Heterogeneity in the nonplanarity and arterial curvature of arteriovenous fistulas in vivo.

OBJECTIVE: Native arteriovenous fistulas (AVFs) for hemodialysis are susceptible to nonmaturation. Adverse features of local blood flow have been implicated in the formation of perianastomotic neointimal hyperplasia that may underpin nonmaturation. Whereas computational fluid dynamic simulations of idealized models highlight the importance of geometry on fluid and vessel wall interactions, little is known in vivo about AVF geometry and its role in adverse clinical outcomes. This study set out to examine the three-dimensional geometry of native AVFs and the geometric correlates of AVF failure. METHODS: As part of an observational study between 2013 and 2016, patients underwent creation of an upper limb AVF according to current surgical best practice. Phase-contrast magnetic resonance imaging was performed on the day of surgery to obtain luminal geometry along with ultrasound measurements of flow. Magnetic resonance imaging data sets were segmented and reconstructed for quantitative and qualitative analysis of local geometry. Clinical maturation was evaluated at 6 weeks. RESULTS: There were 60 patients who were successfully imaged on the day of surgery. Radiocephalic (n = 17), brachiocephalic (n = 40), and brachiobasilic (n = 3) fistulas were included in the study. Centerlines extracted from segmented vessel lumen exhibited significant heterogeneity in arterial nonplanarity and curvature. Furthermore, these features are more marked in brachiocephalic than in radiocephalic fistulas. Across the cohort, the projected bifurcation angle was 73 ± 16 degrees (mean ± standard deviation). Geometry was preserved at 2 weeks in 20 patients who underwent repeated imaging. A greater degree of arterial nonplanarity (log odds ratio [logOR], 0.95 per 0.1/vessel diameter; 95% confidence interval [CI], 0.22-1.90; P = .03) and a larger bifurcation angle (logOR, 0.05 per degree; 95% CI, 0.01-0.09; P = .02) are associated with a greater rate of maturation, as is fistula location (upper vs lower arm; logOR, -1.9; 95% CI, -3.2 to 0.7; P = .002). CONCLUSIONS: There is significant heterogeneity in the three-dimensional geometry of AVFs, in particular, arterial nonplanarity and curvature. In this largest cohort of AVF geometry to date, the effect of individual geometric correlates on maturation is uncertain but supports the premise that future modeling studies will need to acknowledge the complex geometry of AVFs.

Swirling Flow and Wall Shear: Evaluating the BioMimics 3D Helical Centerline Stent for the Femoropopliteal Segment.

The BioMimics 3D self-expanding nitinol stent represents a strategy for femoropopliteal intervention that is alternative or complementary to deployment of drug-coated stents or balloons. Whereas conventional straight stents reduce arterial curvature and disturb blood flow, creating areas of low wall shear, where neointimal hyperplasia predominantly develops, the helical centerline geometry of the BioMimics 3D maintains or imparts arterial curvature, promotes laminar swirling blood flow, and elevates wall shear to protect against atherosclerosis and restenosis. In the multicenter randomized MIMICS trial, treatment of femoropopliteal disease with the BioMimics 3D (n = 50) significantly improved 2-year primary patency (log-rank test p = 0.05) versus a control straight stent (n = 26), with no cases of clinically driven target lesion revascularization between 12 and 24 months (log-rank test p = 0.03 versus controls). In geometric X-ray analysis, the BioMimics stent was significantly more effective in imparting a helical shape even when the arterial segment was moderately to severely calcified. Computational fluid dynamics analysis showed that average wall shear was significantly higher with the helical centerline stent (1.13 ± 0.13 Pa versus 1.06 ± 0.12 Pa, p = 0.05). A 271-patient multicenter international MIMICS-2 trial and a 500-patient real-world MIMICS-3D registry are underway.

Helical Centerline Stent Improves Patency: Two-Year Results From the Randomized Mimics Trial.

