Abstract
Aims
Left bundle branch pacing (LBBP) maintains left ventricular synchrony but induces right ventricular conduction delay (RVCD). Although anodal-ring capture (ARC) during bipolar LBBP improves RVCD, it is not achieved in all patients receiving LBBP. This study aimed to analyze the factors influencing ARC implementation.
Methods and results
Patients receiving LBBP with intraoperative ARC testing were enrolled. Electrocardiographic parameters were measured, including stimulus-to-QRS duration (stim-QRSd), stimulus-to-left/right ventricular activation time (stim-LVAT/RVAT), and V6-V1 interpeak interval. The distribution of lead-tip sites was described as the corrected longitudinal and lateral distance (longit-/lat-dist). Relative angles of the LBBP lead were measured. Echocardiography in short-axis view was used to measure the intraseptal lead length. Intergroup comparisons, correlation analysis, and stepwise logistic regression were performed. In total, 105 patients were included, among which 65 (62%) patients achieved ARC at a pacing output ≤ 5.0 V/0.5 ms (average 3.1 V/0.5 ms). Anodal-ring capture further shortened the stim-QRSd by 13.1 ± 7.5 ms. Better unipolar-ring (cathodal) threshold and R-wave sensing in LBBP-ARC group indicated the critical role of ring–septum contact in ARC. Longer corrected longit-dist and shorter corrected lat-dist of lead-tip sites were positively correlated with higher success likelihood of ARC, likely due to the greater relative angle in which the lead enters the septum and consequently the longer intraseptal lead length and better ring–septum contact.
Conclusion
This study elucidated the factors affecting the success likelihood of LBBP-ARC. These findings improve the understanding of LBBP-ARC, providing references for future research and clinical practice.
Keywords: Left bundle branch pacing, Anodal-ring capture, Success likelihood, Influencing factor
Graphical Abstract
Graphical Abstract.
ARC, anodal-ring capture; Bi, bipolar pacing; CL, contraction line; LBBP, left bundle branch pacing; Longit-dist, longitudinal distance; Lat-dist, lateral distance; LV, left ventricle; RV, right ventricle; Stim-RVAT, stimulus-to-right ventricular activation time.
What’s new?
Successful anodal-ring capture in left bundle branch pacing (LBBP-ARC) is attributed to favorable ring–septum contact, which is reflected though the better unipolar-ring (cathodal) threshold and R-wave sensing.
An area of lead-tip sites closer to the anterior–middle septum (higher proportion of left anterior fascicle pacing) was identified with higher success likelihood of LBBP-ARC, likely due to the relatively more obliquely upward angle and longer intraseptal length of lead that cause better ring–septum contact.
Anodal-ring capture in left bundle branch pacing further shortened the QRS duration by 13.1 ms on average, and the effect was constant in patient subgroups with different intrinsic QRS types.
Introduction
A high proportion of right ventricular pacing causes adverse effects on cardiac function due to ventricular dyssynchrony.1 To address the issue, His bundle pacing (HBP) was proposed as a solution to achieve faster and synchronized biventricular excitation by directly capturing the His bundle.2,3 However, shortcomings of HBP have been recognized, such as the difficulty in learning, low success rate, progressively elevated threshold, sensing problems, and the incapacity to correct distal bundle branch block.4
Left bundle branch pacing (LBBP) was subsequently developed as a near-physiological pacing modality that partially overcomes the shortcomings of HBP.5,6 Its efficacy in preserving and improving left ventricular (LV) electromechanical synchrony and cardiac function has been shown not inferior to HBP.7–9 However, LBBP induces right ventricular conduction delay (RVCD),10,11 sacrificing the interventricular synchrony, particularly in patients without intrinsic right bundle branch (RBB) or atrioventricular node (AVN) conduction. A small-sample study12 has described the phenomenon of anodal-ring capture (ARC) during bipolar LBBP (LBBP-ARC) that can eliminate the RVCD by capturing the left bundle branch (LBB) and the right ventricular septum (RVS) simultaneously via the lead’s tip and ring electrodes, respectively. This phenomenon was expected to generate more synchronized biventricular excitation than LBBP. Another study13 indicated that QRS duration (QRSd) reduction after ARC during LBB area pacing exhibited a resynchronization effect and was an independent predictor for echocardiographic response in patients with RBB block (RBBB) and heart failure. However, there were ∼40% of patients with successful LBBP that failed to achieve ARC.12 Factors influencing whether ARC can be achieved within an acceptable range of thresholds have never been explored, and operators lack established experience about how ARC is achieved. Therefore, we conducted the present study with expanded sample size and quantitative analysis of fluoroscopic imaging, pacing parameters, electrocardiogram (ECG), and echocardiogram to explore the issue.
Methods
Study population
The study consecutively included patients who received successful LBBP with ARC testing in the second department of the Arrhythmia Center of Fuwai Hospital (Beijing, China) from May 2019 to May 2021. Implanted devices included single-/dual-chamber pacemakers or cardiac resynchronization therapy (CRT) devices, and all procedures were completed by the senior operators in our department. Patients with incomplete ECG data, pacing testing for ARC, or fluoroscopic imaging during the procedure were excluded from the study due to incapability in ARC judgment and image measurement. Baseline clinical and demographic characteristics were collected, and all patients have been provided with written informed consent for device implantation and clinical data use. The Ethics Committee of Fuwai Hospital approved the study (Approval No. 2018-1074), adhering to the Declaration of Helsinki.
