Predictive value of obstructive sleep apnoea assessed by the Berlin Questionnaire for outcomes after the catheter ablation of atrial fibrillation

Transcription

1 Europace (2009) 11, doi: /europace/eup064 CLINICAL RESEARCH Obstructive Sleep Apnoea and Recurrence of Atrial Fibrillation Predictive value of obstructive sleep apnoea assessed by the Berlin Questionnaire for outcomes after the catheter ablation of atrial fibrillation Karuna Chilukuri 1, Darshan Dalal 1, Joseph E. Marine 1, Daniel Scherr 1,2, Charles A. Henrikson 1, Alan Cheng 1, Saman Nazarian 1, David Spragg 1, Ronald Berger 1, and Hugh Calkins 1 * 1 Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; and 2 Division of Cardiology, Department of Medicine, Medical University of Graz, Austria Received 14 November 2008; accepted after revision 18 February 2009; online publish-ahead-of-print 18 March 2009 Aims Obstructive sleep apnoea (OSA) is a risk factor for atrial fibrillation (AF) recurrence after catheter ablation. The purpose of this study is to determine whether OSA assessed by the simple tool, the Berlin Questionnaire (BQ), is useful in predicting the efficacy of catheter ablation of AF.... Methods The patient population consisted of 210 consecutive patients [mean age years, 167 (80%) male, 119 (57%) and results paroxysmal] who underwent catheter ablation of AF and completed the BQ. Clinical success was defined as at least 90% reduction in AF burden after 3-month blanking period. Mean duration of follow-up was months. One hundred and one of the 118 (85%) patients at low risk for OSA had clinical success as opposed to 64 of the 92 (70%) patients at high risk for OSA on BQ (P ¼ 0.005). On multivariate analysis, only high-risk for OSA on BQ emerged as an independent predictor of procedural failure (OR 4.53, CI: , P ¼ 0.02).... Conclusion High risk of OSA on BQ predicts procedural failure after catheter ablation of AF. We recommend the use of BQ for risk-stratifying patients for OSA prior to AF ablation procedures and to identify patients for formal sleep study assessment Keywords Berlin Questionnaire Sleep apnoea Atrial fibrillation Catheter ablation Efficacy Introduction Recent studies have identified obstructive sleep apnoea (OSA) identified with conventional sleep study as a risk factor for atrial fibrillation (AF) recurrence after catheter ablation of AF. 1,2 The Berlin Questionnaire (BQ) is an easily administered tool that can be used to identify individuals at risk of OSA. The BQ has been validated as a diagnostic tool for OSA in a number of patient populations including those with AF, 3 in the primary care setting 4 and in patients with resistant hypertension. 5 The purpose of this study is to determine whether this simple and widely available tool is useful in predicting the efficacy of catheter ablation of AF. Methods Patient population The patient population was comprised of 210 consecutive patients with drug-refractory AF who underwent catheter ablation at the Johns Hopkins Hospital and agreed to participate in this study. The clinical characteristics of the patient population are shown in Table 1. There were 167 men (80%) and the mean age was years. Atrial fibrillation was paroxysmal in 119 (57%) patients and persistent in 91 (43%) patients. The mean body mass index (BMI) was kg/m 2. The mean left atrial diameter was cm. The mean left ventricular ejection fraction was %. Paroxysmal AF was defined as recurrent * Corresponding author. The Johns Hopkins Hospital, 600 North Wolfe Street, Carnegie 530, Baltimore, MD , USA. Tel: þ , Fax: þ , hcalkins@jhmi.edu Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oxfordjournals.org.

