Cardiac Resynchronization Therapy and Clinical Outcomes in Continuous Flow Left Ventricular Assist Device Recipients.

BACKGROUND: Many 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 RESULTS: Analysis 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). CONCLUSIONS: In 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.

Ultrastructure of geniculocortical synaptic connections in the tree shrew striate cortex.

To determine whether thalamocortical synaptic circuits differ across cortical areas, we examined the ultrastructure of geniculocortical terminals in the tree shrew striate cortex to compare directly the characteristics of these terminals with those of pulvinocortical terminals (examined previously in the temporal cortex of the same species; Chomsung et al. [] Cereb Cortex 20:997-1011). 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, whereas 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), 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.

Periprocedural management of anticoagulation in patients taking novel oral anticoagulants: Review of the literature and recommendations for specific populations and procedures.

An increasing number of individuals are on novel oral anticoagulants (NOAC) for anticoagulation instead of vitamin K antagonists (VKA) and roughly 10% of these individuals will require interruption of these agents for procedures annually. Recent evidence surrounding bridging as well as the FDA approval of a new NOAC call for a comprehensive review and update regarding periprocedural NOAC management. The periprocedural management of NOACs involves striking a balance between the risks of bleeding and thromboembolism associated with interruption, bridging, and reinitiation of anticoagulation. NOACs have a distinct pharmacokinetic advantage in this setting with their quick onset and elimination from the body. Procedures at low risk for bleeding do not require interruption and can be scheduled at the start of the next dosing interval. Procedures at moderate-high risk of bleeding require interruption of NOAC for 5 half lives prior to the procedure to allow for adequate elimination of the drug. In light of new evidence highlighting the risks of bleeding, and given shorter "unprotected" times with NOAC interruption versus VKA, patients at low-moderate risk for thromboembolism should not be bridged when "unprotected" time is less than 96 h. For patients at high risk for thromboembolism, individual patient and surgical factors need to be considered before the decision to bridge is made. The benefit of bridging these patients who have a considerable risk of bleeding may not outweigh the benefits. Focused randomized studies on periprocedural management of NOACs are urgently needed.