- Email: [email protected]
Left bundle branch pacing for symptomatic bradycardia: Implant success rate, safety, and pacing characteristics
Accepted Manuscript Left bundle branch pacing for symptomatic bradycardia: Implant success rate, safety and pacing characteristics Yuqiu Li, MD, Keping Chen, MD, PhD, FHRS, Yan Dai, MD, PhD, Chao Li, MD, Qi Sun, MD, PhD, Ruohan Chen, MD, PhD, Michael R. Gold, MD, PhD, FHRS, Shu Zhang, MD, PhD, FHRS PII:
S1547-5271(19)30455-2
DOI:
https://doi.org/10.1016/j.hrthm.2019.05.014
Reference:
HRTHM 8026
To appear in:
Heart Rhythm
Received Date: 16 December 2018
Please cite this article as: Li Y, Chen K, Dai Y, Li C, Sun Q, Chen R, Gold MR, Zhang S, Left bundle branch pacing for symptomatic bradycardia: Implant success rate, safety and pacing characteristics, Heart Rhythm (2019), doi: https://doi.org/10.1016/j.hrthm.2019.05.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Left bundle branch pacing for symptomatic bradycardia: Implant success rate, safety and pacing
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characteristics
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Yuqiu Li, MD*, Keping Chen, MD, PhD, FHRS*, Yan Dai, MD, PhD*, Chao Li, MD*, Qi Sun, MD,
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PhD*, Ruohan Chen, MD, PhD*, Michael R. Gold, MD, PhD, FHRS†, Shu Zhang, MD, PhD, FHRS*
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Institute: * State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital,
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National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union
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Medical College, Beijing, China and
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Charleston, SC, USA.
Division of Cardiology, Medical University of South Carolina,
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Corresponding author: Dr. Keping Chen, State Key Laboratory of Cardiovascular Disease, Arrhythmia
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Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical
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Sciences and Peking Union Medical College, No.167 North Lishi Road, Xicheng District, Beijing,
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100037, China. Tel: +86 10 8832 2295, E-mail address: [email protected].
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Conflict of interest
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Dr. Gold receives consulting fees and honoraria from Medtronic and Boston Scientific. Other authors
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declare that they have no conflicts of interest.
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ACCEPTED MANUSCRIPT Abstract
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Background Among patients with or without left bundle branch block (LBBB), pacing the LBB
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(LBBP) can produce near normalization of QRS duration (QRSd). This has recently emerged as an
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alternative technique to His bundle pacing.
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Objectives To characterize a novel approach for LBBP among patients with a bradycardia indication
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for pacing and to assess implant success rate and mid-term safety.
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Methods Patients with bradycardia indications for pacing underwent LBBP by trans-ventricular-septal
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method in the basal ventricular septum. Procedural success, pacing parameters and complications were
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assessed at implantation and at 3 months follow-up.
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Results This prospective study evaluated 87 patients (sinus node dysfunction 68%; AV conduction
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disease 32%) undergoing pacemaker implantation. LBBP implantation succeeded in 70 (80.5%)
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patients and the remaining 17 patients received right ventricular septal pacing (RVSP). Procedure time
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of LBBP implantation was 18.0±8.8 min with fluoroscopic exposure time of 3.9±2.7 min. LBBP
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produced narrower ECG QRSd than RVSP (113.2±9.9 ms vs 144.4±12.8 ms, p<0.001). There were no
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major implantation-related complications. Pacing threshold was low (0.76±0.22 V at implant and
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0.71±0.23 V at 3 months) with no loss of capture or lead dislodgement observed.
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Conclusion This study demonstrates that in patients with standard bradycardia pacing indications,
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LBBP results in QRS duration< 120 ms in most patients and can be performed successfully and safely
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in the majority of patients.
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Keywords Left bundle branch pacing; Physiological pacing; Bradycardia; Success rate; Pacemaker
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Introduction Cardiac pacing is the only effective therapy for patients with symptomatic bradycardia in the
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absence of reversible causes. Traditional right ventricular apical pacing (RVAP) has been widely used
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for about 50 years. However, RVAP can lead to ventricular electrical and mechanical asynchrony in
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patients who need frequent pacing. As a consequence of such effects, RVAP is associated with an
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increased risk of heart failure, mitral valve dysfunction and atrial fibrillation1-3. Pacing at alternative
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right ventricular sites, such as the septum or outflow tract, have not been shown to be superior to RVAP
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(HBP) is the most commonly employed approach6, 7, with multiple studies demonstrating feasibility
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and clinical benefits 8-11. However, HBP also has some limitations, including high and unstable pacing
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threshold, low R-wave amplitude, damage to the His bundle during implantation, and potential
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limitations in long-term performance6, 12. To help address these issues, techniques for pacing the left
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bundle branch in patients with left bundle branch block were developed13, 14. We recently reported the
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first clinical implementation of LBBP achieved via trans-ventricular-septal approach in bradycardia
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patients which demonstrated low and stable pacing threshold and large R-wave amplitude and shorter
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paced QRS duration (QRSd) compared to RV septal and apical pacing14. The aim of the present study is
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to assess success rate, safety, pacing characteristics and mid-term outcomes of LBBP.
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. Accordingly, there has been increased interest in physiologic pacing techniques. His bundle pacing
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Methods
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Patient selection
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From October 2017 to October 2018, patients who had symptomatic bradycardia with an indication for
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pacemaker implantation according to 2013 ESC/EHRA Guidelines underwent attempts for LBBP at 3
ACCEPTED MANUSCRIPT Beijing Fuwai Hospital after informed written consent was obtained. Patients were excluded if they
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underwent cardiac resynchronization therapy (CRT) or implantable cardioverter defibrillator (ICD)
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implantation. This study was approved by the hospital Institutional Review Board.
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Lead implantation
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An intracardiac electrogram (EGM) from the lead tip and 12-lead surface electrocardiogram (ECG) were simultaneously recorded on a multichannel Bard recorder (Bard Electrophysiology Lab System,
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MA, USA).
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LBBP was achieved by trans-ventricular-septal method in the basal ventricular septum
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(Supplemental Materials, PowerPoint) and performed by using the Select Secure pacing lead (Model
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3830 69cm, Medtronic Inc., Minneapolis, MN, USA) delivered through a fixed curve sheath (C315
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HIS, Medtronic Inc., Minneapolis, MN USA). During implantation, the tip electrode of the lead was
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used for unipolar pacing and recording. There were two methods of LBBP lead implantation. The first
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technique used His bundle region as an anatomic marker. Briefly, the delivery sheath with the lead tip
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just beyond the distal part of the sheath under 30-degree right anterior oblique (RAO) was first inserted
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into the His bundle region where the His bundle potential was recorded. The His bundle region was
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referred as a marker, the sheath with the lead was further advanced towards the ventricular septum.
