Long-term Outcome of Axillo-axillary Bypass in Patients with Subclavian or Innominate Artery Stenosis.

BACKGROUND: Subclavian or innominate artery stenosis (SAS) may cause upper extremity and cerebral ischemia. In patients with symptomatic subclavian or innominate artery stenosis, percutaneous transluminal angioplasty is the treatment of first choice. When percutaneous transluminal angioplasty is technically restricted or unsuccessful, an extrathoracic bypass grafting, such as an axillo-axillary bypass can be considered. The patency rate of axillo-axillary bypass is often questioned. The aim of this study was to assess long-term outcomes of patients undergoing axillo-axillary bypass for subclavian or innominate artery stenosis (SAS) and to provide a literature overview. METHODS: In this single-center study, data from patients who underwent axillo-axillary bypass for symptomatic SAS between 2002 and 2018 were retrospectively analyzed. Bypass material was Dacron® (54%) or polytetrafluoroethylene (PTFE) (46%). Primary outcome was graft patency and secondary outcome was the occurrence of mortality and stroke. In addition, a systematic literature search was performed in MEDLINE and EMBASE databases including all studies describing patency of axillo-axillary bypass. RESULTS: In total, 28 axillo-axillary bypasses had been performed. Cumulative primary, primary-assisted, and secondary patency rates at one year were 89%, 93%, and 96%, respectively. Cumulative primary, primary-assisted, and secondary patency rates at five years were 76%, 84%, and 87%, respectively. The primary-assisted patency rates at five years for Dacron® and PTFE were 93% and 73%, respectively. A total of four primary axillo-axillary bypass occlusions occurred (14%), with a mean of 12 months (range, 0.4-25) after operation. The 30-day mortality was 7%; one patient died after a stroke and one died of a myocardial infarction. At the first postoperative follow-up control, 22 of the 26 remaining patients (85%) had relief of symptoms. The literature search included 7 studies and described a one-year primary patency range of 93-100% (n = 137) and early postoperative adverse events included death (range, 0-13%) and stroke (range, 0-5%). CONCLUSIONS: Patency rates of axillo-axillary bypasses for patients with a symptomatic SAS are good. However, the procedural complication rate in this series is high and attention should be paid to intervention indication.

Heterogeneity in Standard Operating Procedures for Catheter Directed Thrombolysis for Peripheral Arterial Occlusions in The Netherlands: A Nationwide Overview.

OBJECTIVE: Catheter directed thrombolysis (CDT) for acute arterial occlusions of the lower extremities is associated with a risk of major bleeding complications. Strict monitoring of vital functions is advised for timely adjustment or discontinuation of thrombolytic treatment. Nevertheless, current evidence on the optimal application of CDT and use of monitoring during CDT is limited. In this study the different standard operating procedures (SOPs) for CDT in Dutch hospitals were compared against a national guideline in a nationwide analysis. METHODS: SOPs, landmark studies, and national and international guidelines for CDT for acute lower extremity arterial occlusions were compared. The protocols of 34 Dutch medical centres where CDT is performed were assessed. Parameters included contraindications to CDT, co-administration of heparin, thrombolytic agent administration, angiographic control, and patient monitoring. RESULTS: Thirty-four SOPs were included, covering 94% of medical centres performing CDT in the Netherlands. None of the SOPs had identical contraindications and a strong divergence in relative and absolute grading was found. Heparin and urokinase dosages differed by a factor of five. In 18% of the SOPs heparin co-administration was not mentioned. Angiographic control varied between once every 6 h to once every 24 h. In 76% of the SOPs plasma fibrinogen levels were used for CDT dose adjustments. However, plasma fibrinogen level threshold values for treatment adjustments varied between 2.0 g/L and 0.5 g/L. CONCLUSION: The SOPs for CDT for acute arterial occlusions of the lower extremities differ greatly on five major operating aspects among medical centres in the Netherlands. None of the SOPs exactly conforms to current national or international guidelines. This study provides direction on how to increase homogeneity in guideline recommendations and to improve guideline adherence in CDT.

Factors Associated with Hospital Dependent Delay to Carotid Endarterectomy in the Dutch Audit for Carotid Interventions.

