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Clinical impact of screening for sleep related breathing disorders in atrial fibrillation
International Journal of Cardiology 154 (2012) 256–258
Contents lists available at ScienceDirect
International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Clinical impact of screening for sleep related breathing disorders in atrial fibrillation David R. Altmann a,d,1, Elke Ullmer b, Hans Rickli a,1, Micha T. Maeder c, Christian Sticherling d, Beat A. Schaer d, Stefan Osswald d, Peter Ammann a,⁎ a
Division of Cardiology, Kantonsspital St. Gallen, Switzerland Division of Pulmonary Diseases, Kantonsspital St. Gallen, Switzerland Baker IDI Heart and Diabetes Institute Melbourne, Australia d Division of Cardiology, University of Basel Hospital, Switzerland b c
a r t i c l e
i n f o
Article history: Received 8 June 2010 Accepted 10 September 2010 Available online 13 October 2010 Keywords: Atrial fibrillation Sleep related breathing disorder Apnea–hypopnea-index Daytime sleepiness Epworth sleepiness scale
a b s t r a c t Objective: The aim of this study was to quantify daytime symptoms in atrial fibrillation (AF) patients with and without sleep related breathing disorders (SRBD). Background: SRBD are common in patients with AF but little is known about daytime symptoms among those with SRBD. Methods: Patients with AF admitted to clinics of two tertiary referral hospitals for a variety of different cardiovascular diseases were screened with a trans-nasal airflow measurement device allowing measurement of the apnea–hypopnea-index. Data on cardiac risk factors, left ventricular ejection fraction (LVEF) and cardiac medication were collected. Presence of SRBD was defined as an AHI ≥ 15/h. The Epworth sleepiness scale (ESS) was used to quantify daytime symptoms. Results: Of 102 screened patients 8 were excluded due to device malfunction (n = 1), dislocation of nasal cannula (n = 6), or hyperthyroidism (n = 1). Among the remaining 94 patients, 40 (43%) were diagnosed with SRBD. Patients with and without SRBD had similar age, body mass index, LVEF and cardiac medication. The prevalence of coronary artery disease was higher in patients with SRBD than in those without (50 vs. 17%; p = 0.0007). ESS score was low and similar in both groups (no SRBD: median 4, interquartile range (IQR) 2–4 vs. SRBD: 5, IQR 3–8; p = 0.14). Only 6/40 (5%) of the patients underwent overnight polysomnography and 2 (5%) started CPAP ventilation during follow-up. Conclusions: Even though SRBD are common in patients with AF, the prevalence of daytime symptoms is rare. Consequently, most patients will not initiate CPAP ventilation after positive SRBD screening. © 2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Approximately 1–5% of the adult population of western countries suffer from sleep related breathing disorders (SRBD) [1,2]. In recent years several studies demonstrated a relationship between SRBD and AF in subjects with a variety of cardiovascular conditions, including patients with congestive heart failure and patients with a primary diagnosis of AF [3,4]. Although known risk factors, such as age, arterial hypertension and obesity are common in patients with AF and SRBD, an independent association between both conditions is suspected. Gami et al. first described a high prevalence of sleep apnea syndrome diagnosed by questionnaire in patients with a variety of cardiovascular conditions including heart failure [3]. Recurrence of AF after electrical cardioversion has been shown to be lower in subjects with appropriate treatment for SRBD compared to those without [5]. An association ⁎ Corresponding author. Department of Internal Medicine, Division of Cardiology, Kantonsspital St. Gallen, Rorschacherstrasse 95, CH-9007 St. Gallen, Switzerland. Tel.: + 41 71 494 11 11; fax: + 41 71 494 63 35. E-mail address: [email protected] (P. Ammann). 1 David R. Altmann and Hans Rickli contributed equally to the work. 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.09.034
between SRBD and AF has also been described in subjects without evidence of structural heart disease and normal LVEF [4] whereas another study found sleep apnea to be common in subjects with lone AF but not more common compared to control subjects without AF [6]. Proposed pathophysiological mechanisms to explain the occurrence of AF in patients with SRBD include a reduction in oxygen saturation and hypercapnic phases due to repetitive hypopneic and apneic phases leading e.g. to chemoreceptor activation and arousals with consecutive increasing sympathetic neural activity [7]. In general, SRBD is suspected in the presence of combined night- and daytime symptoms, such as nightly gasping or excessive daytime sleepiness, especially in the presence of SRBD risk factors. However, cardiologists rarely refer their AF patients for SRBD screening. This study sought to investigate the prevalence of SRBD in patients with AF using an overnight screening analysis and to quantify daytime symptoms by questionnaire in those with and without SRBD. 2. Materials and methods Patients with paroxysmal or persistent non-valvular AF admitted to two tertiary referral hospitals due to a variety of cardiac conditions were screened for the presence of
