International Journal of Cardiology 176 (2014) 1447–1448
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Excessive daytime sleepiness and central sleep apnea in patients with stable heart failure Wolfram Grimm a,⁎, Olaf Hildebrandt b, Christoph Nell b, Ulrich Koehler b a b
Department of Cardiology, University Hospital of Marburg and Gießen, Philipps-University Marburg, Marburg, Germany Sleep Disorder Unit, Department of Pneumology, University Hospital of Marburg and Gießen, Philipps-University Marburg, Marburg, Germany
a r t i c l e
i n f o
Article history: Received 6 August 2014 Accepted 9 August 2014 Available online 17 August 2014 Keywords: Excessive daytime sleepiness Central sleep apnea Heart failure
Central sleep apnea (CSA) is a highly prevalent but underdiagnosed finding in patients with chronic stable heart failure (HF) due to left ventricular (LV) systolic dysfunction [1]. In contrast to obstructive sleep apnea (OSA), which has been shown to be associated with excessive daytime sleepiness (EDS) in patients with and without left ventricular dysfunction [2], the relationship between EDS and CSA remains controversial [3–8]. We prospectively performed cardiorespiratory polysomnography in 267 patients with stable systolic HF and LV ejection fractions ≤50% by echocardiography. Patients were excluded from this study if they had a history of sleep disordered breathing or predominantly obstructive sleep apnea. The study protocol was reviewed and approved by the ethics committee of the University of Marburg. Written informed consent had been obtained from all study patients. The Epworth Sleepiness Scale (ESS) was used to measure self-reported daytime sleepiness using an ESS cut point ≥11 to define EDS as described previously in detail [9,10]. Polysomnography revealed CSA with an AHI ≥15/h in 122 of 267 HF patients (43%) and no or mild sleep apnea with an AHI b 15/h in the remaining 142 patients (67%) (Tables 1 and 2). EDS was identified in 19 of 122 patients with CSA compared to 17 of 151 patients without CSA (15.6% versus 11.2%, p = 0.23). AHI and ESS did not show a significant correlation (Fig. 1). The remaining findings of polysomnography
⁎ Corresponding author at: Department of Cardiology, Philipps-University Marburg, Baldingerstraße, 35033 Marburg, Germany. Tel.: + 49 6421 586 9748; fax: +49 6421 586 8954. E-mail address: [email protected] (W. Grimm).
http://dx.doi.org/10.1016/j.ijcard.2014.08.069 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
including total sleep time sleep efficiency, and indices of oxygen desaturations also failed to show a significant association to EDS (Table 2). The only clinical variable associated with EDS was NYHA class III with a relative risk of 2.78 (95% CI: 1.30–5.91, p = 0.01) compared to NYHA class I or II (Fig. 2). Our study resulted in 3 clinically important observations: first, only 13% of patients with stable HF report EDS using the Epworth Sleepiness Scale with a cut-point ≥11. Second, EDS in HF patients is not associated with CSA, AHI and any other sleep study parameters. Finally, NYHA functional HF class is the only clinical variable with a significant association to EDS suggesting an important link between self-reported daytime sleepiness and functional HF severity. The median ESS score in our study was 6.0, which is consistent with the results of Riegel et al. [8], who also found a median ESS of 6.0 in 280 HF patients without a significant association between EDS and sleep-disordered breathing during diagnostic sleep studies. The variables associated with EDS in the
Table 1 Presenting characteristics by daytime sleepiness. All patients
ESS b11
ESS ≥11
Patients, n (%) Age, years Men, n (%) Body mass index, kg/m2 Diabetes mellitus, n (%) Chronic kidney disease, n (%) Atrial fibrillation Left bundle branch block LV ejection fraction, % LV end-diastolic diameter, mm Ischemic cardiomyopathy Nonischemic cardiomyopathy Brain natriuretic peptidea
267 (100) 60 ± 14 201 (75) 28 ± 5 75 (28) 84 (32) 70 (26) 50 (19) 34 ± 10 61 ± 9 124 (46) 143 (54) 685 ± 852
231 (87) 60 ± 14 174 (75) 27 ± 5 61 (26) 72 (31) 65 (28) 44 (19) 34 ± 10 61 ± 9 106 (46) 125 (54) 673 ± 821
36 (13) 60 ± 13 27 (75) 29 ± 5 14 (39) 12 (33) 5 (14) 6 (17) 36 ± 12 60 ± 8 18 (50) 18 (50) 754 ± 1028
NYHA heart failure class Class I Class II Class III
39 (15) 99 (37) 129 (48)
37 (16) 90 (39) 104 (45)
2 (6) 9 (25) 25 (69)
0.006
Heart failure medication Digitalis ACE inhibitors or ARBs Diuretics Aldosterone antagonists ß-Blockers
55 (21) 177 (66) 194 (73) 105 (39) 211 (79)
50 (22) 154 (67) 167 (72) 93 (40) 183 (87)
5 (814) 23 (64) 27 (75) 12 (33) 28 (78)
0.284 0.743 0.735 0.429 0.843
a
Available in 251 patients.
