CLINICAL RESEARCH
Europace (2014) 16, 241–245 doi:10.1093/europace/eut306
Pacing and resynchronization therapy
Does atrial pacing lead to atrial fibrillation in patients with sick sinus syndrome? Insights from the DANPACE trial
1
Department of Cardiology, Aalborg University Hospital, Cardiovascular Research Centre, DK-9000, Denmark; and 2Aarhus University Hospital, Skejby, DK-8200 Aarhus, Denmark
Received 24 March 2013; accepted after revision 9 September 2013; online publish-ahead-of-print 29 October 2013
Aims
Paroxysmal atrial fibrillation (AF) is common in patients with sick-sinus syndrome (SSS) and pacemakers leading to morbidity and an increased risk of stroke or death. Previous studies indicate that atrial pacing may precipitate AF. We investigated the relation between atrial pacing and the occurrence of AF during long-term follow-up among patients with SSS, no prior AF, and dual-chamber pacemakers (DDDRs). ..................................................................................................................................................................................... Methods We analysed data from 396 patients who received DDDR pacemakers in the DANPACE trial. The percentage of atrial and results pacing (%AP) was compared with the number of mode-switch (MS) episodes collected by the pacemaker at each followup as an indicator of AF. Mean follow-up was 4.2 + 2.4 years. The mean proportion of atrial and ventricular pacing was 59 + 31 and 65 + 33%, respectively. Approximately 72% developed AF as indicated by MS episodes at some point during follow-up. Unadjusted regression analysis indicated a relation between %AP and AF (P ¼ 0.04), but after adjustment for possible confounders (sex, age, hypertension, diabetes, myocardial infarction, PQ interval, and left atrial diameter) there was no significant relationship (P ¼ 0.37). ..................................................................................................................................................................................... Conclusion Atrial fibrillation is very common among patients with SSS. No association between %AP and development of AF was found in patients with SSS. Future trials may randomize patients to different levels of AP exposure.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Sick sinus syndrome † Sinoatrial node † Pacemakers † Atrial fibrillation † Pacing
Introduction Paroxysmal atrial fibrillation (AF) is common in patients with sicksinus syndrome (SSS) and pacemakers leading to morbidity and an increased risk of stroke or death.1 Patients with SSS and bradycardia can be treated by single lead atrial (AAIR) or dual-chamber pacemakers (DDDR)2 – 4 and require various degrees of atrial pacing to maintain adequate functional capacity. Although both AAIR and DDDR pacing preserve the normal sequential activation of the atria and ventricles, small studies as well as a meta-analysis have previously indicated that atrial pacing may precipitate AF.5,6 The mode-switch (MS) feature in DDDRs detects atrial tachyarrhythmias and is a sensitive and specific indicator of AF.7,8 In the
present study, we examined patients with no previous history of AF who received DDDR pacemakers in the DANPACE trial,4 with the aim of determining the effect of atrial pacing on the occurrence of AF among patients with SSS.
Methods Study design The DANPACE trial has been described previously.4 The current study included a cohort of all patients who during the DANPACE trial were randomly assigned to DDDR, and treated with DDDR pacing due to SSS and bradycardia. Furthermore, all patients who were randomized to AAIR
* Corresponding author. Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Hobrovej 16-18, Postbox 365, DK-9100 Aalborg, Denmark. Tel: +45 9932 4205; fax: +45 9932 2361, E-mail: [email protected]
†
Participants in The Danish Multicenter Randomized Trial on Single Lead Atrial Pacing vs. Dual Chamber Pacing in Sick Sinus Syndrome (DANPACE) are listed in the Appendix.
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected].
Downloaded from http://europace.oxfordjournals.org/ at Sydney Jones Library, University of Liverpool on October 7, 2014
Søren Hjortshøj 1*, Sam Riahi1, Jens Cosedis Nielsen 2, Flemming Skjøth 1, Søren Lundbye-Christensen 1, and Henning R. Andersen 2, on behalf of the DANPACE Investigators†
242
What’s new? † Atrial fibrillation is very common among patients with sicksinus syndrome. † No association between increasing atrial pacing and development of atrial fibrillation was found. † Future randomized trials should expose patients to different degrees of atrial pacing to investigate any causal relationship between atrial pacing and atrial fibrillation.
Implantation and programming of pacemakers Bipolar leads were implanted in the right atrium and ventricle. Contemporary DDDR pacemakers from Boston Scientific, Medtronic, and St Jude Medical were used. The rate adaptive function was activated in all pacemakers and programmed with a lower rate of 60 b.p.m. and an upper rate of 130 b.p.m. In patients with DDDR pacemakers, the paced atrioventricular interval was programmed to 140 – 220 ms according to a prespecified algorithm.4 The maximum tracking rate was individualized and the MS function was activated. Mode switch occurred, when the atrial rate exceeded 170 – 180 b.p.m. for a given number of beats or period of time according to the default settings of the manufacturer of the pacemaker. Atrial sensitivity was programmed to 0.5 mV.
of 30 min was recorded as 0 h, whereas 31 min were recorded as 1 h. Analyses for MS durations of 6 and 24 h as the criterion for AF were also carried out.
Statistical analysis A crude analysis is reported for the occurrence of MS since last interrogation/follow-up. The potentially non-linear relationship between development of %AP and AF was analysed by fitting splines9 in a logistic regression with %AP being a time-varying covariate. Serial correlation was accounted for by using a population averaged generalized estimation equation.10 Adjustments for pre-specified confounders known to be associated with AF were performed [sex, age, hypertension, diabetes, previous myocardial infarction (MI), PQ interval, and left atrial diameter]. Statistical tests were two-tailed, and P , 0.05 was considered significant. Stata version 11.2 (StataCorp. 2009. Stata: Release 11. Statistical Software. Stata Corp. LP) was used.
Results Population A total of 746 patients received DDDR pacemakers in the trial and were eligible for evaluation at 3 months follow-up. Twenty-five patients were excluded from the analysis due to crossover to other programming modes, e.g. VVI mode at the time of first follow-up. A further 325 patients had a previous history of AF (tachycardia–bradycardia) and were also excluded. Therefore, the data analysis is based on a total of 2058 follow-up visits in 396 patients spanning over a period of 4.2 + 2.4 years. Table 1 displays the baseline characteristics of our patient cohort with DDDR pacemakers without a previous history of AF. The mean proportion of atrial and ventricular pacing was 59 + 31 and 65 + 33%, respectively.
