Repeatability, and Intra-Observer and Interobserver Agreement of Two Dimensional Perfusion Angiography in Patients with Chronic Limb Threatening Ischaemia.

OBJECTIVE: Two dimensional (2D) perfusion angiography is a method that provides quantitative foot perfusion information from standard digital subtraction angiography acquisitions. The aim of this study was to test the reliability of this method in patients with chronic limb threatening ischaemia (CLTI) by investigating repeatability, and intra-observer and interobserver agreement. METHODS: Twenty patients with CLTI and a below the knee endovascular revascularisation were included in a prospective clinical study. Prior to treatment two perfusion angiography runs were acquired with a five minute interval without performing an intervention. In these recordings, regions of interest were selected and time density curves and perfusion parameters were determined. To investigate intra-observer agreement one observer performed five measurements on the same acquisition for each patient. To investigate interobserver agreement three observers performed measurements on the same acquisition for each patient. Results were presented in Bland-Altman plots and as the intraclass correlation coefficient per parameter. RESULTS: Two patients were excluded from repeatability analyses because of major motion artefacts. Repeatability analyses of the 18 remaining patients showed excellent correlation for every parameter (> .96). Intra-observer and interobserver agreement for all 20 patients were excellent for all parameters (1.00). CONCLUSION: Repeatability and intra-observer and interobserver agreement of 2D perfusion angiography in patients with CLTI were found to be excellent. It is therefore a reliable tool when used according to the standardised methods described in this study.

Pre-operative Patient Specific Flow Predictions to Improve Haemodialysis Arteriovenous Fistula Maturation (Shunt Simulation Study): A Randomised Controlled Trial.

OBJECTIVE: An arteriovenous fistula (AVF) needs to mature before it becomes suitable to cannulate for haemodialysis treatment. Maturation importantly depends on the post-operative flow increase. Unfortunately, 20-40% of AVFs fail to mature (FTM). A patient specific computational model that predicts immediate post-operative flow was developed, and it was hypothesised that providing information from this model for planning of fistula creation might reduce FTM rates. METHODS: A multicentre, randomised controlled trial in nine Dutch hospitals was conducted in which patients with renal failure who were referred for AVF creation, were recruited. Patients were randomly assigned (1:1) to the control or computer simulation group. Both groups underwent a work up, with physical and duplex ultrasonography (DUS) examination. In the simulation group the data from the DUS examination were used for model simulations, and based on the immediate post-operative flow prediction, the ideal AVF configuration was recommended. The primary endpoint was AVF maturation defined as an AVF flow ≥500 mL/min and a vein inner diameter of ≥4 mm six weeks post-operatively. The secondary endpoint was model performance (i.e. comparisons between measured and predicted flows, and (multivariable) regression analysis for maturation probability with accompanying area under the receiver operator characteristic curve [AUC]). RESULTS: A total of 236 patients were randomly assigned (116 in the control and 120 in the simulation group), of whom 205 (100 and 105 respectively) were analysed for the primary endpoint. There was no difference in FTM rates between the groups (29% and 32% respectively). Immediate post-operative flow prediction had an OR of 1.15 (1.06-1.26; p < .001) per 100 mL/min for maturation, and the accompanying AUC was 0.67 (0.59-0.75). CONCLUSION: Providing pre-operative patient specific flow simulations during surgical planning does not result in improved maturation rates. Further study is needed to improve the predictive power of these simulations in order to render the computational model an adjunct to surgical planning.

Pros and Cons of 3D Image Fusion in Endovascular Aortic Repair: A Systematic Review and Meta-analysis.

PURPOSE: To systematically review and meta-analyze the added value of 3-dimensional (3D) image fusion technology in endovascular aortic repair for its potential to reduce contrast media volume, radiation dose, procedure time, and fluoroscopy time. METHODS: Electronic databases were systematically searched for studies published between January 2010 and March 2016 that included a control group describing 3D fusion imaging in endovascular aortic procedures. Two independent reviewers assessed the methodological quality of the included studies and extracted data on iodinated contrast volume, radiation dose, procedure time, and fluoroscopy time. The contrast use for standard and complex endovascular aortic repairs (fenestrated, branched, and chimney) were pooled using a random-effects model; outcomes are reported as the mean difference with 95% confidence intervals (CIs). RESULTS: Seven studies, 5 retrospective and 2 prospective, involving 921 patients were selected for analysis. The methodological quality of the studies was moderate (median 17, range 15-18). The use of fusion imaging led to an estimated mean reduction in iodinated contrast of 40.1 mL (95% CI 16.4 to 63.7, p=0.002) for standard procedures and a mean 70.7 mL (95% CI 44.8 to 96.6, p<0.001) for complex repairs. Secondary outcome measures were not pooled because of potential bias in nonrandomized data, but radiation doses, procedure times, and fluoroscopy times were lower, although not always significantly, in the fusion group in 6 of the 7 studies. CONCLUSION: Compared with the control group, 3D fusion imaging is associated with a significant reduction in the volume of contrast employed for standard and complex endovascular aortic procedures, which can be particularly important in patients with renal failure. Radiation doses, procedure times, and fluoroscopy times were reduced when 3D fusion was used.

