TY - JOUR
AU - Zou,, Jiangang
AB - Abstract Aims Left bundle branch pacing (LBBP) recently emerges as a novel pacing modality. We aimed to evaluate the feasibility and cardiac synchrony of permanent LBBP in bradycardia patients. Methods and results Left bundle branch pacing was successfully performed in 56 pacemaker-indicated patients with normal cardiac function. Left bundle branch pacing was achieved by penetrating the interventricular septum (IVS) into the left side sub-endocardium with the pacing lead. His-bundle pacing (HBP) was successfully performed in another 29 patients, 19 of whom had right ventricular septal pacing (RVSP) for backup pacing. The QRS duration, left ventricular (LV) activation time (LVAT), and mechanical synchrony using phase analysis of gated SPECT myocardial perfusion imaging were evaluated. Paced QRS duration in LBBP group was significantly shorter than that in RVSP group (117.8 ± 11.0 ms vs. 158.1 ± 11.1 ms, P < 0.0001) and wider than that in HBP group (99.7 ± 15.6 ms, P < 0.0001). Left bundle branch potential was recorded during procedure in 37 patients (67.3%). Left bundle branch pacing patients with potential had shorter LVAT than those without potential (73.1 ± 11.3 ms vs. 83.2 ± 16.8 ms, P = 0.03). Left bundle branch pacing patients with potential had similar LV mechanical synchrony to those in HBP group. R-wave amplitude and capture threshold of LBBP were 17.0 ± 6.7 mV and 0.5 ± 0.1 V, respectively at implant and remained stable during a mean follow-up of 4.5 months without lead-related complications. Conclusion Permanent LBBP through IVS is safe and feasible in bradycardia patients. Left bundle branch pacing could achieve favourable cardiac electrical and LV mechanical synchrony. Left bundle branch pacing, His-bundle pacing, Right ventricular septal pacing, Myocardial perfusion imaging, Mechanical synchrony What’s new? Permanent left bundle branch pacing (LBBP) through the interventricular septum using the Select Secure pacing lead (model 3830, Medtronic Inc., bipolar, fixed helix screw) is safe and feasible in bradycardia patients. Similar with His-bundle pacing (HBP), LBBP preserved better electrical and left ventricular mechanical synchrony compared with right ventricular septal pacing (RVSP). Left bundle branch pacing exhibited stable parameters of higher R-wave amplitudes and lower capture thresholds than HBP. Left bundle branch pacing is a promising physiological pacing technique that can be an alternative to RVSP or HBP in bradycardia patients. Introduction Cardiac pacing remains the effective therapy for sinus node dysfunction (SND) or atrioventricular block (AVB). Conventional right ventricular apical pacing (RVAP) was associated with higher rates of atrial fibrillation (AF), pacing-induced cardiomyopathy, and mortality.1–3 Approximately 15–20% of the patients with ventricular pacing percentage over 20% developed heart failure during follow-up.4,5 Pursuit of alternate pacing sites has been widely studied but no definitive conclusion is reached.6 Recent studies showed that His-bundle pacing (HBP) is superior in preserving electrical synchrony and left ventricular (LV) function compared with right ventricular pacing (RVP).7,8 However, lead placement for HBP is technically challenging due to its anatomic location and long-term capture thresholds of HBP have been found to be significantly higher than those of RVP. Left ventricular septal pacing (LVSP) by transvenous approach through the interventricular septum (IVS) in humans was first introduced in 2016 and demonstrated to maintain acute LV pump function.9 Animal studies of LVSP have also shown its safety and feasibility and the pacing leads remained electrically and mechanically stable during 4-month follow-up.10 This pacing modality by using a custom pacing lead with extended helix was considered to be an alternative and preferable approach for antibradycardia pacing. However, LVSP was initially used in only 10 patients and its long-term outcome was not reported. Recently, Huang’s case report showed that pacing the left bundle branch (LBB) restored LV function in one patient with heart failure by correcting left bundle branch block (LBBB).11 This novel method of LBB pacing (LBBP) was also reported to produce narrow QRS duration with low pacing threshold in 20 patients by Chen et al.12 However, the effect of LBBP on cardiac synchrony was still unknown. Our previous study showed that HBP could achieve normal electrical and LV mechanical synchrony.6 Whether LBBP could maintain favourable synchrony like HBP needed to be clarified. The objectives of our study were (i) to investigate the feasibility of LBBP through the IVS in bradycardia patients with normal cardiac function; (ii) to compare