https://orcid.org/0009-0006-4684-9765
Abstract
The relationship between sleep and arrhythmias is well established. Furthermore, the association between obstructive sleep apnoea (OSA) and bradyarrhythmias is well described. However, only a few cases of bradyarrhythmias observed during rapid eye movement (REM) sleep or REM sleep-related bradyarrhythmia syndrome, as it is known, have been documented in the literature.
Here, we report another example of this syndrome. This was diagnosed during polysomnography in a middle-aged male and was independent of OSA. Several pauses, up to 5.7 s in duration, were observed during the study. A decision was made not to insert a pacemaker in this instance.
The mechanism behind such bradyarrhythmias is not well established. However, features of autonomic lability were observed on the patient’s electrocardiogram monitoring during stress testing. Such autonomic lability with vagal predominance may be the driver of the bradyarrhythmias. It is unknown whether they represent a benign incidental finding or not due to limited case numbers. Furthermore, there is currently no clear consensus on their management. This stresses the need for further research to confirm their pathophysiological basis and develop clearer management strategies.
Nocturnal bradyarrhythmias are common and are believed to mostly be physiological, vagally mediated asymptomatic events, which do not require intervention. Patients should be screened for obstructive sleep apnoea, including soliciting suspicious symptoms and then a sleep study if warranted. Treatment should be initiated accordingly.
Patients should also be screened for pathological causes of the arrhythmias (e.g. structural heart disease) and other indications for pacemaker insertion.
There is currently no clear consensus on the management of rapid eye movement sleep-related bradyarrhythmias. While many patients have undergone pacemaker insertion, the evidence supporting this is scant. Patients should be managed on a case-by-case basis and counselled about the limited evidence and the benefits and risks of treatment.
Introduction
Rapid eye movement (REM) sleep-related bradyarrhythmia syndrome is a condition whereby bradyarrhythmias occur exclusively during REM sleep phase.1 Most of the cases documented report bradyarrhythmias secondary to sinus arrest and third-degree atrioventricular (AV) block.2–6 Here, we describe a further example of this rare disorder, but in this case the bradyarrhythmia was secondary to high-grade AV block.
Summary figure
| Investigation | Result |
|---|---|
| Echocardiogram | No underlying structural heart disease |
| Telemetry | Nocturnal pauses |
| Holter monitoring | Nocturnal pauses (up to 12 s) secondary to atrioventricular (AV) block. No daytime pauses |
| Exercise stress test | PR interval of 210 ms decreased to 176 ms during peak exercise and prolonged to 250 ms in recovery period |
| Epworth Sleepiness Scale | Score = 3 (normal daytime sleepiness) |
| Full polysomnographic study | Pauses (up to 5.7 s) secondary to ‘high-grade’ AV block observed during rapid eye movement sleep |
| Investigation | Result |
|---|---|
| Echocardiogram | No underlying structural heart disease |
| Telemetry | Nocturnal pauses |
| Holter monitoring | Nocturnal pauses (up to 12 s) secondary to atrioventricular (AV) block. No daytime pauses |
| Exercise stress test | PR interval of 210 ms decreased to 176 ms during peak exercise and prolonged to 250 ms in recovery period |
| Epworth Sleepiness Scale | Score = 3 (normal daytime sleepiness) |
| Full polysomnographic study | Pauses (up to 5.7 s) secondary to ‘high-grade’ AV block observed during rapid eye movement sleep |
| Investigation | Result |
|---|---|
| Echocardiogram | No underlying structural heart disease |
| Telemetry | Nocturnal pauses |
| Holter monitoring | Nocturnal pauses (up to 12 s) secondary to atrioventricular (AV) block. No daytime pauses |
| Exercise stress test | PR interval of 210 ms decreased to 176 ms during peak exercise and prolonged to 250 ms in recovery period |
| Epworth Sleepiness Scale | Score = 3 (normal daytime sleepiness) |
| Full polysomnographic study | Pauses (up to 5.7 s) secondary to ‘high-grade’ AV block observed during rapid eye movement sleep |
| Investigation | Result |
|---|---|
| Echocardiogram | No underlying structural heart disease |
| Telemetry | Nocturnal pauses |
| Holter monitoring | Nocturnal pauses (up to 12 s) secondary to atrioventricular (AV) block. No daytime pauses |
| Exercise stress test | PR interval of 210 ms decreased to 176 ms during peak exercise and prolonged to 250 ms in recovery period |
| Epworth Sleepiness Scale | Score = 3 (normal daytime sleepiness) |
| Full polysomnographic study | Pauses (up to 5.7 s) secondary to ‘high-grade’ AV block observed during rapid eye movement sleep |
Case presentation
A 50-year-old male was referred for a polysomnographic or sleep study by his cardiologist for two reasons. First, he was found to have multiple nocturnal pauses on telemetry and subsequent Holter monitoring. These pauses were up to 12 s in length and were secondary to AV nodal block. The patient was asymptomatic during them, and there were no pauses detected during daytime. Second, his partner had witnessed him having apnoeic episodes and waking up gasping for air on occasion. He was also experiencing nocturia and insomnia that raised the possibility of a diagnosis of obstructive sleep apnoea (OSA), which could be contributing to the pauses.