D.R. Altmann et al. / International Journal of Cardiology 154 (2012) 256–258
257
SRBD with a validated device based on trans-nasal airflow measurement [8] (MicroMesam®, ResMed GmbH & Co. KG, Switzerland). The device allows overnight respiratory pressure measurements via a nasal cannula and automated analysis of apnea, hypopnea and snoring episodes. Apnea was defined as cessation of airflow N 10 s and hypopnea as a N 50% reduction of airflow lasting N 10 s. The apnea–hypopnea-index (AHI) is calculated by dividing the number of apneas and hypopneas per hour of sleep and is an index of disease severity (mild 5–14, moderate 15–30, and severe greater than 30). Data from sleep studies were stored digitally and reviewed by an experienced pneumonologist (E.U.). Subtypes of SRBD include obstructive (OSA) and central sleep apnea (CSA) which can only be differentiated by overnight polysomnography (PSG) with an electroencephalography study for assessing sleep apnea. A screening analysis based on trans-nasal airflow measurement does not allow further differentiation of SRBD. To assess daytime symptoms all patients completed the Epworth sleepiness scale questionnaire (ESS) [9,10] on the day of the screening analysis. A score ≥10 of 24 possible points is considered sleepy. Patients who had at least moderate SRBD (AHI ≥ 15/h) according to the current guidelines [11] were informed about their suspected breathing disorder and the association between SRBD and adverse cardiovascular events. They were offered to undergo overnight PSG to confirm the diagnosis, differentiate the cause of SRBD, and to initiate continuous positive airway pressure (CPAP) ventilation if necessary. AF was diagnosed by ECG, and in case of paroxysmal AF an ECG demonstrating AF had to be available from the medical charts. Data on body mass index (BMI), cardiac risk factors and medication were collected. Left ventricular ejection fraction (LVEF) and left atrial size were determined using transthoracic echocardiography. Left atrial size was measured in the parasternal long axis view and was considered enlarged when N 40 mm. Finally, patients with SRBD were compared to patients without. Exclusion criteria were: significant valvular heart disease and transient or reversible cause of AF (i.e. following heart surgery within the last 6 months or hyperthyroidism). The study was approved by the local ethics committee.
Table 1 Baseline characteristics.
2.1. Statistical analysis
Mean± standard deviation. Median (interquartile ranges). AHI = apnea–hypopnea-index.
Categorical data are presented as numbers (percentages) and continuous data as mean ± standard deviation or median (interquartile range) as appropriate. Fisher's exact test was used to compare categorical variables, chi-square for unpaired nominal variables and unpaired Student's-t-test or Mann Whitney statistics to compare continuous variables as appropriate. A p b 0.05 was considered to indicate statistical significance. Analyses were performed using Prism software package version 5.0 (Graph Pad Software for Mac OS X, Inc.).
of 43% of SRBD using an overnight screening device based on trans-nasal airflow pressure measurement. This finding is consistent with previous studies, which used different methods to diagnose SRBD [3,12]. The novel finding of our study is that daytime sleepiness was low in patients with SRBD, even in subjects with high AHI. Daytime sleepiness has been investigated in subjects with systolic heart failure and SRBD with divergent results [13,14]. However, heart failure might contribute to daytime sleepiness but in daily practice subjective sleepiness in AF patients is not frequently reported. Daytime sleepiness was low in our AF patient cohort and only 15% of our SRBD patients were willing to undergo PSG after positive screening analysis. The main reason for refusing further clarification was the absence of excessive daytime sleepiness and therefore only 5% (2/40) accepted CPAP ventilation, which was of benefit in one patient in terms of improvement of daytime sleepiness (ESS before/after treatment 14/5 points). Thus, the absence of subjective daytime sleepiness will not reliably rule out the presence of SRBD in patients with AF. This finding is
