Right ventricular pacing (RVP) is recommended for patients with symptomatic bradyarrhythmia and cardiac conduction dysfunction [1]. Although RVP is a well-established pacing strategy in clinical practice, it has been demonstrated that chronic RVP may lead to electrical and mechanical dyssynchrony and is associated with an increased risk of atrial fibrillation (AF), heart failure (HF) hospitalization, left ventricular (LV) dysfunction, and increased mortality [2, 3, 4]. Cardiac resynchronization therapy (CRT), which improves mechanical dyssynchrony through the electrical activation of the heart in a coordinated manner, can overcome the limitations of RVP; it is mainly used to treat patients with HF and ventricular systolic dyssynchrony [5, 6]. While it has been established that CRT with biventricular pacing (BVP) is superior to RVP in patients with atrioventricular block and reduced left ventricular ejection fraction [7], patient response to BVP was variable and 30%–40% of patients did not experience any benefit from BVP, including patients with narrow QRS duration and those with right bundle branch block [8, 9, 10]. Subsequently, two physiological pacing strategies, His bundle pacing (HBP) and left bundle branch pacing (LBBP), have become effective alternatives to CRT. HBP, a feasible alternative to CRT, directly paces the His-Purkinje system to activate the ventricles and physiologically achieve synchronous contraction [11, 12]. However, its steeper and longer learning curve, higher pacing thresholds, and lower implantation success rates have limited its clinical application [13]. Therefore, as a novel pacing technology first reported by Huang et al. [14] in 2017, LBBP directly captures the left bundle branch through deep septal pacing and is gradually being widely used in clinical practice because of its low pacing threshold, lead stability, normal ventricular sensing, and correction of distal conduction system disease [15].

Several studies have demonstrated the effectiveness and safety of LBBP. Meta-analyses have demonstrated that compared with other pacing strategies, LBBP was associated with better performance in pacing parameters and improved clinical outcomes, such as a lower capture threshold and larger R-wave amplitude at implantation, shortened QRS duration, and greater improvement in LVEF [16, 17, 18, 19]. While most studies mainly focus on the electrocardiogram characteristics and pacing parameters of LBBP compared with those of other pacing strategies [20, 21, 22], only few studies report the risk of AF in LBBP; in addition, the sample sizes of these studies were relatively small [23, 24, 25, 26]. To the best of our knowledge, only one meta-analysis reported as a conference abstract showed that physiological pacing (including HBP and LBBP) was not associated with AF risk reduction compared with RVP (odds ratio (OR) 0.95, 95% CI 0.76–1.18) [27]. No meta-analysis has specifically evaluated the risk of AF in patients receiving LBBP compared with other pacing strategies.

A study investigating the predictors of AF in patients with pacemakers found that pacemaker detected AF in 51.8% of patients without AF history during a mean follow-up of 52 months [28]. LBBP-associated improvements in biventricular synchrony and atrial function can theoretically reduce the risk of AF. Therefore, this systematic review and meta-analysis aimed to compare AF risk associated with LBBP with that of other pacing strategies.

This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and registered in PROSPERO database (CRD42022367476) [29].

This systematic review and meta-analysis aimed to evaluate AF risk in LBBP compared with that in other pacing strategies. We found that the incidence of AF in the LBBP group was much lower than that in other pacing strategies (BVP and RVP). Compared to BVP or RVP, LBBP was associated with reduced AF risk. Similar outcomes of LBBP as regard AF have been observed among patients of different races. Our findings suggest that the risk of AF may be reduced in patients with LBBP compared with those with BVP or RVP.