Left bundle branch pacing implantation procedure
The previously described transseptal approach was utilized.14,15 The 3830 lead (1.4 mm, SelectSecure™, Medtronic) was introduced to the RVS via the C315HIS sheath (Medtronic) and screwed to the LBB area. The methodology for lead-implanted site selection was reported in the previous study.15
During implantation procedure, the paced QRS morphology was monitored. The 12-lead ECG with intracardiac electrogram (EGM) was simultaneously displayed and recorded at a sweep speed of 100 mm/s using the Bard system (Bard LabSystem Pro EP Recording System 2.4a.65.0, USA). Successful LBBP16 would manifest as a QRS pattern of RBB conduction delay (Qr, qR, or rsR′), and LBB capture was confirmed for all enrolled patients by at least one of the following conditions: selective LBBP (s-LBBP), transition from non-selective LBBP (ns-LBBP) to left ventricular septal pacing (LVSP) during threshold testing, or an abrupt shortening (>10 ms) of the stimulus-to-left ventricular activation time (stim-LVAT) in lead V6 while increasing the pacing output (Figure 1A).
Figure 1.
Pacing ECG and duration changes after anodal-ring capture. (A) Electrocardiogram demonstrating LBB potential, LVSP to ns-LBBP transition, and ARC. (B) Illustrations of LBBP and LBBP-ARC. (C) Comparable stim-LVAT but significantly shortened stim-QRSd after ARC. ARC, anodal-ring capture; AVN, atrioventricular node; EGM, intracardiac electrogram; IVS, interventricular septal; LBB, left bundle branch; RBB, right bundle branch; LBBP, LBB pacing; LVSP, left ventricular septal pacing; NS, non-significance; ns-LBBP, non-selective left bundle branch pacing; VS, intrinsic rhythm. ***P < 0.001.
Testing scheme and criteria of anodal-ring capture
Once successful LBBP was achieved and the C315HIS sheath was pulled back to the atria, pacing testing was carried out, including the unipolar-tip (−), unipolar-ring (−), and bipolar (tip−ring+) parameters.
During unipolar-tip testing, the R-wave amplitude, impedance, capture threshold, and transition threshold (if applicable) were examined. These parameters were also tested during unipolar-ring testing.
During bipolar testing, in addition to the items in unipolar-tip testing, the ARC threshold was evaluated. Successful ARC was defined as an improvement of RVCD when increasing pacing output (≤5.0 V/0.5 ms) during bipolar LBBP (Figure 1B), resulting in the disappearance or near disappearance of the final R-wave in lead V1 (Figure 1A).12 If patients exhibited s-LBBP at lower outputs, ns-LBBP might be reached first and the process would continue until ARC was achieved or the highest output was reached. Failing to achieve ARC at any pacing output or the threshold > 5.0 V/0.5 ms was considered unsuccessful (LBBP-alone). The reasons for using 5.0 V/0.5 ms as the cutoff are presented in Supplementary material online, Discussion.
Electrocardiogram parameters
Electrocardiogram parameters were measured from the pacing stimulus (Figure 1A), including the stimulus-to-QRS duration (stim-QRSd), stim-LVAT in lead V6 (V6 R-wave peak time), and stimulus-to-right ventricular activation time (stim-RVAT) in lead V1 (V1 R-wave peak time). The V6-V1 interpeak interval was calculated by subtracting stim-LVAT from stim-RVAT, reflecting the discrepancy in excitation time between LV and RV or the interventricular electrical dyssynchrony.17 To reflect the QRS axis direction, R/(Q + S) ratios were measured in leads II and III; an ‘upward’ direction was defined as R/(Q + S) > 1, whereas a ‘downward’ direction was defined as R/(Q + S) ≤ 1.15 The change in stim-QRSd (Δstim-QRSd) was calculated by subtracting the stim-QRSd immediately before ARC from that after ARC. A negative value indicates the shortening of stim-QRSd. All ECG measurements were conducted in the Bard system at a sweep speed of 100 mm/s. At least three QRS complexes were measured, and the average value was calculated.
Distance parameters of lead-tip sites and relative angles of leads
A quantitative coordinate system15 developed from the novel nine-partition method18,19 was applied to describe the distribution of lead-tip sites in RAO 30° view at the end-diastolic phase. The measured distance parameters included the length of the contraction line (CL), distance from CL to apex (CL-apex-dist), longitudinal distance (longit-dist), and lateral distance (lat-dist) (Figure 2A). Corrected longit-dist and corrected lat-dist were created to eliminate the influence of interindividual variations in cardiac sizes.15 Detailed definitions, conversion methods, and reliability levels are provided in Supplementary material online, Table S1.
Figure 2.
Measurement of distance parameters and the distribution of lead-tip sites. (A) Measuring method of distance parameters at end-diastolic phase in RAO 30°. (B) Lead-tip sites of LBBP-ARC (upper cluster) were closer to the anterior–middle septum than sites of LBBP-alone group (lower cluster). (C) Significantly longer corrected longit-dist but shorter corrected lat-dist in the LBBP-ARC group. Abbreviations as in Tables 1 and 2. ***P < 0.001.
