Europace Advance Access published online on November 12, 2008
Europace, doi:10.1093/europace/eun315
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CLINICAL RESEARCH
Obstructive sleep apnoea risk profile and the risk of recurrence of atrial fibrillation after catheter ablation
1 Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Chaoyang District, Beijing 100029, People's Republic of China; 2 Department of Respiratory Medicine, Beijing An Zhen Hospital, Capital Medical University, Beijing, People's Republic of China
Manuscript submitted 16 August 2008. Accepted after revision 27 October 2008.
* Corresponding author. Tel: +86 10 64456412, Fax: +86 10 64456078, Email: chshma{at}vip.sina.com
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Abstract |
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Aims: The aim of this study was to identify the impact of obstructive sleep apnoea (OSA) on recurrence after catheter ablation of paroxysmal atrial fibrillation (AF).
Methods and results: One hundred and seventy-eight consecutive patients with paroxysmal AF who underwent index circumferential pulmonary vein (PV) isolation were prospectively enrolled. The patients were divided into high risk (HR group) and low risk (LR group) for OSA group with Berlin questionnaire. Of the 178 patients, 104 (58.4%) were in the HR group and 74 (41.6%) were in the LR group. After a mean follow-up of 344 ± 137 (91–572) days, 44 patients (24.7%) experienced recurrence, and the recurrence rate did not differ between the HR (25.0%) and LR groups (24.3%, P = 0.855). Cox analysis revealed that PV isolation was the only independent predictor of recurrence (hazard ratio 5.11, 95% confidence interval 1.42–18.47, P = 0.013). There was no significant difference in the incidence of complications between the HR and LR groups (2.9 vs. 1.9%, P = 0.729).
Conclusion: The recurrence rate and incidence of complications did not differ in patients with different risk profiles for OSA. The presence of OSA should not lower the decision threshold to choose an ablative procedure in paroxysmal AF.
Key Words: Atrial fibrillation, Catheter ablation, Obstructive sleep apnoea, Recurrence
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Introduction |
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As the most common sustained cardiac arrhythmia, atrial fibrillation (AF) affects more than 2 million patients in the USA.1
In recent studies, it was shown that the prevalence and incidence of AF were significantly higher in patients with obstructive sleep apnoea (OSA) and vice versa.2,3 For example, Gami et al.3 found that the proportion of patients with OSA was significantly higher in the AF group than in the general cardiology group (49 vs. 32%). Atrial fibrillation and OSA share many risk factors including male gender, obesity, hypertension, and congestive heart failure.4 In patients with untreated OSA, intermittent hypoxemia, hypercapnia, chemoreceptor excitation, autonomic nerve imbalance, severe pressure surges, and inflammation may initiate AF.5–8 As OSA plays an important role in the pathogenesis of AF, patients with untreated OSA have a higher recurrence of AF after electrical cardioversion than those without OSA.9 Previous studies have examined some predictors of AF recurrence after catheter ablation;10,11 however, there are few data on addressing the impact of OSA on recurrence after catheter ablation of paroxysmal AF. As most of the AF pathogenic factors present in patients with OSA persist after ablation, it is reasonable to hypothesize that OSA increases the risk of recurrence of AF after catheter ablation. Here, we carried out a prospective study to assess the impact of OSA on recurrence of AF after catheter ablation. |
Methods |
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Study subjects
Consecutive patients with refractory symptomatic paroxysmal AF who referred to Beijing An Zhen Hospital (affiliated with Capital Medical University) for index circumferential pulmonary vein (PV) radio frequency ablation from January 2007 to November 2007 were enrolled. Exclusion criteria included left atrial/left atrial appendage thrombus and OSA, which had already been treated with continuous positive airway pressure. All patients signed a written informed consent, and the study was approved by the Institutional Review Board. Overweight and obesity were categorized according to the guidelines for prevention and control of overweight and obesity in Chinese adults [normal weight: body mass index (BMI), 18.5 to <24.0 kg/m2; overweight: BMI, 24.0 to <28 kg/m2; obese: BMI,
28.0 kg/m2].12 Blood samples were drawn on the morning of admission for the assessment of serum C-reactive protein by immunonephelometry using the Dade Behring BNIII analyser protocol (Dade Behring, USA).
