Use of Polymer-Jacketed, Tapered-Tip, Low-Force Guidewires With Composite-Core, Dual-Coil Design as Part of the Antegrade Approach to Coronary Chronic Total Occlusions.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Angiographic predictors of adverse outcomes after percutaneous coronary intervention in patients with radiation associated coronary artery disease.

OBJECTIVES: To determine procedural predictors of long-term outcomes for patients with radiation associated coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). BACKGROUND: Patients who develop CAD after external beam radiation therapy (XRT) for cancer are at high-risk for adverse events following PCI. It is unknown if specific angiographic features can predict outcomes in this population. METHODS: This is an observational study of 157 patients with malignancy who received XRT prior to PCI. Rates of major adverse cardiovascular and cerebrovascular events (MACCEs; all-cause mortality, myocardial infarction, repeat revascularization, or stroke) were compared across patient characteristics over time with the Cox proportional hazards and Kaplan-Meier's analyses. RESULTS: During follow-up of 5.4 ± 4.5 years, 91 (58%) patients had MACCE. On Kaplan-Meier's analysis of angiographic characteristics, MACCE was more frequent in patients with at least moderate target vessel calcification (P = 0.023), ostial stenosis (P = 0.049), target vessel diameter ≥ 3.0 mm (P = 0.018), a SYNTAX score ≥ the median of 11 (P = 0.014), or bare metal stenting (BMS)/balloon angioplasty (BA) compared to drug-eluting stenting (DES) (P = 0.006). Cardiac death was more frequent in patients with SYNTAX score ≥ 11 (P = 0.028) or BMS (P = 0.043). After multivariable adjustment for both angiographic and clinical characteristics, independent predictors of MACCE were BMS placement (P = 0.013), chronic kidney disease ≥ stage 3 (P = 0.019), New York Heart Association (NYHA) heart failure class ≥3 (P = 0.034), and SYNTAX score ≥ 11 (P = 0.041). CONCLUSIONS: In patients previously exposed to XRT treated with PCI, independent angiographic predictors of MACCE include SYNTAX score ≥ 11 and BMS placement, suggestive that DES should be preferred in this population.

Acute myocardial infarction.

Acute myocardial infarction has traditionally been divided into ST elevation or non-ST elevation myocardial infarction; however, therapies are similar between the two, and the overall management of acute myocardial infarction can be reviewed for simplicity. Acute myocardial infarction remains a leading cause of morbidity and mortality worldwide, despite substantial improvements in prognosis over the past decade. The progress is a result of several major trends, including improvements in risk stratification, more widespread use of an invasive strategy, implementation of care delivery systems prioritising immediate revascularisation through percutaneous coronary intervention (or fibrinolysis), advances in antiplatelet agents and anticoagulants, and greater use of secondary prevention strategies such as statins. This seminar discusses the important topics of the pathophysiology, epidemiological trends, and modern management of acute myocardial infarction, focusing on the recent advances in reperfusion strategies and pharmacological treatment approaches.

Variability in Antithrombotic Therapy Regimens Peri-TAVR: A Single Academic Center Experience.

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.

Dabigatran excess: case report and review of the literature.

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.

Diagnostic value of N-methyl-D-aspartate receptor antibodies in women with new-onset epilepsy.

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.

Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies.

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 consciousness), 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.

Adenylate kinase 5 autoimmunity in treatment refractory limbic encephalitis.

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.

Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma.

OBJECTIVE: To report the autoantigens of a new category of treatment-responsive paraneoplastic encephalitis. METHODS: Analysis of clinical features, neuropathological findings, tumors, and serum/cerebrospinal fluid antibodies using rat tissue, neuronal cultures, and HEK293 cells expressing subunits of the N-methyl-D-aspartate receptor (NMDAR). RESULTS: Twelve women (14-44 years) developed prominent psychiatric symptoms, amnesia, seizures, frequent dyskinesias, autonomic dysfunction, and decreased level of consciousness often requiring ventilatory support. All had serum/cerebrospinal fluid antibodies that predominantly immunolabeled the neuropil of hippocampus/forebrain, in particular the cell surface of hippocampal neurons, and reacted with NR2B (and to a lesser extent NR2A) subunits of the NMDAR. NR2B binds glutamate and forms heteromers (NR1/NR2B or NR1/NR2A/NR2B) that are preferentially expressed in the adult hippocampus/forebrain. Expression of functional heteromers (not single subunits) was required for antibody binding. Eleven patients had teratoma of the ovary (six mature) and one a mature teratoma in the mediastinum; five of five tumors examined contained nervous tissue that strongly expressed NR2 subunits and reacted with patients' antibodies. Tumor resection and immunotherapy resulted in improvement or full recovery of eight of nine patients (paralleled by decreased antibody titers); two of three patients without tumor resection died of neurological deterioration. Autopsies showed extensive microgliosis, rare T-cell infiltrates, and neuronal degeneration predominantly involving, but not restricted to, the hippocampus. INTERPRETATION: Antibodies to NR2B- and NR2A-containing heteromers of the NMDAR associate with a severe but treatment-responsive encephalitis. Our findings provide a diagnostic test and suggest a model of autoimmune NMDAR-related encephalitis with broad implications for other immune-mediated disorders of memory, behavior, and cognition.