The Long QT Syndrome Overview and Management

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The Long QT Syndrome Overview and Management

• Developed by Arthur J. Moss, M.D.
• Founder and Director
• International Long QT Registry
• Rochester, NY

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Sudden Cardiac Death (SCD)

• Affects 325,000 each year in U.S. 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 coronary anomalies
• Myocarditis
• Hypertrophic and other cardiomyopathies
• Wolff-Parkinson-White Syndrome (WPW)
• Channelopathies such as Long QT Syndrome

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Long QT Syndrome

• Uncommon genetic disorder (13,000))
• ECG evidence QTc interval prolonged
• gt 450ms in males
• gt 460ms in females
• Hallmark arrhythmia Torsade de pointes VT
• Primary symptom Syncope
• Peak risk of SCD children and young adults

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LQTS Historical Aspects

• 1957 1st LQTS family reported
• 1971 1st LQTS Rx (left stellate ganglionectomy
  Moss McDonald)
• 1958-1970 25 LQTS cases reported
• 1979-2007 International LQTS Registry
• 1995-2007 10 LQTS loci and hundreds of
  mutations identified

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LQTS Clinical Features

• Symptoms
• Palpitations
• Syncope
• Seizures
• Sudden death

• ECG Signs
• Prolonged QTc
• Torsade de pointes
• T-wave alternans

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LQTS Identification of Risk

• Aborted cardiac arrest
• Family history of unexplained syncope or sudden
  death lt 50 years of age
• History of seizures or congenital deafness
• Prolonged QTc on ECG
• Positive genetic test

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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

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Syncope
Abrupt Onset
Slow Onset
Abrupt Onset
Abrupt Offset
Slow Offset
Slow Offset
Hyperventilation
Seizure disorder
Hypoglycemia
Obstructive
Vascular
Arrhythmic
Vasovagal, Orthostatic Hypertension
Aortic Stenosis,HCM, Myxoma
Bradycardia Tachycardia
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Causes of Arrhythmic Syncope

• Very rapid ventricular tachycardia (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)

Torsades de pointe
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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 ECG Patterns
Circ 199285Suppl II140-I144
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What Should You do with the ECG?

• Do not rely on computer interpretation
• Obtain independent review of the ECG
• Have experienced cardiologist manually measure
  QTc interval
• If the ECG is suspicious for LQTS, refer patient
  for cardiac evaluation Pediatric cardiologist
  or electrophysiologist

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LQTS Phenotype-Genotype

• 10 genotypes hundreds of 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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T-wave Morphology in LQTS by Genotype
LQT3
LQT2
LQT1
Moss AJ, et al. Circulation 1995922929-2934
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Probability of Cardiac Events
                                                
                       
Circ 200110389-95
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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 200110389-95Mayo Clin Proc.
1999741088-1094
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Triggers for Syncope in LQTS
Percent
Circ 200110389-95
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Drugs in Long QT

• Certain drugs may provoke life-threatening
  arrhythmias in LQTS patients
• Examples
• Antiarrhythmic procainamide, quinidine,
  amiodarone, sotalol
• Antibiotic/antifungal erythromycin, Avelox,
  Bactrim, Septra, clindamycin, gatifloxacin
• Psychotropics Haldol, Risperdal, Thorazine,
  tricyclics
• Other epinephrine, diuretics, albuterol,
  methadone

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Drugs in Long QT

• LQTS patients should avoid all nonessential
  medications
• Prescription
• Over-the-counter
• Dietary and herbal supplements
• For more information see www.qtdrugs.org

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Treatments Options

• Beta blockers
• Pacemakers
• Implantable Cardioverter Defibrillators (ICDs)
• Left stellate ganglionectomy
• Gene-specific therapy

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Management by Genotype

• LQT1 and LQT2 benefit most from ß-blocker
  therapy
• Benefit of ß-blocker therapy less clear
  in LQT3.
• ICDs indicated
• patient presents as SCD survivor or aborted
  cardiac arrest
• ß-blockers not effective in preventing cardiac
  events

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Limitations of ?-blockers in LQTS

• SCD can occur despite ?-blockers Rx
• Long-term compliance with daily therapy is
  problematic
• Usual side effects of ?-blockers

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ICD Experience in LQTS

• ICD indicated for all patients with documented
  VT, ventricular fibrillation (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 Discharge following TdP and VF

• Sinus rhythm

Torsade de pointes
VF, ICD shock, sinus rhythm
NEJM 2000342398
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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. 19991002431-2436
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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
• LQTS and ICDs

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Case Study 1

• 13 year old female presents with syncope while
  swimming
• QTc prolongation on ECG (gt 500ms)
• Beta-blocker therapy initiated
• No further cardiac events noted over 5 years
• Can you withdraw beta-blocker therapy?
• Is an ICD indicated?

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Case Study 1 - Discussion

• In most cases, once started therapy should be
  considered life-long.
• QTc is significant removing therapy is very
  risky.
• Females with LQTS at higher risk of SCD than
  males.
• Patient should not be in competitive sports, and
  no unsupervised swimming.
• Risk of SCD exists some might consider ICD

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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 2

• Options
• Implant ICD
• Encourage patient to continue ß-blocker
• Both ICD and ß-blocker
• ICD without ß-blocker not recommended necessary
  to decrease event rate.
• Screen other family members with ECG

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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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Case Study 3

• 2-3 of males at this age have QTc gt 450ms 10
  of males with LQTS have QTc in 420 450ms
  range.
• Get ECGs from parents and siblings
• Cardiology/EP consult
• Genetic testing to clarify

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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
  (C.A.R.E.) Foundation www.longqt.org
• International Registry for Drug-Induced
  Arrhythmias, including drugs to use with caution
  or avoid in Long QT patients www.qtdrugs.org

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Cardiac Arrhythmias Research and Education
(C.A.R.E.) Foundation, Inc. (800)
404-9500 care_at_longqt.org www.longqt.org