DNGR-1-tracing marks an ependymal cell subset with damage-responsive neural stem cell potential

Cells with latent stem ability can contribute to mammalian tissue regeneration after damage. Whether the central nervous system (CNS) harbors such cells remains controversial. Here, we report that DNGR-1 lineage tracing in mice identifies an ependymal cell subset, wherein resides latent regenerative potential. We demonstrate that DNGR-1-lineage-traced ependymal cells arise early in embryogenesis (E11.5) and subsequently spread across the lining of cerebrospinal fluid (CSF)-filled compartments to form a contiguous sheet from the brain to the end of the spinal cord. In the steady state, these DNGR-1-traced cells are quiescent, committed to their ependymal cell fate, and do not contribute to neuronal or glial lineages. However, trans-differentiation can be induced in adult mice by CNS injury or in vitro by culture with suitable factors. Our findings highlight previously unappreciated ependymal cell heterogeneity and identify across the entire CNS an ependymal cell subset wherein resides damage-responsive neural stem cell potential

Outcome of Primary Prevention Implantable Cardioverter Defibrillator Therapy According to New York Heart Association Functional Classification

International audienceWe aimed to assess if the outcome of primary prevention implantable cardioverter defibrillators (ICDs) without cardiac resynchronization therapy is dependent on New York Heart Association (NYHA) class. Among the participants of Defibrillateur Automatique Implantable-Prevention Primaire (DAI-PP; NCT01992458) multicenter cohort study, 155 patients in NYHA class I, 504 in NYHA class II, and 188 in NYHA class III had a QRS width <120 ms and were implanted with an ICD without cardiac resynchronization therapy and, thus, were eligible for the purpose of this analysis. Total and specific mortalities and the incidence of appropriate therapies were assessed for every NYHA. During 2,606 patient-years (3.1 +/- 2.1 years), 104 (12.3%) subjects died and 188 (22.2%) experienced appropriate therapies. After adjustment, overall mortality increased with NYHA class (adjusted hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.11 to 2.41, p = 0.014), driven by an increase in cardiovascular death. Conversely, incidence of appropriate ICD intervention was comparable among the 3 NYHA groups (NYHA class I 7.43, NYHA class II 7.91, and NYHA class III 12.10 per 100 patient-years; HR 1.19, 95% CI 0.89 to 1.59, p = 0.231). Incidence of ICD-unresponsive sudden death was very low and also comparable (NYHA class I 0.22, NYHA class II 0.36, and NYHA class III 0.83 per 100 patient years (HR 6.34, 95% CI 0.32 to 124.49, p = 0.224). No significant differences were observed in the other specific modes of death. In conclusion, although patients in NYHA class III have higher overall mortality, they experience a comparable incidence of appropriate ICD therapies. The low incidence of ICD-unresponsive sudden death in all assessed NYHA classes also supports the efficacy of ICDs, irrespective of NYHA class. (C) 2016 Elsevier Inc. All rights reserved

Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke

International audienceBackground and Purpose— There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF. Methods— This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population. Results— Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA 2 DS 2 -VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8–9.0). New AF patients had higher CHA 2 DS 2 -VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF. Conclusions— Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis

Prediction of Nonarrhythmic Mortality in Primary Prevention Implantable Cardioverter-Defibrillator Patients With Ischemic and Nonischemic Cardiomyopathy

International audienc

Primary Prevention Implantable Cardioverter Defibrillator (ICD) Therapy in Women-Data From a Multicenter French Registry

International audienceBACKGROUND: There are limited data describing sex specificities regarding implantable cardioverter defibrillators (ICDs) in the real-world European setting. METHODS AND RESULTS: Using a large multicenter cohort of consecutive patients referred for ICD implantation for primary prevention (2002-2012), in ischemic and nonischemic cardiomyopathy, we examined the sex differences in subjects' characteristics and outcomes. Of 5539 patients, only 837 (15.1%) were women and 53.8% received cardiac resynchronization therapy. Compared to men, women presented a significantly higher proportion of nonischemic cardiomyopathy (60.2% versus 36.2%, P\textless0.001), wider QRS complex width (QRS \textgreater120 ms: 74.6% versus 68.5%, P=0.003), higher New York Heart Association functional class (≥III in 54.2%♀ versus 47.8%♂, P=0.014), and lower prevalence of atrial fibrillation (18.7% versus 24.9%, P\textless0.001). During a 16 786 patient-years follow-up, overall, fewer appropriate therapies were observed in women (hazard ratio=0.59, 95% CI 0.45-0.76; P\textless0.001). By contrast, no sex-specific interaction was observed for inappropriate shocks (odds ratio ♀=0.84, 95% CI 0.50-1.39, P=0.492), early complications (odds ratio=1.00, 95% CI 0.75-1.32, P=0.992), and all-cause mortality (hazard ratio=0.87 95% CI 0.66-1.15, P=0.324). Analysis of sex-by- cardiac resynchronization therapy interaction shows than female cardiac resynchronization therapy recipients experienced fewer appropriate therapies than men (hazard ratio=0.62, 95% CI 0.50-0.77; P\textless0.001) and lower mortality (hazard ratio=0.68, 95% CI 0.47-0.97; P=0.034). CONCLUSIONS: In our real-life registry, women account for the minority of ICD recipients and presented with a different clinical profile. Whereas female cardiac resynchronization therapy recipients had a lower incidence of appropriate ICD therapies and all-cause death than their male counterparts, the observed rates of inappropriate shocks and early complications in all ICD recipients were comparable. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT0199245