Clinical outcomes of left bundle branch pacing compared to right ventricular apical pacing in patients with atrioventricular block

Abstract Background Left bundle branch pacing (LBBP) can produce near normalization of QRS duration. This has recently emerged as alternative technique to right ventricular pacing and His bundle pacing. Hypothesis The purpose of this study is to evaluate clinical outcomes of LBBP compared to right ventricular apical pacing (RVAP). Methods A total of 70 AVB patients with indications for ventricular pacing were retrospectively studied. LBBP was attempted in 33 patients, classified as LBBP group. The other patients were classified as RVAP group. Pacing parameters, electrocardiogram and echocardiogram characteristics, heart failure hospitalization (HFH), and atrial fibrillation (AF) were evaluated perioperatively and at follow‐ups. Patients were followed in the device clinic for a minimum of 12 months and up to 24 months at a 3–6 monthly interval. Results LBBP was successful in 29 of 33(87.9%) patients while all 37 of the remaining patients successfully underwent RVAP. Paced QRS duration was significantly narrower in the LBBP group compare to RVAP(110.75 ± 6.77 ms vs. 154.29 ± 6.96 ms, p = .000) at implantation, and the difference persisted during follow‐ups. Pacing thresholds (at implantation: 0.68 ± 0.22 V in the LBBP group and 0.73 ± 0.23 V in the RVAP group, p = .620) remained low and stable during follow‐ups. The cardiac function in the LBBP group remained stable during follow‐ups (LVEF%:55.08 ± 4.32 pre‐operation and 54.17 ± 4.34 at the end of follow‐up, p = .609), and better than RVAP group (LVEF%: 54.17 ± 4.34 vs. 50.14 ± 2.14, p = .005). Less HFH was observed in the LBBP group (2/29,6.89%) compared to RVAP group (10/37,27.03%). Conclusions The present investigation demonstrates the safety and feasibility of LBBP that produces narrower paced QRS duration than RVAP. LBBP is associated with reduction in the occurrence of pacing‐induced left ventricular dysfunction and HFH compared to RVAP in patients requiring permanent pacemakers.

For decades, permanent cardiac pacing has been an effective treatment for patients with sick sinus syndrome (SSS) or high-degree atrio-ventricular (AV) block. As a conventional pacing strategy, right ventricular apical pacing (RVAP) is easily accessible, stable, and well tolerated. 1 However, multiple studies have shown that RVAP may lead to pacing-induced cardiomyopathy (PiCMP) and heart failure (HF), is associated with atrial fibrillation (AF), heart failure hospitalization (HFH), and mortality. 2,3 The most important reasons are interventricular dyssynchrony and burden of right ventricular (RV) pacing. 4 Recognition of the deleterious effect of RVAP pacing has led to a continued search for alternate pacing sites, such as RV mid-septal or outflow tract pacing. But recent studies show that they did not offer any benefits in terms of clinical outcomes over apical lead position. [4][5][6] In 2000, the pioneering investigation of permanent His bundle pacing (HBP) was first described by Deshmukh et al. in a small series of patients with AF and dilated cardiomyopathy. 7 Since then, the feasibility and safety of permanent HBP has been demonstrated by several investigators, and HBP is associated with reduction in the combined endpoint of death and HFH compared to RV pacing. [8][9][10] Although HBP is a physiological alternative to RV pacing, it has not become mainstream therapy, owing to technical challenges and higher and unstable pacing thresholds. In addition, there are longer implantation time, lower R wave amplitude, higher pacing lead revision rate. 8,11 In 2017, Huang et al. described an case report, who was troubled by dilated cardiomyopathy (DCM) and left bundle branch block (LBBB), and treated with left bundle branch pacing (LBBP); found improvements in cardiac function (LVEF got higher, from 32% to 62%). 12 The feasibility and safety of LBBP has subsequently been demonstrated by several studies. LBBP may be a new pacing strategy, on account of low threshold and narrow paced ECG QRS duration. 13 The aim of this study was to evaluate the clinical outcomes of LBBP compared to RVAP ( Figure 1).

| Study population
This was a single-center, retrospective, observational study. We studied patients referred to Zhenjiang NO1 People's hospital, from January 2018 to December 2018 for permanent pacemaker implantation for standard indications. 14 All patients were troubled by high-degree atrial-ventricular (AV) block or three-degree AV block. The patients in this study were divided into two groups based on the pacing site. One group of patients received traditional RVAP (RVAP group) and the other group received LBBP pacing (LBBP group). All patients were >18 years of age; patients were excluded if they were younger than 18 years of age, underwent cardiac resynchronization therapy or had existing cardiac implantable devices. All patients have signed written informed consent agreeing to the implantation procedure, and the protocol was approved by the hospital Institutional Review Board. was positioned in the right ventricular apex in a standard fashion. In both groups, dual-chamber pacemakers were implanted with the atrial pacing leads being implanted in the right atrial appendage.

