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									              Sleep Apnea & Ventricular
              Arrhythmias: Interaction and Clinical
              Implications


              Henry Nguyen
              Sarah Tierney




Document ID
Sleep Disordered Breathing (SDB)

 Definition: Sleep-disordered breathing refers to an abnormal
 respiratory pattern (ie, apneas, hypopneas, or respiratory effort
 related arousals) or an abnormal reduction in gas exchange (ie,
 hypoventilation) during sleep. It alters sleep duration and
 architecture if repetitive, which may result in daytime symptoms,
 signs, or organ system dysfunction. Definitions follow:

     •Apneas: Cessation or near cessation of airflow
     •Hypopneas: Reduction of airflow to a degree that is
     insufficient to meet the criteria of apnea
     •Respiratory effort related arousals (RERAs): A sequence
     of breaths that lasts at least 10 seconds, characterized by
     increasing respiratory effort or flattening of the nasal pressure
     waveform, and leads to an arousal from sleep, but does not
     meet the criteria of an apnea or hypopnea
     •Abnormal reduction in gas exchange
                              [Iber, C et al, American Academy of Sleep Medicine. 2007]
Epidemiology

• Sleep apnea syndrome affects 5% of the North American
  population [Young et al. Am J Respir Crit Care Med. 2005]
• Ventricular arrhythmias have been associated with Sleep
  Disordered Breathing (SDB) [Mehra et al. Am J Respir Crit Care Med. 2006]
     • Complex ventricular ectopy was found in 25% of patients with
       SDB vs. 14.5% in those without SDB.
     • Non-sustained ventricular tachycardia (NSVT) occurred in
       5.3% of patients with SDB vs 1.2% of those without SDB.
Epidemiology-continued

•   Sleep Disordered Breathing has been associated with ventricular
    arrhythmias
    •   Patients with established ventricular arrhythmias, without
        heart failure, were found to have a high prevalence of Sleep
        Disordered Breathing (SDB). [Koshino et al. Am J Cardiol. 2008]
    •   62% of asymptomatic patients with implantable cardiac
        defibrillators (ICDs), due to decreased left ventricular
        function, were found to meet the criteria for apnea.
        [Grimm et al. Pacing and Clin Electrophysiol. 2009]
Diagnostic Criteria
Polysomnography is the gold standard for diagnosing Sleep
  Disordered Breathing (SDB).
• Indexes used to assess the severity of SDB include:
 • AHI: Apnea-hyponea index
   Number of Apneic or hyponeic episodes per hour of sleep
   AHI > 5 = OSA
 • RDI: Respiratory disturbance index
   Number of apneas, hypopneas, and RERAs per hour of sleep.
   Generally larger than AHI due to RERA inclusion.


ECG identifies episodes of ventricular arrhythmia
Patients with known
       SDB.....
Compared patients with and without Sleep Disordered Breathing (SDB) for presence of
ventricular arrhythmias




 •Complex ventricular ectopy was found in 25% of patients with SDB Vs. 14.5% in
 those without SDB.

 • Non-sustained ventricular tachycardia (NSVT) was found in 5.3% of patients with
 SDB Vs 1.2% in those without SDB.
After adjusting for confounding factors (age, sex, BMI, and coronary
heart disease), patients with Sleep Disordered Breathing (SDB) were
3.40 and 1.74 times more likely to experience Nonsustained
Ventricular Tachycardia (NSVT) and Complex Ventricular Ectopy
(CVE) as compared to patients without SDB respectively.
- This suggests that in the setting of SDB, there is an increased risk of
ventricular arrhythmias
                                       • CPAP therapy decreases
                                       cardiovascular related deaths vs that
                                       of null treatment

                                       • 7% of total untreated patients died
                                       from sudden cardiac death vs 0% in
                                       CPAP treated group

                                       • Sudden cardiac death was
                                       responsible for 44% of the total
                                       cardiovascular deaths in the
                                       untreated group and 0% in CPAP
                                       treated group.



CPAP, as a treatment of Sleep Disordered Breathing (SDB), decreases
rates of Sudden Cardiac Death (SCD) which reinforces SDB as a risk
factor for SCD
• Patients with OSA were more likely to
suffer Sudden Cardiac Death (SCD) from
12-6AM

• Patients with an AHI score >40 were 2.61
times as likely to suffer SCD from 12-6AM
SUGGESTED VENTRICULAR ORIGIN OF
  RHYTHM ABNORMALITIES IN OSA
           PATIENTS:
  Patients with known
cardiovascular disease....
Patients with ICDs who are asymptomatic for
Sleep Disordered Breathing (SDB), have a
higher rate of undiagnosed SDB




                   CSA = Central Sleep Apnea
                   OSA = Obstructive Sleep Apnea
Evaluated the prevalence of Sleep Disordered Breathing (SDB) in patients with severe ventricular
arrhythmias and normal left ventricular (LV) function
      •Although higher prevalence of SDB in this population, there was no significant difference
      seen between 2 groups evaluated
      •However n of 35, and limited to patient cohort of Japanese origin so limited extrapolation
      potential
                                       • 41% of patients with known
                                       coronary artery disease and no
                                       suspected Sleep Disordered
                                       Breathing (SDB) were found to
                                       have an AHI>15

