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Systematic review

Obstructive sleep apnoea–hypopnoea and arrhythmias: new updates Enrico Vizzardi, Edoardo Sciatti, Ivano Bonadei, Antonio D’Aloia, Antonio Curnis and Marco Metra Aims Obstructive sleep apnoea–hypopnoea (OSAH) is a prevalent condition characterized by repetitive pharyngeal collapse during sleep, leading to hypoxemia, hypercapnia, and persistent inspiratory efforts against an occluded airway until arousal. Several studies demonstrated that OSAH exerts acute and chronic effects on the cardiovascular system. Thus, although being a respiratory problem, the most important consequences of OSAH are cardiovascular, among which there are arrhythmias. The purpose of this review is to systematically analyse what has been recently published about the relationship between OSAH and every cardiac arrhythmia separately.

increased according to the severity of the disturbance and may be reduced by continuous positive airway pressure therapy, preventing pace-maker implantation. Finally, atrial fibrillation, resistance against antiarrhythmic drugs and recurrences after surgical procedures are strongly related to OSAH.

Methods We searched Pubmed, Scopus, Web of Science and Cochrane Collaboration databases for ‘OSAHS arrhythmias’, ‘OSAH arrhythmias’ and ‘OSA arrhythmias’. We analyse 1298 articles and meta-analyses, excluding already edited reviews.

J Cardiovasc Med 2014, 15:000–000

Results Arrhythmias, especially of ventricular origin, are frequent in OSAH. Ventricular premature beats, couplets and ventricular tachycardia runs are even more frequent in patients suffering from heart failure. They may be due to left heart remodelling, overwork and ischaemia and can explain at least some sudden deaths occurring between midnight and 6 a.m. Sinus pauses and atrioventricular blocks are

Introduction Obstructive sleep apnoea–hypopnoea (OSAH) is a condition characterized by repetitive pharyngeal collapse during sleep that leads to markedly reduced (hypopnoea) or absent (apnoea) airflow for at least 10 s, followed by hypoxemia and hypercapnia, persistent inspiratory efforts against an occluded airway and termination by arousal from sleep.1 An OSAH that causes daytime sleepiness is named OSAHS (OSAH syndrome). Severity of OSAH is determined by the apnoea–hypopnoea index (AHI) measured during polysomnography (PSG, the diagnostic gold standard), which represents the number of obstructive respiratory events lasting longer than 10 s per hour of sleep. An AHI less than 5 is considered as normal, 5–14 mild, 15–29 moderate and at least 30 is classified as severe OSAH.2–4 The Epworth Sleepiness Scale (ESS)5 and Berlin Questionnaire6 are two of the widely prescreening tools for people who may suffer from sleep disorders. OSAH is estimated to affect 4% of middle-aged men and 2% of middle-aged women,7 but up to 93% of women and 1558-2027 ß 2014 Italian Federation of Cardiology

Conclusion Arrhythmias are frequent in OSAH. Treatment of OSAH may reduce some of them. An implantable cardioverter-defibrillator and continuous positive airway pressure should be considered in some patients.

Keywords: apnoea, arrhythmias, atrial fibrillation, obstructive sleep apnoea, sudden cardiac death Section of Cardiovascular Diseases, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Study of Brescia, Brescia, Italy Correspondence to Enrico Vizzardi, MD, Section of Cardiovascular Diseases, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Study of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy Tel: +390303995679; fax: +390303996801; e-mail: [email protected] Received 6 October 2013 Revised 17 February 2014 Accepted 17 February 2014

82% of men suffering from OSAH are not diagnosed.8 Recently, the pace-maker transthoracic impedance sensor that derives minute ventilation to regulate rate adaptation can be used to automatically detect sleepdisordered breathing9; Shalaby et al.10 proved that 67% of patients with a pace-maker had moderate to severe OSAH and that 53% of them had a severe one. Interestingly, only 8% of them knew the diagnosis before the study. OSAH is strongly linked to obesity and other major risk factors are male sex, abnormalities in craniofacial morphology and increasing age (fifth–seventh decade of life). Apnoeas and hypopnoeas exert several acute and chronic effects on the cardiovascular system. Acute effects are dominated by hypoxemia, hypercapnia, exaggerated negative intrathoracic pressure and arousals.11–18 Chronic effects include autonomic dysregulation, chronic inflammation, procoagulant state, insulin resistance, endothelial dysfunction, oxidative stress and accelerated atherosclerosis.19–36 OSAH is frequent among patients with heart DOI:10.2459/JCM.0000000000000043

