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Europace 2003 5(3):267-273; doi:10.1016/S1099-5129(03)00041-2
© 2003 by European Society of Cardiology
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Paroxysmal atrial fibrillation prevention by pacing in patients with pacemaker indication

I. F. Lozano1, A. Vincent2, J. Roda3, M. Méndez4, J. M. M. Ferrer5, F. Andrade6, J. J. Manzano7, R. Ceres8, J. Errejon8 and J. Toquero1

1Hospital Puerta de Hierro Madrid 28029, Spain; 2Vitatron Holland; 3Hospital General Universitario Valencia, Spain; 4Hospital Militar Gómez Ulla Madrid, Spain; 5Hospital Txagorritxu Vitoria, Spain; 6Hospital del Insalud Mérida, Spain; 7Hospital Dr Negrin, Las Palmas de Gran Canaria Spain; 8Hospital General de Albacete Albacete, Spain

Manuscript submitted 7 August 2002. Accepted after revision 29 March 2003.

Correspondence: Ignacio Fernández Lozano, Hospital Puerta de Hierro, C/Julio Palacios 20, 1° D, Madrid 28029, Spain. Tel.: +34-917337835; Fax: +34-913737091; E-mail: ifernandezl{at}sego.es


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
AIMS: The prevent-atrial fibrillation (AF) registry analyses the clinical relevance and usefulness of the four preventive pacing algorithms, available in a family of cardiac stimulators, to prevent atrial fibrillation.

METHODS AND RESULTS: This study is a prospective, non-randomized, multicentre registry. Patients are eligible for the registry if they have sick sinus syndrome (SSS) with or without pre-existing atrial fibrillation. The preventive pacing algorithms were programmed for each patient on an individual basis using the diagnostic features of the devices. In the period from April 2000 to April 2001 a total of 68 patients (33 male, 35 female) has been included in the registry in 14 hospitals in Spain. Mean age was 72±12 years and the pacemaker indication was SSS in 15 patients (22%) and SSS with paroxysmal AF in 53 patients (78%). The median AF burden for the total group (n=32) was significantly reduced from 3.9 to 1.3% (67%, P=0.034, Wilcoxon signed rank test). The decrease in AF burden was accompanied by a non-significant decrease in the median number of episodes per day from 1.47 to 0.64 (a decrease of 56%). The average atrial pacing % was increased from 72 to 78%.

CONCLUSIONS: The prevent-AF registry demonstrated the usefulness of four preventive pacing algorithms in daily clinical practice. During the registry a significant reduction in AF burden and all other endpoints was observed. Dedicated diagnostics were key to adapting the optimal pacing therapy during follow-up.

Key Words: Atrial fibrillation, electrical stimulation, pacemaker, atrial fibrillation burden, sick sinus syndrome, pacing algorithms


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Atrial fibrillation(AF) is the most common sustained cardiac arrhythmia in clinical practice affecting the patient's prognosis[1Go–3]Go. Present pharmacological treatment is frequently ineffective and it provokes side-effects[4Go–8]Go. Therefore, interest in alternative treatments has increased during recent years[9Go–14]Go.

Physiological cardiac pacing has proved to be more effective than VVI mode in preventing AF episodes during follow-up in patients with implantable pacemaker indications[15Go–17]Go. Nowadays there are several ongoing investigations, which use different methods of atrial pacing to prevent and treat paroxysmal AF episodes[18Go–20]Go. Recently, AF prevention pacing algorithms have become available in some pacemakers for daily clinical practice[21,Go22]Go. These specific pacing algorithms aim to prevent the occurrence of episodes of paroxysmal AF by adapting the pacing rate upon detection of an impending arrhythmia. The safety and efficacy of these algorithms has been studied in a prospective randomized trial, named AFT, the results of which have recently been communicated[23Go–25]Go. The primary pacemaker indication for this study was the presence of drug-refractory AF with or without bradycardia.