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Once the lead touched the right side of the septum and paced QRS morphology showed ECG LBBB
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morphology during pacing with an output of 5V/0.5ms, the lead was pointed towards the left side of the
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septum and screwed in place. During the lead advancement procedure, paced QRS morphology and
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pacing impedance were closely monitored. Once paced QRS morphology showed right bundle branch
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delay (RBBD; usually QR or rSR in ECG lead V1/2) or near normal QRS complex, the lead
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advancement was stopped. In the second technique, the sheath was directly inserted into the right
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the tip of the sheath. Subsequently, the sheath and the lead touched the right side of the septum and
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pacing with an output of 2.0 V/0.5ms was applied. Once the paced ECG QRS morphology presented as
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LBBB morphology frequently with a notch (also called “W” waveform) at the nadir of the QRS
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waveform in ECG lead V1, then the lead was then fixed at this position with 4–5 clockwise rotations.
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High quality fluoroscopic radiograph confirmed the tip of the lead towards the septum in 30-degree left
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anterior oblique (LAO). Then the lead was screwed towards the left side of the septum under 30-degree
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RAO. Once paced QRS morphology became RBBD or near normal QRS complex, the lead
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advancement was stopped. The depth of the lead inside the ventricular septum could be estimated by
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fluoroscopic imaging with contrast injection (Supplemental Materials, Video 1). If an acceptable LBBP
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could not be achieved after attempts at 3 locations, then the lead was placed in the right ventricular
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As shown in Figure 1, in some special cases, especially in patients with bundle branch block, two
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sets of 3830 lead and C315 His delivery sheath were used to find an optimal pacing site. The first lead
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was placed in the His bundle region as an anatomic marker, and the second lead was then positioned in
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left bundle branch region. Once LBBP was acceptable, the first lead was then moved to the right
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atrium.
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Definitions
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The criteria for LBBP were as defined previously14: (1) left bundle branch potential could be
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recorded; (2) the interval from pacing to ECG QRS was significantly shorter than the interval of His
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pacing to ECG QRS reported previously; (3) 12-lead ECG showed the pattern of RBBD during LBBP
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or correction of LBBB if the patient had ECG LBBB; and (4) a fast LV peak activation time in ECG 5
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V5/6 is observed. Selective LBBP is defined as follows:
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1.
There is an isoelectric interval between pacing spike and ECG QRS.
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The pacing spike-QRS interval is almost identical with the left bundle potential-QRS
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interval.
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3.
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Non-selective LBBP is defined by the following criteria:
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There is no isoelectric interval between pacing spike and surface ECG QRS complex.
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The local ventricular electrogram shows a direct capture of local tissue by the pacing
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stimulus.
Examples of selective and non-selective LBBP are shown in figure 2 and 3. Device programming
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A local ventricular electrogram is present as a discrete component.
Ventricular safety pacing and auto capture management were activated. AV delay programming
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should be individualized, taking into consideration of the AV conduction times and the presence of
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heart block. The automatic AV search function was routinely turned on in patients with sick sinus
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syndrome (SSS) and intermittent AV block (AVB).
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Data collection and follow-up
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Demographic and medical history were collected at enrollment. Pacing electrical parameters
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(pacing threshold, lead impedance, and R-wave amplitude), ECG and intracardiac EGM pattern, QRSd,
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LV peak activation time, the pacing-QRS interval, the amplitude of left bundle branch potential, the
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interval from left bundle branch potential to the beginning of ECG QRS, fluoroscopy exposure time
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and imaging data were recorded during implantation. Patients were followed at pre-discharge and 3 6
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significant increases in pacing threshold, loss of capture, and lead dislodgement were tracked during
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follow-up visits.
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Statistical analysis
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The mean and standard deviation were used as the descriptive statistics for continuous variables
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and the number and percentage as descriptive statistics for categorical variables. Differences between
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two groups were compared using Student’s t-test for continuous variables. Paired t-test was used to
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compare the differences between two means within the same group. Analysis of variance (ANOVA)
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test was performed for multiple comparisons among three or more conditions and post hoc tests with
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least-significant difference were performed for the variables that showed a statistically significant
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difference. A two-sided P value <0.05 was considered statistically significant. All statistical analyses
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were performed using SPSS Statistics version 22.0 (Chicago, IL, USA).
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Results
Between October 2017 and October 2018, a total of 87 patients with bradycardia underwent
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LBBP attempts. Indications for pacemaker implantation were sinus node dysfunction in 59 patients
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(68%) and AV conduction disease in 28 patients (32%). The left ventricular ejection fraction (LVEF)
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was 62.9±5.6%. Baseline patient characteristics are shown in Table 1.
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Implantation results
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LBBP was successful in 70 (80.5%) patients and the remaining 17 patients received right ventricular
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septal pacing (RVSP). For LBBP, a single-chamber pacemaker was implanted in 2 (2.3%) patients and
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a dual-chamber pacemaker in the remaining 68 (97.1%) patients. Mean procedure time of LBBP
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unsuccessful LBBP implantation was due to the failure of the lead tip to advance successfully to the
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left side of the septum. In these instances, the lead tip remained on the right side of the septum or was
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in the middle of the septum, but could not reach the left side of the septum. Possible causes of these
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failures may be related to the direction that the tip advanced with deployment, lead design limitation or
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local hypertrophied myocardium.
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ECG characteristics
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There was a typical transition of ECG morphology during the lead implantation for LBBP. During
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the process of deploying the pacing lead from the right to the left side of the septum, the paced ECG
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morphology changed from LBBB to RBBD with a gradual change of the notch morphology in V1 lead
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(Figure 4).
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The average QRS duration (QRSd) was 105.5±22.2 ms, and the paced QRSd was 113.2±9.9 ms
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(P<0.05). During the implantation procedure, the paced QRSd during LBBP was significantly shorter
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than pacing at the right side of the septum (113.2±9.9 ms vs. 139.5±12.8ms, P<0.001). Moreover, QRS
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duration was < 120 ms in 56 (80%) of patients with LBBP and no patient (0%) with right septal pacing
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(p<0.001). LV peak activation time was 79.7±8.5 ms during LBBP, which is shorter than pacing at the
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right side of the septum (103.3±11.4, P<0.001). A left bundle branch potential was recorded in 46
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patients (66%), with a mean amplitude of 0.17±0.16mV. LBB potential injury current was observed in
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36 patients (78%). The interval from left bundle branch potential to onset of the QRS on surface ECG
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was 25.6±4.7ms. There was a trend towards shorter paced QRSd among patients with recorded left
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bundle branch potential during intrinsic rhythm compared with patients without left bundle branch
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potential (110.7±9.0 ms vs. 116.2±11.0 ms, P= 0.069).
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left bundle potential-QRS interval (25.6±4.7 ms). During non-selective LBBP, there was no delay in
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the onset of the QRS with no isoelectric interval.
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Pacing electrical parameters and complications
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All patients completed pre-discharge follow-up, and 47 patients reached 3 months post
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implantation and completed 3-month follow-up. Pacing threshold, R-wave amplitude, and lead
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impedance at implantation, pre-discharge, and after 3 months are summarized in Table 2. During the
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follow-up, the pacing threshold remained low while R-wave amplitude increased and pacing
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impedance decreased over the follow-up time.