2 Sleep apnoea predicts outcomes after AF ablation 897 Table 1 Clinical characteristics of all patients (n 5 210) Age (years) Male (%) 167 (80) AF type Paroxysmal (%) 119 (57) Non-paroxysmal (%) 91 (43) Hypertension (%) 106 (50) Diabetes mellitus (%) 19 (9) Body mass index (kg/m 2 ) Left atrial diameter (cm) Left ventricular ejection fraction (%) Number of failed anti-arrhythmic drugs AF (2 episodes) that terminated spontaneously within 7 days. Persistent AF was defined as recurrent AF which sustained beyond 7 days, or necessitated pharmacologic or electrical cardioversion. 6,7 Study protocol and ablation procedure The study protocol was approved by the Institutional Review Board of the Johns Hopkins Hospital. Written informed consent was obtained from all the patients prior to the ablation procedure. High-resolution computed tomographic imaging of the heart to evaluate the left atrial anatomy was performed within 24 h prior to the procedure. Baseline clinical and demographic data were obtained and entered into a longitudinal database. The approach used for catheter ablation of AF at our institution has been described previously. 8 Although most of the patients were ablated under conscious sedation, general anaesthesia was used in 14 (7%) patients at the discretion of the physician performing the procedure. All patients underwent radiofrequency catheter ablation to achieve electrical isolation of pulmonary veins (PVs) guided by the electroanatomical mapping. The electrical isolation was confirmed by a circular multipolar electrode mapping catheter (Lasso, Biosense, Diamond Bar, CA, USA, or Orbiter PV, Bard Electrophysiology, Lowell, MA, USA). The procedural endpoint was PV isolation in both paroxysmal and persistent patients. Pulmonary vein isolation was confirmed in both sinus rhythm and after pacing from the coronary sinus or left atrial appendage (in the case of left-sided PVs). The patients were discharged the following day if they had no complications. Berlin Questionnaire Shown in Table 2 is the BQ administered to all the patients in the study. The presence of OSA was determined by the BQ, a validated instrument in patients with AF with a sensitivity of 0.86, a specificity of 0.89, and a positive predictive value of 0.97 for OSA when compared with the polysomnography. 3 Berlin Questionnaire has three categories. Category 1 has five questions about snoring, Category 2 has three questions about daytime somnolence, and Category 3 has one question about the history of hypertension. In addition, the questionnaire also collects information about age, gender, height, and weight (to calculate the BMI). The overall score is based on the patient s response to each of the three categories. The patients are classified as high risk for OSA if two or more categories are positive and low risk if less than two categories were positive. Follow-up Patients were seen in an outpatient clinic 3 months after the ablation procedure. The follow-up evaluation consisted of a detailed history, physical examination, and a 12-lead electrocardiogram (ECG). To prevent short-term recurrences of AF, patients were continued on the stable anti-arrhythmic drug treatment they presented with at the time of referral for catheter ablation for at least until 3 months after the catheter ablation procedure. Seventy of the 210 (33%) of our patients received amiodarone after the ablation. There was no difference observed in the use of amiodarone post-procedure between patients with low-risk and high-risk BQ scores (31% vs. 35%, P ¼ 0.49). Patients were then followed up by the referring physician on a regular basis and routine ECGs were obtained at each clinic visit regardless of symptoms. Direct telephone follow-up was conducted for all patients at 3, 6, 9, and 12 months and then at least once a year after that. Patients with symptoms compatible with an arrhythmia underwent event monitoring. If asymptomatic AF was detected on routine ECG or event monitor, it was considered as a true recurrence and treated as such, regardless of the symptoms. Patients who were free of AF after 3 months had their anti-arrhythmic drug discontinued. Patients in whom recurrent AF developed more than 3 months after the ablation procedure were restarted on anti-arrhythmic drug therapy. If the patients remained symptomatic for more than 3 months after the catheter ablation procedure despite being restarted on anti-arrhythmic drug treatment, a clinically indicated second ablation procedure was offered to the patient. Outcomes Any episode of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial tachycardia, and atrial flutter) after the initial 3-month blanking period that lasting 30 s or longer was considered as an AF recurrence. The first 3 months after the ablation were considered as the blanking period. Complete success was defined as recommended by the HRS Consensus Document 6 as the absence of AF or other atrial tachycardias while off anti-arrhythmic drug therapy after blanking period. Improvement was defined as either: (i) 90% reduction in AF burden while off anti-arrhythmic drug therapy or (ii) 90% reduction