Download Severe Obstructive Sleep Apnea Is Associated With Left Ventricular

Severe Obstructive Sleep Apnea Is
Associated With Left Ventricular
Diastolic Dysfunction*
Jeffrey W. H. Fung, MBChB; Thomas S. T. Li, MBChB;
Dominic K. L. Choy, MBBS; Gabriel W. K. Yip, MBChB;
Fanny W. S. Ko, MBChB; John E. Sanderson, MD; and
David S. C. Hui, MBBS, FCCP
Introduction: Hypertension is common in patients with obstructive sleep apnea (OSA). However, the
effect of OSA on ventricular function, especially diastolic function, is not clear. Therefore, we have
assessed the prevalence of diastolic dysfunction in patients with OSA and the relationship between
diastolic parameters and severity of OSA.
Methods: Sixty-eight consecutive patients with OSA confirmed by polysomnography underwent
echocardiography. Diastolic function of the left ventricle was determined by transmitral valve
pulse-wave Doppler echocardiography. Various baseline characteristics, severity of OSA, and echocardiographic parameters were compared between patients with and without diastolic dysfunction.
Results: There were 61 male and 7 female patients with a mean age of 48.1 ⴞ 11.1 years, body mass index
of 28.5 ⴞ 4.3 kg/m2, and apnea/hypopnea index (AHI) of 44.3 ⴞ 23.2/h (mean ⴞ SD). An abnormal
relaxation pattern (ARP) in diastole was noted in 25 patients (36.8%). Older age (52.7 ⴞ 8.9 years vs
45.1 ⴞ 11.3 years, p ⴝ 0.005), hypertension (56% vs 20%, p ⴝ 0.002), and a lower minimum pulse oximetric
saturation (SpO2) during sleep (70.5 ⴞ 17.9% vs 78.8 ⴞ 12.9%, respectively; p ⴝ 0.049) were more common
in patients with ARP. By multivariate analysis, minimum SpO2 < 70% was an independent predictor of ARP
(odds ratio, 4.34; 95% confidence interval, 1.23 to 15.25; p ⴝ 0.02) irrespective of age and hypertension.
Patients with AHI > 40/h had significantly longer isovolumic relaxation times than those with AHI < 40/h
(106 ⴞ 19 ms vs 93 ⴞ 17 ms, respectively; p ⴝ 0.005).
Conclusion: Diastolic dysfunction with ARP was common in patients with OSA. More severe sleep apnea
was associated with a higher degree of left ventricular diastolic dysfunction in this study.
(CHEST 2002; 121:422– 429)
Key words: diastolic dysfunction; echocardiography; obstructive sleep apnea
Abbreviations: A ⫽ late peak atrial systolic velocity; AHI ⫽ apnea/hypopnea index; ARd ⫽ duration of pulmonary-atrial
reversal signal; ARP ⫽ abnormal relaxation pattern; BMI ⫽ body mass index; CHF ⫽ congestive heart failure;
CI ⫽ confidence interval; CPAP ⫽ continuous positive airway pressure; CSR-CSA ⫽ Cheyne-Stokes respiration with central
sleep apnea; D ⫽ peak diastolic flow velocity in the pulmonary vein; DHF ⫽ diastolic heart failure; DT ⫽ deceleration time;
E ⫽ early peak transmitral flow velocity; E/A ratio ⫽ ratio between the early peak transmitral flow velocity and the late peak
atrial systolic velocity; ESS ⫽ Epworth Sleepiness Scale; IVRT ⫽ isovolumic relaxation time; LV ⫽ left ventricular;
LVEF ⫽ left ventricular ejection fraction; LVH ⫽ left ventricular hypertraophy; LVM ⫽ left ventricular mass; LVMI ⫽ left
ventricular mass index; OR ⫽ odds ratio; OSA ⫽ obstructive sleep apnea; S ⫽ peak systolic flow velocity in the pulmonary
vein; SDB ⫽ sleep-disordered breathing; Spo2 ⫽ pulse oximetric saturation
bstructive sleep apnea (OSA) syndrome is a
O common
disorder affecting 2 to 4% of middle*From the Divisions of Cardiology (Drs. Fung, Yip, and Sanderson) and Respiratory Medicine (Drs. Li, Choy, Ko, and Hui),
Department of Medicine and Therapeutics, Chinese University
of Hong Kong, Prince of Wales Hospital, Shatin, New Territories,
Hong Kong.