3. Results One-hundred-and-two patients with persistent (73%) and paroxysmal (27%) AF were screened for the presence of SRBD. Eight patients were excluded due to device malfunction (n= 1), dislocation of nasal cannula (n= 6) and hyperthyroidism (n= 1). In the remaining 94 patients (age 69± 11 years), 43% (40/94) were diagnosed with SRBD. Baseline characteristics of the study population are presented in Table 1. There were no significant differences between patients with and without SRBD with respect to cardiovascular risk factors such as age, gender, BMI, prevalence of hypertension, diabetes, and smoking status. LVEF, left atrial enlargement and cardiac medication, including the use of antiarrhythmic drugs were similar in both groups. AHI was significantly higher in the SRBD group compared to patients without SRBD [20 (15–44) vs. 7 (2–11)/h; p = 0.0001]. ESS was low and similar in both groups [no SRBD: 4 (2–4) vs. SRBD: 5 (3–8); p = 0.14] (Fig. 1). The prevalence of coronary heart disease (CAD) was higher in the SRBD group [9/54 (17%) vs. 20/40 (50%); p = 0.0007] (Table 2). Only 6 (15%) patients who were diagnosed with SRBD agreed to an overnight PSG study (Table 2). In all patients who completed PSG, diagnosis of SRBD was confirmed. Four patients were diagnosed with OSA and two as having CSA. Only two patients, both diagnosed with OSA accepted initiation of CPAP therapy. Of those, one patient, who had significant daytime sleepiness reflected by an ESS score of 14 points, reported reduced daytime sleepiness after initiation of CPAP therapy (ESS 5) and therefore accepted long-term CPAP therapy. The other patient withdrew CPAP one month after initiation because of absence of daytime symptoms before, and during CPAP ventilation, respectively. 4. Discussion In patients with a variety of cardiovascular diseases and concomitant persistent or paroxysmal non-valvular AF we determined a prevalence
Characteristic
Value
n Age (years) Male, n (%) Body mass index, kg/m2 Normal (b 25 kg/m2), n (%) Overweight (≥ 25 and b 30 kg/m2), n (%) Obese (≥30 kg/m2), n (%) Left ventricular ejection fraction, % Left atrial size enlargement, n (%) Sleep related breathing disorder (AHI ≥ 15), n (%) Mild SRBD (AHI 15–30), n (%) Severe SRBD (AHI N 30), n (%) Coronary artery disease, n (%) Persistent atrial fibrillation, n (%) Paroxysmal atrial fibrillation, n (%) Arterial hypertension, n (%) Diabetes mellitus, n (%) Current smoking, n (%) Reasons for admission, n (%) Symptomatic atrial fibrillation Suspected ischemic cardiomyopathy Acute coronary syndrome Congestive heart failure Syncope Other
94 69 ± 11 60 (64) 28 (25–31) 27 (29) 36 (38) 31 (33) 50 ± 12 79 (84) 40 (43) 21 (22) 19 (20) 29 (31) 69 (73) 25 (27) 70 (74) 20 (21) 27 (29) 37 (39) 17 (18) 6 (6) 14 (15) 2 (2) 18 (19)
Fig. 1. Apnea–hypopnea-index (AHI) and daytime sleepiness assessed by the Epworth sleepiness scale score (ESS) in patients with and without sleep related breathing disorders (SRBD). Per definition AHI was high in patients diagnosed with SRBD compared to those without, whereas daytime sleepiness assessed by the ESS was low and similar in both, those with and without SRBD. Box plots (25th and 75th percentiles, horizontal line indicates the median value) and whiskers (minimum to maximum).
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D.R. Altmann et al. / International Journal of Cardiology 154 (2012) 256–258
Table 2 Results and findings.
Age (years) Male, n (%) Body mass index, kg/m2 Normal (b25 kg/m2), n (%) Overweight (≥25 and b30 kg/m2), n (%) Obese (≥30 kg/m2), n (%) Left ventricular ejection fraction, % Left atrial size enlargement, n (%) Coronary artery disease, n (%) Persistent atrial fibrillation, n (%) Arterial hypertension, n (%) Diabetes mellitus, n (%) Current smoking, n (%) Apnea–hypopnea-index, h−1 b Epworth sleepiness scale, points Overnight polysomnography, n (%)b Medication, n (%) Betablocker ACE-I or ARB Calcium channel blocker Amiodarone Digoxin Anticoagulation
No SRBD
SRBD
n = 54
n = 40
p
68 ± 12 34 (63) 28 (26–33) 12 (22) 21 (39) 21 (39) 52 ± 13 43 (80) 9 (17) 36 (67) 16 (30) 12 (22) 14 (26) 7 (2–11) 4 (2–6)
70 ± 10 26 (65) 27 (24–30) 15 (38) 15(38) 10 (25) 49 ± 12 36 (90) 20 (50) 33 (83) 8 (20) 8 (20) 13 (33) 20 (15–44) 5 (3–8) 6 (15)
0.34 1.00 0.12 0.20a
28 (52) 8 (15) 11 (20) 9 (17) 8 (15) 36 (67)
25 (63) 9 (23) 8 (20) 7 (18) 5 (13) 27 (68)
0.40 0.39 1.00 1.00 1.00 1.00
0.24 0.26 0.0007 0.10 0.34 1.00 0.50 0.0001 0.14
elevated BMI or hypertension was low and the presence of significant SRBD defined as an AHI N 15 was the strongest independent risk factor for the development of AF after multivariate analysis [4]. We found a high prevalence of CAD in patients with SRBD compared to those without, a finding, which has been reported previously [20]. SRBD has also been described as a predictor for CAD [21]. We cannot exclude a selection bias as 18% (17/94) of our study population was referred to our hospitals for clarification of suspected CAD with coronary angiography. However, significant CAD was only diagnosed in 5/17 (29%) of these patients. 5. Conclusions SRBD is frequent in patients with AF but typical symptoms of SRBD such as daytime sleepiness and obesity as a risk factor for OSA are rare. Although every effort had been made to convince patients with SRBD to undergo PSG, only 15% underwent PSG and in only 5% of patients CPAP ventilation was started on. Acknowledgements The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. We would like to thank Mirjam Schefer for her tireless efforts in patient recruitment and data collection [22].
