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Right ventricular (RV) failure remains a major complication after surgical implantation of a left ventricular assist device (LVAD). While the use of a percutaneous RV assist device has been described as a short‐term bridge to recovery in end‐stage heart failure patients with early post‐operative RV failure after index LVAD implant, management of refractory late RV failure remains challenging in these patients. We report the first successful case of extended Impella RP use as a safe and effective bridge to orthotopic heart transplant in an LVAD patient with refractory, haemodynamically significant late RV failure. The Impella RP provided support for 37 days. Haemodynamically intolerant arrhythmia precluded use of inotropic support. No adverse complications related to percutaneous Impella RP support were seen. We also review potential considerations for mechanical circulatory support strategies in this setting: central RV assist device cannulation requires sternotomy incision that can impact subsequent cardiac surgeries, while percutaneous Protek Duo insertion requires adequate vessel size and patency. With an LVAD in situ, veno‐arterial extracorporeal membrane oxygenation was not considered for isolated RV support in this case. The patient is currently over 6 months post‐orthotopic heart transplant.

To investigate the impact of novel, polymer-jacketed, tapered-tip, low-force guidewires with composite-core, dual-coil design (Fielder XT-R and Fielder XT-A; Asahi Intecc) on antegrade wire escalation (AWE) crossing of coronary chronic total occlusion (CTO) lesions.From March of 2017 to December 2018, a total of 164 consecutive CTO lesions at a single institution were treated with a primary AWE strategy using either Fielder XT-R or XT-A (XTRA) as the starting wire regardless of lesion characteristics. Success rates, wiring times, and complications were analyzed.The mean Japanese (J)-CTO score was 3.71 ± 1.27, mean PROGRESS-CTO score was 2.46 ± 1.15, and mean PROGRESS-CTO Complications score was 3.9 ± 2.0. Mean CTO length was 25.0 ± 0.5 mm, 48 lesions (29.3%) were previously bypassed, 77 lesions (47.0%) had moderate to severe calcification, and 62 lesions (37.8%) had moderate to severe tortuosity. Antegrade success rates using XTRA wires were 79%, 60%, and 17% of lesions with J-CTO scores of 0-1, 2-3, and 4-5, respectively. In successful antegrade XTRA cases, median wiring times were 6.5 min (interquartile range [IQR], 5.0-11.0 min), 9.0 min (IQR, 4.2-14.0 min), and 12.0 min (IQR, 9.0-15.0 min) for J-CTO scores of 0-1, 2-3, and 4-5, respectively, and differed non-significantly according to J-CTO score (P=.20). Complication rates were low (In-hospital major adverse cardiac event rate, 1.3%) with no wire perforations caused by XTRA wires.Use of Fielder XTRA wires as part of an AWE strategy in CTO percutaneous coronary interventions may facilitate more efficient antegrade lesion crossing and overall procedural success in lesions that have been traditionally challenging to treat using an antegrade-first approach.

Introduction Optimal antithrombotic therapy after transcatheter aortic valve replacement (TAVR) remains unclear. We evaluated the association between antithrombotic regimens and outcomes in TAVR patients. Methods We retrospectively analyzed consecutive patients who underwent TAVR at a single academic center from April 2009 to March 2014. Antithrombotic regimens were classified as single or dual antiplatelet therapy (AP), single antiplatelet plus anticoagulant (SAC), or triple therapy (TT). The primary endpoint was a composite of death, myocardial infarction (MI), stroke, and major bleeding. Adjusted hazard ratios (HRs) were obtained with best subset variable selection methods using bootstrap resampling. Results Of 246 patients who underwent TAVR, 241 were eligible for analysis with 133, 88, and 20 patients in the AP, SAC, and TT groups, respectively. During a median 2.1-year follow-up, 53.5% had at least one endpoint—the most common was death (68%), followed by major bleeding (23%), stroke (6%), and MI (3%). At 2 years, the composite outcome occurred in 70% of TT, 42% of SAC, and 31% of AP patients. Compared to AP, adjusted HRs for the composite outcome were 2.88 [95% Confidence intervals (CI) (1.61–5.16); p = 0.0004] and 1.66 (95% CI [1.13-2.42]; p = 0.009) in the TT and SAC groups, respectively. Mortality rates at 2 years were 61% in the TT, 32% in the SAC, and 26% in the AP groups (p = 0.005). Conclusions The risk of the composite outcome of death, MI, stroke, or major bleeding at 2-year follow-up was significantly higher in TAVR patients treated with TT or SAC versus AP, even after multivariate adjustment.

