Ventricular Lead Positioning Within the Left Conduction System in Permanent Cardiac Pacing: A Systematic Review and Meta-analysis

Ventricular Lead Positioning Within the Left Conduction System in Permanent Cardiac Pacing: A Systematic Review and Meta-analysis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 19 September 2025 V1 Latest version Share on Ventricular Lead Positioning Within the Left Conduction System in Permanent Cardiac Pacing: A Systematic Review and Meta-analysis Authors : Mateus Barros de Araújo 0009-0000-0500-8990 [email protected] , Gustavo Toaiari Staico , Felipe Vieira Santana , Vitor Bastos Lovisi , Guilherme de Carvalho 0000-0001-8587-875X , and Leonardo Antunes Mesquita Authors Info & Affiliations https://doi.org/10.22541/au.175826532.24187642/v1 Published Journal of Interventional Cardiac Electrophysiology Version of record Peer review timeline 223 views 118 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Left bundle branch pacing (LBBP) and left bundle fascicular pacing (LBFP) are conduction system pacing techniques that preserve physiological ventricular activation. Whether proximal or distal capture yields superior electrical or echocardiographic outcomes is uncertain. Objective: To systematically evaluate and compare LBFP versus left bundle branch trunk pacing (LBTP) in terms of electrical synchrony and echocardiographic characteristics in patients requiring permanent cardiac pacing. Methods: We searched PubMed, Embase, and Cochrane through May 21, 2025, for randomized and observational studies comparing LBFP with LBTP. Outcomes of interest included QRS duration, V6 R-wave peak time (RWPT), left ventricular activation time (LVAT), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and pacing thresholds. Statistical analysis was performed using a random-effects model, with heterogeneity assessed using I 2 statistics. Risk of bias was evaluated using the ROBINS-I. Results: Six studies involving 2,989 patients (1,241 LBFP; 249 LBTP) were included. LBFP was associated with a significantly shorter V6-RWPT (mean difference: –3.50 ms; 95% CI: –5.74 to –1.26; p=0.002), suggesting improved electrical synchrony. No significant differences were observed in QRS duration, LVAT, LVEF, LVEDD, or pacing thresholds. Both modalities demonstrated high procedural success and low, stable capture thresholds. Conclusion: LBFP achieved faster ventricular activation compared with LBTP, while maintaining comparable mechanical performance and pacing stability. Its broader anatomical accessibility and favorable electrical profile support LBFP as a practical alternative particularly when proximal conduction capture is not feasible. Further randomized trials are warranted to assess long-term outcomes. Keywords: Conduction system pacing; left bundle branch pacing; fascicular pacing; ventricular synchrony; permanent pacemaker; meta-analysis; cardiac resynchronization Glossary of Abbreviations: CSP : Conduction system pacing; HBP : His bundle pacing; LBBAP : Left bundle branch area pacing; LBBP : Left bundle branch pacing (proximal/trunk); LBFP : Left bundle fascicular pacing; LBTP : Left bundle trunk pacing; LVAT : Left ventricular activation time; LVEDD : Left ventricular end-diastolic diameter; RWPT : R-wave peak time (lead V6); ROBINS-I : Risk of Bias in Non-Randomized Studies of Interventions; RoB 2 : Cochrane Risk of Bias 2.0 tool; PROSPERO : International Prospective Register of Systematic Reviews; NYHA : New York Heart Association (functional class). Introduction Permanent cardiac pacing remains a cornerstone in the treatment of symptomatic bradyarrhythmias and advanced atrioventricular conduction disturbances. While right ventricular pacing (RVP) is widely practiced, its long-term use has been associated with electrical dyssynchrony, adverse left ventricular (LV) remodeling, and pacing-induced cardiomyopathy (1,2). These limitations have prompted increasing interest in conduction system pacing (CSP) techniques that preserve or restore physiologic ventricular activation (3,4). Among CSP strategies, His bundle pacing (HBP) was the first to demonstrate direct engagement of the native conduction system (5). However, technical challenges—such as high capture thresholds and lead instability—have hindered its broad adoption (6,7). More recently, left bundle branch area pacing (LBBAP) has emerged as a promising alternative, offering lower and more stable pacing thresholds while maintaining near-physiological ventricular activation (8,9). LBBAP encompasses two distinct anatomical targets: left bundle branch pacing (LBBP), which captures the proximal trunk of the left bundle, and left bundle fascicular pacing (LBFP), which targets distal branches such as the anterior, posterior or septal fascicles (10). Although both techniques aim