Combined effects of high atrial septal pacing and reactive atrial antitachycardia pacing for reducing atrial fibrillation in sick sinus syndrome

Abstract Background It is unknown whether atrial fibrillation (AF) burden varies by pacing site in patients with reactive atrial antitachycardia pacing (rATP). We aimed to compare AF burden in patients with high atrial septal pacing (HASp) via delivery catheter and right atrial appendage pacing (RAAp) in patients with sick sinus syndrome (SSS). Methods We retrospectively identified 109 patients with a history of paroxysmal AF and SSS who had received dual‐chamber pacemaker implantation between January 2017 and December 2019, of whom 39 and 70 patients had HASp and RAAp, respectively. rATP was initiated after a 1‐month post‐implantation run‐in period. Results Patients with HASp had a significantly shorter P‐wave duration during atrial pacing than those with RAAp (99.3 ± 10.4 vs. 116.0 ± 14.3 ms, p < .001). During the 3‐year follow‐up period, the incidence of an AF lasting longer than 1 or 7 days was significantly lower (hazard ratio [HR], 0.45; p = .016; HR, 0.24; p = .004) than in those with RAAp. The median time of AF/AT per day in the follow‐up periods was significantly shorter in the HASp group than in the RAAp group (10 vs. 18 min/day, p = .018). Atrial lead division did not occur in the HASp group during the follow‐up period. Conclusions HASp via delivery catheter is as safe as RAAp, and HASp combined with rATP is effective for reducing AF burden in patients with SSS and paroxysmal AF.


| INTRODUC TI ON
Atrial fibrillation (AF) is a common arrhythmia in patients with cardiac implantable electronic devices (CIEDs). Some studies have reported that right atrial appendage pacing (RAAp) exacerbates interatrial conduction delay (IACD), whereas high atrial septal pacing (HASp) may decrease AF incidence and duration. [1][2][3] However, other studies have shown that right atrial septal pacing alone did not suppress AF. 4,5 Previous methods of atrial lead implantation have used tined or screw leads. Lead implantation in patients with high atrial septum (HAS) is difficult using a screw lead alone because there is no pectinate muscle on the atrial septum. Therefore, RAAp remains the first-line choice for atrial pacing sites. 6 Recently, a delivery catheter method became available; HAS lead implantation is easy and accurate using this device. 7 AF is irregular and is not susceptible to pace termination.
However, when AF becomes slower, organized rhythms, including atrial flutter (AFL) or atrial tachycardia (AT), emerge, which can be terminated using antitachycardia pacing (ATP). 8 Reactive atrial antitachycardia pacing (rATP) is a second-generation iteration of atrial ATP and has been reported to suppress chronic AF development in patients with CIEDs and a history of paroxysmal or persistent AF/ AT in a randomized multicenter international trial (MINERVA trial). 9 Given that much of the substrate for atrial arrhythmias is known to be located in the left atrium (LA), HASp may improve rATP efficacy owing to the closer proximity of the pacing site to the reentrant circuit. Therefore, we hypothesized that accurate HASp combined with rATP is effective for reducing AF burden in patients with sick sinus syndrome (SSS) because HASp may reduce AF incidence.
Furthermore, rATP is more effective in patients with HAS than in those with right atrial appendage (RAA).

| Study population
This was a retrospective, single-center, observational study that was Inc.) at Kurashiki Central Hospital were included in this study. rATP, atrial rate stabilization (ARS), and post-mode switch overdrive pacing (PMOP) were started in all patients 1 month following pacemaker implantation. Patients with a history of cardiac surgery, a history of catheter ablation, and persistent AF for more than 7 days at the time of rATP initiation were excluded. As implantation of HASp was first performed in our hospital beginning in January 2019, all patients treated before this date were implanted with RAAp. After January 2019, all patients were implanted with HASp ( Figure 1). Of 125 screened patients, 109 met the inclusion criteria. Of these, 39 and 70 patients were assigned to the HASp and RAAp groups, respectively. Patients underwent follow-up examination in their respective therapy groups at 1 and 6 months after implantation and thereafter every 6 months until the 36th month after implantation.

| Implantation procedure
In patients with HAS, atrial lead position was determined using fluoroscopy; right atrium angiography was performed superior to the foramen ovale. A Medtronic Select Secure 3830 lead and a C315 Delivery Catheter (S4 or S5) were used to perform HASp. With the fluoroscope in the left anterior oblique position, the delivery catheter was rotated toward the interatrial septum. The catheter was withdrawn until the tip was straightened at the roof of the right atrium. The confluence of the atrial septum and the right atrial roof was confirmed in this area by injecting a contrast medium from the catheter. Subsequently, the fluoroscope was switched to the right anterior oblique view, and the catheter was positioned anteriorly. Finally, the lead was advanced through a delivery catheter, screwed toward the left side of the HAS, and lead sensing and pacing tests were performed (Figure 2A). The Medtronic 5076 lead or Medtronic 4574 lead was used to implant RAA leads using standard techniques ( Figure 2B).