P 0.918 0.966 0.118 0.121 0.848 0.101 0.822 0.235 0.550 0.645 0.603
1448
W. Grimm et al. / International Journal of Cardiology 176 (2014) 1447–1448
Table 2 Polysomnography results.
Patients, n (%) Epworth Sleepiness Scale score AHI, n/h AHI b15/h, n (%) AHI ≥15/h, n (%) AHI N30/h, n (%) Central apnea index, n/h Obstructive apnea index, n/h Mixed apnea index, n/h Hypopnea index, n/h Total in bed time, min Total sleep time, min Arousals, n/h Sleep stage 1, % TST Sleep stage 2, % TST Sleep stages 3 and 4, % TST Rapid eye movement, % TST Sleep efficiency, % Sleep latency, min Mean O2-saturation, % O2-saturation b90%, % TST
All patients
ESS b11
ESS ≥11
267 (100) 6.3 ± 3.6 19.1 ± 18.9 151 (57) 116 (43) 67 (25) 14.8 ± 17.4 0.6 ± 1.9 0.9 ± 3.8 2.7 ± 4.9 512 ± 43 304 ± 96 15 ± 9 20 ± 17 47 ± 15 19 ± 13 15 ± 8 60 ± 18 45 ± 51 94.7 ± 3.1 20 ± 33
231 (87) 5.4 ± 2.8 18.4 ± 18.3 134 (58) 97 (42) 57 (25) 14.4 ± 17.2 0.7 ± 1.9 0.7 ± 2.9 2.7 ± 4.9 512 ± 42 305 ± 92 15 ± 9 20 ± 17 47 ± 15 19 ± 11 15 ± 8 60 ± 18 45 ± 50 94.8 ± 3.1 18 ± 31
36 (13) 12.6 ± 1.8 b0.001 23.2 ± 21.6 0.106 17 (47) 0.225 19 (53) 10 (28) 0.426 17.3 ± 18.7 0.361 0.4 ± 1.4 0.512 2.3 ± 7.1 0.207 3.2 ± 4.4 0.498 510 ± 48 0.896 299 ± 118 0.766 15 ± 12 0.788 20 ± 14 0.829 48 ± 14 0.580 17 ± 13 0.343 15 ± 7 0.939 58 ± 21 0.636 43 ± 58 0.844 94.1 ± 3.2 0.235 27 ± 42 0.157
P
study by Riegel et al. [8] included poorer sleep quality, lack of physical activity, not taking a diuretic, and NYHA functional HF class IV. In contrast to Riegel et al. [8], we excluded patients with NYHA class IV heart failure, because our study was designed to evaluate the relation between EDS and CSA in stable chronic HF rather than end-stage heart failure. In addition, Riegel et al. [7] investigated the influence of EDS using an ESS cut-point ≥6 and impaired cognition on health-related quality of life in their cohort of 280 HF patients. As a result, EDS significantly contributed to impaired quality of life in addition to impaired cognition. These findings are not consistent with the results of a study by Carmona-Bernal et al. [3], who found a significantly decreased quality of life in HF patients with versus without CSA using the Minnesota Living with Heart Failure Questionnaire despite similar ESS scores in both patient groups suggesting that elevated ESS scores as a surrogate for EDS do not predict quality of life in HF patients. Redecker et al. [4–6] investigated the association between sleep disordered breathing, insomnia symptoms and daytime sleepiness in 173 patients with chronic stable HF. As a result, Redecker et al. [4] found a high prevalence of 51% of insomnia symptoms including difficulty initiating sleep, maintaining sleep, or waking too early in the morning in their HF population. Consistent with the results of our study, Redecker et al. [4] found a significant association between EDS using an ESS cut-point ≥11 and NYHA functional HF class. In addition, insomnia symptoms were associated with EDS and decrements in functional performance including the sixminute walk test [4]. Insomnia symptoms as well as EDS, however,
Fig. 1. Correlation between apnea–hypopnea index (AHI) and ESS-Score.
