Left ventricular septal pacing versus left bundle branch pacing in the treatment of atrioventricular block

Abstract Background This study aimed to evaluate the feasibility and clinical response of LVSP as an alternative to LBBP. Methods This was a retrospective study of pacemaker implantation, and 46 consecutive patients with pacemaker implantation were enrolled in the study. The patients were divided into the LBBP and LVSP groups. Electrocardiogram characteristics, pacing parameters, cardiac function, and safety events were assessed during implantation and 12‐month follow‐up. Results The procedure time was significantly increased in the LBBP group compared with the LVSP group (53.52 ± 14.39 min vs. 38.13 ± 11.52 min, respectively, p = .000). The pacing QRS duration (PQRSD) decreased by 14.09 ± 41.80 ms in the LBBP group and increased by 9.70 ± 29.60 ms in the LVSP group (p = .031). Furthermore, the left ventricle activation time (LVAT) was shorter in the LBBP group than in the LVSP group (48.70 ± 13.67 ms vs. 58.70 ± 13.67 ms, p = .032). During the 12‐month follow‐up, pacing thresholds remained low and stable, and there was no significant decrease in cardiac function. No adverse event was observed during the follow‐up period. Conclusions Both LBBP and LVSP are safe and feasible methods. LVSP is a good option when multichannel electrophysiological instruments are not available and when the time available for the procedure is limited.

Left bundle branch pacing (LBBP) is a newly discovered physiological pacing, and its safety has been proven by many studies Zang et al., 2019). LBBP can be achieved with a high success rate and low capture thresholds. Left ventricular dysfunction improved significantly during follow-up (Ravi et al., 2020).
However, LBBP, under the monitoring of multichannel electrophysiological instruments, must find P potential to accurately locate the electrode and repeatedly test the pacing threshold and impedance to prevent the electrode from penetrating the left ventricular membrane into the heart chambers and thus inducing a thrombus.
Its operation takes a long time and may increase the chances of developing complications. The electrode of the left ventricular septal pacing (LVSP) is implanted in the interventricular septum, and its depth is more than half of the septum (Mills et al., 2009;Peschar et al., 2003), but with a certain distance from the left ventricular membrane surface; thus, it saves time to measure the parameters and blindly operated without a multichannel instrument.
LBBP and LVSP share similar characteristics regarding lead placement in the left septum; however, LBBP is characterized by left septal subendocardial lead placement and confirmation of left bundle branch (LBB) capture using pacing maneuvers (Huang et al., 2019). In contrast, LVSP is achievable over a larger area and with shallower lead positions (Wu et al., 2020).
Moreover, the hemodynamic effect of LVSP pacing in the acute phase is similar to that of His pacing (Salden et al., 2020). It is, therefore, worth investigating the possible short-term safety and efficacy achieved with LVSP compared with LBBP. To this end, this article compared the clinical outcomes of LVSP and LBBP implantation in the right ventricle.

| Study population
All the patients from the First Affiliated Hospital of Wannan Medical College who received implantable dual-chamber or single-chamber pacemakers according to the established guidelines from April 2019 to December 2020 were included in this study. Inclusion and exclusion criteria: the study subjects were all single-or dual-chamber pacemaker patients treated with LBBP or LVSP implantation. Two groups of patients were formed: the LBBP group (n = 23) included 12 men and 11 women with an average age of 72.04 years old, and the LVSP group (n = 23) included 11 men and 12 women with an average age of 71.08 years old.
At the time of procedures, paced QRS duration (PQRSD), QRS duration (QRSD), and left ventricle activation time (LVAT) were recorded for comparison between groups. At the one-year follow-up, the index of capture threshold (V), R-wave amplitude (mV), impedance (Ω), and echocardiography, including left ventricular end-diastolic diameter (LVEDD, mm) and left ventricular ejection fraction (LVEF, %), were analyzed. The protocol was approved by the hospital Institutional Review Board, and written informed consent was collected from all the patients.

| LBBP
The implantation of the left bundle electrode was achieved following the previous work in literature Huang et al., 2019). First, the C315 delivery sheath was inserted via the axillary vein to the His bundle region in the atrioventricular septum. Next, the 3830-pacing lead was advanced through the sheath to detect the His potential under the fluoroscopic right anterior oblique (RAO) 30°, and the image was used as a reference. The sheath with the pacing lead was further moved down 10~20 mm along the ventricular

| LVSP
The 3830-electrode was implanted medially in the ventricular septum with a rotation depth of more than half of the septal thickness ( Figure 2d). The parameters of the pacing threshold, perception, operation time, PQRSD, LVAT, and complication were recorded.

| Statistics analysis
The SPSS software version 22.0 (IBM, Armonk, New York) was used to perform all the statistical analyses. Normally distributed continuous data were expressed as the mean ± SD, while categorical data were described as the number (%), and t or χ 2 test was used to examine the aforementioned differences. All the tests were two-sided, and a p-value < .05 was considered to be statistically significant.

| Baseline characteristics
The study cohort consisted of patients with sinus node dysfunction and AV conduction block. The left ventricular ejection fraction (LVEF) was 58.89 ± 11.93%, with four heart failure patients having a low LVEF (EF <35%) and two patients with failed cardiac resynchronization therapy/defibrillation (CRT/D). Three patients diagnosed with pacemaker-induced cardiomyopathy (PICM) with EF <50% were upgraded to LBBP. Furthermore, 43 patients were implanted with DDD pacemakers and 3 patients were implanted with VVI pacemakers. There were no statistically significant differences in clinical baseline data between the two groups (Table 1).