in AF burden while using a previously ineffective anti-arrhythmic after the blanking period. Atrial fibrillation burden was determined based on the combination of frequency and duration of the AF episodes. Clinical success was determined by combining the patients with complete success and improvement. Failure was defined as inability to achieve either endpoint. Major complications were defined as those that required intervention, resulted in long-term disability, or prolonged the hospitalization. Statistical analysis Continuous variables are presented as mean + 1SD and were analysed with t-tests. Categorical variables are presented as percentages and were analysed by x 2 analysis or Fisher s exact test, as appropriate. Univariate and multivariate logistic regression analysis was performed to determine independent predictors of outcome after the catheter ablation procedure. All analyses were performed using STATA statistical software (version 9, College Station, TX, USA). P-values,0.05 were considered significant. Results The mean follow-up duration was months. Of the 210 patients who underwent catheter ablation for AF, 118 (56%)

3 898 K. Chilukuri et al. Table 2 Berlin Questionnaire patients were identified as low risk for OSA and the remaining 92 (44%) patients were identified as high risk for OSA by the BQ. Shown in Table 3 are the clinical characteristics of patients identified as low risk and high risk for OSA by the BQ. Patients with high-risk BQ had more persistent AF, higher BMI, and more often had hypertension than patients with low-risk BQ. There was no significant difference in the mean duration of fluoroscopy ( vs min, P ¼ 0.11) between patients with low-risk and high-risk BQ scores. Procedure duration was slightly longer in patients with high-risk BQ, a trend of borderline significance ( vs min, P ¼ 0.054). Ninety-one (43%) of the 210 patients had complete success after the procedure. Of these 91 patients, 56 (62%) were at low risk for OSA as opposed to 35 (38%) with high-risk BQ score (P ¼ 0.019). Among the 74 patients with improvement, 45 (61%) patients had low-risk BQ score and the remaining 29 (39%) patients had high-risk BQ score (P ¼ 0.02). Of the 45 patients with failure, 17 (38%) had a low-risk BQ score as opposed to the 28 (62%) patients with high-risk BQ score (P ¼ 0.02). Among the 210 patients, 165 (78%) patients met the criteria for clinical success after the catheter ablation of AF. One hundred and one of the 118 (85%) patients at low risk for OSA on BQ had clinical success as opposed to 64 of the 92 (70%) patients at high risk for OSA on BQ (P ¼ 0.005). Among the 119 patients with paroxysmal AF, 67 of the 76 (88%) patients at low risk for OSA on BQ had clinical success after catheter ablation of AF, whereas 32 of the 43 (74%) patients at high risk for OSA on BQ had clinical success (P ¼ 0.054). Among the 91 patients with persistent AF, 34 of the 42 (81%) patients at low risk for OSA on BQ had clinical success as opposed to 32 of the 49 (65%) patients at high risk for OSA on BQ (P ¼ 0.096). Shown in Table 4 are the variables analysed for the predictors of clinical success (n ¼ 165) vs. failure (n ¼ 45) in patients after catheter ablation of AF. Among the variables which we examined, high risk on BQ was identified as a predictor of outcome based on univariate analysis, while the type of AF showed a strong trend as a predictor of outcome (OR 1.88, CI: , P ¼ 0.06). Multivariate analysis identified only high risk of OSA on BQ as an independent predictor of failure after catheter ablation. It conferred a 4.5-fold higher risk for failure after catheter ablation of AF (OR 4.53, CI: , P ¼ 0.02). Complications Among the 210 patients, 5 major complications occurred (2.4%). Of the four patients (1.9%) who developed major vascular complications, two patients required surgical intervention.

4 Sleep apnoea predicts outcomes after AF ablation 899 Another patient (0.5%) experienced a transient ischaemic attack immediately after the procedure, which completely resolved within hours. All the patients are doing well on follow-up without any sequelae. There was no difference in the rate of major complications between the patients with low-risk and highrisk BQ scores. Discussion The results of this study identify the BQ for the assessment of OSA risk as a useful tool in predicting the outcomes after the catheter ablation of AF. In this study, we found that a high-risk score on this Table 3 Baseline characteristics of patients with low-risk and high-risk BQ Low risk High risk P-value (n 5 118) (n 5 92)... Age (years) Male (%) 90 (76) 77 (84) 0.18 Paroxysmal AF (%) 76 (64) 43 (47) 0.01* BMI at time of ablation ,0.01* (kg/m 2 ) Hypertension (%) 43 (36) 63 (68),0.01* Diabetes mellitus (%) 10 (8) 9 (10) 0.74 AF duration (years) Follow-up duration after the last procedure (months) Left ventricular ejection fraction (%) Procedure time (min) Fluoroscopy duration (min) Left atrial size (cm) *P, 0.05 is considered as a significant value. simple questionnaire was associated with a significant increase in the probability of failure after catheter