Download Sleep-Related Breathing Disorders Are Associated With Ventricular

Sleep-Related Breathing Disorders Are
Associated With Ventricular Arrhythmias
in Patients With an Implantable
Cardioverter-Defibrillator*
Joachim Fichter, MD, PhD; Dirk Bauer, MD; Spyridon Arampatzis, MD;
Roland Fries, MD; Armin Heisel, MD, PhD; and
Gerhard Walter Sybrecht, MD, PhD
Study objectives: The aim of this study was to examine the influence of sleep-related breathing
disorders (SBDs) on the occurrence of ventricular arrhythmias in patients with reduced left
ventricular ejection fraction (LVEF), and life-threatening ventricular tachyarrhythmias treated
with an implantable cardioverter-defibrillator.
Patients: Thirty-eight patients with LVEF of 36 ⴞ 13% (mean ⴞ SD) underwent a sleep study.
When an apnea-hypopnea index (AHI) > 10/h occurred, SBD was diagnosed.
Measurements and results: In patients with SBDs, ventricular arrhythmias (couplets, triplets,
short runs) were recorded simultaneously by Holter ECG and differentiated in episodes with and
without disordered breathing. An apnea-associated arrhythmia index (AI) was defined as the
number of ventricular arrhythmias occurring simultaneous to disordered breathing. Accordingly,
a nonapnea-associated arrhythmia index (NAI) was calculated as the number of ventricular
arrhythmias during normal breathing. SBDs were diagnosed in 14 patients: Cheyne-Stokes
respiration (CSR) [n ⴝ 8; AHI, 32.1 ⴞ 25.0/h], and obstructive sleep apnea (OSA) [n ⴝ 6; AHI,
34.1 ⴞ 14.6/h]. Four patients in the OSA group and four patients in the CSR group had
ventricular arrhythmias during sleep, revealed by Holter ECG. In these eight patients, the AI was
significantly higher than the NAI (20.9 ⴞ 18.8/h vs 4.9 ⴞ 3.3/h, respectively).
Conclusions: These data show that ventricular arrhythmias occurred significantly more often in
association with disordered breathing in patients at high risk for arrhythmias and reduced LVEF.
(CHEST 2002; 122:558 –561)
Key words: implantable cardioverter defibrillator; left ventricular dysfunction; sleep-related breathing disorders;
ventricular arrhythmias
Abbreviations: AHI ⫽ apnea-hypopnea index; AI ⫽ apnea-associated arrhythmia index; CSR ⫽ Cheyne-Stokes respiration; ICD ⫽ implantable cardioverter-defibrillator; LVEF ⫽ left ventricular ejection fraction; NAI ⫽ nonapneaassociated arrhythmia index; OSA ⫽ obstructive sleep apnea; PVC ⫽ premature ventricular contraction; REM ⫽ rapid
eye movement; SBD ⫽ sleep-related breathing disorder
leep-related breathing disorders (SBDs) are assoS ciated
with cardiac arrhythmias, conduction abnormalities,1 frequent arousals,2 and potentially lifethreatening arrhythmias.3,4 It has been shown that
patients with cardiac dysfunction frequently have
SBDs.2,5,6
Only few data are available about ventricular
*From the Department of Internal Medicine V (Drs. Fichter,
Bauer, Arampatzis, and Sybrecht), and the Department of Internal Medicine III (Drs. Fries and Heisel), Universitätskliniken des
Saarlandes, Homburg/Saar, Germany.
Manuscript received June 29, 2001; revision accepted February
28, 2002.
Correspondence to: Joachim Fichter, MD, PhD, Paracelsus
Hospital, Am Natruper Holz 69, 49076 Osnabrueck, Germany;
e-mail: [email protected]
arrhythmias and sleep apnea in patients with underlying severe cardiac diseases. Some authors7,8 have
reported a nocturnal increase in frequency of venFor editorial comment see page 398
tricular arrhythmias in patients with heart disease.
Other studies3,9 –12 did not show a relationship or
only showed a weak relationship between ventricular
arrhythmias and SBDs. However, in the majority of
these studies, patients without significant cardiac or
respiratory comorbidities were examined.