Mean ± standard deviation. Median (interquartile ranges). ACE-I = angiotensin converting enzyme inhibitor, ARB = angiotensin receptor blocker. a Chi-square test for normal, obese and overweight patients. b Only patients with an AHI≥15/h were invited to undergo overnight polysomnography.
References
of interest as evidence of a treatment benefit in patients with AF and SRBD is emerging. Kanagala et al. reported a higher recurrence of AF burden after electrical cardioversion in untreated AF patients with OSA compared to patients with CPAP ventilation after a mean follow-up of 12 months (recurrence rate 42% vs. 82%, p = 0.013) [5]. In addition, OSA was an independent predictor for recurrence of AF after pulmonary vein radiofrequency catheter ablation [15]. Our finding of similar BMI in patients with and without SRBD is unexpected as obesity is a major risk factor for OSA in the general population [16,17]. Multiple mechanisms, i.e. alteration of the upper airway structure and function with consecutive airway narrowing and collapse have been proposed to explain obesity as a risk factor for SRBD. The previous reports on the association between SRBD and AF conducted in patients with cardiovascular diseases with and without impaired LVEF show similar BMI in subjects with and without SRBD [3,4]. Subjects with a primary diagnosis of OSA referred for electrical cardioversion of AF however, had a significantly higher BMI compared to controls [5] and in subjects without known AF obesity was an independent risk factor for incident AF besides the magnitude of nocturnal oxygen desaturation. Thus, even though findings are divergent, one could speculate, that mechanisms other than obesity might explain the association between SRBD and AF in non-obese patients with cardiovascular disorders. Proposed mechanisms to explain the occurrence of SRBD in patients with AF, i.e. hypoxemia and hypercapnia with chemoreceptor activation leading to peripheral vasoconstriction, increased free-radical production and pulmonary vasoconstriction, increasing right ventricular afterload [18] might also be due to CSA. Variation in intrathoracic pressure due to ineffective respiratory effort against a closed upper respiratory airway however, is the hallmark of OSA and the thin-walled atria may be most vulnerable to these forces, which, over time, might contribute to chamber enlargement [19]. Even though we investigated a heterogeneous AF population LVEF was not reduced and similar in those with and without SRBD. Stevenson et al. recently demonstrated a high prevalence of SRBD in subjects with AF and a normal LVEF, even though subjects were younger compared to ours (56 ± 12 vs. 69 ± 11 years). In addition the prevalence of traditional risk factors for sleep apnea, such as an
[1] Davies RJ, Stradling JR. The epidemiology of sleep apnoea. Thorax 1996;51(Suppl 2): S65–70. [2] Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet 2009;373:82–93. [3] Gami AS, Pressman G, Caples SM, et al. Association of atrial fibrillation and obstructive sleep apnea. Circulation 2004;110:364–7. [4] Stevenson IH, Teichtahl H, Cunnington D, Ciavarella S, Gordon I, Kalman JM. Prevalence of sleep disordered breathing in paroxysmal and persistent atrial fibrillation patients with normal left ventricular function. Eur Heart J 2008;29: 1662–9. [5] Kanagala R, Murali NS, Friedman PA, et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation 2003;107:2589–94. [6] Porthan KM, Melin JH, Kupila JT, Venho KK, Partinen MM. Prevalence of sleep apnea syndrome in lone atrial fibrillation: a case–control study. Chest 2004;125:879–85. [7] Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Ann Intern Med 2005;142:187–97. [8] Wang Y, Teschler T, Weinreich G, Hess S, Wessendorf TE, Teschler H. Validation of microMESAM as screening device for sleep disordered breathing. Pneumologie 2003;57:734–40. [9] Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:540–5. [10] Bloch KE, Schoch OD, Zhang JN, Russi EW. German version of the Epworth sleepiness scale. Respiration 1999;66:440–7. [11] Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999;22:667–89. [12] Mehra R, Benjamin EJ, Shahar E, et al. Association of nocturnal arrhythmias with sleep-disordered breathing: the Sleep Heart Health Study. Am J Respir Crit Care Med 2006;173:910–6. [13] Arzt M, Young T, Finn L, et al. Sleepiness and sleep in patients with both systolic heart failure and obstructive sleep apnea. Arch Intern Med 2006;166:1716–22. [14] Javaheri S, Parker TJ, Liming JD, et al. Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations. Circulation 1998;97:2154–9. [15] Jongnarangsin K, Chugh A, Good E, et al. Body mass index, obstructive sleep apnea, and outcomes of catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2008;19:668–72. [16] Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 2002;165:1217–39. [17] Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA 2000;284:3015–21. [18] Stoohs R, Guilleminault C. Cardiovascular changes associated with obstructive sleep apnea syndrome. J Appl Physiol 1992;72:583–9. [19] Caples SM, Somers VK. Sleep-disordered breathing and atrial fibrillation. Prog Cardiovasc Dis 2009;51:411–5. [20] Mooe T, Rabben T, Wiklund U, Franklin KA, Eriksson P. Sleep-disordered breathing in men with coronary artery disease. Chest 1996;109:659–63. [21] Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J 2006;28:596–602. [22] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
Contents lists available at ScienceDirect
International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Clinical impact of screening for sleep related breathing disorders in atrial fibrillation David R. Altmann a,d,1, Elke Ullmer b, Hans Rickli a,1, Micha T. Maeder c, Christian Sticherling d, Beat A. Schaer d, Stefan Osswald d, Peter Ammann a,⁎ a
Division of Cardiology, Kantonsspital St. Gallen, Switzerland Division of Pulmonary Diseases, Kantonsspital St. Gallen, Switzerland Baker IDI Heart and Diabetes Institute Melbourne, Australia d Division of Cardiology, University of Basel Hospital, Switzerland b c
a r t i c l e
i n f o
Article history: Received 8 June 2010 Accepted 10 September 2010 Available online 13 October 2010 Keywords: Atrial fibrillation Sleep related breathing disorder Apnea–hypopnea-index Daytime sleepiness Epworth sleepiness scale
a b s t r a c t Objective: The aim of this study was to quantify daytime symptoms in atrial fibrillation (AF) patients with and without sleep related breathing disorders (SRBD). Background: SRBD are common in patients with AF but little is known about daytime symptoms among those with SRBD. Methods: Patients with AF admitted to clinics of two tertiary referral hospitals for a variety of different cardiovascular diseases were screened with a trans-nasal airflow measurement device allowing measurement of the apnea–hypopnea-index. Data on cardiac risk factors, left ventricular ejection fraction (LVEF) and cardiac medication were collected. Presence of SRBD was defined as an AHI ≥ 15/h. The Epworth sleepiness scale (ESS) was used to quantify daytime symptoms. Results: Of 102 screened patients 8 were excluded due to device malfunction (n = 1), dislocation of nasal cannula (n = 6), or hyperthyroidism (n = 1). Among the remaining 94 patients, 40 (43%) were diagnosed with SRBD. Patients with and without SRBD had similar age, body mass index, LVEF and cardiac medication. The prevalence of coronary artery disease was higher in patients with SRBD than in those without (50 vs. 17%; p = 0.0007). ESS score was low and similar in both groups (no SRBD: median 4, interquartile range (IQR) 2–4 vs. SRBD: 5, IQR 3–8; p = 0.14). Only 6/40 (5%) of the patients underwent overnight polysomnography and 2 (5%) started CPAP ventilation during follow-up. Conclusions: Even though SRBD are common in patients with AF, the prevalence of daytime symptoms is rare. Consequently, most patients will not initiate CPAP ventilation after positive SRBD screening. © 2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Approximately 1–5% of the adult population of western countries suffer from sleep related breathing disorders (SRBD) [1,2]. In recent years several studies demonstrated a relationship between SRBD and AF in subjects with a variety of cardiovascular conditions, including patients with congestive heart failure and patients with a primary diagnosis of AF [3,4]. Although known risk factors, such as age, arterial hypertension and obesity are common in patients with AF and SRBD, an independent association between both conditions is suspected. Gami et al. first described a high prevalence of sleep apnea syndrome diagnosed by questionnaire in patients with a variety of cardiovascular conditions including heart failure [3]. Recurrence of AF after electrical cardioversion has been shown to be lower in subjects with appropriate treatment for SRBD compared to those without [5]. An association ⁎ Corresponding author. Department of Internal Medicine, Division of Cardiology, Kantonsspital St. Gallen, Rorschacherstrasse 95, CH-9007 St. Gallen, Switzerland. Tel.: + 41 71 494 11 11; fax: + 41 71 494 63 35. E-mail address: [email protected] (P. Ammann). 1 David R. Altmann and Hans Rickli contributed equally to the work. 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.09.034