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failure with reduced or preserved ejection fraction, affecting 30% of them37 and may contribute to its onset and progression.38,39 The most frequently related cardiovascular diseases are hypertension, heart failure, stroke, coronary artery disease (CAD), pulmonary hypertension and arrhythmias40–50 (Fig. 1). Wilcox et al.51 added OSAH to syndrome X setting up the term ‘syndrome Z’, as OSAH patients have many features in common with those with syndrome X, although OSAH could increase the cardiovascular risk. Differently from OSAHS, central sleep apnoea (CSA) is characterized by the absence of airflow for at least 10 s accompanied by no respiratory effort (thus without rib cage and abdominal movements) and results from instability in the chemoreflex control of breathing. The term includes Cheyne–Stokes respiration, an oscillation of ventilation between apnoea and hyperpnoea with a crescendo–diminuendo pattern according to serum partial pressures of oxygen and carbon dioxide. This periodic respiration occurs while both awake and asleep and is also very common among patients who suffered from heart failure, being present in 30–40% of them.52,53 Even CSA is thought to predispose to arrhythmias54 and AHI measured during PSG classifies its severity. According to the American Academy of Sleep Medicine, continuous positive airway pressure (CPAP) is the therapy of choice for mild, moderate and severe OSAH.2 It is useful for ventilator support as well as a tool for

secondary prevention of cardiac problems.38,55–64 The severity of OSAH is associated with mortality and CPAP may reduce it.40,65–67

Materials and methods The purpose of this review is to systematically analyse what has been recently published about the relationship between OSAH and arrhythmias. In particular, we focused on electrophysiological consequences, clinical sequelae and different therapeutic approach than nonOSAH patients. We searched PubMed, Scopus, Web of Science and Cochrane Collaboration databases for the following three keywords: ’OSAHS arrhythmias’, ‘OSAH arrhythmias’ and ‘OSA arrhythmias’. We found 1298 items and we carefully analysed every published article and metaanalysis, excluding reviews. Then, for every article, we considered its own bibliography to find other important references.

Results Sudden cardiac death

Multiple mechanisms may increase the risk of sudden cardiac death (SCD) in OSAH patients. First, apnoeic episodes may favour myocardial ischaemia through hypoxemia and increased sympathetic tone, and a proinflammatory and procoagulant state. Second, cardiac death may be caused by sinus arrest or atrioventricular block

Fig. 1

OSAH

i parasympathetic tone

h sympathetic tone

h heart rate

Hypoxemia and hypercapnia

Arousals

i myocardial O2 delivery

h blood pressure

i intrathoracic pressure

Oxidative stress, inflammation, endothelial dysfunction, procoagulant state, amyloid

Hypertension, atherosclerosis, myocardial ischemia, left ventricle hypertrophy and failure, cardiac arrhythmias, cerebrovascular disease, metabolic abnormalities

h left ventricle wall tension and cardiac O2 demand

Pathophysiology of obstructive sleep apnoea–hypopnoea (OSAH) consequences upon the cardiovascular system.

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while asleep due to the prevalence of vagal tone (see next section). Third, myocardial ischaemia, fibrosis and wall stress due to hypertension and concentric hypertrophy68 favour early or delayed after depolarizations and reentry, increasing the risk of ventricular arrhythmias and SCD. In 1991, Gami et al.69 first demonstrated that a history of ‘habitual’ snoring obtained from relatives of dead patients was associated with SCD in the early morning (P < 0.01) with an odds ratio (OR) of 4. Zeidan-Shwiri et al.70 reviewed the death certificates of 112 patients who suddenly died from cardiovascular causes who had previously undergone a PSG. They demonstrated that from

midnight to 6 a.m., SCD occurred in 46% of people with OSAH, as compared with 21% of people without OSAH (P ¼ 0.01), 16% of the general population (P < 0.001). People with SCD from midnight to 6 a.m. had a significantly higher AHI than those with SCD during other intervals, and the AHI correlated directly with the relative risk (RR) of SCD from midnight to 6 a.m. For people with OSAH, the RR of SCD from midnight to 6 a.m. was 2.57 [95% confidence interval (CI) 1.87–3.52]. The authors concluded that patients with OSAH have a peak time of SCD significantly different from people without it (Table 1).66,68–82

Principal characteristics of cited studies regarding obstructive sleep apnoea–hypopnoea and ventricular arrhythmias/sudden cardiac death

Table 1 Ref.

