Download Cardiac Rhythm Disturbances in the Obstructive

Cardiac Rhythm Disturbances in the
Obstructive Sleep Apnea Syndrome*
Effects of Nasal Continuous Positive Airway
Pressure Therapy
Joseph Harbison, MB, BCh; Philip O’Reilly MB, BCh; and
Walter T. McNicholas MD, FCCP
Study objectives: A high incidence of nocturnal cardiac rhythm disturbances among patients with
obstructive sleep apnea (OSA) syndrome has been described in some reports, but not in others.
We wished to examine the prevalence of significant cardiac rhythm disturbance in patients with
established moderate to severe OSA syndrome and, in particular, to assess the impact of nasal
continuous positive airway pressure (nCPAP) therapy.
Design and setting: A prospective study of consecutive eligible patients in a dedicated sleep
disorders unit of a university teaching hospital.
Measurements and results: Holter monitoring was performed for 18 h in 45 patients with
previously diagnosed OSA syndrome (mean [SD] apnea/hypopnea frequency [AHI] of 50 [23]/h)
and repeated within 2 to 3 days after institution of nCPAP therapy. Investigators were blinded to
the patients’ treatments during data analysis. Thirty-five patients were found to have some cardiac
rhythm disturbance, but only 8 had pathologically significant disturbances (ventricular tachycardia or
fibrillation, complex ventricular ectopy, new-onset supraventricular tachycardia other than sinus
tachycardia, pauses of > 2 s, and second- or third-degree heart block). Significant rhythm disturbances occurred only during the nighttime, and there was a significant correlation between OSA
severity and the severity of rhythm disturbance (p ⴝ 0.04, r ⴝ 0.301). No significant correlation was
found between OSA severity and any other anthropometric parameter measured. nCPAP therapy
resulted in abolition of rhythm disturbance in seven of these eight patients; the eighth patient was
found to have coexisting severe aortic valve disease requiring valve replacement.
Conclusion: The data indicate that OSA syndrome predisposes to clinically significant cardiac rhythm
disturbances that can be successfully controlled by nCPAP therapy.
(CHEST 2000; 118:591–595)
Key words: arrhythmia; CPAP; sleep apnea
Abbreviations: AHI ⫽ apnea/hypopnea frequency; BMI ⫽ body mass index; nCPAP ⫽ nasal continuous positive airway
pressure; OSA ⫽ obstructive sleep apnea; OSAS ⫽ obstructive sleep apnea syndrome
cardiac rhythm disturbances have been
N octurnal
reported to be common in patients with obstruc-
tive sleep apnea (OSA) syndrome (OSAS) but also in
control subjects.1–5 Indeed, rhythm disturbances
such as bradycardia with or without alternating
tachycardia6 –9 have been regarded as a typical feature of OSAS.10 However, the incidence of pathologically significant rhythm disturbances, such as
heart block, supraventricular tachycardia, and ventric-
*From the Department of Respiratory Medicine and the Respiratory Sleep Laboratory, St. Vincent’s University Hospital, Dublin, Ireland.
Manuscript received August 10, 1999; revision accepted April 12,
2000.
Correspondence to: Walter T. McNicholas, MD, FCCP, Department of Respiratory Medicine, St. Vincent’s University Hospital,
Elm Park, Dublin 4, Ireland; e-mail: [email protected]
ular arrhythmia, is less clear-cut.4,11–14 The incidence of
pathologically significant rhythm disturbances assumes
particular clinical significance in view of the reported
increase in cardiovascular morbidity and mortality
among patients with OSAS,15–18 and the potential
impact of nasal continuous positive airway pressure
(nCPAP) therapy on these disturbances.15
Using an ambulatory ECG monitor before and
after institution of nCPAP therapy, we prospectively
examined the prevalence of cardiac rhythm disturbances in a group of consecutive patients with
previously diagnosed OSAS. The principal study aim
was to establish the frequency of pathologically
significant cardiac rhythm disturbances in the group
and, in particular, to determine the effect of nCPAP
on these disturbances.