Diagnosis of obstructive sleep apnoea
The presence of OSA was diagnosed by the Berlin questionnaire, a validated instrument designed to identify individuals with OSA.13 Patients and their bed partners completed the Berlin questionnaire at enrolment. The questionnaire includes one introductory and four follow-up questions about snoring, three questions about daytime somnolence (including one concerning sleepiness while driving), and one question about history of hypertension. It also collects information about age, gender, race and ethnicity, height, weight, and neck circumference. Patients were considered ‘high risk’ for having OSA if they had a positive response to at least two of the following three criteria: (i) persistent symptoms (more than three times per week) for at least two snoring questions, (ii) persistent (>3 times per week) somnolence during daytime and/or while driving, and (iii) history of hypertension or a BMI >30 kg/m2. The questionnaire had high internal validity (Cronbach correlations 0.86–0.92) and performed accurately, with a sensitivity of 86%, a specificity of 77%, and a positive predictive value of 89% in a primary care setting.13 Epworth sleepiness scale was also performed in the whole population.14
We validated the accuracy of the questionnaire in our study population by assessing its results in patients who accepted our suggestion to undergo formal sleep studies both in the high risk for OSA (HR) group and in the low risk for OSA (LR) group. Recordings were performed overnight, with continuous monitoring of the electroencephalogram, oronasal airflow (by airflow pressure transducer), chest and abdominal respiratory movements, arterial oxygen saturation (by pulse oximetry), body position, and snoring noise (Embletta PDS, Medcare Flaga, Iceland). The apnoea–hyponoea index (AHI) was calculated as the average number of apnoeas and hypopneas per hour of sleep. The diagnosis of OSA was established if AHI 5, according to the sleep study criteria recommended by the Chinese Medical Association.15
Electrophysiological study, mapping, ablation, and follow-up
The ablation procedure was performed in post-absorptive state under conscious sedation.16 All anti-arrhythmic drugs, with the exception of amiodarone, had been discontinued for at least 5 half-lives. We employed the technique of circumferential PV ablation guided by three-dimensional left atrial mapping, which had been described previously in detail.10 Briefly, left atrium was explored using a trans-septal approach. Left atrial geometry was reconstructed with a 3.5 mm tip ablation catheter (Navi-Star ThermoCool, Biosense-Webster, USA) in a CARTO system. A continuous irrigated radio frequency ablation was performed along each PV antrum in order to encircle the ipsilateral PVs (target temperature: 43°C, maximum power: 35 W, infusion rate: 17 mL/min). Procedural endpoints were completeness of continuous circular lesions and electrical isolation of all PVs identified by a decapolar circumferential mapping catheter (Lasso, Biosense-Webster). If a typical atrial flutter had been documented before the procedure, the tricuspid isthmus responsible for this tachycardia was identified and ablated.
After the procedure, all patients received anti-arrhythmic drugs if there were neither contraindications nor intolerance. If no recurrent atrial tachyarrhythmia occurred after 2 or 3 months, the drug treatment was discontinued. All asymptomatic patients were followed up with a 12-lead electrocardiogram and 24 h Holter recordings before discharge and at 1, 3, 6, and 12 months after the ablative procedure. If the patient was symptomatic, a new electrocardiogram was obtained. Additionally, telephone interviews were conducted monthly in all patients by a physician, and trans-telephonic event recorders (Life Care Networks, China) were performed in patients who accepted this monitoring following the physician's recommendation. Recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia (documented by electrocardiogram or Holter recordings) beyond 3 months after the index catheter ablation.