| Implantation results
As shown in Table 2, of the 23 patients who successfully underwent LBBP, 22 (95.65%) patients were implanted with dual-chamber pacemakers and 1 (4.35%) with a single-chamber pacemaker. On the contrary, of the 23 patients in the LVSP group, 21 (91.30%) were implanted with dual-chamber pacemakers and 2 (8.70%) were implanted with single-chamber pacemakers. The operation time was significantly longer in the LBBP group compared with the LVSP group (38.13 ± 11.52 minutes vs. 53.52 ± 14.39 minutes, respectively, p = .000) (Figure 3). In addition, no procedure-related complications and adverse events were reported in either group.

| Pacing parameters and cardiac function
Ventricular lead parameters, that is, the capture threshold, Rwave amplitude, and ventricular impedance, did not differ significantly between the two groups during the procedure and at the 1-year follow-up. Although the pacing thresholds in both groups increased slightly from 0.70 ± 0.14 V to 0.88 ± 0.18 V (p = .001) in LBBP group and from 0.66 ± 0.18 V to 0.82 ± 0.19 V (p = .004),

| ECG characteristics
Compared with the ECG parameters before and after pacing, there was no significant difference in the QRSD before pacing between the two groups. After the procedure, the PQRSD decreased by 14.09 ± 41.80 ms in the LBBP group and increased by 9.70 ± 29.60 ms in the LVSP group, with a significant difference in the changes (104.26 ± 19.00 ms vs. 118.09 ± 23.20 ms, respectively, p = .032). Furthermore, the activation time of the left ventricle was shorter in the LBBP group than in the LVSP group (48.70 ± 13.67 ms vs. 58.70 ± 13.67 ms, respectively, p = .032) (Table 3, Figure 3).

| DISCUSS ION
Our study demonstrated the LBBP and LVSP pacing methods are both safe and effective. Compared with LVSP, LBBP is more physiologically compatible as it shortens the QRS duration and activates the left ventricle earlier, but LVSP is a good option when critical equipment is lacking or time is limited.  Note: Continuous data are presented as mean ± standard deviation (SD), and categorical data are presented as the number of subjects (n) and percentage (%). p-value <.05 was considered to be statistically significant.
The feasibility of LVSP has been proven by a series of experiments from basic research to clinical practice. In 1970, Dirk Durer mapped the human heart in vitro and pointed out that the earliest exciting site in the ventricle is the left ventricular septum (Durrer et al., 1970). Therefore, the best pacing site should be the closest    LBBP is a creative development based on LVSP and His pacing.

TA B L E 3 Comparison of pacing parameters and echocardiographic data of the LBBP group and the LVSP group
In 2017, Huang reported that a patient with CRT failure underwent LVSP treatment and confirmed that the pacing electrode was successfully implanted into the LBB; the threshold (0.5 V, 0.5 ms) pacing could capture LBB and correct CLBBB. After 1-year of follow-up, patients had a stable pacing threshold, an increase in EF from 32% to 62%, and a decrease in left ventricular end-diastolic diameter (LVEDD) from 76 mm to 42 mm (Huang et al., 2017). This shows that LVSP can selectively lower the threshold value of pacing the distal part of LBB across the pathological part of LBB and achieve physiological pacing similar to that of His bundle pacing (Sharma et al., 2017). Since then, the safety of LBBP has been confirmed by the research performed at several single centers in China Gao et al., 2020;Guo et al., 2020). This study showed that LBBP pacing could shorten the QRS time and activate the ventricles earlier than LVSP, more physiological pacing. Because of this feature, LBBP was used as an escalation therapy for three patients with PICM.
LBBP combines the common advantages of LVSP and His pacing and compensates for their shortcomings. Although His pacing is the most physiologic one, its clinical application is limited by its shortcomings such as low perception, high capture threshold, and operational complexity. In particular, the progression of His bundle lesions distally poses a potential problem for His pacemaker therapy in AVB patients (Vijayaraman, Chung, et al., 2018;Vijayaraman, Naperkowski, et al., 2018), often requiring the im-

| CON CLUS ION
Both LBBP and LVSP are safe and feasible approaches. LBBP is consistent with physiological pacing, but LVSP is a good option in the absence of electrophysiological multichannel instruments and in cases where procedure time is limited.

E TH I C S A PPROVA L A N D CO N S E NT TO PA RTI CI PATE
This study was approved by the ethics committee of the First Affiliated Hospital of Wannan Medical College. Written informed consent was obtained from all patients.

CO N S E NT FO R PU B LI C ATI O N
Informed consent for the publication of the report was obtained from the patient and study participants in written form.

CO N FLI C T O F I NTE R E S T S
The authors declare that they have no competing interests.

F I G U R E 3
Comparison of the operation time and ECG parameters between the LBBP and LVSP groups. PQRSD, paced QRS duration; QRSD, QRS duration; ΔQRSD = QRSD-PQRSD; LVAT, left ventricle activation time. Values are mean; p < .05 was considered to be statistically significant

AUTH O R S' CO NTR I B UTI O N S
YZ, the first author, wrote the manuscript. JFW, YQW, YWY, SBR, and CLJ performed the pacemaker implantation. All authors read and approved the final manuscript. All authors agreed to their contributions.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data are available from the corresponding author upon reasonable request due to privacy or other restrictions.