1. Introduction

Definitions / Impact. Atrial fibrillation (AF) and sleep apnea-hypopnea syndrome (SAHS)

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice.1 Accounting for one-third of hospital admissions for cardiac arrhythmias, AF represents an important challenge because it is associated with increased rates of heart failure, thromboembolic events, cerebrovascular accidents, and death.2 The incidence and prevalence of AF increase with age, increasing twofold to threefold between the ages of 60 and 80 years. About 8.8 million people in Europe (2% of the population) and 1 million people in Spain have AF. 3,4 These figures are expected to increase with increases in life expectancy and the progressive aging of the population. In addition to being associated with structural heart disease, AF is also associated with extracardiac factors such as systemic arterial hypertension, diabetes mellitus, obesity, and obstructive sleep apnea-hypopnea syndrome (SAHS), among others.5 In fact, obesity is a well-established risk factor for developing AF, and the risk increases with increases in body mass index.6

SAHS is the most prevalent nocturnal respiratory disorder in our society. It is characterized by repeated episodes of upper respiratory tract obstruction during sleep that lead to a progressive increase in respiratory efforts, intermittent oxygen desaturation, and sleep fragmentation, night after night.7 SAHS should be suspected in any patient who reports intense snoring with observed nocturnal apneas, poor nocturnal rest, and/or excessive daytime sleepiness, especially if the patient is obese or overweight. SAHS has harmful effects on cognitive-behavioral, respiratory, cardiac, metabolic, and inflammatory components of health. Thus, SAHS can lead to worsening quality of life,8 hypertension,9,10 cardiovascular disease,11 cerebrovascular disease,12 and traffic accidents.13 Fortunately, there are effective treatments for SAHS, such as nocturnal administration of continuous positive airway pressure (CPAP). Thus, considering the medical complications of SAHS, its repercussions on social life and work, and its negative impact on the quality of life, this disease is a public health problem, and physicians must therefore identify patients that can benefit from treatment.14 Various studies have shown that the failure to diagnose and treat patients with SAHS results in a twofold to threefold increase in the use of resources.15,16 SAHS is estimated to affect 17% of men and 9% of women 50 to 70 years old. These estimates are clearly higher than those two decades ago and most likely reflect the growing worldwide obesity epidemic17 since obesity is a risk factor for developing SAHS.

2. Concurrence. Risk factors. Common pathophysiological mechanisms

In recent decades, owing to increased obesity/overweight and cardiovascular disease in our society, the prevalences of AF and SAHS have increased. AF and SAHS share risk factors and complex, probably bidirectional, pathophysiological mechanisms; thus, SAHS can lead to AF, but AF can also contribute to the development of SAHS. Epidemiologic studies have identified a significant association between SAHS and AF; patients with SAHS have two to four times greater risk of AF than those without SAHS.18 Moreover, the frequency of cardiac arrhythmias increases as the apnea-hypopnea index, a measure of the severity of SAHS, increases.19 Other studies have found that more than 50% of patients with AF have SAHS.20

Ineffective inspiratory efforts against an occluded upper airway during apnea cause an abrupt decrease in intrathoracic pressure, resulting in an increase in the transmural pressure of the heart, which is also increased by hyperactivation of the sympathetic nervous system. The intermittent low oxygen saturation resulting from repeated apneas are associated with hemodynamic changes in left and right heart function, with progressively abnormal ventricular filling that can favor cardiac dysfunction and is also associated with changes in the structure and function of the atria. SAHS is associated with vascular changes related with the induction of a proinflammatory state and oxidative stress.21 These changes can be partially reversible when the harmful effects of the apneas are eliminated by treatment with CPAP.22

Despite the robust evidence of an association between SAHS and AF, the potential causative role of SAHS in the development of AF remains to be elucidated, since the disorders share risk factors that can confound this association. Experimental studies with animal models suggest that intermittent nocturnal hypoxia and fluctuations in intrathoracic pressure SAHS predispose to AF by electrical and structural remodeling. Different animal models have shown that exposure to increasing degrees of chronic intermittent hypoxia leads to an imbalance in the autonomic system that precipitates electrical changes in the atria that could predispose to the development of AF.23,24 Similarly, murine models have shown that applying fluctuations in intrathoracic pressure that mimic those occurring in SAHS also results in changes in electrical and structural remodeling in the atria that can lead to AF.25