ablation, independent of other co-morbidities associated with a higher likelihood of failure. Previous studies have shown a strong association between OSA and recurrences of AF. 1,2,9 Intermittent hypoxemia, sympathetic activation, pressor surges, transmural pressure changes, systemic inflammation and endothelial dysfunction 10 are some of the mechanisms by which OSA predisposes to the development of AF. 11 The intermittent occlusion of airway in patients with OSA contributes to the negative intrathoracic pressure which increases the transmural gradient across the left atrium and contributes to the increased left atrial size. Sleep apnoea-induced vasoconstriction also leads to increased afterload and left ventricular diastolic dysfunction, which may further increase left atrial size. Left atrial stretch is shown to promote PV arrhythmogenicity 12,13 and with prolonged fibrosis may contribute to perpetuation of AF. 1 Older patients with larger left atrial size, sleep apnoea, hypertension, or persistent AF were found more likely to develop acute PV reconnection after catheter ablation. 2 Population-based cohort studies have shown that 1 in 5 adults have at least mild OSA and 1 in 15 have moderate or severe OSA. 11 The prevalence is two to three times higher in patients with cardiovascular disease. The prevalence of OSA as assessed by the BQ in our patient population is 44%. This high prevalence is in accord with the 49% prevalence reported by Gami et al. 3 Although patients with high-risk BQ had more persistent AF, hypertension, and higher BMI than low-risk BQ patients, only the presence of OSA assessed by high-risk BQ was predictive of a higher risk of failure in the multivariate analysis. These findings are similar to the results reported by Jongnarangsin et al. 1 There was no significant difference in the outcome based on the type of AF on multivariate analysis. Among patients with paroxysmal AF, 88% patients at low risk for OSA on BQ had clinical success as opposed to 74% patients at high risk for OSA on BQ (P ¼ 0.054). Although the P-value is of borderline significance, it does suggest a strong trend and raises the possibility that the BQ may be more predictive of ablation success in paroxysmal AF patients than in those with persistent AF. However, further studies are Table 4 Predictors of outcome after catheter ablation of AF for patients with clinical success vs. failure (n 5 210) Variables Univariate analysis... Multivariate analysis... Odds ratio 95% confidence interval P-value Odds ratio 95% confidence interval P-value... Age Female AF duration BMI Left atrial size Left ventricular ejection fraction Persistent AF Hypertension Diabetes mellitus High-risk Berlin Questionnaire * * *P, 0.05 is considered significant.

5 900 K. Chilukuri et al. required to prove this hypothesis. Although obesity is a modifiable risk factor for AF, 14 it was not an independent predictor of outcome after catheter ablation of AF. This finding is in accord with the results reported in previous studies. 1,15 It is possible that the ongoing hypoxia, hypercapnia, pressor surges, transmural changes, inflammation, and left atrial stretch associated with OSA promote emergence of new triggers and perpetuate the maintenance of AF. 1 Whether the treatment of OSA improves outcomes after catheter ablation of AF is unknown. Kanagala et al. 9 prospectively analysed 39 patients with OSA and AF and compared them with 79 patients with AF and no OSA. They found that the patients with untreated OSA had a higher recurrence of AF after cardioversion when compared with patients with treated OSA or without OSA. The patients with low-risk BQ for OSA had a better outcome when compared with high-risk BQ for OSA. This is in contrast to the results reported by Padeletti et al. 16 Seventy-two patients with paroxysmal AF who had pacemakers implanted for sinus bradycardia were asked to complete the BQ at enrolment and at 4-month follow-up visit. In this study, AF recurrence and AF burden were similar in high-risk and low-risk BQ patients. Our study differs from the above study since we looked at the outcomes after catheter ablation of AF in paroxysmal and persistent patients. The mean follow-up duration in our study is over 2 years and our sample size is larger. Also the prevalence of OSA in our study is 44% which is higher than the 28% prevalence reported by Padeletti et al. 16 Patients with OSA undergoing ablation under conscious sedation tend to snore. This might cause catheter instability during the ablation and may lead to non-transmural lesions and a higher incidence of PV reconnection. This might be a possible explanation for the poor outcome in patients with high-risk BQ score. However, there is no difference in the rate of PV reconnection between the low-risk and the high-risk BQ patients noted in this study. Limitations One limitation of this study is that the BQ was administered to all the patients after the ablation. We asked our patients to complete the BQ based on their symptoms before the ablation procedure. However, there is a possibility of recall bias. Our study is unique since all 210 patients underwent assessment for OSA with BQ. Although the gold standard for diagnosis of sleep apnoea is an overnight polysomnography, it is expensive and time-consuming. Moreover, BQ has been validated for diagnosis of OSA in AF population in prior studies and has been shown to have 86% sensitivity when compared with polysomnography. 