants
and very young children.
Mutations in the genes contributing to
at least three different repolarizing
currents have been identified: IKr
(KCNH2), IKs (KCNQ1), and IK1
(KCNJ2).
► All these mutations result in gain of
function, thus accelerating
repolarization and accounting for the
clinical features of the disease.
►
Secondary causes of SQTS
► Hypercalcaemia,
► Hyperkalemia,
► Hyperthermia,
► Acidosis,
► Digoxin
therapy.
► The
most cardinal clinical
manifestations include atrial and
ventricular fast rhythm (AF , VF).
► Suspected SQTS in :
-Short Q-T interval (less than 350msec)
-Lone AF or primary VF.
-Family history of SCD ,CA ,SIDS ,
syncope.
-One of the channelopathies results in
SIDS.
► ICDs
are the most effective therapy,
although the frequent coexistence of
atrial fibrillation and prominent T
waves that results in oversensing may
increase the risk of inappropriate
shocks in these patients.
Management of SQTS
► High
risk for SCD.
► Lack of drugs in preventing SCD.
► ICD for secondary prevention of VF.
► ICD in selected patients for primary
prevention of VF.
**No risk stratification parameters that
identify patient with high risk of SCD
► Antiarrhthmic
drugs for SQTS are
progressing and may be used as a
bridge to ICD.
► Sotalol ,Ibutilide ,Flecanide proved
ineffective.
► Quinidine normalizes QT interval at
resting HR in small number of patients
resulting in prolonged ventricular
effective refractory period.
►