True bipolar or extended bipolar left ventricular pacing is associated with better survival in cardiac resynchronization therapy patients

BackgroundLimited studies are available on the clinical significance of left ventricular (LV) lead polarity in patients undergoing cardiac resynchronization therapy (CRT), with a recent study suggesting better outcomes with LV true bipolar pacing.ObjectiveWe aimed to determine whether true bipolar LV pacing is associated with reduced mortality in a large, real‐life CRT cohort, followed by remote monitoring.MethodsWe analyzed de‐identified device data from CRT patients followed by the Boston Scientific LATITUDE remote monitoring database system. Patients with LV bipolar leads paced between the LV ring and LV tip were identified as true bipolar and those with LV bipolar leads paced between LV tip or LV ring and right ventricular (RV) coil were identified as extended bipolar. Patients with unipolar leads were identified as unipolar.ResultsOf the 59 046 patients included in the study, 2927 had unipolar pacing, 34 390 had extended bipolar pacing, and 21 729 had true bipolar pacing. LV true bipolar pacing was associated with a significant 30% lower risk of all‐cause mortality as compared to unipolar pacing (hazards ratio [HR] = 0.70, 95% CI: 0.62‐0.79, P < .001), after adjustment for age, gender, LV lead impedance, LV pacing threshold, and BIV pacing percentage <95%. Extended bipolar LV pacing was also associated with 24% lower risk of all‐cause mortality when compared to unipolar LV pacing (HR = 0.76, 95% CI: 0.68‐0.85; P < .001). However, there were no differences in outcomes between true bipolar and extended bipolar LV pacing (HR = 0.97, 95% CI: 0.93‐1.01; P = .198).ConclusionTrue bipolar or extended bipolar LV pacing is associated with a lower risk of mortality in CRT patients as compared to unipolar LV pacing.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154901/1/pace13889_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154901/2/pace13889.pd

Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages

Milk fat globule epidermal growth factor 8 (Mfge8) is a soluble glycoprotein known to regulate inflammation and immunity by mediating apoptotic cell clearance. Since fibrosis can occur as a result of exaggerated apoptosis and inflammation, we set out to investigate the hypothesis that Mfge8 might negatively regulate tissue fibrosis. We report here that Mfge8 does decrease the severity of tissue fibrosis in a mouse model of pulmonary fibrosis; however, it does so not through effects on inflammation and apoptotic cell clearance, but by binding and targeting collagen for cellular uptake through its discoidin domains. Initial analysis revealed that Mfge8–/– mice exhibited enhanced pulmonary fibrosis after bleomycin-induced lung injury. However, they did not have increased inflammation or impaired apoptotic cell clearance after lung injury compared with Mfge8+/+ mice; rather, they had a defect in collagen turnover. Further experiments indicated that Mfge8 directly bound collagen and that Mfge8–/– macrophages exhibited defective collagen uptake that could be rescued by recombinant Mfge8 containing at least one discoidin domain. These data demonstrate a critical role for Mfge8 in decreasing the severity of murine tissue fibrosis by facilitating the removal of accumulated collagen