Carotid plaque hemorrhage on magnetic resonance imaging strongly predicts recurrent ischemia and stroke.

OBJECTIVE: There is a recognized need to improve selection of patients with carotid artery stenosis for carotid endarterectomy (CEA). We assessed the value of magnetic resonance imaging (MRI)-defined carotid plaque hemorrhage (MRIPH) to predict recurrent ipsilateral cerebral ischemic events, and stroke in symptomatic carotid stenosis. METHODS: One hundred seventy-nine symptomatic patients with ≥ 50% stenosis were prospectively recruited, underwent carotid MRI, and were clinically followed up until CEA, death, or ischemic event. MRIPH was diagnosed if the plaque signal intensity was >150% that of the adjacent muscle. Event-free survival analysis was done using Kaplan-Meier plots and Cox regression models controlling for known vascular risk factors. We also undertook a meta-analysis of reported data on MRIPH and recurrent events. RESULTS: One hundred fourteen patients (63.7%) showed MRIPH, suffering 92% (57 of 62) of all recurrent ipsilateral events and all but 1 (25 of 26) future strokes. Patients without MRIPH had an estimated annual absolute stroke risk of only 0.6%. Cox multivariate regression analysis proved MRIPH as a strong predictor of recurrent ischemic events (hazard ratio [HR] = 12.0, 95% confidence interval [CI] = 4.8-30.1, p < 0.001) and stroke alone (HR = 35.0, 95% CI = 4.7-261.6, p = 0.001). Meta-analysis of published data confirmed this association between MRIPH and recurrent cerebral ischemic events in symptomatic carotid artery stenosis (odds ratio = 12.2, 95% CI = 5.5-27.1, p < 0.00001). INTERPRETATION: MRIPH independently and strongly predicts recurrent ipsilateral ischemic events, and stroke alone, in symptomatic ≥ 50% carotid artery stenosis. The very low stroke risk in patients without MRIPH puts into question current risk-benefit assessment for CEA in this subgroup.

Haematological risk factors predicting clinical success in transarterial embolisation for acute gastrointestinal bleeding.

OBJECTIVES: Evaluate clinical outcomes in transarterial embolisation (TAE) for acute gastrointestinal bleeding (GIB) and determine risk factors for 30-day reintervention for rebleeding and mortality. METHODS: TAE cases were retrospectively reviewed between March 2010 and September 2020 at our tertiary centre. Technical success (angiographic haemostasis following embolisation) was measured. Uni- and multivariate logistic regression analysis were performed to identify risk factors for clinical success (absence of 30-day reintervention or mortality) following embolisation for active GIB or empirical embolisation for suspected bleeding. RESULTS: TAE was conducted in 139 patients (92 (66.2%) male; median age:73, range: 20-95 years) for acute upper GIB (n = 88) and lower GIB (n = 51). TAE was technically successful in 85/90 (94.4%) and clinically successful in 99/139 (71.2%); with 12 (8.6%) reintervention cases for rebleeding (median interval 2 days) and 31 (22.3%) cases of mortality (median interval 6 days). Reintervention for rebleeding was associated with haemoglobin drop > 40 g l-1 from baseline based on univariate analysis (p = 0.047). 30-day mortality was associated with pre-intervention platelet count < 150×109 l-1 (p < 0.001, OR 7.35, 95% CI 3.05-17.71) and INR > 1.4 (p < 0.001, OR 4.75, 95% CI 2.03-11.09) on multivariate logistic regression analysis. No associations were found for patient age, gender, antiplatelet/anticoagulation prior to TAE, or when comparing upper and lower GIB with 30-day mortality. CONCLUSION: TAE had excellent technical success for GIB with relatively high (1-in-5) 30-day mortality. INR > 1.4 and platelet count < 150×109 l-1 were individually associated with TAE 30-day mortality, and pre-TAE > 40 g l-1 haemoglobin decline with rebleeding requiring reintervention. ADVANCES IN KNOWLEDGE: Recognition and timely reversal of haematological risk factors may improve TAE periprocedural clinical outcomes.

Feasibility of arterial spin labeling in evaluating high- and low-flow peripheral vascular malformations: a case series.

