Impact of pacing configuration and right ventricular lead location on dynamic atrioventricular delay optimization

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abbott Introduction Automatic adjustment of atrioventricular delay (AVD) with SyncAV has been shown to improve electrical synchronization. However, the effect of pacing configuration and right ventricular (RV) lead location on SyncAV programming is unknown. Purpose Evaluate the effect of pacing configuration and lead location on SyncAV optimization during biventricular (BiV) and LV-only pacing, with and without MultiPoint Pacing (MPP). Methods Patients with LBBB and QRS duration (QRSd) ≥ 150 ms scheduled for CRT-P/D device implantation with quadripolar LV lead were enrolled in this prospective study. RV lead location was classified at implant by the operator via fluoroscopy. QRSd was measured post-implant from 12-lead surface ECG by blinded experts during the following pacing modes: intrinsic conduction, BiV (BiV = RV + LV1), MPP (MPP = RV + LV1 + LV2), LV-only single-site (LVSS = LV1 only), and LV-only MPP (LVMPP = LV1 + LV2). For each mode, SyncAV was enabled (e.g. BiV + SyncAV) with the patient-tailored SyncAV offset that minimized QRSd. For BiV and LVSS, LV1 was the latest activating LV cathode; for MPP and LVMPP, LV1 + LV2 were the two LV cathodes with the widest possible separation (≥30mm). All modes used minimal RV-LV and LV1-LV2 delays. Results Fifty-three patients (68% male, 36% ischemic, 26% ejection fraction, 169 ms intrinsic QRSd) completed device implant and QRSd assessment. RV leads were implanted in either the septum (48%) or apex (52%), according to implanting physician preference. Relative to intrinsic conduction, BiV + SyncAV and MPP + SyncAV reduced QRSd by 23% and 27%, respectively (p < 0.01). LVSS + SyncAV reduced QRSd by 22% (p < 0.01 vs BiV + SyncAV), and LVMPP + SyncAV reduced QRSd by 25% (p < 0.05 vs MPP + SyncAV). RV apex or septum lead location did not have a significant impact on QRS reduction for each pacing configuration. As a percent of PR interval, optimal SyncAV offsets were similar for BiV + SyncAV and MPP + SyncAV (16% vs 13%, p = 0.05), and for LVSS + SyncAV and LVMPP + SyncAV (18% vs 21%, p = 0.46), but were significantly higher for LV-only settings vs. corresponding BiV/MPP settings (p < 0.05 for both pairs). For BiV + SyncAV, apical vs septal RV leads required greater SyncAV offsets (22% vs 11%, p < 0.05). SyncAV offsets also tended to be higher in apical vs septal RV leads for MPP (21% vs 11%), LVSS (20% vs 15%), and LVMPP (25% vs 16%), but without statistical significance. Conclusion SyncAV improves acute electrical synchronization in CRT patients with LBBB, particularly with patient-specific SyncAV programming. Pacing configuration (RV + LV or LV only, with or without MPP) and RV lead location (apex or septum) could potentially influence optimal SyncAV programming. Abstract Figure

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Telomere Length Shows No Association with BRCA1 and BRCA2 Mutation Status

This study aimed to determine whether telomere length (TL) is a marker of cancer risk or genetic status amongst two cohorts of BRCA1 and BRCA2 mutation carriers and controls. The first group was a prospective set of 665 male BRCA1/2 mutation carriers and controls (mean age 53 years), all healthy at time of enrolment and blood donation, 21 of whom have developed prostate cancer whilst on study. The second group consisted of 283 female BRCA1/2 mutation carriers and controls (mean age 48 years), half of whom had been diagnosed with breast cancer prior to enrolment. TL was quantified by qPCR from DNA extracted from peripheral blood lymphocytes. Weighted and unweighted Cox regressions and linear regression analyses were used to assess whether TL was associated with BRCA1/2 mutation status or cancer risk. We found no evidence for association between developing cancer or being a BRCA1 or BRCA2 mutation carrier and telomere length. It is the first study investigating TL in a cohort of genetically predisposed males and although TL and BRCA status was previously studied in females our results don't support the previous finding of association between hereditary breast cancer and shorter TL

Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

Long term conservation of electrical synchrony by multipoint pacing with dynamic atrioventricular delays

