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Europace Advance Access originally published online on November 16, 2007
Europace 2007 9(12):1124-1128; doi:10.1093/europace/eum242
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

PACING FOR ATRIAL FIBRILLATION

Septal atrial pacing for the prevention of atrial fibrillation

Nina Hakacova1, Dusan Velimirovic2, Peter Margitfalvi3, Robert Hatala3 and Thomas A. Buckingham3,*

1 Children's Cardiac Centre, Bratislava, Slovak Republic; 2 Institute for Cardiovascular Diseases, Clinical Center of Serbia, Belgrade, Serbia and Montenegro; 3 Slovak Cardiovascular Institute, Pod Krasnou Horkou 1, Bratislava 83348, Slovak Republic

Manuscript submitted 14 November 2006. Accepted after revision 12 October 2007.

* Corresponding author. Tel: +421 905 978573; fax: +421 2 6545 8182. E-mail address: buckint{at}gmail.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Statistics
 Results
 Discussion
 References
 
Aims: Atrial fibrillation (AF) produces significant morbidity and mortality. The current method of permanent pacing of the right atrium (RA) may cause delayed interatrial conduction and predispose to AF. We hypothesized that atrial septal pacing would reduce AF compared with high RA pacing.

Methods and results: The patients were randomized into two groups. After randomization, patients received a dual-chamber rate-responsive device capable of mode-switching with advanced telemetry features. Devices were programmed in a standardized manner. To be eligible, the patients were required to have a conventional indication for a permanent pacemaker and recurrent paroxysmal AF. Group 1 was paced from high RA and Group 2 was paced from the atrial septum. Analysis of 43 patients who have completed 6 months of follow-up and 22 patients who completed 12 months of follow-up showed no significant differences in the number of mode-switching episodes or in AF burden between groups (P = NS by Mann–Whitney) although there was a trend for less AF with septal pacing. There were no differences in thresholds, sensing, or lead impedance. Lead parameters remained stable over time and there were no displacements of the electrodes after implantation. No patient experienced lead-related complications. A significant variability in AF burden was noted in this patient population.

Conclusions: Implantation of an atrial-active fixation lead on the atrial septum is safe and feasible. However, this study showed no significant difference between septal pacing and high atrial pacing, using the endpoints of AF duration and number of AF episodes.

Key Words: Atrial fibrillation, Atrial septal pacing, High atrial pacing, Bachmann’s bundle


   Introduction
Top
 Abstract
 Introduction
Methods
 Statistics
 Results
 Discussion
 References
 
Atrial fibrillation (AF) is the most common cardiac rhythm disturbance and contributes substantially to cardiac morbidity and mortality. It carries a considerable risk of thromboembolism and sustained AF, with an uncontrolled ventricular response rate can cause congestive heart failure with an increased risk of death.1Go Since AF initiates negative processes of remodelling within the atrial myocardium, it has tendency to perpetuate itself.2Go

The occurrence of AF increases with age, with a prevalence rising from 0.5% of people in their 50s to nearly 10% of the octogenarian population. Treatments which prevent episodes of AF or which terminate it immediately after its onset are able to prevent or at least to delay its progression to chronic AF.3Go

Potential therapies of atrial fibrillation
The possible mechanisms of the activation and perpetuation of AF have significant implications for potential therapies. Long-term antiarrhythmic drug therapy has been used for the maintenance of sinus rhythm in patients with paroxysmal AF (PAF). However, many patients with PAF experience AF recurrences over the long term. Non-pharmacological therapies have been investigated, including surgery, internal defibrillators, catheter ablation, pacemakers, or the combination of catheter ablation with atrial pacing and ventricular pacing.4Go–8Go

Recently, techniques of multisite atrial pacing have been introduced. For example, bi-atrial9Go–12Go and interatrial septal pacing13Go showed promising preliminary results in AF prevention. Permanent single-chamber atrial pacing may seem obsolete.14Go The prevention of AF may relate to the maintenance of atrioventricular synchrony, prevention of bradycardia, and/or an altered activation sequence in the atria. We sought to compare standard high right atrial (RA) pacing with septal pacing in a randomized clinical trial.