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During the implantation procedure, there were no major implantation-related complications. One
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patient who was receiving dual antiplatelet therapy developed a pocket hematoma. In 11 patients, a
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right bundle branch block (RBBB) developed during the implant procedure that resolved in all subjects
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before hospital discharge. No patients showed loss of capture nor lead dislodgement during follow-up.
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Discussion
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The present study describes implantation and 3-month follow-up of a novel approach for left
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ventricular pacing to achieve more physiologic ventricular activation compared to RVSP. The main
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findings of this study are that a high success rate of LBBP (80.5%) can be achieved with stable and low
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pacing thresholds over mid-term follow-up. Moreover, there were no serious complications resulting
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from this procedure. Of note, previous studies have shown successful LBBP, but the success rate and
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more long term pacing stability from a large, consecutive series have not been reported13, 14.
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The QRS duration on the surface ECG is a surrogate of ventricular activation time. It is interesting 9
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complete RBBB. This finding may be due to retrograde activation of the right bundle with pacing or
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connections between the main right and left bundles15, 16. Further studies are needed to help sort out the
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mechanism of relatively short paced QRS durations with this technique. Mafi-Rad et. al. investigated
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left ventricular septal pacing (LVSP) by transvenous approach through the interventricular septum and
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found that QRS duration was shorter during LVSP (144±20 ms) than during RVAP (172±33 ms)17.
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Since the pacing lead in Mafi-Rad’s study might not be at or near the left bundle branch, the QRS
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duration (144±20 ms) in that study seems much longer than that during LBBP (113±10 ms) in our
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study.
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The success rate of LBBP in this series is similar to what has been reported with early attempts at
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His bundle pacing18. Further studies are needed to understand both the learning curve of this technique
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as well as the limitations of successful LBB capture. Possible explanations for failure to achieve LBB
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capture include: (1) the inability of the lead to penetrate sufficiently deep in the septum to reach the left
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bundle; (2) the sheath being malpositioned such that the lead is not advanced perpendicular to the
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ventricular septum (Supplemental Material, Figure S1); (3) the failure of the lead tip to be deployed to
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the left side of the septum due to lead design limitation or local hypertrophied myocardium. During
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lead deployment, the flexibility of the delivery sheath, especially the distal part, might decrease by
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repeated procedural maneuvers, such that the lead tip could not be advanced through the sheath. This is
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also the possible reason for failure of achieving LBB capture. It is common to reposition pacing leads
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during right ventricular apical pacing and septal pacing. However, LBBP is achieved by
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trans-ventricular-septal method in the basal ventricular septum, so multiple repositioning attempts
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could cause damage to myocardial tissue and even possible perforation. Thus, we limited the number of
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attempts for LBBP as a precaution which may have decreased success rate. In 2000, Deshmukh et. al. conducted the pioneering investigation of permanent HBP by using a
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traditional pacing lead in a small number of heart failure patients and achieved a success rate of 66%19.
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The development of site-selective implantation tools, including the 3830 pacing lead and the C315 HIS
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delivery sheath, made HBP more feasible20. Vijayaraman et al.21 reported the success rate of 95% in 42
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patients with atrial fibrillation undergoing AV node ablation in a very experienced center. To date, the
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success rate of HBP has been reported to vary from 56% to 95%22-26, which is similar to the success
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rate of 80.5% with LBBP in the present study. With the improvement of implantation tools and
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techniques for standardized LBBP implantation, we expect an increase in success rate. The mean
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duration of fluoroscopy for HBP had ranged from 8-23 minutes.8, 22, 27. LBBP was performed with
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significantly less fluoroscopic exposure time (3.9±2.7 min) in the present study, which may be another
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benefit of this approach.
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Our previous study had demonstrated shorter QRSd with LBBP than with either RVSP or RVAP,
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suggesting that LBBP produces better ventricular electrical synchronization14. Similar results were
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shown in the present study using a different method to perform LBBP. Monitoring the paced ECG
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while deploying the lead was helpful to guide lead placement. During implantation, the ECG transition
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was continuously monitored, and checked with every two to three turns of the lead helix. A notch (“W”
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waveform) in lead V1 gradually shifted and finally disappeared when the tip was advanced from the
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right to the left side of the septum. This observation can be used as a safety check to determine where
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the pacing lead is in the septum and when the advancement of the pacing lead should be stopped. In
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contrast, no change in ECG morphology with advancement of the lead suggests that the lead was not
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advanced into the left side of the septum or this position was not suitable for LBBP. In this scenario, the
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lead should be repositioned. In the present study we demonstrate evidence for both selective and nonselective capture of the
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LBB. Given the immediate proximity of the muscular septum and non-penetrating portion of the left
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bundle, nonselective capture would be expected intuitively to be the more probable pattern. However
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selective capture can be observed especially at low output and/or pulse width. An example of the latter
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is seen in Figure 3 where selective capture occurs at a pulse width of 0.06 msec. The clinical
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implications of these findings are not currently known and will require further study.
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As LBBP is achieved by trans-ventricular-septal method, ventricular septum perforation can occur.
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However, because the diameter of the current lead is 1.4mm, no serious ventricular septal defect is
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expected even if perforation occurs. Nevertheless, it is important to monitor the transition of paced
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QRS morphology, lead impedance and pacing threshold. A low capture threshold and a high pacing
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impedance suggested the pacing lead remained in the septum while a sudden decrease of lead
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impedance and loss of capture indicated the tip of the lead entering the left ventricle. The thickness of
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ventricular septum is normally 6 to 11 mm. The helix electrode length of the lead is 1.8 mm and the
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space from the ring electrode to the helix is 9 mm. The onset of the ring electrode capture at an output
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of 5V/0.5msec suggests that the tip of the lead is likely at or near the left side of the ventricular septum.
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Any further advancement of the lead should be conducted carefully. It is noteworthy that no implant
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complications were noted when taking these precautions.
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There are several advantages of LBBP over HBP. First, high pacing threshold and threshold
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increase over time is relatively frequent with HBP, likely due to the anatomical characteristics of the
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His bundle, inadequate fixation, local fibrosis, tricuspid valve motion, and pathological progression in
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His bundle region. HBP capture threshold shows a clinically significant increase over time in 12
ACCEPTED MANUSCRIPT approximately 10% patients28. LBBP is achieved by trans-ventricular-septal method and the pacing
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lead is positioned in the basal ventricular septum. Left bundle branch usually spreads below the
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membranous septum with well-defined dimensions and there is less fibrosis wrapped than His bundle29.
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Thus, it is not surprising that a lower pacing threshold was noted. Second, because the pacing lead tip
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of LBBP bypasses the vulnerable region of the His bundle, the pacing threshold is stable. Third, since
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the pacing tip is fixed at or near the left bundle branch with nearby myocardial tissue and myocardium
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can be captured at the pacing output, there is no need to implant a back-up lead in case of loss of
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capture. Finally, R-wave amplitude recorded at the site of LBBP is high, which is important for
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appropriate sensing and capture management by a pacemaker. HBP mimics native conduction since
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both fascicles are activated antegradely, however LBBP maintains antegrade activation of the left
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fascicular system and often generates a near normal QRS complex, possibly due to retrograde or
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trans-ventricular-septal activation of the RBB.
