Done by:
Dr. Ayman Bukhari
Dr. Amin Zagzoog
Supervised by:
Dr. Mona Kholeif
Consultant Cardiologist

• Long QT syndrome (LQTS) is a disorder characterized by a prolongation of the QT interval on ECG and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death.
• The Bazett formula is used to calculate the QTc, as follows: QTc = QT/square root of the R-R interval.

Group Prolonged
Children and adolescents (<15 y)
>0.46
Men >0.45
Women >0.46
Borderline
0.44-0.46
0.43-0.45
0.45-0.46
Reference
<0.44
<0.43
<0.45

• This uncommon disease was first described in 1957 in family in which several children with QT prolongation, congenital bilateral neural deafness, and syncopal episodes , with a family pattern suggesting autosomal-recessive inheritance (Jervell and Lange-Nielsen syndrome ).
• Romano ward syndrome has autosomal dominant pattern.
• The LQTS can be congenital, as an inherited disorder usually involving a mutation of an ion channel gene, or can be acquired as an adverse response to medication, metabolic abnormalities, or bradyarrhythmias
• Torsade de pointes (TdP) or "twisting of points" is the specific type of polymorphic ventricular tachycardia (VT) associated with either form of the LQTS.

• The prevalence of LQTS is difficult to estimate. However, given the currently increasing frequency of diagnosis, LQTS may be expected to occur in 1 in 10,000 individuals.
• New cases of long QT syndrome are diagnosed more in female patients
(60-70% of cases) than male patients. The female predominance may be related to the relatively prolonged QTc (as determined by using the Bazett formula)
• No clear evidence suggests race-related differences in the occurrence of long QT syndrome.
• LQT1, LQT2, and LQT3 account for most cases of LQTS, with estimated prevalences of 45%, 45%, and 7%, respectively

• Acquired :
-polymorphic VT is most commonly precipitated by a characteristic sequence of long-short RR intervals. This interval is normally caused by a ventricular premature beat followed by a compensatory pause . Polymorphic
VT can similarly occur in association with bradycardia or frequent pauses; as a result, the acquired form of
LQTS is called "pause-dependent" LQTS .
• Congenital:
- TdP typically follows a sudden adrenergic surge. Such patients are considered to have "catecholaminedependent" LQTS

Torsade de pointes
The electrocardiographic rhythm strip shows torsade de pointes, a polymorphic ventricular tachycardia associated with QT prolongation. There is a short, preinitiating RR interval due to a ventricular couplet which is followed by a long, initiating cycle resulting from the compensatory pause after the couplet.

Representation of an action potential in ventricular myocardial cells. An action potential is generated when the membrane potential is partially depolarized from the resting level (Em) to the threshold potential (Et). The ensuing rapid
phase 0 depolarization is mediated by sodium entry into the cells due to a marked increase in the number of open sodium channels in the cell membrane. Repolarization in phases 1 and 3 results from potassium exit from the cells as the sodium channels are closed and potassium channels opened. The phase 2 plateau reflects the slow entry of calcium into the cells, which counteracts the effect of potassium exit. Sodium leaves and potassium reenters the cells during phase 4 recovery via the Na-K-ATPase pump

1)Prolonged repolarization and EADs
• Prolongation of the QT interval may be associated with the presence of early after depolarizations (EADs). EADs are single or multiple oscillations of the membrane potential that can occur during phase 2 or 3 of the action potential. EADs occur in association with prolongation of the repolarization phase of the action potential.
• The development of EADs is potentiated by bradycardia, hypokalemia, hypomagnesemia and a long list of medications.

www.resident
and staff.com

2) Increased sympathetic activity
• Evidence supporting the significance of sympathetic activity in LQTS includes observations on the impact of the stellate ganglia. The activity of the left sympathetic stellate ganglion is greater than that of the right ganglion in normal individuals. In addition, the left stellate ganglion innervates the majority of the ventricle .
• Increased activity of the left stellate ganglion or reduced activity of the right stellate ganglion leads to increased sympathetic innervation of the heart. Studies in both animals and humans have demonstrated that right stellectomy or stimulation of the left stellate ganglion both prolong the
QTinterval and alter T wave morphology in a manner that mimics the surfaceECG found in patients with LQTS.