   Methods
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 Abstract
 Introduction
 Methods
Statistics
 Results
 Discussion
 References
 
Study population
To be eligible, a patient was required to have a conventional indication for a permanent pacemaker and recurrent PAF. The study population consisted of patients with an established Class 1 and 2 indications for a permanent pacemaker (American Heart Association). In addition, patients had one of the following risk factors for PAF:

Inclusion criteria:

  1. prior symptomatic episodes of PAF in the last 6 months were documented by ECG or Holter. Note that this includes patients who have undergone cardioversion in the last 6 months and have one of the following:
    1. mild-to-moderate mitral stenosis grade 1 or 2 (American Heart Association),
    2. left atrial (LA) enlargement >55 mm on echocardiogram,
    3. recurrent atrial flutter, or
    4. sick sinus syndrome.

Exclusion criteria:
  1. patent foramen ovale or atrial septal aneurysm;
  2. prior surgery involving the RA (coronary bypass or valvular heart surgery) if performed <10 days before entry into the study;
  3. severe mitral stenosis.

Study protocol
Patients who met the inclusion criteria for the study received a permanent pacemaker from October 2002 to December 2003. Patients were randomized into two groups. After randomization, they received a dual-chamber rate-responsive device (DDDR) capable of mode-switching and with advanced telemetry features. Group l received atrial pacing using a single-active fixation lead in the atrial septum above the bundle of His near the foramen ovale, and Group 2 received ‘standard’ RA pacing—a single-active fixation lead was placed in the high RA. Devices were programmed in a standardized manner.

After hospital discharge, patients were followed at 1 week, 1 month, 3 months, and every 3 months thereafter. They underwent clinical assessment, a standard 12-lead ECG, and interrogation of the pacemaker at every visit. We counted the number of mode switches (each mode switch was taken to represent a recurrence of AF) and the total duration of AF after 6 months of follow-up and after 12 months of follow-up. To examine the safety of septal and atrial pacing, we checked whether all parameters were stable and whether there was a displacement of the electrode.

Implantable devices
The devices were St Jude Medical Integrity DR, Affinity DR, or Trilogy DR models and were programmed in both groups in a standard manner, which was designed to overdrive the atria (DDDR mode).

The requirements of the pacemaker were:

  1. rate-responsive or sensor-based pacing;
  2. mode switching with telemetry recording of mode switching episodes.

the atrial leads were St Jude Medical Tendril SDX-active fixation leads. The position of the septal atrial lead is shown in Figure 1a and b. The second lead was placed at the right ventricular apex. Figure 2 is a 12-lead ECG showing normal sinus rhythm and septal atrial activation (lead is placed above the bundle of His).


Figure 1
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  		Figure 1 (A) X-ray in AP projection. One lead is in high right atrium and the other is in the right ventricle. (B) X-ray in AP projection. The arrow points to the septal lead. The second lead is in the ventricle.

 


Figure 2
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  		Figure 2 Electrocardiogram. The left half of the tracing is in normal sinus rhythm and the right half shows atrial septal pacing.

 
Programmed parameters
The lower rate was set to 70. Rate adaptive pacing was used with a maximum rate of 110 and mode switches were programmed to occur for atrial rates > 225 bpm. The distance between the electrodes was 13.8 mm.

The endpoints
The endpoints assessed in our study were:

  1. the number of AF episodes between septal and high atrial-paced patients;
  2. the total duration of the AF episodes between septal vs. high atrial-paced patients;
  3. the safety of septal pacing.


   Statistics
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 Introduction
 Methods
 Statistics
Results
 Discussion
 References
 
Data are presented as mean ± SD. A value of P < 0.05 was considered statistically significant. We used non-parametric statistical methods, i.e. the Mann–Whitney test, to compare the two groups.


   Results
Top
 Abstract
 Introduction
 Methods
 Statistics
 Results
Discussion
 References
 
Patient characteristics are shown in Tables 1 and 2. There were 43 patients who completed 6 months of follow-up and 22 patients who completed 12 months of follow-up. The success of atrial septal pacing was judged by pacemaker interrogation of the AF burden or the total duration of AF, and the number of mode switching episodes (number of AF episodes). The results are shown in Tables 3 and 4 and Figures 3 and 4. Table 3 shows the analysis of 43 patients who completed 6 months of follow-up and Table 4 shows the analysis of 22 patients who completed 12 months of follow up. The proportion of ventricular pacing was 89 ± 21% (median 98%) in patients paced at the standard RA location and 91 ± 22% (median 98%) in those paced in the atrial septum (NS by Mann–Whitney Utest). No significant differences were found in the number of total mode switching episodes between groups (P = NS by Mann–Whitney). Likewise, there was no significant difference in total AF burden (duration of AF) (P = NS). There were more mode switches and longer durations of AF in patients paced in the high RA than the atrial septum, but this did not reach statistical significance. This difference tended to become larger after 12 months of follow-up compared with 6 months of follow-up. Lead parameters remain stable over time and there were no lead-related complications.