Table 1 Baseline characteristics of study cohort (N 5 396) with DDDR without known AF at study inclusion Characteristic
No AF prior to implantation of DDDR pacemaker
................................................................................ Female gender, n (%)
221 (56)
Age (years), mean + SD Hypertension, n (%)
72.0 + 12.3 136 (34)
Previous myocardial infarction, n (%) 48 (12)
Patient follow-up Follow-up took place after 3 months and again every year after implantation up to 10 years. Mean follow-up was 5.4 + 2.6 years. At each planned follow-up visit, a printout of the pacemaker memory data accumulated since the previous resetting of the memory was obtained. The percentage of atrial pacing (%AP) at each follow-up was calculated using the number of paced and the number of sensed beats. The occurrence and duration of MS events were recorded.
Definition of atrial fibrillation Episodes of MS detected by the pacemaker at yearly follow-up visits were used as a surrogate marker of AF. The total duration of MS episodes were rounded to the nearest number of whole hours. Thus, a total MS duration
Diabetes, n (%) Previous stroke, n (%)
43 (11) 26 (7)
Left ventricular ejection fraction reduced (,50%), n (%) PQ interval (ms), mean + SD
27 (8) 180 + 31
Medication at randomization Anticoagulation Beta-blocker
24 (6) 58 (15)
Calcium-channel blocker
71 (18)
Digoxin Antiarrythmics class I and III
12 (3) 0 (0)
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pacing, and who received a DDDR pacemaker at the time of first pacemaker implantation (typically due to a low Wenckebach point) (N ¼ 46), were included in the analysis. Patients who on randomization had electrocardiogram documented AF (tachycardia – bradycardia) or had a previous history of paroxysmal AF were excluded from the analysis, as were patients who died before their first follow-up visit. The criteria for inclusion in the DANPACE trial were: symptomatic bradycardia; documented sino-atrial block or sinus arrest with pauses .2 s or sinus bradycardia ,40 b.p.m. for .1 min while awake; PR interval ≤0.22 s if aged 18 – 70 years or PR interval ≤0.26 s if aged ≥70 years; and QRS width ≤0.12 s. The main exclusion criteria were: atrioventricular block; bundle branch block; long-standing persistent AF (.12 months); AF with ventricular rate ,40 b.p.m. for ≥1 min or pauses .3 s; a positive test for carotid sinus hypersensitivity. Enrolment began in March 1999 and was terminated in June 2008. Patients were followed until September 2009. The trial was conducted in accordance with the Helsinki Declaration and approved by the regional Ethics Committee and the Danish Data Protection Agency. All patients gave written informed consent before inclusion.
S. Hjortshøj et al.
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Does atrial pacing lead to AF in patients with SSS?
Atrial pacing and atrial fibrillation
1.0
Mode switch
0.8 0.6 0.4 0.2 Number of patients 0 375 361 309 261 209 167 114 76 0 2 4 6 Follow-up years
43 8
4 10
Figure 1 Mean proportion of patients with mode-switch (MS) episodes at different follow-up visits with 1 SD. Number of patients at each follow-up below figure.
Discussion In this study, we found no significant association between increasing %AP and subsequent occurrence of AF in patients with SSS, although unadjusted results suggested an inversely proportional relationship. Previously, Adelstein and Saba5 found that in patients with heart failure undergoing cardiac resynchronization therapy (CRT), increasing %AP was a significant predictor of AF development, and in a recent meta-analysis, Elkayam et al.6 showed that atrial pacing was a predisposing factor for development of AF. The reason for the apparent association between atrial pacing and AF is not clear and may be multifactorial. First, patients needing atrial pacing may have more diseased atria in which AF is more likely to develop, e.g. in heart failure patients. Secondly, atrial pacing may itself cause AF by different mechanisms: pacing the right atrium may induce atrial dyssynchrony and subsequent AF.11 Further, right atrial pacing may lead to prolonged atrioventricular conduction times, which in turn can promote AF.11 – 13 Also, increases in conduction times can lead to more ventricular pacing, which, in some studies, has been established to promote AF in patients with SSS.13 – 15 Pacing from the low interatrial septum has been suggested to be superior to right atrial appendage pacing in terms of AF prevention in patients with SSS, but the subject remains controversial.16 A relatively low number of patients in the DANPACE cohort had pre-existing cardiovascular disease, e.g. ischaemic heart disease and hypertension, and only a modest number of patients developed heart failure during the trial indicating the relatively benign course of SSS apart from the development of AF.17 Thus, patients with SSS may respond differently or not at all to atrial pacing compared with other patient groups, e.g. CRT patients. While atrial pacing by some researchers is considered potentially pro-arrhythmogenic, others have focused on atrial overdrive pacing strategies for the prevention of AF. Results from previous trials with overdrive pacing have not shown a convincing benefit in terms of AF prevention, and these trials included only modest sample sizes.18 – 20 Recently, the ASSERT trial with 2580 patients was not able to demonstrate any benefit of continuous atrial overdrive pacing.21 In the current study, we also show that a very high number of patients (72%) developed AF during follow-up. Notably, during the first year after implantation the proportion of patients with MS episodes since last follow-up was .50%, underscoring the importance of regular follow-up procedures of SSS patients to detect patients with AF requiring anticoagulation treatment. A recent study by Svendsen et al.22 has shown that the rate of stroke was similar in the single-chamber and dual-chamber pacemaker arms in the DANPACE trial. For the whole DANPACE trial, the authors did not find an association between AF and stroke, and they speculate that patients with AF (due to taking part in a randomized trial) were adequately anticoagulated and therefore less likely to develop stroke. Interestingly, the authors also report a higher ‘MS burden’ among patients with DDDRs who developed stroke during follow-up, thus supporting an association between AF and stroke after all.
