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.