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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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