Effects of Different Atrial Pacing Modes on Atrial Electrophysiology
Implicating the Mechanism of Biatrial Pacing in Prevention of Atrial Fibrillation
Background Multiple-site atrial pacing has been shown to prevent recurrence of atrial fibrillation. However, information about the mechanisms of different atrial pacing modes in prevention of atrial fibrillation was not clear.
Methods and Results Forty-two patients without structural heart disease were classified into group 1 and group 2 according to absence or presence of clinical atrial fibrillation, respectively. Atrial conduction time and electrogram width of the right posterior interatrial septum (RPS) were measured during drive-train stimulation (S1) and early extrastimulation (S2). The locations of S1 were the high right atrium (HRA), distal coronary sinus (DCS), or both sites simultaneously. Effective refractory periods (ERPs) of the HRA and DCS were also determined during S1 stimulation at each site and during biatrial pacing. The ERPs were not different between single-site atrial pacing and biatrial pacing. In contrast, early S2 stimulation at the HRA caused greater atrial conduction delay and greater increment of electrogram width of the RPS in patients with a history of atrial fibrillation. Biatrial pacing significantly reduced the conduction delay and electrogram width of the RPS caused by HRA extrastimulation. In addition, in 17 group 2 patients, atrial fibrillation was induced by an early HRA S2 coupled to HRA pacing. However, with the same coupling interval of S2 at HRA, only 6 of them had the arrhythmia induced during biatrial pacing. Furthermore, conduction delay and increase of electrogram width caused by early S2 at the HRA were reduced by biatrial pacing only in patients whose arrhythmia induction was successfully prevented by biatrial pacing.
Conclusions Biatrial pacing reduced both the atrial conduction delay and increase of electrogram width at the RPS caused by early S2 at HRA, and these effects could prevent induction of atrial fibrillation.
Atrial fibrillation is a common cardiac arrhythmia. It impairs synchronized atrioventricular contraction and increases the risk of systemic thromboembolism, which causes significant cardiovascular morbidity and mortality.1,2 Maintenance of sinus rhythm can restore atrial contraction, improve hemodynamic performance of the heart, and reduce the risk of systemic embolism. Class IA, IC, or III antiarrhythmic drugs were used to convert atrial fibrillation and maintain sinus rhythm, but up to 50% of patients experienced recurrence in the long-term treatment.3 In addition, the proarrhythmic effects of these agents limited their widespread use, especially in patients with poor ventricular function.4-7 Nonpharmacological therapies such as maze operation, catheter ablation, atrial pacing, and defibrillation were investigated as alternative treatments.8-12 Atrial pacing has been shown to be associated with a lower incidence of atrial fibrillation in patients with sick sinus syndrome.11-15 Recently, chronic atrial pacing has been shown to prevent recurrence of atrial fibrillation, and multiple-site atrial pacing offered more benefits than single-site atrial pacing.11,12 Site-dependent atrial conduction delay was suggested to play a crucial role in the induction of atrial fibrillation; furthermore, inhomogeneous conduction and dispersion of refractoriness were implicated as two major substrates for sustenance of atrial fibrillation.16-18 However, information about the electrophysiological characteristics during multiple-site atrial pacing in patients with and without atrial fibrillation and the mechanism of different atrial pacing modes in prevention of atrial fibrillation were not clear. This study was conducted to evaluate the effects of different atrial pacing modes on atrial electrophysiology and their possible mechanisms in prevention of atrial fibrillation.
This study population consisted of 26 men and 16 women with a mean age of 54±14 years (range, 25 to 72 years). All patients were free of structural heart disease assessed with echocardiography, coronary angiography, and contrast ventriculography. They were divided into two groups according to absence or presence of clinically documented atrial fibrillation. Group 1 included 17 patients, 9 men and 8 women, with a mean age of 49±14 years, with clinically documented supraventricular tachycardia (9 with manifest Wolff-Parkinson-White syndrome and 8 with a concealed accessory pathway located in the free wall), and none of these patients had a history of atrial fibrillation or flutter. Group 2 included 25 patients with clinically documented paroxysmal atrial fibrillation (3 with manifest Wolff-Parkinson-White syndrome, 8 with a concealed accessory pathway, and 14 with paroxysmal atrial fibrillation). There was no significant difference in age between the two groups (49±14 versus 54±14 years, P>.05).