To describe the angle at which the lead enters the septum, the relative angle was measured in LAO 30° view at the end-diastolic phase. First, the reference line was drawn along the spine at the cardiac level to eliminate the influence of patients’ posture; then a line perpendicular to the spine line was created. The lead direction was defined as a line running along the tip and ring electrodes. The relative angle was the angle between the lead direction and the second line (Figure3A and B). Blinded to patient information, all imaging measurement was performed at end-diastolic phase using LibreCAD 2.1.3 software with three repetitions by different authors, and the average value was taken.
Figure 3.
Measurement and comparison of relative angles of the LBBP lead. (A, B) Measuring method of relative angles in two cases with LBBP-alone and LBBP-ARC, respectively. (C) Comparison of relative angles between LBBP-alone and LBBP-ARC groups. (D) Significant negative linear correlation between relative angles and corrected lat-dist. (E) The lead enters the septum obliquely upward when the tip is located closer to the anterior–middle septum with greater intraseptal length and easier ARC, but more vertically at lower positions with less intraseptal length. PCC, Pearson’s correlation coefficient. Other abbreviations as in Tables 1 and 2.
Echocardiography showing the intraseptal lead length
In order to directly display the intraseptal length of the lead, post-operative echocardiograms were searched for all enrolled patients to find available data. The short-axis view of two-dimension echocardiogram was used to measure the length (Figure 4A). Measurement was performed at end-diastolic phase by the experienced doctor from the ultrasound department of Fuwai Hospital.
Figure 4.
Comparison of intraseptal lead length measured by echocardiography between LBBP-ARC (n = 22) and LBBP-alone (n = 9) groups. (A) Echocardiogram measuring the intraseptal lead length in short-axis view. (B) LBBP-ARC group had significantly longer intraseptal length of lead than LBBP-alone group. Abbreviations as in Table 1.
Statistical analysis
Continuous variables were reported as mean ± SD for normal distribution or median [Interquartile range IQR] for skewed distribution and compared by the independent sample t-test or Wilcoxon's rank-sum test. Pairwise t-tests were used for paired data, such as stim-QRSd and stim-LVAT before and after ARC. Categorical variables were presented as number (%) and compared using χ2 or Fisher's exact test. Linear regression and Pearson’s correlation coefficient (PCC) were used to examine the correlation between variables. Prior to the regression analysis, residual normality and homogeneity were assessed. Multivariate logistic regression with two-way stepwise selection based on Akaike information criterion (AIC) was performed to identify independent factors contributing to successful ARC. A variance inflation factor (VIF) < 5 indicated the absence of multicollinearity. Adjusted restricted cubic splines (RCSs) were utilized to illustrate the dose–response relationships between variables and outcomes with cutoffs. Receiver operating characteristic (ROC) curves were used to evaluate predictive value of parameters by the area under the curve (AUC) with optimized cutoffs. Positive predictive value (PPV), specificity, and sensitivity were also calculated. All tests were two-sided with a significance level of 0.05. Statistical analysis and data visualization were performed in R (4.2.1) and RStudio (2022.07.1 + 554).
Results
Baseline and pacing characteristics
A total of 204 patients with successful LBBP were screened, among which 105 patients with intact ARC testing, ECG, and imaging data were included in analysis (see Supplementary material online, Figure S1). Baseline characteristics are presented in Table 1. Most patients required pacemaker implantation due to atrioventricular block (AVB, 69.5%) with normal cardiac function [LV ejection fraction, 63 (60, 65)%] and a narrow QRS complex (68.3%).
Table 1.
Baseline characteristics
| Characteristics | All patients (n = 105) | LBBP-ARC (n = 65) | LBBP-alone (n = 40) | P value |
|---|---|---|---|---|
| Age (years) | 65 (55, 72) | 65 (55, 72) | 65.5 (56.8, 72) | 0.96 |
| Male sex | 54 (51.4) | 36 (55.4) | 18 (45.0) | 0.30 |
| Pacing indication | ||||
| Sick sinus syndrome | 17 (16.2) | 10 (15.4) | 7 (17.5) | 0.79 |
| Atrioventricular block | 73 (69.5) | 44 (67.7) | 29 (72.5) | 0.67 |
| AF with bradycardia | 9 (8.6) | 6 (9.2) | 3 (7.5) | 1.00 |
| Heart failure | 6 (5.7) | 5 (7.7) | 1 (2.5) | 0.40 |
| LVEF (%) | 63 (60, 65) | 63 (60, 65) | 62 (60, 65) | 0.97 |
| LVEDD (mm) | 49 (46, 54) | 48 (46, 54) | 49 (45.8, 52) | 0.99 |
| IVST (mm) | 10 (8, 10) | 10 (8, 10) | 9 (8, 10) | 0.21 |
| Intrinsic QRSd (ms) | 108 (98, 142) | 110 (99.5, 142.5) | 106 (97.5, 118.5) | 0.17 |
| Intrinsic LVAT (ms) | 42 (38, 50) | 42 (38, 52) | 41 (34, 48) | 0.18 |
| Intrinsic QRS type | ||||
| Narrow (<120 ms) | 71/104a (68.3) | 39/64 (60.9) | 32/40 (80) | 0.07 |
| LBBB | 7/104a (6.7) | 6/64 (9.4) | 1/40 (2.5) | 0.25 |
| RBBB | 24/104a (23.1) | 17/64 (26.6) | 7/40 (17.5) | 0.34 |
| IVCD | 2/104a (1.9) | 2/64 (3.1) | 0 | 0.52 |
Data were presented as n (%), mean ± SD, and median (IQR).
