Lesion Index-guided workflow for the treatment of paroxysmal atrial fibrillation is safe and effective - Final results from the LSI Workflow Study.

Background: Pulmonary vein isolation (PVI) ablation is a standard therapy for paroxysmal atrial fibrillation (PAF). Lesion Index (LSI) is a metric to guide radiofrequency (RF) ablation using the TactiCath Ablation Catheter, Sensor Enabled with the EnSite Cardiac Mapping System (Abbott). Objective: This study (NCT-03906461) was designed to capture best practices using LSI-guided catheter ablation to treat PAF subjects in a real-world setting. Methods: This prospective single-arm observational study enrolled 143 PAF subjects in the United States, Europe, and Japan undergoing de novo PVI with RF ablation. PVI lesions were assigned to 10 anatomically defined segments. Mean LSIs achieved for all lesions were analyzed. Follow-up was conducted between 3-6 months and 12 months after the procedure. Results: Pulmonary veins were isolated in all subjects. The mean achieved LSI was 4.9, with lower values in Europe (4.4) and Japan (4.5) than the United States (5.5). First-pass success, defined as no gaps requiring touch-up ablation after 20 minutes post isolation, was achieved in 76.2% of subjects. Use of high LSI (≥5) resulted in shorter procedure, RF, and fluoroscopy times and fewer touch-up ablations compared to low LSI (<5). At 12 months, 99.3% of subjects were free from procedure- or device-related serious adverse events and 95.7% (112/117) (35.0% on antiarrhythmic drugs) were free from recurrence and/or a repeat ablation procedure for atrial fibrillation / atrial flutter / atrial tachycardia. Conclusion: LSI-guided ablation strategies proved safe and effective despite differences in LSI workflows. Use of high LSI values resulted in shorter procedure, RF, and fluoroscopy times and fewer touch-up ablations compared to low LSI.

Inpatient mortality and healthcare resource utilization of nontraumatic intracerebral hemorrhage complications in the US.

OBJECTIVE: Nontraumatic, primary intracerebral hemorrhage (ICH) accounts for 2 million strokes worldwide annually and has a 1-year survival rate of 50%. Recent studies examining functional outcomes from ICH evacuation have been performed, but limited work has been done quantifying the incidence of subsequent complications and their healthcare economic impact. The purpose of this study was to quantify the incidence and healthcare resource utilization (HCRU) for major complications that can arise from ICH. METHODS: The IBM MarketScan Research databases were used to retrospectively identify patients with ICH from 2010 to 2015. Complications examined included cerebral edema, hydrocephalus, venous thromboembolic events (VTEs), pneumonia, urinary tract infections (UTIs), and seizures. For each complication, inpatient mortality and HCRU were assessed. RESULTS: Of 25,322 adult patients included, 10,619 (42%) developed complications during the initial admission of ICH: 22% had cerebral edema, 11% hydrocephalus, 10% pneumonia, 6% UTIs, 5% seizures, and 5% VTEs. The inpatient mortality rates at 7 and 30 days for each complication of ICH ranked from highest to lowest were hydrocephalus (24% and 32%), cerebral edema (15% and 20%), pneumonia (8% and 18%), seizure (7% and 13%), VTE (4% and 11%), and UTI (4% and 8%). Hydrocephalus had the highest total cost (median $92,776, IQR $39,308-$180,716) at 7 days post-ICH diagnosis and the highest cumulative total cost (median $170,839, IQR $91,462-$330,673) at 1 year post-ICH diagnosis. CONCLUSIONS: This study characterizes one of the largest cohorts of patients with nontraumatic ICH in the US. More than 42% of the patients with ICH developed complications during initial admission, which resulted in high inpatient mortality and considerable HCRU.

Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM), late-stage cancer when malignant cells migrate to the subarachnoid space (SAS), have an extremely poor prognosis. Current treatment regimens fall short in effectively reducing SAS tumor burden. Neurapheresis therapy is a novel approach employing filtration and enhanced circulation of the cerebrospinal fluid (CSF). Here, we examine the in vitro use of neurapheresis therapy as a novel, adjunctive treatment option for LM by filtering cells and augmenting the distribution of drugs that may have the potential to enhance the current clinical approach. METHODS: Clinically relevant concentrations of VX2 carcinoma cells were suspended in artificial CSF. The neurapheresis system's ability to clear VX2 carcinoma cells was tested with and without the chemotherapeutic presence (methotrexate [MTX]). The VX2 cell concentration following each filtration cycle and the number of cycles required to reach the limit of detection were calculated. The ability of neurapheresis therapy to circulate, distribute, and maintain therapeutic levels of MTX was assessed using a cranial-spinal model of the SAS. The distribution of a 6 mg dose was monitored for 48 h. An MTX-specific ELISA measured drug concentration at ventricular, cervical, and lumbar sites in the model over time. RESULTS: In vitro filtration of VX2 cancer cells with neurapheresis therapy alone resulted in a 2.3-log reduction in cancer cell concentration in 7.5 h and a 2.4-log reduction in live-cancer cell concentration in 7.5 h when used with MTX. Cranial-spinal model experiments demonstrated the ability of neurapheresis therapy to enhance the circulation of MTX in CSF along the neuraxis. CONCLUSION: Neurapheresis has the potential to act as an adjunct therapy for LM patients and significantly improve the standard of care.