the electrical and mechanical synchrony of LBBP with those of HBP and right ventricular septal pacing (RVSP); and (iii) to report the stability of lead parameters. Methods Study population We prospectively enrolled 59 consecutive pacemaker-indicated patients for SND or AVB or AF with slow ventricular rate from January to September 2018 according to 2013 European Society of Cardiology (ESC) guidelines on cardiac pacing.13 Patients with any condition of the following were excluded: (i) LV ejection fraction (LVEF) less than 55% assessed by echocardiography; (ii) previously implanted with any cardiac devices; (iii) unwilling or unable to undergo SPECT myocardial perfusion imaging (MPI) assessment. Another 29 HBP patients who met the same inclusive standard and completed SPECT MPI examination were included from September 2014 to September 2018 and were designed as the comparison group. The study was approved by the hospital ethics committee and all patients provided written informed consent to participate in the study. Implantation procedure The implantation was performed using the Select Secure pacing lead (model 3830, 69 cm, Medtronic Inc., Minneapolis, MN, USA) delivered through a fixed-curve sheath (C315 His, Medtronic Inc.). The pacing lead was introduced transvenously into the right ventricle and screwed into the IVS until LV septum was reached, without protruding into the LV cavity. The schematic representation of LBBP is shown in Figure 1. Figure 2 exemplifies the steps performed during the implantation procedure. Figure 1 Open in new tabDownload slide Schematic representations of LBBP, HBP, and RVSP. For LBBP, the pacing lead (Select Secure 3830) is introduced transvenously into the right ventricle through C315 His-sheath (left panel) and screwed into the IVS until LBB is reached (right panel). While HBP lead is implanted at His-bundle area and RVSP lead is placed at right side of the IVS. The left panel was adopted from the education material provided by the manufacturer Medtronic Inc. HBP, His-bundle pacing; IVS, interventricular septum; LBB, left bundle branch; LBBP, left bundle branch pacing; RVSP, right ventricular septal pacing. Figure 1 Open in new tabDownload slide Schematic representations of LBBP, HBP, and RVSP. For LBBP, the pacing lead (Select Secure 3830) is introduced transvenously into the right ventricle through C315 His-sheath (left panel) and screwed into the IVS until LBB is reached (right panel). While HBP lead is implanted at His-bundle area and RVSP lead is placed at right side of the IVS. The left panel was adopted from the education material provided by the manufacturer Medtronic Inc. HBP, His-bundle pacing; IVS, interventricular septum; LBB, left bundle branch; LBBP, left bundle branch pacing; RVSP, right ventricular septal pacing. Figure 2 Open in new tabDownload slide Implantation procedure of LBBP. His-bundle electrogram was identified at the RAO 25° position (A, arrow) and fluoroscopic image of the lead position was recorded as a reference (F). A ‘W’-shaped pacing morphology (B, red circle and arrow) in surface lead V1 was observed at the anterior lower site of the His-bundle position, perpendicular to the right side of IVS (G), before screwing in the lead tip. A rightward shift of the second notch in the ‘W’-shaped pacing morphology can be observed as the lead tip was gradually screwed into the IVS (C, blue circle and arrow). The lead tip was determined in the final position once a QR or rSR morphology in surface lead V1 was achieved (D, purple circle and arrow). LBB potential was defined as a discrete potential before the QRS complex at the final lead location and was measured (E, dash arrow). The penetration depth in the IVS was finally assessed by injecting a small amount of contrast medium through the sheath in LAO 45° (H). The final lead tip position was confirmed below the sub-endocardium of left side of IVS by computed tomography (I). IVS, interventricular septum; LAO, left anterior oblique; LBB, left bundle branch; RAO, right anterior oblique. Figure 2 Open in new tabDownload slide Implantation procedure of LBBP. His-bundle electrogram was identified at the RAO 25° position (A, arrow) and fluoroscopic image of the lead position was recorded as a reference (F). A ‘W’-shaped pacing morphology (B, red circle and arrow) in surface lead V1 was observed at the anterior lower site of the His-bundle position, perpendicular to the right side of IVS (G), before screwing in the lead tip. A rightward shift of the second notch in the ‘W’-shaped pacing morphology can be observed as the lead tip was gradually screwed into the IVS (C, blue circle and arrow). The lead tip was determined in the final position once a QR or rSR morphology in surface lead V1 