Guideline recommendations on minimal blood vessel diameters and arteriovenous fistula outcomes.

OBJECTIVE: Clinical guidelines provide recommendations on the minimal blood vessel diameters required for arteriovenous fistula creation but the evidence for these recommendations is limited. We compared vascular access outcomes of fistulas created in agreement with the ESVS Clinical Practice Guidelines (i.e. arteries and veins >2 mm for forearm fistulas and >3 mm for upper arm fistulas) with fistulas created outside these recommendations. METHODS: The multicenter Shunt Simulation Study cohort contains 211 hemodialysis patients who received a first radiocephalic, brachiocephalic, or brachiobasilic fistula before publication of the ESVS Clinical Practice Guidelines. All patients had preoperative duplex ultrasound measurements according to a standardized protocol. Outcomes included duplex ultrasound findings at 6 weeks after surgery, vascular access function, and intervention rates until 1 year after surgery. RESULTS: In 55% of patients, fistulas were created in agreement with the ESVS Clinical Practice Guidelines recommendations on minimal blood vessel diameters. Concordance with the guideline recommendations was more frequent for forearm fistulas than for upper arm fistulas (65% vs 46%, p = 0.01). In the entire cohort, agreement with the guideline recommendations was not associated with an increased proportion of functional vascular accesses (70% vs 66% for fistulas created within and outside guideline recommendations, respectively; p = 0.61) or with decreased access-related intervention rates (1.45 vs 1.68 per patient-year, p = 0.20). In forearm fistulas, however, only 52% of arteriovenous fistulas created outside these recommendations developed into a timely functional vascular access. CONCLUSIONS: Whereas upper arm arteriovenous fistulas with preoperative blood vessel diameters <3 mm had similar vascular access function as fistulas created with larger blood vessels, forearm arteriovenous fistulas with preoperative blood vessel diameters <2 mm had poor clinical outcomes. These results support that clinical decision-making should be guided by an individual approach.

Neither inflammatory bowel disease nor immunosuppressants are associated with an increased risk of severe COVID-19: an observational Dutch cohort study.

Conflicting data about inflammatory bowel disease [IBD] and immunosuppressants are risk factors for severe COVID-19 confuse patients and healthcare providers. Clinical reports with longer follow-up are lacking. A retrospective search was performed for severe COVID-19 (hospital admission and/or mortality) one year after the SARS-CoV-2 outbreak in an IBD cohort from one of the most affected Dutch regions. Cohort characteristics were explored by value-based healthcare data, including immunotherapy. COVID-19 cases were detected by ICD-10 codes and further examined for IBD determinants (including medication) and COVID-19 characteristics (intensive care admission, respiratory support, treatment, mortality). The national mortality register was consulted, ensuring detection of patients that died without admission. Results were compared with regional and national general population registries. The IBD cohort consisted of 1453 patients (51% Crohn's disease, 54% women, 39.9% using immunotherapy), including children. Biologics use increased during the study. Eight cases (0.55%) had severe COVID-19: seven were hospitalized (0.48%, 95% confidence interval [CI] 0.21-1.04), and two died (0.14%, CI 0.002-0.55). Six patients had comorbidity, one used immunotherapy, and four had no medication. Both deceased patients were older than 80 years, had severe comorbidity, but used no immunotherapy. Hospitalization occurred significantly more in the IBD cohort than regionally (0.18%, CI 0.17-0.19, p = 0.015), but not significantly more than nationally (0.28%, CI 0.279-0.284). Mortality was equal in IBD patients, regionally (0.11%, CI 0.10-0.12) and nationally (0.13%, CI 0.125-0.128). Neither IBD nor immunosuppressants are associated with increased risks of severe COVID-19 in an observational study with one-year follow-up.