| Follow-up
Patient demographics, medical history, electrocardiographic and echocardiographic findings were collected routinely. Electrocardiogram and echocardiography were performed by specialists in our hospital, LVEF is calculated by Simpson method. Pacing parameters(capture threshold, impedance, and sensing anplitude) were recorded at implant and during device follow-ups. Patients were followed in the device clinic for a minimum of 12 months and up to 24 months at a 3-6 monthly interval.
HFH and new-onset AF were tracked at follow-ups. HFH was defined as an unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with symptoms and signs consistent with heart failure, evaluated by two independent cardiologists. New-onset AF was obtained via pacemaker program controller, defined as AF that lasted more than 30 s.

| Statistical analysis
Continuous variables were summarized as mean ± SD, categorical variables were summarized as number and percentages. Differences in mean values between two groups or two time points were compared using Student t-test for continuous variables. The χ 2 test or Fisher's exact test (if the sample size was less than 40 or the minimum theoretical frequency was less than (1) were used for categorical variables.  The mean age was 65.50 ± 8.79 years with males accounting for 58.6% of the study cohort. Prior history of heart failure and atrial fibrillation was present in 17.14% (n = 12) and 10.00% (n = 7), respectively. The mean follow-up in the LBBP group was 17.40 ± 3.41 months compared to 18.00 ± 3.30 months (p = .69) in the RVAP group, and no patient was lost to follow up. Baseline demographics, pre-implantation medical history, left ventricular ejection fraction and QRS width were similar between the two groups. Baseline characteristics are shown in Table 1.

| Implant outcomes
There were no significant differences in sensing amplitude, pacing impedance, and capture threshold between LBBP group and RVAP group at implantation and at last follow-up (  (Figure 1), and the difference persisted during follow-up.
The LBB potential was recorded in 58.6% of LBBP patients, and the interval from LBB potential to the beginning of ECG QRS was 22.26 ± 4.32 ms. QRS duration was 108.84 ± 6.56 ms during LBBP in patients with recorded LBB potential during intrinsic rhythm and 113.67 ± 7.26 ms during LBBP in patients without recorded LBB potential (p = .386). At the end of follow-up, we found the left ventricular end diastolic dimension (LVDD) was shorter and the LVEF% was higher in the LBBP group, significantly.
We compared the pacing parameters before and after surgery. As shown in Table 3,pacing parameters remained stable during follow-up period, including the pacing threshold, sensing amplitude and impedance in two groups. In the LBBP group, the paced QRS duration was 111.83 ± 6.89 at last follow-up, that was not different from that at implantation (110.75 ± 6.77, p = .684). In patients with LBBP, we observed a stable LVEF (55.08 ± 4.32 vs. 54.17 ± 4.34, p = .609) and LVDD (48.71 ± 3.27 vs. 47.58 ± 3.29, p = .700). On the contrary, in patients with RVAP, the LVEF got lower (56.29 ± 5.40 vs. 50.14 ± 2.14, p = .005) and the LVDD got longer (46.92 ± 4.93 vs. 49.79 ± 1.85, p = .046) during follow-ups (Table 3). HBP, such as a high capture threshold, lead dislocation rate, particularly in those with pathological disease in the conduction system. [8][9][10][11] The QRS duration has been accepted as a surrogate for the evaluation of electrical synchrony. 16  Complications regarding LBBP should be noted except for conventional complications of transvenous pacing. Though none was observed in our study, complications like lead perforation, ventricular septal coronary damage and lead fracture should be taken seriously.

T A B L E 1 : Patient baseline characteristics
LBBP is a feasible, safety and most important, physiological pacing procedure. Our study provides basis for its widespread clinical use.
We believe the study will offer some help for further researches.

| Study limitations
Several limitations should be mentioned. First, this was a retrospective and observational study in a single centre, therefore, the results may be not representative. Second, the definition, evaluation standard and operating procedure of LBBP have not been normalized and unified, the success rate and outcomes may not be exactly the same. Large, prospective, randomized trials are necessary to evaluate the procedure's safety, and to prove mortality and heart failure benefits attributable to LBBP.

| CONCLUSIONS
The present investigation demonstrates the safety and feasibility of LBBP that produces narrower paced QRS duration than RVAP. The LBBP low capture threshold and high R-wave sensing amplitude favor long-term pacing management and device longevity. LBBP is associated with reduction in the occurrence of pacing-induced left ventricular dysfunction and HFH compared to RVAP in patients requiring permanent pacemakers.