© 2005 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
Comparison of immediate and delayed automatic antitachycardia pacing for the termination of atrial tachyarrhythmias
Department of Cardiology and Pneumology, Georg-August-University Göttingen, Germany
Manuscript submitted 18 August 2004. Accepted after revision 25 January 2005.
*Corresponding author. Herzzentrum, Abteilung Kardiologie und Pneumologie, Klinikum der Georg-August Universität Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. Tel.: +49 551 39 9625; fax: +49 551 39 9628. E-mail address: dirkvollmann2000{at}aol.com (D. Vollmann).
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Abstract |
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AIMS: Automatic atrial antitachycardia pacing (ATP) can terminate atrial tachyarrhythmias (ATs) in patients with an implanted device. We investigated if the programmable delay between AT onset and ATP influences therapy efficacy.
METHODS: Patients with intermittent ATs and an implanted DDDRP pacemaker were randomized to receive ATP either immediately or 30 min after AT detection. After four months stored data were interrogated, AT-related symptoms were assessed, and patients crossed over to the alternative treatment arm for another four months. Stored atrial electrograms were analyzed for degree of AT organization and ATP success.
RESULTS: In 22 patients (64% male; 72 ± 7 years), ATP success rates were higher during immediate than during delayed ATP (device classification: 59 ± 7% vs. 22 ± 5%, P < 0.01; manual analysis: 36 ± 6% vs. 12 ± 5%, P < 0.01). Higher efficacy of immediate ATP was associated with a larger proportion of organized (Type I) AT prior to therapy (71% vs. 44% during delayed ATP). No difference was found in total AT numbers and duration, AT burden or related symptoms.
CONCLUSIONS: The programmable delay between arrhythmia onset and therapy delivery significantly influences the success-rate of ATP. However, a higher efficacy of immediate compared with delayed ATP does not translate into a reduction of AT burden or related symptoms.
Key Words: atrial tachyarrhythmias, atrial fibrillation, atrial pacing, antitachycardia pacing, pacing algorithm
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Introduction |
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A substantial proportion of patients with a dual chamber pacemaker are afflicted with atrial tachyarrhythmias (ATs), and their therapeutic management is important because of associated symptoms and morbidity. Analysis of pacemaker memory data has shown that a high proportion of AT episodes is, at least temporarily, amenable to device-based automatic atrial antitachycardia pacing (ATP) [1]
. The success-rate of ATP for the termination of AT approximates to 50% [2] and has been shown to be high in slow, organized episodes and low in fast, disorganized AT [1]. Within minutes after the onset of an AT episode, acceleration and disorganization may result from a shortening of the atrial refractory period [3]. A retrospective analysis suggests that the ATP success-rate decreases with the time interval between AT onset and application of the first pacing sequence [4]. Based on these findings, we hypothesized that the programmable delay between AT onset and ATP delivery may be a determinant of therapy efficacy. In this prospective, randomized cross-over trial we compared the efficacy of immediate and delayed ATP in patients with an implanted pacemaker and paroxysmal and/or persistent ATs.
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Methods |
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Study population
Patients were eligible for the study if they had a class I indication for permanent pacing, if paroxysmal or persistent ATs had been documented prior to device implantation, and if a special pacemaker (description see later) had been implanted at least three months earlier. Patients with permanent AF, myocardial infarction or cardiac surgery within the last three months, or New York Heart Association functional class IV heart failure were excluded. Patients were excluded from the final data analysis if the atrial electrogram of stored AT episodes revealed undersensing or oversensing errors or if less than two AT episodes had been stored per treatment period. The study complied with the Declaration of Helsinki, the study protocol was approved by the Institutional Ethical Committee, and all patients gave written informed consent.