Supported by Chinese University of Hong Kong direct grant (ref.
2040898).
Manuscript received February 26, 2001; revision accepted August 15, 2001.
Correspondence to: David S. C. Hui, MBBS, FCCP, Department
of Medicine and Therapeutics, Chinese University of Hong Kong,
Prince of Wales Hospital, Shatin, New Territories, Hong Kong;
e-mail: [email protected]
aged adults.1,2 Excessive daytime sleepiness is a
major consequence of OSA, due to sleep fragmentation triggered by repetitive episodes of partial or
complete upper-airway obstruction.3
In a retrospective study by He et al,4 patients with
OSA with an apnea index ⬎ 20/h had a higher
morbidity and mortality rates related to vascular
events than patients with an apnea index ⬍ 20/h.
There is growing evidence that patients with OSA
have an increased risk of having cardiovascular complications, such as hypertension, cardiac arrhythmia,5
myocardial infarction,6 pulmonary hypertension,7
and stroke.8 Several epidemiologic studies9 –13 have
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shown an independent association between sleepdisordered breathing (SDB) and hypertension after
controlling for confounding factors such as age, body
mass index (BMI), sex, alcohol, and smoking. A
recent case control study14 has also shown that
patients with OSA have increased ambulatory diastolic BP both day and night and increased systolic
BP at night.
In a study of 200 consecutive Hong Kong Chinese
patients presenting clinically with congestive heart failure (CHF), Yip et al15 showed that diastolic heart
failure (DHF) is more common than systolic heart
failure, with 66% of these patients having a normal left
ventricular (LV) ejection fraction (LVEF). Chan et al16
performed sleep studies on 20 Chinese patients with
symptomatic DHF and found 55% of patients to have
significant SDB of the obstructive type with an apnea/
hypopnea index (AHI) ⬎ 10/h. Patients with DHF and
SDB may be associated with worse diastolic dysfunction than those without SDB. Nevertheless, the relationship between diastolic dysfunction and OSA is not
clear. This study investigates the prevalence of diastolic
dysfunction in patients with newly diagnosed OSA and
assesses whether there is any correlation between the
severity of OSA and the degree of diastolic dysfunction.
Materials and Methods
Patients
We recruited 68 consecutive patients with newly diagnosed
OSA from our sleep unit at the Prince of Wales Hospital for this
study.
Sleep Study
Significant OSA was defined as an AHI ⱖ 5 events per hour of
sleep as shown by overnight polysomnography (Alice 4; Healthdyne; Atlanta, GA) plus self-reported sleepiness. Subjective
sleepiness was evaluated by the Epworth sleepiness scale
(ESS),17,18 a questionnaire specific to symptoms of daytime
sleepiness, and the subjects were asked to score the likelihood of
falling asleep in eight different situations with different levels of
stimulation, adding up to a total score of 0 to 24.
Overnight polysomnography recorded EEG, electro-oculogram, submental electromyogram, bilateral anterior tibial electromyogram, ECG, chest and abdominal wall movement by
inductance plethysmography, airflow by a nasal pressure transducer (PTAF; Pro-Tech; Woodinville, WA) and backed up by
oronasal airflow measured with a thermistor and finger pulse
oximetry as in our previous study.19 Sleep stages were scored
according to standard criteria by Rechtshaffen and Kales.20
Apnea was defined as cessation of airflow for ⬎ 10 s, and
hypopnea was defined as a reduction of airflow ⱖ 50% for 10 s
plus an oxygen desaturation of ⬎ 4% or an arousal.
