Pub Date: Monday, Aug 01, 2022
Author: Bige Ozkan MD, Chiadi E. Ndumele MD, PhD, FAHA
The incidence and prevalence of cardiac arrhythmias have been increasing1, driven in large part by rising rates of atrial fibrillation (AF) the most common sustained form of arrhythmia. Arrhythmias are linked to several adverse clinical outcomes, including stroke, heart failure, and all-cause mortality. There is therefore a growing need to enhance strategies for the prevention and mitigation of arrhythmias in the population, which involves identifying and addressing risk factors for arrhythmia development. An important and underrecognized risk factor for arrhythmias in the population is sleep disordered breathing (SDB), which served as the impetus for this important scientific statement.
SDB is characterized by the reduction (hypopnea) or cessation (apnea) of airflow during sleep, which affects approximately 1 billion individuals worldwide2, with prevalence estimates ranging from 9-38%3. The two main categories of sleep disordered breathing are obstructive sleep apnea (OSA), which results from mechanical obstruction of the airway, and central sleep apnea (CSA), which is characterized by the lack of respiratory effort mediated by the central nervous system. OSA is the predominant form of SDB, and as OSA is closely linked to excess adiposity, its prevalence is unsurprisingly rising significantly in concert with the obesity epidemic.
As detailed in the scientific statement, SDB is associated with various forms of arrhythmias, including atrial fibrillation, ventricular tachyarrhythmias, and bradycardias. There are the most data about the relationship between OSA and atrial fibrillation. OSA is more prevalent among those with than those without atrial fibrillation (21-74% vs. 3-49%)4. Large cohort studies demonstrate that individuals with severe OSA5 or severe nocturnal hypoxemia6 have a higher risk of atrial fibrillation, an association that is independent of other risk factors. A more limited number of studies indicate that CSA is also associated with incident atrial fibrillation7.
Importantly, there are significant sociodemographic disparities in the prevalence of SDB, atrial fibrillation, and the risk for related clinical complications. Such disparities are largely driven by more adverse social determinants of health among individuals from race/ethnic minority groups and from socially disadvantaged populations, which impact access to care, self-management, lifestyle behaviors, psychosocial stress, and many other factors that influence health outcomes. Social determinants also underlie disparities in the prevalence of cardiometabolic risk factors such as obesity, hypertension, and diabetes that increase the risk of both SDB and atrial fibrillation. Inequities in the diagnosis and management of SDB and related comorbidities contribute to demographic differences in the likelihood of complications from atrial fibrillation.8,9
In addition to atrial fibrillation, SDB is also associated with ventricular arrhythmias and bradycardias. Individuals with SDB are more likely to have ventricular ectopy, with a dose-response relationship with the severity of SDB10. Additionally, SDB is associated with the risk of sudden cardiac death, independent of other cardiovascular risk factors. In current guidelines, a class IIb recommendation recognizes apnea and hypoxia as risk factors for sudden cardiac death among persons with SDB11. SDB and apnea-associated hypoxia also increase the likelihood of bradyarrhythmias. Consequently, the 2018 ACC/AHA/HRS guideline recommends treatment of SDB to decrease the frequency of nocturnal bradycardias and improve cardiovascular outcomes, which may eliminate the need for a pacemaker12.
This scientific statement details multiple potential mechanisms underlying the link between SDB and arrhythmias. These include the effects of autonomic activation in response to obstructive respiratory events, arrhythmogenesis from chronic intermittent hypoxia and carbon dioxide fluctuations, the mechanical effects of intrathoracic pressure fluctuations, alterations of circadian rhythms, and structural and electrical cardiac remodeling related to chronically untreated SDB. Deleterious changes in cardiac structure and function are exacerbated by the common presence of obesity among those with SDB, which is linked to increased atrial volume, diastolic dysfunction, and fibrosis13 that contribute to increased arrhythmogenicity. The local inflammatory effects of epicardial adipose tissue further promote atrial arrhythmias. Reduced intrathoracic pressure, as well as the imbalance of increased sympathetic activation in contrast to reduced parasympathetic activity, are the primary driving mechanisms behind ventricular tachyarrhythmias and subsequent sudden cardiac death. Conversely, enhanced parasympathetic tone and vagal stimulation of the carotid body cause bradyarrhythmias during apnea-associated hypoxia.
While there is significant data supporting the risks for arrhythmias associated with SDB, there is relatively limited data regarding effective management strategies. Current guidelines recommend weight loss, positive airway pressure (PAP) application, and surgical correction of anatomical obstructions as first-line treatment options for OSA14. Observational studies suggest potential benefits of treatment of SDB on the burden of arrhythmias. Individuals with OSA have a greater recurrence of AF after catheter ablation15, and CPAP treatment is associated with decreased recurrence rates of AF after ablation16. However, there have only been a small number of randomized controlled trials assessing the impact of continuous positive airway pressure (CPAP) to treat OSA on the burden of atrial fibrillation. Clinical trials have demonstrated conflicting results on atrial fibrillation, but many have had significant limitations, including limited statistical power, the lack of consideration of atrial fibrillation as a primary outcome, and the use of 12-lead ECGs rather than continuous monitoring to ascertain atrial fibrillation recurrence.
This scientific statement details many important future directions for the field. There is clearly a need for more widespread recognition, among clinicians and within the lay community, of the relationship between SDB and cardiac arrhythmias. Such increased recognition should be accompanied by increased screening for SDB in patients with arrhythmias, with a goal of improved quality of life and reduced arrhythmia burden. Patients who have arrhythmias that persist despite rate and rhythm control measures, or those with concomitant risk factors, would benefit the most from routine SDB screening and assessment. Furthermore, early identification and management of SDB might prevent long-term cardiac remodeling that further precipitates arrhythmias.