LQT1 (Romano ward Syndrome)
LQT2
LQT3
LQT4
LQT5
LQT6
LQT7 (Anderson syndrome)
Chromosomal
Locus
11p15.5
7q35-36
3p21-24
4q25-27
21q22.1-22.2
21q22.1-22.2
17q23.1-q24.2
Mutated Gene
Ion Current
Affected
KVLQT1, or KCNQ1
(heterozygotes)
HERG, KCNH2
SCN5A
ANK2, ANKB
KCNE1
(heterozygotes)
MiRP1, KNCE2
KCNJ2
Potassium (I
Ks
)
Potassium (I
Kr
)
Sodium (I
Na
)
Sodium, potassium and calcium
Potassium (I
Ks
)
Potassium (I
Kr
)
Potassium (I
K1
)

Type of LQTS
LQT8 (Timothy syndrome)
LQT9
LQT10
LQT11
LQT12
JLN1
JLN2
Chromosomal
Locus
12q13.3
3p25.3
11q23.3
7q21-q22
11p15.5
21q22.1-22.2
Mutated Gene
Ion Current
Affected
CACNA1C
CAV3
SCN4B
AKAP9
SNTAI
KVLQT1, or KCNQ1
(homozygotes)
KCNE1
(homozygotes)
Calcium (I
Ca-Lalpha
)
Sodium (I
Na
)
Sodium (I
Na
)
Potassium (I
Ks
)
Sodium (I
Na
)
Potassium (I
Ks
)
Potassium (I
Ks
)

1)Anti-arrhythmic: 4) Anti-psychotic
-Amiodarone -Chlorpromazine
-Disopyramide -Haloperidol
-Dofetilide -Ziprasidone
2)Antibiotics: -Olanzpine
-Levofloxacin 5) Diuretics
-Erythromycin -Indapamide
-Gatifloxacin 6)Anti histamine
-Clarithromycin
3) Anti-depressant 7) Anti-cancer
-Fluoxetine
-Paroxetine
-Tamoxifen
-Arsenic trioxide

• Long QT syndrome (LQTS) is usually diagnosed after a person has a cardiac event
(eg, syncope, cardiac arrest). In some situations, LQTS is diagnosed after a family member suddenly dies. In some individuals, LQTS is diagnosed because an ECG shows QT prolongation.
• A history of cardiac events is the most typical clinical presentation in patients with
LQTS.
– LQT1 :usually have cardiac events preceded by exercise or swimming. Sudden exposure of the patient's face to cold water is thought to elicit a vagotonic reflex.
– LQT2: may have arrhythmic events after an emotional event, exercise, or exposure to auditory stimuli (eg, door bells, telephone ring)
– LQT3: usually have events during night sleep.
• Obtain information about hearing loss (deficit) in a patient and his or her family members to determine a possibility of Jervell and Lang-Nielsen (JLN) syndrome.

•
•
•

• Findings on physical examination usually do not indicate a diagnosis of long QT syndrome (LQTS)
• excessive bradycardia for their age
• hearing loss (congenital deafness), indicating the possibility of JLNsyndrome
• Skeletal abnormalities, such as short stature and scoliosis are seen in LQT7 (Andersen syndrome)
• congenital heart diseases, cognitive and behavioral problems, musculoskeletal diseases, and immune dysfunction may be seen in those with LQT8
(Timothy syndrome).