Fig. 2. Box plot for ESS scores stratified for NYHA heart failure class.
could not be explained by sleep-disordered breathing [4,5]. In contrast to sleep-disordered breathing, nocturia was associated with EDS in the cohort of 173 HF patients reported by Redeker et al. [6]. The prevalence of EDS was significantly higher in patients with severe nocturia (40%) compared to patients with moderate nocturia (26%) or compared to patients without nocturia (12%). Thus, improving nocturia by optimizing HF therapy may help to improve sleep quality as well as EDS. In conclusion, only a minority of HF patients suffer from EDS, although CSA is common in patients with stable HF. Whereas EDS cannot be predicted by the results of polysomnography in HF patients, EDS is significantly related to NYHA functional class suggesting that improving NYHA class by optimized HF therapy may also improve EDS. Future studies need to clarify whether ventilation therapy for severe CSA will improve EDS. Funding support The work was supported by a research grant from the Resmed GmbH & Co. KG, Martinsried, Germany. Conflict of interest Dr. Koehler received grant support from Astrazeneca, Glaxosmithkline, Berlin-Chemie, IFM, Heinen and Loewenstein, Resmed, Respironics, and UCB Biosciences. The remaining authors have no conflict of interest. References [1] Vazir A, Hastings PC, Dayer M, et al. A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction. Eur J Heart Fail 2007;9:243–50. [2] Roure N, Gomez S, Mediano O, et al. Daytime sleepiness and polysomnography in obstructive sleep apnea patients. Sleep Med 2008;9:727–31. [3] Carmona-Bernal C, Ruiz-García A, Villa-Gil M, et al. Quality of life in patients with congestive heart failure and central sleep apnea. Sleep Med 2008;9:646–51. [4] Redeker NS, Jeon S, Muench U, Campbell D, Walsleben J, Rapoport DM. Insomnia symptoms and daytime function in stable heart failure. Sleep 2010;33:1210–6. [5] Redeker NS, Muench U, Zucker MJ, et al. Sleep disordered breathing, daytime symptoms, and functional performance in stable heart failure. Sleep 2010;33:551–60. [6] Redeker NS, Adams L, Berkowitz R, et al. Nocturia, sleep and daytime function in stable heart failure. J Card Fail 2012;18:569–75. [7] Riegel B, Ratcliffe SJ, Weintraub WS, et al. Double jeopardy: the influence of excessive daytime sleepiness and impaired cognition on health-related quality of life in adults with heart failure. Eur J Heart Fail 2012;14:730–6. [8] Riegel B, Ratcliffe SJ, Sayers SL, et al. Determinants of excessive daytime sleepiness and fatigue in adults with heart failure. Clin Nurs Res 2012;21:271–93. [9] Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:540–5. [10] Johns MW. Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep 1992;15:376–81.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Excessive daytime sleepiness and central sleep apnea in patients with stable heart failure Wolfram Grimm a,⁎, Olaf Hildebrandt b, Christoph Nell b, Ulrich Koehler b a b
Department of Cardiology, University Hospital of Marburg and Gießen, Philipps-University Marburg, Marburg, Germany Sleep Disorder Unit, Department of Pneumology, University Hospital of Marburg and Gießen, Philipps-University Marburg, Marburg, Germany
a r t i c l e
i n f o
Article history: Received 6 August 2014 Accepted 9 August 2014 Available online 17 August 2014 Keywords: Excessive daytime sleepiness Central sleep apnea Heart failure
