CASE REPORT
Bradyarrhythmias may induce central sleep apnea in a patientwith obstructive sleep apnea
Shoko Suda • Takatoshi Kasai • Mitsue Kato • Fusae Kawana •
Takao Kato • Ryoko Ichikawa • Hidemori Hayashi •
Takayuki Kawata • Gaku Sekita • Seigo Itoh • Hiroyuki Daida
Received: 17 December 2013 / Accepted: 4 April 2014
� Springer Japan 2014
Abstract The relationship between central sleep apnea
(CSA) and bradyarrhythmia remains unclear. We report the
case of a 70-year-old man with severe obstructive sleep
apnea and bradyarrhythmia due to sick sinus syndrome in
whom concomitant CSA was alleviated after pacemaker
implantation.
Keywords Lung to finger circulation time � Pacemaker �Sick sinus syndrome � Sleep-disordered breathing
Introduction
It is well-recognized that there may be a causal relationship
between sleep-disordered breathing and cardiovascular
disease [1, 2]. In addition, sleep-disordered breathing is
thought to predispose patients to disturbances of cardiac
conduction and cardiac arrhythmia [3, 4]. Several reports
have suggested that obstructive sleep apnea (OSA) can
induce bradyarrhythmia, including sinus pause and heart
block [4–6]. The causal relationship between OSA and
bradyarrhythmia may be explained by an imbalance of the
autonomic nervous system in association with hypoxia
without ventilation during OSA [7]. Conversely, there are
limited data regarding the relationship between central
sleep apnea (CSA) and bradyarrhythmia [8], and it is
unclear whether this relationship is causal. CSA is fre-
quently observed in patients with cardiovascular disease
and can be alleviated by initiating specific therapy for those
with cardiovascular disease [9–11]. Thus, CSA is thought
to be a consequence of cardiovascular disease.
Here, we describe a case of a patient with severe OSA
and bradyarrhythmia due to sick sinus syndrome in whom
concomitant CSA was alleviated after pacemaker
implantation.
Case report
A 70-year-old man with hypertension, diabetes mellitus, and
severe OSA [apnea–hypopnea index (AHI), 65.8 events/h]
was referred by a sleep physician from another institution for
a cardiovascular work-up. A diagnostic polysomnography
had shown frequent episodes of transient drops in heart rate
and coexisting CSA [central apnea index (CAI), 19.9 events/
h, in addition to obstructive apnea index (OAI), 20.2 events/
h]. At the first visit to the cardiology outpatient clinic, the
patient did not complain of excessive daytime sleepiness or
any cardiovascular symptoms. He was overweight (body
mass index, 26.7 kg/m2), but had no other abnormal physical
findings. His electrocardiogram showed sinus rhythm (heart
rate, 56 beats/min) with non-specific ST-T abnormalities in
leads I, aVL, and V4–6. Laboratory tests indicated hyper-
triglyceridemia (triglyceride level, 256 mg/dL) and poor
control of blood glucose (hemoglobin A1c, 8.3 %), but no
elevation in B-type natriuretic peptide (BNP) level (16.5 pg/
mL). An echocardiogram showed mild dilatation of the left
atrium (left atrial dimension, 38 mm) and borderline left
ventricular (LV) hypertrophy (ventricular septum, 11 mm;
S. Suda � T. Kasai � M. Kato � F. Kawana � T. Kato �R. Ichikawa � H. Hayashi � T. Kawata � G. Sekita � S. Itoh �H. Daida
Department of Cardiology, Juntendo University School of
Medicine, Tokyo, Japan
S. Suda � T. Kasai (&) � M. Kato � F. Kawana
Cardio-Respiratory Sleep Medicine, Department of Cardiology,
Juntendo University School of Medicine, 2-1-1 Hongo,
Bunkyo-ku, Tokyo 113-8421, Japan
e-mail: [email protected]
123
Heart Vessels
DOI 10.1007/s00380-014-0511-x
posterior wall, 11 mm), with mild LV diastolic dysfunction
(mitral inflow E/A ratio, 0.7; deceleration time, 259 ms).