Several retrospective studies have described the high incidence of paroxysmal AF in patients suffering from sick sinus syndrome (SSS)[26Go–28]Go. Therefore, this prevent-AF registry will primarily focus on patients with this rhythm disorder and show the experience with the four AF prevention algorithms available in the Vitatron DDDR cardiac stimulators.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The prevent-AF registry is a prospective, non-randomized, multicentre study. Patients are eligible for the registry if they have a pacemaker indication for SSS (I or IIa AHA–ACC classification)[29]Go with or without pre-existing paroxysmal AF.

The Vitatron DDDR cardiac stimulators PreventAF and Selection 9000 are used in this registry. These pacemakers had during the registry the same functionality (the Selection 9000 was not upgraded with AF3.0 software) and included diagnostic features for AF (Fig. 1), such as: total AF burden, number of AF episodes, number of premature atrial complexes (PACs) detailed onset reports of up to 16 episodes (Fig. 2).



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  		Figure 1 Diagnostic features of Vitatron pacemakers.

 



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  		Figure 2 Detailed AF onset report.

 
Four AF prevention pacing algorithms are incorporated: Pace ConditioningTM, Post-PAC ResponseTM, PAC SuppressionTM, and Post-Exercise ResponseTM. Figure 3 shows how they work



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  		Figure 3 Schematic view of four AF prevention pacing algorithms.

 
The Study procedures diagram is summarized in Fig. 4.



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  		Figure 4 Design of the prevent-AF registry.

 
  1. The follow-up schedule started with a maturation phase of two weeks. This phase was used to optimize pacing and sensing parameters. Special attention was paid to the prevention of far-field R wave sensing (FFRS). A postventricular atrial blanking (PVAB) of 150 ms was programmed and atrial leads with a short tip-to-ring distance (10 mm) were implanted in all the patients.
  2. The next phase was a monitoring phase of at least one month with the aim to monitor the occurrence of AF and to collect the individual onset mechanisms by means of the diagnostic information of the cardiac stimulator. During this phase the cardiac stimulator was programmed to conventional dual chamber pacing with the AF prevention algorithms OFF.
  3. During the preventive pacing phase the AF prevention pacing algorithms were programmed based on the analysis of the AF diagnostics according to the recommendations as described in Fig. 5. If PACs were seen prior to the onset of AF the PAC algorithms was activated, if no PACs were present prior to AF onset pace conditioning was recommended. In addition postexercise response was recommended in case a rate decrease prior to AF onset would occur. If no AF episodes were detected it was recommended not to activate any algorithm and monitoring was continued.
  4. Subsequent follow-ups were used to assess the efficacy of the therapy in order to optimize it further based on the physician's judgment.



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  		Figure 5 Programming recommendations in patients with AF during monitoring phase.

 
AF burden is defined as the % of time the patient is in AF (total time of all AF episodes) during the follow-up period. The start of an AF episode is defined as an atrial rate above 170 min–1 for at least six ventricular intervals and the end of an AF episode as an atrial rate below 170 min–1 for at least 30 ventricular intervals.

The relative reduction in AF burden is defined as the % change in AF burden between the follow-ups: i.e. if AF burden changes from 10 to 4% this is a 60% reduction. The primary outcome measure was the change in AF burden between the monitoring and the last follow-up in the preventive pacing phase. Secondary outcome measures were number of AF episodes and % of atrial pacing in each phase.

Since the distribution of AF recurrence does not follow the normal Gaussian distribution, analysis based on the mean is influenced too much by extreme values, e.g. patients in persistent AF or patients with long episodes of AF. Therefore, an analysis based on the median was used because this measure provides a more accurate description of the group.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The Registry was conducted in 14 centres in Spain, in the period from April 2000 to April 2001. A total of 68 patients (33 males, 35 females) was included.

The mean age was 72±12 and the pacemaker indication was SSS in all patients. A total of 53 patients (78%) suffered from paroxysmal AF before implantation.

This report describes a subgroup of 32 patients with pre-existing paroxysmal AF. These patients had at least one AF episode in the monitoring phase and had completed at least one in the following preventive pacing phase. The remaining 36 patients did not show AF during the monitoring phase and were therefore not included in this analysis.

