BackgroundMany patients with heart failure continue cardiac resynchronization therapy (CRT) after continuous flow left ventricular assist device (CF‐LVAD) implant. We report the first multicenter study to assess the impact of CRT on clinical outcomes in CF‐LVAD patients.Methods and ResultsAnalysis was performed on 488 patients (58±13 years, 81% male) with an implantable cardioverter defibrillator (ICD) (n=223) or CRT‐D (n=265) who underwent CF‐LVAD implantation at 5 centers from 2007 to 2015. Effects of CRT on mortality, hospitalizations, and ventricular arrhythmia incidence were compared against CF‐LVAD patients with an ICD alone. Baseline differences were noted between the 2 groups in age (60±12 versus 55±14, P<0.001) and QRS duration (159±29 versus 126±34, P=0.001). Median biventricular pacing in the CRT group was 96%. During a median follow‐up of 478 days, Kaplan–Meier analysis showed no difference in survival between groups (log rank P=0.28). Multivariate Cox regression demonstrated no survival benefit with type of device (ICD versus CRT‐D; P=0.16), whereas use of amiodarone was associated with increased mortality (hazard ratio 1.77, 95% confidence interval 1.1–2.8, P=0.01). No differences were noted between CRT and ICD groups in all‐cause (P=0.06) and heart failure (P=0.9) hospitalizations, ventricular arrhythmia incidence (43% versus 39%, P=0.3), or ICD shocks (35% versus 29%, P=0.2). During follow‐up, 69 (26%) patients underwent pulse generator replacement in the CRT‐D group compared with 36 (15.5%) in the ICD group (P=0.003).ConclusionsIn this large, multicenter CF‐LVAD cohort, continued CRT was not associated with improved survival, hospitalizations, incidence of ventricular arrhythmia and ICD therapies, and was related to a significantly higher number of pulse generator changes.

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To determine whether thalamocortical synaptic circuits differ across cortical areas, we examined the ultrastructure of geniculocortical terminals in the tree shrew striate cortex in order to directly compare the characteristics of these terminals to that of pulvinocortical terminals (examined previously in the temporal cortex of the same species, Chomsung et al. Cerebral Cortex 2010). Tree shrews are considered to represent a prototype of early prosimian primates, but are unique in that sublaminae of striate cortex layer IV respond preferentially to light onset (IVa) or offset (IVb). We examined geniculocortical inputs to these two sublayers labeled by tracer or virus injections, or an antibody against the type 2 vesicular glutamate antibody (vGLUT2). We found that layer IV geniculocortical terminals, as well as their postsynaptic targets, were significantly larger than pulvinocortical terminals and their postsynaptic targets. In addition, we found that 9–10% of geniculocortical terminals in each sublamina contacted GABAergic interneurons, whereas pulvinocortical terminals were not found to contact any interneurons. Moreover, we found that the majority of geniculocortical terminals in both IVa and IVb contained dendritic protrusions, while pulvinocortical terminals do not contain these structures. Finally, we found that synaptopodin, a protein uniquely associated with the spine apparatus, and telencephalin (TLCN, or Intercellular Adhesion Molecule type 5, ICAM5), a protein associated with maturation of dendritic spines, are largely excluded from geniculocortical recipient layers of the striate cortex. Together, our results suggest major differences in the synaptic organization of thalamocortical pathways in striate and extrastriate areas.

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