We present a case series highlighting a novel use of arterial spin labeling (ASL), a MRI perfusion technique, to evaluate both high- and low-flow peripheral vascular malformations (PVMs) across a range of anatomical locations. While the role of ASL in assessing intracranial vascular malformations is more established, there is limited evidence for PVMs. Our results provide preliminary evidence for the feasibility of ASL in imaging PVMs and its potential ability to distinguish between high- and low-flow PVMs. In addition, we demonstrate its ability to identify focal high blood flow, which may indicate the nidus in arteriovenous malformations. Together, these findings have important implications for patient management. We also outline the potential benefits and limitations of ASL in the imaging of PVMs, and provide justification for further validation of its diagnostic performance.

Study protocol for a multicentre comparative diagnostic accuracy study of tools to establish the presence and severity of peripheral arterial disease in people with diabetes mellitus: the DM PAD study.

INTRODUCTION: Peripheral arterial disease (PAD) is a key risk factor for cardiovascular disease, foot ulceration and lower limb amputation in people with diabetes. Early diagnosis of PAD can enable optimisation of therapies to manage these risks. Its diagnosis is fundamental, though challenging in the context of diabetes. Although a variety of diagnostic bedside tests are available, there is no agreement as to which is the most accurate in routine clinical practice.The aim of this study is to determine the diagnostic performance of a variety of tests (audible waveform assessment, visual waveform assessment, ankle brachial pressure index (ABPI), exercise ABPI and toe brachial pressure index (TBPI)) for the diagnosis of PAD in people with diabetes as determined by a reference test (CT angiography (CTA) or magnetic resonance angiography (MRA)). In selected centres, we also aim to evaluate the performance of a new point-of-care duplex ultrasound scan (PAD-scan). METHODS AND ANALYSIS: A prospective multicentre diagnostic accuracy study (ClinicalTrials.gov Identifier NCT05009602). We aim to recruit 730 people with diabetes from 18 centres across the UK, covering primary and secondary healthcare. Consenting participants will undergo the tests under investigation. Reference tests (CTA or MRA) will be performed within 6 weeks of the index tests. Imaging will be reported by blinded consultant radiologists at a core imaging lab, using a validated scoring system, which will also be used to categorise PAD severity. The presence of one or more arterial lesions of ≥50% stenosis, or tandem lesions with a combined value of ≥50%, will be used as the threshold for the diagnosis of PAD. The primary outcome measure of diagnostic performance will be test sensitivity. ETHICS AND DISSEMINATION: The study has received approval from the National Research Ethics Service (NRES) (REC reference 21/PR/1221). Results will be disseminated through research presentations and papers. TRIAL REGISTRATION NUMBER: NCT05009602.

Novel use of arterial spin labelling in the imaging of peripheral vascular malformations.

We present a novel use of arterial spin labelling (ASL), a MRI perfusion technique, to assess a high-flow, peripheral vascular malformation (PVM), specifically a large arteriovenous malformation in the left forearm of a 20-year-old female. While there has been experience with ASL in the assessment of intracranial vascular malformations, there has been no known use of ASL in the evaluation of PVMs. We also discuss the potential benefits and limitations of ASL in the imaging of PVMs. The promising results from this case warrant further research on ASL in the investigation of PVMs.

A comparison of arterial spin labelling with catheter angiography in evaluating arteriovenous malformations: a systematic review.

OBJECTIVES: To compare the performance of arterial spin labelling (ASL) in evaluating arteriovenous malformations (AVMs) against the current gold standard of catheter angiography. METHODS: We systematically reviewed the published literature using EMBASE and Medline. We included studies that compared ASL to catheter angiography in the assessment of AVMs in three outcome domains: detection, angioarchitectural and haemodynamic features. RESULTS: From 314 unique citations, 19 studies representing 289 patients with intracranial AVMs met our inclusion criteria. We did not pool data due to marked heterogeneity in study outcome measures. Seven studies showed high diagnostic performance of ASL in identifying arterial feeders, with sensitivity ranging from 84.6 to 100% and specificity ranging from 93.3 to 100%. Six studies showed strong ability in detecting arteriovenous shunting, with sensitivity ranging from 91.7 to 100% and specificity ranging from 90 to 100%. Seven studies demonstrated that ASL could identify nidal location and size as well as catheter angiography, while five studies showed relatively poorer performance in delineating venous drainage. Two studies showed 100% sensitivity of ASL in the identification of residual or obliterated AVMs following stereotactic radiosurgery. CONCLUSIONS: Despite limitations in the current evidence base and technical challenges, this review suggests that ASL has a promising role in the work-up and post-treatment follow-up of AVMs. Larger scale prospective studies assessing the diagnostic performance of ASL are warranted. ADVANCES IN KNOWLEDGE: ASL demonstrates overall validity in the evaluation of intracranial AVMs.

