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Pacing site‐ and rate‐dependent shortening of retrograde conduction time over the slow pathway after atrial entrainment of fast‐slow atrioventricular nodal reentrant tachycardia

Abstract Introduction We tested our hypothesis that atrial entrainment pacing (EP) of a) the common‐type (com‐) fast‐slow (F/S‐) atypical atrioventricular nodal reentrant tachycardia (AVNRT) using a typical slow pathway (SP), or b) the superior‐type (sup‐) F/S‐AVNRT using a superior SP, both modify the retrograde conduction time across the SP immediately after termination of EP (retro‐SP‐time). Methods We measured the difference in the His‐atrial interval (HA difference) immediately after cessation of EP, performed at 2 ± 2 rates from the high right atrium (HA[1]‐HRA) versus from the proximal coronary sinus (HA[1]‐CS) in 17 patients with com‐F/S‐AVNRT and 11 patients with sup‐F/S‐AVNRT. We also measured the atrial‐His and HA intervals of the first and second cycles immediately after cessation of EP and during stable tachycardia. Results Unequal responses, defined as a ≥ 20‐ms HA difference at ≥1 EP rates, were observed in 16 patients (57%), including 7 with com‐ and 9 with sup‐F/S‐AVNRT. Irrespective of the EP rate, all unequal responses of com‐F/S‐AVNRT were due to a shorter HA[1]‐CS than HA[1]‐HRA, with a mean 34 ± 11 ms HA difference, whereas all unequal responses of sup‐F/S‐AVNRT were due to a longer HA[1]‐CS than HA[1]‐HRA, with a mean 49 ± 25 ms HA difference. The unequal responses resolved within two cycles after the cessation of EP. Conclusions We have identified a little‐known pacing site‐ and pacing rate‐dependent shortening of the retro‐SP‐time.


| INTRODUCTION
The electrophysiological response of reentrant tachycardia after cessation of entrainment pacing (EP) is an important clue to clarify the mechanisms of tachycardia as well as the conductive properties and anatomical location of the reentry circuit. This implies the entrainment rule by which the site of entrainment has no effect on the orthodromic conduction time across the reentry circuit immediately after cessation of pacing. This rule has been amply verified in macroreentrant arrhythmias, such as atrial flutter or ventricular tachycardia associated with structural heart disease, 1,2 in which case the conduction time across the circuit is technically measurable. It has not, however, been unequivocally verified in atypical atrioventricular (AV) nodal reentrant tachycardia (NRT). We have recently observed a unique electrophysiological response upon atrial induction of fast-slow (F/S-) AVNRT, characterized by a shortening of the retrograde conduction time across the slow pathway (SP), which represents a large fraction of the orthodromic conduction time. 3 Therefore, we tested our hypothesis that atrial EP of a) the common-type (com-) F/S-AVNRT using a typical SP, or b) the superior-type (sup-) F/S-AVNRT using a superior SP, 4 both modify the retrograde conduction time immediately after termination of EP (retro-SP-time).

| Study sample, electrophysiological study, and catheter ablation
We prospectively identified 17 patients with com-F/S-and 11 with sup-F/S-AVNRT, who underwent electrophysiological studies and successful EP at ≥1 pacing rates from the high right atrium (HRA) and the proximal coronary sinus (prox-CS), as described later, followed by the successful ablation of an SP. This study, which complied with the guidelines of the Declaration of Helsinki, was approved by the Institutional Review Board of Gunma University Hospital, and all patients were granted their written informed consent to participate.
Electrophysiologic study and catheter ablation were performed as described in detail in previous reports. 4,5 We excluded the diagnosis of AVNRT, AV reentrant tachycardia, and atrial tachycardia, using standard criteria (Table 1). 4,5 2.2 | Study protocol of entrainment pacing and measurement of retro-SP-time EP from the HRA (EP-HRA) and from the prox-CS (EP-CS) was performed during episodes of tachycardia, keeping the cycle lengths (CL) stable and in rapid sequence to blunt the effects of variations in autonomic activity on AV nodal conduction. The CL of all episodes of tachycardia were stable before the initiation of EP. The first stimulus of EP was synchronized to the atrial electrogram during tachycardia, at an interval 10-ms shorter than the tachycardia CL (TCL). The first EP was attempted at an S-S interval 10-30 ms shorter than the TCL; if successful, the next attempts were performed at a gradually shorter S-S interval in decrements of 10 ms, until failure of EP. EP was successful when (1) all atrial and subsequent His bundle electrograms were captured 1:1 via the fast pathway, while keeping the atrio-His (AH) interval constant during EP-HRA and EP-CS at a fixed S-S interval, for up to 10 consecutive paced cycles, and (2) F/S-AVNRT was re-induced and persisted after the cessation of EP. When EP was unsuccessful at baseline, because of termination of the tachycardia during or after pacing, another attempt was made during infusion of isoproterenol. When a > 20-ms difference in stable TCL immediately following EP was observed between EP-HRA and EP-CS, suggesting changes in AV nodal conduction between both EP, the recordings were not retained for the analysis. Values are numbers (%) of observations. *VA dissociation during the initial phase (QRS transition zone) of tachycardia overdrive ventricular pacing. 9,10 unequal responses, we measured the AH and HA intervals of the first and second cycles after cessation of each EP, and during the tachycardia immediately after its CL had stabilized.