Healthcare Economics of Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage in the United States.

Hydrocephalus is one of the most common sequelae after aneurysmal subarachnoid hemorrhage (aSAH), and it is a large contributor to the condition's high rates of readmission and mortality. Our objective was to quantify the healthcare resource utilization (HCRU) and health economic burden incurred by the US health system due to post-aSAH hydrocephalus. The Truven Health MarketScan® Research database was used to retrospectively quantify the prevalence and HCRU associated with hydrocephalus in aSAH patients undergoing surgical clipping or endovascular coiling from 2008 to 2015. Multivariable longitudinal analysis was conducted to model the relationship between annual cost and hydrocephalus status. In total, 2374 patients were included; hydrocephalus was diagnosed in 959 (40.4%). Those with hydrocephalus had significantly longer initial lengths of stay (median 19.0 days vs. 12.0 days, p < .001) and higher 30-day readmission rates (20.5% vs. 10.4%, p < .001). With other covariates held fixed, in the first 90 days after aSAH diagnosis, the average cost multiplier relative to annual baseline for hydrocephalus patients was 24.60 (95% CI, 20.13 to 30.06; p < .001) whereas for non-hydrocephalus patients, it was 11.52 (95% CI, 9.89 to 13.41; p < .001). The 5-year cumulative median total cost for the hydrocephalus group was $230,282.38 (IQR, 166,023.65 to 318,962.35) versus $174,897.72 (IQR, 110,474.24 to 271,404.80) for those without hydrocephalus. We characterize one of the largest cohorts of post-aSAH hydrocephalus patients in the USA. Importantly, the substantial health economic impact and long-term morbidity and costs from this condition are quantified and reviewed.

Novel Dual Lumen Catheter and Filtration Device for Removal of Subarachnoid hemorrhage: First Case Report.

BACKGROUND AND IMPORTANCE: The amount of subarachnoid blood and the presence of toxic blood breakdown products in the cerebrospinal fluid (CSF) have long been associated with poor outcomes in aneurysmal subarachnoid hemorrhage. The Neurapheresis™ system (Minnetronix Inc, St. Paul, Minnesota) has been developed to filter CSF and remove blood products, and is being investigated for safety and feasibility in the ExtracorPoreal FILtration of subarachnoid hemorrhage via SpinaL CAtheteR (PILLAR) study. We report the first case using this novel device. CLINICAL PRESENTATION: A 65-yr-old female presented with a ruptured left posterior communicating artery aneurysm. Following placement of a ventriculostomy and coil embolization of her aneurysm, the patient underwent placement of a lumbar dual lumen catheter for CSF filtration as part of the PILLAR study. In this case, a total of 9 h of filtration during 31 h of catheter indwelling resulted in 309.47 mL of processed CSF without complication. Computed tomography images demonstrated an interval reduction of subarachnoid hemorrhage immediately after filtration. The patient was discharged home on postbleed day 11 and at 30 d showed good recovery. CONCLUSION: Safety of the Neurapheresis procedure was confirmed in this first case, and we will continue to evaluate safety of the Neurapheresis system through the PILLAR trial.

Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy.

Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal meningitis worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite a significant improvement in survival compared with uniform mortality without treatment, this drug paradigm has not led to a consistent cure. Neurapheresis therapy, extracorporeal filtration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro filtration of CSF through this platform yielded a 5-log reduction in concentration of the yeast and a 1-log reduction in its polysaccharide antigen over 24 hours. Additionally, an analogous closed-loop system achieved 97% clearance of yeasts from the subarachnoid space in a rabbit model over 4-6 hours. This is the first publication demonstrating the direct ability to rapidly clear, both in vitro and in vivo, the otherwise slowly removed fungal pathogen that directly contributes to the morbidity and mortality seen in CM.