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Figure 1 displays a crude analysis of the occurrence of one or more MS episode at different follow-up visits collected since the latest earlier follow-up interrogation. Approximately 72% developed AF as indicated by at least one MS episode (≥31 min) during follow-up. During the first year after implantation, the proportion of patients with MS episodes increased from 50% but levelled off during the remaining observation period at 60– 70%. The figure displays large standard deviations at 8 –10 years of follow-up reflecting a small number of participating patients at these time points. To describe a possible effect of atrial pacing, splines were fitted with MS at individual follow-ups and %AP being a time-varying covariate. Figure 2 displays a crude analysis indicating the association between the probability of observing MS (≥31 min) since last followup in relation to the proportion of time in atrial pacing (%AP). The curve shape is essentially the same at all time points (P ¼ 0.93) and exhibits a clear relationship with %AP (P ¼ 0.04). For most curves, there is a twophased course with a tendency to a decrease in the proportion of MS episodes with higher %AP, although a peak in MS is seen with 70% AP. However, when adjusting for possible confounders (sex, age, hypertension, diabetes, MI, PQ interval, and left atrial diameter), the curve shape remains the same at all time points (P ¼ 0.20), but there is no significant association with %AP (P ¼ 0.37). In these analyses, the criterion for AF detection was defined by MS ≥ 1 h (rounded to 1 h if ≥31 min). Further analyses with MS durations of 6 and 24 h as the criterion for AF were also carried out, but the above-mentioned curves remained the same for both crude and adjusted analysis and with essentially similar P values. A simulation study was designed to evaluate the statistical power of our analysis. Based on the final crude analysis, a number of datasets of binary MS indicators were simulated with the same population characteristics as the present data, but with varying effect sizes. The effect size, b, is the ratio between the highest and the lowest proportion and varied relative to the present study from b ¼ 0.0, 0.1, 0.2,. . ., 2.0. Hence, the effect size in the present study corresponds to b ¼ 1, no effect to b ¼ 0, and twice the effect to b ¼ 2 etc. For each effect size, 1000 datasets were simulated. Each set of data were analysed using the same model as in the crude analysis. The
statistical power is defined as the proportion of datasets with significant test results. The observed power in the current analysis (b ¼ 1) was 90.4%, and a power of 80% was reached when the simulated effect size was approximately b ¼ 0.9 corresponding to a slightly flattened curve shape.
244
S. Hjortshøj et al.
3 months
1 year
2 years
3 years
100 80 Proportion of MS (%)
60 40 20 100 80 60
20 0
50
100 0
50
4 years
5 years
6 years
7 years
100
100
Proportion of MS (%)
80 60 40 20 100
Conclusion
80 60 40 20
Proportion of MS (%)
0
50
100 0
50
100
The present study did not find an association between increasing atrial pacing and development of AF. Whether any causal relationship exists between atrial pacing and AF should be the focus of future randomized trials, exposing patients to different degrees of atrial pacing.
9 years
8 years 100
Conflict of interest: J.C.N. received speakers fees from Biotronik and research grant for the MANTRA-PAF trial from BiosenseWebster. All the other authors declare no conflicts of interest.
80 60 40
Funding
20 0
50
100
0
50
100 %AP
Figure 2 Spline analysis with indication of the association between the probability of observing MS since last follow-up in relation to the proportion of time in atrial pacing (%AP). The curve shape is the same at all follow-up visits (P ¼ 0.93).
The DANPACE trial was funded by unrestricted grants from Medtronic, St Jude Medical, Boston Scientific, Ela Medical, Pfizer, and the Danish Heart Foundation (10-04-R78-A2954-22779).
Supplementary data A full list of investigators, advisory board members, and details of the safety and ethical committee and clinical event committee are available as supplementary material online.
Limitations Episodes of MS were used as a surrogate marker of AF, and sensitivities and specificities of the used MS algorithms are thus crucial. Pacemakers from five different manufacturers were used in the DANPACE trial, thus introducing different MS algorithms. However, the manufacturer of individual pacemakers was not recorded in DANPACE, and it is thus not possible to discriminate between the various algorithms. However, it is widely accepted that today’s MS algorithms display exhibit a very high degree of sensitivity and specificity for the reliable detection of AF.7,8,23 The occurrence of AF may sometimes lead to undersensing in the atrium and thus inappropriate atrial pacing. However, given the efficiency of modern MS algorithms, we consider it unlikely that this would not result in MS episodes which would be
References 1. Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak R et al.; MOST Investigators. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST). Circulation 2003;107:1614 –9. 2. Nielsen JC, Kristensen L, Andersen HR, Mortensen PT, Pedersen OL, Pedersen AK. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol 2003;42:614 –23. 3. Sweeney MO, Bank AJ, Nsah E, Koullick M, Zeng QC, Hettrick D et al.; Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACe) Trial. Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med 2007;357:1000 – 8. 4. Nielsen JC, Thomsen PE, Hojberg S, Moller M, Vesterlund T, Dalsgaard D et al.; DANPACE Investigators. A comparison of single-lead atrial pacing with dualchamber pacing in sick sinus syndrome. Eur Heart J 2011;32:686 – 96.
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40
detected at the next scheduled follow-up. Although patients with known AF prior to pacemaker implantation were excluded from the study cohort, some patients may have had episodes of undiagnosed AF. It may be argued that by using MS durations of 1 h (rounded to 1 h if ≥31 min) as the criterion for AF, we may detect clinically irrelevant episodes of atrial tachycardia and possibly far-field R-wave oversensing, thus overestimating the true incidence of AF. Today, it is not possible to make adjudications of electrogram tracings from the pacemaker memory to exclude significant overdiagnosis of AF. However, we performed the same analyses with MS durations of 6 and 24 h as the criterion for AF leading to similar results. The use of beta-blockers may inhibit the sinus node and thus cause an increase in %AP. It was, however, impossible to satisfactorily adjust for beta-blocker use because of the heterogeneity of drugs and doses used and their wide variation in patient effects. It is possible that various atrial lead positions, e.g. septal vs. lateral/appendage, may determine propagation of pacing impulses in the atria thus contributing differently to the development of AF. In the present study, we did not have information on the exact position of the atrial lead, yet most leads were implanted in the right atrial appendage or on the lateral wall of the right atrium as is practice in most clinics today.
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Does atrial pacing lead to AF in patients with SSS?
