Sudden Cardiac Death

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Sudden Cardiac Death

• Liam Penney
• London February 2009

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Sudden Cardiac Death

• Scale of the Problem?
• 12 all natural death
• CAD and SCD
• 1st manifestation of CAD in 25 is SCD
• 50 CAD/CHF patients die suddenly

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Magnitude of SCD in US
SCD claims more lives each year than these other
diseases combined
1 U.S. Census Bureau, Statistical Abstract of
the United States 2001. 2 American Cancer
Society, Inc., Surveillance Research, Cancer
Facts and Figures 2001. 3 2002 Heart and Stroke
Statistical Update, American Heart Association. 4
Circulation. 20011042158-2163.
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Causes of Cardiac Arrest
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Secondary Prevention of SCD

• AVID Trial
• 1993 - 1997, n 1016
• Life-threatening ventricular arrhythmia
• ICD vs Class III (Amiodarone)

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AVID Trial
N Engl J Med 1997 337 1576-83
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Primary Prevention of SCD

• MADIT-II Trial

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MADIT-II

• Chronic CAD with prior MI
• EF lt0.30
• No requirement for NSVT or EPS
• ICD vs Conv medical Rx

NEJM March 21 2002
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MADIT-IIKaplan-Meier Survival by Treatment Group
0.78
0.69
0.69
P0.007
(probability of survival)
(probability of survival)
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SCD Number of Events and Event Rates Over 1 Year
J Am Coll Cardiol 200648e247-e346
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High Mortality Despite ICD Therapy
Amiovirt Trial
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Rare Syndromes

• Long QT Syndrome
• Brugada Syndrome
• Catecholaminergic Polymorphic Ventricular
  Tachycardia (CPVT)
• These syndromes are by definition rare -
  estimated prevalence below 5 in 10 000
• Heart is structurally normal

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SCD Young Athletes
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Genetics of Pro-arrhythmic Syndromes

• The most common are DNA variants called
  polymorphisms
• Single nucleotide polymorphisms (SNPs)
• Millions of SNPs are present in the DNA of each
  individual, a specific combination of
  polymorphisms in different genes, interacting
  with a specific trigger or substrate, may be
  required to create a risk for SCD

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Genetics

• Some individuals can have inherited abnormalities
  that are not manifest until triggered by an
  external event e.g.
• catecholamine levels
• certain drugs that alter repolarisation

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Examples of Drugs Causing QT Prolongation

• Anti-histamines
• Antibiotics e.g. clarithromycin, erythromycin
• Antiemetics e.g. domperidone, droperidol
• Antipsychotics e.g. chlorpromazine, haloperidol,
  thioridazine
• Methadone, Cisapride
• Anti-arrhythmics e.g. Disopyramide, Sotalol,
  Quinidine

Drug-induced prolongation of the QT interval. N
Engl J Med 2004350101322
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QT Interval
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ECG of a Woman on Thioridazine After VF Arrest

• A QTc interval of 619 ms
• B ECG 3 days after withdrawal of thioridazine
  (QTc 399 ms)

Yap Y.G. et al Heart 2003
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QTc Values normal and prolonged QT interval
after correction with Bazetts formula
By age 50, gender differences in QT intervals
have largely equalized
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Long QT Syndrome

• Two patterns of inheritance
• the more common autosomal dominant Romano-Ward
  and Timothy syndromes
• the much rarer autosomal recessive cases. are
  often associated with congenital deafness (the
  Jervell Lange-Nielsen syndrome
• Mutations in 8 genes have been identified 7 of
  them encode cardiac ion channel subunits, mainly
  potassium channels

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Long QT Syndrome

• QT interval duration is the strongest predictor
  of risk for cardiac events in LQTS
• QTc exceeding 500 ms identifies patients with the
  highest risk of becoming symptomatic by age 40
• A normal QT interval in family member a good
  prognosis
• Treatment includes
• Beta blockade
• Left Cardiac Sympathetic Denervation
• Permanent pacemaker
• AICD

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Drug Induced Torsade de Pointes

• Note the typical short-long-short initiating
  ventricular cycle, and abnormal TU wave

Yap, Y. G. et al. Heart 2003891363-1372
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Torsade de Pointes

• A self-limiting Torsades de Pointes (TdP)
• B TdP leading to ventricular fibrillation

Yap, Y. G. et al. Heart 2003891363-1372
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Long QT SyndromeRisk Stratification
Priori SG et al. N Engl J Med 2003
3481866-1874.
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Prolonged QT Interval

• A prolonged QTc interval is also an independent
  predictor of SCD in other cardiac conditions
• QTc greater than 420 ms has been shown to have a
  higher risk of cardiovascular death relative to a
  shorter QTc. And a QTc greater than 440 ms
  significantly predicted cardiovascular death with
  adjusted relative risk of 2.1

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Congenital Short QT Syndrome
Stephenson, E. A. et al. Circulation
20071161062-1080
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Catecholaminergic Polymorphic Ventricular
Tachycardia (CPVT)

• Ventricular arrhythmias develop during physical
  activity or acute emotion in the presence of an
  unremarkable resting ECG.
• autosomal dominant and autosomal recessive.
• Mutations in the cardiac Ryanodine receptor
  (RyR2) gene
• Beta-blockade effective but 30 need AICD

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Brugada Syndrome
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Type 1 Brugada Syndrome
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Brugada Syndrome

• ECG J-point segment elevation in leads V1 to V3
  and RBBB in some
• ECG pattern can be present intermittently.
• The disease is autosomal dominant
• 90 of the affected individuals are male.
• Only 1 Brugada syndrome disease gene has been
  identified so far, the cardiac sodium channel
  gene (SCN5A)
• The high incidence of SCD warrants ICD in
  symptomatic or otherwise high-risk individuals

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Brugada Syndrome
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Brugada Syndrome normal variant
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Brugada Syndrome
Stephenson, E. A. et al. Circulation
20071161062-1080
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Brugada patient arrhythmia provoked by
Procainamide
Stephenson, E. A. et al. Circulation
20071161062-1080
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Sudden Cardiac Death

• Liam Penney
• London February 2009