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Limitations
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This study should be interpreted in light of certain methodologic limitations. First, the sample
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size was relatively small as a single center study. More data are needed to confirm our findings.
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Selective LBBP may not be clearly observed at implantation because the far-field recording by the
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pacing lead is used and may not show the discrete EGM for selective LBBP. In addition, more long
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term follow-up is needed to assess the stability of pacing in this region of the heart. Finally, the role of
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LBBP needs to be explored for other pacing indications such as CRT.
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Conclusions 13
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80.5% of patients in a consecutive series. The accurate location for LBBP can be targeted during
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implantation given the characteristic changes in paced QRS morphology during lead deployment. The
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low pacing output and high R-wave amplitude during LBBP favor long-term pacing management and
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device longevity. LBBP produces a narrow QRS duration and short LV peak activation time, suggesting
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synchronized ventricular activation. LBBP may be an ideal option for patients in need of ventricular
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pacing once long-term safety and clinical benefits are confirmed.
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Acknowledgement: None.
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Funding: This research did not receive any specific grant from funding agencies in the public,
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commercial, or not-for-profit sectors.
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Preserved and Reduced Left Ventricular Ejection Fraction. J Am Heart Assoc 2017;6: e005309.. 10.
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Huang W, Su L, Wu S, et al. Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block. Heart 2018. doi: 10.1136/heartjnl-2018-313415.
11.
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Yu Z, Chen R, Su Y, et al. Integrative and quantitive evaluation of the efficacy of his bundle related pacing in comparison with conventional right ventricular pacing: a meta-analysis. BMC
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2017;17:221. doi: 10.1186/s12872-017-0649-4. 12.
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Subzposh FA, Vijayaraman P. Long-Term Results of His Bundle Pacing. Card Electrophysiol Clin 2018;10:537-542.
13.
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Huang W, Su L, Wu S, et al. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol
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2017;33:1736.e1731-1736.e1733.
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14.
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Chen K, Li Y, Dai Y, et al. (2018). Comparison of electrocardiogram characteristics and pacing parameters between left bundle branch pacing and right ventricular pacing in patients receiving
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pacemaker therapy. Europace, doi:10.1093/europace/euy252. 15.
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16.
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James TN, Sherf L. Fine structure of the His bundle. Circulation 1971;44:9-28.
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Barba-Pichardo R1, Moriña-Vázquez P, Venegas-Gamero J, Maroto-Monserrat F, Cid-Cumplido
M, Herrera-Carranza M. Permanent His-bundle pacing in patients with infra-Hisian atrioventricular block. Rev Esp Cardiol 2006;59:553-558.
17.
Mafi-Rad M, Luermans JG, Blaauw Y, Janssen M, Crijns HJ, Prinzen FW, et al. Feasibility and
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Acute Hemodynamic Effect of Left Ventricular Septal Pacing by Transvenous Approach
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Through the Interventricular Septum. Circ Arrhythm Electrophysiol 2016; 9: e003344. 16
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18.
Bhatt AG, Musat DL, Milstein N, et al. The Efficacy of His Bundle Pacing: Lessons Learned
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From Implementation for the First Time at an Experienced Electrophysiology Center. JACC Clin
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Electrophysiol 2018;4:1397-1406. 19.
Deshmukh P, Casavant DA, Romanyshyn M, Anderson K. Permanent, direct His-bundle pacing:
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a novel approach to cardiac pacing in patients with normal His-Purkinje activation. Circulation
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2000;101:869-877. 20.
Gammage MD, Lieberman RA, Yee R, et al. Multi-center clinical experience with a lumenless,
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catheter-delivered, bipolar, permanent pacemaker lead: implant safety and electrical
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performance. Pacing Clin Electrophysiol 2006;29:858-865.
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21.
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Vijayaraman P, Subzposh FA, Naperkowski A. Atrioventricular node ablation and His bundle pacing. Europace 2017;19:iv10-iv16.
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Barba-Pichardo R, Manovel Sanchez A, Fernandez-Gomez JM, Morina-Vazquez P,
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Venegas-Gamero J, Herrera-Carranza M. Ventricular resynchronization therapy by direct
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His-bundle pacing using an internal cardioverter defibrillator. Europace 2013;15:83-88. 23.
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pacing in cardiac resynchronization therapy patients: A crossover design comparison. Heart
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rhythm 2015;12:1548-1557.
24.
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Ajijola OA, Upadhyay GA, Macias C, Shivkumar K, Tung R. Permanent His-bundle pacing for
cardiac resynchronization therapy: Initial feasibility study in lieu of left ventricular lead. Heart
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Lustgarten DL, Crespo EM, Arkhipova-Jenkins I, et al. His-bundle pacing versus biventricular
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rhythm 2017;14:1353-1361. 25.
Vijayaraman P, Naperkowski A, Ellenbogen KA, Dandamudi G. Electrophysiologic Insights Into Site of Atrioventricular Block: Lessons From Permanent His Bundle Pacing. JACC Clin 17
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Electrophysiol 2015;1:571-581. 26.
Occhetta E, Bortnik M, Magnani A, et al. Prevention of ventricular desynchronization by permanent para-Hisian pacing after atrioventricular node ablation in chronic atrial fibrillation: a
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crossover, blinded, randomized study versus apical right ventricular pacing. J Am Coll Cardiol
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2006;47:1938-1945.
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27.
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Zanon F, Baracca E, Aggio S, et al. A feasible approach for direct his-bundle pacing using a new steerable catheter to facilitate precise lead placement. J Cardiovasc Electrophysiol
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2006;17:29-33. 28.
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388 389 390 391 392 393
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Elizari MV. The normal variants in the left bundle branch system. J Electrocardiol 2017; 50:389-399.
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implants. Heart rhythm 2018;15:1428-1431.
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Table 1. Baseline Patient Characteristics All (n=87) Age (years)
63.8±11.4 31 (35.60)
Sinus node dysfunction (%)
59 (67.80)
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Men (%)
AV conduction disease (%)
28 (32.20)
Coronary artery disease (%)
22 (25.30)
Diabetes mellitus (%)
18 (20.69) 50 (57.50)
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Hypertension (%) Atrial fibrillation (%)
LVEDD (mm) Dual-chamber pacemaker implanted (%) Single-chamber pacemaker implanted (%) QRSd (ms)
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Normal QRS complex, LBBB, RBBB
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20 (22.73) 62.86±5.64 47.81±5.08 84 (96.60) 3 (3.40) 106.84±23.28 76,
6,
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Data are presented as mean ± standard deviation (SD) for continuous variables, and number of subjects
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(n) and percentage (%), respectively, for categorical variables.
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LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; QRSd, QRS
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duration.
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Table 2. Electrical Parameters Visit
Pacing
R-wave amplitude, mV
Impedance, Ohms
700.14±134.87
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11.99±5.36
Pre-discharge (n =70)
0.51±0.10
16.16±6.48
3-month follow-up (n =47)
0.71±0.23
16.90±6.78
Values are mean ± SD.
