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5 2011
ABSTRACT
Background: Sleep-disordered breathing (SDB) is common in patients with reduced ejection fraction
(EF). However, little is known about the prevalence of SDB in a general heart failure population including
patients with preserved EF (HFPEF).
Methods: We prospectively enrolled stable heart failure outpatients from our heart failure clinic to assess
the prevalence of SDB independent of systolic left ventricular function.
Results: Among 115 patients (62% with reduced EF, 38% with preserved EF, New York Heart Association Class II-IV) SDB was present in 81% (27% central sleep apnea, 54% obstructive sleep apnea
[OSA]). HFPEF patients had SDB in 80% of the cases, 62% had OSA. This group had significantly
more hypertension.
Conclusions: This study shows a high prevalence of SDB in a general heart failure population, also in
patients with HFPEF. These patients have predominantly OSA. Especially in patients with HFPEF
SDB should be kept in mind and referral to a sleep specialist should be considered. (J Cardiac Fail
2011;17:420e425)
Key Words: Sleep-disordered breathing, obstructive sleep apnea, preserved ejection fraction.
Chronic heart failure (HF) represents a common and serious health problem. Incidence and prevalence are on the
rise.1 Patients with clinical symptoms of HF are a heterogeneous group. Approximately 40% have HF with preserved
ejection fraction (HFPEF), increasing with age.2 The prognosis for chronic HF continues to be serious with a 1-year
mortality rate of 30%.3 Survival rates of HFPEF patients
seems to be better than in patients with reduced ejection
fraction (EF), but are still high with a mortality rate of
more than 30% within 4 years.4
Selection of Population
Patients were consecutively enrolled from the outpatient HF
clinic of Lovisenberg Diakonale Sykehus in a time period between
June 2006 and December 2008. The diagnosis of HF was defined
by clinical signs and symptoms, measurement of NT-proBNP, and
assessment of left ventricular function according to the American
College of Cardiology/American Heart Association and European
Society of Cardiology guidelines.11,12 Subjects were included if
they had clinically stable HF and their medication fully uptitrated
as recommended in the HF guidelines.11,12 Further inclusion criteria were: New York Heart Association (NYHA) functional Class
420
Herrscher et al
421
Statistics
Statistical analyses were performed using SPSS (version 17.0)
software (SPSS Inc. Chicago, IL). Differences between groups
were assessed using the unpaired Students t-test for parametric results and the Mann-Whitney rank sum test for nonparametric data.
Chi-square test was used to compare proportions between groups.
A value of P ! .05 was considered statistically significant.
Results
Evaluated Parameters
Comorbidity data, NYHA functional class, current medication,
body mass index (BMI), age, sex, and etiology of HF, as registered
in our HF database, were used for statistical analysis. All patients
had 2-dimensional echocardiographic assessment of left ventricular EF. EF was determined by using the apical four chamber view,
Simpsons method. Parasternal M-mode and Doppler recordings
were done to complete the echocardiographic examination. The
latest EF measurement after uptitration of HF medication was
used for study purpose. The mean time interval from echo to sleep
study was 3 to 4 months. Patients with EF $45% were considered
to be in the HFPEF group. Parameters of diastolic function were
not available on all patients.
Subjects were assessed with 2 questionnaires the same day the
sleep study was performed: The Epworth Sleepiness Scale (ESS)
and The Minnesota Living with Heart Failure Questionnaire
(MLHFQ).
Blood samples were obtained the morning after the sleep study.
Subjects were fasting for at least 8 hours.
Patient Characteristics
A total of 115 patients (24 females, 91 males) were enrolled into the study; 120 patients met the inclusion criteria
and 5 subjects refused to participate because of reasons of
inconvenience. Sixty-two percent of our population had reduced EF, 38% were patients with HFPEF. The baseline
characteristics between these 2 groups were significantly
different in etiology of HF and NYHA class. Patients
with reduced EF had a higher N-terminal prohormone brain
natriuretic peptide (NT-proBNP) and used more bblockers, angiotensin-converting enzyme (ACE) inhibitors
or angiotensin receptor blockers (ARBs), diuretics, and
aldosterone-antagonists. Patients with HFPEF had significantly more hypertension. There were no significant differences in sex, age, BMI, quality of life, or sleepiness
(Table 1).
SDB
Cardiorespiratory Polygraphy
Subjects underwent an in-home, unattended overnight polygraphy with a standard 10-channel recording device (Embletta, ResMed, Norway). Nasal air flow (nasal pressure transducer),
thoracic and abdominal movements (respiratory inductance plethysmography), pulse oximetry, body position, and a 3-channel electrocardiogram were recorded continuously. Data were downloaded
and scored at the sleep laboratory, Lovisenberg by 1 single qualified SDB specialist, using Somnologica for Embletta software
(Medcare, Embla, the Netherlands).
