Transcript No Slide Title

The Long QT Syndrome
Overview and Management
Edited by A.Kharazi M.D
Cardiac electrophysiologist
LQTS Outline
• Background
• Identification
• Therapies Available
• Current Management
• Ongoing Research
• Case Studies
• Conclusions
Long QT Syndrome
Background and the Risk of
Sudden Cardiac Death
Sudden Cardiac Death (SCD)
• Affects 350,000 - 400,000 each year in
the US alone
• Only 5% of victims survive
• Causes of SCD may include structural heart
disease or a genetic channelopathy
• Recognition of risk factors can help identify
those at risk of SCD
Risk Factors for SCD in
Young People
• Structural congenital heart disease - before
and after corrective surgery
• Congenital anomalies of coronaries
• Myocarditis
• Hypertrophic and other cardiomyopathies
• Wolff-Parkinson-White Syndrome
• Long QT Syndrome
LQTS: Historical Aspects
1957:
1st LQTS family reported
1963-1964: Romano-Ward Syndrome
1958-1970: 25 LQTS cases reported
1971:
1st LQTS Rx (left stellate
ganglionectomy)
1979:
LQTS Registry Started
1991-2001: 6 LQTS genes identified
Long QT Syndrome
• Genetic disorder (1:5,000-10,000)
• ECG evidence: QTc interval prolonged
• >440 ms in males
• >450 ms in females
• Hallmark arrhythmia: Torsade de pointes VT
• Primary presenting symptom: Syncope
• SCD in children or young adults
LQTS: Identification
LQTS: Identification of Risk
• Most common presenting symptom:
unexplained syncope.
• Syncope on exertion in pediatric patients
should be considered malignant until proven
otherwise.
• History & ECG:
– Onset and offset of syncopal episode
– Siblings, or family members with unexplained syncope or
sudden death
– Family history of “seizures” or congenital deafness
– Prolonged QTc on ECG
Syncope
Slow Onset
Slow Offset
Abrupt Onset
Abrupt Offset
Hyperventilation
Abrupt Onset
Slow Offset
Seizure disorder
Hypoglycemia
Obstructive
Arrhythmic
Vascular
Aortic Stenosis,
HCM, Myxoma
Brady
Tachy
Vasovagal,
Orthostatic
Hypertension
Causes of Arrhythmic Syncope
• Very rapid VT or TdP, with hypotension
• Atrial fibrillation or atrial flutter with very
rapid ventricular response as in WPW
• AV block
• Sinus arrest
Holter ECG Recording in LQTS Patient with Syncope
(representative strips of ECG recording, part 1 of 2)
Holter ECG Recording in LQTS Patient with Syncope
(representative strips of ECG recording, part 2 of 2)
LQTS: Clinical Features
Symptoms
ECG Signs
• Syncope
• Prolonged QTc
• Seizures
• Torsade de pointes
• Sudden death
• Palpitations or
“chest pain”
LQTS ECG Patterns
Circ 1992;85[Suppl I]:I140-I144
Additional LQTS ECG Patterns
Circ 1992;85[Suppl I]:I140-I144
What Should You do
with the ECG?
• Don’t rely on computer evaluation of ECG
• Obtain an independent review of the ECG
• Have an experienced cardiologist measure
the QTc interval
• If the ECG is suspicious for LQTS, refer the
patient for cardiac evaluation
LQTS: Diagnostic Criteria
• ECG findings:  QTc, TdP, notched
T waves, slow heart rate for age
• Clinical history: syncope, seizures, aborted
cardiac arrest
• Family history: family member with LQTS,
unexplained SCD in a first-degree relative
who was <55yrs of age
Circ 1993;88:782-784
QTc Interval and Risk
Risk for Cardiac Event
2.8
2.2
1.6
1.0
440
520
600
QTc
AJC 1993;72:21B
680
LQTS: Who is at Risk for SCD?
• Aborted cardiac arrest
• Family history of unexplained
sudden death
• Syncope
• Torsade de pointes
• T-wave alternans
• Prolonged QTc
Probability of Cardiac Event in LQTS
Probands
Affected
Undetermined
Unaffected
Circ 1991;84:1136-1144
Triggering Events for
Syncope or SCD
• 3 main factors contributing to syncope
or SCD
– Exercise (LQT1), especially swimming
– Emotions or emotional stress (LQT2)
– Events occurring during sleep or at rest,
with or without arousal (LQT2 or LQT3)
Circ 2001;103:89-95
Mayo Clin Proc. 1999;74:1088-1094
Occurrence of
Gene-Specific Triggers
70
Exercise
Emotional Stress
Rest
62
Percent
60
50
43
40
30
39
29
26
19
20
13
10
13
3
0
LQT1
Circ 2001;103:89-95
LQT2
LQT3
Basis for the Long QT Syndrome
JCE 1999;10:1664-1683
LQTS: Phenotype-Genotype
Considerations
• 6 genotypes; ~200 different mutations
• Clinical differences among LQT1, LQT2,
& LQT3 genotypes
• Clinical variability within a genotype
• Clinical variability among members of
a family with the same gene mutation
suggests presence of modifier genes
T-wave Morphology in LQTS
by Genotype
Moss AJ, et al. Circulation 1995;92:2929-2934
Probability of a Cardiac Event
No. of Subjects
LQT1 group
LQT2 group
LQT3 group
NEJM 1998;339:960-965
112
72
62
72
56
56
36
29
36
27
16
24
19
11
16
Therapies Available and
Current Management
Drugs in Long QT
• Certain drugs may provoke life-threatening
arrhythmias in LQTS patients
– Examples:
• Antiarrhythmic: procainamide, quinidine, amiodarone, sotalol, et al
• Antihistamine: astemizole, terfenadine, et al
• Antimicrobial/antifungal: thiomethoprim sulfa, erythromycin,
ketoconazole, et al
• Psychotropics: haloperidol, risperidone, thioridazine, tricyclics, et al
• Other: epinephrine, diuretics, cisapride, bepridil, ketanserin, et al
• Avoid nonessential OTC medications
• For more information see: www.qtdrugs.org
Current Treatments
• Left stellate ganglionectomy (occasionally
utilized in infants and patients refractory
to other forms of therapy)
• Beta blockers
• Pacemakers
• Implantable Cardioverter Defibrillators (ICDs)
Management by Genotype
• LQT1 and LQT2 benefit the most from
ß-blocker therapy
• The benefit of ß-blocker therapy is less
clear in LQT3.