Introduction Automatic adjustment of atrioventricular delay (AVD) with SyncAV has been shown to improve electrical synchronization. However, the long term effects of SyncAV optimization on electrical synchrony are unknown. Purpose Evaluate the effect of SyncAV programming on 6-month (6mo) QRS duration during biventricular (BiV) and left ventricle only MultiPoint Pacing (MPP). Methods Patients with LBBB and QRS duration (QRSd) ≥ 150 ms scheduled for CRT-P/D device implantation with quadripolar LV lead were enrolled in this prospective study. QRSd was measured post-implant from 12-lead surface ECG by blinded experts during the following pacing modes: intrinsic conduction, MPP (MPP=RV+LV1+LV2) and LV-only MPP (LVMPP=LV1+LV2). For each mode, SyncAV was enabled (e.g. MPP+SyncAV) with the patient-tailored SyncAV offset that minimized QRSd. Patients were then randomized 1:1 to receive MPP+SyncAV or LVMPP+SyncAV with the optimal offset identified at implant, and QRSd was re-evaluated at the 6mo follow-up. Results Fifty-nine patients (72% male, 41% ischemic, 26% ejection fraction, 166 ms intrinsic QRSd) completed device implant and QRSd assessment. Relative to intrinsic conduction at implant, the MPP+SyncAV group (n=30) had a QRSd reduction of 26% at implant (162 to 122 ms, p<0.001), and 20% at 6mo (162 to 130 ms, p<0.001). The LVMPP+SyncAV group (n=29) had a QRSd reduction of 24% at implant (165 to 128 ms, p<0.001), and 15% at 6mo (165 to 140 ms, p<0.001). In the MPP+SyncAV group, 28/30 (93%) of patients had more than 10% reduction in QRSd with respect to intrinsic at implant, with 27/30 (90%) maintaining this trend at 6 mo follow up. With LVMPP+SyncAV pacing, only 25/29 (86%) of patients had more than 10% reduction in QRSd with respect to intrinsic at implant, and this reduced to 18/29 (62%) maintaining this trend at 6 mo follow up. Conclusion MPP combined with SyncAV significantly improved acute electrical synchrony at implant in CRT patients with LBBB, as assessed by QRSd reduction. Significant QRSd reduction was maintained at 6 months post-implant by both biventricular and LV-only MPP configurations

Carbon dioxide capture and separation techniques for advanced power generation point sources

The capture/separation step for carbon dioxide (CO2) from large-point sources is a critical one with respect to the technical feasibility and cost of the overall carbon sequestration scenario. For large-point sources, such as those found in power generation, the carbon dioxide capture techniques being investigated by the in-house research area of the National Energy Technology Laboratory possess the potential for improved efficiency and costs as compared to more conventional technologies. The investigated techniques can have wide applications, but the research has focused on capture/separation of carbon dioxide from flue gas (postcombustion from fossil fuel-fired combustors) and from fuel gas (precombustion, such as integrated gasification combined cycle – IGCC). With respect to fuel gas applications, novel concepts are being developed in wet scrubbing with physical absorption; chemical absorption with solid sorbents; and separation by membranes. In one concept, a wet scrubbing technique is being investigated that uses a physical solvent process to remove CO2 from fuel gas of an IGCC system at elevated temperature and pressure. The need to define an ideal solvent has led to the study of the solubility and mass transfer properties of various solvents. Fabrication techniques and mechanistic studies for hybrid membranes separating CO2 from the fuel gas produced by coal gasification are also being performed. Membranes that consist of CO2-philic silanes incorporated into an alumina support or ionic liquids encapsulated into a polymeric substrate have been investigated for permeability and selectivity. An overview of two novel techniques is presented along with a research progress status of each technology

Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme?

Most malignant brain tumours contain various numbers of cells with characteristics of activated or dysmorphic macrophages/microglia. These cells are generally considered part of the tumour stroma and are often described as TAM (tumour-associated macrophages). These types of cells are thought to either enhance or inhibit brain tumour progression. Recent evidence indicates that neoplastic cells with macrophage characteristics are found in numerous metastatic cancers of non-CNS (central nervous system) origin. Evidence is presented here suggesting that subpopulations of cells within human gliomas, specifically GBM (glioblastoma multiforme), are neoplastic macrophages/microglia. These cells are thought to arise following mitochondrial damage in fusion hybrids between neoplastic stem cells and macrophages/microglia