Hypertension was defined if patients were receiving antihypertensive medications without regard to the actual measurement of
BP, or having a systolic BP ⬎ 140 mm Hg or a diastolic BP ⬎ 90
mm Hg9,11 on awakening following completion of polysomnography. Patients received their usual cardiac medications, includ-
ing antihypertensive agents. Exclusion criteria included malignant hypertension, unstable angina, renal failure, recent
myocardial infarction, and significant valvular heart disease.
Echocardiography
Following confirmation of significant OSA by polysomnography, echocardiography (System FIVE; GE Vingmed; Horten,
Norway) was performed to assess the LV size with systolic
function assessed by fractional shortening obtained from Mmode recordings of LV systolic and diastolic dimensions,21 as well
as by the LVEF estimated from the two-dimensional Simpson’s
method.22 An LVEF ⬎ 50% was regarded as normal. LV diastolic
dysfunction was assessed principally by Doppler echocardiography for patients with significant OSA, and normal LV systolic
function was assessed as previously described.23 The pulse-wave
Doppler echocardiographic sample volume was placed at the
mitral valve leaflet in the apical four-chamber view. The diastolic
parameters were measured from at least three beats and were
defined as follows: E-wave, early maximal transmitral flow velocity; A-wave, peak velocity during atrial contraction in late diastole; and ratio between the early peak transmitral flow velocity
(E) and late peak atrial systolic velocity (A) [E/A ratio], expressed
in terms of peak velocities; and deceleration time (DT), calculated and expressed as the time for the peak filling velocity
(E-wave) to fall to zero. Pulse-wave Doppler echocardiographic
sample volume was then placed at the inflow area to measure the
isovolumic relaxation time (IVRT), the time from aortic valve
closure to the onset of mitral valve inflow. The pulse-wave
Doppler echocardiographic sample volume was then placed
inside the pulmonary vein in the apical four-chamber view. The
pulmonary venous flow parameters were defined as follows:
S-wave, peak systolic flow velocity in the pulmonary vein (S);
D-wave, peak diastolic flow velocity in the pulmonary vein (D);
and duration of pulmonary-atrial reversal signal (ARd). Diastolic
function of the left ventricle was divided into four patterns:
normal, abnormal relaxation pattern (ARP), pseudonormal pattern, and restrictive filling pattern depending on the abovementioned transmitral and pulmonary venous parameters and
IVRT. A schematic drawing for the various diastolic dysfunction
patterns is shown in Figure 1. Left ventricular mass (LVM) was
estimated by M-mode echocardiography. LVM index (LVMI,
grams per meters squared) was calculated from LVM corrected
by body surface area.
Statistical Analysis
All data were presented as mean ⫾ SD unless otherwise stated.
Comparisons between patients with and without diastolic dysfunction in relation to age, sex, cardiovascular risk factors,
echocardiographic parameters, and severity of OSA were performed by ␹2 and unpaired t tests. For qualitative data, Fisher’s
Exact Test was used when expected p value was ⬍ 5. A p value
of ⬍ 0.05 was used to indicate differences between the groups
that were statistically significant. Data analysis was performed
with a commercially available statistical analysis software package
(SPSS 10.0 for Windows; SPSS; Chicago, IL).
Results
There were 61 male and 7 female consecutive
patients with significant OSA. Mean age was
48.1 ⫾ 11.1 years; mean BMI was 28.5 ⫾ 4.3 kg/m2.
Thirty-two patients (47%) had hypertension, but
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Figure 1. Schematic drawing illustrating the four transmitral and pulmonary venous flow patterns for
LV diastolic function. The upper tracing in each panel illustrates transmitral flow, while lower tracing
illustrates pulmonary flow. Left upper panel: normal transmitral flow pattern: E/A ratio ⬎ 1; DT, 180
to 240 ms; and IVRT, 70 to 110 ms. Normal pulmonary flow pattern: S/D ratio ⬎ 1; pulmonary atrial
reversal (AR) velocity ⬍ 25 cm/s; and duration (d) of mitral A-wave/ARd ⬎ 1. Right upper panel:
abnormal relaxation transmitral flow pattern: E/A ratio ⬍ 1; DT ⬎ 240 ms; and IVRT ⬎ 110 ms.
