Next Article in Journal
Feasibility and Clinical Outcomes of Robot-Assisted Sacrocolpopexy Using Autologous Round Ligament Grafts: A Novel Non-Mesh Surgical Approach for Pelvic Organ Prolapse
Previous Article in Journal
Unplanned Postoperative Angiography After Isolated Coronary Artery Bypass Grafting: State of the Art and Future Perspective
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Medicina
Volume 61
Issue 7
10.3390/medicina61071240
medicina-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

Conduction System Pacing Versus Biventricular Cardiac Resynchronization Pacing: Meta-Analysis on Outcomes in Patients with Non-Left Bundle Branch Block

by
Xuanming Pung
1,†,
Joe J. L. Chua
1,†,
Khi Yung Fong
2,
Yi Yi Chua
1,
Germaine J. M. Loo
1,
Jonathan W. S. Ong
1,
Julian C. K. Tay
1,
Hooi Khee Teo
1,
Yue Wang
3,
Colin Yeo
3,
Eric T. S. Lim
1,
Kah Leng Ho
1,
Daniel T. T. Chong
1,
Chi Keong Ching
1 and
Vern Hsen Tan
3,*
1
Department of Cardiology, National Heart Centre Singapore, Singapore 169609, Singapore
2
Department of General Medicine, Changi General Hospital, Singapore 529889, Singapore
3
Department of Cardiology, Changi General Hospital, Singapore 529889, Singapore
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Medicina 2025, 61(7), 1240; https://doi.org/10.3390/medicina61071240
Submission received: 17 June 2025 / Revised: 5 July 2025 / Accepted: 7 July 2025 / Published: 9 July 2025
(This article belongs to the Section Cardiology)
Browse Figures
Versions Notes

Abstract

Background and Objectives: The role of biventricular pacing (BVP) is less well-established in patients with heart failure with reduced ejection fraction (HFrEF) without left bundle branch block (LBBB). Conduction system pacing (CSP) has gained significant traction and may provide a safe and more physiological alternative to BVP in these patients. A few small studies studying this question have reported conflicting results. This meta-analysis aims to compare procedural and clinical outcomes between CSP and BVP in this group. Materials and Methods: An online literature search was systematically conducted to retrieve studies comparing CSP and BVP in HFrEF patients with non-LBBB. Four studies with 461 patients were included. Results: Implant-derived paced QRS duration was significantly shorter (mean difference [MD] −19.7 ms, 95% confidence interval [CI] −36.2 to −3.3, p = 0.0355) with CSP. Echocardiographic response with significantly greater improvement in left ventricular ejection fraction (MD 5.6%, 95% CI 3.1 to 8.0, p = 0.0106) was also observed with CSP. There were no statistically significant differences in clinical outcomes such as all-cause mortality (relative risk [RR] 0.53, 95% CI 0.18 to 1.60, p = 0.133) and heart failure hospitalization (RR 0.54, 95% CI 0.19 to 1.56, p = 0.129). Conclusions: This meta-analysis suggests that CSP may have better electrical synchrony and echocardiographic response compared to BVP in HFrEF patients with non-LBBB. Further randomized studies with longer follow-up may be required to elucidate potential benefits in clinical outcomes.

1. Introduction

Cardiac physiologic pacing refers to any form of cardiac pacing intended to restore or preserve synchrony of ventricular contraction. In patients with heart failure with reduced ejection fraction (HFrEF), this can be achieved by either engaging the intrinsic conduction system via conduction system pacing (CSP) or biventricular pacing (BVP) with a coronary sinus branch or left epicardial or endocardial lead [1].
Extensive evidence and guidelines support the use of BVP as cardiac resynchronization therapy (CRT) in HFrEF patients [1,2]. However, the electromechanical and clinical benefits attained from BVP appear largely limited to patients with left bundle branch block (LBBB) morphology [3]. In comparison, CSP—encompassing His-bundle pacing (HBP) and left bundle branch pacing (LBBP)—has been shown in a recent meta-analysis of randomized controlled trial to be superior to BVP with respect to shortening of QRS duration, improvement in left ventricular ejection fraction, and improvement in New York Heart Association (NYHA) class [4]. However, whether this extends to the non-LBBB group is unclear.
One clear challenge of CRT pertains to pre-existing non-LBBB electrocardiogram patterns [5]. To address this question, we conducted a meta-analysis of existing studies to evaluate electrocardiographic, echocardiographic, and clinical outcomes of CSP versus BVP in HFrEF patients with non-LBBB.

2. Materials and Methods

2.1. Literature Search

This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO; identifier: CRD420251051545) [6].
An electronic literature search from inception until 30 April 2024 was conducted by two independent investigators (K.Y.F. and V.H.T.) on PubMed, Embase, and Scopus for relevant articles using the concepts of CSP, HBP, LBBP, non-LBBB, and HFrEF. The full search strategy is shown in Table S1. The bibliographies of included studies were screened, and a search on Google Scholar using the first and last authors of each included study was conducted to ensure inclusion of all relevant studies. Retrieved abstracts and full texts were reviewed by two independent investigators (K.Y.F. and V.H.T.), with conflicts being resolved via group consensus among all authors.
Prospective or retrospective studies reporting comparisons of the procedural and clinical outcomes between HFrEF patients with non-LBBB who underwent CSP versus BVP were included. Similar studies that studied HFrEF patients regardless of QRS morphology but reported group data for the non-LBBB cohort were also included. Case reports, case series, reviews, and conference abstracts were excluded. Studies that did not report group data for the non-LBBB cohort were also excluded, e.g., [7].
A standardized data collection template with predefined data fields, including study characteristics, patient demographics, and outcomes, was used for data extraction by two independent investigators. Studies were assessed for risk of bias using the Newcastle–Ottawa scale [8].

