Heart Vessels DOI 10.1007/s00380-014-0511-x


Bradyarrhythmias may induce central sleep apnea in a patient with 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 Ó 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

limited data regarding the relationship between central sleep apnea (CSA) and bradyarrhythmia [8], and it is unclear whether this relationship is causal. CSA is frequently 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.

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

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]

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 hypertriglyceridemia (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;


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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 polysomnography 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 circulation time, MA mixed apnea, OA obstructive sleep apnea, REM rapid eye movement, SO2 oxyhemoglobin saturation

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 diagnostic 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 polysomnography that was associated with a prolonged lung-tofinger 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


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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 echocardiogram 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 bradyarrhythmias has been suggested [5, 7], there are limited data supporting relationship between CSA and bradyarrhythmia [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 associated 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 conjunction 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 polysomnography, 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 significantly 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 therapies for each cardiovascular condition [9–11]. Littman and colleagues reported a case series suggesting a relationship 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 bradyarrhythmiarelated 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 following cardiac transplantation was accompanied by complete 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 pacemaker implantation, the effect of these factors may be reduced, leading to a shortened circulation time and alleviation 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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Bradyarrhythmias may induce central sleep apnea in a patient with obstructive sleep apnea.

The relationship between central sleep apnea (CSA) and bradyarrhythmia remains unclear. We report the case of a 70-year-old man with severe obstructiv...
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