Atrial ERP and Conduction Time Determination at Different Atrial Pacing Modes
The study protocol was approved by the Committee on Human Subject Research at this institution. As described previously, all patients were studied in the postabsorptive, nonsedated state after giving a written, informed consent, and all antiarrhythmic drugs were discontinued for >5 half-lives.19-21 Three quadripolar electrode catheters (2–5-2 configuration, Mansfield Scientific Corp) were introduced from the right and left femoral veins and positioned in the HRA, the His bundle area, and the RPS near the coronary sinus ostium. The location of the CS ostium was demarcated as in a previous report.22 A steerable decapolar 7F catheter (Daig Corp) was inserted via the right internal jugular vein into the CS as distal as possible. The five pairs of electrodes had 2-mm interelectrode spacing within each pair and 5-mm spacing between each pair (2-5-2-5-2-5-2-5-2 configuration).
Bipolar stimulation with a pulse width of 2 ms and output of twice diastolic threshold was performed at the distal electrode pairs of the HRA and CS catheter. Surface ECG leads I, II, and V1 and eight intracardiac electrograms (one each from the HRA, His bundle area, and RPS and five from the CS) were displayed on an oscilloscope and recorded at a paper speed of 200 mm/s, as needed (PPG, MIDAS 2500). Intracardiac electrograms were filtered from 30 to 500 Hz.
ERPs of the HRA were determined with a drive cycle length of 600 ms delivered at the HRA alone and at both the HRA and DCS simultaneously. Similarly, ERPs of the DCS were determined with a drive cycle length of 600 ms delivered at the DCS alone and at both the DCS and HRA simultaneously. Each ERP determination was performed after continuous atrial pacing at a 600-ms cycle length for 2 minutes. An extrastimulus (S2) was initially delivered at a coupling interval less than the atrial refractory period, and it was incremented by 2 ms every fourth beat until atrial capture. The atrial ERP was defined as the longest S1-S2 interval that consistently failed to evoke an atrial depolarization.
Conduction times from HRA to RPS, HRA to His bundle area, and HRA to DCS were measured at baseline drive-train stimulation (S1), the earliest premature capture beat during S1 pacing at the HRA alone. Conduction times from the HRA to the other atrial sites were also measured at the earliest premature capture beat during S1 pacing at both the HRA and DCS simultaneously. Similarly, conduction times from DCS to RPS, DCS to His bundle area, and DCS to HRA were measured at baseline drive-train stimulation, the earliest premature capture beat during S1 pacing at the CS alone. Conduction times from DCS to the other atrial sites were also measured at the earliest premature capture beat during S1 pacing at both the HRA and DCS simultaneously
The induction of atrial fibrillation by early premature extrastimulation (up to 10 ms above the ERP) was repeated twice during HRA or biatrial pacing. To avoid the interference of atrial fibrillation with subsequent conduction time and ERP determination, the sequence of stimulation was from the DCS, biatria, and HRA. If atrial fibrillation was induced by extrastimulation, it was allowed to convert to sinus rhythm spontaneously. The ERP and conduction time determinations were restarted at least 15 minutes after an atrial fibrillation episode.
Conduction Characteristics of the Posterior Interatrial Septum
The electrogram of the width of the RPS was used to reflect the local anisotropic factor that underlie the pattern of conduction change.16 The electrogram width of the RPS (recorded from the distal pair of RPS electrodes) was measured from the beginning of the first deflection from the isoelectric line to the end of the last deflection from the isoelectric line.
All data are presented as mean±SD. The differences between groups were analyzed with two-factor ANOVA with Duncan’s multiple-range test for multiple comparisons. Student’s t test was used to compare all paired data in the same group. A value of P<.05 was considered statistically significant.
ERP and Conduction Time at Drive-train Stimulation
The diastolic threshold of the DCS was higher than that of HRA (0.69±0.18 versus 0.59±0.21 mA, P=.04). Also, the ERP of the HRA was significantly shorter than the ERP of the DCS (207±27 versus 241±22 ms, P<.001). The ERPs at each site were similar during single-site or biatrial drive (HRA: 207±27 versus 206±28 ms, P>.05; DCS: 241±22 versus 241±23 ms, P>.05). The intra-atrial and interatrial conduction times during HRA and DCS pacing with a cycle length of 600 ms were summarized in the Table⇓. To eliminate the influence of local latency at the stimulation site, all the measured conduction time was normalized with latency at the stimulation site. Comparing these data revealed that conduction time from the HRA pacing site to the RPS was significantly longer than that from the DCS pacing site to the RPS (Table⇓). However, conduction time from the HRA to the DCS was similar to that from the DCS to the HRA, and conduction time from the HRA to the His bundle area was similar to that from the DCS to the His bundle area. Furthermore, comparison between group 1 and group 2 showed that group 2 patients had a longer conduction time from the HRA or DCS to other atrial sites.
