Efficacy of Pacing Therapies for Treating Atrial Tachyarrhythmias in Patients With Ventricular Arrhythmias Receiving a Dual-Chamber Implantable Cardioverter Defibrillator
Background— Although overdrive pacing for treating atrial flutter is well established, the efficacy of device-based atrial pacing for treating spontaneous atrial tachyarrhythmias in patients with implantable cardioverter defibrillators (ICD) is unknown. This study evaluated the efficacy of novel pacing therapies for treating atrial tachyarrhythmias in patients receiving a dual-chamber ICD to treat ventricular tachyarrhythmias.
Methods and Results— A Jewel AF ICD was implanted in 537 patients with ventricular arrhythmia who were followed for 11.4±8.2 months (74% had a documented history of atrial tachyarrhythmias). The device discriminated atrial tachycardia (AT) from atrial fibrillation (AF) on the basis of cycle length and regularity, and it used 3 different methods of overdrive atrial pacing (Ramp, Burst+, and 50-Hz burst) to treat AT episodes and one method (50-Hz burst) to treat AF episodes. Pacing successfully terminated 59% of 1500 spontaneous AT episodes in 127 patients and 30% of 880 AF episodes in 101 patients (P<0.001). With AT and AF episodes combined, pacing efficacy was 48%. Pacing efficacy was significantly reduced at AT cycle lengths ≤220 ms and AF cycle lengths ≤160 ms (P<0.01) The median time from pacing to AT/AF termination was 1.1 minute for the pacing successes and 96 minutes for the failures (P<0.001).
Conclusions— Atrial pacing terminated 48% of AT/AF episodes in patients with a history of ventricular arrhythmias. Pacing efficacy was greater for device-classified AT than AF. Pacing efficacy was significantly influenced by tachycardia cycle length. Successful pacing significantly reduces the time required for AT/AF termination.
Received April 3, 2001; revision received June 8, 2001; accepted June 20, 2001.
Atrial tachyarrhythmias represent a significant challenge in patients who have received an implantable cardioverter-defibrillator (ICD) to treat life-threatening ventricular arrhythmias.1,2 In addition to increasing the possibility of inappropriate ventricular shocks, atrial tachyarrhythmias may also increase the risk of heart failure3 and stroke.4 Drug therapy for atrial tachyarrhythmias in patients with ICDs is often unsatisfactory due to limited drug efficacy and ventricular proarrhythmia. A new dual-chamber ICD (Medtronic model 7250) has been introduced; it classifies an atrial tachyarrhythmia as atrial tachycardia (AT) or atrial fibrillation (AF) on the basis of cycle length and regularity and has independently programmable pacing and shock therapy for AT, AF, ventricular tachycardia, and ventricular fibrillation. Furthermore, the device is a dual-chamber pacemaker with algorithms to prevent atrial tachyarrhythmias. The purpose of the present investigation was to evaluate the efficacy of pacing therapies for the termination of atrial tachyarrhythmias in patients with ventricular tachyarrhythmias. In addition, this study assessed the relationship between therapy efficacy and the cycle length of the atrial tachyarrhythmia at the time of therapy.
A Jewel AF ICD was implanted in 537 patients who had a clinical indication for the implantation of a ventricular ICD. In 398 patients (74%), device implantation required at least 2 documented episodes of (symptomatic or asymptomatic) AF and/or AT in the year before implantation, with a 12-lead ECG documentation of at least one episode. Patients with chronic AF were excluded.
A right atrial and right ventricular bipolar electrode were required for pacing and sensing. In addition, one high-voltage ventricular and one high-voltage supraventricular electrode (in the right atrium or superior vena cava) were required for shock therapy. All patients gave written, informed consent according to a protocol approved by the Human Subjects Committee of the institution at which the devices were implanted.
Ventricular therapies were enabled in all patients. Selection of atrial detection and therapy settings were left to the implanting physician’s discretion. Patients were followed-up with routine device interrogations at 1 month, 3 months, and 6 months after implantation and then every 6 months thereafter.
Detection and Termination of AT/AF Episodes
A dual-chamber algorithm (PR logic) is used to discriminate ventricular from supraventricular tachyarrhythmias on the basis of the ratio and timing of P-waves with respect to R-waves.5 Atrial tachyarrhythmias are detected when the median atrial cycle length (12 beats) is less than the programmed AT or AF detection interval (Figure 1) and the P:R ratio is greater than 1:1 for at least 32 ventricular beats.6 The device discriminates AT from AF on the basis of 2 programmable detection zones, which may overlap (Figure 1). If the median atrial cycle length is in the overlap zone, the rhythm is classified as AT if it is regular and AF if it is irregular.