OBJECTIVES: As the risk of a recurrent neurological event in patients with symptomatic carotid stenosis requiring carotid endarterectomy (CEA) is highest in the early phase after the first neurological event, guidelines recommend operating on these patients as soon as possible or at least within 14 days of their initial event. However, in real world practice this is often not met. The aim of this study is to identify factors that cause hospital dependent delay to CEA. METHODS: All consecutive patients with symptomatic carotid stenosis undergoing CEA registered in the mandatory Dutch Audit for Carotid Interventions from January 2014 up to and including December 2017 were included in the current analysis. Univariable followed by multivariable logistic regression was used to identify independent factors associated with hospital dependent waiting time, defined as time from the first consultation at any hospital to CEA of more than 14 days. RESULTS: A total of 8620 patients were included. The median time to CEA was 11 days (IQR 8-14). Seventy-eight per cent of patients underwent CEA within 14 days of first hospital consultation. Factors associated with a hospital dependent waiting time longer than 14 days were age (OR 0.99 per year, 95% CI 0.98-0.99), any previous CEA (OR 1.67, 95% CI 1.32-2.09), ocular symptoms as index event (OR 1.31, 95% CI 1.15-1.50), and indirect referral (OR 1.53, 95% CI 1.34-1.73). Hospital surgical volume was not identified as a factor for delay, except for the delay of indirectly referred patients where high volume hospitals reported the shortest delay. CONCLUSION: This cohort derived from a validated nationwide prospective audit identified younger age, previous CEA, ocular symptoms, and indirect referral as hospital dependent factors for delay. High volume hospitals had a similar hospital dependent waiting time to middle and low volume hospitals. However, high volume hospitals had more indirect referrals, implying that their logistics are more efficiently organised.

Unexpected Cardiac Computed Tomography Findings in Patients With Postoperative Myocardial Injury.

BACKGROUND: Postoperative myocardial injury (PMI) is a strong predictor of mortality after noncardiac surgery. PMI is believed to be attributable to coronary artery disease (CAD), yet its etiology is largely unclear. We aimed to quantify the prevalence of significant CAD in patients with and without PMI using coronary computed tomography angiography (CCTA). METHODS: This prospective cohort study included patients of 60 years or older without a history of cardiac disease and with and without PMI after intermediate- to high-risk noncardiac surgery. PMI was defined as any serum troponin I level ≥60 ng/L on the first 3 postoperative days. Main exclusion criteria were known cardiac disease and postoperative ischemic symptoms or electrocardiography abnormalities. Noninvasive imaging consisted of a postoperative CCTA. Main outcome was CAD defined as >50% coronary stenosis on CCTA. RESULTS: The analysis included 66 patients. Median peak troponin levels in the PMI (n = 46) and control group (n = 20) were 150 (interquartile range, 120-298) vs 15 (interquartile range, 10-31) ng/L (P < .01). CAD was found in 23 patients with PMI (50%) vs 3 without PMI (15%; relative risk, 3.3; 95% confidence interval, 1.1-9.8). Remarkably, pulmonary embolism was present in 15 patients with PMI (33%) versus in 4 without PMI (20%; relative risk, 1.6; 95% confidence interval, 0.6-4.3). None of the patients died within 30 days. CONCLUSIONS: In patients without a history of cardiac disease, PMI after noncardiac surgery was associated with CAD. In addition, a clinically silent pulmonary embolism was found in one-third of patients with PMI. This urges further research to improve clinical workup using imaging and may have important clinical implications.

Validation of the Automated Electronic Microemboli Detection System in Patients Undergoing Carotid Endarterectomy.

PURPOSE: To assess the diagnostic value of automatic embolus detection software (AEDS) in transcranial Doppler (TCD) monitoring for the detection of solid microemboli in patients at risk for perioperative stroke during carotid endarterectomy (CEA). MATERIALS AND METHODS: In 50 patients undergoing CEA, perioperative TCD registration was recorded. All recorded events, identified and saved by the AEDS, were analyzed off-line doubly by two human experts (HEs) within a time frame of > 4 months. The inter- and intraobserver variability was assessed. The overall agreement with the HEs, the sensitivity, specificity, negative and positive predictive values (NPV and PPV) of the AEDS were computed for different cut-offs (patient displaying perioperative 5, 10, 20, 25, or 50 microemboli). RESULTS: 77 233 events were analyzed. The inter- and intraobserver variability was good (min κ = 0.72, max κ = 0.79). AEDS and the HEs identified 760 and 470 solid emboli, respectively. The agreement between AEDS and the HEs for solid emboli detection was poor (κ = 0.24, SE = 0.016). The specificity and NPV were high (99.2 % and 99.6 %) but the sensitivity and PPV were low (30.6 % and 19.8 %). Applying a threshold of > 20 microemboli resulted in the best sensitivity (100.0 %), specificity (84.4 %), PPV (42.7 %), NPV (100.0 %) and area under the curve (0.898). However, 58.3 % of the patients were false positive as classified by AEDS. CONCLUSION: In this validation cohort, AEDS has insufficient agreement with HEs in the identification of solid emboli. AEDS and HEs disagree with respect to the identification of specific patients at risk. Therefore, AEDS cannot be used as a standalone system to identify patients at risk for perioperative stroke during CEA.