was achieved (D, purple circle and arrow). LBB potential was defined as a discrete potential before the QRS complex at the final lead location and was measured (E, dash arrow). The penetration depth in the IVS was finally assessed by injecting a small amount of contrast medium through the sheath in LAO 45° (H). The final lead tip position was confirmed below the sub-endocardium of left side of IVS by computed tomography (I). IVS, interventricular septum; LAO, left anterior oblique; LBB, left bundle branch; RAO, right anterior oblique. Specifically, venous access was obtained via the left axillary vein or subclavian vein. The pacing lead was inserted through the C315 His-sheath. An intracardiac electrogram was recorded from the lead tip using the electrophysiological recording system (Bard Electrophysiology Lab System, MA, USA). His-bundle electrogram was identified at the right anterior oblique (RAO) 25° position (Figure 2A) and fluoroscopic image of the lead position was recorded as a reference (Figure 2F). In the process of advancing the pacing lead, fluoroscopic image and pacing parameters and morphologies were monitored to avoid displacement of the lead or perforation of IVS. The sheath and lead tip were first advanced to the anterior lower site of the His-bundle position, and subsequently rotated in a counterclockwise fashion to place the lead tip in a perpendicular orientation to the IVS (Figure 2G). A ‘W’-shaped pacing morphology in surface lead V1 was observed at this location (Figure 2B). As the lead tip was gradually screwed into the IVS, a rightward shift of the second notch in the ‘W’-shaped pacing morphology can be observed (Figure 2C). The lead tip was considered to be in the final position once a QR or rSR morphology in surface lead V1 was achieved (Figure 2D). Moreover, at this final lead location, a discrete potential before the QRS complex often existed, and we defined this potential as the LBB potential (Figure 2E). The PV interval was also measured from the potential to the onset of QRS complex (Figure 2E). The penetration depth in the IVS was finally assessed by injecting a small amount of contrast medium through the sheath in left anterior oblique 45° (Figure 2H). Echocardiography was performed to detect the lead position and computed tomography (CT) scan was used in some patients to evaluate the lead depth in the IVS before discharge (Figure 2I). Programming of devices All patients were implanted with a dual-chamber pacemaker (Medtronic Inc., Minneapolis, MN, USA). For patients with sinus rhythm, the right atrial lead was connected to the atrial port and the LBBP or HBP lead was connected to the ventricular port. The device was programmed at DDDR mode. For patients with AF, the LBBP or HBP lead was connected to the atrial port and the remaining lead which was implanted in right ventricular septum was connected to the ventricular port. The device was programmed at DVIR mode with the ventricular safety pacing turned off and a short atrioventricular interval of 120 ms. All LBBP leads were programmed at tip unipolar pacing with amplitude of 3.0 V at pulse width of 0.5 ms to avoid septal anodal pacing. Cardiac electrical synchrony evaluation Cardiac electrical synchrony was assessed using the QRS duration of a 12-lead surface electrocardiogram (ECG). The surface ECG was obtained before and after the implantation. The QRS duration was measured from the onset of intrinsic or paced QRS to the end of QRS complex in all 12 leads. Left ventricular electrical synchrony was assessed using the LV activation time (LVAT) which was estimated by measuring the time from the intracardiac pacing spike to the R-wave peak of QRS complex in lead V5 and V6. The widest paced QRS duration and the wider LVAT were adopted for analyses. Two independent experienced ECG specialists blinded to the study measured these two parameters. Left ventricular mechanical synchrony evaluation Left ventricular mechanical synchrony was evaluated by phase analysis of SPECT MPI within 1 week after the implantation. As described previously,14 at about 60 min after injection of 25–30 mCi of Tc-99m sestamibi, a SPECT scan was acquired from RAO 45° to LAO 45° (180° orbit).