Europace Advance Access originally published online on March 29, 2007
Europace 2007 9(5):289-293; doi:10.1093/europace/eum006
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ATRIAL TACHYARRHYTHMIA
On the role of ventricular conduction time in rate stabilization for atrial fibrillation
Micro Systems Engineering, Inc., 6024 SW Jean Road, Lake Oswego, OR 97035, USA
Manuscript submitted 12 September 2006. Accepted after revision 17 December 2006.
* Corresponding author. Tel: +503 635 4016; fax: +503 635 9610. E-mail address: jie.lian{at}biotronik.com
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Abstract |
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Aim: Ventricular pacing (VP) could stabilize the ventricular rhythm in atrial fibrillation (AF). This study investigates the role of ventricular conduction time (VCT) in rate stabilization for AF.
Methods and results: A novel computer model was used to generate various patterns of RR intervals in AF. For each model configuration, the rate stabilization effect of VP was compared with respect to different VCTs. In all tested cases, the ventricular rate in AF could be stabilized at pacing intervals longer than the shortest spontaneous RR intervals. For each model configuration, slightly longer pacing interval (difference <100 ms) was needed to achieve 95% VP when the antegrade/retrograde VCT was increased from 10/10 to 110/110 ms, whereas the VCT had less effect at lower pacing rate. Although longer VCT was associated with increased percentage of ventricular fusion, its role was diminished at higher pacing rate when more retrograde waves could conduct to the atrium.
Conclusion: Ventricular conduction time has limited effects on rate stabilization, which could be explained by multi-level interactions between antegrade waves induced by AF and retrograde waves induced by VP.
Key Words: Rate stabilization, Atrial fibrillation, Ventricular pacing, Ventricular conduction time
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Introduction |
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Atrial fibrillation (AF) remains the most common tachyarrhythmia that causes significant morbidity and mortality.1
It has been recognized that the irregular ventricular rhythm in AF has adverse haemodynamic effects independent of the fast ventricular rate.2–4
It is known that ventricular pacing (VP) at cycle length close to the mean spontaneous RR intervals not only can eliminate long ventricular pauses but also can suppress short conducted ventricular cycles.5 Recent studies have further demonstrated that some specially designed VP protocols could regularize the ventricular rhythm in AF without significantly altering the mean ventricular rate.6–12 However, the underlying mechanism of ventricular rate stabilization remains controversial.13–17
According to the decremental conduction theory, Watanabe and Watanabe ascribed the suppression of shorter RR intervals by VP to His–Purkinje conduction delays.13 On the other hand, Wittkampf et al. explained the rate stabilization by a postulated atrioventricular (AV) nodal pacemaker model, in which the VP-induced retrograde waves either collide with the AF-induced antegrade waves in the ventricle, or invade the AV node and reset the nodal pacemaker.14,15 Recently, these two hypotheses were directly tested in a clinical study designed to compare the rate stabilization effects between His bundle pacing and right ventricle apex pacing. Contrary to both the hypotheses, no measurable difference of regularization was found between the two pacing sites, suggesting ventricular conduction delays do not account for the rate stabilization.18 However, one of the major limitations of their experiment was the limited and fixed pacing rates (60, 80, 100, and 120 ppm), which might potentially mask different rate stabilization effects when the difference in pacing intervals was <100 ms. Moreover, the novel findings of the study were overshadowed by the lack of mechanistic explanations.
More recently, a novel AF-VP model was developed to elucidate the effects of VP on the ventricular rhythm during AF.19 We have demonstrated that this model could account for most known experimental observations, including the various patterns of RR interval distribution in AF, the biphasic relationship between atrial and ventricular rates in AF, and the intrinsic RR cycle length-dependent rate stabilization effects of the VP.19 We have further validated this model through simulated atrial pacing protocols, by reproducing some major experimental results obtained in isolated rat hearts.20
In this study, we use this new computer model to examine further the role of VCT in rate stabilization for AF, and provide insights on the mechanism of ventricular rate regularization through VP.
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Methods |
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AF-VP model
As illustrated in Figure 1, the AF-VP model consists of four inter-connected components: AF generator, AV junction (AVJ), ventricle, and electrode (see for details19).
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The AF generator produces random AF impulses that bombard the AVJ. The arrival of the AF impulses is modelled as a truncated Poisson process that has a mean arrival rate
. On the other hand, the retrograde conducted wave escaping the AVJ either collides with an incoming AF impulse or causes the AF generator to reset its timing cycle.