Design

Patients

Diagnostic method

Cardiac monitoring

Results

Mehra et al.71

Case–control

228 severe OSAH vs. 338 healthy

PSG

12-lead ECG during PSG

Mehra et al.72

Cohort study

2911 unselected OSAH

PSG

12-lead ECG during PSG

Seppa¨la¨ et al.68 Retrospective

460 cases of sudden death

Interview to closest cohabiting individuals

None

Gami et al.69

Retrospective

112 cases of SCD

PSG

None

Doherty et al.66

Retrospective

None

Craig et al.73

Case–control

168 unselected OSAH PSG (only 107 treated with CPAP) 83 moderate–severe OSAH PSG

Nonsustained ventricular tachycardia OR 3.40, complex ventricular premature beats OR 1.74 Increasingly OSAH quartile and hypoxia level associated with increasing complex ventricular ectopy Cardiovascular death more common among habitually or often snoring and more often while sleeping. Habitual snoring risk factor for morning death OSAH patient died more likely between 12 p.m. and 6 a.m. (RR 2.57). People died in those hours had higher AHI SCD more common in untreated group Nonreduction of ventricular ectopics with CPAP Premature ventricular complex significantly different, reduced by CPAP SCD predicted by age, AHI, mean and lowest nocturnal O2 saturation Ventricular premature beats higher during simulated apnoea or hypopnoea

Abe et al.

74

Gami et al.75 Camen et al.76

Ryan et al.77

Nonrandomized 197 mild, 368 moderate, PSG prospective 785 severe OSAH, 44 healthy (316 CPAP therapy) Observational 10 701 adults PSG prospective undergone PSG Uncontrolled 41 healthy volunteers Simulated obstructive hypopnoea (inspiration through a threshold load), and apnoea (Mu¨ller manoeuvre) Case–control 40 HF patients with OSAH PSG (20) or CSA (20)

Ryan et al.78

Case–control

18 HF patients with OSAH (10 CPAP and 8 non-CPAP)

PSG

Bitter et al.79

Case–control

472 HF patients with ICD (189 CPAP and 283 non-CPAP)

PSG

Fichter et al.80

Uncontrolled

38 HF patients

PSG

Javaheri et al.81 Uncontrolled

86 HF patients

PSG

214 patients with ICD or CRT-D

Nasal-pressure recording

Anselme et al.

82

Cohort

24-h Holter ECG 12-lead ECG during PSG None Continuous ECG recording

12-lead ECG during Ventricular premature beats more PSG frequent during apnoeic phase in OSAH and hyperpnoeic phase in CSA 12-lead ECG during 58% reduction of ventricular PSG premature beats with 1-month CPAP ICD activity and Time to the first appropriate recording cardioverter-debrillator therapy and the first appropriately monitored ventricular arrhythmia shorter with CPAP Holter ECG during Ventricular arrhythmias (couplets, PSG triplets, short runs) more frequent during OSAH or CSA episode Holter ECG during Number of arousals associated PSG with VT and AHI with couplets 24-h Holter ECG Ventricular tachyarrhythmias more frequent in moderate– severe OSAH

AHI, apnoea–hypopnoea index; CPAP, continuous positive airway pressure; CRT-D, cardiac resynchronization therapy-defibrillator; CSA, central sleep apnoea; ECG, electrocardiogram; HF, heart failure; ICD, implantable cardioverter defibrillator; OR, odds ratio; OSAH, obstructive sleep apnoea–hypopnoea; PSG, polysomnography; RR, relative risk; SCD, sudden cardiac death; VT, ventricular tachycardia.