: P <0.001 at implantation vs. Pre-discharge, 3-month follow-up; 3-month follow-up.
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501.01±96.88 472.40±91.41
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0.76±0.22
: P<0.001 pre-discharge vs.
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At implantation (n =70)
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ACCEPTED MANUSCRIPT Figure 1. Fluoroscopic projections showing dual leads with one lead for His bundle location and the
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second lead for left bundle branch pacing. Panel A: the first pacing lead (His lead) in the His bundle
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region; Panel B: the second pacing lead (LBB lead) on the right side of the septum before screwing;
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Panel C: the tip of LBB lead perpendicular to the septum; Panel D: LBB lead in the left bundle branch
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region on the left side of the septum after screwing the lead.
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dysfunction. Panel A: the left bundle branch potential during intrinsic rhythm (red asterisks); Panel B:
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selective left bundle branch pacing with discrete local ventricular electrogram (black arrow) at LBBP
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threshold (0.2V/0.5ms); Panel C: non-selective left bundle branch pacing with local myocardial fusion
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(red circle) during pacing at 0.5V/0.5ms, there is no discrete local ventricular electrogram.
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ACCEPTED MANUSCRIPT 455 Figure 3. Post-implantation 12-Lead ECG of selective left bundle branch pacing and non-selective left
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bundle branch pacing in a patient with sinus node dysfunction. Panel A: selective left bundle branch
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pacing without local myocardial fusion (red circle) during pacing at 1.25V/0.06ms; Panel B:
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non-selective left bundle branch pacing with local myocardial fusion (red circle) during pacing at
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1.5V/0.06ms. (5mm/mV, 50mm/s).
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ACCEPTED MANUSCRIPT 468 Figure 4. 12-Lead ECG and EGM showing the change of the notch in V1 lead (red frame) during
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rotating the lead from the right side (far left ECG) to the left side (ECG far right) of the septum.
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S1547-5271(19)30455-2
DOI:
https://doi.org/10.1016/j.hrthm.2019.05.014
Reference:
HRTHM 8026
To appear in:
Heart Rhythm
Received Date: 16 December 2018
Please cite this article as: Li Y, Chen K, Dai Y, Li C, Sun Q, Chen R, Gold MR, Zhang S, Left bundle branch pacing for symptomatic bradycardia: Implant success rate, safety and pacing characteristics, Heart Rhythm (2019), doi: https://doi.org/10.1016/j.hrthm.2019.05.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Left bundle branch pacing for symptomatic bradycardia: Implant success rate, safety and pacing
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characteristics
3 Short title: Left bundle branch pacing
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Yuqiu Li, MD*, Keping Chen, MD, PhD, FHRS*, Yan Dai, MD, PhD*, Chao Li, MD*, Qi Sun, MD,
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PhD*, Ruohan Chen, MD, PhD*, Michael R. Gold, MD, PhD, FHRS†, Shu Zhang, MD, PhD, FHRS*
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Institute: * State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital,
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National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union
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Medical College, Beijing, China and
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Charleston, SC, USA.
Division of Cardiology, Medical University of South Carolina,
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†
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Corresponding author: Dr. Keping Chen, State Key Laboratory of Cardiovascular Disease, Arrhythmia
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Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical
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Sciences and Peking Union Medical College, No.167 North Lishi Road, Xicheng District, Beijing,
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100037, China. Tel: +86 10 8832 2295, E-mail address: [email protected].
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Conflict of interest
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Dr. Gold receives consulting fees and honoraria from Medtronic and Boston Scientific. Other authors
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declare that they have no conflicts of interest.
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Word count: 4959 1
ACCEPTED MANUSCRIPT Abstract
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Background Among patients with or without left bundle branch block (LBBB), pacing the LBB
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(LBBP) can produce near normalization of QRS duration (QRSd). This has recently emerged as an
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alternative technique to His bundle pacing.
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Objectives To characterize a novel approach for LBBP among patients with a bradycardia indication
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for pacing and to assess implant success rate and mid-term safety.
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Methods Patients with bradycardia indications for pacing underwent LBBP by trans-ventricular-septal
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method in the basal ventricular septum. Procedural success, pacing parameters and complications were
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assessed at implantation and at 3 months follow-up.
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Results This prospective study evaluated 87 patients (sinus node dysfunction 68%; AV conduction
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disease 32%) undergoing pacemaker implantation. LBBP implantation succeeded in 70 (80.5%)
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patients and the remaining 17 patients received right ventricular septal pacing (RVSP). Procedure time
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of LBBP implantation was 18.0±8.8 min with fluoroscopic exposure time of 3.9±2.7 min. LBBP
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produced narrower ECG QRSd than RVSP (113.2±9.9 ms vs 144.4±12.8 ms, p<0.001). There were no
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major implantation-related complications. Pacing threshold was low (0.76±0.22 V at implant and
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0.71±0.23 V at 3 months) with no loss of capture or lead dislodgement observed.
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Conclusion This study demonstrates that in patients with standard bradycardia pacing indications,
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LBBP results in QRS duration< 120 ms in most patients and can be performed successfully and safely
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in the majority of patients.
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Keywords Left bundle branch pacing; Physiological pacing; Bradycardia; Success rate; Pacemaker
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Introduction Cardiac pacing is the only effective therapy for patients with symptomatic bradycardia in the
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absence of reversible causes. Traditional right ventricular apical pacing (RVAP) has been widely used
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for about 50 years. However, RVAP can lead to ventricular electrical and mechanical asynchrony in
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patients who need frequent pacing. As a consequence of such effects, RVAP is associated with an
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increased risk of heart failure, mitral valve dysfunction and atrial fibrillation1-3. Pacing at alternative
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right ventricular sites, such as the septum or outflow tract, have not been shown to be superior to RVAP
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3-5
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(HBP) is the most commonly employed approach6, 7, with multiple studies demonstrating feasibility
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and clinical benefits 8-11. However, HBP also has some limitations, including high and unstable pacing
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threshold, low R-wave amplitude, damage to the His bundle during implantation, and potential
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limitations in long-term performance6, 12. To help address these issues, techniques for pacing the left
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bundle branch in patients with left bundle branch block were developed13, 14. We recently reported the
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first clinical implementation of LBBP achieved via trans-ventricular-septal approach in bradycardia
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patients which demonstrated low and stable pacing threshold and large R-wave amplitude and shorter
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paced QRS duration (QRSd) compared to RV septal and apical pacing14. The aim of the present study is
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to assess success rate, safety, pacing characteristics and mid-term outcomes of LBBP.
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. Accordingly, there has been increased interest in physiologic pacing techniques. His bundle pacing
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Methods
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Patient selection
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From October 2017 to October 2018, patients who had symptomatic bradycardia with an indication for
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pacemaker implantation according to 2013 ESC/EHRA Guidelines underwent attempts for LBBP at 3
ACCEPTED MANUSCRIPT Beijing Fuwai Hospital after informed written consent was obtained. Patients were excluded if they
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underwent cardiac resynchronization therapy (CRT) or implantable cardioverter defibrillator (ICD)
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implantation. This study was approved by the hospital Institutional Review Board.