We investigated patients with impaired left ventricular function and a history of malignant, drugresistant ventricular tachyarrhythmia who received
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Clinical Investigations
an implantable cardioverter-defibrillator (ICD). The
goal was to assess the influence of SBDs on ventricular arrhythmias in these patients.
Materials and Methods
Patients
Of 43 consecutive ICD recipients, 38 patients gave informed
consent to participate in a sleep study in our sleep laboratory. In
these 38 patients, the indication for implantation of an ICD was
documented spontaneous, life-threatening ventricular tachyarrhythmias. An invasive angiographic study was performed to
assess left ventricular function before the sleep study. Underlying
cardiac diseases included coronary heart disease (74%), dilatative
cardiomyopathia (21%), and idiopathic ventricular tachyarrhythmia (5%). All patients except one were receiving individual
therapy with angiotensin-converting enzyme inhibitors and class
III antiarrhythmics.
In a second step, ventricular arrhythmias (including couplets,
triplets, and ventricular short runs) were compared with associated episodes of disordered breathing in the two-channel ECG of
the polysomnogram. The occurrence of ventricular arrhythmias
within the time of the beginning and the end of an apnea or
hypopnea was taken as apnea/hypopnea-associated events.
The total time of normal and disordered breathing episodes
was measured by evaluation of the polysomnogram. An apneaassociated arrhythmia index (AI) was defined as the number of
ventricular arrhythmias occurring simultaneous with disordered
breathing episodes divided by the disordered breathing time
period (in hours). Accordingly, a nonapnea-associated arrhythmia
index (NAI) was calculated as the number of ventricular arrhythmias during normal breathing divided by the nondisordered
breathing time period.
Statistical Analysis
All data were expressed as mean values ⫾ SD. Comparisons of
the sleep laboratory data were made with a Wilcoxon signed-rank
test. A two-tailed, paired t test was used to compare the AI and
the NAI.
Measurements
Polysomnography consisted of continuous polygraphic recording from surface leads for EEG, electro-oculography, and electromyography (CNS 1000 P; Viasys; Wuerzburg, Germany).
Thoracoabdominal excursions were measured qualitatively by
pneumatic respiration transducers placed over the rib cage and
abdomen. Airflow was quantified by an oronasal thermocouple.
Arterial blood saturation was recorded by oximetry. A microphone was placed at the fossa jugularis for detection of tracheal
sounds. Body position and leg movements were recorded by
electromyography. For ECG recording, a simultaneous Holter
ECG was used to detect ventricular arrhythmias (couplets,
triplets, short runs) during sleep.
Before each of the measurements, the clocks of the sleep
laboratory and the Holter ECG were synchronized exactly and
times were checked for accordance after the measurement.
Polysomnography was terminated after final waking. All patients
were adapted to the sleep laboratory at the time of the initial
evaluation.
Data Collection and Analysis
Polysomnograms were scored by visual evaluation according to
standard criteria. Polysomnography records were scored for
sleep, breathing, oxygenation, and movement in 30-s periods.
Sleep data were staged (stages 1, 2, 3, and 4 and rapid eye movement [REM] sleep) according to the system of Rechtschaffen and
Kales.13 An abnormal breathing event during sleep was defined
according to the commonly used criterion of either a complete
cessation of airflow lasting ⱖ 10 s (apnea) or a discernible
reduction in respiratory airflow accompanied by a decrease of
ⱖ 4% in oxyhemoglobin saturation (hypopnea). Patients were
defined as having Cheyne-Stokes respiration (CSR) if they had
absence of thoracoabdominal movement for at least 10 s and a
crescendo-decrescendo pattern of the movements during hyperpnea, regularly alternating with central apneas and hypopneas at
a rate of ⬎ 10/h.