15. Acosta H, Viafara LM, Izquierdo D, Pothula VR, Bear J, Pothula S et al. Atrial lead placement at the lower atrial septum: a potential strategy to reduce unnecessary right ventricular pacing. Europace 2012;14:1311 –16. 16. Hermida JS, Kubala M, Lescure FX, Delonca J, Clerc J, Otmani A et al. Atrial septal pacing to prevent atrial fibrillation in patients with sinus node dysfunction: results of a randomized controlled study. Am Heart J 2004;148:312 –7. 17. Riahi S, Nielsen JC, Hjortshoj S, Thomsen PE, Hojberg S, Moller M et al.; DANPACE Investigators. Heart failure in patients with sick sinus syndrome treated with single lead atrial or dual-chamber pacing: no association with pacing mode or right ventricular pacing site. Europace 2012;14:1475 –82. 18. Carlson MD, Ip J, Messenger J, Beau S, Kalbfleisch S, Gervais P et al.; Atrial Dynamic Overdrive Pacing Trial (ADOPT) Investigators. A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT). J Am Coll Cardiol 2003;42:627 – 33. 19. Schuchert A, Rebeski HP, Peiffer T, Bub E, Dietz A, Mortensen K et al.; 3:4 Study Group. Effects of continuous and triggered atrial overdrive pacing on paroxysmal atrial fibrillation in pacemaker patients. Pacing Clin Electrophysiol 2008;31:929–34. 20. Sanagala T, Johnston SL, Groot GD, Santucci P, Rhine DK, Varma N. Left atrial mechanical responses to right ventricular pacing in heart failure patients: implications for atrial fibrillation. J Cardiovasc Electrophysiol 2011;22:866 – 74. 21. Hohnloser SH, Healey JS, Gold MR, Israel CW, Yang S, van Gelder I et al.; ASSERT Investigators. Atrial overdrive pacing to prevent atrial fibrillation: insights from ASSERT. Heart Rhythm 2012;9:1667 – 73. 22. Svendsen JH, Nielsen JC, Darkner S, Jensen GV, Mortensen LS, Andersen HR; DANPACE Investigators. CHADS2 and CHA2DS2-VASc score to assess risk of stroke and death in patients paced for sick sinus syndrome. Heart 2013;99:843 –8. 23. Kristensen L, Nielsen JC, Mortensen PT, Pedersen AK, Andersen HR. Evaluation of pacemaker telemetry as a diagnostic feature for detecting atrial tachyarrhythmias in patients with sick sinus syndrome. Europace 2004;6:580 – 5. doi:10.1093/europace/eut233 Online publish-ahead-of-print 4 August 2013
EP CASE EXPRESS
.............................................................................................................................................................................
Treatment of obstructive sleep apnoea improves metabolic conditions and prevents initiation of antiarrhythmic therapy in a patient with atrial fibrillation Dominik Linz*, Christian Ukena, and Hans-Ruprecht Neuberger Universita¨tsklinikum des Saarlandes, Klinik fu¨r Innere Medizin III, 66421 Homburg/Saar, Germany
* Corresponding author. Tel: +49 6841 16 23372; fax: +49 6841 16 23369, Email: [email protected]
% sleeping time
% sleeping time
No CPAP After 3 months of CPAP A 56-year-old man with symptomatic paroxysmal Max. Desaturation: 63% Max. Desaturation: 88% 100% 100% AHI: 75/hour atrial fibrillation (AF) and severe metabolic synAHI: 5/hour 80% 80% 60% 60% drome presented to our clinics with recurrent 40% 40% symptomatic AF with seven AF episodes within 20% 20% 0% 0% the last 3 months. All of them were associated 100% 90% 80% 70% 60% 100% 90% 80% 70% 60% % saturation below % saturation below with presentation at the clinic and two of them were terminated by electrical cardioversion. Detailed medical history taking revealed that all ECV ECV AF episodes occurred during night and severe Symptomatic AF episodes Symptomatic AF episodes sleepiness during daytime (Epworth Sleepiness CPAP No CPAP -3 months +3 months Scale score ¼ 15). A 24 h electrocardiogramHolter monitoring showed a high incidence of premature atrial contractions (PACs). Severe obstructive sleep apnoea [OSA; apnoea hypoxia index (AHI): 75/h] was diagnosed in a following sleep study. Appropriate continuous positive airway pressure (CPAP) therapy showed an improvement of OSA severity (AHI: 5/h), reduced maximal desaturation during sleep from 63 to 88%, and completely inhibited recurrence of symptomatic AF episodes during 3 months after start of CPAP therapy (Figure). Occurrence of PACs was reduced from 640/24 to 51/24 h. Interestingly, CPAP therapy also resulted in a clear improvement of metabolic conditions, which could not be treated by drugs before. Importantly, the initiation of a specific antiarrhythmic therapy could be prevented. Particularly in AF patients with metabolic syndrome, a detailed screening for OSA is important and its therapy may be helpful to reduce the number of symptomatic AF episodes and atrial ectopy.
The full-length version of this report can be viewed at: http://www.escardio.org/communities/EHRA/publications/ep-case-reports/ Documents/treatment-of-obstructive-sleep.pdf. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected].
Downloaded from http://europace.oxfordjournals.org/ at Sydney Jones Library, University of Liverpool on October 7, 2014
5. Adelstein E, Saba S. Right atrial pacing and the risk of postimplant atrial fibrillation in cardiac resynchronization therapy recipients. Am Heart J 2008;155:94 –9. 6. Elkayam LU, Koehler JL, Sheldon TJ, Glotzer TV, Rosenthal LS, Lamas GA. The influence of atrial and ventricular pacing on the incidence of atrial fibrillation: a meta-analysis. Pacing Clin Electrophysiol 2011;34:1593 –9. 7. Passman RS, Weinberg KM, Freher M, Denes P, Schaechter A, Goldberger JJ et al. Accuracy of mode switch algorithms for detection of atrial tachyarrhythmias. J Cardiovasc Electrophysiol 2004;15:773 –7. 8. de Voogt WG, van Hemel NM, van de Bos AA, Koistinen J, Fast JH. Verification of pacemaker automatic mode switching for the detection of atrial fibrillation and atrial tachycardia with Holter recording. Europace 2006;8:950 –61. 9. Harrell FE. Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis. New York, NY: Springer-Verlag; 2001. 10. Liang K, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13 –22. 11. Xie JM, Fang F, Zhang Q, Chan JY, Yip GW, Sanderson JE et al. Atrial dysfunction and interatrial dyssynchrony predict atrial high rate episodes: insight into the distinct effects of right atrial appendage pacing. J Cardiovasc Electrophysiol 2012;23:384 –90. 12. Yasuoka Y, Abe H, Umekawa S, Katsuki K, Tanaka N, Araki R et al. Interatrial septum pacing decreases atrial dyssynchrony on strain rate imaging compared with right atrial appendage pacing. Pacing Clin Electrophysiol 2011;34:370 –6. 13. Nielsen JC, Thomsen PE, Hojberg S, Moller M, Riahi S, Dalsgaard D et al.; DANPACE investigators. Atrial fibrillation in patients with sick sinus syndrome: the association with PQ-interval and percentage of ventricular pacing. Europace 2012;14:682 –9. 14. Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 1997;350:1210 –6.