The mean±standard deviation duration of the monitoring phase was 67.1±33 days and the preventive phase was 100.1±45 days. The AF prevention algorithms were programmed individually as shown in Table 1 (n=32). In nine patients all four algorithms were activated.


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  		Table 1 Programming of the AF prevention pacing algorithms

 
Primary outcomes
The median AF burden for the total group (32 patients) was reduced from 0.94 to 0.3 h day–1 (from 3.9 to 1.3%) (Wilcoxon test: P=0.034) representing a 67% reduction (Fig. 6). Figure 7 shows the Box and whisker plot with the quartiles of the distribution of AF burden for the group during the monitoring and preventive pacing phases.



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  		Figure 6 Median AF burden during the monitoring and preventive pacing phase.

 



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  		Figure 7 Box and whisker plot of AF burden.

 
Of the 32 patients, 24 (75%) showed a decrease in AF burden. Nineteen (59%) of the patients experienced a relative reduction in AF burden of 50% or more (Fig. 8).



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  		Figure 8 Relative reduction in AF burden per patient (n=32).

 
Secondary outcomes
A non-significant reduction in the number of episodes was observed from 1.47 episodes per day during the monitoring phase to 0.64 during the preventive pacing phase (a relative reduction of 56%). The average atrial pacing % was increased from 72 to 78%, which means only a 13% increase (Table 2).


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  		Table 2 Secondary outcomes

 
Drug therapy
One of the registry recommendations was to continue with the pre-existing antiarrhythmic treatment as much as possible. Eight patients began the registry with antiarrhythmic drugs. During the registry the drug therapy was changed in seven patients: in three of them an antiarrhythmic drug was added, in two patients a drug was changed and in two patients a drug was discontinued due to AF reduction and symptom relief.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In this registry, these new pacemakers have proved to be very useful for the diagnosis of paroxysmal AF episodes and for the prevention of these episodes by pacing algorithms. Pacemaker diagnostic functions provide valuable information about the occurrence and development of AF in each patient. By this means, the diagnostic information was used to adapt the pacemaker therapy to each patient on an individual basis. In our opinion, this explains the successful results obtained in the patients in spite of the short follow-up duration.

The reduction in the median AF burden was 67% between first and last follow-up with only slight increase in the % of atrial pacing from 72 to 78%. This was the result of the fact that the ‘pace conditioning’, which is the particular algorithm of the four prevention algorithms that overdrives the atrium the most, was activated in only 50% of the patients. The other three AF prevention pacing algorithms only pace the atrium if triggers for atrial fibrillation are present for a short period of time.

Another relevant registry feature is the high reliability of the data obtained. In the AFT[23Go–25]Go study, in which the efficiency of the same prevention algorithms was analyzed, many episodes were excluded from the analysis due to atrial undersensing or FFRS. However, in our registry only two episodes were excluded due to FFRS. Probably, choosing bipolar atrial leads with a short tip-to-ring distance (±10 mm) and programming an atrial blanking of 150 ms explain the low incidence of FFRS found in our registry. Although selecting a long PVAB of 150 ms does not compromise the detection of AF, it may cause problems of undersensing of atrial flutter[30]Go.

Our data show the typical limitations of all registries, in which the patients are not blinded or randomized and there is no fixed protocol. However, this registry describes the clinical usefulness of AF prevention algorithms available in these cardiac stimulators. This evidence was also shown in the AFT study.

The main value of our registry is the analysis of the usefulness of these algorithms in daily clinical practice. The population studied included patients with SSS with or without paroxysmal AF and represents a significant % of patients with a pacemaker indication. The follow-up protocol is very simple and can be performed in any hospital. Therefore, the results of the registry can be very useful when selecting and programming dual chamber pacemakers in patients with SSS.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
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A. R.J. Mitchell and N. Sulke
How do atrial pacing algorithms prevent atrial arrhythmias?
Europace, January 1, 2004; 6(4): 351 - 362.
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