AF, atrial fibrillation; ARC, anodal-ring capture; IVCD, intraventricular conduction delay; IVST, interventricular septal thickness; LBBB, left bundle branch block; LBBP, left bundle branch pacing; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; QRSd, QRS duration; LVAT, left ventricular activation time; RBBB, right bundle branch block.
One patient without intrinsic rhythm was supported by temporary pacing.
Sixty-five patients (62%) demonstrated ARC at a pacing output ≤ 5.0 V/0.5 ms [49 (75.4%) had an ARC threshold ≤ 3.5 V/0.5 ms], with the average ARC threshold of 3.1 ± 0.9 V/0.5 ms. Stimulus-to-QRS duration was significantly shortened after ARC (152.4 ± 11.3 vs. 139.3 ± 11.0 ms, P < 0.0001; Δstim-QRSd = −13.1 ± 7.5 ms), while stim-LVAT remained constant (72.2 ± 9.3 vs. 71.8 ± 9.5 ms, P = 0.08) (Figure 1C).
In patients unable to achieve ARC at an output ≤ 5.0 V/0.5 ms (LBBP-alone), three reached ARC at 10 V/0.5 ms, while one reached ARC at 6.0 V/0.5 ms. Other patients showed no signs of ARC within 5.0 V/0.5 ms, without documenting the exact thresholds. Similar baseline characteristics were observed between the two groups (Table 1).
Comparisons between successful anodal-ring capture and left bundle branch pacing-alone groups
In the unipolar-tip (−) testing (Table 2), no significant differences were observed between the two groups regarding pacing parameters, LBB potential or s-LBBP proportions, and stim-LVAT, indicating their similar performance in LBBP. However, stim-QRSd, stim-RVAT, and V6-V1 interpeak intervals were significantly longer in the LBBP-ARC group by ∼7 ms compared to those in the LBBP-alone group. Moreover, a higher proportion of upward QRS [R/(Q + S) > 1] in lead III was observed in the LBBP-ARC group than in the LBBP-alone group (40 vs. 15%, P = 0.01), suggesting a higher pacing site in the former group.
Table 2.
Comparisons of pacing and distance parameters between LBBP-ARC and LBBP-alone
| Parameters | All patients (n = 105) | LBBP-ARC (n = 65) | LBBP-alone (n = 40) | P value |
|---|---|---|---|---|
| Unipolar tip (−) testing | ||||
| Threshold (V/0.5 ms) | 0.8 (0.5, 1.0) | 0.7 (0.5, 0.9) | 0.8 (0.5, 1.0) | 0.30 |
| Impedance (ohm) | 753.7 ± 166.2 | 734.9 ± 160.0 | 784.2 ± 173.5 | 0.15 |
| R-wave amplitude (mV) | 10 (6.8, 15.0) | 9.9 (6.3, 15) | 10.7 (7.3, 14.4) | 0.50 |
| LBB potential | 72 (68.6) | 41 (63.1) | 31 (77.5) | 0.18 |
| Selective LBBP | 33 (31.4) | 18 (27.7) | 15 (37.5) | 0.39 |
| ns-LBBP to LVSP transition | 49 (46.7) | 33 (50.8) | 16 (40.0) | 0.38 |
| stim-LVAT abruptly shortened >10 ms | 23 (21.9) | 14 (21.5) | 9 (22.5) | 0.91 |
| stim-QRSd (ms) | 149.6 ± 11.2 | 152.4 ± 11.3 | 145.1 ± 9.4 | <0.001 |
| stim-LVAT (ms) | 72.5 ± 8.5 | 72.2 ± 9.3 | 73.0 ± 7.2 | 0.65 |
| stim-RVAT (ms) | 108.6 ± 9.2 | 111.0 ± 9.6 | 104.9 ± 7.1 | <0.001 |
| V6-V1 interpeak interval (ms) | 36.1 ± 10.7 | 38.7 ± 11.2 | 31.9 ± 8.5 | <0.001 |
| Upward QRS in II ECG lead | 71 (67.6) | 46 (70.8) | 25 (62.5) | 0.38 |
| Upward QRS in III ECG lead | 32 (30.5) | 26 (40) | 6 (15) | 0.01 |
| Unipolar ring (−) testing | ||||
| Capture threshold (V/0.5 ms) | 1.0 (0.7, 1.4) | 0.8 (0.7, 1.0) | 2.3 (1.0, 4.0)a | <0.0001 |
| Capture threshold ≤ 5 V/0.5 ms | 93 (88.6) | 65 (100) | 28 (70.0)a | <0.001 |
| Impedance (ohm) | 473.7 ± 87.5 | 480.5 ± 76.1 | 459.6 ± 107.3 | 0.34 |
| R-wave amplitude (mV) | 7.4 (4.3, 10.6) | 9.0 (6.2, 12.5) | 4.2 (3.4, 5.5) | <0.0001 |
| stim-QRSd (ms) | 165.5 ± 15.0 | 166.6 ± 16.0 | 163.3 ± 12.6 | 0.28 |