The optimal strategies for screening for SDB in the population need to be elucidated, given that the gold standard of polysomnography is not feasible for such purposes. Validated screening tests, smartphones and watches, home sleep apnea tests, and machine learning-based models all demonstrate some potential for screening. There is a particular need to develop strategies for enhanced screening among race-ethnic minorities and in socially disadvantaged groups, where delays in SDB diagnosis contribute to greater complications. Screening strategies developed in predominantly White populations might have lower predictive performance for individuals from different racial/ethnic backgrounds17, and therefore validation is needed in more diverse populations. There is also need for future studies in patients with SDB that better characterize cardiac structural changes, adiposity measures, clinical and social risk factors, and the specific subtype of SDB, to increase our understanding of the pathways linking SDB to arrhythmias.
Most notably, as emphasized by the authors of this statement, there is a need for adequately powered randomized controlled trials to assess whether interventions to treat SDB can mitigate the associated arrhythmia risk. Such trials should be diverse, including traditionally underrepresented populations where social determinants may impact risk. Additionally, there is a need to develop and assess the impact of tailored treatments for the different forms of SDB, so that the management approach truly reflects the underlying pathophysiology, with the potential for greater clinical effectiveness.
In conclusion, this AHA scientific statement summarizes the current literature and identifies the evidence gaps regarding SDB and arrhythmias. Moving forward, there is a need for more widespread recognition of and screening for SDB in patients with arrhythmias, more diverse research populations to identify and address clinical and sociodemographic subgroups with excess risk, and well-powered randomized trials to definitively assess the impact of SDB management on arrhythmia burden.
Mehra R, Chung MK, Olshansky B, Dobrev D, Jackson CL, Kundel V, Linz D, Redeker NS, Redline S, Sanders P, Somers VK; on behalf of the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology; and Stroke Council. Sleep-disordered breathing and cardiac arrhythmias in adults: mechanistic insights and clinical implications: a scientific statement from the American Heart Association [published online ahead of print August 1, 2022]. Circulation. doi: 10.1161/CIR.0000000000001082
- Kornej, J., Borschel, C. S., Benjamin, E. J. & Schnabel, R. B. Epidemiology of Atrial Fibrillation in the 21st Century: Novel Methods and New Insights. Circ Res 127, 4-20, doi:10.1161/CIRCRESAHA.120.316340 (2020).
- Benjafield, A. V. et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med 7, 687-698, doi:10.1016/S2213-2600(19)30198-5 (2019).
- Senaratna, C. V. et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev 34, 70-81, doi:10.1016/j.smrv.2016.07.002 (2017).
- Linz, D., Nattel, S., Kalman, J. M. & Sanders, P. Sleep Apnea and Atrial Fibrillation. Card Electrophysiol Clin 13, 87-94, doi:10.1016/j.ccep.2020.10.003 (2021).
- Cadby, G. et al. Severity of OSA is an independent predictor of incident atrial fibrillation hospitalization in a large sleep-clinic cohort. Chest 148, 945-952, doi:10.1378/chest.15-0229 (2015).
- Kendzerska, T. et al. Sleep Apnea Increases the Risk of New Hospitalized Atrial Fibrillation: A Historical Cohort Study. Chest 154, 1330-1339, doi:10.1016/j.chest.2018.08.1075 (2018).
- Tung, P. et al. Obstructive and Central Sleep Apnea and the Risk of Incident Atrial Fibrillation in a Community Cohort of Men and Women. J Am Heart Assoc 6, doi:10.1161/JAHA.116.004500 (2017).
- Pranathiageswaran, S., Badr, M. S., Severson, R. & Rowley, J. A. The influence of race on the severity of sleep disordered breathing. J Clin Sleep Med 9, 303-309, doi:10.5664/jcsm.2572 (2013).
- Dudley, K. A. & Patel, S. R. Disparities and genetic risk factors in obstructive sleep apnea. Sleep Med 18, 96-102, doi:10.1016/j.sleep.2015.01.015 (2016).
- Mehra, R. et al. Nocturnal Arrhythmias across a spectrum of obstructive and central sleep-disordered breathing in older men: outcomes of sleep disorders in older men (MrOS sleep) study. Arch Intern Med 169, 1147-1155, doi:10.1001/archinternmed.2009.138 (2009).
- Priori, S. G. et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 36, 2793-2867, doi:10.1093/eurheartj/ehv316 (2015).
- Kusumoto, F. M. et al. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 74, e51-e156, doi:10.1016/j.jacc.2018.10.044 (2019).
- Chung, M. K. et al. Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation: A Scientific Statement From the American Heart Association. Circulation 141, e750-e772, doi:10.1161/CIR.0000000000000748 (2020).
- Qaseem, A. et al. Management of obstructive sleep apnea in adults: A clinical practice guideline from the American College of Physicians. Ann Intern Med 159, 471-483, doi:10.7326/0003-4819-159-7-201310010-00704 (2013).
- Sato, A., Naito, R. & Kasai, T. Screening for Sleep Apnea in Atrial Fibrillation Prior to Catheter Ablation. Circ J 85, 261-263, doi:10.1253/circj.CJ-20-1284 (2021).
- Kanagala, R. et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation 107, 2589-2594, doi:10.1161/01.CIR.0000068337.25994.21 (2003).
- Johnson, D. A. et al. Prevalence and correlates of obstructive sleep apnea among African Americans: the Jackson Heart Sleep Study. Sleep 41, doi:10.1093/sleep/zsy154 (2018).
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