Europace (2014) 16, 241–245 doi:10.1093/europace/eut306
Pacing and resynchronization therapy
Does atrial pacing lead to atrial fibrillation in patients with sick sinus syndrome? Insights from the DANPACE trial
1
Department of Cardiology, Aalborg University Hospital, Cardiovascular Research Centre, DK-9000, Denmark; and 2Aarhus University Hospital, Skejby, DK-8200 Aarhus, Denmark
Received 24 March 2013; accepted after revision 9 September 2013; online publish-ahead-of-print 29 October 2013
Aims
Paroxysmal atrial fibrillation (AF) is common in patients with sick-sinus syndrome (SSS) and pacemakers leading to morbidity and an increased risk of stroke or death. Previous studies indicate that atrial pacing may precipitate AF. We investigated the relation between atrial pacing and the occurrence of AF during long-term follow-up among patients with SSS, no prior AF, and dual-chamber pacemakers (DDDRs). ..................................................................................................................................................................................... Methods We analysed data from 396 patients who received DDDR pacemakers in the DANPACE trial. The percentage of atrial and results pacing (%AP) was compared with the number of mode-switch (MS) episodes collected by the pacemaker at each followup as an indicator of AF. Mean follow-up was 4.2 + 2.4 years. The mean proportion of atrial and ventricular pacing was 59 + 31 and 65 + 33%, respectively. Approximately 72% developed AF as indicated by MS episodes at some point during follow-up. Unadjusted regression analysis indicated a relation between %AP and AF (P ¼ 0.04), but after adjustment for possible confounders (sex, age, hypertension, diabetes, myocardial infarction, PQ interval, and left atrial diameter) there was no significant relationship (P ¼ 0.37). ..................................................................................................................................................................................... Conclusion Atrial fibrillation is very common among patients with SSS. No association between %AP and development of AF was found in patients with SSS. Future trials may randomize patients to different levels of AP exposure.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Sick sinus syndrome † Sinoatrial node † Pacemakers † Atrial fibrillation † Pacing
Introduction Paroxysmal atrial fibrillation (AF) is common in patients with sicksinus syndrome (SSS) and pacemakers leading to morbidity and an increased risk of stroke or death.1 Patients with SSS and bradycardia can be treated by single lead atrial (AAIR) or dual-chamber pacemakers (DDDR)2 – 4 and require various degrees of atrial pacing to maintain adequate functional capacity. Although both AAIR and DDDR pacing preserve the normal sequential activation of the atria and ventricles, small studies as well as a meta-analysis have previously indicated that atrial pacing may precipitate AF.5,6 The mode-switch (MS) feature in DDDRs detects atrial tachyarrhythmias and is a sensitive and specific indicator of AF.7,8 In the
present study, we examined patients with no previous history of AF who received DDDR pacemakers in the DANPACE trial,4 with the aim of determining the effect of atrial pacing on the occurrence of AF among patients with SSS.
Methods Study design The DANPACE trial has been described previously.4 The current study included a cohort of all patients who during the DANPACE trial were randomly assigned to DDDR, and treated with DDDR pacing due to SSS and bradycardia. Furthermore, all patients who were randomized to AAIR
* Corresponding author. Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Hobrovej 16-18, Postbox 365, DK-9100 Aalborg, Denmark. Tel: +45 9932 4205; fax: +45 9932 2361, E-mail: [email protected]
†
Participants in The Danish Multicenter Randomized Trial on Single Lead Atrial Pacing vs. Dual Chamber Pacing in Sick Sinus Syndrome (DANPACE) are listed in the Appendix.
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected].
Downloaded from http://europace.oxfordjournals.org/ at Sydney Jones Library, University of Liverpool on October 7, 2014
Søren Hjortshøj 1*, Sam Riahi1, Jens Cosedis Nielsen 2, Flemming Skjøth 1, Søren Lundbye-Christensen 1, and Henning R. Andersen 2, on behalf of the DANPACE Investigators†
242
What’s new? † Atrial fibrillation is very common among patients with sicksinus syndrome. † No association between increasing atrial pacing and development of atrial fibrillation was found. † Future randomized trials should expose patients to different degrees of atrial pacing to investigate any causal relationship between atrial pacing and atrial fibrillation.
Implantation and programming of pacemakers Bipolar leads were implanted in the right atrium and ventricle. Contemporary DDDR pacemakers from Boston Scientific, Medtronic, and St Jude Medical were used. The rate adaptive function was activated in all pacemakers and programmed with a lower rate of 60 b.p.m. and an upper rate of 130 b.p.m. In patients with DDDR pacemakers, the paced atrioventricular interval was programmed to 140 – 220 ms according to a prespecified algorithm.4 The maximum tracking rate was individualized and the MS function was activated. Mode switch occurred, when the atrial rate exceeded 170 – 180 b.p.m. for a given number of beats or period of time according to the default settings of the manufacturer of the pacemaker. Atrial sensitivity was programmed to 0.5 mV.
of 30 min was recorded as 0 h, whereas 31 min were recorded as 1 h. Analyses for MS durations of 6 and 24 h as the criterion for AF were also carried out.
Statistical analysis A crude analysis is reported for the occurrence of MS since last interrogation/follow-up. The potentially non-linear relationship between development of %AP and AF was analysed by fitting splines9 in a logistic regression with %AP being a time-varying covariate. Serial correlation was accounted for by using a population averaged generalized estimation equation.10 Adjustments for pre-specified confounders known to be associated with AF were performed [sex, age, hypertension, diabetes, previous myocardial infarction (MI), PQ interval, and left atrial diameter]. Statistical tests were two-tailed, and P , 0.05 was considered significant. Stata version 11.2 (StataCorp. 2009. Stata: Release 11. Statistical Software. Stata Corp. LP) was used.
Results Population A total of 746 patients received DDDR pacemakers in the trial and were eligible for evaluation at 3 months follow-up. Twenty-five patients were excluded from the analysis due to crossover to other programming modes, e.g. VVI mode at the time of first follow-up. A further 325 patients had a previous history of AF (tachycardia–bradycardia) and were also excluded. Therefore, the data analysis is based on a total of 2058 follow-up visits in 396 patients spanning over a period of 4.2 + 2.4 years. Table 1 displays the baseline characteristics of our patient cohort with DDDR pacemakers without a previous history of AF. The mean proportion of atrial and ventricular pacing was 59 + 31 and 65 + 33%, respectively.