[AQ: Please check whether edit made to the sentence ‘As described previously …’ is appropriate.] After gated SPECT MPI acquisition, the gated planar images were exported and transferred for processing by a phase analysis tool (Emory Cardiac Toolbox version 4 with SyncTools).15 Phase analysis was independently performed by one specialist blinded to the study at University of Southern Mississippi (Z.W.H.). Phase standard deviation (PSD) and phase histogram bandwidth (PHB) were used to quantify LV mechanical synchrony. Follow-up All patients underwent transthoracic echocardiography (TTE) by one experienced specialist who was blinded to the study at baseline and 6-month follow-up. Left ventricular ejection fraction, LV end-systolic diameter (LVESD), and LV end-diastolic dimension (LVEDD) were measured. Lead parameters, including R-wave amplitudes, capture thresholds, and pacing impedances were measured during procedure, before discharge, and at 1- and 6-month follow-up. Statistical analysis Categorical variables were expressed as frequencies or percentages and continuous variables were summarized as mean ± standard deviation. Student’s t-test was applied for continuous variables and χ2 test was used for categorical data. One or two analysis of variance analysis was performed for multiple group data. A P-value less than 0.05 was considered statistically significant. SPSS 21.0 (IBM Corp, Armonk, NY, USA) was used to perform all statistical analyses. Results Patients A total of 56 patients (mean age of 68.3 ± 11.8 years; 36 males) with successful LBBP and 29 (mean age of 69.1 ± 10.4 years; 19 males) with successful HBP as comparison (19 with RVSP for backup pacing) were analysed in the study. Table 1 shows the baseline characteristics of the patients. Of the patients with LBBP, 16 patients were diagnosed of SND, 21 of AVB, and 19 of permanent AF with slow ventricular rate. In the HBP group, 10 patients had SND and 19 had permanent AF with slow ventricular rate. All patients had normal LV diameter and systolic function assessed by echocardiography. In LBBP patients, the mean IVS thickness was 10.6 ± 0.9 mm. More patients with permanent AF were included in HBP group. Baseline echocardiographic measurements were similar between the two groups (Table 1). Table 1 Patient characteristics LBBP (n = 56) HBP (n = 29) P-value Gender (male) 36 (64.3) 19 (65.5) 0.91 Age (years) 68.3 ± 11.8 69.1 ± 10.4 0.76 Indications 0.0005  SND 16 (28.6) 10 (34.5)  AVB 21 (37.5)  AF with slow ventricular rate 19 (33.9) 19 (65.5) Intrinsic QRS duration (ms) 108.5 ± 28.8 100.6 ± 20.3 0.19 LVEF (%) 63.8 ± 3.2 63.3 ± 5.8 0.61 LVEDD (mm) 48.6 ± 4.1 50.4 ± 5.9 0.10 LBBP (n = 56) HBP (n = 29) P-value Gender (male) 36 (64.3) 19 (65.5) 0.91 Age (years) 68.3 ± 11.8 69.1 ± 10.4 0.76 Indications 0.0005  SND 16 (28.6) 10 (34.5)  AVB 21 (37.5)  AF with slow ventricular rate 19 (33.9) 19 (65.5) Intrinsic QRS duration (ms) 108.5 ± 28.8 100.6 ± 20.3 0.19 LVEF (%) 63.8 ± 3.2 63.3 ± 5.8 0.61 LVEDD (mm) 48.6 ± 4.1 50.4 ± 5.9 0.10 AF, atrial fibrillation; AVB, atrioventricular block; LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; LBBP, left bundle branch pacing; HBP, His-bundle pacing; SND, sinus node dysfunction. Open in new tab Table 1 Patient characteristics LBBP (n = 56) HBP (n = 29) P-value Gender (male) 36 (64.3) 19 (65.5) 0.91 Age (years) 68.3 ± 11.8 69.1 ± 10.4 0.76 Indications 0.0005  SND 16 (28.6) 10 (34.5)  AVB 21 (37.5)  AF with slow ventricular rate 19 (33.9) 19 (65.5) Intrinsic QRS duration (ms) 108.5 ± 28.8 100.6 ± 20.3 0.19 LVEF (%) 63.8 ± 3.2 63.3 ± 5.8 0.61 LVEDD (mm) 48.6 ± 4.1 50.4 ± 5.9 0.10 LBBP (n = 56) HBP (n = 29) P-value Gender (male) 36 (64.3) 19 (65.5) 0.91 Age (years) 68.3 ± 11.8 69.1 ± 10.4 0.76 Indications 0.0005  SND 16 (28.6) 10 (34.5)  AVB 21 (37.5)  AF with slow ventricular rate 19 (33.9) 19 (65.5) Intrinsic QRS duration (ms) 108.5 ± 28.8 100.6 ± 20.3 0.19 LVEF (%) 63.8 ± 3.2 63.3 ± 5.8 0.61 LVEDD (mm) 48.6 ± 4.1 50.4 ± 5.9 0.10 AF, atrial fibrillation; AVB, atrioventricular block; LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; LBBP, left bundle branch pacing; HBP, His-bundle pacing; SND, sinus node dysfunction. Open in new tab Left bundle branch pacing, His-bundle pacing, and right ventricular septal pacing lead implantation Left bundle branch pacing was successfully performed in 56 patients. According to the pacing polarity in leads II and III, pacing sites were classified as high (polarities in both leads were positive, 18 patients), low (polarities in both leads were negative, 9 patients), and intermediate positions (excluding high and low positions, 29 patients). The mean fluoroscopy exposure time of LBBP lead implantation was 6.3 ± 4.4 min. His-bundle pacing was successfully performed in 29 patients. Among them, 18 patients received selective HBP and 19 AF patients were implanted with RVSP leads for backup pacing. Lead parameters Figure 3 shows the lead parameters including R-wave amplitudes, capture thresholds, and pacing impedances at 1-week after implantation, 1-month and 6-month follow-up. Compared with HBP patients, LBBP patients had lower capture thresholds at pulse width of 0.5 ms (0.5 ± 0.1 V vs. 1.4 ± 0.8 V, P < 0.0001) and higher R-wave amplitude (17.0 ± 6.7 mV vs. 4.4 ± 4.3 mV, P < 0.0001) at baseline. The