Implanted system and programming
All patients had a DDDRP pacemaker (AT500TM, model 7253, Medtronic Inc., Minneapolis, MN, USA) implanted together with bipolar atrial and ventricular leads in conventional positions. In addition to conventional antibradycardia pacing, the AT500TM offers several diagnostic and therapeutic features for the management of paroxysmal and persistent AT. These features have been described in detail elsewhere [4,5]. In this study, ATs were detected if the median atrial cycle length (CL) was 
330 ms and if the atrial:ventricular ratio was >1:1 for at least 12 ventricular beats. ATP was applied to ATs with a CL between 220 ms and 330 ms and to regular ATs (CL variability <25%) with a CL between 180 ms and 220 ms. The device considers an ATP therapy as successful if five consecutive atrial beats are classified as sinus rhythm within 3 min after the last ATP sequence and before redetection of an AT. Determined by the protocol, a delay of either 0 or 30 min between AT onset and ATP delivery was programmed. Details of programming of ATP therapy settings are shown in Table 1. In all patients the DDDR mode, three preventive pacing algorithms (Atrial Preference PacingTM, Atrial Rate StabilizationTM, Post Mode Switching Overdrive PacingTM), and DDIR mode switch function were programmed.
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Study protocol
After randomization, either immediate or delayed ATP (time between AT detection and therapy delivery 0 or 30 min) was programmed and the device memory was cleared. Patients were blinded with regard to the programmed delay. All other pacing and sensing parameters and the antiarrhythmic drug therapy were kept unchanged throughout both study periods. After four months, patients returned to the pacemaker clinic and were asked to complete a questionnaire on AT-related symptoms (Atrial Fibrillation Symptom Frequency and Severity Scale) [6]
. Thereafter, the device memory was interrogated, all data were printed out and saved to disk, and memory functions were cleared. Patients then crossed over to the other study arm. Four months later, they were asked again to complete the questionnaire on AT-related symptoms and memory data were printed out and stored to disk.
Study endpoints
Primary study endpoint was the success-rate of ATP during the period with immediate vs. the period with delayed ATP. Secondary endpoints were (1) the device-derived number and duration of AT episodes; (2) the device-derived proportion of AT episodes treated with ATP; (3) the device-derived cumulative time that the patients spent in AT (AT burden); and (4) the AT-related symptom frequency and severity scores.
Data analysis
The number of detected AT episodes, the number of ATs treated by ATP, the number of episodes treated with success (as classified by the device), total AT burden and stored atrial electrograms (EGMs) were interrogated from the device memory at the end of each study period. Atrial EGMs with marker annotations and atrial intervals were stored for a maximum of 35 treated AT episodes per patient in each study period. All stored EGMs were carefully reviewed by two investigators to determine the degree of AT organization before therapy delivery and to verify the success of ATP. We adopted the method described by Israel et al. [1] to classify AT episodes into three types: Type I (organized AT, median CL 
200 ms), Type II (neither Type I nor Type III) and Type III (disorganized AT, CL < 200 ms). Based on manual analysis, success of ATP was defined as AT termination within 5 s after the last therapy sequence. The success-rate of ATP was calculated in each patient as the proportion between the number of AT episodes terminated by ATP and the total number of treated AT episodes. The calculation of the scores for AT-related symptoms has been described in detail elsewhere [6]. Briefly, for each of 16 symptoms, a patient is assigned a numerical score from 0 to 4 (0 = never, 4 = always) denoting how frequently the symptom is experienced. The scores are added to construct a cumulative frequency score between 0 and 64. In a similar way, the patient is assigned a score for the severity of each symptom (1 = mild, 2 = moderate, 3 = severe). No score is assigned if the patient did not experience the symptom. The sum of scores produces a cumulative severity score between 0 and 48. For statistical analysis, all data were first assessed with regard to normal distribution. Normally distributed data are expressed as mean ± standard error of the mean and were compared using Student's t-test. If no normal distribution was present, median values were compared using nonparametric testing (Wilcoxon signed rank test). A P-value <0.05 was considered statistically significant.
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Results |
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Patients
A total of 54 patients was included in the study. Twenty-two patients experienced at least two AT episodes during each study period. The data analysis was based on this patient population. Baseline characteristics are summarized in Table 2. Paroxysmal ATs had been documented in 20 patients (91%), persistent ATs in nine (41%). None of the enrolled patients excluded from data analysis had less than two AT episodes during one study period because of the development of persistent or permanent AT. Antiarrhythmic medication and pacemaker programming (except for the tested ATP delay) did not change during follow-up.