Introduction The aim of this study was to describe peri-procedural antithrombotic use in patients undergoing transcatheter aortic valve replacement (TAVR) at a single academic medical center. Methods Retrospective collection of antiplatelet and anticoagulant use during the index hospitalization for all patients undergoing TAVR at our institution from April 2009 through March 2014. Results Of a total of 255 patients undergoing the procedure, 132 (51%) had an indication for anticoagulation pre-TAVR and 92 (70% of those with an indication) were on treatment. On discharge, 106 patients (44% of total surviving to discharge, 73% of those surviving with an indication for anticoagulation) were treated with oral anticoagulation. Of these patients, 89 (84%) were discharged on aspirin and an oral anticoagulant without clopidogrel. Only 122 (51% of total patients) were discharged on the regimen of aspirin and clopidogrel alone. Conclusion Peri-procedural antithrombotic regimens vary greatly following TAVR. More than half of patients have an indication for anticoagulation following the procedure. Most patients at our institution who require anticoagulation are discharged on aspirin and an oral anticoagulant, though the optimal regimen requires further investigation. Electronic supplementary material The online version of this article (doi:10.1007/s40119-015-0050-2) contains supplementary material, which is available to authorized users.

Polymer-jacketed, tapered-tip, soft (

Introduction Novel oral anticoagulants are increasingly used for stroke prophylaxis in patients with non-valvular atrial fibrillation. While these agents offer a more predictable pharmacokinetic profile, the lack of readily available laboratory tests to monitor the level of anticoagulation and absence of an antidote or established therapies to reverse the anticoagulant effect make management of cases of over-anticoagulation challenging. Case Report In this case report an 87-year-old man with a history of atrial fibrillation presented with dabigatran excess in the setting of life-threatening, acute renal and hepatic failure. The authors review the use of dabigatran in elderly patients, the available data on management of patients with excess anticoagulation, and the potential options for reversal of the anticoagulation effect. Conclusion Further investigation into reliable means of monitoring and reversing the anticoagulant effect of dabigatran is crucial to the management of such patients.

Summary Background A severe form of encephalitis associated with antibodies against NR1–NR2 heteromers of the NMDA receptor was recently identified. We aimed to analyse the clinical and immunological features of patients with the disorder and examine the effects of antibodies against NMDA receptors in neuronal cultures. Methods We describe the clinical characteristics of 100 patients with encephalitis and NR1–NR2 antibodies. HEK293 cells ectopically expressing single or assembled NR1–NR2 subunits were used to determine the epitope targeted by the antibodies. Antibody titres were measured with ELISA. The effect of antibodies on neuronal cultures was determined by quantitative analysis of NMDA-receptor clusters. Findings Median age of patients was 23 years (range 5–76 years); 91 were women. All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation. 58 (59%) of 98 patients for whom results of oncological assessments were available had tumours, most commonly ovarian teratoma. Patients who received early tumour treatment (usually with immunotherapy) had better outcome (p=0·004) and fewer neurological relapses (p=0·009) than the rest of the patients. 75 patients recovered or had mild deficits and 25 had severe deficits or died. Improvement was associated with a decrease of serum antibody titres. The main epitope targeted by the antibodies is in the extracellular N-terminal domain of the NR1 subunit. Patients' antibodies decreased the numbers of cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect that could be reversed by antibody removal. Interpretation A well-defined set of clinical characteristics are associated with anti-NMDA-receptor encephalitis. The pathogenesis of the disorder seems to be mediated by antibodies. Funding National Institutes for Health, University of Pennsylvania Institute for Translational Medicine, Lankenau Institute for Medical Research, Foederer Foundation of the Children's Hospital of Philadelphia.

We report two men with limbic encephalitis (LE) refractory to corticosteroids, IVIg and plasma exchange. Both patients had serum/CSF antibodies that reacted with the cytoplasm of neurons. Probing of a hippocampal cDNA library resulted in the isolation of adenylate kinase 5 (AK5). Patients' antibodies, but not those of 111 controls, recognized AK5-expressing phage plaques. Human AK5-affinity purified antibodies reproduced the neuronal immunolabeling of patients' antibodies, and co-localized with a rabbit AK5 antibody, confirming that the brain autoantigen was AK5. Detection of antibodies to AK5 in LE patients carries a poor prognosis, and suggests the prompt use of aggressive immunosuppression.