Statistical analysis
All analyses were performed with the SPSS software version 13.0. Continuous data are presented as mean ± standard deviation. Univariate analysis to assess the predictive value of clinical variables on AF recurrence was computed using the unpaired independent samples t-test for continuous variables and the 
2 test and Fisher's exact test if necessary for categorical variables. A Kaplan–Meier estimation with a log-rank test served for the unadjusted analysis of the impact of OSA on recurrence of AF. Cox proportional hazards regression was employed to examine the risks for recurrence. All probability values were two-sided, and a P-value less than 0.05 was considered significant.
Based on an assumption that sinus rhythm would be maintained in 75 and 50% of the patients in the LR and HR groups, respectively, and the proportion of groups would be 1:1,3 a minimum of 170 patients was required at a power of 90% to reach a two-tailed alpha of 0.05. Considering the possibility of drop-outs, we planned to increase the number of patients by 5%.
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Validation of Berlin questionnaire
Thirty patients underwent overnight sleep studies. Compared with the gold standard of an overnight sleep study, the Berlin questionnaire performed with 100.0% sensitivity, 30.0% specificity and had a positive predictive value of 74.1% and a negative predictive value of 100% for OSA. The mean AHI was 28.5 ± 22.7 and 2.2 ± 1.4 in the HR and LR groups, respectively (P = 0.001).
Characteristics of the high- and low-risk groups
Of the 178 patients, 104 (58.4%) had high risk for OSA. The characteristics of the HR and LR groups were shown in Table 1. The prevalences of hypertension, overweight, and obesity were significantly higher in the HR group than in the LR group. The patients in the HR group had older age, larger left atrial diameter, higher BMI, and longer neck circumference. The proportion of the angiotensin-converting enzyme inhibitors or angiotensin receptor blocker medication was significantly higher in the HR group than in the LR group.
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Obstructive sleep apnoea and recurrence
After a mean follow-up of 344 ± 137 (91–572) days, 44 patients (24.7%) experienced recurrence with the mean time of 160 ± 94 days. Eight of the 44 patients (18.2%) underwent formal sleep studies before the ablative procedure. As it was shown in Figure 1, the recurrence rate was 24.3% in the HR group and 25.0% in the LR group (P = 0.855). It was shown in Table 2 that PV isolation was the only univariate predictor of AF recurrence. After adjustment for age, AF duration, BMI, hypertension, structural heart disease, OSA, C-reactive protein, angiotensin-converting enzyme inhibitors or angiotensin receptor blocker medications, and statins medication, the Cox analysis revealed that PV isolation was the only independent predictor of recurrence (hazard ratio 5.11, 95% confidence interval 1.42–18.47, P = 0.013). The other variates including OSA (hazard ratio 0.94, 95% confidence interval 0.43–2.04, P = 0.876) were not independent predictors of recurrence.
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Procedure outcome and complications
There were no significant differences in procedural time, fluoroscopy time, and PV isolation rate between the two groups (Table 1). Seventeen of the 19 patients who underwent a redo procedure had PV reconnections. Procedural complications occurred in the HR group with pulmonary embolism (one case) and femoral haematoma (one case) and occurred in the LR group with PV stenosis (one case) and femoral haematoma (one case). Significant difference in the incidence of complications between the LR and HR groups was not observed (2.9 vs. 1.9%, P = 0.729).
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Discussion |
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The findings presented in this study are as follows: (i) more than half of the patients who underwent catheter ablation of AF are in the high-risk profile for OSA; (ii) PV isolation is an independent predictor of AF recurrence; (iii) although AF and OSA share many risk factors, high risk for OSA is not a predictor of recurrence after catheter ablation of paroxysmal AF with both univariate and multivariate analyses.
The relationship between OSA and AF has been explored extensively. In a recent study, it was found that OSA was an independent risk factor for incident AF in individuals <65 years of age.2 It is speculated that some unique interactions exist between the pathogenic factors of OSA and AF. For example, in patients with OSA, amyloidosis, inflammation, mechanical effects of apnoea, hypoxemia, sympathetic hyperactivity, and myocardial ischaemia may initiate AF and other cardiac arrhythmias;5–8,17 some of those factors are well known to favour AF initiation and maintenance.