| stim-LVAT (ms) | 104.6 ± 14.8 | 105.1 ± 14.6 | 103.5 ± 15.3 | 0.63 |
| Distance parameters | ||||
| Length of CL (mm) | 150.7 ± 13.4 | 153.1 ± 13.8 | 146.9 ± 11.9 | 0.02 |
| CL-apex-dist (mm) | 119.0 ± 11.7 | 119.4 ± 11.9 | 118.3 ± 11.6 | 0.67 |
| Longit-dist (mm) | 27.2 ± 11.0 | 30.0 ± 10.1 | 22.7 ± 10.9 | 0.001 |
| Lat-dist (mm) | 81.8 ± 14.9 | 78.8 ± 15.4 | 86.6 ± 12.7 | 0.008 |
| Corrected longit-dist (mm) | 27.0 ± 10.1 | 29.8 ± 9.2 | 22.6 ± 10.1 | <0.001 |
| Corrected lat-dist (mm) | 82.0 ± 14.5 | 77.6 ± 14.3 | 89.0 ± 12.0 | <0.0001 |
Data were presented as n (%), mean ± SD, and median (IQR).
ARC, anodal-ring capture; CL, contraction line; CL-apex-dist, distance from CL to apex; Lat-dist, lateral distance; LBBP, left bundle branch pacing; Longit-dist, longitudinal distance; stim-LVAT, stimulus-to-left ventricular activation time; stim-QRSd, stimulus-to-QRS duration; stim-RVAT, stimulus-to-right ventricular activation time; V6-V1 interpeak interval, stim-RVAT minus stim-LVAT.
Ten patients could not achieve unipolar-ring (−) capture at 5.0 V/0.5 ms without documenting the exact threshold.
In the unipolar-ring (−) testing (Table 2), patients with LBBP-ARC demonstrated lower RVS capture thresholds [0.8 (0.7, 1.0) vs. 2.3 (1.0, 4.0) V/0.5 ms, P < 0.0001] and higher R-wave amplitude [9.0 (6.2, 12.5) vs. 4.2 (3.4, 5.5) mV, P < 0.0001] than those in the LBBP-alone group, indicating favorable ring–septum contact in patients achieving LBBP-ARC. Receiver operating characteristic curves confirmed the value of the unipolar-ring threshold (AUC 0.80, cutoff 1.25 V/0.5 ms) and R-wave sensing (AUC 0.81, cutoff 6.55 mV) in ARC prediction (see Supplementary material online, Figure S2), further confirming the notion that excellent ring–septum contact is the foundation of ARC.
In terms of the distribution of lead-tip sites, patients who achieved LBBP-ARC had significantly longer corrected longit-dist (29.8 ± 9.2 vs. 22.6 ± 10.1 mm, P < 0.001) but shorter corrected lat-dist (77.6 ± 14.3 vs. 89.0 ± 12.0 mm, P < 0.0001) than those in the LBBP-alone group (Table 2 and Figure 2C). Lead-tip sites in these two groups were distributed in two different clusters, and the cluster of LBBP-ARC was located closer to the anterior–middle septum (Figure 2B).
Correlation analysis revealed significant positive linear correlations among the stim-QRSd, stim-RVAT, V6-V1 interpeak interval during unipolar LBBP, and the corrected longit-dist (see Supplementary material online, Figure S3). It is rational that RVCD (stim-RVAT) contributes to interventricular dyssynchrony (V6-V1 interpeak interval) and prolonged stim-QRSd during LBBP. Additionally, upward QRS direction in lead III during LBBP was correlated with shorter corrected lat-dist instead of other parameters (see Supplementary material online, Figure S4).
Influencing factors of successful anodal-ring capture in left bundle branch pacing
After elucidating the intervariable correlations, univariate logistic regression analysis revealed the significant positive correlations between the success likelihood of LBBP-ARC and stim-QRSd (per 5 ms, OR 1.38, 95% CI 1.14–1.72, P = 0.002), stim-RVAT (per 5 ms, OR 1.52, 95% CI 1.19–2.00, P = 0.002), and V6-V1 interpeak interval (per 5 ms, OR 1.38, 95% CI 1.13–1.71, P = 0.002) during unipolar LBBP, as well as the corrected longit-dist (per 5 mm, OR 1.37, 95% CI 1.11–1.72, P = 0.004). Conversely, longer corrected lat-dist (per 5 mm, OR 0.71, 95% CI 0.59–0.84, P < 0.001) was correlated with lower success likelihood of ARC.