Figure 3
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  		Figure 3 (A) Number of mode switches (NoMS) after 6 months. Comparison between Group 1 (septal pacing) and Group 2 (high atrial pacing). There were no significant differences between groups. (B) Total duration of atrial fibrillation (DoF) after 6 months. Comparison between Group 1 (septal pacing) and Group 2 (high atrial pacing). There were no significant differences between groups.

 


Figure 4
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  		Figure 4 (A) Number of mode switches (NoMS) after 12 months. Comparison between Group 1 (septal pacing) and Group 2 (high atrial pacing). There were no significant differences between groups. (B) Total duration of atrial fibrillation (DoF) after 12 months. Comparison between Group 1 (septal pacing) and Group 2 (high atrial pacing). There were no significant differences between groups.

 


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  		Table 1 Characteristics of the patients after 6 months of follow-up

 


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  		Table 2 Characteristics of the patients after 12 months of follow-up

 


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  		Table 3 Comparison of septal and high atrial pacing after 6 months of follow-up

 


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  		Table 4 Comparison of septal and high atrial pacing after 12 months of follow-up

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Statistics
 Results
 Discussion
References
 
Atrial fibrillation is a common clinical arrhythmia, which is difficult to manage clinically. Consequently, there are an increasing number of therapies under investigation. Some clinical data suggest that atrial pacing might prevent PAF,15Go and several clinical trials have shown that atrial or dual-chamber pacing in patients with bradycardia reduces the incidence of AF.16Go–18Go In recent years, various types of atrial pacing that might reduce the occurrence of AF have been studied. One important factor predisposing to re-entry is an increased dispersion of atrial refractoriness.19Go Dispersion of refractoriness can be reduced by shortening total atrial activation.20Go,21Go Therefore, it may be desirable to find a location from which the stimulation of both atria is rapid and uniform.22Go,23Go Septal pacing provides shorter atrial activation times, compared with high atrial activation and offers an attractive alternative to dual-site atrial pacing.

The majority of atrial leads are positioned in the RA appendage. It is possible that stimulation in this site results in delayed activation of areas of the atria that are important in the initiation of PAF.23Go It is difficult to estimate the effect of high RA pacing alone on PAF from the literature because of conflicting data. In the Atrial Pacing Periablation for Paroxysmal Atrial Fibrillation (PA3) Study,24Go high atrial pacing did not prevent PAF in patients without bradycardia over the short term. The patient population selected was different than ours and the follow-up was shorter by 3 months. In our study, 43 patients completed 6 months of follow-up and 22 patients completed 12 months of follow-up.

Several reports have suggested that site-specific atrial pacing, e.g. Bachmann’s bundle,25Go–28Go LA, or dual-site atrial pacing,27Go–29Go might be more effective by virtue of shortening the total interatrial activation times.30Go Multisite pacing has generally positive results.31Go–33Go However, the usual methods of bi-atrial stimulation require two leads: one placed in the RA and another in the LA, using the coronary sinus. The LA can be paced by placing a lead in the proximal coronary sinus. This approach has the disadvantage of requiring an extra lead, which increases costs and the difficulty of the implant procedure.34Go Septal atrial pacing is a simple method, which may produce simultaneous bi-atrial stimulation, using a single lead. Prior clinical trials of atrial septal pacing have given mixed results. The study by Bailin of Bachmann’s bundle pacing (high interatrial septum) showed positive results with a longer survival free of AF in the group treated with septal pacing.25Go A study by Padeletti et al.35Go in 2001 showed benefit of septal pacing in 46 patients randomized to RA appendage pacing or septal pacing in the prevention of PAF. However, a later, larger multicentre study of the combined effect of septal pacing and AF/atrial tachycardia pacing prevention algorithms failed to show benefit of atrial septal pacing.36Go

In our group of patients with drug refractory PAF, septal atrial pacing had a small incremental antifibrillatory effect compared with RA pacing, but this was not statistically significant. Another goal of our study was also to examine the safety and flexibility of septal pacing. We saw no electrode displacements, and lead parameters were stable all during the follow-up.