Table 1 Baseline characteristics of study cohort (N 5 396) with DDDR without known AF at study inclusion Characteristic
No AF prior to implantation of DDDR pacemaker
................................................................................ Female gender, n (%)
221 (56)
Age (years), mean + SD Hypertension, n (%)
72.0 + 12.3 136 (34)
Previous myocardial infarction, n (%) 48 (12)
Patient follow-up Follow-up took place after 3 months and again every year after implantation up to 10 years. Mean follow-up was 5.4 + 2.6 years. At each planned follow-up visit, a printout of the pacemaker memory data accumulated since the previous resetting of the memory was obtained. The percentage of atrial pacing (%AP) at each follow-up was calculated using the number of paced and the number of sensed beats. The occurrence and duration of MS events were recorded.
Definition of atrial fibrillation Episodes of MS detected by the pacemaker at yearly follow-up visits were used as a surrogate marker of AF. The total duration of MS episodes were rounded to the nearest number of whole hours. Thus, a total MS duration
Diabetes, n (%) Previous stroke, n (%)
43 (11) 26 (7)
Left ventricular ejection fraction reduced (,50%), n (%) PQ interval (ms), mean + SD
27 (8) 180 + 31
Medication at randomization Anticoagulation Beta-blocker
24 (6) 58 (15)
Calcium-channel blocker
71 (18)
Digoxin Antiarrythmics class I and III
12 (3) 0 (0)
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pacing, and who received a DDDR pacemaker at the time of first pacemaker implantation (typically due to a low Wenckebach point) (N ¼ 46), were included in the analysis. Patients who on randomization had electrocardiogram documented AF (tachycardia – bradycardia) or had a previous history of paroxysmal AF were excluded from the analysis, as were patients who died before their first follow-up visit. The criteria for inclusion in the DANPACE trial were: symptomatic bradycardia; documented sino-atrial block or sinus arrest with pauses .2 s or sinus bradycardia ,40 b.p.m. for .1 min while awake; PR interval ≤0.22 s if aged 18 – 70 years or PR interval ≤0.26 s if aged ≥70 years; and QRS width ≤0.12 s. The main exclusion criteria were: atrioventricular block; bundle branch block; long-standing persistent AF (.12 months); AF with ventricular rate ,40 b.p.m. for ≥1 min or pauses .3 s; a positive test for carotid sinus hypersensitivity. Enrolment began in March 1999 and was terminated in June 2008. Patients were followed until September 2009. The trial was conducted in accordance with the Helsinki Declaration and approved by the regional Ethics Committee and the Danish Data Protection Agency. All patients gave written informed consent before inclusion.
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Does atrial pacing lead to AF in patients with SSS?
Atrial pacing and atrial fibrillation
1.0
Mode switch
0.8 0.6 0.4 0.2 Number of patients 0 375 361 309 261 209 167 114 76 0 2 4 6 Follow-up years
43 8
4 10
Figure 1 Mean proportion of patients with mode-switch (MS) episodes at different follow-up visits with 1 SD. Number of patients at each follow-up below figure.
Discussion In this study, we found no significant association between increasing %AP and subsequent occurrence of AF in patients with SSS, although unadjusted results suggested an inversely proportional relationship. Previously, Adelstein and Saba5 found that in patients with heart failure undergoing cardiac resynchronization therapy (CRT), increasing %AP was a significant predictor of AF development, and in a recent meta-analysis, Elkayam et al.6 showed that atrial pacing was a predisposing factor for development of AF. The reason for the apparent association between atrial pacing and AF is not clear and may be multifactorial. First, patients needing atrial pacing may have more diseased atria in which AF is more likely to develop, e.g. in heart failure patients. Secondly, atrial pacing may itself cause AF by different mechanisms: pacing the right atrium may induce atrial dyssynchrony and subsequent AF.11 Further, right atrial pacing may lead to prolonged atrioventricular conduction times, which in turn can promote AF.11 – 13 Also, increases in conduction times can lead to more ventricular pacing, which, in some studies, has been established to promote AF in patients with SSS.13 – 15 Pacing from the low interatrial septum has been suggested to be superior to right atrial appendage pacing in terms of AF prevention in patients with SSS, but the subject remains controversial.16 A relatively low number of patients in the DANPACE cohort had pre-existing cardiovascular disease, e.g. ischaemic heart disease and hypertension, and only a modest number of patients developed heart failure during the trial indicating the relatively benign course of SSS apart from the development of AF.17 Thus, patients with SSS may respond differently or not at all to atrial pacing compared with other patient groups, e.g. CRT patients. While atrial pacing by some researchers is considered potentially pro-arrhythmogenic, others have focused on atrial overdrive pacing strategies for the prevention of AF. Results from previous trials with overdrive pacing have not shown a convincing benefit in terms of AF prevention, and these trials included only modest sample sizes.18 – 20 Recently, the ASSERT trial with 2580 patients was not able to demonstrate any benefit of continuous atrial overdrive pacing.21 In the current study, we also show that a very high number of patients (72%) developed AF during follow-up. Notably, during the first year after implantation the proportion of patients with MS episodes since last follow-up was .50%, underscoring the importance of regular follow-up procedures of SSS patients to detect patients with AF requiring anticoagulation treatment. A recent study by Svendsen et al.22 has shown that the rate of stroke was similar in the single-chamber and dual-chamber pacemaker arms in the DANPACE trial. For the whole DANPACE trial, the authors did not find an association between AF and stroke, and they speculate that patients with AF (due to taking part in a randomized trial) were adequately anticoagulated and therefore less likely to develop stroke. Interestingly, the authors also report a higher ‘MS burden’ among patients with DDDRs who developed stroke during follow-up, thus supporting an association between AF and stroke after all.