Following the two-way stepwise selection of these five variables, three variables remained in the multivariate logistic model (AIC = 112.8) (Figure 5A). Every 5 mm increase in the corrected longit-dist was correlated with a 43% rise in ARC success likelihood (per 5 mm, OR 1.43, 95% CI 1.27–1.87, P = 0.005) while decreasing corrected lat-dist by 5 mm was associated with a 45% increase in ARC success likelihood (per 5 mm, OR 0.69, 95% CI 0.55–0.83, P = 0.0003). Nonetheless, it was important to note that the corrected longit-dist should not exceed the upper limit of 49.1 mm, which corresponded to its maximal value of all participants and ∼2/5 (41.2%) of the mean CL-apex-dist (119 mm). Similarly, the corrected lat-dist should be kept higher than 41.6 mm, which represents its minimum value among all enrolled sites and ∼1/3 (27.6%) of the mean length of CL (150.7 mm). On the other hand, longer stim-RVAT during LBBP (per 5 ms, OR 1.38, 95% CI 1.05–1.82, P = 0.02, VIF = 1.01) was also associated with successful ARC after stepwise selection. Adjusted RCSs further confirmed the corresponding dose–response relationships between the success likelihood of ARC and these three variables (Figure 5B–D). The cutoffs of corrected longit-dist and corrected lat-dist were 26.9 mm (∼1/5 of the mean CL-apex-dist) and 82.7 mm (∼3/5 of the mean CL length), respectively. It was observed that the condition ‘corrected lat-dist ≤ 82.7 mm’ had better PPV (78.8 vs. 71.2%), specificity (72.5 vs. 62.5%), and sensitivity (63.0 vs. 56.9%) than ‘corrected longit-dist ≥ 26.9 mm.’ The highest PPV (84.6%) and specificity (90.0%) were reached when both conditions were satisfied, but the sensitivity (33.8%) fell to the bottom (Table 3).
Figure 5.
Multivariate logistic analysis of successful LBBP-ARC. (A) Variables remaining in the multivariate model after stepwise selection. (B, C) Adjusted restricted cubic splines elucidate positive dose–response relationships of LBBP stim-RVAT and corrected longit-dist to successful LBBP-ARC. (D) Negative relationship of corrected lat-dist to successful LBBP-ARC. OR, odds ratio; VIF, variance inflation factor. Other abbreviations as in Tables 1 and 2.
Table 3.
Predictive value of different conditions
| Conditions | LBBP-ARC | LBBP-alone | PPV (%) | SPE (%) | SEN (%) |
|---|---|---|---|---|---|
| Corrected longit-dist ≥ 26.9 mm | 37 | 15 | 71.2 | 62.5 | 56.9 |
| Corrected lat-dist ≤ 82.7 mm | 41 | 11 | 78.8 | 72.5 | 63.0 |
| Both distance conditions satisfied | 22 | 4 | 84.6 | 90 | 33.8 |
| LBBP stim-RVAT ≥ 108 ms | 41 | 15 | 73.2 | 62.5 | 63.1 |
PPV, positive predictive value; SEN, sensitivity; SPE, specificity. Other abbreviations as in Table 2.
Based on experience, a site closer to the anterior septum is likely associated with a more obliquely upward direction in which the lead enters the septum. In order to evaluate the hypothesis, the relative angle in LAO 30° view was measured for each patient (Figure3A and B), finding that the LBBP-ARC group had a larger relative angle than the LBBP-alone group with marginal significance (22.2 ± 11.5° vs. 18.1 ± 11.4°, P = 0.077) (Figure 3C). Besides, significant negative correlation was revealed between the corrected lat-dist and the relative angle of leads (β = −0.50, P < 0.0001, PCC = −0.62) (Figure 3D). Further, post-operative echocardiograms were searched, and finally, the data of 31 patients were available, among which 22 patients were LBBP-ARC and 9 patients were LBBP-alone. Comparison indicated that the intraseptal lead length (Figure 4A) of LBBP-ARC patients was significantly longer than that of LBBP-alone patients (11.9 ± 2.1 vs. 10.1 ± 1.9 mm, P = 0.036) (Figure 4B). It can be rationally concluded that leads in the LBBP-ARC group were more closer to the anterior septum (shorter corrected lat-dist) and likely to enter the septum in an obliquely upward direction (larger relative angles), possibly leading to a longer intraseptal length and better ring–septum contact (Figures 3E and 4B).
QRS duration shortening after anodal-ring capture
In patients with LBBP-ARC, a significant reduction in stim-QRSd was noted after ARC compared to pure LBBP (Δstim-QRSd = −13.1 ± 7.5 ms, P < 0.0001). Similar average levels of ARC thresholds (ranged from 3.0 to 3.3 V/0.5 ms) and comparable shortening degrees of stim-QRSd were found in all subgroups with different intrinsic QRS types (average Δstim-QRSd were −12.7, −13.8, and −16.3 ms in the narrow, RBBB, and LBBB subgroups, respectively) (see Supplementary material online, Table S2).
