Cardiac resynchronization performed by LBBaP‐CRT in patients with cardiac insufficiency and left bundle branch block

Abstract Objective To evaluate the efficacy and safety of left bundle branch area pacing (LBBaP) in patients with heart failure and left bundle branch block (LBBB), and to compare the clinical effects with traditional cardiac resynchronization therapy (CRT). Methods Thirty‐two patients with dilated cardiomyopathy complicated by cardiac insufficiency and left bundle branch block were divided into CRT group and LBBaP group. Parameters including pacing threshold, R‐wave amplitude, pacing impedance and operation time, and X‐ray exposure time were recorded. The left ventricular ejection fraction (LVEF), left ventricular end‐diastolic diameter (LVEDD), and left ventricular end‐systolic diameter (LVESD) were examined by echocardiography. The changes of QRS complex before and after operation were compared. Results Compared with CRT group, the LBBaP group spent less time on total operation time and X‐ray exposure time and had stable electrode parameters including pacing threshold, R‐wave amplitude, and lead impedance after 12‐month follow‐up. In addition, LBBaP can achieve narrow QRS complex (117.15 ± 9.91) ms immediately than that in CRT group (130.32 ± 12.41) ms. The change of QRS between LBBaP is (50.30 ± 23.79) ms and CRT group is (33.15 ± 20.22) ms. After 6 months' follow‐up in LBBaP group, EF was higher than that before operation. Followed up for 12 months after operation, EF and LVEDD in LBBaP group were significantly improved compared with those before operation. Conclusion Left bundle branch area pacing is a safe and effective resynchronization method for patients with cardiac insufficiency and asynchronization, which can achieve same clinical effects to CRT.


| INTRODUC TI ON
Cardiac insufficiency is a serious manifestation of dilated cardiomyopathy, which affects the quality of life and life expectancy of patients. Although cardiac resynchronization therapy (CRT) is recommended by the guidelines as a recommendation for patients with left bundle branch block (LBBB) with cardiac insufficiency, the clinical 30% non-response rate of CRT is a problem that cannot be ignored (Dickstein et al., 2008;Vijayaraman et al., 2017). Therefore, we were pursuing new effective treatment for dilated cardiomyopathy (DCM) patients with cardiac insufficiency all the time. In the year 2000, (Deshmukh et al., 2000) successfully performed His bundle pacing (HBP) on patients with atrial fibrillation accompanied by cardiac insufficiency but without intraventricular block with the help of steel wire and general active spiral electrode for the first time. This study was followed up for 2 years, and the results confirmed that the improvement of cardiac function in patients underwent HBP pacing was better than that of right ventricular pacing. Further studies have confirmed that 52% of bundle branch block (BBB) can be eliminated by HBP ( Barba-Pichardo et al., 2010); therefore, physiological pacing can effectively improve left and right ventricular electrical synchronization.
Physiological pacing is the best pacing mode we are pursuing at present, including His bundle pacing and left bundle branch area pacing (LBBaP). Because of the anatomical characteristics, the left bundle branch area is not enclosed by fibrous sheaths similar to those around the His bundle, the left bundle branch, and the Purkinje fibers are all exposed under the endocardium of left ventricle. Therefore, LBBaP has the advantages of lower threshold and more stable position over His bundle pacing (Chen et al., 2019;Zhang et al., 2019) and can correct left bundle branch block directly, so it is especially suitable for DCM patients with LBBB. With the development of assistive tools, implantation of electrode in left bundle branch area has become easier.
In this study, we retrospectively studied the improvement of cardiac electromechanical synchronization in DCM patients with cardiac insufficiency treated before and after left bundle branch area pacing, furthermore to explore the application prospects of LBBaP in the treatment of DCM patients with cardiac insufficiency.  (Pinto et al., 2016) and have CRT indication (Ponikowski et al., 2016): QRS complex is more than 150 ms with LBBB, left ventricular ejection fraction (LVEF) <35% still has symptoms of persistent cardiac insufficiency symptoms after standard drug treatment, and ischemic cardiomyopathy was excluded by coronary angiography or coronary CTA within 1 year.