Information stored by the device on treated episodes includes the date, time of the event, median PP, episode duration, therapy sequences, and therapy outcome. The device also stores 5 s of electrogram before therapy and marker events and PP, PR, and RR interval information for 60 events before therapy and 60 events before termination. Appropriate detection of spontaneous AT/AF was determined from an investigator review of the electrograms and intervals stored before therapy.
Atrial therapies to treat AT/AF episodes include pacing (Ramp, Burst+, and 50-Hz burst) and high-voltage shocks (0.4 to 27 J). For AT episodes, the first 3 programmable therapies are pacing and the last 3 are shocks. The first 2 therapies may be programmed for either Burst+ or Ramp, but the third therapy can only be programmed for a 50-Hz burst. For AF episodes, the first programmable therapy is pacing (50-Hz burst) followed by a maximum of 5 shocks. There is a programmable delay (0 to 24 hours) between AT/AF detection and the onset of therapy, which is programmed separately for pacing and shocks. For Burst+ and Ramp therapy, pacing pulses (AOO) are delivered as a percentage (programmable) of the AT cycle length, and the AA interval is progressively decreased until all sequences have been delivered or until the AA interval reaches the programmed limit (150 ms, nominal). For Burst+ therapy, after the delivery of a train of pulses, 2 premature stimuli are delivered at progressively shorter coupling intervals (programmable). If the therapy fails and AT/AF is redetected, a programmed interval decrement is subtracted from all intervals before the next sequence is delivered. For Ramp therapy, each pulse in the train is delivered at progressively shorter coupling intervals on the basis of a programmed interval decrement. If a sequence fails and AT/AF is redetected, one additional pacing pulse is added to the next sequence. For 50-Hz burst therapy, a train of pulses is delivered at 20-ms intervals for a variable duration (0.5 to 3 s).
The rhythm (AT or AF) detected at the time of the first pacing therapy was used to classify the entire episode, regardless of subsequent rhythm transitions between AT and AF. For the analysis of therapy efficacy, all spontaneous arrhythmia episodes that had an onset ≤1.0 minute from the device-defined termination of the preceding episode were considered a continuation of that episode. These “continuation” episodes included episodes where there was early recurrence of AT/AF after an appropriate device-defined termination or the device-defined termination was inappropriate and AT/AF was redetected. For a therapy to be classified as successful in this analysis, 5 consecutive sinus beats had to be detected within 1 minute of the end of a pacing sequence and sinus rhythm had to persist for at least 1 minute before the detection of another AT/AF episode.
SAS was the statistical software used for all analyses. Continuous data were reported as the mean±SD or as the median and 25% to 75% quartile. Pacing efficacy was expressed as the incidence of successful terminations. The number of spontaneous episodes in individual patients who received therapy varied, which introduced bias in the efficacy calculations. Therefore, efficacy calculations were adjusted using the Generalized Estimating Equation (GEE) method with an exchangeable correlation structure to remove bias.7 This technique yields an average therapy efficacy that is based on the number of patients, the number of episodes per patient, and the magnitude of the correlation between responses within patients. The null hypothesis was rejected when P≤0.05.
Patient demographics are shown in Table 1. The 537 patients with an implanted device were followed for 11.4±8.2 months (range, 0 to 33 months). In 381 of these patients, pacing therapies for AT and/or AF were enabled at some time during the follow-up. Spontaneous atrial tachyarrhythmias were detected and treated by the device in 167 patients during a follow-up time of 14.1±7.4 months (range, 0.5 to 29.6 months). Atrial electrograms and marker intervals were available for review in 3500 episodes. After review by the investigators, 3154 of these 3500 episodes were classified as appropriate. Of the 3154 treated episodes, 774 (25%) recurred within 1 minute from the preceding episode and were classified as continuation episodes. Thus, therapy efficacy was computed from the analysis of 2380 episodes that were preceded by at least 1 minute of sinus rhythm. The median number of episodes per patient was 6 (25% to 75% quartiles, 2 to 17). Because shocks were delivered to treat only 8% of these episodes and atrial defibrillation threshold testing was not mandatory, shock efficacy was excluded in this analysis.