The patient’s past medical history included elective stenting of his left anterior descending artery. The pauses were observed on telemetry monitoring after the stent was inserted and prompted further prolonged monitoring with a Holter. He had no structural heart disease on echocardiogram. He had no other significant medical history and had a normal cardiovascular examination. His body mass index was 26, and he was a non-smoker. He had a high level of fitness and regularly engaged in intensive aerobic exercise.
His Epworth Sleepiness Scale score was 3, and his standardized tonsillar hypertrophy grading scale score was 1 giving him a low pre-test probability of OSA. However, he underwent a full polysomnographic study to elucidate further the nature of these pauses.
The pauses were replicated during polysomnography and occurred exclusively during REM sleep (Figure 1). Several pauses were observed, and the longest was 5.7 s long. They were preceded by episodes of sinus bradycardia (lowest 29 b.p.m.) and PR interval prolongation (up to 288 ms). His electrocardiogram (ECG) demonstrated persistence of the P waves throughout the pauses with the last P wave conducting the next QRS complex. This was consistent with second-degree ‘high-grade’ AV block. The pauses were not associated with apnoeas or hypoxia, nor did they occur while the patient was awake. This excluded a possible relationship of the pauses with OSA.
An example of a nocturnal pause (5.7 s) observed during a 30 s epoch of rapid eye movement sleep. Conjugate irregular eye movements typical of rapid eye movement sleep are seen on electrooculography with low-amplitude desynchronized theta electroencephalogram activity with the presence of saw-tooth waves (C3:A2 and C4:A1). Some irregularity of breathing, which is typical of rapid eye movement sleep, was observed, but the pause is not associated with apnoea or hypoxaemia. High-grade atrioventricular block is observed with three non-conducted P waves indicated by black arrows contained within a black box. EMG, electromyogram; PLM, periodic limb movement; RIP, respiratory inductance plethysmography; Pleth, plethysmography; Pos, position.
The sleep study was otherwise largely unremarkable. The patient slept for 6 h with a normal sleep efficiency of 82%. Sleep was exclusively in the supine position, and only infrequent snoring was observed. No episodes of gasping or waking were observed during the pauses, making it unlikely such symptoms were related to the pauses. His apnoea–hypopnoea index was 5/h consistent with borderline or mild OSA and his average SpO2, was 94% with a nadir of 84%. There was no significant periodic limb movement observed, which would point to a parasomnia diagnosis.
Given the borderline diagnosis of OSA, continuous positive airway pressure (CPAP) treatment was not indicated. A trial of a mandibular enhancement device was offered to the patient if he wished to pursue treatment. After much consideration, in conjunction with the patient, a decision was made not to insert a pacemaker. The decision was made with reference to current guidelines as the pauses occurred exclusively at night-time, and he was asymptomatic. The patient remains well to this day.
Discussion
Nocturnal arrhythmias are a relatively common finding in the general population and can be physiological or pathological.1 Sleep-related pathologies like OSA are associated with the development of tachyarrhythmia and bradyarrhythmias.7 Obstructive sleep apnoea is a strong risk factor for the development of atrial fibrillation (AF), and treatment can prevent its development.8 Patients with untreated OSA have higher levels of recurrence of AF following treatment. Obstructive sleep apnoea also causes bradyarrhythmias in up to 18% of patients, which include AV block, sinus pauses, and asystole. Like AF, commencement of CPAP leads to significant reductions in these bradyarrhythmias.7
Non-pathological arrhythmias also occur during sleep. Rapid eye movement sleep-related bradyarrhythmia syndrome occurs independently of OSA and is believed to be non-pathological.1 The first case reported was by Guilleminault et al.,2 which described episodes of sinus arrest in otherwise healthy young adults. Since then, only a few additional cases have been described, predominantly in otherwise healthy middle-aged men.1–6 Only two case reports documented bradyarrhythmias secondary to second-degree heart block, similar to this case.9,10
Although only a few cases of REM sleep-related bradyarrhythmia have been identified, it is likely that the actual prevalence is much higher given its asymptomatic nature. Furthermore, many of these arrhythmias were identified incidentally during sleep studies or during investigation into unrelated symptoms.
