Conduction system pacing (CSP), including His-bundle pacing (HBP) and left bundle branch area pacing (LBBaP), is a physiological pacing method, which can more effectively protect cardiac function, achieve electric resynchronization in HF and left branch bundle block patients by improving electromechanical synchronization[28-29]. Studies have demonstrated the feasibility and the clinical benefits of permanent HBP and LBBaP. It is known that CSP can produce physiological ventricular activation sequence, especially the ventricular activation conduction sequence of the HBP is almost as same as that of the normal heart rhythm, which can keep the atrioventricular, left and right ventricles and intraventricular synchronization to the greatest extent[30].
However, HBP has some limitations, such as operational difficulty with relatively long fluoroscopic exposure times and sometimes high and unstable pacing capture threshold. Moreover, HBP often fails to provide adequate pacing in patients with infra‐Hisian block or proximal left bundle branch block (LBBB). So left bundle branch area pacing (LBBaP) has emerged as an alternative method for delivering physiological pacing to achieve electrical synchrony of the left ventricle, especially in patients with infra-nodal atrioventricular block and LBBB. The proximal left bundle branches run through the left ventricular septum and fan out to form a wider target for pacing compared to the His bundle[31-32]. The criteria for LBBaP confirmed by electrical characteristics are described as: 1. Paced morphology of RBBB pattern; 2. Identification of the LBB potential; 3. Pacing stimulus to left ventricular activation time (Stim-LVAT); 4. Determination of selective (S-LBBP) and nonselective (NS-LBBP) LBBP; 5. Double electrode mapping verification (if achievable); 6. There is damage current. LBBP has been reported to offer low pacing thresholds, higher R waves and since the distal conduction system is targeted, has a lower theoretical risk for the development of distal conduction block[33].
Although LBBaP is widely recognized and accepted by clinicians, however, due to the relative complexity of the surgical process the same as HBP, it is also difficult for many primary hospitals lacking relevant equipment to carry out such operations. The difficulty of attempt to accurately identify the HBP and LBBP pacing area and successfully capture of His or LBB, and more complicate of the surgical procedure compared with right ventricular pacemaker, all these reasons limit the promotion and application of the LBBaP. Moreover, the success of the CSP operation mainly depends on intracardiac electrogram using electrophysiological multichannel recorder, such as the identification of the His or left bundle potential, the determination of Stim-LVAT and damage current, etc. So the application and promotion of the HBP and LBBaP is mainly limited to cardiac catheterization operating room equipped with intracardiac electrogram, and most of them are only available and capable to carry out in large general hospitals and cardiovascular catheterization room with related instruments. Meanwhile, the operators need to go through a certain period of professional training time to master the technical points, but for doctors who have not receiving standardized professional training and in basic care hospitals where the intracardiac electrogram are not available, it is relatively difficult for them to receive standardized professional training, and equipped with a standardized system to carry out the standardized pacing operation procedure of CSP. Therefore, we hope to seek a simple, feasible and safe method, which can also achieve the LBBaP without using electrophysiological multichannel recorder, and achieve the purpose of maintaining the maximize physiologic pacing and preserve cardiac synchronization.