The programming of AT/AF detection and the pacing therapies was examined at the time of the first treated episode in each patient. The median AF detection interval was 270 ms (25% to 75% quartile, 270 to 270 ms), the median AT detection interval was 320 ms (25% to 75% quartile, 320 to 340 ms), and the median minimum AT detection interval was 170 ms (25% to 75% quartile, 170 to 200 ms). The median programmed delay from detection to the onset of pacing was 1 minute (range, 0 to 120 minutes).
The cycle length of the 2380 treated AT/AF episodes and the overall efficacy of the pacing therapies are shown in Table 2. The average cycle length of the AT episodes (278±56 ms) was significantly longer than the average cycle length of the AF episodes (204±35 ms, P<0.0001). Pacing successfully terminated 58.5% of AT episodes compared with 29.8% of 880 AF episodes (P<0.001). With AT and AF episodes combined, pacing efficacy was 47.9%. There were no episodes of ventricular tachycardia or ventricular fibrillation induced by the atrial pacing therapies.
AT episodes that were successfully terminated by pacing received a median of 2 pacing sequences (25% to 75% quartile, 1 to 4), whereas episodes that were pacing failures received a median of 10 sequences (25% to 75% quartile, 1 to 7). The AF episodes that were successfully terminated by pacing received a median of 3 sequences (25% to 75% quartile, 2 to 24), whereas episodes that were pacing failures received a median of 6 sequences (25% to 75% quartile, 3 to 18). For both AT and AF episodes, the difference in the number of pacing sequences (success versus failure) was highly significant (P<0.001, Wilcoxon signed-rank test).
A subanalysis was performed to compare the efficacy of Burst+ versus Ramp therapy for AT episodes. When Burst+ was the initial therapy (591 episodes), efficacy was 48.4% (GEE adjusted estimate, 35.2%). When Ramp was the initial therapy (726 episodes), efficacy was 41.3% (GEE adjusted estimate, 35.5%). The difference between the 2 therapies was not significant.
To determine if any of the clinical characteristics of the patients at the time of implant predicted pacing efficacy, a multivariate analysis was performed using all of the clinical variables and antiarrhythmic medications listed in Table 1. For AT episodes, the only independent predictor of pacing efficacy was a history of atrial flutter (P=0.025). For AF episodes, there were no independent predictors of efficacy.
Examples of pacing therapies that terminated AT/AF episodes are shown in Figures 2 and 3⇓. An episode of AT that was terminated with Burst+ therapy is shown in Figure 2, whereas an AF episode that was terminated with 50-Hz burst therapy is shown in Figure 3. Although the rhythm in Figure 3 was classified as AF on the basis of the median AA interval (180 ms), the atrial complexes in the electrogram are discrete and suggest that this rhythm might have been an organized AT.
The effect of the AT/AF cycle length on pacing efficacy is shown in Table 3. The cycle length was determined from the median of the last 12 atrial events in the marker channel just before the onset of the first therapy. The AT and AF episodes were divided into 5 to 7 groups so that each group covered a minimum of 20 ms. The efficacy was 29% for AT episodes with cycle lengths ≤190 ms and increased to >65% for AT episodes with cycle lengths ≥320 ms. The difference in the efficacy for episodes with cycle lengths ≤220 ms compared with episodes with cycle lengths ≥230 ms was highly significant (P<0.001). For AF episodes, the efficacy was 11% for episodes with cycle lengths ≤160 ms and increased to 41% for episodes with cycle lengths ≥250 ms. The difference in efficacy for cycle lengths ≤160 ms compared with episodes with cycle lengths ≥170 ms was significant (P<0.01). Multivariate analysis showed that the influence of cycle length on pacing efficacy was independent of other clinical variables or the use of antiarrhythmic drugs (P<0.01).
The effect of the delay from AT/AF detection to the onset of therapy is shown in Table 4. The AT and AF episodes were divided into 3 groups, with delays of 0, 1 to 5, and 10 to 120 minutes. The median delay from detection to the onset of pacing therapy for all episodes was 1 minute (range, 0 to 120 minutes). There was no significant change in efficacy as delay increased from 0 to 1 to 5 minutes. However, as the delay increased to 10 to 120 minutes, there was a significant reduction in pacing efficacy for both AT and AF episodes (P<0.01). Multivariate analysis revealed that a delay of ≤5 minutes was an independent predictor of efficacy (P<0.005).