The average number of episodes of apnea and hypopnea per
hour of sleep (the apnea-hypopnea score) was calculated as the
summary measurement of SBD. SBD was diagnosed when an
apnea-hypopnea index (AHI) ⬎ 10/h was documented. When
apnea and hypopnea were scored, the scorer was blinded to the
results of the ECG.
www.chestjournal.org
Results
The sleep study was accomplished after a mean
time period of 35.8 ⫾ 18.1 months after ICD implantation. The polysomnography of 38 patients with
an ICD yielded the diagnosis of SBD in 16 patients
(42%): CSR respiration in 8 patients and obstructive
sleep apnea (OSA) in 8 patients. Two patients with
SBD (one patient with CSR and one patient with
OSA) could not be evaluated because of insufficient
technical quality of the Holter ECG recording. Of
these 14 patients, 8 patients had ventricular arrhythmias during sleep. In these eight patients, 3,309
apneas and hypopneas, 185 apnea-associated ventricular short runs, and 162 nonapnea-associated short
runs were found and evaluated for interference. The
evaluation of Holter ECG for ventricular arrhythmias in coincidence with apneas/hypopneas during
sleep showed a significant higher levels of AI vs NAI
(21.8 ⫾ 18.2 vs 4.9 ⫾ 3.3; Fig 1). The comparison of
Figure 1. Comparison of the number of ventricular arrhythmias
occurring simultaneous to disordered breathing (AI) and ventricular arrhythmias occurring during the time of normal breathing
(NAI) in all patients with SBDs and ventricular tachyarrhythmias
during sleep. *Indicates patients with CSR.
CHEST / 122 / 2 / AUGUST, 2002
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559
patients with an ICD with and without ventricular
arrhythmias showed no significant difference in age,
left ventricular ejection fraction (LVEF), underlying
cardiac diseases, and polysomnographic-based data
(Table 1). The sleep data of the 14 patients are
shown in Table 2. No significant differences were
detected in the amount of total sleep time, stages 1
and 2 sleep, stages 3 and 4 sleep, and REM sleep.
Only few data are available regarding the relationship between SBD and ventricular arrhythmias in
patients with underlying cardiac disease and impaired left ventricular function.6 In this study, the
coincidence of disordered breathing and ventricular
arrhythmias in patients with ICDs was investigated.
Although it was not primarily expected when analyzing the data of the literature, we found a surprisingly
high prevalence of SBD (41%) in the 38 patients
with ICDs. In a subgroup of the patients with SBDs,
premature ventricular contractions (PVCs) occurred
significantly more often during disordered breathing.
This high prevalence of SBD in patients with
ICDs is comparable with other studies in patients
with impaired cardiac function.5 CSR was the most
common SBD in our study group. It has been shown
that CSR is associated with a higher mortality in
patients with congestive heart failure.14 As a consequence, CSR probably has a relevant impact on the
survival of these patients by increasing sympathetic
neuronal activity, which is evoked by concomitant
apneas or hypopneas leading to hypoxemia, hypercapnia, and arousals during sleep.15–18
Several contributing factors of SBDs might have
played a role in inducing PVCs: (1) activation of the
sympathetic nervous system induced by linkage to
Table 1—Characteristics of Patients With Diagnosed
SBD and Absence of Ventricular Arrhythmias During
Sleep or Evidence of Ventricular Arrhythmias
During Sleep*
SBD
Without
SBD With
Arrhythmias Arrhythmias
(n ⫽ 6)
(n ⫽ 8)
p Value
Age, yr
68.5 ⫾ 7.2 62.0 ⫾ 6.8
LVEF, %
32.5 ⫾ 5.3 35.0 ⫾ 11.8
CSR
3
4
Angiotensin-converting enzyme
6
8
inhibitors
Class III antiarrhythmics
6
7
Coronary heart disease
4
6
AHI, per h
43.3 ⫾ 22.1 31.2 ⫾ 16.7
Characteristics
SBD With
Arrhythmias
SBD Without
Arrhythmias
p Value
TST, min
Stage 1 and 2, min
Stage 3 and 4, min
REM sleep, min
REM/TST, %
347 ⫾ 49
280 ⫾ 74
42 ⫾ 16
22 ⫾ 20
8⫾7
300 ⫾ 58
260 ⫾ 47
18 ⫾ 13
26 ⫾ 20
7⫾7
NS
NS
NS
NS
NS
*Data are presented as mean ⫾ SD. TST ⫽ total sleep time; see
Table 1 for expansion of abbreviation.