lead parameters of LBBP remained stable during follow-up (Figure 3). Figure 3 Open in new tabDownload slide Lead parameters of LBBP, HBP, and RVSP. LBBP and RVSP leads had much higher R-wave amplitudes and lower capture thresholds than HBP. The lead parameters of the three pacing modes remained stable during 6-month follow-up. HBP, His-bundle pacing; LBBP, left bundle branch pacing; RVSP, right ventricular septal pacing. Figure 3 Open in new tabDownload slide Lead parameters of LBBP, HBP, and RVSP. LBBP and RVSP leads had much higher R-wave amplitudes and lower capture thresholds than HBP. The lead parameters of the three pacing modes remained stable during 6-month follow-up. HBP, His-bundle pacing; LBBP, left bundle branch pacing; RVSP, right ventricular septal pacing. Complications Acute lead dislodgement occurred in one patient during withdrawal of the sheath, and the patient underwent reimplantation successfully. No patient with loss of capture, lead removal, or late lead dislodgement was observed. Echocardiography showed that the pacing lead was positioned at the sub-endocardium of IVS in all patients. Twenty-nine patients received CT scan and no perforation into LV cavity was observed. Electrical synchrony evaluation QRS duration Paced QRS duration was slightly wider than baseline in LBBP group (117.8 ± 11.0 ms vs. 108.5 ± 28.8 ms, P = 0.02, Figure 4). No difference in QRS duration was detected between baseline and post-implantation for HBP (100.6 ± 20.3 ms vs. 99.7 ± 15.6 ms, P = 0.86). Left bundle branch pacing patients had significantly shorter paced QRS duration compared with RVSP group (117.8 ± 11.0 ms vs. 158.1 ± 11.1 ms, P < 0.0001), but wider than HBP patients (99.7 ± 15.6 ms, P < 0.0001). Paced QRS duration of LBBP remained unchanged at the mean period of 4.5-month follow-up (118.4 ± 11.3 ms). Figure 4 Open in new tabDownload slide Comparison of QRS durations of LBBP, HBP, and RVSP. The typical 12-lead surface ECGs of LBBP, HBP, and RVSP in two patients were shown in the left panel (A). Paced QRS duration of LBBP was slightly wider than that of baseline. No difference was found between baseline and paced QRS duration in HBP. LBBP patients showed significantly better electrical synchrony than RVSP, but slightly worse than HBP (B). ECG, electrocardiogram; HBP, His-bundle pacing; LBBP, left bundle branch pacing; RVSP, right ventricular septal pacing. Figure 4 Open in new tabDownload slide Comparison of QRS durations of LBBP, HBP, and RVSP. The typical 12-lead surface ECGs of LBBP, HBP, and RVSP in two patients were shown in the left panel (A). Paced QRS duration of LBBP was slightly wider than that of baseline. No difference was found between baseline and paced QRS duration in HBP. LBBP patients showed significantly better electrical synchrony than RVSP, but slightly worse than HBP (B). ECG, electrocardiogram; HBP, His-bundle pacing; LBBP, left bundle branch pacing; RVSP, right ventricular septal pacing. Left bundle branch potential and PV interval Left bundle branch potential was recorded in 37 patients (37/55, 67.3%). Left bundle branch potential in one patient was unable to be recorded due to ventricular pacing dependence. In the first 20 patients, the percentage of recorded LBB potential was 55% (11/20). However, for the latter 20 patients, the percentage increased to 80% (16/20). According to whether LBB potential was recorded, LBBP patients were divided into LBB potential positive group (LBBP+ group) and LBB potential negative group (LBBP− group). Mean PV interval was 22.0 ± 3.7 ms in the LBBP+ group. Left ventricular activation time Mean LVAT of tip-paced QRS complex in LBBP patients was 76.2 ± 14.0 ms, which is significantly shorter than that of ring-paced QRS duration (101.1 ± 14.2 ms, P < 0.0001). Patients in LBBP+ group had a shorter tip-paced LVAT compared with those in LBBP− group (73.1 ± 11.3 ms vs. 83.2 ± 16.8 ms, P = 0.03, Figure 5). Figure 5 Open in new tabDownload slide LVAT of tip and ring paced ECGs in LBBP patients. One patient with recorded LBB potential (red arrow) had short LVAT of 62 ms (A) and the other patient without LBB potential had wide LVAT of 96 ms (B). Both patients had wide LVAT in ring-paced ECGs. LVAT of tip-paced QRS complex in LBBP patients was significantly shorter than that of ring-paced QRS duration (C). Patients in LBBP+ group had a shorter tip-paced LVAT compared with those in LBBP− group (C). ECG, electrocardiogram; LBBP, left bundle branch pacing; LBBP+, LBBP with recorded LBB potential; LBBP−, LBBP without potential; LVAT, left ventricular activation time. Figure 5 Open in new tabDownload slide LVAT of tip and ring paced ECGs in LBBP patients. One patient with recorded LBB potential (red arrow) had short LVAT of 62 