Short‐term and intermediate‐term performance and safety of left bundle branch pacing

Abstract Introduction Left bundle branch pacing (LBBP) is a promising new method for patients with pacing indications. This study aims to evaluate the safety and feasibility of LBBP in a relatively longer time span. Methods and Results A total of 164 patients were recruited for LBBP in this study. Among these patients, 148 patients had pacing indications due to symptomatic bradycardia while the other 16 patients had indications for cardiac resynchronization therapy (CRT). LBBP was successful in 89.0% (146/164) of all recruited patients. Intracardiac and surface electrographic parameters and image data were documented during the LBBP procedure. The mean paced QRS duration (pQRSD) and the mean stimulus to left ventricular activation time (stim‐LVAT) was 106.0 ± 12.9 ms and 64.4 ± 13.7 ms respectively. Left bundle branch (LBB) potentials were recorded in 89 patients. Forty‐three of whom had sick sinus syndrome (SSS), and 46 had atrioventricular block (AVB). The presence of LBB potential was more common in patients with SSS (82.7% vs 57.5%, P = .002). No significant differences in pQRSD, stim‐LVAT, or capture threshold were detected between patient groups with or without LBB potential. Patients were followed up at 1 month, 3 months, 6 months, and 1 year after the procedure. Pacing parameters and the echocardiographic data remained stable within a mean follow‐up period of 8.6 ± 4.3 months. No serious complication caused by this procedure was found in this study. Conclusions Successful LBBP carried an aspect of short pQRSD and stim‐LVAT while the LBB potential was not the prerequisite and necessary feature. The LBBP procedure had a high success rate with satisfied and stable lead parameters during short and intermediate‐term observations.


| INTRODUCTION
The adverse effects of right ventricular apex (RVA) pacing have long been realized, including electrical and mechanical asynchrony that will increase the risk of atrial fibrillation, heart failure, and bring a higher mortality rate. 1,2 Initial investigations have confirmed the feasibility and safety of left bundle branch pacing (LBBP) via shortterm and medium-term follow-ups in relatively small cohorts. [3][4][5][6] As LBBP is an innovative technique, there is only limited information about its outcomes in a relatively longer term. In this report, we

| Lead implantation
LBBP was achieved by a transventricular septal method in the basal ventricular septum as described elsewhere. 7 Briefly, the Select Secure (model 3830, 69 cm, Medtronic Inc, Minneapolis, MN) pacing lead was introduced through a fixed curve sheath (C315 HIS, Medtronic Inc) toward the right ventricle beyond the tricuspid annulus.
During the procedure, the His bundle region was identified as an anatomic marker before further advancing the lead toward the cardiac apex by 1.0 to 2.0 cm. Once the paced QRS morphology showed a "W" pattern in V1, the lead was perpendicularly screwed in. When screwing, the unipolar electrode pacing pattern and impedance were consecutively monitored. The lead was finally fixed when the paced QRS morphology showed a "QR/Qr" pattern in V1, and the stimulus to left ventricular activation time (stim-LVAT) was the shortest and consistent during high and low outputs in V5 or V6. 8 The right atrial lead was implanted in the right atrial appendage and connected to the atrial port. The LBBP lead was connected to the ventricular port if a dual-chamber pacemaker was implanted. For patients who failed in LBBP, right ventricular septal pacing (RVSP) was performed as an alternative. The LV leads were implanted in the lateral or postlateral left ventricular vein if possible as mentioned elsewhere. 9 In patients with normal sinus rhythm undergoing CRT-pacemakers(P), the LBBP lead was connected to the right ventricular (RV) port and the left ventricular (LV) lead to the LV port. In patients with normal sinus rhythm undergoing CRT-defibrillators(D), the LBBP lead was connected to the LV port and an implantable cardioverter-defibrillator lead was implanted in the RVA and connected to RV port.