We did not find a significant difference in the number of AF episodes and the duration of AF between the septal vs. high atrial pacing group. This may be due to the limited number of patients relative to the high variability of the AF burden in this patient population.

Supported by an unrestricted grant from St Jude Medical.


   References
Top
 Abstract
 Introduction
 Methods
 Statistics
 Results
 Discussion
 References
 
[1] Benjamin EJ, Wolf PA, Agostino RB. Impact of atrial fibrillation on the risk of death. Circulation (1998) 98:946–52.[Abstract/Free Full Text]

[2] Kumagai K, Akimitsu S, Kawahira K, et al. Electrophysiological properties in chronic lone atrial fibrillation. Circulation (1991) 84:1662–700.[Abstract/Free Full Text]

[3] Funck RC, Pomsel K, Grimm W, et al. Prevention of atrial arrhythmias by pacing. Herz (2001) 26:18–29.[CrossRef][Web of Science][Medline]

[4] Anderson HC, Nielsen JC, Thomsen PEB, et al. Long term follow-up of patients from a randomized trial of atrial versus ventricular pacing for sick sinus syndrome. Lancet (1997) 305:1210–6.

[5] Chirife R, Ortega DF, Salazar A. Nonphysiological left heart AV intervals as a result of DDD and AAL pacing. Pacing Clin Electrophysiol (1991) 14:1752–6.[CrossRef][Medline]

[6] Grosfeld MJ, Res JC, Vos DH, et al. Testing a new mechanism for left interventricular septal pacing: the transseptal route; a feasibility and safety study. Europace (2002) 4:439–44.[Abstract/Free Full Text]

[7] Leclercq C, Cazeau S, Ritter P, et al. A pilot experience with permanent biventricular pacing to treat advanced heart failure. Am Heart J (2000) 140:62–70.

[8] Prakash A, Delfaut P, Ryszard BK, et al. Regional right and left atrial activation patterns during single and dual site atrial pacing in patients with atrial fibrillation. Am J Cardiol (1998) 82:1197.[CrossRef][Web of Science][Medline]

[9] Daubert C, Mabo P, Berder V, et al. Atrial tachyarrhytmias associated with high degree interatrial conduction block. Prevention by permanent atrial resynchronization. Eur J Cardiac Pacing Electrophysiol (1994) 4:35–44.

[10] Saksena S, Prakash A, Hill M, et al. Prevention of recurrent atrial fibrillation with chronic dual-site right atrial pacing. J Am Coll Cardiol (1996) 28:687–94.[Abstract]

[11] Leclercq JF, De Sisti A, Fiorello P, et al. Is dual site better than single site atrial pacing in the prevention of atrial fibrillation? Pacing Clin Electrophysiol (2000) 23:2101–7.[CrossRef][Medline]

[12] Saksena S, Prakash A, Ziegler P, et al. Improved suppression of recurrent atrial fibrillation with dual-site right atrial pacing and antiarrhythmic drug therapy. J Am Coll Cardiol (2002) 40:1140–50.[Abstract/Free Full Text]

[13] Padeletti L, Porciani C, Cilella A, Ticci P, Vena S, Costoli A, et al. Interatrial septum pacing a new approach to prevent recurrent atrial fibrillation. J Interven Electrophysiol (1999) 3:35–43.[CrossRef]

[14] Barold SS. Permanent single chamber atrial pacing is obsolete. Pacing Clin Electrophysiol (2001) 24:271–81.[CrossRef][Medline]

[15] Mehra R, Hill MRS. Prevention of atrial fibrillation/flutter by pacing techniques. In: Interventional Electrophysiology: A Textbook—Saksena S, Luderitz B, et al, eds. (1996) 2nd ed. Armonk, NY: Futura Publishing Co. 521–40.