• ICDs indicated:
– if the patient presents as SCD survivor or
aborted cardiac arrest
– if ß-blockers are not effective in preventing
cardiac events
LQTS: Cardiac Events Before and
After -blockers
Probands
(n=581)
(n=288)
5.2
4.5
Risk exposure, yrs
(pre- and post- B)
Pre-B
Pts with events
Number events
Events/pt
Events/pt/year
Circ 2000;101:616-623
AFM†
Post- B
Pre- B
Post B
462
1671
3.0
194*
623*
1.1*
92
245
0.9
49*
138*
0.5*
1.0
0.3*
0.3
0.15*
†Affected
Family Member
* P<0.01 vs. pre--blocker
Efficacy of
-blockers in LQTS
• Significant reduction in frequency of
syncopal events
• Cardiac events continued to occur
• May reduce the rate of SCD
• Reductions in rate of cardiac events
– 0.97±1.42 to 0.31±0.86 events/year in probands
– 0.26±0.84 to 0.15 ±0.69 events/year in affected
family members
• P<0.001
Circ 2000;101:616-623
Probability of Cardiac Event
Circ 2000;101:616-623
Cumulative Probability of
LQTS- Related Death w/ ß-blockers
Circ 2000;101:616-623
Limitations of -blockers
in LQTS
• SCD can occur despite Rx with
-blockers
• Long-term compliance with daily
therapy is problematic
• Usual side effects of -blockers
ICD Experience in LQTS
• An ICD is indicated for all patients with
documented VT, VF or aborted cardiac
arrest
• Prevents SCD in patients with prior
cardiac events
• Provides a back-up for patients on
-blocker therapy who continue to
be symptomatic
ICD Experience in LQTS
N
88
Age at ICD, y
23±10
Female
71%
QTc, sec
0.52±0.06
-B before/after ICD
82% / 89%
ACA before/after ICD
48% / 4%
Death after ICD
0 in 2.5yr (0.1-9.0yr)
A.J. Moss; AHA Abstracts Online. 1999.
Pacemaker Experience
in LQTS
• Reduces frequency of syncope in pts.
with bradycardia-triggered events
• Most useful when combined with
-blocker therapy
• Does not prevent SCD in long-term
therapy
• Appears most useful in patients with
LQT3 and bradycardia
Circ. 1999;100:2431-2436
Sinus rhythm
NEJM 2000;342:398
Sinus rhythm
Torsade de pointes
NEJM 2000;342:398
Sinus rhythm
Torsade de pointes
Ventricular fibrillation and sinus rhythm
NEJM 2000;342:398
Ongoing Research
LQTS: Studies in Progress
• LQTS Registry: risk-factor identification
• Trigger factors
• New gene identification – LQTx ?
• Exercise stress testing for diagnosis
and risk stratification
• Modifier genes
• Mutation-specific therapy
Case Studies
Case Study 1
• 13 year old male presents with syncope
while swimming
• QTc prolongation on ECG (>500ms)
• Beta-blocker therapy initiated
• No further cardiac events noted over 5 years
• Can you consider withdrawing beta-blocker
therapy?
• Is an ICD indicated?
Case Study 2
• Young male athlete diagnosed with LQTS
• Beta-blockers prescribed
• Patient stops drugs because he feels better
without them
• What should the physician do?
Case Study 3
• 15 year old male
• ECG as part of routine physical
• QTc = 450ms
• Asymptomatic
• No family history
• Question: Is this LQTS?
Conclusions
• Unexplained syncope with exertion in children
and young adults should be considered
serious until proven otherwise.
• ECGs should be obtained on the patient and
read by a cardiologist or pediatric cardiologist
if patient is a child.
• ECGs should be obtained on all immediate
family members.
• Referral to a cardiac specialist if suspicious
for LQTS.
Long QT Resources
• Cardiac Arrhythmias Research and Education
(CARE) Foundation: www.longqt.org
• Cardiac Arrest Survivors Network (CASN):
www.casn-network.org
• International Registry for Drug-Induced
Arrhythmias, including drugs to use with
caution or avoid in Long QT patients:
www.qtdrugs.org