ms (A) and the other patient without LBB potential had wide LVAT of 96 ms (B). Both patients had wide LVAT in ring-paced ECGs. LVAT of tip-paced QRS complex in LBBP patients was significantly shorter than that of ring-paced QRS duration (C). Patients in LBBP+ group had a shorter tip-paced LVAT compared with those in LBBP− group (C). ECG, electrocardiogram; LBBP, left bundle branch pacing; LBBP+, LBBP with recorded LBB potential; LBBP−, LBBP without potential; LVAT, left ventricular activation time. Left ventricular mechanical synchrony evaluation Figure 6 shows LV mechanical synchrony parameters (PSD and PHB) in HBP, LBBP+, LBBP−, and RVSP groups. Left ventricular synchrony in LBBP+ group was significantly better than that in LBBP− group (PSD, 15.1° ± 5.3° vs. 20.6° ± 7.2°, P = 0.006; PHB, 46.2° ± 13.4° vs. 62.2° ± 19.1°, P = 0.0009). Patients in LBBP+ group had similar LV mechanical synchrony to those in HBP group (PSD, 15.1° ± 5.3° vs. 13.9° ± 5.8°, P = 0.80; PHB, 46.2° ± 13.4° vs. 41.3° ± 12.6°, P = 0.51). There were no differences in LV mechanical synchrony among patients with high, medium, or low pacing positions. Figure 6 Open in new tabDownload slide Left ventricular mechanical synchrony of LBBP, HBP, and RVSP. PSD and PHB measured by phase analyses of SPECT MPI in different pacing modes were shown in this figure. LV synchrony in LBBP+ group was significantly better than that in LBBP− group. Patients in LBBP+ group had similar LV mechanical synchrony to those in HBP group (A). Patients in both RVSP and LBBP− groups had similar LV mechanical synchrony (A). One LBBP patient with potential had similar mechanical synchrony with intrinsic rhythm (B). The other HBP patient also showed similar mechanical synchrony with intrinsic rhythm and better than RVSP (C). LBBP, left bundle branch pacing; LBBP+, LBBP with recorded LBB potential; LBBP−, LBBP without potential; LV, left ventricular; HBP, His-bundle pacing; MPI, myocardial perfusion imaging; PHB, phase histogram bandwidth; PSD, phase standard deviation; RVSP, right ventricular septal pacing. Figure 6 Open in new tabDownload slide Left ventricular mechanical synchrony of LBBP, HBP, and RVSP. PSD and PHB measured by phase analyses of SPECT MPI in different pacing modes were shown in this figure. LV synchrony in LBBP+ group was significantly better than that in LBBP− group. Patients in LBBP+ group had similar LV mechanical synchrony to those in HBP group (A). Patients in both RVSP and LBBP− groups had similar LV mechanical synchrony (A). One LBBP patient with potential had similar mechanical synchrony with intrinsic rhythm (B). The other HBP patient also showed similar mechanical synchrony with intrinsic rhythm and better than RVSP (C). LBBP, left bundle branch pacing; LBBP+, LBBP with recorded LBB potential; LBBP−, LBBP without potential; LV, left ventricular; HBP, His-bundle pacing; MPI, myocardial perfusion imaging; PHB, phase histogram bandwidth; PSD, phase standard deviation; RVSP, right ventricular septal pacing. Clinical and echocardiographic outcome All LBBP patients survived without any symptoms of heart failure during a mean follow-up of 4.5 ± 2.4 months. Twenty patients fulfilled 6-month echocardiographic follow-up. The echocardiographic data, including LVEF, LVESD, and LVEDD remained unchanged during follow-up (Supplementary material online, Figure S1). Twenty-six patients (45.6%) with ventricular pacing percentage over 40% were also followed-up. No patient developed heart failure and aggravated tricuspid regurgitation. Discussion This study first demonstrated the feasibility and safety of permanent LBBP through the IVS approach. Similar with HBP, LBBP preserved better electrical and LV mechanical synchrony compared with RVSP. Left bundle branch pacing exhibited stable parameters of higher R-wave amplitudes and lower capture thresholds than those of HBP. Feasibility and safety of permanent left bundle branch pacing Mafi-Rad et al.9 first reported permanent LVSP using a special pacing lead with a 4-mm helix to penetrate the IVS into the LV septum. Their study initially applied intracardiac echocardiography (ICE) to guide lead positioning on the IVS and increased the safety of the procedure. However, in their last two patients, ICE guidance was not needed due to gained experience. In the early stage of our study, we implanted the pacing lead with a 1.8 mm helix under the guidance of transoesophageal echocardiography (TOE) or TTE in 10 patients. The echocardiography could guide the lead perpendicularly against the IVS and show the position of the lead tip. In subsequent patients, LBBP leads were successfully implanted only depending on the fluoroscopy, paced V1 ECG morphology, and lead parameters. Both procedure time and