Transcript Long QT syndrome

Long QT syndrome
Done by:
Dr. Ayman Bukhari
Dr. Amin Zagzoog
Supervised by:
Dr. Mona Kholeif
Consultant Cardiologist
Introduction
• 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.
Definition of QTc Based on Age- and
Sex-Specific Criteria
Group
Prolonged
Borderline
Reference
Children and
adolescents (<15 y)
>0.46
0.44-0.46
<0.44
Men
>0.45
0.43-0.45
<0.43
Women
>0.46
0.45-0.46
<0.45
Introduction
•
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.
Torsades de pointes
Prevalance
• 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
Pathophysiology
• 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.
Pathophysiology
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
Pathophysiology
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.
Early Afterdepolarization
www.resident and staff.com
Signal averaged Electrocardiogram
Pathophysiology
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.
Genetic Type of Long QT syndrome
Chromosomal
Locus
Mutated Gene
Ion Current
Affected
LQT1 (Romano
ward Syndrome)
11p15.5
KVLQT1, or KCNQ1
(heterozygotes)
Potassium (IKs)
LQT2
7q35-36
HERG, KCNH2
Potassium (IKr)
LQT3
3p21-24
SCN5A
Sodium (INa)
LQT4
4q25-27
ANK2, ANKB
Sodium, potassium
and calcium
LQT5
21q22.1-22.2
KCNE1
(heterozygotes)
Potassium (IKs)
LQT6
21q22.1-22.2
MiRP1, KNCE2
Potassium (IKr)
LQT7 (Anderson
syndrome)
17q23.1-q24.2
KCNJ2
Potassium (IK1)
Genetic Type of Long QT syndrome
Type of LQTS
Chromosomal
Locus
Mutated Gene
Ion Current
Affected
LQT8 (Timothy
syndrome)
12q13.3
CACNA1C
Calcium (ICa-Lalpha)
LQT9
3p25.3
CAV3
Sodium (INa)
LQT10
11q23.3
SCN4B
Sodium (INa)
LQT11
7q21-q22
AKAP9
Potassium (IKs)
SNTAI
Sodium (INa)
LQT12
JLN1
11p15.5
KVLQT1, or KCNQ1
(homozygotes)
Potassium (IKs)
JLN2
21q22.1-22.2
KCNE1
(homozygotes)
Potassium (IKs)
Drugs That Prolong QT
1)Anti-arrhythmic:
-Amiodarone
-Disopyramide
-Dofetilide
2)Antibiotics:
-Levofloxacin
-Erythromycin
-Gatifloxacin
-Clarithromycin
3) Anti-depressant
-Fluoxetine
-Paroxetine
4) Anti-psychotic
-Chlorpromazine
-Haloperidol
-Ziprasidone
-Olanzpine
5) Diuretics
-Indapamide
6)Anti histamine
7) Anti-cancer
-Tamoxifen
-Arsenic trioxide
History
•
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.
History
• Medication
• Family history
• Analysis of repolarization duration (QTc) and
morphology on the patient's ECG and on ECGs
of the patient's relatives frequently leads to
the proper diagnosis.
Physical Examination
• 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).
Physical Examination
• Also perform the physical examination to
exclude other potential reasons for arrhythmic
and syncopal events in otherwise healthy
people (e.g, heart murmurs caused by
hypertrophic cardiomyopathy, valvular
defects).
Diagnostic criteria for long QT syndrome
Criterion
Points
ECG Finding
QTc
>480
3
460-469
2
450-459 in male patient
1
Torsade de pointes‡
2
T-wave alternans
1
Notched T wave in 3 leads
1
Low heart rate for age§
0.5
Clinical history
Syncope
With stress
2
Without stress
1
Congenital deafness
0.5
Family history
A. Family members with definite LQTS#
1
B. Unexplained sudden cardiac death <30 y in an immediate family member
0.5
Investigation
1)Laboratory Studies
-
Serum potassium
Serum magnesium
Thyroid function Test
Genetic Testing
2) Imaging Studies
-
Echocardiography
MRI
Investigation
3)ECG
-
-
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
4)Electrophysiological studies
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.
Managament
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
Managament
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
Managment
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.
Suggested Risk-Stratification Scheme
for ACA or SCD in LQTS Patients
Ilan Goldenberg, MD, Arthur J. Moss, MD
Rochester, New York, American Journal of Cardiology 2008
Managament
Electrocardiogram
Symptoms
Family history
Treatment
Prolong QT
None
None
None
Prolong QT
None
SCD , Syncope due
to LQTS
Beta-blockers
Prolong QT
Syncope
Prolong QT
SCD
SCD , Syncope due
to LQTS
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
Classification of Cardiomyopathy
www.ahajournals.org
Summary
- Prevalence
- Types
- Drugs
- ECG
References
1)Essential Cardiac Electrophysiology
Zainul Abedin and Robert Conner
2)Long QT syndrome
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
Thank You