BACKGROUND: Reintervention in the femoropopliteal artery is frequent and a major driver of cost-effectiveness. High wall shear generated by swirling blood flow is associated with reduced occurrence of atherosclerosis and restenosis. This trial investigated the clinical and hemodynamic outcomes of the BioMimics 3D self-expanding tubular nitinol stent with helical centerline geometry compared with a straight stent in the femoropopliteal artery. METHODS AND RESULTS: In a prospective, multicenter, randomized controlled trial, 76 patients with symptomatic peripheral arterial disease were randomized 2:1 to receive a helical or a straight stent. An independent core laboratory adjudicated angiographic and ultrasound parameters. The primary safety end point was freedom from a composite of all death, target limb amputation, and target lesion revascularization at 30 days. The primary effectiveness end point was freedom from clinically driven target lesion revascularization at 6 months. Patency was a secondary end point. Subjects were followed up for 2 years from intervention. The primary safety (1-sided P<0.01) and efficacy (1-sided P<0.001) end points for the helical stent were met. The proportion of patients treated with the helical stent who maintained patency at 12 and 24 months was 80% and 72%, respectively, compared with 71% and 55% for the control group. The difference was significant through 24 months (P=0.05). Freedom from clinically driven target lesion revascularization for the helical compared with straight stent was 91% versus 92% at 12 months and 91% versus 76% at 24 months. CONCLUSIONS: Both groups had similar safety outcomes and clinically driven target lesion revascularization to 2 years. However, after placement of a BioMimics 3D helical stent, there was improved patency to 2 years. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02163863.

Index proposal and basic estimator study for quantification of oscillation of the secondary flow pattern in tortuous vessels.

The development of atherosclerosis has been shown to correlate with regions of low wall shear stress and seemingly reduced mass transport. The local tortuosity of the arteries and local secondary flow oscillation also seem to be negatively correlated with the local occurrence of the disease. However there is currently no tool or physiological parameter that can be measured non-invasively to assess the local oscillation of the flow. Standard Colour Doppler imaging of secondary flow patterns during the blood pulse is studied and illustrated, and the local oscillation of the secondary flow pattern is proposed as an index, which could be an indicator of the likelihood of future disease development. Preliminary results are presented using a basic estimator developed for the proof of concept in the case of swirling flow, and based on colour-coded video signals collected in different configurations. In vitro results show that there is a correspondence between the Doppler patterns and the secondary flow patterns, the repeatability of the measures, and that the proposed index and its estimator reflect a joint influence of the local oscillation of the secondary flow pattern and of the flow rate. On another hand, while in vivo results still suffer from instabilities, noise and from scanners and processing limitations, they demonstrate that it is possible to use Colour Doppler imaging to image and characterize in vivo the secondary flow patterns and their oscillations non-invasively, and that it is possible for a trained clinician to perform manually such Doppler measurements for processing.

Preliminary comparative study of small amplitude helical and conventional ePTFE arteriovenous shunts in pigs.

Intimal hyperplasia (IH), which causes occlusion of arterial bypass grafts and arteriovenous (A-V) shunts, develops preferentially in low wall shear, or stagnation, regions. Arterial geometry is commonly three-dimensional, generating swirling flows, the characteristics of which include in-plane mixing and inhibition of stagnation. Clinical arterial bypass grafts are commonly two-dimensional, favouring extremes of wall shear. We have developed small amplitude helical technology (SwirlGraft) devices and shown them to generate physiological-type swirling flows. Expanded polytetrafluorethylene (ePTFE) grafts, although widely used as A-V shunts for renal dialysis access, are prone to thrombosis and IH. In a small preliminary study in pigs, we have implanted SwirlGraft ePTFE carotid artery-to-jugular vein shunts on one side and conventional ePTFE carotid artery-to-jugular vein shunts contralaterally. There was consistently less thrombosis and IH in the SwirlGraft than conventional shunts. At eight weeks (two animals), the differences were marked, with virtually no disease in the SwirlGraft devices and occlusion of the conventional grafts by thrombosis and IH. The study had limitations, but the lesser pathology in the SwirlGraft devices is likely to have resulted from their geometry and the associated swirling flow. The results could have implications for vascular biology and prolongation of the patency of arterial bypass grafts and A-V shunts.

Three-dimensional reconstruction of autologous vein bypass graft distal anastomoses imaged with magnetic resonance: clinical and research applications.

High-resolution magnetic resonance imaging was combined with computational modeling to create focused three-dimensional reconstructions of the distal anastomotic region of autologous vein peripheral bypass grafts in a preliminary series of patients. Readily viewed on a personal computer or printed as hard copies, a detailed appreciation of in vivo postoperative features of the anastomosis is possible. These reconstructions are suitable for analysis of geometric features, including vessel caliber, tortuosity, anastomotic angles, and planarity. Some potential clinical and research applications of this technique are discussed.