Although LV systolic function was preserved (LV ejection
fraction, 72 %), LV filling and cardiac output were impaired
(E/e0, 13.6; cardiac output, 3.1 L). During 24-h ambulatory
Holter monitoring performed 2 weeks after the initial visit,
the patient experienced an episode of syncope at awakening
(09:00 h) and he, therefore, visited the emergency unit of our
institution. The electrocardiogram taken at the emergency
visit showed sinus pause followed by escape beats (Fig. 1a).
In addition, the Holter recording at 09:00 h showed a sinus
pause for 9 s (Fig. 1b). His diagnosis was severe,
symptomatic bradyarrhythmia associated with sick sinus
syndrome. A cardiac pacemaker (DDD mode: heart rate,
60 beats/min) was implanted immediately.
After the pacemaker was implanted, the patient’s diag-
nostic polysomnography was reviewed. We found frequent
episodes of sinus pause with escape beats similar to the
electrocardiography findings at the emergency visit. We
also found increasing CSA toward the end of the poly-
somnography that was associated with a prolonged lung-to-
finger circulation time (LFCT), lasting for 18 s during the
first third of the night to 27 s during the last third of the
night (Fig. 1c, d). Polysomnography was performed
Fig. 1 The clinical findings. a The electrocardiogram taken at the
emergency visit showing sinus pause followed by escape beats.
b Holter recording at 09:00 h showing sinus pause for 9 s. c A
hypnogram for diagnostic polysomnography revealing increasing
central sleep apnea (blue line) toward the end of the polysomnog-
raphy and prolonged LFCT. Note that the LFCT is prolonged from
18 s during the first third of the night to 27 s during the last third of
the night. d In diagnostic polysomnography, there are periodic pattern
of central apneas, during which movements of the ribcage and
abdomen are absent. The duration from the onset of the first breath
terminating the apnea to the nadir of the subsequent dip in SO2
measured at the finger indicates an LFCT of 27 s (an average of ten
consecutive apnea–hyperpnea cycles during stage 2 sleep), which is
considerably long. e While reassessing polysomnography 2 weeks
after pacemaker implantation, typical OSA events are noted, during
which out-of-phase movements of the chest and abdomen are
predominant. Note that the LFCT is maintained from 17 s at the
first third of the night to 18 s at the last third of the night. Abd.
abdominal movement, CA central apnea, CSA central sleep apnea,
ECG electrocardiogram, HR heart rate, LFCT lung-to-finger circula-
tion time, MA mixed apnea, OA obstructive sleep apnea, REM rapid
eye movement, SO2 oxyhemoglobin saturation
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123
2 weeks after the pacemaker was implanted. The results
indicated that severe OSA remained, but there were no
signs of sinus arrest and CSA was alleviated (AHI
49.4 events/h; OAI 46.9 events/h; CAI 2.5 events/h).
There was no prolongation of LFCT (LFCT remained
constant from 17 s during the first third of the night to 18 s
during the last third of the night) (Fig. 1e). An echocar-
diogram after the pacemaker implantation showed none to
minimal changes in cardiac functions (mitral inflow
E/A ratio, 0.6; deceleration time, 232 ms; LV ejection
fraction, 65 %; E/e0, 14.1; and cardiac output, 2.9 L). Since
severe OSA remained, continuous positive airway pressure
(CPAP) therapy was initiated for treatment of severe
residual OSA. OSA was alleviated by automated CPAP
mode with pressure range from 4 to 8 cm H2O.
Discussion
Although a causal relationship between OSA and brad-
yarrhythmias has been suggested [5, 7], there are limited
data supporting relationship between CSA and bradyar-
rhythmia [8], and it remains unclear whether there is a
causal relationship between them. In general, CSA occurs
when the partial pressure of carbon dioxide (pCO2) falls
below the apnea threshold due to hyperventilation associ-
ated with pulmonary congestion [12]. Low cardiac output
and prolonged circulation time may also play a role in
prolonging the periodic breathing cycle [12]. Since in our
case the frequency of CSA episodes increased towards the
end of the polysomnography study, overnight deterioration
in cardiac function and worsening of pulmonary congestion
due to frequent episodes of bradyarrhythmia, in conjunc-
tion with OSA episodes, might have predisposed this
patient to CSA. This is further supported by the observation
that LFCT was prolonged during the initial diagnostic
polysomnography, but after the pacemaker was implanted
LFCT was not prolonged, as reassessed on polysomnog-
raphy, since LFCT is inversely associated with cardiac
output [12]. In addition, since CSA was alleviated when a
constant heart rate was maintained after the pacemaker was
implanted, CSA is more likely a consequence than a cause
of bradyarrhythmia. This is similar to the findings in a
previous study in which arterial overdrive pacing signifi-
cantly reduced the number of respiratory events [13]. This
is in agreement with the results of previous reports stating
that in patients with heart failure or valvular heart disease,
CSA could be alleviated by the initiation of specific ther-
apies for each cardiovascular condition [9–11]. Littman
and colleagues reported a case series suggesting a rela-
tionship between bradyarrhythmia and CSA; however, they
did not specifically address causality [8]. Thus, our findings
are the first to suggest the possibility that bradyarrhythmia
can cause CSA.
There may be other possible mechanisms to explain the
causal relationship between bradyarrhythmia and CSA in
our case. Alterations in heart rate and atrioventricular delay
can affect the respiratory system via changes in cardiac
output. For instance, when the cardiac output is reduced
because of a reduction in heart rate, ventilation may be
reduced concomitantly because of reduced CO2 transport to
the lung [14, 15]. Thus, the alteration in heart rate caused
by sick sinus syndrome, as observed in our case, might
induce oscillation in the central ventilatory drive and
consequently cause CSA. However, the lack of data on
alterations in CO2 level is a limitation of our report.
Increased chemosensitivity, which is associated with
overactivation of the sympathetic nervous system caused
by bradyarrhythmia, can predispose patients to CSA [9]. In
addition, OSA per se or the presence of diabetic autonomic
dysfunction may also alter CO2 chemosensitivity and play
other roles [16, 17] independent of the bradyarrhythmia-
related overactivation of sympathetic nervous system.
Since we do not have any data on chemosensitivity, this is
another limitation.
Ryan and colleagues [18] reported that a spontaneous
conversion from predominantly CSA to OSA in association
with an improvement in cardiac function. In addition, it has
been reported that improvement in cardiac function fol-
lowing cardiac transplantation was accompanied by com-
plete resolution of CSA or conversion to predominantly
OSA [10]. These observations suggest that, in patients with
cardiac dysfunction, OSA and CSA may be a part of the
spectrum of periodic breathing: the predominant type can
transform over time in response to alterations in cardiac
function. Alteration of ventilatory drive, which is elevated
in association with pulmonary congestion and enhanced
chemosensitivity, may contribute to this transformation.
When a constant heart rate is maintained after the pace-
maker implantation, the effect of these factors may be
reduced, leading to a shortened circulation time and alle-
viation of CSA. In the present case report, this patient
might have previously had an obstructive respiratory
physiology that was masked by the effects of elevated
ventilatory drive; amelioration of the elevated drive
unmasked the obstructive phenotype. These are possible
explanations for the increase in OSA (doubling) after
alleviation of CSA.
Although the underlying mechanisms remain unclear,
the present report highlights the existence of a causal
relationship between bradyarrhythmia and CSA.
Conflict of interest Takatoshi Kasai received unrestricted research
funding from Philips Respironics, Teijin Home Healthcare, and
Fukuda Denshi. The other authors report no conflicts of interest.
Heart Vessels
123
References
1. Kasai T, Floras JS, Bradley TD (2012) Sleep apnea and cardio-
vascular disease: a bidirectional relationship. Circulation
126:1495–1510
2. Naito R, Sakakura K, Kasai T, Dohi T, Wada H, Sugawara Y,
Kubo N, Yamashita S, Narui K, Ishiwata S, Ohno M, Ako J,
Momomura S (2012) Aortic dissection is associated with inter-
mittent hypoxia and re-oxygenation. Heart Vessels 27:265–270
3. Maeno K, Kasai T, Kasagi S, Kawana F, Ishiwata S, Ohno M,
Yamaguchi T, Narui K (2013) Relationship between atrial con-
duction delay and obstructive sleep apnea. Heart Vessels 28:
639–645
4. Guilleminault C, Connolly SJ, Winkle RA (1983) Cardiac
arrhythmia and conduction disturbances during sleep in 400
patients with sleep apnea syndrome. Am J Cardiol 52:490–494
5. Becker H, Brandenburg U, Peter JH, Von Wichert P (1995)
Reversal of sinus arrest and atrioventricular conduction block in
patients with sleep apnea during nasal continuous positive airway
pressure. Am J Respir Crit Care Med 151:215–218
6. Roche F, Xuong AN, Court-Fortune I, Costes F, Pichot V, Du-
verney D, Vergnon JM, Gaspoz JM, Barthelemy JC (2003)
Relationship among the severity of sleep apnea syndrome, car-
diac arrhythmias, and autonomic imbalance. Pacing Clin Elec-
trophysiol 26:669–677
7. Leung RS (2009) Sleep-disordered breathing: autonomic mech-
anisms and arrhythmias. Prog Cardiovasc Dis 51:324–338
8. Littmann L, Nesbit RM, Blackwell JM (2010) ‘‘Awakenings’’:
electrocardiographic findings in central sleep apnea. Ann Non-
invasive Electrocardiol 15:387–391
9. Tamura A, Kawano Y, Naono S, Kotoku M, Kadota J (2007)
Relationship between beta-blocker treatment and the severity of
central sleep apnea in chronic heart failure. Chest 131:130–135
10. Mansfield DR, Solin P, Roebuck T, Bergin P, Kaye DM,
Naughton MT (2003) The effect of successful heart transplant
treatment of heart failure on central sleep apnea. Chest
124:1675–1681
11. Rubin AE, Gottlieb SH, Gold AR, Schwartz AR, Smith PL
(2004) Elimination of central sleep apnoea by mitral valvulo-
plasty: the role of feedback delay in periodic breathing. Thorax
59:174–176
12. Kasai T (2012) Sleep apnea and heart failure. J Cardiol 60:78–85
13. Garrigue S, Bordier P, Jais P, Shah DC, Hocini M, Raherison C,
Tunon De Lara M, Haissaguerre M, Clementy J (2002) Benefit of
atrial pacing in sleep apnea syndrome. N Engl J Med
346:404–412
14. Manisty CH, Willson K, Davies JE, Whinnett ZI, Baruah R,
Mebrate Y, Kanagaratnam P, Peters NS, Hughes AD, Mayet J,
Francis DP (2008) Induction of oscillatory ventilation pattern
using dynamic modulation of heart rate through a pacemaker. Am
J Physiol Regul Integr Comp Physiol 295:R219–R227
15. Baruah R, Manisty CH, Giannoni A, Willson K, Mebrate Y,
Baksi AJ, Unsworth B, Hadjiloizou N, Sutton R, Mayet J, Francis
DP (2009) Novel use of cardiac pacemakers in heart failure to
dynamically manipulate the respiratory system through algorith-
mic changes in cardiac output. Circ Heart Fail 2:166–174
16. Dempsey JA, Smith CA, Blain GM, Xie A, Gong Y, Teodorescu
M (2012) Role of central/peripheral chemoreceptors and their
interdependence in the pathophysiology of sleep apnea. Adv Exp
Med Biol 758:343–349
17. Tantucci C, Bottini P, Fiorani C, Dottorini ML, Santeusanio F,
Provinciali L, Sorbini CA, Casucci G (2001) Cerebrovascular
reactivity and hypercapnic respiratory drive in diabetic auto-
nomic neuropathy. J Appl Physiol (1985) 90:889–896
18. Ryan CM, Floras JS, Logan AG, Kimoff RJ, Series F, Morrison
D, Ferguson KA, Belenkie I, Pfeifer M, Fleetham J, Hanly PJ,
Smilovitch M, Arzt M, Bradley TD (2010) Shift in sleep apnoea
type in heart failure patients in the CANPAP trial. Eur Respir J
35:592–597
Heart Vessels
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