Central sleep apnea (CSA) is a highly prevalent but underdiagnosed finding in patients with chronic stable heart failure (HF) due to left ventricular (LV) systolic dysfunction [1]. In contrast to obstructive sleep apnea (OSA), which has been shown to be associated with excessive daytime sleepiness (EDS) in patients with and without left ventricular dysfunction [2], the relationship between EDS and CSA remains controversial [3–8]. We prospectively performed cardiorespiratory polysomnography in 267 patients with stable systolic HF and LV ejection fractions ≤50% by echocardiography. Patients were excluded from this study if they had a history of sleep disordered breathing or predominantly obstructive sleep apnea. The study protocol was reviewed and approved by the ethics committee of the University of Marburg. Written informed consent had been obtained from all study patients. The Epworth Sleepiness Scale (ESS) was used to measure self-reported daytime sleepiness using an ESS cut point ≥11 to define EDS as described previously in detail [9,10]. Polysomnography revealed CSA with an AHI ≥15/h in 122 of 267 HF patients (43%) and no or mild sleep apnea with an AHI b 15/h in the remaining 142 patients (67%) (Tables 1 and 2). EDS was identified in 19 of 122 patients with CSA compared to 17 of 151 patients without CSA (15.6% versus 11.2%, p = 0.23). AHI and ESS did not show a significant correlation (Fig. 1). The remaining findings of polysomnography
⁎ Corresponding author at: Department of Cardiology, Philipps-University Marburg, Baldingerstraße, 35033 Marburg, Germany. Tel.: + 49 6421 586 9748; fax: +49 6421 586 8954. E-mail address: [email protected] (W. Grimm).
http://dx.doi.org/10.1016/j.ijcard.2014.08.069 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
including total sleep time sleep efficiency, and indices of oxygen desaturations also failed to show a significant association to EDS (Table 2). The only clinical variable associated with EDS was NYHA class III with a relative risk of 2.78 (95% CI: 1.30–5.91, p = 0.01) compared to NYHA class I or II (Fig. 2). Our study resulted in 3 clinically important observations: first, only 13% of patients with stable HF report EDS using the Epworth Sleepiness Scale with a cut-point ≥11. Second, EDS in HF patients is not associated with CSA, AHI and any other sleep study parameters. Finally, NYHA functional HF class is the only clinical variable with a significant association to EDS suggesting an important link between self-reported daytime sleepiness and functional HF severity. The median ESS score in our study was 6.0, which is consistent with the results of Riegel et al. [8], who also found a median ESS of 6.0 in 280 HF patients without a significant association between EDS and sleep-disordered breathing during diagnostic sleep studies. The variables associated with EDS in the
Table 1 Presenting characteristics by daytime sleepiness. All patients
ESS b11
ESS ≥11
Patients, n (%) Age, years Men, n (%) Body mass index, kg/m2 Diabetes mellitus, n (%) Chronic kidney disease, n (%) Atrial fibrillation Left bundle branch block LV ejection fraction, % LV end-diastolic diameter, mm Ischemic cardiomyopathy Nonischemic cardiomyopathy Brain natriuretic peptidea
267 (100) 60 ± 14 201 (75) 28 ± 5 75 (28) 84 (32) 70 (26) 50 (19) 34 ± 10 61 ± 9 124 (46) 143 (54) 685 ± 852
231 (87) 60 ± 14 174 (75) 27 ± 5 61 (26) 72 (31) 65 (28) 44 (19) 34 ± 10 61 ± 9 106 (46) 125 (54) 673 ± 821
36 (13) 60 ± 13 27 (75) 29 ± 5 14 (39) 12 (33) 5 (14) 6 (17) 36 ± 12 60 ± 8 18 (50) 18 (50) 754 ± 1028
NYHA heart failure class Class I Class II Class III
39 (15) 99 (37) 129 (48)
37 (16) 90 (39) 104 (45)
2 (6) 9 (25) 25 (69)
0.006
Heart failure medication Digitalis ACE inhibitors or ARBs Diuretics Aldosterone antagonists ß-Blockers
55 (21) 177 (66) 194 (73) 105 (39) 211 (79)
50 (22) 154 (67) 167 (72) 93 (40) 183 (87)
5 (814) 23 (64) 27 (75) 12 (33) 28 (78)
0.284 0.743 0.735 0.429 0.843
a
Available in 251 patients.
