Permanent Bilateral Carotid Filters for Stroke Prevention in Atrial Fibrillation.

PURPOSE OF REVIEW: A novel permanent carotid filter device for percutaneous implantation was developed for the purpose of stroke prevention. In this review, we cover rationale, existing preclinical and clinical data, and potential future directions for research using such a device. RECENT FINDINGS: The Vine™ filter was assessed for safety in sheep and in 2 observational human studies, the completed CAPTURE 1 (n = 25) and the ongoing CAPTURE 2 (planned n = 100). CAPTURE 1 has shown high procedural and long-term implant safety. A control group was not available for comparison. A mechanical filter for permanent stroke prevention can be implanted bilaterally in the common carotid artery safely and efficiently. A randomized trial is planned for 2021 (n = 3500, INTERCEPT) to demonstrate superiority of a filter + anticoagulation strategy over anticoagulation alone in patients at high risk for ischemic stroke.

A Permanent Common Carotid Filter for Stroke Prevention in Atrial Fibrillation: Ex Vivo and In Vivo Pre-Clinical Testing.

BACKGROUND AND PURPOSE: A novel, permanent, bilateral, common carotid artery (CCA) coil filter implant was designed to capture stroke-producing emboli in atrial fibrillation patients. Under ultrasound guidance, it is automatically deployed through a 24-guage needle and is retrievable up to 4 h post-procedure. We assessed the feasibility, safety, and effectiveness of the CCA filter in pre-clinical testing. METHODS: In a pulsatile flow simulator, the filter's embolic capture efficiency and integrity of simulated (1.2 mm diameter nylon balls) and actual thromboemboli were tested. Implant insertion, retrieval, and chronic safety were tested in sheep by ultrasound and X-ray. At termination, the CCAs were explanted and examined by pathology, histopathology and scanning electron microscopy. The fate of captured emboli was evaluated in sheep 3 weeks after upstream injection of autologous thromboemboli. RESULTS: In the flow simulator, 10 filters captured 29 of 29 (100%) 1.2 mm diameter nylon balls. In the thromboemboli integrity test, all captured thromboemboli (99 of 99) were adherent to the filter, without fragmentation. All sheep (n = 30/60 implants) underwent successful CCA filter implantation. During follow-ups at 4, 12, 13, 23, and 31 weeks (6 sheep/12 implants at each follow-up), there were no (0%) major bleeds, CCA damage/stenosis, implant migration, flow obstruction, or thrombi detected by ultrasound. Two organized microthrombi (<100 µm) were observed by histopathology at the puncture site. After 3 weeks, autologous captured thromboemboli (n = 10) either completely regressed (5 of 5) or did not progress (5 of 5). CONCLUSION: These favorable pre-clinical results prompt clinical testing of the CCA filter in stroke prevention clinical trials.

A novel carotid device for embolic diversion: lessons learned from a "first in man" trial in patients with atrial fibrillation.

PURPOSE: This study was designed to investigate a novel device that was developed to direct emboli away from the internal carotid artery to the external carotid artery to prevent embolic stroke while avoiding the necessity for anticoagulation with warfarin. METHODS: A stent-like, self-expandable filter was developed consisting of fine cobalt alloy mesh. After promising preclinical animal testing, the device was implanted into the common carotid artery extending into the external carotid artery in three patients with atrial fibrillation, each of whom were at high-risk for cerebral emboli and were suboptimal candidates for anticoagulation. Follow-up was performed clinically and with carotid duplex ultrasound. RESULTS: The implantation was successful in all three patients. Unrestricted flow through the filter was demonstrated in each patient at 6 months by duplex sonography. However, at 7 months ultrasound demonstrated occlusion of the internal carotid artery filter in one patient, which was subsequently confirmed by angiography. Subtotal filter occlusion occurred in a second patient at 14 months. Neither patient had clinical symptoms. Both internal carotid arteries were successfully recanalized using standard angioplasty techniques without complication. The third patient had completely normal carotid blood flow at 29 months follow-up. CONCLUSIONS: Implantation of a novel device intended to divert emboli away from the internal carotid artery was feasible, but resulted in occlusive neointimal proliferation in two of three patients. These results demonstrate a discrepancy from the findings of preclinical animal studies and human investigation.

Bolus guide: a novel insulin bolus dosing decision support tool based on selection of carbohydrate ranges.