In our study, the implantation process of LBBaP will be performed according to the standardized implantation operation procedure. The only difference is that during the operation, before the 315His sheath withdrawal, the operator could not refer to the multi-channel intracardiac electrogram, but could refer to the surface multi-lead ECG monitoring and intracavity signal diagram of pacemaker programmer. In our study, we refer to the change of electrocardiogram of the monitoring ECG lead as the basis for achieving pacing in the left bundle branch area, that is, the ventricular premature beat presented as the right bundle branch block form during the 3830 electrode been twisted from the right ventricular septum to the left ventricular septum (basically in consistent with the ventricular premature beat pattern observed during routine standard LBBaP), and at the same time, small or relative high r waves (that is, the pacing QRS wave of the V1 lead is sR, Sr, rSr, etc.) can been observed in the pacing QRS wave of the V1 lead. In addition, we can roughly evaluate the peak time (such as LVAT) and the QRS width of the pacing QRS in V5 lead seen in the monitoring ECG. At the same time, the combination of paced QRS in lead V5 and lead II/III/aVF can roughly help to determine the electrode position, that is, under normal circumstances, if the direction of the main wave in lead II/III/aVF is upright, the electrode position is generally located in the high or middle interventricular septum. On the other hand, if the direction of the main wave in lead II/III/aVF is negative, the electrode position is often located in the low interventricular septum. What is more, if the QRS in lead V5 has a deep s wave, the electrode position may be biased towards the apex. In addition, p potential could been observed in some patients in the intraluminal signal map of the pacemaker programmer, which is also a strong evidence to help us determine whether the left bundle branch area pacing is achieved. At the same time, in order to ensure the safety of patients, we will measure the pacing electrode parameters of 3830 electrodes both in unipolar and bipolar pacing mode, including capture threshold, lead impedance, and R‐wave amplitude of unipolar and bipolar pacing, to confirm that all parameters are acceptable. In most patients, the ring electrode may enter the ventricular septum, and we also measured the ring electrode capture threshold to assess the depth of the pacing lead inside the ventricular septum. By observing the premature beats during the operation, the paced QRS morphology, and the intracavity electrocardiogram of the pacemaker programmer, we can evaluate and assess whether LBBaP has been successfully achieved without an intracardiac electrogram. Of course, in the end, when the 3830 lead have been withdrawn, we will fix the 3830 lead and start to record the parameters of LBBaP using the intracardiac electrogram both in unipolar and bipolar pacing mode to verify whether LBBaP has been achieved, and to verify its effectiveness and feasibility.
We think our research is very meaningful, it is proposed for the first time in our research, the possibility of realizing LBBaP without an intracardiac electrogram. The concept of LBBaP without a multi-conductive physiological instrument is innovative, feasible and applicable for clinical significance. It provides a broader platform for the promotion and clinical application of CSP. We hope to refer to the "simplified LBBaP procedure-nine-zone method" (referred to as the "nine-zone method"), which is currently more clinically used, and combine the multi-lead surface ECG monitoring and pacing programmers to achieve the LBBaP, and verify its effectiveness and feasibility. If the method of our study proves to be feasible, safe and effective, it will be applicable for many catheterization labs in primary hospitals without multi-channel intracardiac electrogram, and also operators can refer to the operation method in our study to perform LBBaP, and benefit more patients.
Limitations
First, though the proposed study is designed as a prospective study, it will be a single-center study, which may cause the baseline drift of the selected patients. At the same time, the study sample size will be relatively small, and we need studies with larger sample sizes and multi-centers to confirm our results. Moreover, each pacemaker operator has different experience, which may also lead to differences in the success rate of LBBaP between different operators, as operators with more experience of LBBaP will have a higher implant success rate.
Inclusion criteria
1) Age> 18 years old;
2) indications for bradycardia permanent pacemaker implantation, preoperative cardiac ultrasonography EF>50%;
3) Sign the informed consent form;
4) Patients who are expected to successfully implant pacemaker in accordance with the conventional LBBaP implantation procedure.
Exclusion criteria
1) Patients who need cardiac resynchronization therapy, that is, patients with CRT-P or CRT-D indications;
2) There are other contraindications for permanent pacemaker implantation;
3) Patients with indications of ICD implantation;
4) Women who are pregnant or expect to become pregnant or breast-feeding within one year;
5) Participated in or are participating in additional clinical trials within the last three months;
6) Poor compliance, unable to carry out the plan strictly, and unable to participate in the follow-up for a variety of reasons;
7) Vulnerable groups, incorporating individuals with mental illness, critically ill patients, pregnant women, minors, cognitively impaired people, etc.;
8) Any other circumstances that the investigator considers inappropriate to participate in the trial.
Trial status
The recruitment of participants started on January 1, 2021, and is expected to continue until December 31, 2023.
On submission for publication, version 1.0 of the protocol is being used. 1 January 2021.