The pathophysiology behind REM sleep-related bradyarrhythmias is not well characterized but is thought to be related to an imbalance of autonomic cardiac neural inputs. Studies on normal subjects have demonstrated how nocturnal heart rate and blood pressure are governed by a complex inter-play between the sympathetic and para-sympathetic nervous systems. These changes in heart rate are accounted for by their chronotropic and dromotropic effects. Pronounced changes in sympathetic and para-sympathetic drive occur during sleep, particularly during REM phase, where increased heart rate variability (HRV) is observed. Heart rate variability is an index of sympathetic and para-sympathetic activity.11 Somers et al.12 demonstrated how REM sleep is characterized by sympathetic dominance by measuring nerve impulses of muscle blood vessels. This is associated with increased heart rate, respiratory rate, and blood pressure. This contrasts with non-REM sleep, which is usually para-sympathetic dominant with the opposite physiological effects including reduced heart rate. Therefore, intermittent bradycardia observed during REM sleep is a paradoxical response and may suggest brief bursts of vagal dominance. The low-to-high frequency ratio (LF/HF), an index of HRV spectra, can be used to assess sympathovagal dominance. Janssens et al.1 found that patients with REM sleep-related bradyarrhythmias had reduced switch to an increased LF/HF ratio, which is typically observed during REM sleep, relative to a matched control population. This was suggestive of a relative increase in para-sympathetic activity (HF component). Whether this is caused by an increase in vagal tone or decreased sympathetic drive, or a combination of both, is unknown. Somers et al.12 also demonstrated how momentary restoration of muscle tone during REM sleep (REM twitch) can cause a cessation of sympathetic nerve discharge. It is unknown whether the above effects are central or peripheral (baroreflex) in origin. Over-production of acetylcholine, the neurotransmitter involved in the para-sympathetic response, or an over-sensitivity of their receptors has been hypothesized as possible aetiologies. This hypothesis is supported by a reduction in the frequency of REM-related sinus pauses and bradyarrhythmias following a vagotomy procedure where part of the vagus nerve is removed.13 Furthermore, administration of atropine (an acetylcholine receptor inhibitor) has been shown to decrease REM-related sinus arrests.2
The patient’s resting ECG demonstrated first-degree heart block with a PR interval of 210 ms. However, his PR interval normalized at peak exercise (heart rate of 176 b.p.m.) during stress testing correlating with high sympathetic input. The 1:1 AV nodal conduction was observed at peak heart rate. His PR interval then increased to 250 ms during the recovery period, which is associated with high vagal tone. There were no ischaemic changes observed during stress testing. On Holter monitoring, the patient’s nocturnal pauses were preceded by episodes of sinus bradycardia, and there was no evidence of interventricular conduction delay. Furthermore, the patient had a high level of fitness, which is known to cause increased resting vagal tone.14 Together, these factors favour autonomic lability as the driver of the observed nocturnal bradyarrhythmia over an underlying intrinsic AV nodal pathology or His-Purkinje conduction disease.
According to the ACC/AHA guidelines (2021), patients with nocturnal bradyarrhythmias should be screened for OSA and REM sleep-related bradyarrhythmia syndrome. This should involve the solicitation of suspicious symptoms and then a sleep study if warranted. Treatment with CPAP therapy or conservative measures (e.g. diet, lifestyle) reduces the episodes of bradycardia, and pacemaker insertion should be avoided if possible.
There is currently no strong consensus on the management of REM sleep-related bradyarrhythmia syndrome. The ESC guidelines on cardiac pacing and cardiac resynchronization therapy (2021) state that ‘although most cases quoted in the literature have been treated with pacemakers, the evidence for this is scant, and there is no consensus on how to treat these patients’. They also state that ‘nocturnal bradyarrhythmias are common in the general population. In most circumstances, these are physiological, vagally mediated asymptomatic events, which do not require intervention’.
The ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay (2018) states that, ‘in patients with sleep-related sinus bradycardia or transient sinus pauses occurring during sleep, permanent pacing should not be performed unless other indications for pacing are present’. However, this does not relate to the management of nocturnal pauses secondary to AV block, like in this patient. The guidelines do state that ‘in patients with acquired second-degree Mobitz type II atrioventricular block, high-grade atrioventricular block, or third-degree atrioventricular block not attributable to reversible or physiologic causes, permanent pacing is recommended regardless of symptoms’. Anecdotal evidence suggests that pacing should be considered in those with daytime symptoms.15 As the patient was asymptomatic with exclusively nocturnal pauses that were considered to be physiological, he did not meet any of the indications for pacing according to these guidelines. However, the guidelines lack clarity on the nature of the bradyarrhythmia and the duration of the pauses. Some patients with REM sleep-related bradyarrhythmia syndrome have had pacemakers inserted or have undergone cardioneural ablation, while others have not been treated. Currently, there is no evidence to suggest adverse outcomes for those who were not treated. However, this cohort consists of only a small number of patients. Due to the paucity of evidence, each patient should be managed on a case-by-case basis. Patients should be carefully screened for other indications for pacing (e.g. structural heart disease). The lack of clear evidence should be explained to the patient as well as the risk vs. benefit of pacing vs. not pacing.
In conclusion, this report describes a rare case of a bradyarrhythmia secondary to high-grade AV block observed during REM sleep, independent of OSA. Although this condition may represent a benign incidental finding, its true relevance is still unclear due to the limited number of cases identified and its asymptomatic nature. Furthermore, guidelines for treatment are not well established. This stresses the need for further research to confirm the pathophysiology and develop clear management strategies for these arrhythmias.
Lead author biography
William Griffin is a medical trainee in Ireland. He has interests in both respiratory medicine and cardiology. He has a research interest in nocturnal arrhythmias.
Consent: The authors confirm that written consent for submission and publication of this case report including images and associated text has been obtained from the patient in line with the COPE guidance.
Funding: None declared.
Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
References
Author notes
Conflict of interest: None declared.
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