It is well known that RVP is associated with an increased risk of AF. Although the exact mechanism of AF induced by ventricular pacing is not clear, it is generally accepted that left atrial dysfunction due to left ventricular dyssynchrony caused by ventricular pacing may be the cause [34]. BVP can maintain atrioventricular synchrony and better preserve physiological function, thereby reducing the risk of AF. The Mode Selection Trial in Sinus-Node Dysfunction (MOST) trial, which included 1014 sinus-node dysfunction (SND) patients with a median of 33.1 months of follow-up, found that dual-chamber pacing was associated with a 21% AF risk reduction (21.4% vs 27.1%; HR: 0.79 (0.66–0.94); p = 0.008) compared with ventricular pacing [35]. A subgroup analysis of the MOST trial involving patients with SND and normal QRS duration at baseline found a positive relationship between the cumulative percentage of VP (Cum%VP) and AF risk in both the dual-chamber pacing and ventricular pacing groups, which suggested that ventricular desynchronization induced by right ventricular apical pacing in the dual-chamber mode offsets the benefit of AV synchrony and increases AF risk [2]. The Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACe) trial further illustrated that dual-chamber minimal ventricular pacing was associated with an absolute risk reduction of 4.8% and a relative risk reduction of 40% for persistent AF compared with conventional dual-chamber pacing, indicating that reduced ventricular pacing in the dual-chamber mode prevents ventricular desynchronization [36]. Therefore, a more physiological pacing approach may help ameliorate ventricular dysfunction or atrioventricular asynchrony caused by ventricular pacing.

HBP maintains physiological electrical activation and reduces the risk of AF. Pastore et al. [37] illustrated that the location of RVP may affect the risk of AF, and the risk of AF in the Hisian area was lower than that in the right ventricular septal and apex (16.9% vs 25.7% vs 28.0%). Ravi et al. [24] found that HBP, compared with conventional RVP, was associated with a lower risk of new-onset AF, and the benefit was more pronounced in patients with a higher burden of ventricular pacing. However, significant difference in AF disease progression was observed between HBP and RVP in patients with previously diagnosed AF [38]. In addition, another study by Pastore et al. [39] further demonstrated that HBP was associated with a lower risk of persistent AF than a dual-chamber pacemaker with unnecessary ventricular pacing (DDD-VPA) and that the benefit of HBP was mainly found in patients with a basal PR greater than 180 ms. All these studies suggest that a more physiological pacing helps preserve AV dyssynchrony and thus prevent the onset of AF.

Therefore, LBBP, which belongs to the same physiological pacing category as HBP, can theoretically reduce the incidence of AF. Our findings indicate that LBBP is associated with a 67% reduction in AF risk compared with RVP, and a 53% reduction in AF risk compared with BVP. However, there are some limitations of this study. First, as LBBP is a relatively novel pacing technology, only 5 studies were included in our meta-analysis, of which 3 were prospective, 2 were retrospective, and none were RCTs, the small number of studies may yield biased results, especially for the AF incidence rate of BVP and RVP. Several large RCTs have reported the AF incidence involving BVP and RVP, which suggested that the AF incidence following BVP ranged from 8.5% to 23.0% [2, 35, 40, 41] and following RVP ranged from 9.3% to 28.0% [2, 35, 37]. Our studies estimated the AF incidence rate is 6.1% and 19.4% in BVP and RVP, respectively, and the incidence of AF in BVP may be underestimated. Data from real-world studies with larger samples are needed. Additionally, as none RCTs has reported the AF risk between LBBP and other pacing stratigies, large RCTs are needed to confirm the benefit of LBBP in reducing the risk of AF. Second, because the risk of AF varies and the effect of pacing varies in patients with different characteristics, more subgroup analyses according to patient characteristics are warranted. However, because individual data were not available, we only conducted subgroup analyses by Asian and non-Asian, long-term AF and short-term AF. Other subgroup analyses, such as with and without HF at baseline, need to be further explored. Furthermore, two studies showed that LBBP is more likely to be beneficial than RVP in patients with a higher ventricular pacing burden [23, 24]. Since QRS duration and PR intervals have been shown to be associated with an increased risk of AF [42, 43], further studies should also be conducted to determine whether the benefit of LBBP compared with BVP in reducing the risk of AF differs in patients with long versus short QRS duration, as well as long versus short PR intervals. Additionally, there is no comparative study of AF risk between LBBP and BVP under brady indication, which requires more research.

This meta-analysis found that LBBP, compared with BVP and RVP, was associated with a lower risk of AF. Whether LBBP is superior to other pacing strategies in reducing the risk of new-onset AF needs to be confirmed in large-sample randomized controlled trials.

The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author.

JD came up the idea and supported the work. BL drafted the manuscript. BL, WLD, YKL, YLL and YQW participated in the data collection. YKL performed the analysis. WLD, YKL, YLL, YQW and JD contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Not applicable.

The author would like to thank Editage for technical editing of the manuscript.

This research received no external funding.

The authors declare no conflict of interest.