Novel diagnostic and imaging techniques in endovascular iliac artery procedures.

INTRODUCTION: Endovascular revascularization has become the preferred treatment for most patients with iliac artery obstructions, with a high rate of clinical and technical success. AREAS COVERED: This review will describe novel developments in the diagnosis and treatment of iliac artery obstructions including the augmentation of preprocedural imaging with advanced flow models, image fusion techniques, and state-of-the-art device-tracking capabilities. EXPERT OPINION: The combination of these developments will change the endovascular field within the next 5 years, allowing targeted iliac treatment without the need for radiographic imaging or iodinated contrast media.

The use of 3D image fusion for percutaneous transluminal angioplasty and stenting of iliac artery obstructions: validation of the technique and systematic review of literature.

INTRODUCTION: The effect of the insertion of guidewires and catheters on fusion accuracy of the three-dimensional (3D) image fusion technique during iliac percutaneous transluminal angioplasty (PTA) procedures has not yet been investigated. EVIDENCE ACQUISITION: Technical validation of the 3D fusion technique was evaluated in 11 patients with common and/or external iliac artery lesions. A preprocedural contrast-enhanced magnetic resonance angiogram (CE-MRA) was segmented and manually registered to a cone-beam computed tomography image created at the beginning of the procedure for each patient. The treating physician visually scored the fusion accuracy (i.e., accurate [<2 mm], mismatch [2-5 mm], or inaccurate [>5 mm]) of the entire vasculature of the overlay with respect to the digital subtraction angiography (DSA) directly after the first obtained DSA. Contours of the vasculature of the fusion images and DSAs were drawn after the procedure. The cranial-caudal, lateral-medial, and absolute displacement were calculated between the vessel centerlines. To determine the influence of the catheters, displacement of the catheterized iliac trajectories were compared with the noncatheterized trajectories. Electronic databases were systematically searched for available literature published between January 2010 till August 2017. EVIDENCE SYNTHESIS: The mean registration error for all iliac trajectories (N.=20) was small (4.0±2.5 mm). No significant difference in fusion displacement was observed between catheterized (N.=11) and noncatheterized (N.=9) iliac arteries. The systematic literature search yielded 2 manuscripts with a total of 22 patients. The methodological quality of these studies was poor (≤11 MINORS Score), mainly due to a lack of a control group. CONCLUSIONS: Accurate image fusion based on preprocedural CE-MRA is possible and could potentially be of help in iliac PTA procedures. The flexible guidewires and angiographic catheters, routinely used during endovascular procedures of iliac arteries, did not cause significant displacement that influenced the image fusion. Current literature on 3D image fusion in iliac PTA procedures is of limited methodological quality.

Hemodynamic significance assessment of equivocal iliac artery stenoses by comparing duplex ultrasonography with intra-arterial pressure measurements.

BACKGROUND: This study evaluated the accuracy of duplex ultrasonography (DUS)-based peak systolic velocity ratio (PSVR) and ipsilateral common femoral artery (CFA) velocity waveform analysis to identify a hemodynamically significant equivocal iliac artery stenosis (30-75% lumen diameter reduction). Intra-arterial pressure measurements were used as a reference. METHODS: In a previously performed prospective study (NTR5085), 30 patients with 35 iliac artery stenoses underwent intra-arterial angiography. To determine the hemodynamic significance of the iliac artery stenoses, intra-arterial translesional pressure measurements were performed under hyperemic conditions. Preprocedural DUS was obtained of the iliac and femoral arteries. PSVR over the iliac lesions was determined, and ipsilateral CFA velocity waveforms were retrospectively classified. The intraobserver and interobserver agreement for CFA velocity waveform classification were evaluated. Sensitivity, specificity, and overall accuracy were calculated by comparing PSVR, velocity waveform analysis, and a combination of these parameters to the intra-arterial translesional pressure gradient. A translesional pressure gradient ≥10 mmHg, PSVR ≥2.5, and a monophasic or biphasic CFA velocity waveform were considered to be indicative for a hemodynamically significant iliac artery stenosis. RESULTS: For classification of ipsilateral CFA velocity waveforms, intraobserver and interobserver agreement were 0.94 and 0.82, respectively. A PSVR ≥2.5 could identify a hemodynamically significant stenosis with 83% sensitivity, 67% specificity, and an overall accuracy of 77%. When both a monophasic and a biphasic velocity waveform were considered to indicate a hemodynamically significant iliac artery stenosis, sensitivity was 78%, specificity was 50%, and the overall accuracy was 69%. The combination of a PSVR ≥2.5 with either a monophasic or a biphasic CFA velocity waveform was found in 20 stenoses and resulted in 94% sensitivity, 75% specificity, and 90% accuracy. When the remainder of the stenoses (N.=15) was classified by means of the PSVR, the overall accuracy remained 77%. CONCLUSIONS: DUS is a very useful noninvasive imaging modality to determine the significance of an iliac artery stenosis. A combination of translesional PSVR ≥2.5 with either a monophasic or a biphasic ipsilateral CFA ultrasound waveforms has a good accuracy and helps to select patients that benefit most from follow-up examination by computed tomography angiography or magnetic resonance angiography.