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Hung et al.83 showed that implantable cardioverter-defibrillator (ICD) discharges were higher among patients with sleep-disordered breathing than those who had not (73 vs. 47%; P ¼ 0.02). By means of logistic regression, they identified these disturbances as a predictor of any appropriate ICD therapy (OR 4.4, 95% CI 1.4–15.3; P ¼ 0.01). The risk for ventricular arrhythmias was higher in those patients solely due to an increase in events occurring between midnight and 6 a.m. (OR 5.6, 95% CI 2.0–15.6; P ¼ 0.001), with no discernible effect on appropriate ICD therapy during nonsleeping hours (OR 0.7, 95% CI 0.2–2.3; P ¼ 0.61). The authors concluded that there is a rationale for screening for OSAH those patients who have had appropriate ICD therapy if device interrogation reveals a predominance of nocturnal onset of arrhythmias.83 Campos-Rodriguez et al.67 ran a prospective study to assess cardiovascular deaths among 107 patients treated with CPAP and 61 intolerant of it. Cardiovascular deaths were more common in the untreated group than in the CPAP-treated group (14.8 vs. 1.9%, respectively; P ¼ 0.009).67 In a recent longitudinal study of 10 701 patients followed-up for 15 years after PSG, the authors found that SCD was best predicted by age more than 60 years (hazard ratio 5.53, 95% CI 3.84– 7.94), AHI >20 (hazard ratio 1.60, 95% CI 1.14–2.24) and nocturnal hypoxemia identified by mean O2 saturation less than 93% (hazard ratio 2.93, 95% CI 1.98–4.33) and lowest less than 78% (hazard ratio 2.60, 95% CI 1.85– 3.65, all P < 0.0001).84 Ventricular arrhythmias seem to be the mechanism more likely to explain the increased mortality of patients’ sleep disturbances.73 In the general population, ventricular arrhythmias are mostly suppressed overnight because of the prevalence of the vagal tone. In fact, non-OSAH patients die from SCD principally at 6–10 a.m. In contrast, in OSAH, patients have an increased sympathetic drive during night and this may explain the higher RR of SCD during sleep.72,85 Electrocardiographic changes

Camen et al.76 randomized 41 OSAH patients on CPAP therapy to 2 weeks withdrawal or continued therapy. At baseline and after 2 weeks, every patient underwent a PSG and a 12-lead ECG in order to calculate indices of cardiac repolarization [QTc, T peak to T end (TpTec) intervals] and dispersion of repolarization (TpTe/QT ratio). Compared with therapeutic CPAP, subtherapeutic CPAP for 2 weeks was associated with a significant increase in the length of the QTc and TpTec intervals (both P < 0.001) and in the TpTe/QT ratio (P ¼ 0.020). Moreover, the change in AHI from baseline was significantly correlated to that of QTc and of TpTec intervals (r ¼ 0.60, 95% CI 0.36–0.77, P ¼ 0.001 and r ¼ 0.45, 95% CI 0.17–0.67, P ¼ 0.003, respectively).76 In another study, 41 healthy volunteers had continuous ECG recordings before, during and after simulated obstructive hypopnoea (inspiration through a threshold load), simulated apnoea (Mu¨ller manoeuvre, inspiration against an

occluded mouthpiece), end-expiratory central apnoea and normal breathing, in a randomized order. Both simulated obstructive hypopnoea and apnoea significantly increased TpTec interval (P ¼ 0.010 and P ¼ 0.002, respectively), whereas only apnoea prolonged the QTc interval (P ¼ 0.035). There were no significant changes of the QTc and TpTec intervals during central end-expiratory apnoea. In addition, ventricular and supraventricular premature beats were more frequent during simulated hypopnoea or apnoea (P ¼ 0.008 for both).86 Finally, a cross-sectional study of 221 patients who underwent a PSG revealed a positive correlation between AHI and QRS duration (r ¼ 0.141, P ¼ 0.03); interestingly, the mean QRS duration prolonged significantly as OSAH worsened (P ¼ 0.001). These findings may explain the arrhythmic risk associated with OSAH.77 Ventricular arrhythmias