•

Criterion
ECG Finding
QTc
>480
460-469
450-459 in male patient
Torsade de pointes‡
T-wave alternans
Notched T wave in 3 leads
Low heart rate for age§
Clinical history
Syncope
With stress
Without stress
Congenital deafness
Family history
A. Family members with definite LQTS#
B. Unexplained sudden cardiac death <30 y in an immediate family member
Points
2
1
0.5
1
2
3
2
1
1
0.5
1
0.5

Serum potassium
Serum magnesium
Thyroid function Test
Genetic Testing
Echocardiography
MRI

LQTS patients frequently show abnormal T-wave morphology, and careful evaluation of all 12 leads is recommended to determine the presence or absence of even subtle changes in T-wave shape. This is particularly important and useful in patients with QTc durations in thegray zone of 0.42-0.47s, where the diagnosis is uncertain based on just QTc.
Individuals with QTc < 0.5s are frequently referred for exercise ECG testing, 24hour Holter monitoring, or sometimes event monitoring. The diagnostic value of these modalities in borderline cases is still controversial

T-wave morphology by LQTS genotype: LQT1: typical broad-based T-wave pattern
(corrected QT [QTc] 570 ms); LQT2: typical bifid
T-wave (QTc 583 ms); and LQT3: typical late-onset peaked/biphasic T-wave (QTc 573 ms

Marked prolongation of QT interval in a 15-year-old male adolescent with long QT syndrome (LQTS) (R-R =
1.00 s, QT interval = 0.56 s, QT interval corrected for heart rate [QTc] = 0.56 s). Abnormal morphology of repolarization can be observed in almost every lead (ie, peaked T waves, bowing ST segment). Bradycardia is a common feature in patients with LQTS.

Direct current shock non synchrnoized
Discontinuation of the offending agent
• Any offending agent should be withdrawn.
• Predisposing conditions such as hypokalemia, hypomagnesaemia, and bradycardia should be identified and corrected
Suppression of early after depolarizations
• Magnesium is the drug of choice for suppressing EADs and terminating the arrhythmia. This is achieved by decreasing the influx of calcium, thus lowering the amplitude of EADs.
Isoproterenol
• This drug can be used in bradycardia-dependent torsade that usually associated with acquired long QT syndrome (pause-dependent).
Temporary transvenous pacing

1)Beta-blockers
• The protective effect of beta-blockers is related to their adrenergic blockade that diminishes the risk of cardiac arrhythmias. They may also reduce the QT interval in some patients.
• Propranolol and nadolol are the beta-blockers most frequently used, though atenolol and metoprolol are also prescribed in patients with LQTS.
2)Implantable Cardioverter-defibrillator (ICD)
• It was shown to be highly effective to prevent sudden cardiac death (SCD) in highrisk patients i.e patient with syncopal attack

3) Left cervicothoracic stellectomy
 Although this technique decreases the risk of cardiac events, it does not eliminate the risk. Therefore, ICD is superior therapy to cervicothoracic stellectomy
.

Ilan Goldenberg, MD, Arthur J. Moss, MD
Rochester, New York, American Journal of Cardiology 2008

Electrocardiogram Symptoms
Prolong QT
Prolong QT
None
None
Prolong QT
Prolong QT
Syncope
SCD
Family history
None
Treatment
None
SCD , Syncope due to LQTS
SCD , Syncope due to LQTS
Beta-blockers
Beta-blockers , ICD
Beta-blockers, ICD

Probability of LQTS-Related Events by Gender
Kaplan-Meier estimates of the cumulative probability of (A) a first cardiac event (syncope, aborted cardiac arrest [ACA], or sudden cardiac death [SCD]) and (B) a first life-threatening cardiac event (ACA or SCD) from age 1 through
75 years by gender in 3,779 long QT syndrome (LQTS) patients from the International
LQTS Registry

www.ahajournals.org

Zainul Abedin and Robert Conner
Ali A Sovari, MD, Research Fellow, Division of Cardiology, David Geffen School of
Medicine,University of California, Los Angeles (UCLA) Abraham G Kocheril, MD, FACC, FACP,
Professor of Medicine, Director of Clinical Electrophysiology, University of Illinois at Chicago;
Ramin Assadi, MD, Staff Physician, Department of Internal Medicine, Loma Linda University