3 Despite the variable predictive accuracy of BQ as reported in some studies, 17,18 the high proportion of patients at risk for OSA in our sample may have minimized the potential misclassification error. The outcome definitions were based on monitoring all the patients with review of symptoms, and Holter monitors at 3-month intervals. However, we realize that more frequent electrocardiographic monitoring might have reduced the success rate further. Conclusions In conclusion, the prevalence of OSA in patients with AF, as assessed by BQ, is very high. Patients at high risk for OSA assessed by the BQ have a high rate of AF recurrence when compared with patients at low risk for OSA after catheter ablation of AF. We recommend the BQ for risk-stratifying patients for OSA prior to the AF ablation procedures and to identify patients for formal sleep study assessment. Whether aggressive management of OSA will result in improved clinical outcomes after catheter ablation of AF warrants further investigation. Conflict of interest: none declared. Funding Dr K.C. was supported by The Norbert and Louise Grunwald Cardiac Arrhythmia Research Fund. Dr D.S. was supported by the FWF Austrian Science Fund. References 1. Jongnarangsin K, Chugh A, Good E, Mukerji S, Dey S, Crawford T et al. Body mass index, obstructive sleep apnea, and outcomes of catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2008;19: Sauer WH, McKernan ML, Lin D, Gerstenfeld EP, Callans DJ, Marchlinski FE. Clinical predictors and outcomes associated with acute return of pulmonary vein conduction during pulmonary vein isolation for treatment of atrial fibrillation. Heart Rhythm 2006;3: Gami AS, Pressman G, Caples SM, Kanagala R, Gard JJ, Davison DE et al. Association of atrial fibrillation and obstructive sleep apnea. Circulation 2004;110: Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med 1999;131: Gus M, Gonçalves SC, Martinez D, de Abreu Silva EO, Moreira LB, Fuchs SC et al. Risk for obstructive sleep apnea by Berlin Questionnaire, but not daytime sleepiness, is associated with resistant hypertension: a case-control study. Am J Hypertens 2008;21: Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ et al. HRS/EHRA/ ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2007;4: Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. ACC/ AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines. Circulation 2006;114: Cheema A, Dong J, Dalal D, Vasamreddy CR, Marine JE, Henrikson CA et al. 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6 Sleep apnoea predicts outcomes after AF ablation Ahmadi N, Chung SA, Gibbs A, Shapiro CM. The Berlin questionnaire for sleep apnea in a sleep clinic population: relationship to polysomnographic measurement of respiratory disturbance. Sleep Breath 2008;12: Chung F, Yegneswaran B, Liao P, Chung SA, Vairavanathan S, Islam S et al. Validation of the Berlin questionnaire and American Society of Anesthesiologists checklist as screening tools for obstructive sleep apnea in surgical patients. Anesthesiology 2008;108: IMAGES IN ELECTROPHYSIOLOGY doi: /europace/eup123 Online publish-ahead-of-print 15 May Intracardiac echocardiography for visualization of the Eustachian valve during radiofrequency ablation of typical atrial flutter Gábor Bencsik*, Róbert Pap, and László Sághy Second Department of Internal Medicine and Cardiology Centre, University of Szeged, 6726 Szeged, Korányi fasor 6, Hungary * Corresponding author. Tel/Fax: þ , blackdoor@t-online.hu We performed a conventional, fluoroscopy-guided ablation of ongoing typical atrial flutter at the preferred isthmus site. Despite 150 min of procedure time (using a 4 mm, irrigated tip catheter with settings of 438C, 40 W and irrigation rate of 40 ml/min), block on the isthmus was not achieved. No atrial signals were left on the line of ablation. Through the left femoral vein, we introduced an intracardiac echocardiography probe and found a highly prominent Eustachian valve (EV; see Figure 1 and Supplementary material online, Movie S1) with high-voltage atrial potential at the edge of the EV. After ablation at this point, the flutter was terminated and bidirectional block was confirmed. Supplementary material Supplementary material is available at Europace online. Figure 1 An intracardiac echocardiographic picture presenting a prominent, muscular, and actively contracting Eustachian valve (EV), which could only be engaged by curving the ablation catheter (Abl) into full circle (arrowheads) to touch the anterior surface of the valve. Muscle fibres running in the EV were likely responsible for resistant transisthmic conduction. CS, coronary sinus; Tr, tricuspid valve; IVC, inferior vena cava; RV, right ventricle. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oxfordjournals.org.