3. Impact of SAHS on AF (progression, recurrence, quality of life).

The prevalence of AF is constantly increasing. Numerous studies have established a correlation between AF and various potentially modifiable risk factors such as obesity, SAHS, hypertension, and sedentary lifestyle. Treating these comorbidities can significantly reduce the negative impact of AF and its rate of recurrence after cardioversion or ablation. Thus, the classical treatment of AF based on cardiac ablation and/or antiarrhythmic drug therapy may not be sufficient. A multidimensional approach combining prevention and optimization of modifiable risk factors for AF is probably necessary to increase the success rate. 26-28

Patients with SAHS also have an increased risk of AF, and nocturnal CPAP reduces this risk. In the first year after electrical cardioversion, the rate of recurrence of AF is 82% in patients with SAHS not treated with CPAP, twice the rate in those correctly treated.29 Moreover, the rate of recurrence of AF in patients who have undergone radiofrequency ablation of the pulmonary veins is higher in those with untreated SAHS than in those without SAHS,30,31 and the rate of recurrence in those with treated SAHS is similar to the rate in those without SAHS. The Outcomes Registry for Better Informed Treatment of AF,32 which included 10132 patients with AF, found that those who had SAHS (18% of all patients) required more admissions to hospital, although the risk of death due to cardiovascular causes and the overall risk of death were similar in patients with and without SAHS. However, patients with SAHS receiving appropriate CPAP treatment were less likely to progress to permanent AF (HR 0.66; 95% CI, 0.46–0.94; p = 0.02). The mechanism through which CPAP reduces the risk of AF recurring remains to be determined, but correcting nocturnal apneas may minimize certain changes in cardiac structure induced by SAHS. On the other hand, CPAP could also mitigate other risk factors (e.g., hypertension) that are common to both SAHS and AF.

4. Benefits of treating SAHS in patients with AF.

Patients with AF and symptoms suggestive of SAHS need to undergo the appropriate diagnostic workup and, if necessary, CPAP treatment for their respiratory disorder to correct apneas to optimize the treatment of AF and especially to reduce its recurrence.33 The American Academy of Sleep Medicine recommends a sleep study to rule out SAHS in patients with AF and compatible symptoms (snoring, observed apneas, poor nocturnal rest, excessive daytime sleepiness).34 For various reasons, however, this recommendation is not vigorously followed in clinical practice. Many specialists managing AF are largely unaware of the high prevalence of concomitant SAHS and clinical suspicion of SAHS in patients with AF is often lower than it should be. Furthermore, the care pathways for referring patients with clinical suspicion are not well standardized in all centers. The current evidence clearly indicates that a multidisciplinary approach is the best way to ensure optimal treatment for AF, with referral to a specialist in sleep medicine for screening for SAHS and nocturnal CPAP treatment when necessary.

To this end, it is crucial to obtain high-quality sleep studies with optimal validity and interpretation to guarantee the correct diagnosis of SAHS. It is equally important to provide individualized management of SAHS. The correct diagnosis and treatment of SAHS by a team of experts in sleep medicine can help guarantee optimal control of AF, preventing recurrence and progression. Finally, appropriately applied nocturnal CPAP benefits patients with SAHS and associated symptoms (poor nocturnal rest, tiredness/fatigue, and daytime sleepiness) by improving sleep quality and overall quality of life.

5. Conclusions

  • The classical treatment of AF based on cardiac ablation and/or antiarrhythmic drugs may be insufficient to ensure optimal management. To increase the success rate of AF treatment, it is best to employ a multidisciplinary approach focusing on multiple dimensions, combining the prevention and optimization of modifiable risk factors, such as SAHS. Left untreated, SAHS can increase the risk of recurrence of AF; fortunately, correcting SAHS with CPAP significantly reduces the risk of recurrence.
  • Patients with AF and symptoms suggestive of SAHS (snoring, observed apneas, poor nocturnal rest, excessive daytime sleepiness) should undergo sleep studies to screen for SAHS. To optimize the treatment of AF and especially to reduce its rate of recurrence, nocturnal respiratory disorders should be treated with nocturnal CPAP to correct apneas.