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Atrial ATP
A total of 24 359 AT episodes was detected by the device. According to counter data, ATP was delivered for 10 026 AT episodes. ATP was delivered for 86 ± 5% of all AT episodes during immediate therapy, whereas delayed ATP was delivered for only 28 ± 7% of the episodes (P < 0.01). The average daily amount of treated AT episodes was 3.5 ± 1.9 during immediate and 0.4 ± 0.2 during delayed ATP. In two patients, persistent AT only occurred during delayed ATP. On the other hand, three patients had an episode of persistent AT only with immediate ATP. No ventricular proarrhythmia was observed as a consequence of atrial ATP therapies.
The success-rate of ATP for the termination of AT is illustrated in Fig. 1A. According to the device-based classification of 10 026 treated episodes, the success-rate was higher during immediate than during delayed ATP (59 ± 7% vs. 22 ± 5%, P < 0.01). A manual EGM analysis was performed on 720 AT episodes from 22 patients. Appropriate atrial sensing was verified in all episodes. The device-based success-rate for the selected episodes was 64 ± 7% for immediate and 24 ± 6% for delayed ATP (P < 0.01). Manual analysis confirmed the difference in success-rate between immediate and delayed ATP (36 ± 6% vs. 12 ± 5%, P < 0.01), but overall success-rates were significantly lower compared with the device-based classification (P < 0.05).
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Analysis of atrial EGM morphology revealed a higher percentage of slow, organized (Type I) AT and a lower proportion of intermediate (Type II) and fast, irregular (Type III) AT during immediate ATP compared with delayed therapy (Fig 1B). ATP success-rates for Types I, II and III AT were 39%, 26% and 15% with immediate ATP and 15%, 7% and 4% with delayed ATP.
Frequency, duration and cumulative burden of atrial tachyarrhythmias
Programming of either immediate or delayed ATP had no significant effect on the median number of AT episodes per day (0.3 vs. 0.7; P = n.s.) and on the total AT burden (3.5 vs. 4.1 h per week; P = n.s.) (Fig. 2A). The device counter automatically grouped detected AT episodes into eight duration bands. The distribution in AT duration was similar during immediate and delayed ATP (Fig. 3). The majority of all episodes terminated within the first 10 min after onset, irrespective of the programmed ATP delay.
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Frequency and severity of AT-related symptoms
Cumulative scores for the frequency and the severity of symptoms associated with AT are illustrated in Fig. 2B. All 22 patients completed the questionnaires after both study periods. As shown, there was no difference in the cumulative scores for frequency (median 14.0 vs. 15.0; mean 12.2 ± 1.9 vs. 12.5 ± 1.9, P = n.s.) and severity (median 9.5 vs. 11.0; mean 9.6 ± 1.5 vs. 10.2 ± 1.6, P = n.s.) of symptoms between immediate and delayed ATP. In addition, no significant difference was found if for each patient the number of existing symptoms or if for each symptom the proportion of affected patients was compared between the two groups.
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Discussion |
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Main study findings
This study demonstrates that the programmable delay between AT onset and ATP delivery significantly influences the success-rate of atrial pacing therapies. A lower success-rate of delayed ATP is associated with a greater proportion of fast and irregular AT episodes. Despite the impact on termination efficacy, the ATP delay was not found to influence AT episode frequency or duration, total AT burden or arrhythmia-related symptoms.
Termination of atrial tachyarrhythmias by ATP
In our study, the success-rate of ATP for the termination of atrial tachyarrhythmias differed between immediate and delayed therapy and between device- and investigator-based classification of therapy success. Several other studies have analyzed the efficacy of atrial ATP in recent years and found success-rates ranging between 19% and 79% [2]. Gillis et al. [7] and Vollmann et al. [5] compared ATP success-rates based on device classification and manual EGM analysis. Similar to the present finding, the device-based success-rate was 20–40% higher than in the manually reviewed episodes. This difference results, at least in part, from the fact that the device allows a longer time interval (up to 3 min) between ATP delivery and detection of AT termination for the definition of therapy success. Other studies that manually determined the efficacy of ATP used a time interval of 20–30 s for the definition of therapy success [1,7]. The use of a shorter interval between ATP and episode termination reduces the probability of a coincidence of (not successful) ATP delivery and spontaneous AT termination. Since most spontaneous terminations occur within the first minutes after AT onset, the chance of a coincidence between therapy delivery and spontaneous episode termination is higher if ATP is delivered without a delay. Comparing the efficacy of immediate and delayed ATP, we aimed to minimize this potential bias by selecting a very short interval (5 s) between ATP delivery and AT termination for the definition of therapy success.