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Materials and Methods
The study included 45 consecutive patients (41 men, 4 women)
with previously diagnosed moderate to severe OSAS (diagnosed
by standard overnight polysomnography19) who were being evaluated in the hospital for nCPAP therapy. Prior to institution of
nCPAP, 18-h, four-lead, two-channel ambulatory ECG recordings were performed (from 6:00 pm to 12:00 am the next
morning) on each patient using a Holter monitor (Tracker 2
Holter Monitor; Reynolds Medical; Hertford, UK) with concurrent overnight oximetry using a digital oximeter (model 3700e;
Ohmeda; Essex, UK). The ambulatory monitors were fitted to the
patients by experienced staff. Each patient’s identity was kept
anonymous by means of a seven-digit code number, and Holter
tapes bore no evidence of the patients’ identities or date of study.
nCPAP therapy was titrated on the following night using an
nCPAP titrating device (Autoset nCPAP Titrating Device;
ResMed; Sydney, Australia). All patients underwent repeat 18-h
ECG and oximetry while in the hospital within 1 to 2 nights of
instituting nCPAP therapy (ie, within 2 to 3 nights of the initial
Holter studies).
ECG tapes were each interpreted at 60 times normal speed, on
two separate occasions, by experienced medical staff who were
trained in the interpretation of the recordings (J.A.H and P.O’R.),
and who were blinded to the patients’ identities and treatment
status but not to the underlying diagnosis of OSAS. The interpreting system used was a Reynolds Medical Pathfinder 4
(Reynolds Medical). All deviations from normal sinus rhythm
were recorded. In addition to measures of OSAS severity, mean
and lowest percentage of oxygen desaturation (taken from the
initial diagnostic polysomnography records), each patient had
height, weight, and body mass index (BMI) recorded. In addition,
fasting blood glucose and lipids analyses were performed, and all
underwent pulmonary function testing using a computerized
system (Morgan Autolink; Morgan Medical; Rainham, UK).
For the purposes of the present study, rhythm disturbances
considered pathologically significant included ventricular tachycardia or fibrillation, complex ventricular ectopy (including salvoes of three beats or more, recurrent bigeminy, or polygeminy),
new-onset supraventricular tachycardia other than sinus tachycardia, pauses of ⬎ 2 s, and second- or third-degree atrioventricular block. Second- or third-degree atrioventricular block was
defined as intermittent or persistent loss of association between P
waves and QRS complexes seen on the ECG. Other rhythm
disturbances, recorded but not deemed significant, included
isolated dropped beats, asymptomatic sinus bradycardia or tachycardia, and isolated atrial or ventricular premature systoles.20
Statistical analysis was performed using a commercial statistics
package (SPSS 9.0.0, SPSS; Chicago, IL). The hospital ethics
committee approved the study, and informed consent was obtained from each patient.
Results
Anthropometric and clinical details are given in
Table 1. The study population included a broad
spectrum of OSAS severity, although most patients
had severe disorders. The mean fasting cholesterol
was just above the upper limit of normal for our
laboratory (5.8 mmol/L), indicating a high incidence
of hypercholesterolemia in the study population.
Following tape analysis, the patients were classified
into three groups: group 0, those with no rhythm
disturbances; group 2, those with significant
Table 1—Anthropometric and Clinical Details of the
Study Population (n ⴝ 45)*
Variables
Age, yr
AHI, per h
BMI, kg/m2
Systolic BP, mm Hg
Diastolic BP, mm Hg
Fasting total cholesterol, mmol/L
Fasting serum glucose, mmol/L
Peak expiratory flow rate, % predicted
FEV1, % predicted
FVC, % predicted
Values
50 (13.1)
50 (23.3)
32.7 (6.0)
132 (14.8)
80 (16.7)
5.9 (1.1)
5.7 (0.65)
101 (20)
97 (18)
98 (16)
*Data are presented as mean (SD).
rhythm disturbances; and group 1, those with other
rhythm disturbances based on the criteria given
above.
Of the 45 patients who underwent ambulatory
ECG monitoring prior to commencement of nCPAP
therapy, 35 patients (78%) were noted to have some
nocturnal rhythm disturbance. However, of these,
only 8 patients (18%) demonstrated rhythm disturbances that were pathologically significant; details of
these dysrhythmias before and after CPAP therapy
are provided in Table 2. Table 2 does not include
other rhythm disturbances, present in all of these
patients, which were considered not pathologically
significant, as described above. Recurring sinus
pauses during sleep were the most common dysrhythmia (six patients), lasting 10 s. One patient also
developed an episode of variable second-degree
atrioventricular block lasting 4.5 min, and one patient developed two salvoes of three ventricular
ectopic beats. One patient developed intermittent
ventricular bigeminy with sinus bradycardia for prolonged periods (ⱖ 20 min) during sleep; this patient
had marked ventricular ectopy in the intervening
periods and also suffered pauses of 3 s. All of these
rhythm disturbances occurred between the hours of
11:00 pm and 7:00 am, and no significant rhythm
disturbances were noted in patients 1 to 7 outside of
these hours. Significant rhythm disturbance persisted in only one patient after institution of nCPAP
(patient 8, Table 2). This patient had ischemic
cardiomyopathy and severe aortic stenosis, requiring
surgical intervention and aortic valve replacement.