| Patients selection
In addition, the percentage of ventricular pacing was 98%-100% in all patients.
Patients with the following diseases were excluded: (1) bradycardia or malignant arrhythmia caused by reversible factors such as drug and electrolyte disorders; (2) acute myocardial infarction, acute cardiac insufficiency, severe liver and kidney insufficiency, acute and chronic infections, and other patients who are not suitable for surgery at present; (3) MRI findings in patients with myocardial fibrosis at the target electrode implantation site; (4) pregnant or lactating women; and (5) patients with mental disease or psychiatric disorder.
All patients were divided into CRT group and LBBaP group according to surgical methods. Implants in patients with left bundle pacing were performed by the same cardiologists. All the patients were informed of the operation method and signed the informed consent before operation. This study was approved by the Ethics Committee of Beijing Anzhen Hospital.
Before operation, basic information about the patients was collected, including gender, age, height, weight, past history including sick sinus syndrome (SSS), atrioventricular block (AVB), atrial fibrillation, coronary heart disease, hypertension, diabetes mellitus, cerebrovascular disease, and hyperlipidemia. QRS complex was measured, and echocardiographic data, including LVEF, left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD), were collected. The pacemaker parameters including pacing threshold, R-wave amplitude, and pacing impedance were observed after operation. The patients were followed up for 1 year. QRS complex and echocardiographic data were compared at 6 months and 12 months after operation.

| LBBaP implantation
Left bundle branch area pacing was performed as described for the HBP method (Huang et al., 2017(Huang et al., , 2019Vijayaraman & Dandamudi, 2016). Briefly, with the aid of the C315/C314 sheath (Medtronic, Inc.), the selected Secure™ lead (model 3830; Medtronic, Inc.) was inserted into the His, and the His potential was measured. Images were obtained under X-ray. Subsequently, the 3830 electrode and C315 sheath tube were pushed together in the apex direction (1-3 cm). When the 2 V output was unipolar paced by the 3830 electrode, the V 1 QRS wave appeared W-

| CRT implantation
LV electrode was implanted into coronary vein by traditional way.

| Statistics analyses
SPSS version 20.0 was used for all statistical analyses. Normally distributed continuous data were expressed as the mean ± SD.
Categorical data were described as the number (%), and chisquare test or Fisher's exact test (if the sample size was less than 40 or the minimum theoretical frequency was less than 1) and used to examine the aforementioned differences. All the tests were two-sided. A p-value <.05 was considered statistically significant.

| Patients characteristics
A total of 32 consecutive patients were enrolled and divided into two groups according to the operation; finally, 19 patients underwent CRT. Three patients underwent LBBaP instead of previous CRT because of poorly ventilated target vein, so finally 13 patients underwent LBBaP.
The mean age of patients in the LBBaP group was (61.77 ± 12.37) years, and there were 8 (61.5%) males. The mean age of patients in the CRT group was (59.32 ± 5.41) years, and there were 15 (78.9%) males. There was no statistically significant difference in gender and age between the two groups. In addition, there were no statistically significant changes in comorbidities such as diabetes mellitus, hypertension, incidence of atrioventricular block, or electrocardiographic and electrocardiographic echocardiographic indices in the two groups. All the clinical baseline data did not statistically differ between the two groups (Table 1).

| Operation time
The total operation time in LBBaP group (90.08 ± 33.40) min was significantly shorter than that of CRT group (158.05 ± 19.05) min, and the X-ray exposure time in LBBaP group (20.46 ± 7.36) min was also significantly shorter than that in CRT group (43.53 ± 10.36) min (Table 2).

| ECG characteristics
The QRS complex of patients in LBBaP group changed significantly.
As LV electrodes rotated from right ventricle to left ventricular subendocardium through interventricular septum, the notch of lead V 1 moved backward and upward gradually, and QRS complex changed from LBBB to RBB. LBB potential injury current was observed in 10 patients (76.9%).
QRS wave narrowed immediately after operation in both groups (
However, LVEDD and LVESD were not significantly different between the two groups (p > .05) (Figure 2A-C).