Effect of Early Extrastimulation on the Atrial Conduction Time
In both group 1 and group 2 patients, we compared the conduction delay (difference of conduction time between baseline drive and extrastimulation) induced by early extrastimuli from the HRA and DCS. Atrial premature stimulation at the HRA caused greater conduction delay to the His bundle area, RPS, and DCS than atrial premature stimulation at DCS (Fig 1⇓). Furthermore, intergroup analysis showed that the conduction delay caused by early premature atrial stimulation at the HRA was significantly greater in the group 2 patients, whereas that caused by early premature atrial stimulation at the DCS was similar between group 1 and group 2 (Fig 1⇓).
Effects of Biatrial Pacing on Conduction Time
When the HRA and DCS were driven simultaneously, the conduction delay caused by premature atrial stimulation at the HRA was significantly reduced, whereas the conduction delay caused by premature atrial stimulation at the DCS did not significantly change in either group 1 or group 2 patients (Fig 1⇑). We further analyzed the coupling interval from the RPS atrial electrogram (of the last S1 pacing beat) to the HRA extrastimulus; the coupling interval during biatrial pacing was significantly longer than that during HRA pacing alone (160±33 versus 127±34 ms, P<.001).
Then, we analyzed the induction of atrial fibrillation in group 2 patients. Atrial fibrillation could be induced with one extrastimulation in 18 patients; 17 patients were induced with extrastimulation from the HRA and 1 patient with extrastimulation from the DCS. The duration of atrial fibrillation ranged from 56 seconds to 12 minutes in the 16 patients whose atrial fibrillation converted to sinus rhythm spontaneously. In 2 patients, atrial fibrillation was sustained for >15 minutes; these patients were converted to sinus rhythm with DC shock. Among the 18 patients with inducible atrial fibrillation, 12 (group 2A) had atrial fibrillation induced with extrastimulation at HRA when the drive-train stimulation was applied at the HRA alone, but it became noninducible when the HRA and DCS were driven simultaneously; in the other 6 patients (group 2B), atrial fibrillation was induced when S1 drive-train was either from the HRA alone or from the HRA and DCS simultaneously. The resting sinus rate and atrial ERP were not different between groups 2A and 2B (759±175 versus 747±124 ms, P>.05; 198±33 versus 192±16 ms, P>.05). Comparing the change of electrophysiological characteristics during biatrial pacing in groups 2A and 2B, we found that group 2A had less conduction delay caused by early premature HRA stimulation than group 2B during biatrial pacing (Fig 2⇓).
Effects of Biatrial Pacing on the Conduction at the Posterior Interatrial Septum
During drive-train stimulation at the HRA, the electrogram width of the RPS area was similar between group 1 and group 2 (Fig 3⇓). In group 1 patients, the electrogram width of the RPS was similar between early HRA and early DCS extrastimuli (47±13 versus 44±13 ms, P>.05). However, the electrogram width of the RPS during early HRA extrastimulation was significantly longer than that during early DCS extrastimulation (47±14 versus 40±10 ms, P=.02) in group 2 patients. Thus, early premature HRA extrastimulation caused a greater increment of electrogram width than did early premature DCS extrastimulation in the group 2 but not group 1 patients (Fig 3⇓).
In group 2A, increase of the electrogram width by the early HRA extrastimulation was significantly reduced when the HRA and DCS were simultaneously stimulated as drive-train (Fig 4⇓). However, this result was not found in group 2B (Fig 4⇓).
Pacing from the HRA led to greater atrial conduction delay than did that from the DCS. This conduction delay was more pronounced in patients with paroxysmal atrial fibrillation than those without this arrhythmia. Furthermore, early premature depolarization at the HRA caused greater atrial conduction delay and increased the electrogram width of the RPS in patients with atrial fibrillation. This phenomenon might be associated with the high possibility of inducing atrial fibrillation at the HRA. Conversely, biatrial pacing was associated with a lower probability of inducing atrial fibrillation than single-site atrial pacing; it did not change the ERP of atrial tissue. Analysis of the changes of electrophysiological characteristics caused by biatrial pacing showed that successful prevention of atrial fibrillation was associated with less atrial conduction delay and less increase of electrogram width of the RPS caused by early premature HRA extrastimulation.
Conduction Delay and Initiation of Atrial Fibrillation or Flutter
Earlier works observed that the onset of spontaneous atrial fibrillation was preceded by early premature atrial depolarization and was usually induced with atrial premature stimulation delivered at the atrial vulnerable period in the electrophysiology laboratory.23,24 In this study, we demonstrated that patients with a clinical history of atrial fibrillation had more atrial conduction delay than those without atrial fibrillation at baseline drive-train stimulation. An early extrastimulation at either the HRA or DCS resulted in further conduction delay because the stimulation was applied at the relative refractory period of atrial tissue. Furthermore, conduction delay caused by HRA extrastimulation was more pronounced than that by CS extrastimulation in patients with or without atrial fibrillation. With respect to the location of extrastimulation, it has been shown that extrastimulation delivered at the HRA was more likely to induce atrial fibrillation than extrastimulation at the CS.16,25,26 In the present study, atrial conduction delay caused by HRA extrastimulation was exaggerated, and the possible anisotropic factor of the RPS (presented as electrogram width of the RPS) was significantly increased by early premature extrastimulation at the HRA but not at the DCS in patients with a history of atrial fibrillation. These findings suggest that atrial conduction delay and the possible anisotropic factor of the RPS, if critical, might serve as a milieu for reentry and initiation of atrial fibrillation.
