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.