| Mechanism of rATP
The rATP algorithm has been previously described in detail. 9

| Data collection and outcomes
We assessed the outcomes of AF/AT and rATP treatment using a remote monitoring system every month as well as through device interrogation every 5-7 months in the outpatient clinic. Clinical data, including age, sex, comorbidities, echocardiographic data, and medications, were assessed from the medical records. Moreover, data regarding atrial lead performance and atrial intervention pacing functions (ARS, PMOP) were collected. The longest P-wave duration in the inferior leads (II, III, and aVF) was measured using a standard surface 12-lead electrocardiogram at the pacemaker implantation day. To verify diagnostic accuracy and rule out far-field R-wave sensing, atrial lead oversensing, pacemaker-mediated arrhythmia, and/or electrical/mechanical interference, AF/AT episodes were confirmed by a clinician. AF/AT burden was derived from pacemaker counters.
The mean percentage of pacing and AF/AT duration/day were calculated in overall observation periods.

| Baseline characteristics
The median follow-up was 36 (range, 12-36) months. Baseline characteristics at the time of pacemaker implantation are shown in

| AF/AT-free survival
The HASp group had a significantly lower incidence of AF/AT lasting was not significantly different between the two groups (HR, 0.36; 95% CI, 0.12-1.1; p = .053) (Figure 3).
Subgroup analyses were conducted to assess the effect of atrial pacing (Ap) on the risk of AF/AT. were not significantly different between the two groups ( Figure S2).
Another subgroup analysis was conducted to assess the effect of  Figure S3).

| AF/AT burden
The median time of AF/AT per day in the follow-up periods was significantly shorter in the HASp group than in the RAAp group (10 vs. 18 min/day, p = .018) ( Table 2).

| DISCUSS ION
AF accounts for approximately 40%-70% of patients with sinus node dysfunction. 12

TA B L E 3 rATP characteristics between the HASp and RAAp groups.
F I G U R E 3 Comparisons of the Kaplan-Meier survival curves of AF-free episodes lasting ≥1 day (A), ≥7 days (B), and ≥ 30 days (C). AF, atrial fibrillation; HASp, high atrial septal pacing; RAAp, right atrial appendage pacing; rATP, reactive atrial antitachycardia pacing.
with RAAp. 2,13 In this study, the mean paced P-wave difference between the two groups was 16.7 ms. We experienced a representative case that total atrial activation time during HASp was shorter than that of RAAp before catheter ablation for AF in the context of SSS after follow-up periods. In that case, the conduction time from pacing to most delayed activation site in the lateral side of LA was 30 ms faster from HAS than that from RAA ( Figure S4).
Furthermore, another subset analysis showed that patients who experienced rATP therapy in the HASp group experienced a decreased number of AF/AT lasting ≥7 days. AF typically originates from the pulmonary veins and LA. Some studies have shown that the dominant frequency of AF is generally higher in the LA than that in the RA. 14

| Study limitations
Our study had some limitations. First, this was a small, single-center, retrospective study and was not randomized. The small number of patients may limit the interpretation of the results. Although we cannot rule out potential bias using our data, baseline characteristics were almost identical between the two groups. Second, the atrial lead position was determined using fluoroscopy, and the right atrium was identified using angiography. Although we used a delivery catheter for accurate atrial septum implantation in the HASp procedure, there may be low atrial septal pacing in the HASp group. As a conduction system pacing mechanism, fluoroscopically and electrically defined HASp may be more beneficial as an alternative to RAAp.
Third, the definition of a successful rATP was termination within 20 s following the last sequence. Therefore, AF/AT may have recurred immediately after the last rATP delivery, and frequent rATP therapies may have been required in some cases. Fourth, not only rATP but ARS and PMOP were also used in this study. These atrial preventive pacing methods are also effective for reducing AF burden. 9 Lastly, this study included patients with a history of PAF and SSS.
The LA-to-RA frequency is attenuated in patients with long-lasting (>1 month) persistent AF. 14 The HAS CL and RAA CL of AF/AT may be the same in patients with long-lasting persistent AF. Furthermore, atrial pacing is not performed during AF/AT, although rATP is operated at that time. This may explain why the number of AF/AT lasting ≥30 days was not significantly different between the pacing sites.
Therefore, the advantage of HASp may be different in patients with persistent AF. Moreover, we did not include patients with atrioventricular block. Low atrial septum pacing (LASp) may be more beneficial for these patients as LASp can shorten atrioventricular conduction and reduce ventricular pacing.

| CON CLUS IONS
In conclusion, HASp using a delivery catheter is as safe as RAAp.
HASp may improve IACD and the success rate of rATP. Therefore, the combination of HASp and rATP may have a synergistic effect in reducing AF in SSS. Further prospective, multicenter studies are warranted to confirm these findings.

ACK N OWLED G M ENTS
We are grateful to Makiko Kanaike, Miho Kobayashi and TakakoYukiyoshi for their editing assistance.

CO N FLI C T O F I NTE R E S T S TATE M E NT
The authors declare no conflict of interests for this article.

E TH I C S S TATEM ENT
This study was approved by Kurashiki Central Hospital Medical Ethics Committee (No. 4086).

PATI E NT CO N S E NT S TATE M E NT
All patients included in this study provided consent to participate.