P 0.918 0.966 0.118 0.121 0.848 0.101 0.822 0.235 0.550 0.645 0.603
1448
W. Grimm et al. / International Journal of Cardiology 176 (2014) 1447–1448
Table 2 Polysomnography results.
Patients, n (%) Epworth Sleepiness Scale score AHI, n/h AHI b15/h, n (%) AHI ≥15/h, n (%) AHI N30/h, n (%) Central apnea index, n/h Obstructive apnea index, n/h Mixed apnea index, n/h Hypopnea index, n/h Total in bed time, min Total sleep time, min Arousals, n/h Sleep stage 1, % TST Sleep stage 2, % TST Sleep stages 3 and 4, % TST Rapid eye movement, % TST Sleep efficiency, % Sleep latency, min Mean O2-saturation, % O2-saturation b90%, % TST
All patients
ESS b11
ESS ≥11
267 (100) 6.3 ± 3.6 19.1 ± 18.9 151 (57) 116 (43) 67 (25) 14.8 ± 17.4 0.6 ± 1.9 0.9 ± 3.8 2.7 ± 4.9 512 ± 43 304 ± 96 15 ± 9 20 ± 17 47 ± 15 19 ± 13 15 ± 8 60 ± 18 45 ± 51 94.7 ± 3.1 20 ± 33
231 (87) 5.4 ± 2.8 18.4 ± 18.3 134 (58) 97 (42) 57 (25) 14.4 ± 17.2 0.7 ± 1.9 0.7 ± 2.9 2.7 ± 4.9 512 ± 42 305 ± 92 15 ± 9 20 ± 17 47 ± 15 19 ± 11 15 ± 8 60 ± 18 45 ± 50 94.8 ± 3.1 18 ± 31
36 (13) 12.6 ± 1.8 b0.001 23.2 ± 21.6 0.106 17 (47) 0.225 19 (53) 10 (28) 0.426 17.3 ± 18.7 0.361 0.4 ± 1.4 0.512 2.3 ± 7.1 0.207 3.2 ± 4.4 0.498 510 ± 48 0.896 299 ± 118 0.766 15 ± 12 0.788 20 ± 14 0.829 48 ± 14 0.580 17 ± 13 0.343 15 ± 7 0.939 58 ± 21 0.636 43 ± 58 0.844 94.1 ± 3.2 0.235 27 ± 42 0.157
P
study by Riegel et al. [8] included poorer sleep quality, lack of physical activity, not taking a diuretic, and NYHA functional HF class IV. In contrast to Riegel et al. [8], we excluded patients with NYHA class IV heart failure, because our study was designed to evaluate the relation between EDS and CSA in stable chronic HF rather than end-stage heart failure. In addition, Riegel et al. [7] investigated the influence of EDS using an ESS cut-point ≥6 and impaired cognition on health-related quality of life in their cohort of 280 HF patients. As a result, EDS significantly contributed to impaired quality of life in addition to impaired cognition. These findings are not consistent with the results of a study by Carmona-Bernal et al. [3], who found a significantly decreased quality of life in HF patients with versus without CSA using the Minnesota Living with Heart Failure Questionnaire despite similar ESS scores in both patient groups suggesting that elevated ESS scores as a surrogate for EDS do not predict quality of life in HF patients. Redecker et al. [4–6] investigated the association between sleep disordered breathing, insomnia symptoms and daytime sleepiness in 173 patients with chronic stable HF. As a result, Redecker et al. [4] found a high prevalence of 51% of insomnia symptoms including difficulty initiating sleep, maintaining sleep, or waking too early in the morning in their HF population. Consistent with the results of our study, Redecker et al. [4] found a significant association between EDS using an ESS cut-point ≥11 and NYHA functional HF class. In addition, insomnia symptoms were associated with EDS and decrements in functional performance including the sixminute walk test [4]. Insomnia symptoms as well as EDS, however,
Fig. 1. Correlation between apnea–hypopnea index (AHI) and ESS-Score.