2.2. Meta-Analysis

The primary outcomes analyzed in this meta-analysis were all-cause mortality, heart failure hospitalization, QRS duration post-implant, and change in left ventricular ejection fraction (LVEF). For continuous outcomes, means and standard deviations were pooled in random-effects meta-analysis to determine mean differences and 95% confidence intervals (CIs). For binary outcomes, numbers of patients per arm and event counts were pooled in random-effects meta-analysis to determine risk ratios and 95% CIs. Missing means and standard deviations were derived from medians and interquartile ranges in accordance with established methods reported by Hozo et al. and Wan et al. [9,10].
Study heterogeneity was stratified as low, moderate, or considerable for I2 values < 40%, 40–75%, and >75%, respectively [11]. Funnel plot symmetries were visually assessed for publication bias. Certainty of evidence was evaluated using the GRADE approach [12]. All statistical analyses were performed with R version 4.3.0 (R Core Team, Vienna, Austria). p < 0.05 was considered to indicate statistical significance.

3. Results

3.1. Study Selection

The initial search contained 1430 studies. After the removal of 190 duplicates, 1240 studies underwent title and abstract screening. Twenty-eight studies were then selected for full-text review, with a final four studies consisting of 461 patients selected for analysis [13,14,15,16]. The PRISMA flow diagram is shown in Figure 1 [17].

3.2. Study Characteristics

The included studies were published between 2022 and 2023, due to the recent increased widespread adoption of CSP and the limited number of eligible studies meeting our criteria. All studies were non-randomized; three were retrospective [13,14,15] and one prospective [16]. Vijayaraman et al. only reported data for the overall cohort and the LBBB group; however, the baseline characteristics, event rates, and hazard ratios for the non-LBBB group were computable from the provided data and were included in the final meta-analysis [13].
A total of 461 patients were studied, with 255 undergoing CSP and 206 undergoing BVP. Baseline characteristics of the included studies are shown in Table 1. The average age of the cohort was 75, with 75% being male. One study only included patients with AV block [14], another only intraventricular conduction delay (IVCD) [16], and the remaining two a mix of patients with right bundle branch block (RBBB), IVCD, AV block, and normal QRS [13,15]. With regards to the method of CSP, two studies used a mix of HBP and LBBP [14,15], one purely used left bundle branch optimized CRT (LOT-CRT) [16], and the last used a mix of all three [13]. The average follow-up duration was variable, ranging from 365 to 810 days. The risk of bias was generally low (Table S2).

3.3. Statistical Analysis

Post-implant QRS duration and LVEF improvement were described in three studies [14,15,16]. The relevant forest plots are shown in Figure 2. Implant-derived paced QRS duration was significantly shorter with CSP (mean difference [MD] −19.7 ms, 95% confidence interval [CI] −36.2 to −3.3, p = 0.0355, I2 = 51%). An echocardiographic response with significantly greater improvement in LVEF was also observed in CSP (MD 5.6%, 95% CI 3.1 to 8.0, p = 0.0106, I2 = 47%).
Clinical outcomes of interest (all-cause mortality and heart failure hospitalization) were described in three studies [13,14,15]. There were no statistically significant differences in both outcomes (all-cause mortality: relative risk [RR] 0.53, 95% CI 0.18 to 1.60, p = 0.133, I2 = 37%; heart failure hospitalization: RR 0.54, 95% CI 0.19 to 1.56, p = 0.129, I2 = 50%), as seen in Figure 3.
Funnel plots for all outcomes were not visually suggestive of publication bias (Figures S1–S4). The GRADE ratings are shown in Table 2.

