Left Ventricular Enlargement, CRT Response and Impact of MultiPoint Pacing.

Background - Left ventricular (LV) epicardial pacing results in slowly propagating paced wavefronts. We postulated that this effect might limit cardiac resynchronization therapy (CRT) efficacy in patients with LV enlargement using conventional biventricular (BiV) pacing with single-site LV pacing, but be mitigated by LV stimulation from 2 widely spaced sites using MultiPoint™ Pacing (MPP-AS: anatomical separation ≥ 30mm). We tested this hypothesis in the multicenter randomized MPP IDE trial. Methods - Following implant, quadripolar BiV pacing was activated in all patients (n=506). From 3 to 9 months postimplant, among patients with available baseline LV end-diastolic volume (LVEDV) measures, 188 received BiV pacing, and 43 received MPP-AS. Patients were dichotomized by median baseline LVEDV indexed to height (LVEDVIMedian). Outcomes were measured by the clinical composite score (CCS, primary efficacy endpoint), quality of life (QOL), LV structural remodeling (↑EF>5% and ↓ESV 10%) and heart failure (HF) event/ cardiovascular death. Results - LVEDVIMedian was 1.1 mL/cm. Baseline characteristics differed in patients with LVEDVI>Median vs. LVEDVI≤Median. Among patients with LVEDVI>Median, BiV was less efficacious compared to patients with LVEDVI≤Median (CCS 65% vs. 79%). In contrast, MPP-AS programming generated greater CCS response (92% vs. 65%, p=0.023) and improved QOL (-31.0±29.7 vs. -15.7±22.1, p=0.038) vs. BiV in patients with LVEDVI>Median. Reverse remodeling trended better with MPP-AS programming. When LVEDVI>Median, HF event rate increased following the 3-month randomization point (0.0150±0.1725 in LVEDVI>Median vs. -0.0190±0.0808 in LVEDVI≤Median, p=0.012) in BiV, but no heart failure event occurred in patients with MPP-AS programming between 3 and 9 months in LVEDVI>Median. All measured outcomes did not differ in patients receiving MPP-AS and BiV pacing with LVEDVI≤Median. Conclusions - Conventional BiV pacing, even with a quadripolar lead, has reduced efficacy in patients with LV enlargement. However, in patients with larger hearts and programmed to MPP-AS the greatest response rate was observed.