Effects of Biatrial Pacing
Interatrial conduction block with retrograde activation of the left atrium was reported to be associated with a high incidence of atrial tachyarrhythmia.27 Daubert et al28 demonstrated that biatrial pacing prevented atrial arrhythmia in patients with advanced interatrial block. Saksena et al11 and Prakash et al12 also demonstrated that multiple-site atrial pacing was more effective in prevention of recurrence of refractory atrial fibrillation than single-site pacing. Previous studies have demonstrated that dispersion of refractoriness and anisotropic conduction were two essential elements for sustaining of atrial arrhythmia.17,18 Biatrial pacing might change the dispersion of refractoriness or anisotropic conduction; thus, it could prevent recurrence of atrial fibrillation. In the present study, we demonstrated that biatrial pacing did not change the ERP; however, biatrial pacing reduced the conduction delay and electrogram width of the RPS caused by early premature depolarization. Prakash and colleagues29 also reported that conduction delay of the early HRA premature beat was less pronounced during dual-site atrial pacing. Furthermore, biatrial pacing provided early activation of the RPS area, which might give this area a longer interval for recovery before the impulse of HRA extrastimulus arrived. This suggestion was supported by our data; the coupling interval from RPS atrial electrogram (the last S1 pacing beat) to HRA extrastimulation was longer during biatrial pacing than that of single HRA pacing. Lehmann et al30 demonstrated that anterograde atrioventricular nodal conduction was enhanced by simultaneous pacing of the atrium and ventricle, possibly from the collision effect. This might provide another explanation why the conduction of the early HRA depolarization was improved during biatrial pacing. Although Wood et al31 showed that dispersion of atrial repolarization could be minimized by left atrial pacing only or by biatrial pacing in the isolated rabbit heart, the difference between repolarization and ERP and the difference between human and in vitro animal studies required more verification.
This study demonstrated that only 6 of the 17 patients with atrial fibrillation induced by early HRA extrastimulation still had atrial fibrillation induced by the same HRA extrastimulation when drive-train stimulations were from the HRA and DCS simultaneously. Furthermore, the conduction delay caused by early HRA extrastimulation could not be reduced by biatrial pacing in the 6 patients whose atrial fibrillation could not be prevented by biatrial pacing. These findings suggested that biatrial pacing prevents the initiation of atrial fibrillation by reducing the conduction delay and increase of electrogram width of the RPS caused by early premature atrial extrastimulation.
First, the patients in group 1 served as normal control subjects, but all of them had an accessory AV pathway. This might produce some bias. However, they all had structurally normal hearts and no clinically documented atrial fibrillation. Second, we could not rule out the effect of biatrial pacing on dispersion of refractoriness. However, it was unlikely to have marked change of dispersion of refractoriness during biatrial pacing, because the ERP of the HRA and DCS was not changed during biatrial pacing. Third, although we did not randomize the mode of atrial pacing, we induced atrial fibrillation repeatedly, thus decreasing the bias. Fourth, we used the local electrogram width of the RPS to reflect the local conduction delay. Direct measurement of conduction velocity at the RPS may provide more solid data. However, it is limited by the complex anatomy of the RPS. Finally, whether the result of short-duration pacing could be extrapolated to long-term prevention needs further investigation.
Patients with a history of atrial fibrillation had exaggeration of atrial conduction delay and increasing electrogram width of the RPS by early HRA extrastimulation. Most of the patients with atrial fibrillation had the arrhythmia induced with extrastimulation at the HRA. By reduction of the atrial conduction delay and electrogram width of the RPS caused by HRA extrastimulation, biatrial pacing made atrial fibrillation less inducible.
Selected Abbreviations and Acronyms
|DCS||=||distal coronary sinus|
|ERP||=||effective refractory period|
|HRA||=||high right atrium|
|RPS||=||right posterior interatrial septum|
This work was supported in part by grants from the National Science Council (NSC-86-2314-B-010-030, 86-2314-B075-034, and 86-2314-B-075-098) and Tzou’s Foundation (VGHYM-S4-30 and VGHYM-S4-31), Taipei, Taiwan.
- Received April 24, 1997.
- Revision received July 24, 1997.
- Accepted August 13, 1997.
- Copyright © 1997 by American Heart Association
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