Fig. 2. Box plot for ESS scores stratified for NYHA heart failure class.
could not be explained by sleep-disordered breathing [4,5]. In contrast to sleep-disordered breathing, nocturia was associated with EDS in the cohort of 173 HF patients reported by Redeker et al. [6]. The prevalence of EDS was significantly higher in patients with severe nocturia (40%) compared to patients with moderate nocturia (26%) or compared to patients without nocturia (12%). Thus, improving nocturia by optimizing HF therapy may help to improve sleep quality as well as EDS. In conclusion, only a minority of HF patients suffer from EDS, although CSA is common in patients with stable HF. Whereas EDS cannot be predicted by the results of polysomnography in HF patients, EDS is significantly related to NYHA functional class suggesting that improving NYHA class by optimized HF therapy may also improve EDS. Future studies need to clarify whether ventilation therapy for severe CSA will improve EDS. Funding support The work was supported by a research grant from the Resmed GmbH & Co. KG, Martinsried, Germany. Conflict of interest Dr. Koehler received grant support from Astrazeneca, Glaxosmithkline, Berlin-Chemie, IFM, Heinen and Loewenstein, Resmed, Respironics, and UCB Biosciences. The remaining authors have no conflict of interest. References [1] Vazir A, Hastings PC, Dayer M, et al. A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction. Eur J Heart Fail 2007;9:243–50. [2] Roure N, Gomez S, Mediano O, et al. Daytime sleepiness and polysomnography in obstructive sleep apnea patients. Sleep Med 2008;9:727–31. [3] Carmona-Bernal C, Ruiz-García A, Villa-Gil M, et al. Quality of life in patients with congestive heart failure and central sleep apnea. Sleep Med 2008;9:646–51. [4] Redeker NS, Jeon S, Muench U, Campbell D, Walsleben J, Rapoport DM. Insomnia symptoms and daytime function in stable heart failure. Sleep 2010;33:1210–6. [5] Redeker NS, Muench U, Zucker MJ, et al. Sleep disordered breathing, daytime symptoms, and functional performance in stable heart failure. Sleep 2010;33:551–60. [6] Redeker NS, Adams L, Berkowitz R, et al. Nocturia, sleep and daytime function in stable heart failure. J Card Fail 2012;18:569–75. [7] Riegel B, Ratcliffe SJ, Weintraub WS, et al. Double jeopardy: the influence of excessive daytime sleepiness and impaired cognition on health-related quality of life in adults with heart failure. Eur J Heart Fail 2012;14:730–6. [8] Riegel B, Ratcliffe SJ, Sayers SL, et al. Determinants of excessive daytime sleepiness and fatigue in adults with heart failure. Clin Nurs Res 2012;21:271–93. [9] Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:540–5. [10] Johns MW. Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep 1992;15:376–81.