A modified version of the 2007 American Academy of Sleep
Medicine criteria for scoring respiratory events was used.13 Obstructive apnea was defined as a $10 seconds cessation of airflow
as measured by nasal pressure associated with the continuation of
thoracic and abdominal effort. Central apnea was defined as $10
seconds cessation of airflow without thoracic and abdominal effort. Hypopnea was defined as a 50% reduction in airflow with either a $3% oxyhemoglobin desaturation or a presumed arousal, as
defined by 10% increase in heart rate. The apnea-hypopnea index
(AHI) was calculated based on total number of events per hour of
total recording time, movement time omitted. SDB was defined as
mild by AHI O5, moderate by AHI $15, and severe by AHI $30.
Another metric of central sleep apnea was also used to define primary Cheyne-Stokes respiration. This is defined as a symmetrical
crescendo-decrescendo respiratory pattern with a O50% difference between peak and nadir nasal pressure or respiratory effort
amplitude, occurring within a 30 to 90-second period. There had
to be at least 3 cycles of Cheyne-Stokes respiratory pattern in
a row and with duration of at least 10 consecutive minutes. Patients with both obstructive and central apneas were classified according to the dominating respiratory sleep pattern.
Patients with HFPEF had nearly the same high prevalence of sleep apnea as the group with reduced EF (80%
vs. 82%), Figure 2. This group had more OSA than CSA,
62% vs. 18%. Subjects with HFPEF and OSA had a higher
BMI (32.0 6 5.8 vs. 27.9 6 4.1, P 5 .02) and more likely
hypertension (74% vs. 35%, P 5 .01) compared with patients with HFPEF without OSA.
Discussion
SDB
This study shows a high prevalence of SDB in a general outpatient HF population treated in a Norwegian
Age (y)
Sex female/male
BMI (kg/m2)
LVEF (%)
NT-proBNP (pg/mL)
Hemoglobin (mg/dL)
HbA1c (%)
Creatinine (mg/dL)
Cholesterol (mg/dL)
NYHA, n (%)
Class II
Class III IV
CRT
MLHFQ
Epworth SS
Etiology
Ischemic
Nonischemic
b-blockers
ACE inhibitor/ARBs
Diuretics
Spironolactone
Digitoxin
Comorbidity
Hypertension
Atrial fibrillation
Diabetes
Stroke
COPD
Total (n 5 115)
Reduced EF (n 5 71)
HFPEF (n 5 44)
62.0 6 9.7
24/91
29.1 6 5.5
38.1 6 13.0
1615 6 2173
14.2 6 1.4
6.2 6 1.1
1.1 6 0.4
174 6 50
61.4 6 9.5
11/60
28.4 6 5.3
29.6 6 8.2
2216 6 2478
14.3 6 1.4
6.4 6 1.4
1.1 6 0.4
170 6 50
62.8 6 10.0
13/31
30.4 6 5.5
51.7 6 5.2*
507 6 474*
14.1 6 1.5
6.0 6 0.8
1.1 6 0.4
182 6 50
89 (77%)
26 (23%)
3 (2%)
42 6 26
5.8 6 4.0
47 (66%)
24 (24%)
3 (4%)
44 6 27
5.6 6 4.0
42 (95%)*
2 (5%)*
0
39 6 24
6.1 6 4.1
63
52
104
106
90
15
15
(55%)
(45%)
(90%)
(92%)
(78%)
(13%)
(13%)
52
19
68
69
61
13
11
(73%)
(27%)
(96%)
(97%)
(86%)
(18%)
(16%)
11
33
35
37
29
2
8
(25%)*
(75%)*
(80%)*
(84%)*
(66%)*
(5%)*
(18%)
47
44
28
12
20
(41%)
(38%)
(24%)
(10%)
(17%)
21
23
17
7
12
(30%)
(32%)
(24%)
(9%)
(17%)
26
21
11
5
8
(59%)*
(48%)
(25%)
(11%)
(18%)
ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; BMI, body mass index; COPD, chronic obstructive lung disease; CRT, cardiac
resynchronization therapy; EF, ejection fraction; Epworth SS, Epworth sleepiness scale; HFPEF, heart failure with preserved ejection fraction; LVEF, left
ventricular ejection fraction; MLHFQ, Minnesota living with heart failure questionnaire; NT-proBNP, N-terminal prohormone brain natriuretic peptide;
NYHA, New York heart association.
Data presented as mean 6 standard deviation or percentage.
*P ! .05, reduced EF vs. HFPEF.
heart failure clinic. Our patients were referred either directly by their primary physicians or by the medical department at the local hospital, reducing the possible
patient selection bias seen at tertiary academic centers.
