Discussions
Our study demonstrated that LV systolic function was significantly improved after LBBAP implantation in patients with HFrEF. Specifically, LBBAP implantation resulted in a greater reduction in paced QRS and improved echocardiographic findings (i.e., LVEF, LVESV, LVESD, LVEDD, and LVEDV). Furthermore, LBBAP implantation significantly improved NYHA classifications and NT-pro BNP levels. Regarding pacing durability, pacing parameters were stable over time. The results were demonstrated in Supplemantary 1 .
The decline in LV systolic function is multifactorial. In clinical practice, this is generally categorized into device-related LV systolic function and others. For device-related LV systolic dysfunction or PICM, chronic RV pacing (RVP) causes worsening of LV systolic function. Initially, RVP has been indicated for severe bradyarrhythmia resulting from complete heart block, but nowadays, there are more indications for RVP implantation in the general population. This pacing causes several adverse events, including cardiac contraction asynchrony, which is linked to PICM and higher mortality. On the other hand, BVP has the potential to reverse LV remodeling and can improve clinical outcomes in patients with PICM. However, this is a non-physiological activation that is limited by its reliance on myocardial cell conduction, and thus, there is a significant proportion of CRT non-responders, at around 30% to 40%. Barba-Pichardo et al. found that HBP could correct LBBB and improve clinical HF symptoms and outcomes in patients with unsuccessful LV lead replacement. Thus, HBP has been explored for several years as an alternative to CRT [27] , and various studies comparing the efficacy and results of HBP and BVP have been discussed[28,29] . These studies found that HBP is superior in conducting electrical cardiac resynchronization, but the pacing output of HBP was substantially high and unstable during long-term follow-up. To overcome the increasing trend of pacing thresholds by HBP, LBBAP was developed as a new pacing strategy to correct PICM after undergoing RVP. This works by bypassing the blocking zone and delivering the electrophysiological signal inside the LV endocardium area, resulting in reverse LV function, narrow QRSd, LBBB correction, and a low and consistent pacing output [30,31] .
Our results were consistent with those of previous meta-analyses, which reported that patients with LBBAP had a greater reduction in paced QRS (mean difference: 27.91 msec; 95% CI, 22.33 to 33.50), as well as a greater improvement in NYHA class (mean difference: 0.59; 95% CI, 0.28 to 0.90) and LVEF (mean difference: 6.77 %; 95% CI, 3.84 to 9.71)[32] . Nevertheless, we included 14 papers in our updated systematic review and meta-analysis, which studied at the clinical outcomes and efficacy of LBBAP in HFrEF. Furthermore, this is the first study to compare the PICM and non-PICM groups. To our knowledge, this is the single largest and most comprehensive meta-analysis on LBBAP for CRT to date.
According to our findings, LBBAP caused a significant narrowing in QRSd, which is an important indicator of electrical conduction disturbance correction and is now the most relevant measure of the influence of CRT on electromechanical resynchronization. High-output unipolar pacing, according to Kailun et al., overcomes the resistivity of longitudinal dissociation fibrous sheaths and captures RBB by overcoming the obstruction via transverse connectivity [33]. Moreover, Ponnusamy et al. [17] discovered that LBBAP was linked to an initial drop in Tpeak-Tend duration and corrected QT interval relative to baseline, followed by a further decrease after memory T-wave resolution. It was also found that Tpeak-Tend/QTc ratio, a better indicator of arrhythmogenesis, reduced from 0.22 ± 0.02 to 0.17 ± 0.01 immediately after LBBAP. This eventually reduced to 0.16 ± 0.01 after 6 weeks, implying that there may be a secondary benefit of reduced arrhythmic risk. T-wave memory impairments were observed in all patients shortly after LBBAP, but this disappeared after 6 weeks.
Interestingly, no statistically significant differences were found in QRSd shortening, pacing parameters, and NYHA class improvements among PICM versus non-PICM groups. Furthermore, we aimed to explore the impact of Chinese outcomes due to their recognition as a pioneer of the LBBAP procedure, but no racial difference was demonstrated in our meta-analysis. Aside from the clinical benefits and electrical synchrony, pacing parameters were also important in pacing treatments, such as pacing threshold and impedance. The pacing thresholds/impedances of the LBBAP group remained relatively stable at 6–12 months of follow-up.
This meta-analysis has several noteworthy limitations. First, majority of the studies included are prospective and retrospective observational studies, meaning that a causal association between improved clinical and echocardiographic outcomes after LBBAP implantation cannot be concluded. Second, only a limited number of studies and patients were included. As a result, additional studies may be required to support these findings. Finally, there was a discrepancy in the definition of QRSd after completion of LBBAP implantation, which represents the correction of electrical dyssynchrony.