In the Sleep Heart Health Study,85 the prevalence of arrhythmias was compared between individuals with (n ¼ 228) and without (n ¼ 338) sleep-disordered breathing. Even after adjusting for age, sex, race and BMI, individuals with sleep-disordered breathing had three times the odds of nonsustained ventricular tachycardia (NSVT) (OR 3.40; 95% CI, 1.03–11.20) and almost twice the odds of complex ventricular premature beats (OR 1.74; 95% CI, 1.11–2.74). A statistically significant correlation was also observed between sleep-disordered breathing and ventricular ectopic beats per hour (P ¼ 0.0003). Later, in a substudy,72 the authors evaluated the role of sleep disturbances as potential triggers of paroxysmal atrial fibrillation (AF) or NSVT. They found that the risk of finding arrhythmias following a respiratory disturbance was nearly 18 times (OR 17.5; 95% CI 5.3– 58.4) higher than following normal breathing. Similar data were found in the MrOS (Osteoporotic Fractures in Men) Sleep Study, in which complex ventricular ectopy (defined as bigeminy, trigeminy, quadrigeminy or NSVT) was strongly associated with the severity of OSAH and hypoxemia (P ¼ 0.01 for both trends) (Table 1).87 A randomized controlled trial compared 1-month therapeutic CPAP vs. nontherapeutic CPAP in patients with moderate to severe OSAH and did not demonstrate a reduction in ventricular (and supraventricular) arrhythmias, albeit the first group experienced a decrease in the mean 24-h heart rate,74 perhaps because the study was underpowered or the CPAP period too short. In contrast, a Japanese study involving 316 OSAH patients demonstrated a reduction in premature ventricular complexes after CPAP (P ¼ 0.016).75 Ventricular premature beats are generally more frequent in patients who suffered from heart failure; they occur during the apnoeic phase in OSAH patients and in the hyperpnoeic period in CSA ones.78 One-month CPAP therapy in people affected by OSAH and heart failure

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reduced by 58% ventricular premature beat frequency during sleep as compared with a control group (P ¼ 0.011).79 A recent study enrolled 472 heart failure patients with an ICD; 189 of them had OSAH or CSA treated with CPAP, while the remaining 283 were the control group. The primary study outcome was eventfree survival time to the first appropriate cardioverterdefibrillator therapy and the secondary outcome was the event-free survival time to the first appropriately monitored ventricular arrhythmia. Both resulted significantly shorter in patients with OSAH and CSA, suggesting that they are independently associated with an increased risk for ventricular arrhythmias and appropriate cardioverterdefibrillator therapy.80 An increased rate of ventricular arrhythmias during episodes of OSAH or CSA in patients with heart failure and reduced ejection fraction was also shown by Javaheri et al.81 and P pin et al.88 AHI and severity of hypoxemia during sleep correlate with appropriate ICD discharges (r ¼ 0.718, P < 0.001 and r ¼ 0.619, P ¼ 0.003, respectively).82 Recently, the relationship between OSAH and ventricular tachyarrhythmias burden has been evaluated by means of a device allowing simultaneous nasal pressure recordings, as a surrogate for PSG, and ECG, in 214 patients with an ICD or CRT. This study confirmed that the number of ventricular tachyarrhythmias was significantly higher in patients with moderate or severe OSAH than in those with mild or nonOSAH. Vice versa, no differences were found between patients with moderate or severe sleep disorders.82 Table 2

Bradiarrhythmias

Bradyarrhythmias and sinus pauses are commonly described in OSAH patients. However, there is a huge variability between studies with rates ranging from 5 to 50%.89–92 The Sleep Heart Health Study did not even find a significant difference among OSAH and nonOSAH patients with regard to sinus pauses and atrioventricular blocks.85 These results could be explained by the lower prevalence of severe OSAH than in older studies (Table 2).71,74,89–96 On the contrary, the European Multicenter Polysomnographic Study showed that long-term paced patients affected by sick sinus syndrome or atrioventricular block suffer OSAH in 58 and 68% of the cases, respectively, and severe OSAH in 27% of the cases. Altogether, the prevalence of undiagnosed OSAH in long-term paced patients was 59%, suggesting that OSAH should be systematically searched for in paced patients. It is still unknown whether OSAH treatment may prevent the development of bradyarrhythmias.37,97 The most common cardiac rhythm abnormality of OSAH patients is severe sinus arrhythmia, characterized by bradycardia during the apnoeic phase (the hypoxic stimulation of the carotid body elicits vagal drive) with subsequent tachycardia on resumption of respiration (lungs stretching inhibits cardiac vagal drive).98 This arrhythmia is virtually universal in patients with severe OSAH and has been proposed as a predictor of a positive diagnosis of

Principal characteristics of cited studies regarding obstructive sleep apnoea–hypopnoea and bradyarrhythmias Design