4. Discussion

4.1. Difference in Outcomes Between CSP and BVP in Non-LBBB

This meta-analysis demonstrates that in HFrEF patients with non-LBBB, CSP significantly shortened QRS duration and improved LVEF but had no difference in clinical outcomes (heart failure hospitalization or all-cause mortality).
Currently, LBBB represents an important electrophysiological substrate for CRT response. Multiple criteria for LBBB have been published to facilitate CRT decisions, with major differences between them [2,18,19,20]. In a study by van Stipdonk and colleagues, LBBB classification was shown to be highly dependent on the criterion used, and only 13.8% of patients satisfied all LBBB criteria [21]. Despite the significant differences in classified LBBB morphology among the studied criteria, the investigators concluded that LBBB was still associated with significant differences in survival free of primary endpoints, regardless of the criterion used. On the other hand, outcomes in non-LBBB patients are less impressive, with only a class 2A recommendation in patients with NYHA class III or greater symptoms [1].
The recent CONSYST-CRT trial demonstrated the clinical and echocardiographic non-inferiority of CSP compared to BVP in patients with an indication for CRT, suggesting that CSP could be an alternative to BVP in all-comers requiring CRT [22]. However, supporting studies specifically examining the non-LBBB group remain scarce, and to date, there are no randomized controlled trials studying this population. As such, the use of CSP in such patients is only supported by a class 2B recommendation (may be reasonable) in contemporary guidelines, and only when effective CRT cannot be achieved with BVP [1].
In our meta-analysis, we analyzed a total of four observational studies (one specifically for non-LBBB patients, and three with outcome data reported for non-LBBB patients) and found that although CSP was associated with shorter QRS durations and greater improvements in LVEF, this did not translate into better clinical outcomes (reduced all-cause mortality or heart failure hospitalization), potentially due to the short follow up durations in the included studies. Of note, a recent meta-analysis also failed to demonstrate a difference in clinical outcomes between CSP and BVP in all-comers; however, follow-up durations in the included studies were also relatively short (ranging from 6 to 12 months) [4].
Interestingly, although the improvement in clinical outcomes in the pooled meta-analysis did not reach significance, there was a signal towards improvement, mainly driven by two out of three of the included studies [13,15]. The third study reported equivocal improvements in clinical outcomes with CSP; however, this may have been influenced by the shorter follow-up (6 months) and the smaller sample size (n = 50) [14]. Additionally, this third study only included patients with a permanent pacing indication due to atrioventricular (AV) block, whereas the other two included patients with prolonged QRS durations due to RBBB and IVCD, as well as patients who required pacing due to AV block. At present, the choice of pacing modality in patients with AV block, a narrow QRS complex, and HFrEF is still controversial [23]. Further work is needed to explore the effect of CSP and BVP on the different subgroups of non-LBBB.
Meta-analyses have previously demonstrated that BVP does not reduce death and heart failure hospitalizations in non-LBBB patients, and CSP may supplant BVP as the preferred pacing or CRT method in such patients if robust clinical benefits are demonstrated [3]. In addition, novel techniques like His-optimized and left bundle branch-optimized CRT have shown promise, with greater electrocardiographic, echocardiographic, and clinical response compared to traditional His bundle pacing [24,25].

4.2. Choosing Between CSP and BVP in Non-LBBB

General procedural outcomes. A study by Sharma et al. studied HBP in patients with HFrEF, RBBB, and QRS duration ≥120 ms. The thresholds for His capture and bundle branch block correction were 1.1 ± 0.6 and 1.4 ± 0.7 V at 1.0 ms, respectively. HBP resulted in a shortening of the QRS duration from 158 ± 24 to 127 ± 17 ms (p = 0.0001), increase in LVEF from 31 ± 10% to 39 ± 13% (p = 0.004), and improvement in NYHA class from 2.8 ± 0.6 to 2 ± 0.7 (p = 0.0001) after a mean follow-up of 15 ± 23 months [26]. Another observational study by Vijayaraman et al. studying LBBP in a similar cohort with indications for CRT or pacing resulted in thresholds of 0.8 ± 0.3 V at 0.5 ms at implantation, which remained stable after a mean follow-up period of 13 ± 8 months. With LBBP, there was a decrease in QRS duration from 156 ± 20 ms at baseline to 150 ± 24 ms (p = 0.01), increase in LVEF from 35 ± 9% to 43 ± 12% (p < 0.01), and improvement in NYHA class from 2.5 ± 0.8 at baseline to 1.7 ± 0.8 (p < 0.01). However, when compared to LBBB, a non-LBBB QRS morphology itself has been shown to triple the likelihood of failed LBBP implantation [27]. Female sex and reduction of QRS duration with LBBP were associated with echocardiographic response and super-response [28].
QRS duration and morphology. The clinical and echocardiographic responses and benefits attained with CSP may differ for specific types of non-LBBB, with IVCD representing a particularly challenging substrate for CSP. Upadhyay and colleagues first demonstrated that HBP did not correct QRS duration in patients with intact Purkinje activation/IVCD [29]. Most recently, out of the 21 patients with IVCD included in the CONSYST-CRT trial, nine of the eleven patients randomized to CSP required crossover, suggesting suboptimal procedural or clinical outcomes in this group [22]. These difficulties, however, do not appear to extend to other non-LBBB morphologies; a study by Vijayaraman et al. showed that the rate of unsuccessful LBBP attempts was high in the IVCD group (p = 0.02) but not in the RBBB group (p = 0.81) [30]. Ultimately, QRS duration has been shown to impact outcomes regardless of non-LBBB morphology. A meta-analysis of five randomized clinical trials highlighted the importance of having a prolonged QRS duration at baseline for CRT to be beneficial in non-LBBB, with its multivariate model highlighting that the sole predictor of CRT effect on outcomes was a QRS duration > 140 ms. Further analysis also demonstrated increasing CRT benefits with increasing QRS duration on all-cause mortality and the composite of first hospitalization for heart failure or death, independent of QRS morphology [31].
AV block. The presence of first-degree AV block has been shown to be an important factor in non-LBBB for patients to benefit from CRT in a sub-study of the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) trial. This study showed that patients with a non-LBBB pattern and prolonged PR interval ≥230 ms demonstrated significant improvement in clinical endpoints with CRT, including reductions in the risk of heart failure and all-cause mortality. Conversely, PR interval duration was not an important consideration in HBP, as positive clinical and echocardiographic benefits were similarly observed in patients with normal PR interval [32]. Notably, HBP has been shown in a recent clinical trial to result in improvements in symptoms and quality of life when compared to no pacing in patients with HFrEF, PR interval ≥200 ms, and either QRS ≤ 140 ms and right bundle branch block [33]. However, HBP may not be suitable in patients with infra-nodal AV block or scheduled AV node ablation [34].
Myocardial scarring. Anatomical factors should also be considered when deciding between CSP and BVP in patients without LBBB. In a study by Ponnusamy et al., findings of transmural scar in the LBBP zone via late gadolinium enhancement on cardiac magnetic resonance imaging predicted procedural failure with 100% sensitivity and 100% specificity [35]. Elliott MK et al. also demonstrated superior electrical resynchronization and greater acute hemodynamic response during biventricular endocardial pacing and LBBP compared to biventricular epicardial pacing. Electrical resynchronization was similar between biventricular endocardial pacing and LBBP; however, the septal scar seemed to attenuate the response to LBBP, possibly due to increased difficulty in penetrating the septum [36].
Valve pathology or planned intervention. The presence of tricuspid regurgitation should prompt further deliberation regarding the modality of pacing. Basal septal LBBP lead placement close to the tricuspid annulus has previously been shown to worsen tricuspid regurgitation, with proposed cutoffs of 16 or 19 mm from the annulus [37,38]. Surgical or percutaneous tricuspid valve interventions, if required, may also lead to inadvertent jailing of the LBBP lead and/or lead damage. In cases where there is tricuspid valve dysfunction, previous transcatheter repair, or a prosthesis in situ, HBP or BVP may be preferred over LBBP in providing electrical resynchronization. On the other hand, HBP may be less preferred in previous or scheduled transcatheter aortic valve implantation or aortic valve surgery due to the risk of compromised HBP lead function following these interventions [34]. Notably, a recent first-in-human study of a leadless LBBP system was recently reported and may represent a solution to these anatomical issues [39].
Summary. From the studies described above, it appears that CSP may be preferred over BVP in non-LBBB if the QRS duration is ≤140 ms or the PR interval is <230 ms, and in the absence of a significant IVCD pattern or specific anatomical contraindications. Future randomized studies focused on non-LBBB patients could elucidate potential clinical benefits of CSP compared to BVP in this patient group. Further data describing the long-term stability of CSP and capabilities in the recruitment of local conduction system tissue are also needed, particularly in the presence of His-Purkinje conduction disease.