The AVJ is modelled as an integrated structure with defined electrical properties. During phase-IV, the AVJ membrane potential (Vm) linearly increases from the resting potential (VR) towards a depolarization threshold (VT) at a rate dV/dt. The AF bombardment causes step increase of Vm by a discrete amount 
V, whereas the retrograde invasion by VP brings Vm to VT directly. The AVJ fires when its Vm reaches VT, generating an activation wave, which starts an antegrade or retrograde AV delay (AVD) according to the direction of activation. If the AVJ is retrogradely activated while an antegrade wave has not finished its AVD or vice versa, a collision occurs within the AVJ, annihilating the activation waves in both directions. The activation of the AVJ also starts a refractory period when the AVJ is non-responsive to stimulation by both AF and VP impulses. Moreover, both the conduction time and the refractory period of the AVJ depend on its recovery time.
After an antegrade AVD, an activation wave is generated in the ventricle that starts an antegrade conduction delay. The delivery of VP also generates an activation wave in the ventricle with a retrograde conduction delay, after which period the retrograde wave reaches the AVJ. When both antegrade and retrograde waves are present in the ventricle, a ventricular fusion causes the extinction of both waves.
The electrode is implanted in the ventricle, and is connected to a pacing device operating in demand mode VVI. If an activation wave propagates to the electrode after an antegrade conduction delay, a ventricular sense (VS) occurs that inhibits the scheduled VP, whereas the timeout of the pacing cycle length (PCL) triggers VP.
Simulation protocols
Table 1 lists five model configurations that were used to generate various patterns of spontaneous RR intervals in AF by programming the range of the AV conduction time (AVD), the AF arrival rate (), the AF impulse strength (V), and the phase-IV depolarization rate of the AVJ (dV/dt). In all simulations, we set VT–VR=50 mV, and set the range of the AVJ refractory period to 50–300 ms.
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In addition, Table 2 lists five pairs of antegrade/retrograde ventricular conduction time (VCT) that were evaluated for each model configuration. The VCT 10/10, 60/60, and 110/110 ms represent fast, moderate, and slow symmetrical ventricular conduction, respectively, while VCT 10/100 and 50/100 ms represent two different types of asymmetrical ventricular conduction.
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For each model configuration and each pair of VCT, the rate stabilization effect of VP was assessed by varying the PCL from sufficiently long that led to 100% VS, down to sufficiently short that resulted in 95% VP (PCL95), with a step size of 10 ms.
For each model configuration, each pair of VCT, and each PCL setting, 10 runs of 500-RR intervals were generated. The minimum, maximum, mean, and SD of spontaneous 500-RR intervals (minRR, maxRR, mRR, and sdRR, respectively) were calculated and then averaged over the 10 runs. The PCL95 was determined for each train of RR intervals. In addition, the percentage of VP (VP%) in 500-RR intervals was separated into three sub-percentiles (Vtr%, Avj%, and Atr%), on the basis of level reached by the retrograde waves: ventricle, AVJ, and atrium, and then respectively averaged over the 10 runs. Paired t-test was used for statistical analysis, and P = 0.05 was chosen for the level of significance.
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Results |
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Tables 3–7 respectively summarize the statistical results corresponding to the five model configurations listed in Table 1. Each table shows the minRR, maxRR, mRR, and sdRR of the intrinsic RR intervals with respect to five different VCT pairs defined in Table 2. In addition, each table shows the PCL95, as well as the three sub-percentiles (Vtr%, Avj%, and Atr%) at 95% VP for each of the VCT pairs.
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There are three findings that are common among the five model configurations.
First, the statistical properties of the spontaneous RR intervals (minRR, maxRR, mRR, and sdRR) are independent of the VCT pairs. In other words, the intrinsic ventricular rhythm in AF is determined at the supraventricular level (AF generator and AVJ properties), but not affected by the VCT.
Second, increasing VCT is associated with corresponding increase of PCL95. The degree of increase in PCL95 is dependent on the AF model configuration. But in all tested cases, the increase in PCL95 is limited to <100 ms when increasing VCT from 10/10 to 110/110 ms. A graded increase of PCL95 is also evident when increasing VCT from 10/10 to 10/100 ms and further up to 50/100 ms. Note that the PCL95 for VCT 50/100 ms lies between those for 60/60 and 110/110 ms.
Third, increasing VCT from 10/10 to 60/60 ms, and from 60/60 ms to 110/110, result in significant decrease in Atr% and increase in Vtr% at PCL95 (all P < 0.005). Similar trend is also observed when increasing VCT from 10/10 to 10/100 ms and further up to 50/100 ms. Thus, the level that the retrograde waves can reach shifts downward (from atrium to AVJ and ventricle) as the VCT increases. Note that the sub-percentiles for VCT 50/100 ms are between those for 60/60 and 110/110 ms.