Factors associated with pseudoaneurysm development and necessity for reintervention: a single centre study.

OBJECTIVE: Evaluate the factors associated with pseudoaneurysm development and morphology. Measure ultrasound-guided thrombin injection (UGTI) and surgical treatment outcomes for pseudoaneurysms, and the necessity for post-primary intervention (reintervention). METHODS: Retrospective analysis of ultrasound scans and CT angiography of peripheral pseudoaneurysm interventions from February 2011 to April 2017. 99 patients (61.6% female) were identified; median age 72 years (range 12-89). Multivariate analysis of patient demographics, including pre-intervention anticoagulant and antiplatelet medication was performed. RESULTS: Primary intervention for peripheral pseudoaneurysms (62.6% common femoral artery) included 93 UGTI and 6 surgical repairs; with 12 reinterventions (9 UGTI and 3 surgical). Pseudoaneurysm incidence for vascular interventional radiology (VIR) was 0.48% (31/6451) and cardiology was 0.24% (60/25,229). Rates for primary success, immediate complications, 30-day mortality and reintervention were measured respectively for UGTI (98.9%, 3.0%, 2.0%, and 11.8%) and surgical repair (100%, 0.0%, 22.2% and 16.7%). Reintervention risk factors included pre-intervention thrombocytopaenia (<150 × 109/L) ( p = 0.025) and pseudoaneurysms following vascular surgery (p = 0.033). Other positive associations for reintervention (non-significant) included use of a sheath size > 6 Fr ( p = 0.108) or arterial closure device ( p = 0.111) during the pseudoaneurysm causative procedure. The pre-intervention warfarin subgroup developed a larger mean pseudoaneurysm sac size (4.21 cm, range 0.9-7.6), compared to no treatment (p = 0.003), aspirin (p = 0.005) and clopidogrel (p = 0.026) subgroups. UGTI dosage for thrombosis had a positive correlation with incremental sac size increase (p < 0.001). CONCLUSION: The main reintervention risk factor was pre-intervention thrombocytopaenia, with additional positive associations including pseudoaneurysms caused by surgery, increased sheath size and arterial closure devices. Warfarinized patients developed larger sac-sized pseudoaneurysms compared with other pre-intervention regimens, with positive correlation of higher UGTI dosage required for thrombosis. ADVANCES IN KNOWLEDGE: Patients with pre-intervention thrombocytopaenia and pseudoaneurysms attributed to vascular surgery are subgroups that may benefit from post-intervention imaging surveillance due to significant reintervention risk.

Circulating Microparticles in Patients with Symptomatic Carotid Disease Are Related to Embolic Plaque Activity and Recent Cerebral Ischaemia.