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Figure 1 displays a crude analysis of the occurrence of one or more MS episode at different follow-up visits collected since the latest earlier follow-up interrogation. Approximately 72% developed AF as indicated by at least one MS episode (≥31 min) during follow-up. During the first year after implantation, the proportion of patients with MS episodes increased from 50% but levelled off during the remaining observation period at 60– 70%. The figure displays large standard deviations at 8 –10 years of follow-up reflecting a small number of participating patients at these time points. To describe a possible effect of atrial pacing, splines were fitted with MS at individual follow-ups and %AP being a time-varying covariate. Figure 2 displays a crude analysis indicating the association between the probability of observing MS (≥31 min) since last followup in relation to the proportion of time in atrial pacing (%AP). The curve shape is essentially the same at all time points (P ¼ 0.93) and exhibits a clear relationship with %AP (P ¼ 0.04). For most curves, there is a twophased course with a tendency to a decrease in the proportion of MS episodes with higher %AP, although a peak in MS is seen with 70% AP. However, when adjusting for possible confounders (sex, age, hypertension, diabetes, MI, PQ interval, and left atrial diameter), the curve shape remains the same at all time points (P ¼ 0.20), but there is no significant association with %AP (P ¼ 0.37). In these analyses, the criterion for AF detection was defined by MS ≥ 1 h (rounded to 1 h if ≥31 min). Further analyses with MS durations of 6 and 24 h as the criterion for AF were also carried out, but the above-mentioned curves remained the same for both crude and adjusted analysis and with essentially similar P values. A simulation study was designed to evaluate the statistical power of our analysis. Based on the final crude analysis, a number of datasets of binary MS indicators were simulated with the same population characteristics as the present data, but with varying effect sizes. The effect size, b, is the ratio between the highest and the lowest proportion and varied relative to the present study from b ¼ 0.0, 0.1, 0.2,. . ., 2.0. Hence, the effect size in the present study corresponds to b ¼ 1, no effect to b ¼ 0, and twice the effect to b ¼ 2 etc. For each effect size, 1000 datasets were simulated. Each set of data were analysed using the same model as in the crude analysis. The
statistical power is defined as the proportion of datasets with significant test results. The observed power in the current analysis (b ¼ 1) was 90.4%, and a power of 80% was reached when the simulated effect size was approximately b ¼ 0.9 corresponding to a slightly flattened curve shape.
244
S. Hjortshøj et al.
3 months
1 year
2 years
3 years
100 80 Proportion of MS (%)
60 40 20 100 80 60
20 0
50
100 0
50
4 years
5 years
6 years
7 years
100
100
Proportion of MS (%)
80 60 40 20 100
Conclusion
80 60 40 20
Proportion of MS (%)
0
50
100 0
50
100
The present study did not find an association between increasing atrial pacing and development of AF. Whether any causal relationship exists between atrial pacing and AF should be the focus of future randomized trials, exposing patients to different degrees of atrial pacing.
9 years
8 years 100
Conflict of interest: J.C.N. received speakers fees from Biotronik and research grant for the MANTRA-PAF trial from BiosenseWebster. All the other authors declare no conflicts of interest.
80 60 40
Funding
20 0
50
100
0
50
100 %AP
Figure 2 Spline analysis with indication of the association between the probability of observing MS since last follow-up in relation to the proportion of time in atrial pacing (%AP). The curve shape is the same at all follow-up visits (P ¼ 0.93).
The DANPACE trial was funded by unrestricted grants from Medtronic, St Jude Medical, Boston Scientific, Ela Medical, Pfizer, and the Danish Heart Foundation (10-04-R78-A2954-22779).
Supplementary data A full list of investigators, advisory board members, and details of the safety and ethical committee and clinical event committee are available as supplementary material online.
Limitations Episodes of MS were used as a surrogate marker of AF, and sensitivities and specificities of the used MS algorithms are thus crucial. Pacemakers from five different manufacturers were used in the DANPACE trial, thus introducing different MS algorithms. However, the manufacturer of individual pacemakers was not recorded in DANPACE, and it is thus not possible to discriminate between the various algorithms. However, it is widely accepted that today’s MS algorithms display exhibit a very high degree of sensitivity and specificity for the reliable detection of AF.7,8,23 The occurrence of AF may sometimes lead to undersensing in the atrium and thus inappropriate atrial pacing. However, given the efficiency of modern MS algorithms, we consider it unlikely that this would not result in MS episodes which would be
References 1. Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak R et al.; MOST Investigators. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST). Circulation 2003;107:1614 –9. 2. Nielsen JC, Kristensen L, Andersen HR, Mortensen PT, Pedersen OL, Pedersen AK. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol 2003;42:614 –23. 3. Sweeney MO, Bank AJ, Nsah E, Koullick M, Zeng QC, Hettrick D et al.; Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACe) Trial. Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med 2007;357:1000 – 8. 4. Nielsen JC, Thomsen PE, Hojberg S, Moller M, Vesterlund T, Dalsgaard D et al.; DANPACE Investigators. A comparison of single-lead atrial pacing with dualchamber pacing in sick sinus syndrome. Eur Heart J 2011;32:686 – 96.
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40
detected at the next scheduled follow-up. Although patients with known AF prior to pacemaker implantation were excluded from the study cohort, some patients may have had episodes of undiagnosed AF. It may be argued that by using MS durations of 1 h (rounded to 1 h if ≥31 min) as the criterion for AF, we may detect clinically irrelevant episodes of atrial tachycardia and possibly far-field R-wave oversensing, thus overestimating the true incidence of AF. Today, it is not possible to make adjudications of electrogram tracings from the pacemaker memory to exclude significant overdiagnosis of AF. However, we performed the same analyses with MS durations of 6 and 24 h as the criterion for AF leading to similar results. The use of beta-blockers may inhibit the sinus node and thus cause an increase in %AP. It was, however, impossible to satisfactorily adjust for beta-blocker use because of the heterogeneity of drugs and doses used and their wide variation in patient effects. It is possible that various atrial lead positions, e.g. septal vs. lateral/appendage, may determine propagation of pacing impulses in the atria thus contributing differently to the development of AF. In the present study, we did not have information on the exact position of the atrial lead, yet most leads were implanted in the right atrial appendage or on the lateral wall of the right atrium as is practice in most clinics today.