Patients

Diagnostic method

Cardiac monitoring

Results

Observational, prospective

239 unselected OSAH

PSG

24-h Holter ECG

Simantirakis et al.90

Observational, prospective

23 moderate–severe OSAH

PSG

Implantable loop recorder

Guilleminault et al.91 Miller92

Uncontrolled Uncontrolled

400 severe OSAH 23 unselected OSAH

PSG PSG

24-h Holter ECG 24-h Holter ECG

Mehra et al.71

Case–control

228 severe OSAH vs. 338 healthy

PSG

12-lead ECG during PSG

Roche et al.93

Case–control

66 OSAH vs. 81 healthy

PSG

Holter ECG during PSG

Abe et al.74

Nonrandomized, prospective

PSG

12-lead ECG during PSG

Harbison et al.94

Observational, prospective

197 mild, 368 moderate, 785 severe OSAH, 44 healthy (316 CPAP therapy) 45 unselected OSAH

Second and third-degree AV block and/or sinus arrest in 7.5% Cardiac pauses (>3 s) and bradycardia (3 s), AV blocks, intraventricular conduction delay Pauses and bradycardia significantly different, sinoatrial and second-degree AV blocks not Sinus bradycardia and pauses (>2 s) significantly different, reduced by CPAP

PSG

Sinus pauses and second-degree AV block resolved in 87.5%

Koehler et al.95

Nonrandomized, prospective

PSG

Becker et al.96

Observational prospective

16 OSAH with nocturnal heart block without electrophysiological abnormalities 17 unselected OSAH patients with heart block

18-h Holter ECG before and after 2–3 days of CPAP 24h Holter ECG before and after CPAP/BiPAP

ECG before and after CPAP

Significantly decrease of heart block, completely abolished in 70.6%

Ref. Becker et al.

89

PSG

AV blocks and sinus arrest completely eliminated in 56%, reduced in 31% patients, unchanged in 13%

AV, atrioventricular; BiPAP, bi-level positive airway pressure; CPAP, continuous positive airway pressure; ECG, electrocardiogram; OSAH, obstructive sleep apnoea– hypopnoea; PSG, polysomnography.

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OSAH.99 Patients with more severe AHI or hypoxia may have vagally mediated episodes of sinus arrest and second and third-degree heart block.93 Simantirakis et al.90 evaluated the 16-month incidence of bradyarrhythmias and the effects of CPAP using an implantable loop recorder in 23 patients with moderate to severe OSAH. During the first 8 weeks, the episodes tended to decrease, and during the last 6 months of follow-up, no new episode was recorded. Interestingly, a simultaneous 48-h Holter ECG recording was less sensitive in showing rhythm.90 A total of 316 OSAH patients underwent CPAP titration and were then reevaluated. CPAP therapy significantly reduced the episodes of sinus bradycardia (P ¼ 0.001), and sinus pauses (P ¼ 0.004).75 These studies, together with older ones,94– 96,100 suggest that bradyarrhythmias are related to the prevalence of vagal tone during apnoeic phases, rather than to structural abnormalities of the conduction system. Moreover, ventricular asystoles during OSAH are not due to pathological mechanisms involving sinus or atrioventricular nodes, as revealed by electrophysiological studies.101 Supraventricular arrhythmias

The Sleep Heart Health Study cited above revealed that premature atrial contractions were significantly more present in OSAH patients (33.8 vs. 24.3%, P ¼ 0.001). Vice versa, supraventicular tachycardia incidence was not different between patients and controls (P ¼ 0.89) (Table 3).26,71,74,85,91,102–112 The prevalence of OSAH in patients with atrial flutter is still unknown. This macroreentry arrhythmia is successfully treated by cavotricuspid isthmus catheter ablation in approximately 91% of cases, but about one-third of patients may develop AF in the long term (52% if AF was present prior to treatment).113,114 A very recent study investigated the role of CPAP therapy in 56 OSAH and non-OSAH patients affected by atrial flutter and undergoing a cavotricuspid isthmus catheter ablation. Around 82% had OSAH and 59% of them were treated with CPAP. Around 38% of all had AF after the procedure, but freedom from AF prior to ablation and CPAP initiation in those patients without previously documented AF at inclusion were associated with a reduction of AF episodes during follow-up (P ¼ 0.019 and P ¼ 0.025, respectively). Inversely, CPAP was not protective from AF recurrence when this arrhythmia was documented prior to ablation (P ¼ 0.25). The authors concluded that screening for OSAH in patients with atrial flutter appears to be a reasonable clinical strategy to reduce the incidence of AF after the procedure.102 To date, whether OSAH favours an unsuccessful cavotricuspid isthmus catheter ablation is unknown. The first evidence of a higher prevalence of AF in people suffering from OSAH was given by Guilleminault et al.91;

