the long qt syndrome: overview and management the long qt syndrome: overview and management
TRANSCRIPT
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The Long QT Syndrome
Overview and Management
Edited by A.Kharazi M.DCardiac electrophysiologist
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LQTS Outline
• Background
• Identification
• Therapies Available
• Current Management
• Ongoing Research
• Case Studies
• Conclusions
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Long QT Syndrome
Background and the Risk of Sudden Cardiac Death
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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
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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
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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
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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
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LQTS: Identification
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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
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Syncope
Slow Onset Abrupt Onset Abrupt Onset
Slow Offset Abrupt Offset Slow Offset
Seizure disorderHyperventilation
Hypoglycemia
Obstructive Arrhythmic Vascular
Aortic Stenosis,HCM, Myxoma
BradyTachy
Vasovagal,Orthostatic
Hypertension
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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
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Holter ECG Recording in LQTS Patient with Syncope (representative strips of ECG recording, part 1 of 2)
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Holter ECG Recording in LQTS Patient with Syncope (representative strips of ECG recording, part 2 of 2)
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LQTS: Clinical Features
Symptoms
• Syncope
• Seizures
• Sudden death
• Palpitations or “chest pain”
ECG Signs
• Prolonged QTc
• Torsade de pointes
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LQTS ECG Patterns
Circ 1992;85[Suppl I]:I140-I144
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Circ 1992;85[Suppl I]:I140-I144
Additional LQTS ECG Patterns
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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
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Circ 1993;88:782-784
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
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AJC 1993;72:21B
QTc Interval and Risk
1.0
1.6
2.2
2.8
440 520 600 680
QTc
Ris
k fo
r C
ard
iac
Eve
nt
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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
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Circ 1991;84:1136-1144
Probands
Affected
UndeterminedUnaffected
Probability of Cardiac Event in LQTS
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Circ 2001;103:89-95Mayo Clin Proc. 1999;74:1088-1094
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)
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Circ 2001;103:89-95
62
26
3
13
43
29
1319
39
0
10
20
30
40
50
60
70
LQT1 LQT2 LQT3
ExerciseEmotional StressRest
Pe
rce
nt
Occurrence of Gene-Specific Triggers
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JCE 1999;10:1664-1683
Basis for the Long QT Syndrome
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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
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Moss AJ, et al. Circulation 1995;92:2929-2934
T-wave Morphology in LQTS by Genotype
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NEJM 1998;339:960-965
Probability of a Cardiac Event
No. of SubjectsLQT1 group 112 72 36 27 19LQT2 group 72 56 29 16 11LQT3 group 62 56 36 24 16
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Therapies Available and Current Management
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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
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Current Treatments
• Left stellate ganglionectomy (occasionally utilized in infants and patients refractory to other forms of therapy)
• Beta blockers
• Pacemakers
• Implantable Cardioverter Defibrillators (ICDs)
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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
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Probands AFM†
(n=581) (n=288)
Risk exposure, yrs 5.2 4.5(pre- and post- B)
Pre-B Post- B Pre- B Post B
Pts with events 462194* 92 49*
Number events 1671 623* 245 138*
Events/pt 3.0 1.1* 0.9 0.5*
Events/pt/year 1.0 0.3* 0.3 0.15*
LQTS: Cardiac Events Before and After -blockers
Circ 2000;101:616-623 †Affected Family Member * P<0.01 vs. pre--blocker
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Circ 2000;101:616-623
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
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Circ 2000;101:616-623
Probability of Cardiac Event
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Cumulative Probability of LQTS- Related Death w/ ß-blockers
Circ 2000;101:616-623
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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
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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
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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.
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Circ. 1999;100:2431-2436
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
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NEJM 2000;342:398
Sinus rhythm
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Sinus rhythm
Torsade de pointes
NEJM 2000;342:398
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Sinus rhythm
Torsade de pointes
Ventricular fibrillation and sinus rhythm
NEJM 2000;342:398
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Ongoing Research
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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
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Case Studies
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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?
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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?
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Case Study 3
• 15 year old male
• ECG as part of routine physical
• QTc = 450ms
• Asymptomatic
• No family history
• Question: Is this LQTS?
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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.
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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