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15. Acosta H, Viafara LM, Izquierdo D, Pothula VR, Bear J, Pothula S et al. Atrial lead placement at the lower atrial septum: a potential strategy to reduce unnecessary right ventricular pacing. Europace 2012;14:1311 –16. 16. Hermida JS, Kubala M, Lescure FX, Delonca J, Clerc J, Otmani A et al. Atrial septal pacing to prevent atrial fibrillation in patients with sinus node dysfunction: results of a randomized controlled study. Am Heart J 2004;148:312 –7. 17. Riahi S, Nielsen JC, Hjortshoj S, Thomsen PE, Hojberg S, Moller M et al.; DANPACE Investigators. Heart failure in patients with sick sinus syndrome treated with single lead atrial or dual-chamber pacing: no association with pacing mode or right ventricular pacing site. Europace 2012;14:1475 –82. 18. Carlson MD, Ip J, Messenger J, Beau S, Kalbfleisch S, Gervais P et al.; Atrial Dynamic Overdrive Pacing Trial (ADOPT) Investigators. A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT). J Am Coll Cardiol 2003;42:627 – 33. 19. Schuchert A, Rebeski HP, Peiffer T, Bub E, Dietz A, Mortensen K et al.; 3:4 Study Group. Effects of continuous and triggered atrial overdrive pacing on paroxysmal atrial fibrillation in pacemaker patients. Pacing Clin Electrophysiol 2008;31:929–34. 20. Sanagala T, Johnston SL, Groot GD, Santucci P, Rhine DK, Varma N. Left atrial mechanical responses to right ventricular pacing in heart failure patients: implications for atrial fibrillation. J Cardiovasc Electrophysiol 2011;22:866 – 74. 21. Hohnloser SH, Healey JS, Gold MR, Israel CW, Yang S, van Gelder I et al.; ASSERT Investigators. Atrial overdrive pacing to prevent atrial fibrillation: insights from ASSERT. Heart Rhythm 2012;9:1667 – 73. 22. Svendsen JH, Nielsen JC, Darkner S, Jensen GV, Mortensen LS, Andersen HR; DANPACE Investigators. CHADS2 and CHA2DS2-VASc score to assess risk of stroke and death in patients paced for sick sinus syndrome. Heart 2013;99:843 –8. 23. Kristensen L, Nielsen JC, Mortensen PT, Pedersen AK, Andersen HR. Evaluation of pacemaker telemetry as a diagnostic feature for detecting atrial tachyarrhythmias in patients with sick sinus syndrome. Europace 2004;6:580 – 5. doi:10.1093/europace/eut233 Online publish-ahead-of-print 4 August 2013
EP CASE EXPRESS
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Treatment of obstructive sleep apnoea improves metabolic conditions and prevents initiation of antiarrhythmic therapy in a patient with atrial fibrillation Dominik Linz*, Christian Ukena, and Hans-Ruprecht Neuberger Universita¨tsklinikum des Saarlandes, Klinik fu¨r Innere Medizin III, 66421 Homburg/Saar, Germany
* Corresponding author. Tel: +49 6841 16 23372; fax: +49 6841 16 23369, Email: [email protected]
% sleeping time
% sleeping time
No CPAP After 3 months of CPAP A 56-year-old man with symptomatic paroxysmal Max. Desaturation: 63% Max. Desaturation: 88% 100% 100% AHI: 75/hour atrial fibrillation (AF) and severe metabolic synAHI: 5/hour 80% 80% 60% 60% drome presented to our clinics with recurrent 40% 40% symptomatic AF with seven AF episodes within 20% 20% 0% 0% the last 3 months. All of them were associated 100% 90% 80% 70% 60% 100% 90% 80% 70% 60% % saturation below % saturation below with presentation at the clinic and two of them were terminated by electrical cardioversion. Detailed medical history taking revealed that all ECV ECV AF episodes occurred during night and severe Symptomatic AF episodes Symptomatic AF episodes sleepiness during daytime (Epworth Sleepiness CPAP No CPAP -3 months +3 months Scale score ¼ 15). A 24 h electrocardiogramHolter monitoring showed a high incidence of premature atrial contractions (PACs). Severe obstructive sleep apnoea [OSA; apnoea hypoxia index (AHI): 75/h] was diagnosed in a following sleep study. Appropriate continuous positive airway pressure (CPAP) therapy showed an improvement of OSA severity (AHI: 5/h), reduced maximal desaturation during sleep from 63 to 88%, and completely inhibited recurrence of symptomatic AF episodes during 3 months after start of CPAP therapy (Figure). Occurrence of PACs was reduced from 640/24 to 51/24 h. Interestingly, CPAP therapy also resulted in a clear improvement of metabolic conditions, which could not be treated by drugs before. Importantly, the initiation of a specific antiarrhythmic therapy could be prevented. Particularly in AF patients with metabolic syndrome, a detailed screening for OSA is important and its therapy may be helpful to reduce the number of symptomatic AF episodes and atrial ectopy.
The full-length version of this report can be viewed at: http://www.escardio.org/communities/EHRA/publications/ep-case-reports/ Documents/treatment-of-obstructive-sleep.pdf. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected].
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5. Adelstein E, Saba S. Right atrial pacing and the risk of postimplant atrial fibrillation in cardiac resynchronization therapy recipients. Am Heart J 2008;155:94 –9. 6. Elkayam LU, Koehler JL, Sheldon TJ, Glotzer TV, Rosenthal LS, Lamas GA. The influence of atrial and ventricular pacing on the incidence of atrial fibrillation: a meta-analysis. Pacing Clin Electrophysiol 2011;34:1593 –9. 7. Passman RS, Weinberg KM, Freher M, Denes P, Schaechter A, Goldberger JJ et al. Accuracy of mode switch algorithms for detection of atrial tachyarrhythmias. J Cardiovasc Electrophysiol 2004;15:773 –7. 8. de Voogt WG, van Hemel NM, van de Bos AA, Koistinen J, Fast JH. Verification of pacemaker automatic mode switching for the detection of atrial fibrillation and atrial tachycardia with Holter recording. Europace 2006;8:950 –61. 9. Harrell FE. Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis. New York, NY: Springer-Verlag; 2001. 10. Liang K, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13 –22. 11. Xie JM, Fang F, Zhang Q, Chan JY, Yip GW, Sanderson JE et al. Atrial dysfunction and interatrial dyssynchrony predict atrial high rate episodes: insight into the distinct effects of right atrial appendage pacing. J Cardiovasc Electrophysiol 2012;23:384 –90. 12. Yasuoka Y, Abe H, Umekawa S, Katsuki K, Tanaka N, Araki R et al. Interatrial septum pacing decreases atrial dyssynchrony on strain rate imaging compared with right atrial appendage pacing. Pacing Clin Electrophysiol 2011;34:370 –6. 13. Nielsen JC, Thomsen PE, Hojberg S, Moller M, Riahi S, Dalsgaard D et al.; DANPACE investigators. Atrial fibrillation in patients with sick sinus syndrome: the association with PQ-interval and percentage of ventricular pacing. Europace 2012;14:682 –9. 14. Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T et al. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet 1997;350:1210 –6.