To determine the effect of the atrial pacing therapies on AT/AF duration, the time from the first pacing therapy to the termination of each episode was analyzed. Excluded from this analysis were 55 episodes in which the episode duration was not available because the device was interrogated while an episode was in progress. The median time to termination for 1140 AT/AF episodes that were terminated by pacing was 1.1 minutes (25% to 75% quartile, 0.4 to 3.6 minutes) compared with 96 minutes (25% to 75% quartile, 18 to 558) for the 1185 pacing failures. When pacing failed, the episodes terminated spontaneously (n=1048) or by a shock (n=137). A paired analysis (Wilcoxon signed-rank test) was performed in patients who had both pacing successes and failures. In 75 patients who provided AT episodes for the paired analysis, the median time to termination was 1.4 minutes (25% to 75% quartile, 0.6 to 3.5 minutes) for the successes compared with 102 minutes (25% to 75% quartile, 24 to 312 minutes) for the failures (P<0.001). In 34 patients who provided AF episodes for the paired analysis, the median time to termination was 3.1 minute (25% to 75% quartile, 1.0 to 5.2 minutes) for the successes compared with 72 minutes (25% to 75% quartile, 30 to 186 minutes) for the failures (P<0.001).
This study demonstrated an overall pacing efficacy of 48% for terminating AT/AF episodes using these pacing therapies. This estimate is conservative because therapies classified by the device as successful were categorized as a failure if AT/AF recurred within 1 minute. Pacing successfully terminated 59% of AT episodes and 30% of AF episodes (P<0.001). Because 63% of the treated episodes were AT, the overall pacing efficacy of 48% reflects an average of the pacing efficacy for AT and AF episodes. The observation that a higher proportion of treated episodes were AT is somewhat surprising because 81% of the patients who had treated episodes presented with a history of AF; only 36% had a history of atrial flutter.
Previous studies have shown that an excitable gap exists during clinical AF and that it is possible to capture local areas of atrial myocardium by overdrive pacing.8–10 However, the mass of atrial muscle captured by the pacing stimuli was not sufficient to terminate AF.8–10 Even when 50-Hz burst pacing was delivered to single or dual sites in the right atrium, AF could not be terminated.11,12 Because AF is difficult to terminate by overdrive pacing, it could be argued that the 30% efficacy of pacing in the present study does not reflect the actual rate of conversion of AF to sinus rhythm. The 30% pacing efficacy could have included some episodes of AT that were classified by the device as AF and were successfully terminated by overdrive pacing (Figure 3). Alternatively, some episodes may have terminated spontaneously during or after a pacing therapy and may have been classified as a therapy success.
The present study establishes the significant independent influence of the AT/AF cycle length on pacing success. Pacing efficacy was significantly reduced for AT cycle lengths ≤220 ms (P<0.001) and for AF cycle lengths ≤160 ms. The effects of cycle length were independent of the use of antiarrhythmic drugs, although it is possible that class I and III drugs may have indirectly influenced pacing efficacy by prolonging the tachycardia cycle length.13,14 The independent effects of cycle length on pacing efficacy for AT episodes confirms previous work in which pacing terminated 78% of atrial flutter episodes when the cycle length was >230 ms but only 58% when the cycle length was <230 ms.15
The influence of the delay from detection to the onset of pacing was analyzed and found to have an effect on pacing efficacy that was independent of the AT cycle length. For both AT and AF episodes, pacing efficacy was optimal when the delay from detection to therapy onset was ≤5 minutes.
A limitation of the present study is the ability of the device to discriminate AT from AF from a single bipolar recording site in the right atrium. Because the algorithm is based only on the median cycle length and cycle length regularity, it is likely that there were some episodes of AF that were classified as AT and some episodes of AT that were classified as AF. Furthermore, spontaneous or pacing-induced rhythm transitions after the initial therapy may have resulted in the delivery of both AT and AF therapies during a single arrhythmia episode.16–18
It is important to note that the AT/AF episodes that were pacing failures lasted for several hours before termination. In contrast, when pacing was successful, the episodes lasted only a few minutes. Prompt detection and termination of AT/AF episodes may reduce the degree of electrophysiological remodeling,19 resulting in longer periods of sinus rhythm between episodes. In addition, early episode termination may reduce symptoms, improve hemodynamic performance, and reduce the risk of stroke. Because the results presented here were from a retrospective analysis, it was not possible to determine if the pacing therapies altered morbidity, mortality, or quality of life. Additional studies will be required to demonstrate the clinical utility of these atrial pacing therapies in ICD patients with atrial tachyarrhythmias.
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