Discussion
Characteristics
Table 2—Sleep Characteristics of Patients With
Diagnosed SBD With or Without Ventricular
Arrhythmias During Sleep*
NS
NS
NS
NS
NS
NS
NS
*Data are presented as mean ⫾ SD or No. NS ⫽ not significant.
episodes of hypoxemia, and (2) hypercapnia, arousals, and temporary hemodynamic alterations related
to increased intrathoracic pressure changes during
OSA. Hypoxemia has been estimated to provoke
PVC, as described by Shephard et al10; however, in
their study, PVC occurred only in one patient with
oxygen desaturations ⬍ 60%, and only patients without cardiac or pulmonary comorbidity were examined. In other studies,11,12 a significantly higher level
of PVCs was not found in patients with SBD.
Guilleminault and coworkers4 presented a large
study of 400 patients with sleep apnea syndrome who
were examined for the presence of various types of
arrhythmias. In 4% of the patients, ventricular arrhythmias (defined as three or more beat runs) were
found, and all had happened during an apneic event.
In a study of ventricular arrhythmias, Flick and
Block19 demonstrated in patients with COPD that
oxygen desaturation can cause PVCs and that oxygen
therapy could dramatically reduce the frequency of
PVCs in a subgroup of patients. In this study, SBD
was not taken into account because SBD was not
regularly diagnosed at the time this study was
conducted.
Our data show that PVCs occur significantly more
often during disordered respiration than during normal breathing in patients with SBDs and ICDs. As
underlying factors, we could not detect any significant difference in LVEF and AHI between the two
groups with and without PVCs during sleep. The
number of patients treated with class III antiarrhythmics, with a history of cardiac resuscitation, or
patients with symptoms of SBD did not significantly
differ in both groups. In another study, we could
show that even ICD-treated ventricular tachyarrhythmias over 2 years were not significantly different in patients with and without SBDs.20
Apneic-specific microchanges during SBD are a
possible mechanism of inducing PVCs; systemic and
pulmonary artery pressure alterations caused by
elevated negative intrathoracic pressure during apneas might be a contributing factor.21–23 Another
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possible explanation could be that ventricular dysrhythmias could be more common with arousals,
which are known to be associated with surges in BP
and presumably in sudden increase in catecholamine
secretion. However, arousals provoked by intrinsic
respiratory stimuli during CSR have relatively little
effect on BP and heart rate.24
The present article provides more specific information regarding what circumstances cause sleep apnea
and arrhythmias to occur. The data show that in the
group of patients at risk for severe ventricular tachyarrhythmias, an association and a simultaneous occurrence of apneas and disordered breathing were found.
These data suggest that SBDs have the potential of
inducing ventricular arrhythmias in patients with reduced left ventricular function. If we consider PVC as
a precursor of ventricular tachyarrhythmias,23 it seems
to be possible that SBDs could provoke malignant
ventricular tachyarrhythmias in these patients.
In summary, we found a high prevalence of SBDs in
patients with ICDs. Ventricular arrhythmias were significantly more often associated with apneas/hypopneas
than with normal breathing in these patients. The data
provide more specific information regarding under
what circumstances sleep apnea and arrhythmias occur.
We could specifically show a coincidence between
events of disordered breathing and arrhythmias that
could be shown for obstructive events as well as for
CSR events. Therefore, we conclude that SBD could
be regarded as a risk factor for ventricular arrhythmias
in these patients. These findings can be applied to a
broader population of patients with ventricular arrhythmias, because no sustained tachyarrhythmic events that
were treated by ICDs occurred in patients in this
investigations. Patients with indication for ICD should
therefore be considered for a sleep study if implantation of this device has been indicated. Furthermore, it
has to be evaluated whether continuous positive airway
pressure therapy, nocturnal oxygen therapy, or other
effective therapies of SBD are able to improve the
outcome of these patients.
ACKNOWLEDGMENT: The authors thank J. Juhàsz for his
helpful comments and suggestions.
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