Background: About 40% of patients with limbic encephalitis do not have detectable CNS antibodies. Some of these patients have immune-mediated limbic encephalitis, but their frequency is unknown. Aims: (1) To determine the spectrum of limbic encephalitis identified on clinical grounds in a single institution, and compare it with that in patients referred for antibody analysis. (2) To correlate clinical outcomes with the cellular location of the autoantigens. Methods: Prospective clinical case studies. Immunohistochemistry with rat brain, live hippocampal neurones, HeLa cells expressing Kv potassium channels and immunoblot. Results: In 4 years, 17 patients were identified in the Hospital of the University of Pennsylvania, Philadelphia, USA, and the serum or CSF samples of 22 patients diagnosed elsewhere were also studied. 9 of our 17 (53%) patients had antibodies to known neuronal antigens (paraneoplastic or voltage gated potassium channels (VGKCs)) and 5 (29%) to novel cell-membrane antigens (nCMAg) typically expressed in the hippocampus and sometimes in the cerebellum. Considering the entire series, 19 of 39 (49%) patients had antibodies to known antigens, and 17 (44%) to nCMAg. Follow-up (2–48 months, median 19 months) was available for 35 patients. When compared with patients with antibodies to intraneuronal antigens, a significant association with response to treatment was found in those with antibodies to cell-membrane antigens in general (VGKC or nCMAg, p = 0.003) or to nCMAg (p = 0.006). Conclusions: (1) 82% of patients with limbic encephalitis prospectively identified on clinical grounds had CNS antibodies; (2) responsiveness to treatment is not limited to patients with VGKC antibodies; (3) in many patients (29% from a single institution), the autoantigens were unknown but were found to be highly enriched in neuronal cell membranes of the hippocampus; and (4) these antibodies are associated with a favourable outcome.

Background In women younger than 45 years, a new form of encephalitis associated with ovarian teratoma and presenting with seizures and psychiatric symptoms has been described. Most patients have antibodies to NR1/NR2 heteromers of the N -methyl-D-aspartate receptor (NMDAR). Objective To assess the frequency and significance of antibodies to NMDAR in otherwise unexplained new-onset epilepsies in young women. Design Prospective cohort study. Setting University department of epileptology. Patients From January 1, 2005, to June 30, 2007, we identified 19 female patients aged 15 to 45 years with unexplained new-onset epilepsy. In addition, we studied 61 cerebrospinal fluid–serum sample pairs from patients with other cryptogenic epilepsies and 11 cerebrospinal fluid–serum sample pairs from surgically treated patients with epilepsy with no evident encephalitic abnormalities. Main Outcome Measures Antibodies to NMDAR and characteristics of affected patients. Results Five of the 19 patients had antibodies against NMDAR. These patients had diffuse cerebral dysfunction and seizure origins. Psychiatric symptoms and pleocytosis were significantly associated with this group of patients. The disease course was episodic, in part relapsing-remitting, with full recoveries either spontaneously or after corticosteroid or intravenous immunoglobulin treatments. Only 1 patient had a neoplasm (multiple neuroendocrine tumors that included the ovaries) identified to date. In the control series, one 22-year-old man with a cryptogenic, severely encephalopathic seizure disorder was NMDAR antibody positive, and he also recovered fully. Conclusions Anti-NMDAR encephalitis accounts for a relevant proportion of otherwise unexplained new-onset epilepsies. Patients harboring NMDAR antibodies usually have prominent psychiatric symptoms and pleocytosis, and they may develop hypoventilation. Anti-NMDAR encephalitis is not always paraneoplastic.

Objective To report the autoantigens of a new category of treatment-responsive paraneoplastic encephalitis.

To report the presence of microscopic neoplasms of the testis in men with anti-Ma2-associated encephalitis (Ma2-encephalitis) and to discuss the clinical implications.Orchiectomy specimens were examined using immunohistochemistry with Ma2 and Oct4 antibodies.Among 25 patients with Ma2-encephalitis younger than 50 years, 19 had germ-cell tumors, and 6 had no evidence of cancer. These 6 patients underwent orchiectomy because they fulfilled five criteria: 1) demonstration of anti-Ma2 antibodies in association with MRI or clinical features compatible with Ma2-encephalitis, 2) life-threatening or progressive neurologic deficits, 3) age50 years, 4) absence of other tumors, and 5) new testicular enlargement or risk factors for germ-cell tumors, mainly cryptorchidism or ultrasound evidence of testicular microcalcifications. All orchiectomy specimens showed intratubular-germ cell neoplasms unclassified type (IGCNU) and other abnormalities including microcalcifications, atrophy, fibrosis, inflammatory infiltrates, or hypospermatogenesis. Ma2 was expressed by neoplastic cells in three of three patients examined. Even though most patients had severe neurologic deficits at the time of orchiectomy (median progression of symptoms, 10 months), 4 had partial improvement and prolonged stabilization (8 to 84 months, median 22.5 months) and two did not improve after the procedure.In young men with Ma2-encephalitis, 1) the disorder should be attributed to a germ-cell neoplasm of the testis unless another Ma2-expressing tumor is found, 2) negative tumor markers, ultrasound, body CT, or PET do not exclude an intratubular germ-cell neoplasm of the testis, and 3) if no tumor is found, the presence of the five indicated criteria should prompt consideration of orchiectomy.

Aspirin (ASA) + clopidogrel is recommended for 3-6 months following transcather aortic valve replacement (TAVR). Many patients undergoing TAVR also have an indication for oral anticoagulation (OAC). Antithrombotic regimens prescribed to these patients have not been well studied. Chart review of all