6. References

  1. Fibrilación auricular. Fundación Española del Corazón. http://www.fundaciondelcorazon.com/informacion-para-pacientes/fibrilacion-auricular/que-es-fibrilacion-auricular.html.
  2. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011;123:e269-367.
  3. Massimo Zoni-Berisso. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol. 2014; 6: 213–220.
  4. Julián Pérez-Villacastín. Epidemiology of Atrial Fibrillation in Spain in the Past 20 Years.. 2013;66(07):561-565.
  5. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014 Dec 2;130(23):2071-104.
  6. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P; ESC Scientific Document Group . 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016 Oct 7;37(38):2893-2962.
  7. Lloberes P, Durán-Cantolla J, Martínez-García MÁ, Marín JM, Ferrer A, Corral J, Masa JF, Parra O, Alonso-Álvarez ML, Terán-Santos J. Diagnosis and treatment of sleep apnea-hypopnea syndrome. Spanish Society of Pulmonology and Thoracic Surgery. Arch Bronconeumol. 2011 Mar;47(3):143-56.
  8. Patil SP, Schneider H, Schwartz AR, Smith PL. Adult obstructive sleep apnea: pathophysiology and diagnosis. Chest. 2007 Jul;132(1):325-37.
  9. Baldwin CM, Griffith KA, Nieto FJ, O’Connor GT, Walsleben JA, Redline S. The association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study. Sleep. 2001 Feb 1;24(1):96-105.
  10. Durán J, Esnaola S, Rubio R, Iztueta A. Obstructive sleep apnea-hypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr. Am J Respir Crit Care Med. 2001 Mar;163(3 Pt 1):685-9.
  11. Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, D’Agostino RB, Newman AB, Lebowitz MD, Pickering TG. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000 Apr 12;283(14):1829-36.
  12. Newman AB, Nieto FJ, Guidry U, Lind BK, Redline S, Pickering TG, Quan SF; Sleep Heart Health Study Research Group. Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. Am J Epidemiol. 2001 Jul 1;154(1):50-9.
  13. Parra O, Arboix A, Bechich S, García-Eroles L, Montserrat JM, López JA, Ballester E, Guerra JM, Sopeña JJ. Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):375-80.
  14. Barbé, Pericás J, Muñoz A, Findley L, Antó JM, Agustí AG. Automobile accidents in patients with sleep apnea syndrome. An epidemiological and mechanistic study. Am J Respir Crit Care Med. 1998 Jul;158(1):18-22.
  15. Phillipson EA. Sleep apnea–a major public health problem. N Engl J Med. 1993 Apr 29;328(17):1271-3.
  16. Bahammam A, Delaive K, Ronald J, Manfreda J, Roos L, Kryger MH. Health care utilization in males with obstructive sleep apnea syndrome two years after diagnosis and treatment. Sleep. 1999 Sep 15;22(6):740-7.
  17. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet. 2016 Apr 2;387(10026):1377-1396.
  18. Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, Sahadevan J, Redline S; Sleep Heart Health Study. Association of nocturnal arrhythmias with sleep-disordered breathing: The SleepHeart Health Study. Am J Respir Crit Care Med. 2006 Apr 15;173(8):910-6.

 