BACKGROUND AND PURPOSE: In order to assess the association of microparticles derived from activated platelets (PMP) or endothelial cells (EMP) with risk markers for recurrent embolic events in patients with symptomatic carotid artery disease, we studied the associations between PMP/EMP and three risk markers: plaque haemorrhage (PH), micro-embolic signals and cerebral diffusion abnormalities. METHODS: Patients with recently symptomatic high-grade carotid artery stenosis (60-99%, 42 patients, 31 men; mean age 75 ± 8 years) and 30 healthy volunteers (HV, 11 men; mean age 56 ± 12 years) were prospectively recruited. Patients were characterised by carotid magnetic resonance imaging (presence of PH [MRI PH]), brain diffusion MRI (cerebral ischaemia [DWI+]) and transcranial Doppler ultrasound (micro-embolic signals [MES+]). PMP and EMP were classified by flow cytometry and expressed as log-transformed counts per microlitre. RESULTS: MES+ patients (n = 18) had elevated PMP (MES+ 9.61 ± 0.57) compared to HV (8.80 ± 0.73; p < 0.0001) and to MES- patients (8.55 ± 0.85; p < 0.0001). Stroke patients had elevated PMP (9.49 ± 0.64) and EMP (6.13 ± 1.0) compared to non-stroke patients (PMP 8.81 ± 0.73, p = 0.026, EMP 5.52 ± 0.65, p = 0.011) and HV (PMP 8.80 ± 0.73, p = 0.007, and EMP 5.44 ± 0.47, p = 0.006). DWI+ patients (n = 16) showed elevated PMP (DWI+ 9.53 ± 0.64; vs. HV, p = 0.002) and EMP (DWI+ 5.91 ± 0.99 vs. HV 5.44 ± 0.47; p = 0.037). Only PMP but not EMP were higher in DWI+ versus DWI- patients (8.67 ± 0.90; p = 0.002). No association was found between PMP and EMP with MRI PH. CONCLUSIONS: PMP and EMP were associated with stroke and recent cerebrovascular events (DWI+) but only PMP were also associated with ongoing (MES+) thrombo-embolic activity suggesting a differential biomarker potential for EMP to index cerebral ischaemia while PMP may predict on-going thrombo-embolic activity.

Risk factors associated with cerebrovascular recurrence in symptomatic carotid disease: a comparative study of carotid plaque morphology, microemboli assessment and the European Carotid Surgery Trial risk model.

BACKGROUND: The European Carotid Surgery Trial (ECST) risk model is a validated tool for predicting cerebrovascular risk in patients with symptomatic carotid disease. Carotid plaque hemorrhage as detected by MRI (MRIPH) and microembolic signals (MES) detected by transcranial Doppler (TCD) are 2 emerging modalities in assessing instability of the carotid plaque. The aim of this study was to assess the strength of association of MES and MRIPH with cerebrovascular recurrence in patients with symptomatic carotid artery disease in comparison with the ECST risk prediction model. METHODS AND RESULTS: One hundred and thirty-four prospectively recruited patients (mean [SD]: age 72 [9.8] years, 33% female) with symptomatic severe (50% to 99%) carotid stenosis underwent preoperative TCD, MRI of the carotid arteries to assess MES, PH, and the ECST risk model. Patients were followed up until carotid endarterectomy, recurrent cerebral event, death, or study end. Event-free survival analysis was done using backward conditional Cox regression analysis.Of the 123 patients who had both TCD and MRI, 82 (66.7%) demonstrated PH and 46 (37.4%) had MES. 37 (30.1%) cerebrovascular events (21 transient ischemic attacks, 6 amaurosis fugax, and 10 strokes) were observed. Both carotid PH (HR=8.68; 95% CI 2.66 to 28.40, P<0.001) as well as MES (HR=3.28; 95% CI 1.68 to 6.42, P=0.001) were associated with cerebrovascular event recurrence. Combining MES and MRIPH improved the strength of association (HR=0.74, 95% CI 0.65 to 0.83; P<0.001). The ECST risk model was not associated with recurrence (HR=0.86; 95% CI 0.45 to 1.65; P=0.65). CONCLUSIONS: The presence of carotid plaque hemorrhage is better associated with recurrent cerebrovascular events in patients with symptomatic severe carotid stenosis than the presence of microembolic signals; combining MES and MRIPH, further improves the association while the ECST risk score was insignificant.

Lower prevalence of carotid plaque hemorrhage in women, and its mediator effect on sex differences in recurrent cerebrovascular events.

BACKGROUND AND PURPOSE: Women are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA) than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH) as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence. METHODS: Prevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50-69%]) who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis. RESULTS: Women with symptomatic carotid stenosis (50%≥) were less likely to have plaque hemorrhage (PH) than men (46% vs. 70%) with an adjusted OR of 0.23 [95% CI 0.10-0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067-0.50) not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15-0.98, P = 0.045). Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect. Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45-0.67, p<0.00001). CONCLUSIONS: MRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA.