Bradyarrhythmias may induce central sleep apnea in a patient with obstructive sleep apnea

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: kasai-t@mx6.nisiq.net

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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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.

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