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Lead implantation
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An intracardiac electrogram (EGM) from the lead tip and 12-lead surface electrocardiogram (ECG) were simultaneously recorded on a multichannel Bard recorder (Bard Electrophysiology Lab System,
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MA, USA).
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LBBP was achieved by trans-ventricular-septal method in the basal ventricular septum
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(Supplemental Materials, PowerPoint) and performed by using the Select Secure pacing lead (Model
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3830 69cm, Medtronic Inc., Minneapolis, MN, USA) delivered through a fixed curve sheath (C315
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HIS, Medtronic Inc., Minneapolis, MN USA). During implantation, the tip electrode of the lead was
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used for unipolar pacing and recording. There were two methods of LBBP lead implantation. The first
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technique used His bundle region as an anatomic marker. Briefly, the delivery sheath with the lead tip
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just beyond the distal part of the sheath under 30-degree right anterior oblique (RAO) was first inserted
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into the His bundle region where the His bundle potential was recorded. The His bundle region was
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referred as a marker, the sheath with the lead was further advanced towards the ventricular septum.
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Once the lead touched the right side of the septum and paced QRS morphology showed ECG LBBB
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morphology during pacing with an output of 5V/0.5ms, the lead was pointed towards the left side of the
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septum and screwed in place. During the lead advancement procedure, paced QRS morphology and
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pacing impedance were closely monitored. Once paced QRS morphology showed right bundle branch
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delay (RBBD; usually QR or rSR in ECG lead V1/2) or near normal QRS complex, the lead
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advancement was stopped. In the second technique, the sheath was directly inserted into the right
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the tip of the sheath. Subsequently, the sheath and the lead touched the right side of the septum and
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pacing with an output of 2.0 V/0.5ms was applied. Once the paced ECG QRS morphology presented as
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LBBB morphology frequently with a notch (also called “W” waveform) at the nadir of the QRS
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waveform in ECG lead V1, then the lead was then fixed at this position with 4–5 clockwise rotations.
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High quality fluoroscopic radiograph confirmed the tip of the lead towards the septum in 30-degree left
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anterior oblique (LAO). Then the lead was screwed towards the left side of the septum under 30-degree
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RAO. Once paced QRS morphology became RBBD or near normal QRS complex, the lead
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advancement was stopped. The depth of the lead inside the ventricular septum could be estimated by
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fluoroscopic imaging with contrast injection (Supplemental Materials, Video 1). If an acceptable LBBP
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could not be achieved after attempts at 3 locations, then the lead was placed in the right ventricular
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As shown in Figure 1, in some special cases, especially in patients with bundle branch block, two
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sets of 3830 lead and C315 His delivery sheath were used to find an optimal pacing site. The first lead
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was placed in the His bundle region as an anatomic marker, and the second lead was then positioned in
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left bundle branch region. Once LBBP was acceptable, the first lead was then moved to the right
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atrium.
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Definitions
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The criteria for LBBP were as defined previously14: (1) left bundle branch potential could be
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recorded; (2) the interval from pacing to ECG QRS was significantly shorter than the interval of His
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pacing to ECG QRS reported previously; (3) 12-lead ECG showed the pattern of RBBD during LBBP
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or correction of LBBB if the patient had ECG LBBB; and (4) a fast LV peak activation time in ECG 5
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V5/6 is observed. Selective LBBP is defined as follows:
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1.
There is an isoelectric interval between pacing spike and ECG QRS.
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2.
The pacing spike-QRS interval is almost identical with the left bundle potential-QRS
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interval.
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3.
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Non-selective LBBP is defined by the following criteria:
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There is no isoelectric interval between pacing spike and surface ECG QRS complex.
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The local ventricular electrogram shows a direct capture of local tissue by the pacing
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stimulus.
Examples of selective and non-selective LBBP are shown in figure 2 and 3. Device programming
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A local ventricular electrogram is present as a discrete component.
Ventricular safety pacing and auto capture management were activated. AV delay programming
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should be individualized, taking into consideration of the AV conduction times and the presence of
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heart block. The automatic AV search function was routinely turned on in patients with sick sinus
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syndrome (SSS) and intermittent AV block (AVB).
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Data collection and follow-up
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Demographic and medical history were collected at enrollment. Pacing electrical parameters
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(pacing threshold, lead impedance, and R-wave amplitude), ECG and intracardiac EGM pattern, QRSd,
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LV peak activation time, the pacing-QRS interval, the amplitude of left bundle branch potential, the
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interval from left bundle branch potential to the beginning of ECG QRS, fluoroscopy exposure time
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and imaging data were recorded during implantation. Patients were followed at pre-discharge and 3 6
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significant increases in pacing threshold, loss of capture, and lead dislodgement were tracked during
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follow-up visits.
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Statistical analysis
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The mean and standard deviation were used as the descriptive statistics for continuous variables
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and the number and percentage as descriptive statistics for categorical variables. Differences between
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two groups were compared using Student’s t-test for continuous variables. Paired t-test was used to
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compare the differences between two means within the same group. Analysis of variance (ANOVA)
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test was performed for multiple comparisons among three or more conditions and post hoc tests with
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least-significant difference were performed for the variables that showed a statistically significant
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difference. A two-sided P value <0.05 was considered statistically significant. All statistical analyses
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were performed using SPSS Statistics version 22.0 (Chicago, IL, USA).
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Results
Between October 2017 and October 2018, a total of 87 patients with bradycardia underwent
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LBBP attempts. Indications for pacemaker implantation were sinus node dysfunction in 59 patients
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(68%) and AV conduction disease in 28 patients (32%). The left ventricular ejection fraction (LVEF)
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was 62.9±5.6%. Baseline patient characteristics are shown in Table 1.
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Implantation results
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LBBP was successful in 70 (80.5%) patients and the remaining 17 patients received right ventricular
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septal pacing (RVSP). For LBBP, a single-chamber pacemaker was implanted in 2 (2.3%) patients and
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a dual-chamber pacemaker in the remaining 68 (97.1%) patients. Mean procedure time of LBBP
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unsuccessful LBBP implantation was due to the failure of the lead tip to advance successfully to the
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left side of the septum. In these instances, the lead tip remained on the right side of the septum or was
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in the middle of the septum, but could not reach the left side of the septum. Possible causes of these
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failures may be related to the direction that the tip advanced with deployment, lead design limitation or
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local hypertrophied myocardium.
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ECG characteristics
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There was a typical transition of ECG morphology during the lead implantation for LBBP. During
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the process of deploying the pacing lead from the right to the left side of the septum, the paced ECG
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morphology changed from LBBB to RBBD with a gradual change of the notch morphology in V1 lead
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(Figure 4).