between SRBD and AF has also been described in subjects without evidence of structural heart disease and normal LVEF [4] whereas another study found sleep apnea to be common in subjects with lone AF but not more common compared to control subjects without AF [6]. Proposed pathophysiological mechanisms to explain the occurrence of AF in patients with SRBD include a reduction in oxygen saturation and hypercapnic phases due to repetitive hypopneic and apneic phases leading e.g. to chemoreceptor activation and arousals with consecutive increasing sympathetic neural activity [7]. In general, SRBD is suspected in the presence of combined night- and daytime symptoms, such as nightly gasping or excessive daytime sleepiness, especially in the presence of SRBD risk factors. However, cardiologists rarely refer their AF patients for SRBD screening. This study sought to investigate the prevalence of SRBD in patients with AF using an overnight screening analysis and to quantify daytime symptoms by questionnaire in those with and without SRBD. 2. Materials and methods Patients with paroxysmal or persistent non-valvular AF admitted to two tertiary referral hospitals due to a variety of cardiac conditions were screened for the presence of
D.R. Altmann et al. / International Journal of Cardiology 154 (2012) 256–258
257
SRBD with a validated device based on trans-nasal airflow measurement [8] (MicroMesam®, ResMed GmbH & Co. KG, Switzerland). The device allows overnight respiratory pressure measurements via a nasal cannula and automated analysis of apnea, hypopnea and snoring episodes. Apnea was defined as cessation of airflow N 10 s and hypopnea as a N 50% reduction of airflow lasting N 10 s. The apnea–hypopnea-index (AHI) is calculated by dividing the number of apneas and hypopneas per hour of sleep and is an index of disease severity (mild 5–14, moderate 15–30, and severe greater than 30). Data from sleep studies were stored digitally and reviewed by an experienced pneumonologist (E.U.). Subtypes of SRBD include obstructive (OSA) and central sleep apnea (CSA) which can only be differentiated by overnight polysomnography (PSG) with an electroencephalography study for assessing sleep apnea. A screening analysis based on trans-nasal airflow measurement does not allow further differentiation of SRBD. To assess daytime symptoms all patients completed the Epworth sleepiness scale questionnaire (ESS) [9,10] on the day of the screening analysis. A score ≥10 of 24 possible points is considered sleepy. Patients who had at least moderate SRBD (AHI ≥ 15/h) according to the current guidelines [11] were informed about their suspected breathing disorder and the association between SRBD and adverse cardiovascular events. They were offered to undergo overnight PSG to confirm the diagnosis, differentiate the cause of SRBD, and to initiate continuous positive airway pressure (CPAP) ventilation if necessary. AF was diagnosed by ECG, and in case of paroxysmal AF an ECG demonstrating AF had to be available from the medical charts. Data on body mass index (BMI), cardiac risk factors and medication were collected. Left ventricular ejection fraction (LVEF) and left atrial size were determined using transthoracic echocardiography. Left atrial size was measured in the parasternal long axis view and was considered enlarged when N 40 mm. Finally, patients with SRBD were compared to patients without. Exclusion criteria were: significant valvular heart disease and transient or reversible cause of AF (i.e. following heart surgery within the last 6 months or hyperthyroidism). The study was approved by the local ethics committee.
Table 1 Baseline characteristics.
2.1. Statistical analysis
Mean± standard deviation. Median (interquartile ranges). AHI = apnea–hypopnea-index.
Categorical data are presented as numbers (percentages) and continuous data as mean ± standard deviation or median (interquartile range) as appropriate. Fisher's exact test was used to compare categorical variables, chi-square for unpaired nominal variables and unpaired Student's-t-test or Mann Whitney statistics to compare continuous variables as appropriate. A p b 0.05 was considered to indicate statistical significance. Analyses were performed using Prism software package version 5.0 (Graph Pad Software for Mac OS X, Inc.).