Abnormal relaxation pulmonary flow pattern: S/D ratio ⬎ 1, AR velocity ⬍ 25 cm/s, and duration of
mitral A-wave/ARd ⬎ 1. Left lower panel: pseudonormalized transmitral flow pattern: E/A ratio ⬍ 1;
DT, 180 to 240 ms; and IVRT, 70 to 110 ms. Pseudonormalized pulmonary flow pattern: S/D ratio ⬍ 1;
AR velocity ⬍ 25 cm/s; and duration of mitral A-wave/ARd ⬍ 1. Right lower panel: restrictive
transmitral flow pattern: E/A ratio ⬎ 1; DT ⬍ 180 ms; and IVRT ⬍ 70 ms. Restrictive pulmonary flow
pattern: S/D ratio ⬍ 1; AR velocity ⬍ 25 cm/s; and duration of mitral A-wave/ARd⬍ 1.
none had a clinical history of heart failure. Mean
ESS score was 12.9 ⫾ 6.0. From the polysomnography, the total sleep time was 6.6 ⫾ 1.2 h, arousal
index was 24.2 ⫾ 12.5/h, AHI was 44.4 ⫾ 23.2/h,
minimum pulse oximetric saturation (Spo2) was
75.8 ⫾ 15.3%, and mean Spo2 was 89.2 ⫾ 3.9%.
From the echocardiography assessment, ARP was
the only diastolic dysfunction pattern detected in our
OSA patient cohort and was noted in 25 patients
(36.8%; 1 female patient). Representative Doppler
echocardiographic flow signals of the normal vs ARP
patterns are shown in Figure 2. Baseline characteristics of patients with normal diastolic function vs
those with ARP diastolic dysfunction are shown in
Table 1. OSA patients with ARP diastolic dysfunc-
tion were older and had a higher prevalence of
hypertension than those with normal diastolic
function.
Polysomnographic and echocardiographic data in
patients with normal diastolic vs those with ARP
diastolic dysfunction are shown in Table 2. Diastolic
dysfunction with ARP was found to be related only to
the minimum Spo2. AHI and mean Spo2 did not
correlate with ARP diastolic dysfunction, while there
was no significant difference between the two groups
in other polysomnographic data. Both groups had
comparable and normal LVEF. By multivariate analysis, minimum Spo2 ⬍ 70% during sleep (odds ratio
[OR], 4.34; 95% confidence interval [CI], 1.23 to
15.25; p ⫽ 0.02), hypertension (OR, 4.05; 95% CI,
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Clinical Investigations
Figure 2. Top: Doppler echocardiographic tracings illustrating normal LV diastolic function (left,
transmitral pulse-wave tracing; right, pulmonary venous pulse-wave tracing). Bottom: Doppler
echocardiographic ARP of LV diastolic dysfunction (left, transmitral pulse-wave tracing; right,
pulmonary venous pulse-wave tracing). V ⫽ position of transducer.
Table 1—Comparison of Baseline Characteristics of
OSA Patients With and Without Diastolic Dysfunction
of ARP*
Table 2—Comparison of Polysomnographic and
Echocardiographic Data in OSA Patients With Normal
and ARP Diastolic Dysfunction
Characteristics
ARP
Normal
p Value
Variables
ARP
Normal
p Value
Male/female patients,
No.
Age, yr
Systolic BP, mm Hg†
Diastolic BP, mm Hg†
BMI, kg/m2
Hypertension
Cerebrovascular
accident
Ischemic heart disease
Diabetes mellitus
24/1
37/6
0.248
53.2 ⫾ 8.7
142.5 ⫾ 16.9
84.4 ⫾ 13.8
29.1 ⫾ 4.8
18 (72.0)
2 (8.0)
45.1 ⫾ 11.3
137.1 ⫾ 18.8
80.6 ⫾ 11.0
28.2 ⫾ 4.1
14 (32.6)
2 (4.7)
0.003‡
0.305
0.288
0.448
0.002‡
0.621
Patients, No.