Compared with the base configuration (Table 3), lengthening the AVD (Table 4) results in increase in minRR (P < 0.001), but non-significant change of other statistical properties of the intrinsic RR intervals. For all VCT pairs, longer AVD is associated with longer PCL95, as well as the increase in Avj% and the decrease in Vtr% and Atr% (i.e., more collisions occur in the AVJ).
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On the other hand, higher spontaneous AVJ activity (Table 5), stronger AF impulse (Table 6), and higher-rate AF (Table 7) all lead to faster ventricular response (decrease in minRR, maxRR, mRR, and sdRR). Meanwhile, the PCL95 is reduced, and the level of retrograde conduction shifts downward (i.e., decrease Atr%, increase Vtr% and Avj%).
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Figure 2 shows the VP% as a function of PCL (vary from 30 ms shorter to 310 ms longer than PCL95), with respect to VCT 10/10 and 110/110 ms for the base configuration (similar results were obtained for other model configurations). As expected, for both VCT pairs, shorter PCL results in more VP, whereas longer PCL leads to more VS. To achieve a certain level of VP%, shorter PCL (including PCL95) is needed for VCT 10/10 compared with VCT 110/110 ms. The separation of the two curves is wider (but limited to <100 ms) at higher VP%, but the difference in PCL gets smaller in order to achieve lower VP%.
The two curves in Figure 2 are redrawn in stacked bar graphs in Figure 3(A) and (B), respectively, by separating VP% into three sub-percentiles according to the level reached by the retrograde waves: ventricle, AVJ, and atrium. For VCT 10/10 ms, the majority of VP-induced retrograde waves conduct to the atrium, although there is a trend of decreasing Atr%, accompanied by decreasing VP% as PCL increases. On the other hand, for VCT 110/110 ms, there is a marked increase in ventricular fusion, which peaks in moderate, and decreases at both low and high rate VP. Note that the share of Atr% falls substantially compared with VCT 10/10 ms, but remains dominant at very short PCL.
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Discussion |
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Using a recently developed AF-VP model,19
we investigated the role of VCT on rate stabilization for AF.
Our data confirmed that intrinsic ventricular rhythm could be suppressed by VP at cycle length longer than the shortest spontaneous RR intervals.5–12 In general, to achieve 95% ventricular capture, shorter pacing interval (PCL95) is needed for higher intrinsic rate.16,17 For example, the difference between PCL95 and minRR is larger for configuration (II) than the other four configurations. However, such a correlation may be altered by other factors. For example, configuration (II) has longer PCL95 than configuration (I) despite of similar mRR. Further evidence is that longer VCT results in longer PCL95 without change of minRR or mRR for each configuration.
A novel finding of this study is that for any given model configuration (which determines the pattern of RR intervals), a slightly longer PCL95 (difference <100 ms) is needed when the antegrade/retrograde VCT is increased from 10/10 to 110/110 ms (Tables 3–7). To achieve a lower percentage of VP, the difference in required PCL (with respect to different VCT) becomes even smaller. In other words, VCT does play—though limited—a role in rate stabilization in AF. A previous study failed to detect the difference in PCL95 between pacing at the His bundle and right ventricular apex, most likely due to limited steps of pacing rates and thus the resolution of PCL.18 In addition, an ordinary catheter was used for His bundle pacing in that study. Without a screw-in lead, it is difficult to achieve His bundle penetration, and may also partly account for the lack of difference in rate stabilization effect between His and apical pacing.
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This study also provides insights into the mechanisms of rate stabilization in AF through VP. In agreement with,19
we have found multi-level interactions between AF-induced antegrade waves and the VP-induced retrograde waves: the latter may cause ventricular fusion, or be blocked in the AVJ, or penetrate to the atrium. As expected, increasing the VCT results in more ventricular fusion beats (i.e., downward shifting of the level of retrograde conduction). Nonetheless, when the PCL is reduced to achieve a higher percentage of VP, more retrograde waves can conduct to the atrium, and the role of VCT is diminished.
Limitations of the study
This study is limited by the nature of simulation. Although the present AF-VP model can account for most known experimental observations,19,20 direct experimental validation of the model, as well as clinical confirmation of the findings of this study are needed.
Also, the data were based on five model configurations and five VCT pairs, which may not cover all possible scenarios. However, the results are consistent among all tested cases, suggesting the generality of the findings.
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Conclusion |
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Using a novel computer model, we demonstrated that the ventricular rhythm in AF could be stabilized by VP at cycle length longer than the shortest intrinsic RR interval. We found that longer VCT results in a slightly longer pacing interval to achieve 95% VP. The limited effect of VCT on rate stabilization could be attributed to the multi-level interactions between antegrade waves induced by AF and retrograde waves induced by VP.
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References |
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