fluoroscopy time decreased with increasing experience. The percentage of recorded LBB potential during the procedure also increased with gained experience. During follow-up, no lead-related complications were observed. R-wave amplitude, capture threshold, and paced QRS morphology remained stable. Left bundle branch pacing vs. right ventricular septal pacing Right ventricular apical pacing was associated with high incidence of heart failure, AF, and mortality because of its abnormal activation propagation and obvious LV contraction delay. Comparative studies between RVSP and RVAP have resulted in controversial outcome and no definitive conclusion could be drawn. One previous study has shown that permanent LVSP could preserve acute LV pump function more effectively than RVSP.9 Our study demonstrated that LBBP, similar to HBP, preserved better electrical and mechanical synchrony than RVSP. Although there was only 10 mm of IVS thickness, the activation propagation between RVSP and LBBP was completely different. In RVSP, trans-septal conduction was delayed and LV activation was dependent on myocardium spreading. However, in LBBP, LV septum was first activated just like normal ventricular activation, and most importantly, left His-Purkinje system might be activated during LBBP, especially in the patients with LBB potential. In our study, QRS duration in LBBP group was significantly shorter than that in RVSP group. Left ventricular mechanical synchrony in LBBP+ group was similar with that in HBP group and better than that in RVSP group. The mechanical synchrony in the LBBP− group was not as good as in the LBBP+ group. In fact, the dispersion of mechanical synchrony in LBBP− group was relatively great. We still observed six patients (33.3%) with short LVAT had better LV mechanical synchrony than those with long LVAT in LBBP− group (Supplementary material online, Figure S2). The mechanisms of better synchrony in patients without LBB potential were unknown and needed further investigation. Left bundle branch pacing vs. His-bundle pacing His-bundle pacing was considered as the physiological pacing modality to date. Vijayaraman et al.7 reported that permanent HBP was associated with reduction in mortality during long-term follow-up compared with RVP. However, some issues with HBP still withheld the widespread application of this method. First, success rate of HBP is highly dependent on the operators’ experience and the difficulty to perform this procedure negatively impacts the promotion of this technique.16 Second, long-term pacing threshold of HBP needs to be further evaluated. Vijayaraman et al.7 reported that His-bundle capture threshold at 5-year follow-up was significantly higher than that at implantation (1.62 ± 1.0 V vs. 1.35 ± 0.9 V at 0.5 ms, P < 0.05). Moreover, 5-year generator replacement rate in HBP was higher than that in RVP (9% vs. 1%). For LBBP, the implantation procedure was relatively easier than HBP. Importantly, R-wave amplitude and pacing threshold of LBBP were more satisfactory and stable than those in HBP. Meanwhile, LBBP could produce similar electrical and mechanical synchrony compared with HBP. Therefore, this novel pacing modality will be more applicable and worth being generalized. Currently, cardiac resynchronization therapy (CRT) is the standard-of-care therapy for heart failure patients with LV dyssynchrony. However, approximately 30% patients showed no response. One cross-over study by Lustgarten et al.17 showed that HBP could achieve comparable clinical outcomes to biventricular pacing. Several other studies also suggested that HBP could be a possible alternative to CRT non-responders and patients who had failed LV lead placement.18–20 One recent case report showed that LBBP could restore LV function in one heart failure patient with LBBB using low and stable pacing output.11 As a result, the feasibility of LBBP as demonstrated in this study raised the possibility that this novel pacing modality can serve as an alternative to CRT, especially in patients with failed LV lead placement or CRT non-responders. Future research should be carried out to compare the efficacy of LBBP with biventricular pacing in patients with heart failure. New concept of left bundle branch pacing: beyond left ventricular septal pacing Left bundle branch pacing in our study is different from LVSP9 in several aspects. First, the mean paced QRS duration in LBBP (mean 117.8 ms) was narrower than that of LVSP (mean 144 ms), suggesting faster LV activation propagation by LBBP than by LVSP. Second, the lead position of LVSP was at the lower LV septum showing negative axis in inferior leads. In most of our LBBP patients, positive axis was present in inferior leads suggesting the pacing site