  1. Tanigawa T, Yamagishi K, Sakurai S, Muraki I, Noda H, Shimamoto T, Iso H. Arterial oxygen desaturation during sleep and atrial fibrillation. Heart. 2006 Dec;92(12):1854-5.
  2. Thomas Bitter. Sleep-disordered Breathing in Patients With Atrial Fibrillation and Normal Systolic Left Ventricular Function. Dtsch Arztebl Int. 2009 Mar; 106(10): 164–170.
  3. Arias MA, Garcia-Rio F, Alonso-Fernandez A, Mediano O, Martınez I, Villamor J, et al. Obstructive sleep apnea syndrome affects left ventricular diastolic function. Effects of nasal continuous positive airway pressure in men. Circulation. 2005;112:375–83.
  4. Baranchuk A, Pang H, Seaborn GEJ, Yazdan-Ashoori P, Redfearn DP, Simpson CS, et al. Reverse atrial electrical remodelling induced by continuous positive airway pressure in patients with severe obstructive sleep apnea. J Interven Card Electrophysiol. 2013;36:247–53.
  5. Dimitri H, Ng M, Brooks AG, Kuklik P, Stiles MK, Lau DH, Antic N, Thornton A, Saint DA, McEvoy D, Antic R, Kalman JM, Sanders P. Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation. Heart Rhythm. 2012 Mar;9(3):321-7.
  6. Iwasaki YK, Kato T, Xiong F, Shi YF, Naud P, Maguy A, Mizuno K, Tardif JC, Comtois P, Nattel S. Atrial fibrillation promotion with long-term repetitive obstructive sleep apnea in a rat model. J Am Coll Cardiol. 2014 Nov 11;64(19):2013-23.
  7. Ramos P, Rubies C, Torres M, Batlle M, Farre R, Brugada J, Montserrat JM, Almendros I, Mont L. Atrial fibrosis in a chronic murine model of obstructive sleep apnea: mechanisms and prevention by mesenchymal stem cells. Respir Res. 2014 Apr 28;15:54.
  8. Du X, Dong J, Ma C. Is Atrial Fibrillation a Preventable Disease?. J Am Coll Cardiol. 2017 Apr 18;69(15):1968-1982.
  9. Sidhu K, Tang A. Modifiable Risk Factors in Atrial Fibrillation: The Role of Alcohol, Obesity, and Sleep Apnea. Can J Cardiol. 2017 Jul;33(7):947-949.
  10. Mahajan R, Pathak RK, Thiyagarajah A, Lau DH, Marchlinski FE, Dixit S, Day JD, Hendriks JML, Carrington M, Kalman JM,Sanders P. Risk Factor Management and Atrial Fibrillation Clinics: Saving the Best for Last?. Heart Lung Circ. 2017 Sep;26(9):990-997.
  11. Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, Shamsuzzaman AS, Somers VK. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003 May 27;107(20):2589-94.
  12. Naruse Y, Tada H, Satoh M, Yanagihara M, Tsuneoka H, Hirata Y, Ito Y, Kuroki K, Machino T, Yamasaki H, Igarashi M, Sekiguchi Y, Sato A, Aonuma K. Concomitant obstructive sleep apnea increases the recurrence of atrial fibrillation following radiofrequency catheter ablation of atrial fibrillation: clinical impact of continuous positive airway pressure therapy. Heart Rhythm. 2013 Mar;10(3):331-7.
  13. Ng CY, Liu T, Shehata M, Stevens S, Chugh SS, Wang X. Meta-analysis of obstructive sleep apnea as predictor of atrial fibrillation recurrence after catheter ablation. Am J Cardiol. 2011 Jul 1;108(1):47-51.
  14. Holmqvist F, Guan N, Zhu Z, Kowey PR, Allen LA, Fonarow GC, Hylek EM, Mahaffey KW, Freeman JV, Chang P, Holmes DN, Peterson ED, Piccini JP, Gersh BJ; ORBIT-AF Investigators. Impact of obstructive sleep apnea and continuous positive airway pressure therapy on outcomes in patients with atrial fibrillation-Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Am Heart J. 2015 May;169(5):647-654.
  15. Qureshi WT, Nasir UB, Alqalyoobi S, O’Neal WT, Mawri S, Sabbagh S, Soliman EZ, Al-Mallah MH. Meta-Analysis of Continuous Positive Airway Pressure as a Therapy of Atrial Fibrillation in Obstructive Sleep Apnea. Am J Cardiol. 2015 Dec 1;116(11):1767-73.
  16. Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, Ramar K, Rogers R, Schwab RJ, Weaver EM, Weinstein MD; Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical guideline for the evaluation, management and long-term care of obstructivesleep apnea in adults. J Clin Sleep Med. 2009 Jun 15;5(3):263-76.