Discussion
We systematically reviewed 10 original studies comparing LBBP and BVP
CRT, which were comprised of patients from 15 centers around the world.
This is the largest, most up-to-date systemic review and meta-analysis
to demonstrate the effectiveness and safety of LBBP CRT to our
knowledge. We found 1) performing LBBP compared to BVP is associated
with shorter procedure and fluoroscopy time. 2) LBBP is associated with
a greater reduction in QRSd and greater LVEF improvement. 3) A composite
of HFH hospitalization and all-cause mortality had a greater reduction
with LBBP as well as a greater improvement in overall function. However,
the reported mortality was low and there was no difference in all-cause
mortality alone. The overall implant success rate was approaching 90%
and complication rates were low. Comparison of implant success rate of
LBBP and BVP was not performed because most included studies only
included historical cohor for BVP which only consist of successfully
implanted cases.
Since the introduction of LBBP, multiple studies have explored the
feasibility, safety, and clinical comparison of other existing pacing
methods in various indications including heart failure requiring
CRT23-30. A previous study had shown LBBP, if
optimized AV delay, can achieve better interventricular synchrony
compared to BVP in ex-vivo heart models18. A
retrospective cohort of 34 patients who underwent LBBP CRT with a
follow-up period of 12 months observed a significant decrease in QRSd,
and improvement in LVEF, LVEDD, NYHA classification, brain natriuretic
peptide (BNP) level, and 6-minute walk test (6MWT). The success rate of
LBBP in the cohort was 100% with stable pacing capture threshold and
R-wave amplitude at the end of 12 months follow-up23.
Another study that compared CSP (87 HBP and 171 LBBP) and BVP also noted
a significantly narrower QRSd, greater LVEF improvement, and lower
composite of HFH and mortality31.
Our findings were also consistent with recently published Left bundle
branch area pacing outcomes: the multicenter European (MELOS) study and
the Left Ventricular Activation Time Shortening With Conduction System
Pacing vs Biventricular Resynchronization Therapy (LEVEL-AT)
trial32, 33. The MELOS study was a registry-based
observational study comprised of 2,533 patients attempted LBBP with
27.5% of whom had an indication from heart failure. The reported
implant success rate in heart failure indication was 82.2%, which was
similar to our finding. The overall complication rate of LBBP in the
MELOS study was 11.68% mainly driven by lead complications including
left ventricle perforation and dislodgement, which was much higher than
our finding. The LEVEL-AT trial was a randomized controlled
noninferiority trial that compared ventricular synchrony in CSP
including HBP and LBBP with BVP in HFrEF patients with indications for
CRT. Of the 35 CSP patients included, the majority of them were
allocated to LBBP (80%). It showed ventricular synchronization achieved
by CSP was non-inferior to BVP. There was a trend towards a greater QRSd
reduction and a lower composite of HFH or mortality after a 6-month
follow-up period but no difference in LVEF improvement. The implant
success rate of LBBP was 82% which was similar to our finding. The high
crossover rate (8/35 crossed over from CSP to BVP and 2/35 corssed over
from CVP to CSP) and small sample size of the trial might limit further
interpretation of results.
The improvement in interventricular synchrony by EKG findings (QRSd) and
clinical outcomes we had observed may not be limited to HFrEF patients
but to patients with heart failure with preserved ejection fraction
(HFpEF) and heart failure with midrange ejection fraction (HFmrEF), as
one recent study suggests27. Echocardiographic
parameters of interventricular synchrony assessment including
interventricular mechanical delay (defined as difference between the
pre-ejection intervals from QRS onset to the beginning of ventricular
ejection at pulmonary and aortic valve level), the regional time
intervals of left ventricular 12 segments between the onset of the QRS
complex and the peak of systolic myocardial velocity during the ejection
phase (Ts), standard deviation of Ts (Ts-SD) and peak strain dispersion
had greater improvement with LBBP compared to BVP but they were only
studied in two of included studies34, 35.
Despite LBBP having greater hemodynamic improvement as well as lower HFH
in our analysis, we did not observe a clear benefit in all-cause
mortality compared to BVP CRT, which can be attributed to the short
follow-up period by most studies included. This was evidenced by the
lower-than-expected mortality rate. The short follow-up can also
potentially preclude the delayed effect in mortality benefit by improved
interventricular synchrony and hemodynamics.
In patients with failed BVP due to CS lead failure or nonresponsive to
BVP, it has been demonstrated that LBBP can be a safe and viable
alternative 36. In the 2021 ESC Guidelines on Cardiac
Pacing and CRT, there was no official recommendation for LBBP pending
more evidence for long-term safety and efficacy from randomized
trials37.
With shorter procedural and fluoroscopy time and possible improved
clinical outcomes, LBBP is a promising and emerging alternative to BVP.
Further studies, especially randomized controlled trials are required to
demonstrate the long-term safety and efficacy of LBBP, and further,
elucidate the clinical benefit of LBBP CRT. ChiCTR200028726 is an
ongoing single-center randomized controlled noninferiority trial aiming
to recruit 180 patients with HFrEF and indication of
CRT38. Patients will be randomized at a 1:1 ratio to
LBBP or BVP CRT. The recruitment period concluded in December 2022. The
completion of this trial and other ongoing trials can potentially better
demonstrate the role of LBBP CRT.