of 43% of SRBD using an overnight screening device based on trans-nasal airflow pressure measurement. This finding is consistent with previous studies, which used different methods to diagnose SRBD [3,12]. The novel finding of our study is that daytime sleepiness was low in patients with SRBD, even in subjects with high AHI. Daytime sleepiness has been investigated in subjects with systolic heart failure and SRBD with divergent results [13,14]. However, heart failure might contribute to daytime sleepiness but in daily practice subjective sleepiness in AF patients is not frequently reported. Daytime sleepiness was low in our AF patient cohort and only 15% of our SRBD patients were willing to undergo PSG after positive screening analysis. The main reason for refusing further clarification was the absence of excessive daytime sleepiness and therefore only 5% (2/40) accepted CPAP ventilation, which was of benefit in one patient in terms of improvement of daytime sleepiness (ESS before/after treatment 14/5 points). Thus, the absence of subjective daytime sleepiness will not reliably rule out the presence of SRBD in patients with AF. This finding is
3. Results One-hundred-and-two patients with persistent (73%) and paroxysmal (27%) AF were screened for the presence of SRBD. Eight patients were excluded due to device malfunction (n= 1), dislocation of nasal cannula (n= 6) and hyperthyroidism (n= 1). In the remaining 94 patients (age 69± 11 years), 43% (40/94) were diagnosed with SRBD. Baseline characteristics of the study population are presented in Table 1. There were no significant differences between patients with and without SRBD with respect to cardiovascular risk factors such as age, gender, BMI, prevalence of hypertension, diabetes, and smoking status. LVEF, left atrial enlargement and cardiac medication, including the use of antiarrhythmic drugs were similar in both groups. AHI was significantly higher in the SRBD group compared to patients without SRBD [20 (15–44) vs. 7 (2–11)/h; p = 0.0001]. ESS was low and similar in both groups [no SRBD: 4 (2–4) vs. SRBD: 5 (3–8); p = 0.14] (Fig. 1). The prevalence of coronary heart disease (CAD) was higher in the SRBD group [9/54 (17%) vs. 20/40 (50%); p = 0.0007] (Table 2). Only 6 (15%) patients who were diagnosed with SRBD agreed to an overnight PSG study (Table 2). In all patients who completed PSG, diagnosis of SRBD was confirmed. Four patients were diagnosed with OSA and two as having CSA. Only two patients, both diagnosed with OSA accepted initiation of CPAP therapy. Of those, one patient, who had significant daytime sleepiness reflected by an ESS score of 14 points, reported reduced daytime sleepiness after initiation of CPAP therapy (ESS 5) and therefore accepted long-term CPAP therapy. The other patient withdrew CPAP one month after initiation because of absence of daytime symptoms before, and during CPAP ventilation, respectively. 4. Discussion In patients with a variety of cardiovascular diseases and concomitant persistent or paroxysmal non-valvular AF we determined a prevalence
Characteristic
Value
n Age (years) Male, n (%) Body mass index, kg/m2 Normal (b 25 kg/m2), n (%) Overweight (≥ 25 and b 30 kg/m2), n (%) Obese (≥30 kg/m2), n (%) Left ventricular ejection fraction, % Left atrial size enlargement, n (%) Sleep related breathing disorder (AHI ≥ 15), n (%) Mild SRBD (AHI 15–30), n (%) Severe SRBD (AHI N 30), n (%) Coronary artery disease, n (%) Persistent atrial fibrillation, n (%) Paroxysmal atrial fibrillation, n (%) Arterial hypertension, n (%) Diabetes mellitus, n (%) Current smoking, n (%) Reasons for admission, n (%) Symptomatic atrial fibrillation Suspected ischemic cardiomyopathy Acute coronary syndrome Congestive heart failure Syncope Other
94 69 ± 11 60 (64) 28 (25–31) 27 (29) 36 (38) 31 (33) 50 ± 12 79 (84) 40 (43) 21 (22) 19 (20) 29 (31) 69 (73) 25 (27) 70 (74) 20 (21) 27 (29) 37 (39) 17 (18) 6 (6) 14 (15) 2 (2) 18 (19)
Fig. 1. Apnea–hypopnea-index (AHI) and daytime sleepiness assessed by the Epworth sleepiness scale score (ESS) in patients with and without sleep related breathing disorders (SRBD). Per definition AHI was high in patients diagnosed with SRBD compared to those without, whereas daytime sleepiness assessed by the ESS was low and similar in both, those with and without SRBD. Box plots (25th and 75th percentiles, horizontal line indicates the median value) and whiskers (minimum to maximum).
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Table 2 Results and findings.