4.3. Limitations

Our meta-analysis included only observational studies, as there were no randomized studies that matched our inclusion criteria. As a result, the GRADE ratings for certainty of evidence ranged from low to very low, highlighting the urgent need for future randomized studies. Study designs, sample sizes, and duration of follow-up were also heterogeneous within the included studies, which may affect the generalizability of our results. The types of non-LBBB patterns included were different between studies; future studies focusing on specific types of non-LBBB (e.g., RBBB, IVCD with and without concomitant AV block indication for pacing) would greatly clarify the distinction between these groups.

5. Conclusions

This meta-analysis suggests that CSP may have better electrical synchrony and echocardiographic response compared to BVP in HFrEF patients with non-LBBB. However, there were no significant differences in clinical outcomes such as all-cause mortality and heart failure hospitalization. Future randomized studies are needed to further elucidate the potential benefits of CSP in this group.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/medicina61071240/s1, Figure S1: Funnel plot for paced QRS duration; Figure S2: Funnel plot for improvement in LVEF; Figure S3: Funnel plot for all-cause mortality; Figure S4: Funnel plot for heart failure hospitalization; Table S1: Full search phrases used for the respective databases; Table S2: Risk of bias in included studies.

Author Contributions

Conceptualization, X.P., K.Y.F., Y.Y.C., G.J.M.L., J.W.S.O., J.C.K.T., H.K.T., Y.W., C.Y., E.T.S.L., K.L.H., D.T.T.C., C.K.C. and V.H.T.; methodology, X.P., K.Y.F. and V.H.T.; software, K.Y.F.; validation, K.Y.F. and V.H.T.; formal analysis, X.P., J.J.L.C., K.Y.F. and V.H.T.; investigation, X.P., J.J.L.C., K.Y.F. and V.H.T.; data curation, X.P., J.J.L.C., K.Y.F. and V.H.T.; writing—original draft preparation, X.P. and J.J.L.C.; writing—review and editing, X.P., J.J.L.C. and V.H.T.; visualization, J.J.L.C. and K.Y.F.; supervision, X.P., C.K.C. and V.H.T.; project administration, X.P., J.J.L.C., Y.Y.C., G.J.M.L., J.W.S.O., J.C.K.T., H.K.T., Y.W., C.Y., E.T.S.L., K.L.H., D.T.T.C., C.K.C. and V.H.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethics approval was not required as this manuscript makes use of publicly available data from published studies.

Informed Consent Statement

Informed consent is not applicable as this manuscript makes use of publicly available data from published studies.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

G.J.M.L. received honoraria from Boston Scientific. H.K.T. received honoraria from Boston Scientific and Biotronik. X.P., J.C.K.T. and K.L.H. received honoraria from Abbott and Boston Scientific. Y.W., C.Y., E.T.S.L., D.T.T.C., C.K.C. and V.H.T. received honoraria from Abbott, Boston Scientific, Biotronik, and Medtronic. The other authors declare no conflicts of interest. These organizations had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Abbreviations

The following abbreviations are used in this manuscript:
AVAtrioventricular
BVPBiventricular pacing
CIConfidence interval
CRTCardiac resynchronization therapy
CSPConduction system pacing
HBPHis bundle pacing
HFrEFHeart failure with reduced ejection fraction
HOT-CRTHis bundle optimized cardiac resynchronization therapy
IVCDIntraventricular conduction delay
LBBBLeft bundle branch block
LBBPLeft bundle branch pacing
LOT-CRTLeft bundle branch optimized cardiac resynchronization therapy
LVEFLeft ventricular ejection fraction
MDMean difference
NYHANew York Heart Association
RRRelative risk
RBBBRight bundle branch block

