Discussion
By properly synchronizing both right and left ventricular contraction,
CRT can reverse the progressive LV dilation (i.e., remodeling)
associated with heart failure, improving systolic/diastolic function
and, subsequently, clinical outcomes. By adding a second LV pacing site,
MultiPoint Pacing has demonstrated promising long-term improvements over
conventional biventricular CRT12–15. Due to the added
programming flexibility of a second LV vector, most MPP devices are left
unoptimized with out-of-the-box settings. For CRT implanting centers to
achieve the response rates reported by early MPP studies, programming
protocols are recommended that often require time-consuming in-clinic
measurements.
In the first randomized, multi-center MPP investigation conducted
entirely in the Middle East, patients were implanted with CRT-D devices
and randomized to receive either BiV or MPP therapy. While LV vector
selection in the BiV group was left to the discretion of the implanting
physician, the VectSelectTM programmer tool (Abbott)
was used to automatically recommend LV vectors for the MPP group, with
no external measurements and minimal physician input.
VectSelect recommends MPP LV pacing vectors based on automatic capture
threshold and RV-LV conduction time measurements. VectSelect provides
two recommendation options for MPP LV cathode pairs: (1) the electrodes
with maximal anatomical separation, and (2) the earliest- and
latest-activating electrodes. Large-scale clinical trials have
previously shown improved response to MPP when LV vectors were selected
with >30 mm anatomical spacing, relative to other MPP
configurations18,19. However, the clinical outcomes
associated with this strategy were only retrospectively evaluated,
leaving it unclear if the vector selection was actually the result of
other forms of optimization. Furthermore, the maximal separation option
for most leads requires availability of the proximal electrode for
>30 mm separation, which typically has higher capture
thresholds. The current study is the first prospective comparison of MPP
and BiV that relied solely on the VectSelectTMprogrammer tool (Abbott) to automatically recommend MPP LV pacing
vectors using the earliest- and latest-activating electrode option.
Relative to patients receiving conventional BiV therapy, a significantly
higher proportion of MPP patients demonstrated an ESV reduction of 15%
or more (primary endpoint), and a significantly higher proportion of MPP
patients experienced an improvement in NYHA functional class. Changes in
ESV, EF, and QRSd all trended toward greater improvement in MPP patients
than BiV patients, although statistical significance was not reached in
this study for these three metrics. Together, these results point to the
enhanced functional and clinical benefits of MPP.
Similar comparisons of MPP and BiV have been reported, but differed in
patient population, LV vector selection strategy, and
inter-/intra-ventricular delay programming. In a single-center,
44-patient study, Pappone et al.12 reported 12-month
MPP vs. BiV responder rates for ESV reduction (ΔESV ≥ 15%) of 76% vs.
57%, and for NYHA class improvement of 90% vs. 84%, respectively.
While these rates were slightly higher than those observed here (68.5%
vs. 50.7% for ESV; 80.8% vs. 60.3% for NYHA), the study by Pappone et
al. included LV vector and inter-/intra-ventricular delay optimization
based on comprehensive acute hemodynamic measurements (invasive
dP/dtmax), rather than leveraging automated LV vector
selection tools and maintaining nominal (i.e., minimal)
inter-/intra-ventricular delays.
In a retrospective study of 110 CRT patients with optimized LV pacing
sites at a single Italian center, Zanon et al.15reported higher 12-month MPP vs. BiV responder rates in terms of ESV
reduction (90% vs. 72%) and NYHA class improvement (95% vs. 78%).
These rates were also slightly higher than this report, even though
inter-/intra-ventricular delays were left at nominal values and not
optimized. However, the target LV vein was selected based on manually
optimization of either Q-LV time or invasive hemodynamics, with an
average of 3 veins tested per patient. In a larger prospective study of
232 patients in 76 Italian centers, Forleo et al.13showed 6-month EF elevations with MPP vs. BiV (10.7% vs. 6.5%) that
were comparable to those reported here (11.9% vs. 8.6%). Still, MPP LV
pacing vector selection was not standardized among centers, and included
both QRS optimization and maximization of electrical delays between
cathodes.
With varied and often time-consuming programming strategies, these
research studies were not designed to identify a simple, efficient MPP
programming guideline for broad clinical application. Furthermore, all
the aforementioned studies were limited to Italian centers, and the
results may not be directly applicable world-wide. Not only can the
results of the current study be more readily applied to patients in the
Middle East, but they may be achievable with minimal physician
intervention and without costly or lengthy optimization protocols.
Moreover, the reverse modeling response to MPP using VectSelect in this
population was not contingent upon commonly cited baseline predictors,
such as age, poor NYHA class, long QRSd, low EF, or negative
comorbidities (e.g. ischemic cardiomyopathy, hypertension, diabetes),
further highlighting its broad application.
The 6-month impact of MPP demonstrated in this study may also point to
longer-term benefits. A recent analysis of 436 CRT patients by Rickard
et al.17 evaluated the ability of early
echocardiographic changes (9-month echocardiographic follow-up time) to
predict longer-term outcomes (5-year clinical follow-up time). Of
commonly used reverse left ventricular remodeling metrics (i.e.,
end-systolic volume, end-diastolic volume, ejection fraction) with
various benchmarks, the analysis identified the combined criteria of ESV
reduction by 10% and EF elevation by 5% as the most appropriate
predictor of patient survival without an LV assist device (LVAD) or
heart transplant. According to this response metric, significantly more
MPP than BiV patients in this Middle Eastern population (65.8% vs.
44.9% ESV+EF responders) are predicted to survive long-term without
requiring more serious intervention.
Limitations
Although LV vector selection, intraventricular delay, and
interventricular delay were all defined a priori for MPP patients, this
study left the atrioventricular delay to the physician’s discretion.
Consequently, the functional and clinical benefits associated with MPP
in this study cannot be attributed to a specific, comprehensive
programming strategy. Similarly, for BiV patients, both the
atrioventricular delay and LV vector selection were left to the
discretion of the implanting physician. A more direct comparison of MPP
vs. BiV would require standardized AVD optimization methods and may
yield different results.