Using this conservative definition, we found that immediate ATP is associated with a higher success-rate and with a greater proportion of slow, organized AT episodes. It has been recognized earlier in retrospective analyses that the success-rate of ATP is higher in AT episodes with a long median atrial cycle length and lower in episodes with a short cycle length [4,5,7,8]. Israel and colleagues found that the success-rate of ATP depends on the degree of AT organization, with pace-termination being more common in highly organized (Type I) AT episodes [1]. In a retrospective analysis, ATP efficacy was inversely related to the AT duration before the first ATP sequence [4]. Our results are in line with these investigations and suggest that the higher proportion of fast and irregular AT episodes accounts, at least in part, for the lower success-rate of delayed ATP. Interestingly, we also found that the success-rates for the different types of AT tended to decrease if ATP was delayed. This may indicate that other factors than AT cycle length and degree of organization contribute to the decrease in ATP efficacy with time.
It has been shown that the majority of AT episodes maintain their type over the first minute after arrhyhtmia onset [1], but this does not exclude that AT episodes accelerate and become less organized after a delay of 30 min. In fact, significant shortening of the atrial refractory period can already occur 10 min after AT onset [3] and can result in AT acceleration. An alternative explanation for the higher proportion of fast and irregular AT episodes during delayed ATP might be that Type I episodes terminate more often spontaneously within the first 30 min after arrhythmia onset.
Impact on AT burden and related symptoms
Despite the effect on ATP success-rate, we found no evidence that the programmable delay between AT onset and therapy delivery influences the frequency or duration of AT episodes or the total AT burden. Other investigators also found that successful AT termination by ATP does not necessarily translate into a reduction in AT burden [9,10]. In the ATTEST study [9], combined activation of preventive pacing and ATP did not reduce AT burden, despite an ATP success-rate of 54%. Hügl et al. [10] report that aggressive incremental ATP increased the success-rate of ATP without changing AT frequency and burden. Given that the number of AT episodes was not different in the two treatment groups, three possible explanations may account for their findings as well as for our results: first, although we used a very conservative definition of ATP success, some AT episodes with ‘successful’ ATP may in fact have been coincidences with spontaneous terminations. Second, ATP delivered immediately after AT onset may terminate many episodes that also would have terminated spontaneously within a short period of time. Third, ATP may decrease the duration of many treated AT episodes, but overall burden may be biased by a few episodes of very long duration [10]. Our finding that the programmable ATP delay has no effect on frequency and severity of arrhythmia-related symptoms is in accordance with the data on number and duration of AT episodes.
Limitations
The present study has several limitations. First, the results of our investigation refer to patients with underlying heart disease and an indication for antibradycardia pacing. The majority of our patients suffered from paroxysmal atrial tachyarrhythmias with a rather low overall AT burden. The results may be different in patients without underlying heart diseases or bradycardia or in patients with predominantly persistent ATs. Second, it is not known if programming of a shorter or a longer delay than 30 min between AT detection and ATP delivery would have yielded changes in therapy efficacy. Third, the device stores a maximum number of 35 AT episodes between interrogations. Manual analysis of these episodes may not be representative for all ATs because they were not stored randomly. Last, the analysis of ATP efficacy may have been influenced by the inter-individual differences in AT episode distribution.
Conclusions
The present study finds that the delay between AT onset and therapy delivery significantly influences the success-rate of ATP. However, the apparent benefit of immediate compared with delayed ATP with regard to the success rate of ATP does not translate into a reduction of AT burden or related symptoms. Therefore, an individualized (‘tailored’) approach may be necessary for device programming. In patients with frequent and short-lasting atrial tachyarrhythmias, a longer delay between episode onset and ATP delivery may decrease battery consumption and increase device longevity.
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References |
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[8] Adler SW 2nd, Wolpert C, Warman EN, Musley SK, Koehler JL, Euler DE. Efficacy of pacing therapies for treating atrial tachyarrhythmias in patients with ventricular arrhythmias receiving a dual-chamber implantable cardioverter defibrillator. Circulation 2001; 104: 887–892.
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