to achieve synchronous LV activation, they differ in anatomical feasibility, electrical performance, and possibly clinical outcomes. Some studies suggest superior electrical resynchronization with LBBP (11,12), whereas others report comparable outcomes between LBBP and LBFP in terms of QRS duration, left ventricular activation time (LVAT), and mechanical synchrony. LBFP may offer technical advantages due to its broader anatomical accessibility (13,14). Despite growing clinical adoption, the comparative efficacy, physiological effects, and outcomes of LBBP versus LBFP remain insufficiently characterized. This systematic review and meta-analysis aimed to compare these pacing strategies with respect to electrophysiological, procedural, and clinical parameters. Methods Study Registration and Reporting Framework This study was registered in PROSPERO (CRD420251061217) and conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (15) and the PRISMA guidelines (16). Eligibility Criteria We included randomized controlled trials and comparative observational studies (prospective or retrospective) that enrolled patients undergoing permanent cardiac pacing targeting the left conduction system (LBBP or LBFP). Studies were eligible if they compared pacing of the left bundle trunk (LBBP) versus left fascicular branches (LBFP: anterior, posterior or septal). Eligible studies reported at least one of the following outcomes: QRS duration or morphology, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, heart failure hospitalization, or mortality (all-cause or cardiovascular). Secondary endpoints included procedural success, pacing thresholds, sensing parameters, lead stability, complications (e.g., lead dislodgment or perforation), and device revisions. Case reports, non-comparative case series, conference abstracts, editorials, reviews, and studies lacking original outcome data were excluded. No restrictions were placed on language or publication date. Search Strategy and Data Extraction A comprehensive literature search was performed on May 21, 2025, using PubMed, Cochrane Library, and Embase. The search strategy included the following terms: (”left bundle branch pacing” OR ”left bundle trunk” OR ”left bundle branch area pacing” OR LBBAP OR LBBP) AND (”left fascicular pacing” OR ”selective bundle pacing” OR ”left anterior fascicular” OR ”left posterior fascicular” OR LBFP). Data were extracted independently by two reviewers and included: (1) QRS duration, (2) LVEF, (3) LV end-diastolic diameter (LVEDD), (4) V6 R-wave peak time (RWPT), (5) LVAT, and (6) pacing thresholds. Disagreements were resolved by consensus. Definitions of outcomes are provided in Supplementary Table 1. Risk of Bias Assessment Risk of bias was independently assessed by two reviewers (FVS and VBL) using validated tools. For non-randomized studies, the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) (17) tool was applied. Discrepancies were resolved by discussion and consensus. Each domain and the overall risk were rated as low, moderate, serious, or critical (ROBINS-I) according to established criteria. Graphical summaries were generated using the robvis visualization tool (Supplementary Figure S1). Statistical Analysis Continuous outcomes were synthesized using mean differences (MDs) and 95% confidence intervals (CIs), employing a random-effects model with inverse-variance weighting. Between-study heterogeneity was quantified using I², τ², and Cochran’s Q statistic. Heterogeneity was classified as low (I² ≤25%), moderate (26–50%), or high (>50%). For studies reporting separate data for left anterior and posterior fascicular pacing, subgroup results were pooled to generate overall LBFP estimates, using Cochrane Handbook formulas. All analyses were performed using RevMan 5.4. Leave-one-out sensitivity analyses were conducted to assess the influence of individual studies on pooled estimates (Supplementary Figure 2). Due to the small number of studies (n=6), publication bias was not formally assessed. The GRADE framework (19) was used to assess the certainty of evidence. Results Study Selection and Characteristics The literature search identified 151 studies. After removing duplicates and applying eligibility criteria, six studies involving 2,989 patients were included (7,12–14,20,21) (Figure 1) . Of these, 1,241 underwent LBFP and 249 received LBBP. Patients undergoing alternative modalities such as LV septal or non-selective conduction pacing were excluded from pooled comparisons. Study characteristics are presented in Table 1 and Supplementary Table S2. Pooled Outcomes QRS Duration No significant difference was observed between LBBP and LBFP (MD: 2.02 ms; 95% CI: -0.70 to 4.74; p = 0.15; I² = 57%). However, a trend toward shorter QRS with LBBP was noted. Sensitivity analysis