| Statistical analysis
Continuous variables are expressed as means ± standard deviation (SD), and categorical variables as counts and percentages.
Differences between two continuous variables were examined by paired or unpaired t-test, while categorical variables were compared using Fisher's exact test. A p-value <.05 was considered statistically significant.

| RESULTS
Between 1 and 8 rates per patient (mean = 2 ± 2) of the EP protocol were successfully delivered among all patients studied ( Table 2). Paired measurements made immediately before delivery of EP revealed a <10-ms difference in the TCL, suggesting that the autonomic nervous tone was not significantly changed by EP, irrespective of the pacing site.
Equal responses at ≥1 rates of EP were observed in 19 patients In both types of AVNRT, the atrial activation sequence during tachycardia remained unchanged after EP, and no relationship between rate of EP and equal or unequal response was observed.

| DISCUSSION
In a high proportion of com-and sup-F/S-AVNRT, a change in the HA interval (unequal response) was observed immediately after EP-HRA and after EP-CS, depending on the rate of EP. Furthermore, the pacing site associated with a shorter HA interval was also related to the type of F/S-AVNRT, that is, the prox-CS site was associated with com-F/S-AVNRT and the HRA site with sup-F/S-AVNRT. Unequal response was limited to the first cycle after cessation of EP.  14 or a re-induction of the tachycardia after its termination by EP. However, these mechanisms hardly explain the existence of pacing site-specific differences in HA intervals at certain EP rates, without change in the atrial activation sequence, and limited to the first cycle after cessation of EP. A disturbance in the tachycardia CL after EP may have occurred, due to the decremental conduction properties of the AV node. 15  We hypothesized that the mechanism of the unequal response is based on the pacing site-dependent effect on the retro-SP-time, limited to the first cycle after cessation of EP. We presumed initially that, in presence of anterograde conduction in the SP during EP, the antidromic wavefront penetrates the SP and collides with the orthodromic wavefront inside the pathway ( Figure 5). Conduction of the orthodromic wavefront within the SP may be decrementally delayed due to an EP rate faster than that of the tachycardia, while the last antidromic wavefront inside the SP may facilitate conduction of the next orthodromic wavefront inside the SP, depending on its frequency-dependent decremental conduction property ( Figure 5).

T A B L E 2 Patients and procedural characteristics
The net balance of these two effects would, therefore, determine the length of the HA interval of the first cycle after cessation of EP.
Moreover, the depth of antidromic penetration of the SP varies, depending on the site of pacing relative to the AV nodal pathways, increasing during EP-CS versus during EP-HRA in com-F/S-AVNRT (left panels in Figure 5A) and during EP-HRA versus during EP-CS in sup-F/S-AVNRT (left panels in Figure 5B). On the other hand, the amount of decremental delay of the orthodromic wavefront inside the SP in response to EP may depend on the decremental properties of the pathway, or the depth of its orthodromic penetration, or both. Finally, the presence of an upper common pathway just above the AV nodal reentry circuit can be excluded in some AVNRT associated with an unequal response elicited by pacing from two different sites. The existence of an upper common pathway remains controversial. 29 However, if it were present, this site selectivity would not be observed. Thus, the upper limb of these reentrant circuits must consist of atrial tissue surrounding the AV node. 24

| CONCLUSIONS
We have identified a little-known pacing site-and pacing ratedependent shortening of the retrograde conduction time over the SP immediately after EP.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author, [Y.K.], upon reasonable request.