| Electrocardiographic measurements
Twelve-lead surface electrocardiography (ECG) was recorded by the GE CardioLab Electrophysiology recording system (GE Healthcare were measured in sequence. First, the QRSD was measured in the 12-lead ECG taken during implantation, and the duration was measured from the first to the last sharp vector of QRS complexes crossing the isoelectric line in 12 leads to the last deflection of the complex. Second, the pQRSD was measured from the onset of the first deviation from baseline for selective LBBP and from the onset of steepest deflection in nonselective LBBP to the end of the last deflection of the QRS complex in 12 leads. The selective LBBP was defined as capturing the LBB with a discrete component between the stimulus and onset of QRS complex under threshold output, while the nonselective LBBP captured both the LBB and the local myocardium and no discrete interval presented between the pacing spike and surface ECG QRS onset. Following that, the stim-LVAT was measured from the pacing stimulus to the peak of R-wave in lead V5 or V6. At last, the PVI was assessed from the LBB potential to the onset of QRS complex.

| Data collection and follow-up
Baseline characteristics of participants were collected at enrollment.
During implantation, the intracardiac, surface electrographic parameters, and imaging data were documented. Lead parameters, ECG morphology, and echocardiographic data, including left ventricular ejection fraction (LVEF), left ventricular end-diastolic internal dimension (LVIDd), and interventricular septal thickness (IVSd) were recorded at least 12 to 24 hours before the procedure and each follow-up visit. Patients were followed up at 3 days after the operation, 1 month, 3 months, 6 months, and 1 year after implantation.
Possible complications such as infections, pericardial effusion, capture threshold elevation, lead dislodgment, and lead deficiencies were routinely tracked. Transient ischemic attacks or stroke-like symptoms were also recorded if there was any. "Chronic capture threshold elevation" was defined as a situation when the threshold was higher than 2.5 V@ 0.4 millisecond or was more than 1 V higher than the threshold instantly after implantation. Location and depth of the lead within the interventricular septum and severity of the tricuspid valve regurgitation (TVR) were assessed at each follow-up visit as well.

| Statistical analysis
Continuous and categorical variables were expressed as the mean ± SD and percentages, respectively. Differences between two groups were compared using the Student t test for continuous variables, and the χ 2 test was used for categorical data. A value of P < .05 was considered statistically significant. All statistical analyses were performed using SPSS Statistics version 22.0 (Chicago, IL).

| Baseline characteristics
In total, 164 consecutive patients with bradycardia-related pacing indications or CRT indications were recruited for LBBP attempts, and the LBBP success rate was 89.0% (146/164). Detailed baseline characteristics of the recruited patients were described in Table 1 Among this cohort, 47.2% (69/146) patients had a follow-up period that equaled to or was longer than 12 months and 63.0% (92/146) patients had a follow-up period that was longer than 6 months. The mean follow-up duration was 8.6 ± 4.3 months (ranges from 3 to 18 months).

| Electrophysiological characteristics
The mean pQRSD and the mean stim-LVAT was 106.0 ± 12.9 milliseconds and 64.4 ± 13.7 milliseconds respectively. Final pQRS morphology in lead V1 was either a QR or Qr type. In 10 patients, a stimulus to QRS interval was identical under the threshold output with an rSR type morphology presented in V1. The initial r wave diminished with the morphology of QRS developed into QR type and stim-LVAT remained consistent as the output elevated ( Figure 1). In most patients, the dynamic change of stim-LVAT could be observed during the lead screwing-in process ( Figure 2 (Figure 3).