References

  1. Chung, M.K.; Patton, K.K.; Lau, C.-P.; Dal Forno, A.R.J.; Al-Khatib, S.M.; Arora, V.; Birgersdotter-Green, U.M.; Cha, Y.-M.; Chung, E.H.; Cronin, E.M.; et al. 2023 HRS/APHRS/LAHRS Guideline on Cardiac Physiologic Pacing for the Avoidance and Mitigation of Heart Failure. Heart Rhythm 2023, 20, e17–e91. [Google Scholar] [CrossRef] [PubMed]
  2. Glikson, M.; Nielsen, J.C.; Kronborg, M.B.; Michowitz, Y.; Auricchio, A.; Barbash, I.M.; Barrabés, J.A.; Boriani, G.; Braunschweig, F.; Brignole, M.; et al. 2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy. Eur. Heart J. 2021, 42, 3427–3520. [Google Scholar] [CrossRef] [PubMed]
  3. Cunnington, C.; Kwok, C.S.; Satchithananda, D.K.; Patwala, A.; Khan, M.A.; Zaidi, A.; Ahmed, F.Z.; Mamas, M.A. Cardiac Resynchronisation Therapy is not Associated with a Reduction in Mortality or Heart Failure Hospitalisation in Patients with Non-Left Bundle Branch Block QRS Morphology: Meta-Analysis of Randomised Controlled Trials. Heart 2015, 101, 1456–1462. [Google Scholar] [CrossRef] [PubMed]
  4. Ferreira Felix, I.; Collini, M.; Fonseca, R.; Guida, C.; Armaganijan, L.; Healey, J.S.; Carvalho, G. Conduction System Pacing versus Biventricular Pacing in Heart Failure with Reduced Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Heart Rhythm 2024, 21, 881–889. [Google Scholar] [CrossRef]
  5. Herweg, B.; Mumtaz, M.; Vijayaraman, P. Conduction System Pacing for CRT: A Physiological Alternative. Arrhythmia Electrophysiol. Rev. 2025, 14, e04. [Google Scholar] [CrossRef]
  6. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  7. Vijayaraman, P.; Pokharel, P.; Subzposh, F.A.; Oren, J.W.; Storm, R.H.; Batul, S.A.; Beer, D.A.; Hughes, G.; Leri, G.; Manganiello, M.; et al. His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy vs Biventricular Pacing. JACC Clin. Electrophysiol. 2023, 9, 2628–2638. [Google Scholar] [CrossRef]
  8. Wells, G.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses 2021. Available online: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed on 6 July 2025).
  9. Hozo, S.P.; Djulbegovic, B.; Hozo, I. Estimating the Mean and Variance from the Median, Range, and the Size of a Sample. BMC Med. Res. Methodol. 2005, 5, 13. [Google Scholar] [CrossRef]
  10. Wan, X.; Wang, W.; Liu, J.; Tong, T. Estimating the Sample Mean and Standard Deviation from the Sample Size, Median, Range and/or Interquartile Range. BMC Med. Res. Methodol. 2014, 14, 135. [Google Scholar] [CrossRef]
  11. Higgins, J.P.T. Measuring Inconsistency in Meta-Analyses. BMJ 2003, 327, 557–560. [Google Scholar] [CrossRef]
  12. Brignardello-Petersen, R.; Bonner, A.; Alexander, P.E.; Siemieniuk, R.A.; Furukawa, T.A.; Rochwerg, B.; Hazlewood, G.S.; Alhazzani, W.; Mustafa, R.A.; Murad, M.H.; et al. Advances in the GRADE Approach to Rate the Certainty in Estimates from a Network Meta-Analysis. J. Clin. Epidemiol. 2018, 93, 36–44. [Google Scholar] [CrossRef]
  13. Vijayaraman, P.; Zalavadia, D.; Haseeb, A.; Dye, C.; Madan, N.; Skeete, J.R.; Vipparthy, S.C.; Young, W.; Ravi, V.; Rajakumar, C.; et al. Clinical Outcomes of Conduction System Pacing Compared to Biventricular Pacing in Patients Requiring Cardiac Resynchronization Therapy. Heart Rhythm 2022, 19, 1263–1271. [Google Scholar] [CrossRef]
  14. Pujol-López, M.; Jiménez Arjona, R.; Guasch, E.; Borràs, R.; Doltra, A.; Vázquez-Calvo, S.; Roca-Luque, I.; Garre, P.; Ferró, E.; Niebla, M.; et al. Conduction System Pacing vs. Biventricular Pacing in Patients with Ventricular Dysfunction and AV Block. Pacing Clin. Electrophysiol. PACE 2022, 45, 1115–1123. [Google Scholar] [CrossRef]
  15. Tan, E.S.J.; Soh, R.; Lee, J.-Y.; Boey, E.; de Leon, J.; Chan, S.P.; Yeo, W.T.; Lim, T.W.; Seow, S.-C.; Kojodjojo, P. Conduction System versus Biventricular Pacing in Heart Failure with Non-Left Bundle Branch Block. J. Cardiovasc. Electrophysiol. 2023, 34, 976–983. [Google Scholar] [CrossRef]
  16. Chen, X.; Li, X.; Bai, Y.; Wang, J.; Qin, S.; Bai, J.; Wang, W.; Liang, Y.; Chen, H.; Su, Y.; et al. Electrical Resynchronization and Clinical Outcomes During Long-Term Follow-Up in Intraventricular Conduction Delay Patients Applied Left Bundle Branch Pacing-Optimized Cardiac Resynchronization Therapy. Circ. Arrhythm. Electrophysiol. 2023, 16, e011761. [Google Scholar] [CrossRef]
  17. Haddaway, N.R.; Page, M.J.; Pritchard, C.C.; McGuinness, L.A. PRISMA2020: An R Package and Shiny App for Producing Prisma 2020-Compliant Flow Diagrams, with Interactivity for Optimised Digital Transparency and Open Synthesis. Campbell Syst. Rev. 2022, 18, e1230. [Google Scholar] [CrossRef]
  18. Strauss, D.G.; Selvester, R.H.; Wagner, G.S. Defining Left Bundle Branch Block in the Era of Cardiac Resynchronization Therapy. Am. J. Cardiol. 2011, 107, 927–934. [Google Scholar] [CrossRef]
  19. Moss, A.J.; Hall, W.J.; Cannom, D.S.; Klein, H.; Brown, M.W.; Daubert, J.P.; Estes, N.A.M.; Foster, E.; Greenberg, H.; Higgins, S.L.; et al. Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events. N. Engl. J. Med. 2009, 361, 1329–1338. [Google Scholar] [CrossRef]