Fluoroscopy with MRA fusion image guidance in endovascular iliac artery interventions: study protocol for a randomized controlled trial (3DMR-Iliac-roadmapping study).

BACKGROUND: Endovascular iliac artery interventions rely on the use of two-dimensional digital subtraction angiographies with an iodinated contrast agent and ionizing radiation. The amount of iodinated contrast agent should be limited because of its potentially nephrotoxic effects. Three-dimensional (3D) image fusion requires registration of a preprocedural magnetic resonance angiogram (MRA) or computed tomography (CT) angiogram to a perprocedurally acquired cone-beam CT or two fluoroscopic orthogonal projections. After registration, the 3D angiography images can be overlaid on the fluoroscopy screen and will follow table and C-arm movements. This study will assess the added value of the 3D image fusion technique in iliac artery interventions regarding the amount of the iodinated contrast agent administered. METHODS/DESIGN: The study cohort will comprise 106 patients (> 18 years) with symptomatic common and/or external iliac artery stenoses or occlusions and a recent (< 6 months) diagnostic MRA from the pelvis through the lower extremities, for which an endovascular intervention is indicated. Patients will be randomized into the control or study group (i.e. treatment without or with 3D image fusion guidance). The primary endpoint is the amount of administered iodinated contrast agent (mL). Secondary outcomes are technical success of the procedure, defined as < 30% residual stenosis over the treated lesion, fluoroscopy time, and radiation dose as dose area product (mGycm2). Patient participation in the study will be completed after hospital discharge. DISCUSSION: This study is a randomized controlled multicenter trial to provide evidence on the effect of the 3D image fusion technique on the amount of administered iodinated contrast during endovascular common and/or external iliac artery interventions. TRIAL REGISTRATION: Nederlands Trial Register, NTR5008 . Registered on 16 December 2014.

In Vivo Validation of Patient-Specific Pressure Gradient Calculations for Iliac Artery Stenosis Severity Assessment.

BACKGROUND: Currently, the decision to treat iliac artery stenoses is mainly based on visual inspection of digital subtraction angiographies. Intra-arterial pressure measurements can provide clinicians with accurate hemodynamic information. However, pressure measurements are rarely performed because of their invasiveness and the time required. Therefore, the aim of the study was to test the feasibility of a computational model that can predict translesional pressure gradients across iliac artery stenoses on the basis of imaging data only. METHODS AND RESULTS: Patients (N=21) with symptomatic peripheral arterial disease and a peak systolic velocity ratio between 2.5 and 5.0 were included in the study. Patients underwent per-procedural 3-dimensional rotational angiography and hyperemic intra-arterial translesional pressure measurements. Vascular anatomical features were reconstructed from the 3-dimensional rotational angiography data into an axisymmetrical 2-dimensional computational mesh, and flow was estimated on the basis of the stenosis geometry. Computational fluid dynamics were performed to predict the pressure gradient and were compared with the measured pressure gradients. A good agreement by overlapping error bars of the predicted and measured pressure gradients was found in 21 of 25 lesions. Stratification of the stenosis on the basis of the predicted pressure gradient into hemodynamic not significant (<10 mm Hg) and hemodynamic significant (≥10 mm Hg) resulted in sensitivity, specificity, and overall predictive values of 95%, 60%, and 88%, respectively. CONCLUSIONS: The feasibility of the patient-specific computational model to predict the hyperemic translesional pressure gradient over iliac artery stenosis was successfully tested. Presented results suggest that, with further optimization and corroboration, the model can become a valuable aid to the diagnosis of equivocal iliac artery stenosis. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR5085.