T A B L E 1 Baseline and procedural characteristics
Lead parameters, including capture threshold, R-wave amplitude and pacing impedance were stable throughout the whole observation period (ranges from 3 to 18 months), which were showed in Table 3.
F I G U R E 1 Electrophysiological characteristics of LBBP. Surface and intracardiac electrograms were taken from patients under LBBP. In the first patient (a), a LBB potential was recorded with the PVI being 20 ms, and the potential to LVAT duration was equal to 67 ms (a1). There was consistency among LVAT at low output (a2, 0.5 V@ 0.4 ms), high output (a3, 5 V@ 0.4 ms) and intrinsic activation. In another patient who underwent LBBP (b), the intrinsic QRS complex presented LBBB morphology, no LBB potential was recorded and the intrinsic LVAT was 116 ms (b1). The paced QRS wave presented "rSR" morphology in V1 with an isoelectric line before the onset of QRS wave which was deemed as selective LBB capture under capture threshold (0.3 V@ 0.4 ms, b2). As the output increased, the isoelectric line disappeared with the "R" wave of V1 decreased and the S wave of V5, V6 shallowed which was deemed as nonselective LBB capture (b3 and b4).   | 1477 achieve a better threshold, and then perforation happened. In the other two patients experienced acute perforation, we were able to record a LBB potential with low amplitude from the tip electrodes, but perforation happened when we were performing one more round of screw-in to achieve a better potential amplitude. For all these three patients had perforation, a decrement of unipolar impedance to below 500 Ω along with a capture threshold increment was noted during the procedure. The leads were successfully repositioned and no pericardial effusion or cerebral ischemia was observed in any of these patients. Many studies have suggested that due to the electrical and ventricular asynchrony in the left ventricle, the high burden of RVA pacing might be detrimental to specific subgroups of patients. 10,11 Among the various physiological pacing strategies that are available, LBBP has been applauded as a feasible strategy for patients with heart failure, especially for those who failed in traditional BiV or His bundle pacing (HBP). 12 Initial investigation also confirmed the safety and feasibility of LBBP during short-term and medium-term followups. 7 In light of LBB's anatomy, satisfied lead parameters could be expected. 19 In this study, we confirmed that capture threshold, impedance, and R-wave amplitude of LBBP were comparable with that of traditional RVA pacing and remained stable throughout the whole observation period. Considering the feasibility LBBP has demonstrated, it's suitable to promote this technique in clinical practice.
According to Upadhyay et al's 20 study, left intra-hisian block is the most common pathophysiological mechanism of LBBB pattern. In that case, a relatively distal site of location may stand more chance in correcting LBBB. There were 16 patients tormented by heart failure complicating with LBBB in this cohort, and 14 out of these 16 patients' LBBB was corrected by LBBP in lieu of permanent HBP.
Though LBBP and HBP have a similar physiological pacing mechanism, that is, the rapid recruitment of left His-Purkinje system, some drawbacks such as higher capture thresholds, lower R-wave amplitudes, atrial oversensing, and increased risk for lead revisions are associated with HBP. 21,22 In the present study, we also proved that LBBP is a preferable option for resynchronization therapy, especially for patients with a failed HBP attempt. Existence of LBB potential during the LBBP procedure can be considered as the strongest evidence of lead being in the periphery of LBB. 24 The amplitude of LBB potential may be affected by many factors such as the direction of the wavefront, the velocity of conduction, the distance of the bundle branch, and the signal of far-field or near field. 8 On the other hand, without retrograde activation of the LBB, the potential may not be visualized in patients with complete LBBB or escape rhythm resulting from a non-LBB fascicle. 7 The LBB potential was not recorded in about one-third patients in our study. No differences lay in pQRSD, stim-LVAT, and capture threshold between LBB potential (+) and LBB potential (−) subgroups.
In that case, we concluded that the existence of LBB potential was not a prerequisite for a successful LBBP procedure.
The right bundle branch is a slender structure 1 to 2 mm in diameter that runs without branching through the interventricular septum and about 1 to 1.5 mm beneath the right interventricular Septal perforation and coronary artery injury need to be avoided during the procedure. 12 In our study, three cases of perforation were documented and no septal branch injury was recorded. According to our experience obtained from this study, (a) elder female patients were more likely to have loose myocardial tissue and therefore de-

CONFLICTS OF INTEREST
The authors declare that there are no conflicts of interest.

ETHICAL APPROVAL
The study was approved by the Ethics Committee of Xiamen Cardi-