  20. Surawicz, B.; Childers, R.; Deal, B.J.; Gettes, L.S. AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram. J. Am. Coll. Cardiol. 2009, 53, 976–981. [Google Scholar] [CrossRef]
  21. Van Stipdonk, A.M.W.; Hoogland, R.; Ter Horst, I.; Kloosterman, M.; Vanbelle, S.; Crijns, H.J.G.M.; Prinzen, F.W.; Meine, M.; Maass, A.H.; Vernooy, K. Evaluating Electrocardiography-Based Identification of Cardiac Resynchronization Therapy Responders Beyond Current Left Bundle Branch Block Definitions. JACC Clin. Electrophysiol. 2020, 6, 193–203. [Google Scholar] [CrossRef]
  22. Pujol-López, M.; Graterol, F.R.; Borràs, R.; Garcia-Ribas, C.; Guichard, J.B.; Regany-Closa, M.; Jiménez-Arjona, R.; Niebla, M.; Poza, M.; Carro, E.; et al. Clinical Response to Resynchronization Therapy: Conduction System Pacing vs Biventricular Pacing. CONSYST-CRT trial. JACC Clin. Electrophysiol. 2025. online ahead of print. [Google Scholar] [CrossRef]
  23. Glikson, M.; Jastrzebski, M.; Gold, M.R.; Ellenbogen, K.; Burri, H. Conventional Biventricular Pacing Is Still Preferred to Conduction System Pacing for Atrioventricular Block in Patients with Reduced Ejection Fraction and Narrow QRS. Europace 2023, 26, euad337. [Google Scholar] [CrossRef]
  24. Zweerink, A.; Zubarev, S.; Bakelants, E.; Potyagaylo, D.; Stettler, C.; Chmelevsky, M.; Lozeron, E.D.; Hachulla, A.-L.; Vallée, J.-P.; Burri, H. His-Optimized Cardiac Resynchronization Therapy With Ventricular Fusion Pacing for Electrical Resynchronization in Heart Failure. JACC Clin. Electrophysiol. 2021, 7, 881–892. [Google Scholar] [CrossRef]
  25. Jastrzębski, M.; Moskal, P.; Huybrechts, W.; Curila, K.; Sreekumar, P.; Rademakers, L.M.; Ponnusamy, S.S.; Herweg, B.; Sharma, P.S.; Bednarek, A.; et al. Left Bundle Branch-Optimized Cardiac Resynchronization Therapy (LOT-CRT): Results from an International LBBAP Collaborative Study Group. Heart Rhythm 2022, 19, 13–21. [Google Scholar] [CrossRef]
  26. Sharma, P.S.; Naperkowski, A.; Bauch, T.D.; Chan, J.Y.S.; Arnold, A.D.; Whinnett, Z.I.; Ellenbogen, K.A.; Vijayaraman, P. Permanent His Bundle Pacing for Cardiac Resynchronization Therapy in Patients With Heart Failure and Right Bundle Branch Block. Circ. Arrhythm. Electrophysiol. 2018, 11, e006613. [Google Scholar] [CrossRef]
  27. Graterol, F.R.; Pujol-López, M.; Borràs, R.; Ayala, B.; Uribe, L.; Guasch, E.; Regany-Closa, M.; Niebla, M.; Carro, E.; Guichard, J.-B.; et al. Predictors of Failed Left Bundle Branch Pacing Implant in Heart Failure with Reduced Ejection Fraction: Importance of Left Ventricular Diameter and QRS Morphology. Heart Rhythm 2024, 21, 2571–2578. [Google Scholar] [CrossRef]
  28. Vijayaraman, P.; Cano, O.; Ponnusamy, S.S.; Molina-Lerma, M.; Chan, J.Y.S.; Padala, S.K.; Sharma, P.S.; Whinnett, Z.I.; Herweg, B.; Upadhyay, G.A.; et al. Left Bundle Branch Area Pacing in Patients with Heart Failure and Right Bundle Branch Block: Results from International LBBAP Collaborative-Study Group. Heart Rhythm O2 2022, 3, 358–367. [Google Scholar] [CrossRef]
  29. Upadhyay, G.A.; Cherian, T.; Shatz, D.Y.; Beaser, A.D.; Aziz, Z.; Ozcan, C.; Broman, M.T.; Nayak, H.M.; Tung, R. Intracardiac Delineation of Septal Conduction in Left Bundle-Branch Block Patterns: Mechanistic Evidence of Left Intrahisian Block Circumvented by His Bundle Pacing. Circulation 2019, 139, 1876–1888. [Google Scholar] [CrossRef]
  30. Vijayaraman, P.; Ponnusamy, S.; Cano, Ó.; Sharma, P.S.; Naperkowski, A.; Subsposh, F.A.; Moskal, P.; Bednarek, A.; Dal Forno, A.R.; Young, W.; et al. Left Bundle Branch Area Pacing for Cardiac Resynchronization Therapy. JACC Clin. Electrophysiol. 2021, 7, 135–147. [Google Scholar] [CrossRef]
  31. Cleland, J.G.; Abraham, W.T.; Linde, C.; Gold, M.R.; Young, J.B.; Claude Daubert, J.; Sherfesee, L.; Wells, G.A.; Tang, A.S.L. An Individual Patient Meta-Analysis of Five Randomized Trials Assessing the Effects of Cardiac Resynchronization Therapy on Morbidity and Mortality in Patients with Symptomatic Heart Failure. Eur. Heart J. 2013, 34, 3547–3556. [Google Scholar] [CrossRef]
  32. Ploux, S.; Whinnett, Z.; Lumens, J.; Denis, A.; Zemmoura, A.; De Guillebon, M.; Ramoul, K.; Ritter, P.; Jaïs, P.; Clementy, J.; et al. Acute Hemodynamic Response to Biventricular Pacing in Heart Failure Patients with Narrow, Moderately, and Severely Prolonged QRS Duration. Heart Rhythm 2012, 9, 1247–1250. [Google Scholar] [CrossRef]
  33. Whinnett, Z.I.; Shun-Shin, M.J.; Tanner, M.; Foley, P.; Chandrasekaran, B.; Moore, P.; Adhya, S.; Qureshi, N.; Muthumala, A.; Lane, R.; et al. Effects of Haemodynamically Atrio-ventricular Optimized His Bundle Pacing on Heart Failure Symptoms and Exercise Capacity: The His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) Randomized, Double-Blind, Cross-over Trial. Eur. J. Heart Fail. 2023, 25, 274–283. [Google Scholar] [CrossRef] [PubMed]