In addition to resolution of rhythm disturbances in
those patients with significant dysrhythmias, nCPAP
was also associated with resolution of rhythm disturbances in those patients with nonsignificant rhythm
disturbances (Group 1).
A Pearson correlation matrix analysis was performed with the statistical software package in which
the grading of dysrhythmia (0, 1, or 2) was related to
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Clinical Investigations
Table 2—Details of Nocturnal Pathologic Dysrhythmias and Impact of nCPAP Therapy*
Patient
No.
Age, yr
AHI, h
1
40
54
2
3
4
5
6
7
32
42
44
51
69
35
48
68
109
55
21
53
8
41
80
Before nCPAP
After nCPAP
Multiple sinus pauses: 5/h ⬎2 s; 10/h of 3 to 5.5 s,
and 1/h of 10-s duration
3 sinus pauses/h, lasting 2 to 3 s
Frequent ventricular extrasystoles, 2 salvoes of 3 PVCs
2 sinus pauses/h, lasting 2.5 to 3 s
2 sinus pauses/h, lasting 2.5 to 3 s
8 sinus pauses of 2- to 3-s duration
1 episode of second-degree atrioventricular block,
lasting 4.5 min; 1 sinus pause of 4 s
Intermittent ventricular bigeminy; 5 sinus pauses of 2to 3-s duration
No pathologic dysrhythmia
No
No
No
No
No
No
pathologic
pathologic
pathologic
pathologic
pathologic
pathologic
dysrhythmia
dysrhythmia
dysrhythmia
dysrhythmia
dysrhythmia
dysrhythmia
Intermittent ventricular bigeminy; 1 salvo of
5 PVCs; 10 sinus pauses, 2- to 4.5-s
duration
*PVC ⫽ premature ventricular contraction.
a range of anthropometric and other variables;
namely, apnea/hypopnea frequency (AHI), mean
oxygen saturation during sleep, age, BMI, systolic
and diastolic BP levels, and fasting lipid and glucose
levels. Only AHI levels showed a significant relationship with the presence of arrhythmias (p ⫽ 0.04;
Table 3).
Discussion
The present findings indicate that cardiac rhythm
disturbances are common during sleep among patients with OSAS, but they are largely abolished
following the institution of nCPAP therapy. The
exclusive nocturnal nature of the rhythm disturbances in these patients contrasts with the more
common pattern of rhythm disturbances in patients
with cardiac disease, where rhythm disturbances are
less frequent during sleep than during wakefulness.21
An interesting finding of the present study is that
severity of OSA was greater in patients with rhythm
disturbances compared with those without (Table 3).
This finding contrasts with other reports that have
failed to show a relationship between the presence of
rhythm disturbances and severity of OSA.14,17,18 Po-
Table 3—AHI per Hour Related to the Pressure or
Absence of Cardiac Dysrhythmias*
AHI, h
Variables
Patients,
No.
Mean
SD
No dysrhythmias (group 0)
Nonsignificant dysrhythmias (group 1)
Significant dysrhythmias (group 2)
10
27
8
38
52
61
26
20
26
*Difference in AHI between groups is significant (p ⫽ 0.04, by
Pearson correlation analysis). See text for details of dysrhythmia
classification.
tential mechanisms for these rhythm disturbances in
patients with OSAS include the recurrent episodes of
hypoxemia and arousal that are typical features of
apnea22 and which are also associated with increased
sympathetic activity and heightened adrenergic response.23,24
The clinical significance of the rhythm disturbances observed in the present study is unclear,
particularly because the majority of the rhythm
disturbances found in our subjects were relatively
mild. There is only limited and inconclusive evidence
in the literature linking dysrhythmias in OSAS patients with excess mortality rates,25–27 although many
units treating patients with respiratory sleep disorders have anecdotal evidence of unexpected sudden
deaths during sleep occurring among their patient
population with OSAS. A systematic review by
Wright and colleagues28 challenged the significance
of OSAS as a risk factor for cardiovascular disease.
Whereas the present study did not use a randomized
controlled design, the strong suppressant effect of
nCPAP on the observed cardiac rhythm disturbances
strongly supports a causal relationship between
OSAS and at least one form of cardiovascular morbidity. However, further studies are required to
establish the pathologic significance of the present
findings.