Discussion
The primary findings were as follows. (i) Sixty-two percent of enrolled patients exhibited ARC in LBBP at an output ≤ 5.0 V/0.5 ms with an average threshold of 3.1 V/0.5 ms; favorable ring–septum contact serves as the foundation of successful ARC. (ii) Longer corrected longit-dist and shorter corrected lat-dist correlated with higher success likelihood of LBBP-ARC, with the cutoffs of 26.9 mm (∼1/5 of the mean CL-apex-dist) and 82.7 mm (∼3/5 of the mean CL length), respectively. (iii) The leads in LBBP-ARC group were found to enter the septum in a more obliquely upward direction, probably contributing to a longer intraseptal lead length and easier ARC. (iv) From LBBP to LBBP-ARC, an average stim-QRSd shortening was 13.1 ms, and similar shortening extent was observed in subgroups with different intrinsic QRS types.
Left bundle branch pacing has been shown to improve or preserved LV electromechanical synchrony,20 but it sacrifices the interventricular synchrony by causing RVCD, particularly in patients lacking intrinsic RBB conduction.10 Studies have reported that the presence of RBBB is significantly associated with an elevated risk of adverse cardiovascular events, heart failure, and all-cause mortality, even in the general population without known cardiovascular diseases.21,22 However, RVCD during LBBP is mainly caused by direct LV septal capture from the tip and left-to-right transseptal conduction delay, which is quite different from RBBB in physiological mechanism. Although RBBB-induced ventricular dyssynchrony may be a potential reason for worse outcomes, subclinical myocardial diseases involving RBB might also exist to cause detrimental effects. Whether there are potential detrimental effects of LBBP-induced RVCD is uncertain. A prior small-sample study12 reported the phenomenon of ARC that simultaneously captures the LBB and RVS through the tip and ring electrodes of the 3830 lead and termed it bilateral bundle branch area pacing. Nevertheless, this term is actually misleading because direct RBB capture was not confirmed and fast RBB engagement was also unlikely, as the basal RV pacing site is far away from the first contact of Purkinje cells and contractile myocytes that is within the papillary muscle. Another study13 suggested that QRSd reduction by ARC during LBB area pacing was an independent predictor of echocardiographic response in patients with RBBB and heart failure. The present study confirmed that ARC during LBBP can further shorten QRSd by an average of 13.1 ms and has comparable effects across different patient subgroups (ranging from 12.7 to 16.3 ms), suggesting the similar resynchronization value in eliminating RVCD based on QRSd. In fact, RVCD during LBBP has been shown to largely depend on the transseptal conduction delay.17,23 Whether it is RVS myocardium or RBB captured has little influence on this mechanism, but possibly the QRSd shortening extent. However, undesirable influence of the non-physiological right-to-left septal depolarization should be considered when RVS myocardium is captured by the ring, which seems to increase the QRS area. QRS area is a vectorcardiographic parameter and its reduction has been found to have predictive value in CRT response.24 Another study25 has found that the reduction of both QRS area and QRSd could independently predict patient outcomes after CRT implantation, and patients with both parameters reduced had better outcomes than those with any one of them reduced. Due to the limitation of technology, this parameter could not be provided in this study.
After evaluating the effects on QRSd shortening, factors impacting the success likelihood of ARC were explored. Homogeneous LBBP performance was observed between the LBBP-ARC and LBBP-alone groups, as reflected by similar stim-LVAT and proportions of s-LBBP and LBB potential, indicating that the lead tips in both groups had reached the same layer of the LBB area. Superior unipolar-ring thresholds and R-wave sensing were found in patients who achieved LBBP-ARC, signifying the better ring–septum contact or greater intraseptal length of the ring electrode, which we consider the foundation of successful ARC. Receiver operating characteristic analysis further confirmed this relationship by elucidating their predictive value. Specially, a unipolar-ring threshold ≤ 1.25 V/0.5 ms or R-wave amplitude ≥ 6.55 mV portended a high probability of ARC with acceptable thresholds. Other factors might indirectly affect ARC by influencing this point.
Quantitative analysis revealed the association between the distribution of lead-tip sites and the success likelihood of ARC. The results suggested that a lead-tip site closer to the anterior septum (shorter corrected lat-dist) or further from the CL (longer corrected longit-dist) is more likely to achieved ARC, as the cutoffs of these two distance parameters showed high PPV and specificity for ARC. Considering the range of all enrolled sites, a target area with higher success likelihood of ARC (OR > 1) was identified within the specific range: 1/5–2/5 of the CL-apex-dist and 1/3–3/5 of the CL length. Fractions rather than absolute values were used because the cutoffs generated by the corrected distance parameters are just applicable to the average cardiac size. Converting these cutoffs to fractions aimed to generalize the results to individuals using the 3830 lead for LBBP implantation. The result also indicated that left fascicular pacing (LFP), especially left anterior fascicular pacing (LAFP), was more common in patients with LBBP-ARC, as the proportion of upward QRS in lead III during unipolar-tip pacing was significantly higher than that in LBBP-alone group (40 vs. 15%), corresponding to the distribution of lead-tip sites. MELOS study26 reported the rate of LFP was 69.5%, similar to the rate of LBBP-ARC (62%) in our study.
To explain the mechanism, we hypothesized that the lead is more inclined to enter the septum obliquely upward when it is situated closer to the anterior septum, owing to the sheath's direction and the curvature of the RVS (Figure 3C–E). Such feature caused a greater intraseptal lead length, which in turn facilitated successful ARC (Figures 3E and 4B). Conversely, the lead will enter the septum more vertically at inferior sites, resulting in shorter intraseptal length and more difficult ARC (Figures 3C–E and 4B). Additionally, the anterior–middle septum is likely to be thicker than other areas due to the uneven distribution of septal thickness.27 Additional information is presented in Supplementary material online, Discussion.