  34. Glikson, M.; Burri, H.; Abdin, A.; Cano, O.; Curila, K.; De Pooter, J.; Diaz, J.C.; Drossart, I.; Huang, W.; Israel, C.W.; et al. European Society of Cardiology (ESC) Clinical Consensus Statement on Indications for Conduction System Pacing, with Special Contribution of the European Heart Rhythm Association of the ESC and Endorsed by the Asia Pacific Heart Rhythm Society, the Canadian Heart Rhythm Society, the Heart Rhythm Society, and the Latin American Heart Rhythm Society. Europace 2025, 27, euaf050. [Google Scholar] [CrossRef] [PubMed]
  35. Ponnusamy, S.S.; Murugan, M.; Ganesan, V.; Vijayaraman, P. Predictors of Procedural Failure of Left Bundle Branch Pacing in Scarred Left Ventricle. J. Cardiovasc. Electrophysiol. 2023, 34, 760–764. [Google Scholar] [CrossRef]
  36. Elliott, M.K.; Strocchi, M.; Sieniewicz, B.J.; Sidhu, B.; Mehta, V.; Wijesuriya, N.; Behar, J.M.; Thorpe, A.; Martic, D.; Wong, T.; et al. Biventricular Endocardial Pacing and Left Bundle Branch Area Pacing for Cardiac Resynchronization: Mechanistic Insights from Electrocardiographic Imaging, Acute Hemodynamic Response, and Magnetic Resonance Imaging. Heart Rhythm 2023, 20, 207–216. [Google Scholar] [CrossRef]
  37. Hu, Q.; You, H.; Chen, K.; Dai, Y.; Lu, W.; Li, Y.; Cheng, C.; Zhou, Y.; Wang, J.; Chen, R.; et al. Distance between the Lead-Implanted Site and Tricuspid Valve Annulus in Patients with Left Bundle Branch Pacing: Effects on Postoperative Tricuspid Regurgitation Deterioration. Heart Rhythm 2023, 20, 217–223. [Google Scholar] [CrossRef]
  38. Li, X.; Zhu, H.; Fan, X.; Wang, Q.; Wang, Z.; Li, H.; Tao, J.; Wang, H.; Liu, Z.; Yao, Y. Tricuspid Regurgitation Outcomes in Left Bundle Branch Area Pacing and Comparison with Right Ventricular Septal Pacing. Heart Rhythm 2022, 19, 1202–1203. [Google Scholar] [CrossRef]
  39. Reddy, V.Y.; Nair, D.G.; Doshi, S.K.; Doshi, R.N.; Chovanec, M.; Ganz, L.; Sabet, L.; Jiang, C.; Neuzil, P. First-in-Human Study of a Leadless Pacemaker System for Left Bundle Branch Area Pacing. Heart Rhythm. 2025. online ahead of print. [Google Scholar] [CrossRef]
Medicina 61 01240 g001
Figure 1. PRISMA flow diagram for the included studies.
Figure 1. PRISMA flow diagram for the included studies.
Medicina 61 01240 g001
Medicina 61 01240 g002
Figure 2. Meta-analysis of (a) QRS duration and (b) LVEF improvement [14,15,16].
Figure 2. Meta-analysis of (a) QRS duration and (b) LVEF improvement [14,15,16].
Medicina 61 01240 g002
Medicina 61 01240 g003
Figure 3. Meta-analysis of (a) all-cause mortality and (b) heart failure hospitalization [13,14,15].
Figure 3. Meta-analysis of (a) all-cause mortality and (b) heart failure hospitalization [13,14,15].
Medicina 61 01240 g003
Table 1. Baseline characteristics of included studies.
Table 1. Baseline characteristics of included studies.
ReferenceStudy TypeNon-LBBB TypeCSP TypeArmnAge, y *Male, %HTN, %DM, %IHD, %AF, %CKD, %NYHA
III–IV, %		Follow Up, Days
Vijayaraman et al., 2022 [13]RetrospectiveRBBB (19%), IVCD (19%),
AVB (40%), normal QRS (21%)		HBP, LBBP, LOT-CRTCSP15273 †7069375466NRNR810
BVP7874 †7377516360NRNR
Pujol-Lopez et al., 2022 [14]RetrospectiveAVBHPB (72%), LBBP (28%)CSP2572 (9)68NRNRNR16NR64365
BVP2569 (8)76NRNRNR16NR72
Tan et al., 2023 [15]RetrospectiveRBBB (51%), IVCD (13%),
AVB (36%)		HBP, LBBPCSP4870 (10)777350635248NR578
BVP4870 (12)807360734652NR728
Chen et al., 2023 [16]ProspectiveIVCDLOT-CRTCSP3064 (13)773020NR37NR63730
BVP5564 (11)872735NR26NR71
* Reported as mean (SD). † The standard error was not computable from the data provided. AF: atrial fibrillation; AVB: atrioventricular block; CSP: conduction system pacing; CKD: chronic kidney disease; DM: diabetes mellitus; HBP: His bundle pacing; HTN: hypertension; IHD: ischemic heart disease; IVCD: intraventricular conduction delay; LBBP: left bundle branch pacing; LOT-CRT: left bundle branch optimized cardiac resynchronization therapy; NR: not reported; NYHA: New York Heart Association; RBBB: right bundle branch block.
Table 2. The GRADE table summary. CI: confidence interval; LVEF: left ventricular ejection fraction; MD: mean difference; RR: relative risk.
Table 2. The GRADE table summary. CI: confidence interval; LVEF: left ventricular ejection fraction; MD: mean difference; RR: relative risk.
OutcomeRelative Effect (95% CI)Number of Participants (Studies)Heterogeneity, %Certainty of Evidence (GRADE)
QRS durationMD −19.7 (−36.2 to −3.3)231 (3 studies)51⊕⊖⊖⊖ Very low *
LVEF improvementMD 5.6 (3.1 to 8.0)231 (3 studies)47⊕⊖⊖⊖ Very low *
All-cause mortalityRR 0.53 (CI 0.18 to 1.60)376 (3 studies)37⊕⊕⊖⊖ Low
Heart failure hospitalizationRR 0.54 (0.19 to 1.56)376 (3 studies)50⊕⊖⊖⊖ Very low *
* Downgraded one level due to moderate heterogeneity.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Pung, X.; Chua, J.J.L.; Fong, K.Y.; Chua, Y.Y.; Loo, G.J.M.; Ong, J.W.S.; Tay, J.C.K.; Teo, H.K.; Wang, Y.; Yeo, C.; et al. Conduction System Pacing Versus Biventricular Cardiac Resynchronization Pacing: Meta-Analysis on Outcomes in Patients with Non-Left Bundle Branch Block. Medicina 2025, 61, 1240. https://doi.org/10.3390/medicina61071240