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The average QRS duration (QRSd) was 105.5±22.2 ms, and the paced QRSd was 113.2±9.9 ms
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(P<0.05). During the implantation procedure, the paced QRSd during LBBP was significantly shorter
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than pacing at the right side of the septum (113.2±9.9 ms vs. 139.5±12.8ms, P<0.001). Moreover, QRS
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duration was < 120 ms in 56 (80%) of patients with LBBP and no patient (0%) with right septal pacing
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(p<0.001). LV peak activation time was 79.7±8.5 ms during LBBP, which is shorter than pacing at the
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right side of the septum (103.3±11.4, P<0.001). A left bundle branch potential was recorded in 46
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patients (66%), with a mean amplitude of 0.17±0.16mV. LBB potential injury current was observed in
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36 patients (78%). The interval from left bundle branch potential to onset of the QRS on surface ECG
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was 25.6±4.7ms. There was a trend towards shorter paced QRSd among patients with recorded left
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bundle branch potential during intrinsic rhythm compared with patients without left bundle branch
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potential (110.7±9.0 ms vs. 116.2±11.0 ms, P= 0.069).
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left bundle potential-QRS interval (25.6±4.7 ms). During non-selective LBBP, there was no delay in
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the onset of the QRS with no isoelectric interval.
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Pacing electrical parameters and complications
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All patients completed pre-discharge follow-up, and 47 patients reached 3 months post
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implantation and completed 3-month follow-up. Pacing threshold, R-wave amplitude, and lead
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impedance at implantation, pre-discharge, and after 3 months are summarized in Table 2. During the
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follow-up, the pacing threshold remained low while R-wave amplitude increased and pacing
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impedance decreased over the follow-up time.
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During the implantation procedure, there were no major implantation-related complications. One
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patient who was receiving dual antiplatelet therapy developed a pocket hematoma. In 11 patients, a
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right bundle branch block (RBBB) developed during the implant procedure that resolved in all subjects
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before hospital discharge. No patients showed loss of capture nor lead dislodgement during follow-up.
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Discussion
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The present study describes implantation and 3-month follow-up of a novel approach for left
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ventricular pacing to achieve more physiologic ventricular activation compared to RVSP. The main
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findings of this study are that a high success rate of LBBP (80.5%) can be achieved with stable and low
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pacing thresholds over mid-term follow-up. Moreover, there were no serious complications resulting
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from this procedure. Of note, previous studies have shown successful LBBP, but the success rate and
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more long term pacing stability from a large, consecutive series have not been reported13, 14.
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complete RBBB. This finding may be due to retrograde activation of the right bundle with pacing or
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connections between the main right and left bundles15, 16. Further studies are needed to help sort out the
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mechanism of relatively short paced QRS durations with this technique. Mafi-Rad et. al. investigated
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left ventricular septal pacing (LVSP) by transvenous approach through the interventricular septum and
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found that QRS duration was shorter during LVSP (144±20 ms) than during RVAP (172±33 ms)17.
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Since the pacing lead in Mafi-Rad’s study might not be at or near the left bundle branch, the QRS
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duration (144±20 ms) in that study seems much longer than that during LBBP (113±10 ms) in our
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study.
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The success rate of LBBP in this series is similar to what has been reported with early attempts at
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His bundle pacing18. Further studies are needed to understand both the learning curve of this technique
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as well as the limitations of successful LBB capture. Possible explanations for failure to achieve LBB
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capture include: (1) the inability of the lead to penetrate sufficiently deep in the septum to reach the left
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bundle; (2) the sheath being malpositioned such that the lead is not advanced perpendicular to the
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ventricular septum (Supplemental Material, Figure S1); (3) the failure of the lead tip to be deployed to
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the left side of the septum due to lead design limitation or local hypertrophied myocardium. During
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lead deployment, the flexibility of the delivery sheath, especially the distal part, might decrease by
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repeated procedural maneuvers, such that the lead tip could not be advanced through the sheath. This is
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also the possible reason for failure of achieving LBB capture. It is common to reposition pacing leads
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during right ventricular apical pacing and septal pacing. However, LBBP is achieved by
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trans-ventricular-septal method in the basal ventricular septum, so multiple repositioning attempts
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could cause damage to myocardial tissue and even possible perforation. Thus, we limited the number of
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attempts for LBBP as a precaution which may have decreased success rate. In 2000, Deshmukh et. al. conducted the pioneering investigation of permanent HBP by using a
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traditional pacing lead in a small number of heart failure patients and achieved a success rate of 66%19.
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The development of site-selective implantation tools, including the 3830 pacing lead and the C315 HIS
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delivery sheath, made HBP more feasible20. Vijayaraman et al.21 reported the success rate of 95% in 42
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patients with atrial fibrillation undergoing AV node ablation in a very experienced center. To date, the
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success rate of HBP has been reported to vary from 56% to 95%22-26, which is similar to the success
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rate of 80.5% with LBBP in the present study. With the improvement of implantation tools and
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techniques for standardized LBBP implantation, we expect an increase in success rate. The mean
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duration of fluoroscopy for HBP had ranged from 8-23 minutes.8, 22, 27. LBBP was performed with
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significantly less fluoroscopic exposure time (3.9±2.7 min) in the present study, which may be another
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benefit of this approach.
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Our previous study had demonstrated shorter QRSd with LBBP than with either RVSP or RVAP,
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suggesting that LBBP produces better ventricular electrical synchronization14. Similar results were
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shown in the present study using a different method to perform LBBP. Monitoring the paced ECG
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while deploying the lead was helpful to guide lead placement. During implantation, the ECG transition
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was continuously monitored, and checked with every two to three turns of the lead helix. A notch (“W”
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waveform) in lead V1 gradually shifted and finally disappeared when the tip was advanced from the
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right to the left side of the septum. This observation can be used as a safety check to determine where
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the pacing lead is in the septum and when the advancement of the pacing lead should be stopped. In
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contrast, no change in ECG morphology with advancement of the lead suggests that the lead was not
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advanced into the left side of the septum or this position was not suitable for LBBP. In this scenario, the
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lead should be repositioned. In the present study we demonstrate evidence for both selective and nonselective capture of the
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LBB. Given the immediate proximity of the muscular septum and non-penetrating portion of the left
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bundle, nonselective capture would be expected intuitively to be the more probable pattern. However
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selective capture can be observed especially at low output and/or pulse width. An example of the latter
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is seen in Figure 3 where selective capture occurs at a pulse width of 0.06 msec. The clinical
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implications of these findings are not currently known and will require further study.
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As LBBP is achieved by trans-ventricular-septal method, ventricular septum perforation can occur.
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However, because the diameter of the current lead is 1.4mm, no serious ventricular septal defect is
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expected even if perforation occurs. Nevertheless, it is important to monitor the transition of paced
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QRS morphology, lead impedance and pacing threshold. A low capture threshold and a high pacing
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impedance suggested the pacing lead remained in the septum while a sudden decrease of lead
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impedance and loss of capture indicated the tip of the lead entering the left ventricle. The thickness of
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ventricular septum is normally 6 to 11 mm. The helix electrode length of the lead is 1.8 mm and the
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space from the ring electrode to the helix is 9 mm. The onset of the ring electrode capture at an output
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of 5V/0.5msec suggests that the tip of the lead is likely at or near the left side of the ventricular septum.
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Any further advancement of the lead should be conducted carefully. It is noteworthy that no implant
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complications were noted when taking these precautions.