BACKGROUND: Optimal continuous subcutaneous insulin infusion (CSII) therapy emphasizes the relationship between insulin dose and carbohydrate consumption. One widely used tool (bolus calculator) requires the user to enter discrete carbohydrate values; however, many patients might not estimate carbohydrates accurately. This study assessed carbohydrate estimation accuracy in type 1 diabetes CSII users and compared simulated blood glucose (BG) outcomes using the bolus calculator and the "bolus guide," an alternative system based on ranges of carbohydrate load. METHODS: Patients (n = 60) estimated the carbohydrate load of a representative sample of meals of known carbohydrate value. The estimated error distribution [coefficient of variation (CV)] was the basis for a computer simulation (n = 1.6 million observations) of insulin recommendations for the bolus guide and bolus calculator, translated into outcome blood glucose (OBG) ranges (< or =60, 61-200, >201 mg/dl). Patients (n = 30) completed questionnaires assessing satisfaction with the bolus guide. RESULTS: The CV of typical meals ranged from 27.9% to 44.5%. The percentage of simulated OBG for the calculator and the bolus guide in the <60 mg/dl range were 20.8% and 17.2%, respectively, and 13.8% and 15.8%, respectively, in the >200 mg/dl range. The mean and median scores of all bolus guide satisfaction items and ease of learning and use were 4.17 and 4.2, respectively (of 5.0). CONCLUSION: The bolus guide recommendation based on carbohydrate range selection is substantially similar to the calculator based on carbohydrate point estimation and appears to be highly accepted by type 1 diabetes insulin pump users.

Compatibility of insulin Lispro, Aspart, and Glulisine with the Solo MicroPump, a novel miniature insulin pump.

BACKGROUND: This study compared the stability of commercially available, rapid-acting insulin in the novel tubeless, skin-adhering Solo insulin pump over 6 days at extreme environmental conditions. METHODS: Forty-eight pumps for each tested analog were loaded with three different insulin lots and operated at 30 U/day (three sets of 12 pumps) and 15 U/day (one set of 12 pumps) with basal/bolus delivery patterns for 6 days under extreme climatic (37 degrees C, 40% relative humidity) and mechanical (35 strokes/min) stresses. The insulin solutions dispensed were sampled periodically and analyzed for potency, related substances, high molecular weight proteins (HMWP), and preservative content by high-performance liquid chromatography techniques. Biological activity (bioidentity) was demonstrated by an abrupt decrease in blood glucose in rabbits. Solutions were inspected for visual appearance and measured for pH levels. RESULTS: During the 6-day sampling period, the potency of all insulin samples was maintained at 95.0-105.0% of the bulk solution concentration of the insulin vials. The levels of HMWP and related substances remained well below labeling limits. The preservative concentration decreased with time but remained bacteriostatic effective. Solutions maintained pH and clarity and were particulate free. The biological activity was verified. CONCLUSIONS: Insulin analogs lispro, aspart, and glulisine maintained physical, chemical, and biological properties for 6 days when used in the Solo MicroPump device.

Use of the site of subcutaneous insulin administration for the measurement of glucose in patients with type 1 diabetes.

OBJECTIVE To simplify and improve the treatment of patients with type 1 diabetes, we ascertained whether the site of subcutaneous insulin infusion can be used for the measurement of glucose. RESEARCH DESIGN AND METHODS Three special indwelling catheters (24-gauge microperfusion [MP] catheters) were inserted into the subcutaneous adipose tissue of subjects with type 1 diabetes (n = 10; all C-peptide negative). One MP catheter was perfused with short-acting insulin (100 units/ml, Aspart) and used for insulin delivery and simultaneous glucose sampling during an overnight fast and after ingestion of a standard glucose load (75 g). As controls, the further two MP catheters were perfused with an insulin-free solution (5% mannitol) and used for glucose sampling only. Plasma glucose was measured frequently at the bedside. RESULTS Insulin delivery with the MP catheter was adequate to achieve and maintain normoglycemia during fasting and after glucose ingestion. Tissue glucose concentrations derived with the insulin-perfused catheter agreed well with plasma glucose levels. Median correlation coefficient and median absolute relative difference values were found to be 0.93 (interquartile range 0.91-0.97) and 10.9%, respectively. Error grid analysis indicated that the percentage number of tissue values falling in the clinically acceptable range is 99.6%. Comparable analysis results were obtained for the two mannitol-perfused catheters. CONCLUSIONS Our data suggest that estimation of plasma glucose concentrations from the glucose levels directly observed at the site of subcutaneous insulin infusion is feasible and its quality is comparable to that of estimating plasma glucose concentrations from glucose levels measured in insulin-unexposed subcutaneous tissue.

A novel endovascular device for emboli rerouting: part I: evaluation in a Swine model.