| DISCUSS ION
QRS wave is a direct and objective indicator of improvement, which can reflect the changes of cardiac electrical synchronization immediately. In this study, LBBaP was performed on patients with LBBB.
QRS complex was significantly shorter immediately after operation.
After LBBaP was performed, we observed that QRS complex was significantly narrowed to (117.15 ± 9.91) ms. It can be seen that electrical synchronization can be achieved immediately after LBBaP.
In addition, LBBaP group can achieve narrower QRS complex than that in CRT group that validated the previous research in our center . We also compared the difference of QRS wave between the two groups and found that LBBaP group performed better. The change of QRS between LBBaP and CRT group also shows significant statistical difference, it can be seen that LBBaP group perform better on the improvement of QRS wave, and LBBaP achieves better effect on electrical resynchronization.
Cardiac resynchronization therapy is traditional method for the treatment of heart failure with biventricular asynchronization in which QRS wave width is greater than 150 ms. However, biventricular pacing is the fusion of left and right two-point pacing, which is different from the normal conduction direction. The left ventricular electrode is located in the epicardium of the left ventricle, and cardiac excitation is from the epicardium to the endocardium, which is contrary to the physiological way of excitation from the endocardium to the epicardium. This is also the  than RVP. The pacing site is far from His bundle, which can surpass the blocking site, and the pacing range is relatively large. Therefore, the pacing threshold is low, the parameters are stable, and the safety is better.
In our study, we can see that the pacing threshold, R-wave amplitude, and lead impedance of left ventricular electrodes were stable after 12 months of follow-up. We carefully evaluated the electrode parameters at postoperative, 6 months, and 12 months after surgery; there was no significant difference among the three point of time. It can be seen that LBBaP is a safe pacing mode.
Professor Chen (Mafi-Rad et al., 2016) also suggested that direct left ventricular middle septal pacing could be considered for LBBaP for those LBB could not be corrected or whose parameters were not good, that is placing the electrode at the middle part of the LV septum by transseptal approach which may achieve a relatively narrow QRS duration it can be an alternative way. In our study, LBBaP performed successfully, so this implantation method was not adopted. We evaluated the improvement of LBBaP on cardiac function by echocardiographic results. After 6 months' follow-up in LBBaP group, EF was significantly higher than that before operation.
Followed up for 12 months after operation, EF and LVEDD in LBBaP group were significantly improved compared with those before operation. And the results of EF and LVEDD between the two groups at 12 months' follow-up were also significantly different. It can be seen that after 1 year of cardiac pacing treatment, LBBaP group performed better in the improvement of EF and LVEDD.
There is obvious advantages of LBBaP group over CRT group; LBBaP has shorter operation time and less radiation damage to the operator. In this study, it can be seen that the total operation time and X-ray exposure time of LBBaP group are significantly shorter than those of CRT group. These findings concluded that LBBaP had better operability and was more friendly to the operators than CRT group. Finally, although the results confirm recent improvements in electrical and structural resynchronization, we still need longer follow-up to evaluate parameters and long-term structural remodeling after electrical resynchronization.

| CON CLUS ION
Left bundle branch area pacing group and CRT group can achieve the same effect in correcting left bundle branch block of ECG and improving cardiac function in patients with dilated cardiomyopathy.
They can effectively shorten QRS wave duration and improve cardiac function. After a medium-term follow-up, LBBaP showed stable threshold and better improvement of QRS wave duration and improved cardiac function. Because of its shorter operation time and X-ray exposure time, and simpler implantation process than CRT, it can be applied to patients with left ventricular electrode implantation difficulties and as a supplementary treatment for patients who cannot benefit from CRT.

CO N FLI C T O F I NTE R E S T
The authors claim that there is no conflict of interest.

E TH I C A L A PPROVA L
This study was approved by the Ethics Committee of Beijing Anzhen Hospital.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.