ESS
Total sleep time, h
Sleep efficiency, %
Arousal index, No./h
AHI
Minimum Spo2, %†
Mean Spo2, %
LVEF, %
E/A ratio
DT, ms
IVRT, ms
25
12.8 ⫾ 6.5
6.4 ⫾ 1.0
62.7 ⫾ 11.0
24.9 ⫾ 12.6
46.2 ⫾ 24.8
70.5 ⫾ 17.9
88.4 ⫾ 4.0
66.6 ⫾ 10.6
0.75 ⫾ 0.12
262.8 ⫾ 64.6
102.2 ⫾ 24.9
43
12.9 ⫾ 5.8
6.7 ⫾ 1.3
87.1 ⫾ 6.9
23.9 ⫾ 12.7
43.3 ⫾ 22.4
78.8 ⫾ 12.9
89.7 ⫾ 3.8
68.2 ⫾ 9.5
1.18 ⫾ 0.25
224.8 ⫾ 60.0
100.0 ⫾ 15.3
0.932
0.411
0.076
0.751
0.634
0.049‡
0.228
0.526
⬍ 0.001‡
0.017‡
0.674
6 (24.0)
7 (28.0)
5 (11.6)
4 (9.3)
0.305
0.084
*Data are presented as mean ⫾ SD or No. (%) unless otherwise
indicated.
†Measured on completion of sleep study.
‡Of statistical significance.
*Data are presented as mean ⫾ SD unless otherwise indicated.
†During sleep.
‡Of statistical significance.
1.20 to 13.68; p ⫽ 0.02), and age ⬎ 55 years (OR,
5.17; 95% CI, 1.39 to 19.28; p ⫽ 0.01) were independent predictors of ARP diastolic dysfunction.
To assess any relationship between severity of
OSA and diastolic parameters, patients were classified into two groups according to the AHI. Patients
with more severe OSA (AHI ⱖ 40/h) had a longer
IVRT than patients with AHI ⬍ 40/h. There were 18
patients and 14 patients with hypertension in the two
groups, respectively (p ⫽ 0.77). There was no significant difference in E, A, E/A ratio, and DT between
these two groups, as shown in Table 3.
The relationship between diastolic parameters,
diastolic BP, mean BP, minimum Spo2 during sleep,
and AHI vs LVMI was analyzed by the Pearson
correlation. LVMI had a significant negative correCHEST / 121 / 2 / FEBRUARY, 2002
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Table 3—Diastolic Parameters Between Two Groups of
OSA Patients With AHI > 40/h vs AHI < 40/h*
Parameters
AHI ⱖ 40/h
(n ⫽ 39)
AHI ⬍ 40/h
(n ⫽ 29)
p Value
E, m/s
A, m/s
E/A ratio
DT, ms
IVRT, ms
0.68 ⫾ 0.12
0.70 ⫾ 0.12
0.98 ⫾ 0.22
248.7 ⫾ 61.6
106.4 ⫾ 19.1
0.72 ⫾ 0.17
0.70 ⫾ 0.27
1.06 ⫾ 0.39
225.4 ⫾ 66.0
92.7 ⫾ 16.6
0.211
0.991
0.299
0.142
0.005†
*Data are presented as mean ⫾ SD.
†Of statistical significance.
lation with peak E-wave velocity (r ⫽ 0.419,
p ⫽ 0.001) and minimum Spo2 during sleep
(r ⫽ 0.257, p ⫽ 0.040), and a positive correlation
with the diastolic BP (r ⫽ 0.325, p ⫽ 0.023) and
mean BP (r ⫽ 0.315, p ⫽ 0.027). LVMI had no
significant correlation with either AHI (r ⫽ 0.109,
p ⫽ 0.393) or mean Spo2 during sleep (r ⫽ 0.143,
p ⫽ 0.269). DT was related to the minimum Spo2
during sleep (r ⫽ 0.27, p ⫽ 0.029), but peak E-wave
velocity was not (r ⫽ 0.14, p ⫽ 0.29).