excluding the MELOS study yielded a significant difference favoring LBBP (MD: 2.98 ms; 95% CI: 0.28 to 5.69; p = 0.03) (Figure 2). V6 R-wave Peak Time (RWPT) LBFP demonstrated significantly shorter V6-RWPT than LBBP (MD: -3.50 ms; 95% CI: -5.74 to -1.26; p = 0.002), suggesting more rapid lateral wall activation and potentially more physiological conduction (Figure 3). Left Ventricular Activation Time (LVAT) Although LVAT was numerically shorter with LBFP, the difference did not reach statistical significance (MD: -1.95 ms; 95% CI: -4.82 to 0.91; p = 0.11) (Figure 4). Left Ventricular Ejection Fraction (LVEF) LBBP was associated with a non-significant trend toward greater improvement in LVEF (MD: 0.61%; 95% CI: -0.99 to 2.21; p = 0.45), suggesting a possible advantage in systolic function (Figure 5). Left Ventricular End-Diastolic Diameter (LVEDD) LVEDD was comparable between pacing modalities (MD: -0.14 mm; 95% CI: -1.88 to 1.59; p = 0.87), suggesting no significant differences in structural remodeling (Figure 6). Pacing Threshold There was no significant difference in capture thresholds between groups (MD: -0.23 V; 95% CI: -0.55 to 0.09; p = 0.10), indicating comparable long-term electrical performance (Figure 7). Discussion In this systematic review and meta-analysis, we compared the electrophysiological and mechanical outcomes of left bundle branch pacing versus left bundle fascicular pacing — two distinct modalities within the spectrum of conduction system pacing. Our main findings were: 1. LBFP was associated with a significantly shorter V6 RWPT, suggesting faster lateral LV activation. 2. QRS duration, LVEF, LV end-diastolic diameter, LVAT, and pacing thresholds did not differ significantly between techniques. 3. A trend toward greater LVEF improvement was noted with LBBP, particularly in patients with reduced baseline systolic function. 4. Both strategies demonstrated favorable safety profiles with low and stable capture thresholds. LBBAP has gained attention as a physiologic alternative to right ventricular pacing and His bundle pacing, offering advantages in electrical synchrony with more favorable implantation characteristics. Within this modality, LBBP targets the proximal left bundle trunk, while LBFP aims to capture distal conduction fibers – typically the anterior, posterior, or septal fascicles – via selective Purkinje network engagement. While previous meta-analyses (22–26) have established the superiority of LBBAP over RVP and HBP in terms of electrical and clinical outcomes, this is, to our knowledge, the first meta-analysis directly comparing proximal (LBBP) and distal (LBFP) pacing sites within the left conduction system. QRS duration is a frequently used intra-procedural surrogate of ventricular synchrony. In our analysis, QRS duration did not differ significantly between LBBP and LBFP, though moderate heterogeneity (I² = 57%) was noted. This variability may reflect differences in measurement methodology (e.g., from pacing spike versus QRS onset), underlying conduction system disease, and high prevalence of non-selective CSP. For instance, Lin (2021) (20), Jastrzebski (2022) (12), Paniagua (2024) (7), and Liu (2025) (21) all measured QRS duration from the pacing spike, which may have led to overestimation, especially in Lin’s cohort where baseline QRS was narrow but paced QRS remained prolonged. In contrast, V6-RWPT — a surrogate marker of lateral wall activation and mechanical synchrony — was significantly shorter with LBFP. This supports the hypothesis that distal Purkinje capture may facilitate more rapid LV activation, potentially offsetting the theoretical advantage of proximal pacing via LBBP. These findings challenge the assumption that more proximal pacing always yields better synchrony. The LBB–V interval, often used for anatomic confirmation of LBBP, was not analyzed comparatively due to its role as a localization marker rather than a functional metric. Interestingly, Lin et al (20) reported unexpectedly similar LBB–V intervals in both pacing groups, potentially reflecting measurement overlap or non-selective capture. LVAT, despite conceptual overlapping with V6-RWPT, showed no significant intergroup difference. V6-RWPT may represent a more clinically relevant marker, given its stronger association with lateral wall activation and response to cardiac resynchronization therapy (CRT). Regarding LVEF, the pooled data demonstrated a non-significant trend favoring LBBP, primarily driven by Liu (2025) (21), which included a population with reduced LVEF — a key difference from other studies focusing on preserved or mildly reduced function. In this context, LBBP may facilitate more effective reverse remodeling in patients with impaired systolic function. This aligns with findings from the MELOS (12) registry, in