Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production.

A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the CSF. To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) versus fourth ventricle (hindbrain) choroid plexus. We find that positional identities of mouse, macaque, and human choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified choroid plexus epithelial cells also predicts their cell-type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each choroid plexus. We propose that regional differences between choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system.

Ventricular Arrhythmias and Sudden Cardiac Death in Left Ventricular Assist Device Patients Without Implantable Cardioverter Defibrillators.

Patients with left ventricular assist devices (LVAD) can develop sustained ventricular arrhythmias (VA). The history and presentation of VA in implantable cardioverter defibrillator (ICD)-naive patients with LVAD is not well described in the literature and the risks/benefits of ICD implantation are unknown. This single-center retrospective cohort study included patients >18 years old who did not have an ICD during LVAD implantation from 2010 to 2022. The primary outcome was VA event rate per 100 patient-years. Two hundred thirty-seven patients underwent LVAD implantation and we identified 46 (19.4%) ICD naive patients. The etiology of heart failure in most patients was nonischemic cardiomyopathy (67.4%). Of all patients, only five were found to have documented VA. Only two episodes of VA occurred in the ambulatory setting. The estimated index VA rate was 5.89 events per 100 patient-years in our entire ICD-naive LVAD population. In the ambulatory ICD-naive population, the estimated VA rate was 2.42 events per 100 patient-years with no associated mortality. The rate of index VA in ICD-naive patients was below thresholds associated with benefits from ICD insertion. No ambulatory mortality from VA was seen and VA was well tolerated by the LVAD population. Perioperative VA in this population is associated with high mortality.