Age (years) Male, n (%) Body mass index, kg/m2 Normal (b25 kg/m2), n (%) Overweight (≥25 and b30 kg/m2), n (%) Obese (≥30 kg/m2), n (%) Left ventricular ejection fraction, % Left atrial size enlargement, n (%) Coronary artery disease, n (%) Persistent atrial fibrillation, n (%) Arterial hypertension, n (%) Diabetes mellitus, n (%) Current smoking, n (%) Apnea–hypopnea-index, h−1 b Epworth sleepiness scale, points Overnight polysomnography, n (%)b Medication, n (%) Betablocker ACE-I or ARB Calcium channel blocker Amiodarone Digoxin Anticoagulation
No SRBD
SRBD
n = 54
n = 40
p
68 ± 12 34 (63) 28 (26–33) 12 (22) 21 (39) 21 (39) 52 ± 13 43 (80) 9 (17) 36 (67) 16 (30) 12 (22) 14 (26) 7 (2–11) 4 (2–6)
70 ± 10 26 (65) 27 (24–30) 15 (38) 15(38) 10 (25) 49 ± 12 36 (90) 20 (50) 33 (83) 8 (20) 8 (20) 13 (33) 20 (15–44) 5 (3–8) 6 (15)
0.34 1.00 0.12 0.20a
28 (52) 8 (15) 11 (20) 9 (17) 8 (15) 36 (67)
25 (63) 9 (23) 8 (20) 7 (18) 5 (13) 27 (68)
0.40 0.39 1.00 1.00 1.00 1.00
0.24 0.26 0.0007 0.10 0.34 1.00 0.50 0.0001 0.14
elevated BMI or hypertension was low and the presence of significant SRBD defined as an AHI N 15 was the strongest independent risk factor for the development of AF after multivariate analysis [4]. We found a high prevalence of CAD in patients with SRBD compared to those without, a finding, which has been reported previously [20]. SRBD has also been described as a predictor for CAD [21]. We cannot exclude a selection bias as 18% (17/94) of our study population was referred to our hospitals for clarification of suspected CAD with coronary angiography. However, significant CAD was only diagnosed in 5/17 (29%) of these patients. 5. Conclusions SRBD is frequent in patients with AF but typical symptoms of SRBD such as daytime sleepiness and obesity as a risk factor for OSA are rare. Although every effort had been made to convince patients with SRBD to undergo PSG, only 15% underwent PSG and in only 5% of patients CPAP ventilation was started on. Acknowledgements The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. We would like to thank Mirjam Schefer for her tireless efforts in patient recruitment and data collection [22].
Mean ± standard deviation. Median (interquartile ranges). ACE-I = angiotensin converting enzyme inhibitor, ARB = angiotensin receptor blocker. a Chi-square test for normal, obese and overweight patients. b Only patients with an AHI≥15/h were invited to undergo overnight polysomnography.
References
of interest as evidence of a treatment benefit in patients with AF and SRBD is emerging. Kanagala et al. reported a higher recurrence of AF burden after electrical cardioversion in untreated AF patients with OSA compared to patients with CPAP ventilation after a mean follow-up of 12 months (recurrence rate 42% vs. 82%, p = 0.013) [5]. In addition, OSA was an independent predictor for recurrence of AF after pulmonary vein radiofrequency catheter ablation [15]. Our finding of similar BMI in patients with and without SRBD is unexpected as obesity is a major risk factor for OSA in the general population [16,17]. Multiple mechanisms, i.e. alteration of the upper airway structure and function with consecutive airway narrowing and collapse have been proposed to explain obesity as a risk factor for SRBD. The previous reports on the association between SRBD and AF conducted in patients with cardiovascular diseases with and without impaired LVEF show similar BMI in subjects with and without SRBD [3,4]. Subjects with a primary diagnosis of OSA referred for electrical cardioversion of AF however, had a significantly higher BMI compared to controls [5] and in subjects without known AF obesity was an independent risk factor for incident AF besides the magnitude of nocturnal oxygen desaturation. Thus, even though findings are divergent, one could speculate, that mechanisms other than obesity might explain the association between SRBD and AF in non-obese patients with cardiovascular disorders. Proposed mechanisms to explain the occurrence of SRBD in patients with AF, i.e. hypoxemia and hypercapnia with chemoreceptor activation leading to peripheral vasoconstriction, increased free-radical production and pulmonary vasoconstriction, increasing right ventricular afterload [18] might also be due to CSA. Variation in intrathoracic pressure due to ineffective respiratory effort against a closed upper respiratory airway however, is the hallmark of OSA and the thin-walled atria may be most vulnerable to these forces, which, over time, might contribute to chamber enlargement [19]. Even though we investigated a heterogeneous AF population LVEF was not reduced and similar in those with and without SRBD. Stevenson et al. recently demonstrated a high prevalence of SRBD in subjects with AF and a normal LVEF, even though subjects were younger compared to ours (56 ± 12 vs. 69 ± 11 years). In addition the prevalence of traditional risk factors for sleep apnea, such as an
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