which proximal CSP was associated with more favorable structural remodeling. Similar trends were also observed in prior meta-analyses comparing HBP and LBBAP (22,23,25,26). LVEDD demonstrated a consistent but non-significant trend toward reduction with LBBP, reinforcing its potential role in reverse remodeling among patients with dilated ventricles. Pacing thresholds did not differ significantly between groups, with both techniques demonstrating low and stable values over time. This contrasts with the higher thresholds often associated with HBP and supports the procedural feasibility of both LBBP and LBFP. Comparison with Recent Randomized Trials From a global perspective of physiologic pacing, recent randomized controlled trials (RCTs) have consistently demonstrated the superiority of CSP over conventional strategies, which provides important context for our findings. In the CRT setting, the LBBP-RESYNC trial (27) showed a greater improvement in LVEF at 6 months with LBBP-CRT compared with biventricular (BiV) pacing in nonischemic cardiomyopathy patients with true left bundle branch block (n=40), while the HOT-CRT trial (28) also demonstrated a greater increase in LVEF at 6 months and a favorable safety profile compared with BiV-CRT (n=100). In the bradycardia setting, a multicenter RCT published in 2025 (29) randomized CSP (His/LBBAP) versus RVP and found better preservation of LVEF at 12 months with CSP, with no significant differences in clinical events or procedural complications. Together, these RCTs reinforce the principle that engaging the conduction system (either His bundle or left bundle area) provides more physiological synchronization than BiV-CRT or conventional RVP. By contrast, our meta-analysis, focused specifically on where to capture within the left bundle branch area (trunk vs fascicles), demonstrated electrical equivalence between LBTP and LBFP in terms of LVAT, with no statistically significant difference. However, we identified a statistically significant difference in V6-RWPT, favoring LBFP, suggesting that distal capture may provide a slightly earlier ventricular activation. Thus, while RCTs clearly establish the superiority of CSP over BiV-CRT or RVP, our pooled analysis indicates that within CSP, the practical choice between LBTP and LBFP should be guided primarily by feasibility and procedural safety, although LBFP may offer a subtle electrical advantage in terms of ventricular synchrony. Clinical Implications and Future Directions The comparable outcomes between LBBP and LBFP support the physiologic validity of both techniques in patients without advanced conduction disease and significant ventricular dysfunction. The shorter V6-RWPT observed with LBFP suggests that distal Purkinje network capture may yield more rapid LV activation, potentially reducing electrical dyssynchrony. Additionally, LBFP was the most frequently achieved capture subtype across studies, underscoring its procedural practicality. However, whether these electrophysiological advantages translate into superior long-term clinical outcomes remains uncertain. Randomized controlled trials with adequate follow-up are needed to clarify the prognostic implications of proximal versus distal CSP and to guide optimal pacing strategies across different patient subsets. Limitations This meta-analysis has several limitations. First, only two studies (Cheng 2024, Lin 2021) reported intra- and inter-observer variability of electrophysiological measurements. Second, long-term clinical outcomes were seldom reported, limiting assessment of sustained efficacy. Third, heterogeneity in measurement protocols and inconsistent LBFP definitions may have introduced bias. Fourth, the absence of randomized controlled trials among the included studies limits causal inference. Finally, the small number of studies available for each outcome precluded formal evaluation of publication bias. Conclusion In this meta-analysis, LBBP and LBFP demonstrated comparable electrical and mechanical outcomes. LBFP was associated with a significantly shorter V6 R-wave peak time, suggesting more rapid left ventricular activation, while no significant differences were observed in QRS duration, LVEF, LV activation time, or pacing thresholds. 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Pacing Clin Electrophysiol PACE. 2023 Jun;46(6):459–66. 25. Parlavecchio A, Vetta G, Caminiti R, Coluccia G, Magnocavallo M, Ajello M, et al. Left bundle branch pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis. Pacing Clin Electrophysiol PACE. 2023 May;46(5):432–9. 26. Kim JA, Kim SE, Ellenbogen KA, Vijayaraman P, Chelu MG. Clinical outcomes of conduction system pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis. J Cardiovasc Electrophysiol. 2023 Aug;34(8):1718–29. 