The Long QT Syndrome Overview and Management Edited by A.Kharazi M.D Cardiac electrophysiologist
LQTS Outline <ul><li>Background  </li></ul><ul><li>Identification </li></ul><ul><li>Therapies Available </li></ul><ul><li>...
Long QT Syndrome Background and the Risk of Sudden Cardiac Death
Sudden Cardiac Death (SCD) <ul><li>Affects 350,000 - 400,000 each year in  the US alone </li></ul><ul><li>Only 5% of victi...
Risk Factors for SCD in  Young People <ul><li>Structural congenital heart disease -  before and after corrective surgery <...
LQTS:  Historical Aspects <ul><li>1957: 1st LQTS family reported </li></ul><ul><li>1963-1964: Romano-Ward Syndrome </li></...
Long QT Syndrome <ul><li>Genetic disorder (1:5,000-10,000) </li></ul><ul><li>ECG evidence:  QTc interval prolonged </li></...
LQTS:  Identification
LQTS: Identification of Risk <ul><li>Most common presenting symptom: unexplained syncope. </li></ul><ul><li>Syncope on exe...
Syncope Slow Onset Abrupt Onset Abrupt Onset Slow Offset Abrupt Offset Slow Offset Seizure disorder Hyperventilation Hypog...
Causes of Arrhythmic Syncope <ul><li>Very rapid VT or TdP, with hypotension </li></ul><ul><li>Atrial fibrillation or atria...
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 <ul><li>Symptoms </li></ul><ul><li>Syncope </li></ul><ul><li>Seizures </li></ul><ul><li>Sudden de...
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? <ul><li>Don’t rely on computer evaluation of ECG </li></ul><ul><li>Obtain an independent...
LQTS:  Diagnostic Criteria <ul><li>ECG findings:    QTc, TdP, notched  T waves, slow heart rate for age </li></ul><ul><li...
QTc Interval and Risk  AJC 1993;72:21B QTc Risk for Cardiac Event
LQTS:  Who is at Risk for SCD? <ul><li>Aborted cardiac arrest </li></ul><ul><li>Family history of unexplained  sudden deat...
Probability of Cardiac Event in LQTS Circ 1991;84:1136-1144 Probands Affected Undetermined Unaffected
Triggering Events for  Syncope or SCD <ul><li>3 main factors contributing to syncope  or SCD </li></ul><ul><ul><li>Exercis...
Occurrence of  Gene-Specific Triggers Circ 2001;103:89-95 Percent
Basis for the Long QT Syndrome JCE 1999;10:1664-1683
LQTS:  Phenotype-Genotype Considerations <ul><li>6 genotypes; ~200 different mutations </li></ul><ul><li>Clinical differen...
T-wave Morphology in LQTS  by Genotype  Moss AJ, et al. Circulation 1995;92:2929-2934
Probability of a Cardiac Event <ul><li>No. of Subjects </li></ul><ul><li>LQT1 group 112 72 36 27 19 </li></ul><ul><li>LQT2...
Therapies Available and  Current Management
Drugs in Long QT <ul><li>Certain drugs may provoke life-threatening  arrhythmias in LQTS patients </li></ul><ul><ul><li>Ex...
Current Treatments <ul><li>Left stellate ganglionectomy (occasionally utilized in infants and patients refractory  to othe...
Management by Genotype <ul><li>LQT1 and LQT2 benefit the most from  ß-blocker therapy </li></ul><ul><li>The benefit of ß-b...
LQTS: Cardiac Events Before and After   -blockers Probands   AFM †   (n=581)   (n=288) Risk exposure, yrs   5.2   4.5 (pr...
Efficacy of   -blockers in LQTS <ul><li>Significant reduction in frequency of  syncopal events </li></ul><ul><li>Cardiac ...
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 <ul><li>SCD can occur despite Rx with   -blockers </li></ul><ul><li>Long-term compli...
ICD Experience in LQTS <ul><li>An ICD is indicated for all patients with documented VT, VF or aborted cardiac arrest </li>...
ICD Experience in LQTS <ul><li>N 88 </li></ul><ul><li>Age at ICD, y 23±10 </li></ul><ul><li>Female 71% </li></ul><ul><li>Q...
Pacemaker Experience  in LQTS <ul><li>Reduces frequency of syncope in pts.  with bradycardia-triggered events </li></ul><u...
<ul><li>Sinus rhythm </li></ul>NEJM 2000;342:398
<ul><li>Sinus rhythm </li></ul>Torsade de pointes NEJM 2000;342:398
<ul><li>Sinus rhythm </li></ul>Torsade de pointes Ventricular fibrillation and sinus rhythm NEJM 2000;342:398
Ongoing Research
LQTS:  Studies in Progress <ul><li>LQTS Registry: risk-factor identification </li></ul><ul><li>Trigger factors </li></ul><...
Case Studies
Case Study 1 <ul><li>13 year old male presents with syncope  while swimming </li></ul><ul><li>QTc prolongation on ECG (>50...
Case Study 2 <ul><li>Young male athlete diagnosed with LQTS </li></ul><ul><li>Beta-blockers prescribed </li></ul><ul><li>P...
Case Study 3 <ul><li>15 year old male </li></ul><ul><li>ECG as part of routine physical </li></ul><ul><li>QTc = 450ms </li...
Conclusions <ul><li>Unexplained syncope with exertion in children and young adults should be considered serious until prov...
Long QT Resources <ul><li>Cardiac Arrhythmias Research and Education (CARE) Foundation:  www.longqt.org </li></ul><ul><li>...
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The Long QT Syndrome: Overview and Management The Long QT Syndrome: Overview and Management

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  • The Long QT Syndrome: Overview and Management The Long QT Syndrome: Overview and Management

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

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