Discussion
Diastolic dysfunction is a condition with increased
resistance to filling of the left ventricle, leading to an
inappropriate rise in the diastolic pressure-volume
relationship and causing symptoms of pulmonary
congestion during exercise. In contrast, DHF indicates that all these changes occur when the patient is
at rest.24 This study with echocardiography has
shown that diastolic dysfunction occurred in 36.8%
of our patients with OSA. An ARP was the only
diastolic dysfunction pattern observed. All these
OSA patients had normal LV systolic function and no
history of overt heart failure. The OSA patients with
diastolic dysfunction were older with a higher prevalence of hypertension, and diastolic dysfunction was
associated with more severe minimum Spo2 during
sleep, irrespective of age or hypertension. In patients
with more severe OSA, as reflected by AHI ⱖ 40/h,
the diastolic parameter, IVRT, was significantly
longer than those with AHI ⬍ 40/h. IVRT is the time
between the closure of the aortic valve and opening
of the mitral valve, and reflects the compliance of the
left ventricle independent of the effect of age.25
The potential mechanisms leading to changes in
cardiac structure and function in patients with OSA
have been studied in animal models. Fletcher et al26
demonstrated ventricular hypertrophy in rats exposed to short bursts of repetitive hypoxia over an
extended period and that intermittent severe hypoxia
can lead to a sustained rise in BP within 35 days.
Brooks et al,27 by inducing OSA via tracheostomy in
the canine model, showed that OSA can lead to the
development of sustained hypertension over approximately 100 days. Parker et al,28 using the same
canine model, showed that in patients with chronic
OSA, acute airway occlusion during sleep is associated with increase in LV afterload and decrease in
fractional shortening, whereas chronic OSA also
leads to sustained decrease in LV systolic performance that can be caused by the development of
systemic hypertension and/or transient increase in
LV afterload during episodes of airway obstruction.
Nevertheless, the observation that severe OSA, induced in the canine model over 3 months, leading to
LV systolic dysfunction, may not be the same in the
human model, as the clinical syndrome severity in
humans is highly variable and typically evolves over
many years.29
There are conflicting data on the effect of OSA on
the cardiac structure and function in human subjects. Increased LV wall thickness independent of
daytime BP has been observed in OSA patients
compared to age-matched and BMI-matched control
subjects, suggesting a direct effect of nocturnal
hypertension.30 A study by Davies et al,31 investigating a small group of OSA patients, snorers, and
control subjects matched for age, sex, obesity, smoking, and alcohol consumption, found no difference
between groups in LV diameter or thickness, or
LVM. Hanly et al32 reported normal indexes of LV
function between a group of typical OSA patients
and a group of habitual snorers without OSA. Noda
et al33 reported LV hypertrophy (LVH) in 41% of 51
OSA patients. Nocturnal hypoxia and apnea index
were significantly correlated with LVH and 24-h BP.
However, obesity was also commonly seen in the
group with LVH, and the relation to preexisting
hypertension was not clear in this uncontrolled
study. However, in a separate study, Noda et al34
showed that the survival rate was significantly lower
among untreated middle-aged Japanese hypertensive patients with OSA than normotensive patients
(57.9% vs 90.4%, respectively). Recently Alchanatis
et al35 reported that LV diastolic function was impaired in 15 OSA patients with neither history of nor
current systemic hypertension, compared to 11 subjects matched for age and BMI. In addition, treatment with nasal continuous positive airway pressure
(CPAP) over 3 months resulted in significant improvement in both LV diastolic function and diastolic
BP, while systolic function and wall thickness remained within normal limits. In our study, LVMI
correlated negatively with the minimum Spo2 during
sleep and positively with the mean BP and the
diastolic BP, suggesting that both hypoxia related to
OSA per se and hypertension may cause LVH and
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impair the diastolic function of the left ventricle.
Nevertheless, OSA may have other unfavorable effects on LV diastolic function independent of LVH.