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There are several advantages of LBBP over HBP. First, high pacing threshold and threshold
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increase over time is relatively frequent with HBP, likely due to the anatomical characteristics of the
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His bundle, inadequate fixation, local fibrosis, tricuspid valve motion, and pathological progression in
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His bundle region. HBP capture threshold shows a clinically significant increase over time in 12
ACCEPTED MANUSCRIPT approximately 10% patients28. LBBP is achieved by trans-ventricular-septal method and the pacing
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lead is positioned in the basal ventricular septum. Left bundle branch usually spreads below the
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membranous septum with well-defined dimensions and there is less fibrosis wrapped than His bundle29.
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Thus, it is not surprising that a lower pacing threshold was noted. Second, because the pacing lead tip
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of LBBP bypasses the vulnerable region of the His bundle, the pacing threshold is stable. Third, since
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the pacing tip is fixed at or near the left bundle branch with nearby myocardial tissue and myocardium
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can be captured at the pacing output, there is no need to implant a back-up lead in case of loss of
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capture. Finally, R-wave amplitude recorded at the site of LBBP is high, which is important for
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appropriate sensing and capture management by a pacemaker. HBP mimics native conduction since
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both fascicles are activated antegradely, however LBBP maintains antegrade activation of the left
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fascicular system and often generates a near normal QRS complex, possibly due to retrograde or
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trans-ventricular-septal activation of the RBB.
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Limitations
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This study should be interpreted in light of certain methodologic limitations. First, the sample
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size was relatively small as a single center study. More data are needed to confirm our findings.
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Selective LBBP may not be clearly observed at implantation because the far-field recording by the
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pacing lead is used and may not show the discrete EGM for selective LBBP. In addition, more long
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term follow-up is needed to assess the stability of pacing in this region of the heart. Finally, the role of
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LBBP needs to be explored for other pacing indications such as CRT.
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Conclusions 13
ACCEPTED MANUSCRIPT Using the technique described in this paper, we were able to safely and successfully perform LBBP in
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80.5% of patients in a consecutive series. The accurate location for LBBP can be targeted during
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implantation given the characteristic changes in paced QRS morphology during lead deployment. The
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low pacing output and high R-wave amplitude during LBBP favor long-term pacing management and
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device longevity. LBBP produces a narrow QRS duration and short LV peak activation time, suggesting
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synchronized ventricular activation. LBBP may be an ideal option for patients in need of ventricular
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pacing once long-term safety and clinical benefits are confirmed.
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Acknowledgement: None.
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Funding: This research did not receive any specific grant from funding agencies in the public,
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commercial, or not-for-profit sectors.
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Huang W, Su L, Wu S, et al. Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block. Heart 2018. doi: 10.1136/heartjnl-2018-313415.
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Subzposh FA, Vijayaraman P. Long-Term Results of His Bundle Pacing. Card Electrophysiol Clin 2018;10:537-542.
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Huang W, Su L, Wu S, et al. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol
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Chen K, Li Y, Dai Y, et al. (2018). Comparison of electrocardiogram characteristics and pacing parameters between left bundle branch pacing and right ventricular pacing in patients receiving
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Mafi-Rad M, Luermans JG, Blaauw Y, Janssen M, Crijns HJ, Prinzen FW, et al. Feasibility and
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Bhatt AG, Musat DL, Milstein N, et al. The Efficacy of His Bundle Pacing: Lessons Learned
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Occhetta E, Bortnik M, Magnani A, et al. Prevention of ventricular desynchronization by permanent para-Hisian pacing after atrioventricular node ablation in chronic atrial fibrillation: a
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Zanon F, Baracca E, Aggio S, et al. A feasible approach for direct his-bundle pacing using a new steerable catheter to facilitate precise lead placement. J Cardiovasc Electrophysiol
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Elizari MV. The normal variants in the left bundle branch system. J Electrocardiol 2017; 50:389-399.
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implants. Heart rhythm 2018;15:1428-1431.
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Vijayaraman P, Ellenbogen KA. Approach to permanent His bundle pacing in challenging
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Table 1. Baseline Patient Characteristics All (n=87) Age (years)
63.8±11.4 31 (35.60)
Sinus node dysfunction (%)
59 (67.80)
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Men (%)
AV conduction disease (%)
28 (32.20)
Coronary artery disease (%)
22 (25.30)
Diabetes mellitus (%)
18 (20.69) 50 (57.50)
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Hypertension (%) Atrial fibrillation (%)
LVEDD (mm) Dual-chamber pacemaker implanted (%) Single-chamber pacemaker implanted (%) QRSd (ms)
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20 (22.73) 62.86±5.64 47.81±5.08 84 (96.60) 3 (3.40) 106.84±23.28 76,
6,
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Data are presented as mean ± standard deviation (SD) for continuous variables, and number of subjects
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(n) and percentage (%), respectively, for categorical variables.
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LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic diameter; QRSd, QRS
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duration.
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Table 2. Electrical Parameters Visit
Pacing
R-wave amplitude, mV
Impedance, Ohms
700.14±134.87
414
11.99±5.36
Pre-discharge (n =70)
0.51±0.10
16.16±6.48
3-month follow-up (n =47)
0.71±0.23
16.90±6.78
Values are mean ± SD.
: P <0.001 at implantation vs. Pre-discharge, 3-month follow-up; 3-month follow-up.
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501.01±96.88 472.40±91.41
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0.76±0.22
: P<0.001 pre-discharge vs.
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At implantation (n =70)
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ACCEPTED MANUSCRIPT Figure 1. Fluoroscopic projections showing dual leads with one lead for His bundle location and the
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second lead for left bundle branch pacing. Panel A: the first pacing lead (His lead) in the His bundle
430
region; Panel B: the second pacing lead (LBB lead) on the right side of the septum before screwing;
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Panel C: the tip of LBB lead perpendicular to the septum; Panel D: LBB lead in the left bundle branch
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region on the left side of the septum after screwing the lead.
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443
dysfunction. Panel A: the left bundle branch potential during intrinsic rhythm (red asterisks); Panel B:
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selective left bundle branch pacing with discrete local ventricular electrogram (black arrow) at LBBP
445
threshold (0.2V/0.5ms); Panel C: non-selective left bundle branch pacing with local myocardial fusion
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(red circle) during pacing at 0.5V/0.5ms, there is no discrete local ventricular electrogram.
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ACCEPTED MANUSCRIPT 455 Figure 3. Post-implantation 12-Lead ECG of selective left bundle branch pacing and non-selective left
457
bundle branch pacing in a patient with sinus node dysfunction. Panel A: selective left bundle branch
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pacing without local myocardial fusion (red circle) during pacing at 1.25V/0.06ms; Panel B:
459
non-selective left bundle branch pacing with local myocardial fusion (red circle) during pacing at
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1.5V/0.06ms. (5mm/mV, 50mm/s).
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ACCEPTED MANUSCRIPT 468 Figure 4. 12-Lead ECG and EGM showing the change of the notch in V1 lead (red frame) during
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rotating the lead from the right side (far left ECG) to the left side (ECG far right) of the septum.
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