was at the upper or middle LV septum. Finally, the discrete LBB potential demonstrated the pacing site was close to LBB trunk and Purkinje network while no such potential was reported in LVSP.9 Pacing the LBB was first introduced by Huang in 2017.11 However, how to define the concept of LBBP or estimate the involvement of LBB is still unknown. In addition, the tiny difference in capture threshold between LBB and surrounding myocardium might make the judgement difficult. LBBP could either directly capture LBB, LBB and nearby myocardium, or nearby myocardium then propagates to LBB, eventually activating the whole left ventricle. Nonetheless, the record of discrete potential from the lead tip during procedure suggested that the pacing site might be at or close to LBB fibres. Our result about the superiority of LV synchrony in the patients with recorded potential also demonstrated the involvement of the His-Purkinje system which could produce more physiological activation and better LV mechanical synchrony. Therefore, LVSP plus the record of LBB potential might generate the new concept of LBBP. The mechanisms are still unknown and further research is warranted. Limitations Left bundle branch pacing achieved by screwing the pacing lead into the left side of the IVS is a novel pacing method and issues such as pacing lead protruding into the LV cavity, thrombosis, injury to coronary arteries in IVS and also lead extraction out of the IVS should be addressed. At the beginning of our study, we applied TOE or TTE to guide the lead implantation. However, after experience gained, we judged the lead depth into the IVS by repeatedly assessing the pacing parameters, especially R-wave amplitude and pacing impedance and injecting small amounts of contrast medium through the sheath to avoid the protrusion. In our study, no such complication was observed. Echocardiography guidance during procedure is a good method to judge the lead position in IVS. Computed tomography scan was applied to determine the lead depth into IVS after procedure in only some patients for the purpose of understanding LBBP, which might increase the radiation exposure and also expenditure to the patient. Echocardiogram was routinely performed to judge the lead position as well as cardiac function before discharge, which was adequate in cost. SPECT MPI was used to evaluate LV mechanical synchrony in this study. However, echocardiography was the most common method to assess LV synchrony. No comparison with echocardiography evaluation was conducted. Since the ring electrode of the pacing lead could not be programmed as unipolar pacing mode in the currently available devices, we could not compare cardiac synchrony between RVSP and LBBP in the same patient. Future pacemaker settings could be adjusted to provide the ring-electrode pacing. This study was a single-centre prospective study and the sample size was relatively small. Although our study demonstrated the novel pacing method was safe and feasible, larger and randomized controlled trials should be conducted to verify its long-term safety and clinical benefits. Conclusions Permanent LBBP through the IVS is safe and feasible and preserves favourable cardiac electrical and LV mechanical synchrony. Technical improvement is needed for a high success rate of LBBP with recorded LBB potential and the long-term outcome of LBBP still needs further investigation. Acknowledgements We would like to thank Dr Weijian Huang (the First Affiliated Hospital of Wenzhou Medical University) for his technical assistance in LBBP procedure. We also thank Dr David E. Haines (Department of Cardiology, Beaumont Hospital) and Dr Xiaohong Zhou (Medtronic Inc.) for their diligent review of our manuscript. Funding This work was supported by National Natural Science Foundation of China (81470457; PI: Jiangang Zou) and Science and Technology Department of Jiangsu Province (BE2016764; PI: Jiangang Zou). Conflict of interest: none declared. References 1 Sweeney MO , Hellkamp AS , Ellenbogen KA , Greenspon AJ , Freedman RA , Lee KL. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction . Circulation 2003 ; 107 : 2932 – 7 . 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Google Scholar Crossref Search ADS PubMed WorldCat Author notes Xiaofeng Hou, Zhiyong Qian and YaoWang authors contributed equally to the study. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Feasibility and cardiac synchrony of permanent left bundle branch pacing through the interventricular septum
JF - Europace
DO - 10.1093/europace/euz188
DA - 2019-11-01
UR - https://www.deepdyve.com/lp/oxford-university-press/feasibility-and-cardiac-synchrony-of-permanent-left-bundle-branch-LSDdzS00VB
SP - 1694
VL - 21
IS - 11
DP - DeepDyve
ER -