[16] Andersen HR, Nielsen JC, Thomsen PE, 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.[CrossRef][Web of Science][Medline]

[17] Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med (2000) 342:1385–91.[Abstract/Free Full Text]

[18] Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med (2002) 346:1854–62.[Abstract/Free Full Text]

[19] Tanabe T, Deguchi Y, Handa S, et al. Longer longitudinal atrial dimension in patients with idiopathic paroxysmal atrial fibrillation: a possible cause of fibrillation. Am Heart J (2001) 142:669–78.[CrossRef][Web of Science][Medline]

[20] Becker R, Senges JC, Bauer A, et al. Suppression of atrial fibrillation by multisite and septal pacing in a novel experimental model. Cardiovasc Res (2002) 54:476–81.[Abstract/Free Full Text]

[21] Takahisa Y, Masatake F, Tsuyoshi S, et al. Effect of atrial septal pacing on P wave duration dispersion and atrial late potentials in patients with paroxysmal atrial fibrillation. Am J Cardiol (2001) 7:785–98.

[22] Manolis AG, Katsivas AG, Vassilopoulos C, et al. Prevention of atrial fibrillation by inter-atrial septum pacing guided by electrophysiological testing, in patients with delay interatrial conduction. Europace (2002) 4:165–74.[Free Full Text]

[23] Anne M, Gillis D, Stuart J, et al. Atrial pacing periablation for prevention of paroxysmal atrial fibrillation. Circulation (1999) 99:2553–8.[Abstract/Free Full Text]

[24] Gillis A, Wyse DG, Connolly SI, et al. Atrial pacing periablation for prevention of paroxysmal atrial fibrillation. Circulation (1999) 99:2553–8.[Abstract/Free Full Text]

[25] Bailin SJ, Adler SW, Giudici MC, et al. Prevention of chronic atrial fibrillation by pacing at Bachmanns bundle. Results of a multicentre trial. J Cardiovasc Electrophysiol (2001) 12:912–7.[CrossRef][Web of Science][Medline]

[26] Spencer WH, Zhu DW, Markowitz T, Badruddin SM, et al. Atrial septal pacing: a method for pacing both atria simultaneously. Pacing Clin Electrophysiol (1997) 20:2793–45.

[27] Fitts S, Hill R, Lehra R, et al. Design and implementation of the dual site atrial pacing to prevent atrial fibrillation. J Interv Card Electrophysiol (1998) 2:139–44.[CrossRef][Web of Science][Medline]

[28] Fragakis N, Shakespeare CF, Lloyd G, et al. Reversion and maintenance of sinus rhythm in patients with permanent atrial fibrillation by internal cardioversion followed by biatrial pacing. Pacing Clin Electrophysiol (2002) 25:278–86.[CrossRef][Medline]

[29] Papageorgiou P, Anselme F, Kirchhof CJHJ, et al. Coronary sinus pacing prevents induction of atrial fibrillation. Circulation (1997) 96:1893–8.[Abstract/Free Full Text]

[30] Buxton A, Josephson M. The role of P wave duration as a predictor of postoperative atrial arrhythmias. Chest (1981) 80:68–73.[CrossRef][Web of Science][Medline]

[31] Delfaut P, Saksena S, Prakash A, et al. Long term outcome of patients with drug refractory atrial flutter and fibrillation after single and dual-site right atrial pacing for arrhythmia prevention. J Am Coll Cardiol (1998) 32:1900–8.[Abstract/Free Full Text]

[32] Leclercq JF, De Sisti A, Fiorello P, et al. Is dual site better than single site atrial pacing in the prevention of atrial fibrillation? Pacing Clin Electrophysiol (2000) 23:2101–7.[CrossRef][Medline]

[33] Levy T, Walker S, Rex S, Rochelle J, Paul V. No incremental benefit of multisite atrial pacing compared with right atrial pacing in patients with drug refractory paroxysmal atrial fibrillation. Heart (2001) 85:48–52.[Abstract/Free Full Text]

[34] Kativas AG, Manolis E, Lazaris C, et al. Atrial septal pacing to synchronize atrial depolarization in patients with delayed interatrial conduction. Pacing Clin Electrophysiol (1998) 21:2220–5.[CrossRef][Medline]

[35] Padeletti L, Pieragnoli P, Ciapetti C, et al. Randomized crossover comparison of right atrial appendage pacing versus interatrial septum pacing for prevention of paroxysmal atrial fibrillation in patients with sinus bradycardia. Am Heart J (2001) 142:1047–55.[CrossRef][Web of Science][Medline]

[36] Padeletti L, Purerfellner H, Adler SW, Waller TJ, Harvey M, Horvitz L, et al, Worldwide ASPECT Investigators. Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia. J Cardiovasc Electrophysiol (2003) 14:1189–95.[CrossRef][Web of Science][Medline]


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