27. Wang Y, Gu K, Zhang W, Zhang Y, Hou X, Qian Z, et al. Left bundle branch pacing versus biventricular pacing for cardiac resynchronization therapy: LBBP-RESYNC trial. J Am Coll Cardiol. 2022;80(13):1205-16. doi:10.1016/j.jacc.2022.07.019. PMID: 36137670. 28. Vijayaraman P, Sharma PS, Lustgarten DL, Ellenbogen KA, Huang W. 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Study Characteristics Cheng, 2024 (N=56) Lin, 2021 (N=68) Liu, 2022 (N=91) Liu, 2025 (N=43) MELOS,2022 (N=2533)† Paniagua, 2024 (N=198) Characteristics LBFP LBTP LBFP LBTP LBFP LBTP LBFP LBTP LBFP LBTP LBFP LBTP 16 18 51 17 43 48 23 20 935 121 173 25 Study cohort design Retrospective Retrospective Prospective Prospective Prospective and retrospective Prospective Follow-up duration 22.1 months 12 months 12 months 6 months 6.4 months NA Age, years 75.6±10.7 74.4±7 63.6±11.5 62.0±11.9 58.1±16.6 58.2±19.6 61.6±12.3 65.2±7.7 73.9±11.8 77.9±10.2 80.1±11.6 Male, total 3 10 20 6 22 24 13 9 1073 (42.4%) 90 12 Diabetes mellitus, total 3 (18.8%) 6 (33.3%) NA 6 (14.0%) 6 (12.5%) 4(17.4%) 8(40%) 738 (29.1%) 51 (29.7%) 6 (24%) Hypertension 11(68.8%) 10(55.6%) 32(62.7%) 8(47.1%) 22 (51.2%) 27 (56.3%) 8 (34.8%) 10 (50%) 1828 (72.2%) 142 (82.6%) 22 (88%) CAD 3 (18.8%) 3 (16.7%) 13(25.5%) 3(17.6%) 8 (18.6%) 10 (20.8%) NA 773 (30.5%) 14 (8.1%) 4 (16%) Atrial fibrillation NA 13(25.5%) 4(23.5%) NA 3 (13%) 2 (10%) 672 (26.5%) 77 (44.8%) 11 (44%) Baseline QRSd. ms 102.1±24.7 108.4±27.1 90.6±6.6 92.7±7.3 94.3±9.3 94.8±9.6 175.8±13.7 174.4±12.2 137.1±35.9 119.2±31.4 103.2±20.5 LVEF, % 66.1±9.1 63.9±6.7 62.3±5.7 61.3±5.4 60.4±6.2 61.1±6.2 27.8±6.0 28.9±6.0 NA 57.7±9.7 58.8±11.6 LVEDD, mm 46.7±4.8 49.0±4.8 47.8±4.3 46.0±4.5 48.7±4.8 49.8±6.3 69.2±7.6 66.6±6.5 NA 45.4±6.4 45.5±7.5 Table 1 – Study Characteristics † Did not display data for the subgroups, only overall study population data. CAD: coronary artery disease; LBFP : left bundle fascicular pacing; LBTP : left bundle trunk pacing; LVEDD : left ventricular end diastolic diameter; LVEF : left ventricular ejection fraction; QRSd : QRS duration Figures Figure 1. PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only Figure 2. QRSd comparison between LBBP and LBFP groups. Fig 2. There was no statistical difference in QRS duration between the compared groups. Figure 3. V6 R-wave Peak Time (RWPT) comparison between LBBP and LBFP groups. Fig 3. There was statistical difference favoring the LBFP group, indicating a possible more rapid lateral wall activation and potentially more physiological conduction. Figure 4. Left Ventricular Activation Time (LVAT) comparison between LBBP and LBFP groups. Fig 4. There was no statistical difference between the compared groups. Figure 5. Left Ventricular Ejection Fraction (LVEF) comparison between LBBP and LBFP groups. Fig 5. There was no statistical difference between the compared groups, indicating similar impact on systolic function. Figure 6. Left Ventricular End-Diastolic Diameter (LVEDD) comparison between LBBP and LBFP groups. Fig 6. There was a similar LVEDD between the compared groups, suggesting no significant differences in structural remodeling. Figure 7. Pacing Threshold comparison between LBBP and LBFP groups. Fig 7. There was a non-statistical difference in the pacing threshold between the compared groups. Information & Authors Information Version history V1 Version 1 19 September 2025 Peer review timeline Published Journal of Interventional Cardiac Electrophysiology Version of Record 29 Apr 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords clinical: implantable devices – lead implantation/extraction clinical: implantable devices – pacemaker-bradyarrhythmias clinical: implantable devices – physiologic pacing Authors Affiliations Mateus Barros de Araújo 0009-0000-0500-8990 [email protected] Universidade da Regiao de Joinville View all articles by this author Gustavo Toaiari Staico Iamspe View all articles by this author Felipe Vieira Santana Universidade Federal de Sergipe - Campus Aracaju View all articles by this author Vitor Bastos Lovisi Instituto Dante Pazzanese de Cardiologia View all articles by this author Guilherme de Carvalho 0000-0001-8587-875X Instituto Dante Pazzanese de Cardiologia View all articles by this author Leonardo Antunes Mesquita Hospital Madre Teresa View all articles by this author Metrics & Citations Metrics Article Usage 223 views 118 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Mateus Barros de Araújo, Gustavo Toaiari Staico, Felipe Vieira Santana, et al. Ventricular Lead Positioning Within the Left Conduction System in Permanent Cardiac Pacing: A Systematic Review and Meta-analysis. Authorea . 19 September 2025. DOI: https://doi.org/10.22541/au.175826532.24187642/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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