BACKGROUND AND PURPOSE: The feasibility and safety of a novel endovascularly delivered tubular mesh designed to reroute emboli away from a critical artery as a means of ischemic stroke prevention was tested in vitro and in vivo. METHODS: Emboli rerouting efficacy was assessed in vitro. Perfusion through the external femoral artery that was jailed by the device, cellular proliferation rate over the jailing mesh, and the resulting tissue coverage of the orifice were assessed in the swine iliofemoral bifurcation. Device-induced embolization was assessed in a swine kidney model. RESULTS: In vitro experiments demonstrated that particles as small as 60% of the pore dimension can be rerouted by the device, although at low efficacy, and rerouting efficacy approached 100% as the particle size approached the pore dimension. Repeat assessment of flow preimplantation and at various follow-up times by Doppler ultrasound showed no significant changes in the perfusion ratio of the jailed branch to the parent artery or the jailed branch to the naive contralateral artery either as a result of device implantation or at the follow-up times. Tissue coverage over the jailed ostium was limited to approximately 12% after stabilization. Cellular proliferation rate gradually decreased to diminishing level approximately 22 weeks postimplantation. The devices implanted across the renal arteries did not demonstrate any device-induced embolization after 1 month. CONCLUSIONS: It is proposed that this device could be used to reroute emboli away from important intracranial vessels as a means of stroke prevention.

Similarity of the swine vasculature to the human carotid bifurcation: analysis of arterial diameters.

PURPOSE: We assessed the similarities of the iliac bifurcation in two breeds of swine to the known human carotid bifurcation, in order to assess its applicability as a preclinical model of the human carotid bifurcation. MATERIALS AND METHODS: Mixed-Landrace crossbreed (domestic; n = 66) and Yucatan miniswine (Yucatan; n = 13) were studied. The diameters of the iliac bifurcation arteries were measured from angiographic pictures, the relations between the arterial diameters and the animal's weight assessed, and diametrical ratios calculated. Findings were compared with the known human carotid bifurcation. RESULTS: The external iliac diameter (approximately 6-7mm) in the lower weight swine was similar to the known human common carotid artery. The best similarity was found between the diametrical ratios of the human internal to common carotid artery (mean 0.63) to the swine profunda to external iliac (means 0.68 and 0.65 for the domestic and Yucatan, respectively). The arterial diameters of the domestic swine were highly correlated with their weight that increased considerably with time, while in the Yucatan group, arterial diameters did not change with increasing weight and the average weight increase rate was low. Thus, the estimated arterial diameter increase rate over time was high in the domestic while minor in the Yucatan group. CONCLUSIONS: Similarities were found between the swine iliac bifurcation arteries to the human carotid bifurcation in terms of diameters, diametrical ratios and angle. The swine iliac bifurcation may be used for preclinical endovascular research of devices intended to the human carotid bifurcation, with miniswine strains a preferable model for long-term studies.

Hemodynamic evaluation of embolic trajectory in an arterial bifurcation: an in-vitro experimental model.

BACKGROUND AND PURPOSE: Despite the importance of embolism as a major cause of brain infarction, little is known about the hemodynamic factors governing the path large emboli tend to follow. Our aim was to test in vitro, whether hemodynamic parameters other than flow ratios between bifurcation branches may affect the distribution of embolic particles in a Y-shaped bifurcation model, used as an analogue to an arterial bifurcation. METHODS: In vitro experiments were conducted using suspensions of sphere-shaped particles (0.6, 1.6, and 3.2 mm) in water-glycerin mixture, using steady and pulsatile laminar flow regimes in a Y-shaped bifurcation model (identical branching angles [theta1=theta2=45 degrees] with one daughter branch diameter wider than the other [D1=6 mm, D2=4 mm]; average Reynolds number 500). RESULTS: Experiments using naturally buoyant particles under steady flow conditions and four outlet-flow ratios revealed that small (0.6 mm) and mid-sized (1.6 mm) particles entered into either the narrower or wider bifurcation daughter branch nonpreferentially, proportionally to the flow ratios. Large particles (3.2 mm), however, preferentially entered the wider daughter branch. Moreover, as the flow ratio increases this phenomenon was augmented. Further experiments revealed that the preference of the wider daughter branch for high particle-to-branch diameter-ratios further increases under pulsatile flow and by the density ratio between particles and fluid. CONCLUSIONS: Particles' distribution in a bifurcation is affected, beyond its outlets-flow-ratios, by the particle-to-branch diameter-ratio. The tendency of large particles to preferentially enter the wider bifurcation branch, beyond the flow ratio, is augmented under pulsatile flow conditions and is affected by particle-to-fluid density-ratio. These findings may have important implications for understanding the hemodynamic mechanisms underlying the trajectory of large emboli.