There is strong epidemiologic evidence showing
an independent association between OSA and hypertension.9 –13 High levels of AHI9 –13 and sleep time
below 90% oxygen saturation11,12 were associated
with greater odds of hypertension in a dose-response
fashion. LV afterload is increased by peripheral
vasoconstriction as a result of recurrent arousals
terminating the obstructive respiratory events and
activating the sympathetic nervous system,36 – 40 and
activation of the arterial chemoreceptors by hypoxia
and hypercapnia. Plasma levels of nitric oxide, a
powerful vasodilator released from the endothelium,
have been shown to be decreased in OSA patients
but can be promptly reversed by nasal CPAP treatment.41,42 More recently Kraiczi et al43 showed in 20
subjects with OSA that worsening nocturnal hypoxemia (measured as minimum Spo2 or percentage of
sleep time with Spo2 below 90%) was associated with
a gradual deterioration of LV diastolic function
(increased interventricular septum thickness, prolonged IVRT, and decreased E/A ratio), as well as
reduced endothelium-dependent dilatory capacity of
the brachial artery.
Other mechanisms that may result in LV dysfunction include increased preload by intermittent negative intrathoracic pressure during apnea, which may
also increase the LV transmural pressure gradient
and impair diastolic relaxation and LV filling.44 – 46
Increase in right ventricular volume, together with
hypoxia-induced pulmonary hypertension, may displace the interventricular septum leftward during
diastole and impair LV filling.47,48 Hypoxia and
hypercapnia may also decrease myocardial contractility.49,50
DHF is more common than systolic heart failure
in our Chinese population.15 SDB of the obstructive
type was noted in 55% of our patients with DHF16;
a lower minimum Spo2 during sleep, but not AHI,
was associated with more severe diastolic dysfunction.16,43 In this study, asymptomatic diastolic dysfunction was prevalent among our OSA patients;
more severe OSA, as reflected by the minimum Spo2
and AHI ⱖ 40/h, was associated with worse diastolic
parameters. It is possible that OSA, through hypoxia,
hypertension, and other mechanisms discussed earlier, causes LV diastolic dysfunction that, in the long
run, may lead to symptomatic DHF.
It is important to keep a high index of suspicion for
OSA when assessing patients with CHF. Not only
can nasal CPAP effectively relieve disabling symptoms such as sleepiness,51 it may potentially improve
LV systolic52 and diastolic function,35 decrease activation of the sympathetic nervous system activity,53
and increase nitric oxide levels41,42 in patients with
both OSA and heart failure. In addition OSA and
Cheyne-Stokes respiration with central sleep apnea
(CSR-CSA) can coexist in patients with CHF; however, in contrast to OSA, CSR-CSA is likely a
consequence rather than a cause of CHF.54 CSRCSA is associated with increased mortality in CHF,
probably because of sympathetic nervous system
activation caused by recurrent apnea-induced hypoxia and arousals from sleep.54 Nasal CPAP can
reduce ventricular irritability,55 improve LVEF, and
reduce the combined mortality-cardiac transplantation rate in such patients.56
There were several limitations in our study. This
study was uncontrolled, and we did not perform 24-h
BP recording and therefore could not demonstrate
any diurnal pattern of changes in BP profile in our
patients. Echocardiography is a well-known operator-dependent investigation, but all our studies were
performed by the same experienced technician to
avoid any individual variation in the assessment.
Clear recordings of diastolic parameters were obtained in all our OSA patients via the transthoracic
approach. Had there been poor transthoracic echocardiographic images in patients with severe obesity,
the transesophageal approach would have been required to assess systolic and diastolic functions. A
longitudinal study with serial echocardiography will
be of great interest to assess whether long-term nasal
CPAP treatment can reverse the diastolic dysfunction in a larger sample size of OSA patients. In
summary, this study has shown that an ARP in
diastole on echocardiography is common in patients
with OSA, and patients with more severe OSA have
a higher degree of diastolic dysfunction of the left
ventricle.
ACKNOWLEDGMENT: The authors thank Ms. Mabel Tong,
M.Y. Leung, and Fanny Chan for their technical support with the
sleep studies, and Ms. Doris Chan, Dr. Anthony T. Chan. and
Mr. K.K. Wong for performing statistical analysis of the data. We
are most grateful to Miss Pearl Ho for performing all of the
echocardiography studies for this project.
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