In this study, 58.4% of the patients with AF who underwent catheter ablation had OSA diagnosed by the Berlin questionnaire. Our study confirms that OSA was highly associated with AF in this population. Further, we sought to address the outcome of catheter ablation of AF in this subgroup of patients. As a pathogenesis factor of AF, it is reasonable to believe that OSA would have an adverse effect and would lower the success rate of catheter ablation of AF. As shown in the Results section and contrary to our hypothesis, OSA did not increase AF recurrence after catheter ablation of paroxysmal AF. As it was shown in Ouyang's studies,18,19 PV reconnection is a dominant factor for atrial tachyarrhythmias after PV isolation. In this study, PV isolation was also independently related to recurrence. It seemed that the underlying AF electrophysiological substrate was critical for AF recurrence after ablation, but that the specific pathogenic factors related to OSA were less contributive. Previous studies have shown contrasted results: Sauer et al.20 showed that OSA was an independent predictor of acute PV reconnection but that acute PV reconnection was not significantly associated with long-term AF control. In contrast, Jongnarangsin et al.21 showed that OSA was a strong predictor of recurrent AF after catheter ablation. Differences between those studies and our work may be presumed partially attributable to the following: (i) This study only enrolled paroxysmal AF, whereas 
30% of chronic AF was included in Jongnarangsin's study. Accordingly, the applied ablative strategy was different. (ii) To avoid considering early and transient recurrence, a blanking period of 8 weeks was applied in Jongnarangsin's study. However, 12 weeks was applied in our study according to the recommendation by HRS expert consensus.22 (iii) The risk profile of OSA was prospectively evaluated by the Berlin questionnaire in all of the populations in this study. However, only 32 patients were diagnosed as OSA by polysomnography in Jongnarangsin's study, whereas the others did not undergo polysomnography studies and were arbitrarily regarded as non-OSA. In a retrospective study like Jongnarangsin's, most of the patients who underwent polysomnography usually had symptoms suggestive of severe OSA. Thus, we respectfully submit that the impact of OSA might have been overestimated in Jongnarangsin's study.
The use of the Berlin questionnaire to identify patients with OSA is a main limitation of our study, because overnight sleep study is considered as the gold standard for the diagnosis of OSA, and only eight of the 44 patients were diagnosed with sleep study who experienced recurrent AF. However, Berlin questionnaire was an established method for OSA diagnosis.13 In addition, we confirmed that it was extremely accurate in the present study population with 100% sensitivity and 30.0% specificity. Another limitation is that the impact of OSA on recurrence was only explored in paroxysmal AF. Thus, the results could not be extended to the other persistent AF. Finally, AF recurrence diagnosis was based on symptoms occurrence, electrocardiogram tracings, and Holter-ECG findings in the present study. Potentially, AF recurrence rate may have been underestimated because asymptomatic AF episodes may have remained undetected after catheter ablation. However, asymptomatic recurrences of AF after an apparently successful catheter ablation procedure for symptomatic paroxysmal AF were infrequent even when continuous atrial monitoring by pacemaker was used for follow-up.23
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Conclusions |
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More than half of the patients who underwent catheter ablation of AF were at high risk for OSA in this population. The recurrence rate and incidence of complications did not differ significantly between the patients with OSA and those without OSA. OSA should be treated in its own right and possibly before ablation is considered. Once the decision has been made that an AF ablation is necessary, the presence of OSA does not appear to have an influence on the outcome of AF ablation.
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Funding |
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This work was supported by the National Science Foundation Council of China (nos 30670843, 30500202, 30570724, and 30770876); Beijing Science Foundation Council (no. 07G0179); and the China ‘863’ Research Project (no. 2006AA02Z4E4).
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Acknowledgements |
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We thank Chang Liu for collecting the data. We appreciate Jérôme Kalifa and Xiu-Lian Sun for revising the manuscript.
Conflict of interest: none declared.
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References |
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