they registered 400 OSAH patients by a polygraph simultaneous to a 24-h Holter ECG and found that 8% of them had a nocturnal paroxysm of AF, which varies from 0.4 to 1% in general population. In the Sleep Heart Health Study, again, even after adjusting for age, sex, race and BMI, individuals with sleep-disordered breathing had four times the odds of AF (OR 4.02; 95% CI 1.03– 15.74).85 In the substudy cited above, the authors evaluated the role of sleep disturbances as potential triggers of paroxysmal AF or NSVT; they found that the risk of finding arrhythmias following a respiratory disturbance was nearly 18 times (OR 17.5; 95% CI 5.3–58.4) higher than following normal breathing.72 Moreover, obesity and OSAH were demonstrated as independent risk factors for AF in people with less than 65 years of age (hazard ratio for OSAH 3.29, 95% CI 1.35–8.04; P ¼ 0.009),103 as well as the degree of oxygen desaturation according to the role of hypoxemia in AF onset.104,115 Various works reported an OSAH prevalence of 43–73% in patients affected by AF105; in addiction, AF and atrial flutter medical treatment results more difficult in patients with sleep-disordered breathing.106,116,117 Acetylcholinedependent potassium channels (IK,ACh) are thought to be one of the most relevant components by which vagal tone induces atrial effective refractory period shortening in the atrium, thus contributing to the genesis and propagation of AF118; amiodarone also blocks these channels and so we can speculate that this could be superior to other drugs in maintaining sinus rhythm. To date, specific studies investigating this superiority are lacking. Moreover, apnoeas and subsequent negative intrathoracic pressure increase cardiac afterload and stimulate myocyte hypertrophy, collagen formation and fibroblasts, which contribute to diastolic dysfunction and left atrium enlargement. Even atrial wall stress during apnoeas inspiratory efforts favours atrial size increase.119,120 In particular, atrial electromechanical coupling, intra-atrial and inter-atrial electromechanical delay measured with tissue Doppler imaging, and P-wave duration and dispersion calculated from 12-lead ECG have been demonstrated higher according to OSAH severity.121,122 CPAP therapy in OSAH patients was demonstrated to reduce paroxysmal AF events (P < 0.001) in the Japanese study by Gami et al.75 Untreated OSAH patients have a major risk of AF recurrence than those treated with nasal CPAP104,115; moreover, OSAH is the strongest predictor of recurrent AF after radiofrequency catheter ablation (OR 3.04, 95% CI 1.11–8.32; P ¼ 0.03)107 or cryoballoon technique (hazard ratio 3.20, 95% CI 1.14–8.95; P ¼ 0.03).108 Again, acute return of pulmonary vein conduction after successful pulmonary vein antrum isolation (PVAI) is more likely to occur in OSAH patients.123 Untreated patients without pulmonary vein antrum triggers have a higher risk of procedure failure (hazard ratio 8.81, 95% CI 4.04–19.23; P < 0.001).109 Two recent works confirmed that AF recurrence after successful PVAI is

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Table 3

Principal characteristics of cited studies regarding obstructive sleep apnoea–hypopnoea and supraventricular tachyarrhythmias

Ref.

Design

Patients

Diagnostic method

Cardiac monitoring

Mehra et al.71

Case–control

228 severe OSAH vs. 338 healthy

PSG

12-lead ECG during PSG

Kaviraj et al.26

Uncontrolled

277 unselected OSAH

PSG

24-h Holter ECG

Case–control

56 patients with atrial flutter undergoing cavotricuspid isthmus ablation; 46 of whom OSAH (27 treated with CPAP) 400 severe OSAH 3542 adults

Obstructive sleep apnoea-hypopnoea and arrhythmias: new updates.

Obstructive sleep apnoea-hypopnoea (OSAH) is a prevalent condition characterized by repetitive pharyngeal collapse during sleep, leading to hypoxemia,...
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