A number of previous reports have examined the
relationship of OSAS to cardiac rhythm disturbances
and myocardial ischemia and the impact of nCPAP
therapy.1,2,5,11,14 –16,18,19,29 Two reports1,2 have demonstrated a high prevalence (58% and 48%, respectively) of cardiac rhythm disturbance, significantly
higher than nonapneic snorers, among large populations of patients with OSA.1 However, other studies
have reported a much lower prevalence of rhythm
disturbances11,14,17,18 that was not significantly different from that of nonapneic snorers.14,17,18 The conCHEST / 118 / 3 / SEPTEMBER, 2000
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trol populations for these studies have generally
consisted of patients undergoing sleep studies for
suspected OSA, but who were found not to have a
significant OSAS.1,14,17,18 Thus, it is difficult to draw
confident conclusions concerning a potential relationship between OSA and cardiac rhythm disturbance because such control populations could not be
considered as normal subjects.
Several reports have examined the impact of
nCPAP on rhythm disturbances and ischemia among
patients with OSAS, and all have demonstrated
objective benefit.5,15,19,29 However, only two previous reports have evaluated the impact of nCPAP on
cardiac rhythm disturbances,5,29 both of which examined OSAS patients with heart block. The present
report represents the first prospective study of the
impact of nCPAP on pathologic rhythm disturbances
among consecutive patients with established OSAS.
We recognize the limitations of our study design
related to the lack of a matched control group and
also to the lack of a randomized, placebo-controlled
follow-up of the impact of nCPAP therapy on patients with cardiac rhythm disturbances. These limitations, although similar to those in previous reports,
prevent us from drawing firm conclusions on the
relative incidence of nocturnal cardiac rhythm disturbances in our patients with OSAS, compared with
normal subjects of similar age. However, we strongly
doubt that these limitations biased our findings or
conclusions for several reasons: first, all patients had
baseline and follow-up studies performed within 3
nights, and no therapeutic intervention was instituted other than nCPAP. Second, the magnitude of
the treatment effect, where seven of eight patients
with significant nocturnal cardiac rhythm disturbances resolved their nocturnal cardiac rhythm disturbance with nCPAP, strongly supports the view
that nCPAP therapy had a beneficial impact on these
dysrhythmias. The one patient whose rhythm disturbances did not resolve with nCPAP therapy had
obvious primary cardiac pathology to account for his
dysrhythmias. Finally, the seven patients whose dysrhythmias resolved with nCPAP demonstrated
rhythm disturbances almost exclusively during sleep.
Previous reports have indicated that cardiac rhythm
disturbances are generally more frequent during
waking hours.21 All of the above considerations
strongly support the view that the cardiac rhythm
disturbances observed were a consequence of the
patients’ OSAS.
The continuous ECG recording provided by the
Holter monitor raises the possibility of using this
device to detect episodes of myocardial ischemia
during sleep, as described in previous reports of
patients with OSAS.15,30 Whereas continuous STsegment monitoring was not directly part of the
present protocol, we did assess the potential usefulness of the Holter monitor to detect myocardial
ischemia. However, we found the Holter monitor to
be unsatisfactory and unreliable in this regard. Two
patients with known ischemic heart disease did not
show evidence of nocturnal ST-segment changes,
despite both having severe OSAS, whereas three
patients who did show episodes of nocturnal STsegment depression ⬎ 1 mm were not found to have
evidence of significant heart disease on further cardiac investigation. However, we must stress that the
present study was not designed to identify myocardial ischemia in patients with OSAS, and our comments in this regard are relevant only to the suitability of the Holter monitor to detect occult myocardial
ischemia. The two-channel ECG recording provided
by this device would not be sufficient to fully assess
the possibility of myocardial ischemia, and the device
is primarily designed for assessing cardiac rhythm
disturbances.
The finding that nCPAP effectively controls cardiac rhythm disturbances implies that routine cardiac monitoring is not indicated in patients with
OSAS treated with nCPAP. However, this conclusion does not apply to those patients who fail to
tolerate nCPAP therapy. Furthermore, compliance
data indicate that patients receiving continuous
home nCPAP therapy use their device for an average
of only 5 h per night.31,32 These findings raise the
possibility of continuing adverse cardiac consequences for patients with OSAS during the hours of
sleep when the patients are not using their nCPAP
devices.33 Further studies will be required to assess
the cardiovascular morbidity and mortality rates of
untreated and undertreated patients with OSAS.
We conclude that cardiac rhythm disturbances
during sleep are common in patients with OSAS, that
they correlate with OSA severity, and that they are
effectively treated by nCPAP therapy.
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