Despite this, our data are consistent with the large scale
studies of Oldenburg and Bitter et al.6,9 That there
were more males than females can be explained by
27 %
60 %
CSA
50 %
OSA
23 %
40 %
30 %
54 %
20 %
29 %
10 %
0%
AHI > 5
AHI >= 15
Fig. 1. Prevalence of sleep-disordered breathing in a stable heart failure population independent of left ventricular ejection fraction. AHI,
apnea-hypopnea index; OSA, obstructive sleep apnea.
Herrscher et al
423
Table 2. Clinical Characteristics of Subjects With SDB versus Those Without SDB
Age (y)
Sex (female/male)
BMI (kg/m2)
AHI (events/h)
ODI (events/h)
Mean O2 (%)
Lowest O2 (%)
LVEF (%)
CRT
NT-proBNP (pg/mL)
Hemoglobin (mg/dL)
HbA1c (%)
Creatinine (mg/dL)
Cholesterol (mg/dL)
NYHA, n
Class II
Class III IV
MLHFQ
Epworth SS
Etiology
Ischemic
Nonischemic
b-blockers
ACE inhibitor/ARBs
Diuretics
Spironolactone
Digitoxin
Comorbidity
Hypertension
Atrial fibrillation
Diabetes
Stroke
COPD
OSA (n 5 62)
CSA (n 5 31)
No SDB (n 5 22)
62.4 6 9.2
15/47
30.2 6 6.0*
25.0 6 21.7*
26.6 6 22.3*
92.5 6 2.8*
78.0 6 7.3*
40.4 6 13.2y
3 (4%)
1294 6 1945
14.1 6 1.5
6.3 6 1.1*
1.0 6 0.3y
178 6 43
62.2 6 10.6
3/28
28.4 6 4.2
26.8 6 13.1*
27.8 6 14.2*
93.5 6 1.7*
81.6 6 6.7*
34.0 6 12.5
0
2181 6 2326
14.7 6 1.4*
6.6 6 1.3*
1.2 6 0.4
170 6 62
60.2 6 10.0
6/16
27.1 6 4.8
2.3 6 1.5
4.6 6 4.4
94.5 6 1.8
87.4 6 3.0
37.3 6 12.0
0
1691 6 2453
13.8 6 1.3
5.9 6 0.3
1.2 6 0.5
170 6 54
46 (74%)
16 (26%)
40.4 6 27.4
5.9 6 4.3
23 (74%)
8 (26%)
44.3 6 24.1
6.2 6 3.9
20 (91%)
2 (9%)
44.1 6 25.8
5.0 6 3.2
32
30
56
56
47
7
13
(52%)
(48%)
(90%)
(90%)
(76%)
(11%)
(21%)
19
12
26
28
27
4
3
(61%)
(39%)
(84%)
(90%)
(87%)
(13%)
(10%)
12
10
21
22
16
4
3
(55%)
(45%)
(96%)
(100%)
(73%)
(18%)
(14%)
33
24
15
5
10
(53%)*,y
(39%)
(24%)
(8%)
(16%)*
8
13
8
3
1
(26%)
(42%)
(26%)
(10%)
(3%)*
6
7
5
3
9
(27%)
(32%)
(23%)
(14%)
(41%)
ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; AHI, apnea hypopnea index; BMI, body mass index; COPD, chronic obstructive lung disease; CRT, cardiac resynchronization therapy; CSA, central sleep apnea; Epworth SS, Epworth sleepiness scale; LVEF, left ventricular ejection
fraction; MLHFQ, Minnesota living with Heart Failure Questionnaire; NT-proBNP, N-terminal prohormone brain natriuretic peptide; NYHA, New York heart
association; ODI, oxygen desaturation index; SDB, sleep-disordered breathing.
Data presented as mean 6 standard deviation or percentage.
*P ! .05, OSA/CSA vs. no SDB.
y
P ! .05, OSA vs. CSA.
a clinically stable condition, supported by low average NTproBNP levels. Acute heart failure decompensation was
one of the exclusion criteria. Despite these facts, we still
70 %
32 %
60 %
CSA
50 %
OSA
40 %
62 %
30 %
20 %
49 %
10 %
0%
red EF
HFPEF
Fig. 2. Sleep-disordered breathing in patients with reduced and preserved ejection fraction. AHI, apnea-hypopnea index; EF, ejection fraction; HFPEF, heart failure with preserved EF; OSA, obstructive sleep apnea.
In contrast to HF patients with reduced systolic function, sleep data are rare in patients with HFPEF. A prevalence of SDB of 80% in patients with HFPEF in our
study is high and equal to the patients with reduced systolic function. Our findings are in accordance with the results of Bitter al, who in the first large scale prevalence
study in 244 patients with HFPEF observed a prevalence
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