                                       • Ventricular Premature
                                       Contraction (VPC)
                                       counts/minute were higher in
                                       those with a larger AHI score
In patients with known coronary artery disease, and asymptomatic
for SDB:
- There exists a correlation between VPC counts/min and severity of
SDB (based on AHI score)
                                                     Interpretation of
                                                     these Findings...
•    Benign Ventricular Premature Contractions (VPCs) likely serve as triggers
     of complex arrhythmias during prolonged apnea episodes (when
     sympathetic dominates over vagal activity)
       • It creates an autonomic environment favoring perpetuation of the arrhythmia
•    Diagnosis and appropriate treatment of obstructive sleep apnea should be
     beneficial in preventing SCD
     • Treatment has been shown to:
        Decrease sympathetic activity,
        Ventricular ectopy,
        Ventricular tachycardia
        Fatal and non-fatal cardiovascular events (cases of severe obstructive sleep apnea)

    • In patient populations referred for assessment of sleep apnea, apnea has
      not been found to increase ventricular arrhythmias.
    • This contrasts patients with coronary artery disease but no suspected
      Sleep Disordered Breathing (SDB)
Summary - Sleep Apnea and Ventricular
Arrhythmia
• Sudden Cardiac Death (SCD), which has been linked to
  Sleep Disordered Breathing (SDB), may be driven by
  ventricular arrhythmias
   CPAP (primary treatment for OSA) improves SCD
     [Doherty et al. Chest. 2005]

   Patients with SDB have a higher incidence of ventricular
    arrhythmias [Mehra et al. Am J Respir Crit Care Med. 2006]
• The proposed pathophsyiologic mechanisms connecting
  SDB to ventricular arrhythmias, and subsequently to SCD
  are outlined below
               Possible Mechanisms

1. Sleep Disordered Breathing (SDB) has an
   increased incidence of cardiovascular events.
   This is associated with increase risk of post-MI
   associated arrhythmias.
             Possible Mechanisms

2. Sleep Disordered Breathing (SDB) may have
   detrimental effects of left ventricular function.
   Deleterious effects of LVEF may lead to
   hormonal or cellular changes. This predisposes
   to cardiac death.
            Possible Mechanisms

3. Premature Ventricular Contractions (PVCs) are
   common in hypertensive patients with left
   ventricular hypertrophy (LVH). Hypertension has
   a significant association with sleep apnea.
                   Possible Mechanisms
4.   Intermittent hypoxemia occurs with Sleep Disordered
     Breathing (SDB)
     •   Severe acute episodes can induce ventricular ectopy.
         [Shamsuzzaman et al.JAMA.2003]

     •   Chronically repetitive oxidative stress may induce
         ventricular remodeling predisposing to arrhythmia
         [Gami et al. J Cardiovasc Electrophysiol.2008]
                       Possible Mechanisms
5. Impaired autonomic control is seen with SDB


             Hypercapnia               Hypoxemia            Apnea


      Increased sympathetic activity                     Imbalance of
  • Via initiation of central and peripheral        parasympathetic activity
                 chemoreflexes


                                   Deleterious effects on HR
                                 variability and cardiac coupling
                                      with ventilatory input
  •      Fluctuating autonomic activity seen in Sleep Disordered Breathing
         (SDB) can effect beat to beat changes in ventricular repolarization,
         which can predispose to ventricular arrhythmia. [Roche et al. 2003]
  •      However, Barta et al reported there were no significant changes in
         QT corrected and QT corrected dispersion. [Barta et al. Clin Cardiol. 2009]
           Possible Mechanisms
6. Chronic elevation of sympathetic tone, as
   seen in Sleep Disordered Breathing
   (SDB), can lead to an increased risk of
   Sudden Cardiac Death (SCD)
                      Recommendations

• Patients with known structural heart disease and are
  symptomatic for Sleep Disordered Breathing (SDB) should
  be referred for polysomnogram.
  [Baranchuk and McIntyre. Iran Cardiovasc Research J. 2009; Watanabe
  et al. Indian Pacing and Electrophysiol J. 2008]

• CPAP therapy should be initiated in patients with
  identifiable SDB and underlying cardiac disease to prevent
  Sudden Cardiac Death.
  [Doherty et al. Chest. 2005]

• Treatment of SDB could reduce the therapies delivered by
  ICDs in patients with proved SDB.
  [Baranchuk and McIntyre. Arrhythmia and Electrophysiology Symposium.
  2009]
               Conclusion
• Sleep Disordered Breathing has been
  linked to ventricular arrhythmia.
• Sleep Disordered Breathing has also been
  linked to sudden cardiac death.
• Patients with known heart disease have
  been shown to have a higher prevalence
  of undiagnosed sleep disordered
  breathing.
• As outlined above, there are proposed
  mechanisms suggesting Sleep Disordered
  Breathing drives the formation of
  ventricular arrhythmias.
                Conclusion
• These studies highlight the importance of
  physician awareness and recognition of
  potential ventricular arrhythmias in
  patients with Sleep Disordered Breathing.
• Management goals should include CPAP
  therapy to minimize Sleep Disordered
  Breathing in order to reduce the risk of
  Sudden Cardiac Death.

								
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