An independent correlation between longer stim-RVAT and successful ARC was also uncovered. Prolonged RVCD during LBBP is primarily due to left-to-right transseptal conduction delay,11,17,23 which is mediated by the vertical myocardial laminar sheets and septal thickness.28 Besides, depth of lead placement might influence stim-RVAT and V6-V1 interpeak interval as well, which was considered less likely because similar LBBP performance has been found between LBBP-ARC and LBBP-alone groups. If deeper or shallower lead placement was the situation that actually existed in the two groups, differences would exist not only in stim-RVAT and V6-V1 interpeak interval, but also in stim-LVAT and the proportions of LBB potential and S-LBBP. Therefore, it is more likely to be considered that longer stim-RVAT was correlated with a thicker septum in the lead-implanted region, which made it easier for the ring electrode to contact and capture the RVS. However, depth of lead deployment is an influencing factor that should be considered in practice.
Based on the results, several approaches were proposed to judge the likelihood of ARC as follows: (i) Before screwing the lead, relative angles can be inspected in LAO 30°, and a more obliquely upward direction of the lead or sheath portends a higher success likelihood of ARC. (ii) Following the placement of the lead, pacing test can be performed and stim-RVAT > 108 ms, unipolar-ring (cathodal) threshold < 1.25 V/0.5 ms, or R-wave sensing > 6.55 mV indicate higher success likelihood of ARC, but these parameters are less useful because ARC testing can be directly performed. (iii) When the initial attempt is unsuccessful or unacceptable, the lead can be repositioned closer to the anterior–middle septum than the original site. However, as the 3830 lead was the only authorized tool for conduction system pacing in our country during the study period, the results were based on this instrument exclusively. Different leads with various interelectrode distance will generate different results. The Solia S lead and Selectra 3D sheath (Biotronik, German) have not been formally utilized in LBBP in our country and the data were limited. However, according to the product manuals, the interelectrode distance of the 3830 lead was shorter than the Solia S lead (9 vs. 10 mm).29 Our center possesses the earliest trial data about the Biotronik tools in our country and the unpublished data indicated that the proportion of ARC in the Solia S60 group was significantly lower than that in the 3830 control group (36.4 vs. 68.6%, P = 0.028). Besides, the average unipolar-ring capture threshold in the Solia S60 group had a tendency to be higher than the 3830 group (1.5 vs. 0.8 V/0.5 ms), which corresponded to the results in this study. Nevertheless, the 3830 lead is still the most popular instrument for LBBP all over the world and this study will provide references when using this kind of leads. Other factors affecting ARC should also be considered when interpreting these results, such as operators’ techniques and experience, heart structure, septal thickness, and myocardium conditions.
Limitations
As a retrospective study, direct measurement of ring–septum contact or intraseptal lead length using the contrast injection was not feasible due to rare clinical use in our center. The study was exclusively based on 3830 lead, and further investigations and comparisons of other instruments are required to offer additional evidence. Only 31 patients had echocardiographic data showing the intraseptal lead length, and more data are required to provide more solid evidence. Cardiac function of most enrolled patients was relatively normal; thus, it should be careful when interpreting the results in heart failure patients.
Conclusions
This study first quantitatively analyzed the influencing factors of LBBP-ARC. A target area for lead tips closer to the anterior–middle septum was identified with a higher success likelihood of ARC, owing to greater relative angles of lead entering the septum and enhanced ring–septum contact. These findings advance the understanding of LBBP-ARC and offer a reference for further exploration into its clinical applications.
Supplementary Material
Acknowledgements
We thank Dr Nan Xu for her help in echocardiography examination and measurement. She is an experienced doctor in the Ultrasound Department of Fuwai Hospital.
Contributor Information
Wenzhao Lu, State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing 100037, China.
Jinxuan Lin, Department of Cardiovascular Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Yao Li, State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing 100037, China.
Qingyun Hu, State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing 100037, China.
Chendi Cheng, State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing 100037, China.
Ruohan Chen, State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing 100037, China.
Yan Dai, State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing 100037, China.
Keping Chen, State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing 100037, China.
Shu Zhang, State Key Laboratory of Cardiovascular Disease, Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing 100037, China.
Supplementary material
Supplementary material is available at Europace online.
Authors’ contributions
W.L., K.C., and Y.D. came up with the conception and designed the study. Data collection and measurement were completed by W.L., J.L., Y.L., Q.H., and C.C. Data analysis, result interpretation, and article drafting were performed by W.L. All the authors participated in LBBP operations, clinical practice, and article revisions. The final approval of the submitted version was performed by K.C., Y.D., and S.Z.
Funding
This work was supported by the National Natural Science Foundation of China (Grant Number 81870260).
Data availability
Data are available upon reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Ethics approval
This work was approved by the Ethics Committee of Fuwai Hospital (Approval No. 2018-1074), obeying the Declaration of Helsinki.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data are available upon reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.