AMA Style

Pung X, Chua JJL, Fong KY, Chua YY, Loo GJM, Ong JWS, Tay JCK, Teo HK, Wang Y, Yeo C, et al. Conduction System Pacing Versus Biventricular Cardiac Resynchronization Pacing: Meta-Analysis on Outcomes in Patients with Non-Left Bundle Branch Block. Medicina. 2025; 61(7):1240. https://doi.org/10.3390/medicina61071240

Chicago/Turabian Style

Pung, Xuanming, Joe J. L. Chua, Khi Yung Fong, Yi Yi Chua, Germaine J. M. Loo, Jonathan W. S. Ong, Julian C. K. Tay, Hooi Khee Teo, Yue Wang, Colin Yeo, and et al. 2025. "Conduction System Pacing Versus Biventricular Cardiac Resynchronization Pacing: Meta-Analysis on Outcomes in Patients with Non-Left Bundle Branch Block" Medicina 61, no. 7: 1240. https://doi.org/10.3390/medicina61071240

APA Style

Pung, X., Chua, J. J. L., Fong, K. Y., Chua, Y. Y., Loo, G. J. M., Ong, J. W. S., Tay, J. C. K., Teo, H. K., Wang, Y., Yeo, C., Lim, E. T. S., Ho, K. L., Chong, D. T. T., Ching, C. K., & Tan, V. H. (2025). Conduction System Pacing Versus Biventricular Cardiac Resynchronization Pacing: Meta-Analysis on Outcomes in Patients with Non-Left Bundle Branch Block. Medicina, 61(7), 1240. https://doi.org/10.3390/medicina61071240

Article Metrics

Back to TopTop