The effect of P2Y12 inhibition on platelet activation assessed with aggregation- and flow cytometry-based assays.

Patients on P2Y12 inhibitors may still develop thrombosis or bleeding complications. Tailored antiplatelet therapy, based on platelet reactivity testing, might reduce these complications. Several tests have been used, but failed to show a benefit of tailored antiplatelet therapy. This could be due to the narrowness of current platelet reactivity tests, which are limited to analysis of platelet aggregation after stimulation of the adenosine diphosphate (ADP)-pathway. However, the response to ADP does not necessarily reflect the effect of P2Y12 inhibition on platelet function in vivo. Therefore, we investigated whether measuring platelet reactivity toward other physiologically relevant agonists could provide more insight in the efficacy of P2Y12 inhibitors. The effect of in vitro and in vivo P2Y12 inhibition on αIIbß3-activation, P-selectin and CD63-expression, aggregate formation, release of alpha, and dense granules content was assessed after stimulation of different platelet activation pathways. Platelet reactivity measured with flow cytometry in 72 patients on P2Y12 inhibitors was compared to VerifyNow results. P2Y12 inhibitors caused strongly attenuated platelet fibrinogen binding after stimulation with peptide agonists for protease activated receptor (PAR)-1 and -4, or glycoprotein VI ligand crosslinked collagen-related peptide (CRP-xl), while aggregation was normal at high agonist concentration. P2Y12 inhibitors decreased PAR-agonist and CRP-induced dense granule secretion, but not alpha granule secretion. A proportion of P2Y12-inhibitor responsive patients according to VerifyNow, displayed normal fibrinogen binding assessed with flow cytometry after stimulation with PAR-agonists or CRP despite full inhibition of the response to ADP, indicating suboptimal platelet inhibition. Concluding, measurement of platelet fibrinogen binding with flow cytometry after stimulation of thrombin- or collagen receptors in addition to ADP response identifies different patients as nonresponders to P2Y12 inhibitors, compared to only ADP-induced aggregation-based assays. Future studies should investigate the value of both assays for monitoring on-treatment platelet reactivity.

A proof-of-concept study of the VeinScrew: A new percutaneous venous closure device.

Objective This study evaluated the concept of percutaneous closure of insufficient veins using the VeinScrew principle. Methods The VeinScrew is designed to place a spring-shaped implant that contracts and clamps around the vein. The ability of the device to occlude adequately was tested in a bench model experiment. The feasibility of accurate placement and adequate venous occlusion was evaluated in an animal experiment and in a human cadaveric experiment. Results The VeinScrew implant occluded up to a pressure of 135 mmHg. In vivo studies confirmed that deployment was challenging but technically feasible, and subsequent phlebography showed closure of the vein. The cadaveric study showed that percutaneous placement of the evolved VeinScrew around the great saphenous vein was feasible and accurate. Conclusions The current studies show the feasibility of the VeinScrew concept. Future developments and translational studies are necessary to determine the potential of this technique as a new option in the phlebologist's toolbox.

Validation of Noninvasive In Vivo Compound Ultrasound Strain Imaging Using Histologic Plaque Vulnerability Features.

BACKGROUND AND PURPOSE: Carotid plaque rupture is a major cause of stroke. Key issue for risk stratification is early identification of rupture-prone plaques. A noninvasive technique, compound ultrasound strain imaging, was developed providing high-resolution radial deformation/strain images of atherosclerotic plaques. This study aims at in vivo validation of compound ultrasound strain imaging in patients by relating the measured strains to typical features of vulnerable plaques derived from histology after carotid endarterectomy. MATERIALS AND METHODS: Strains were measured in 34 severely stenotic (>70%) carotid arteries at the culprit lesion site within 48 hours before carotid endarterectomy. In all cases, the lumen-wall boundary was identifiable on B-mode ultrasound, and the imaged cross-section did not move out of the imaging plane from systole to diastole. After endarterectomy, the plaques were processed using a validated histology analysis technique. RESULTS: Locally elevated strain values were observed in regions containing predominantly components related to plaque vulnerability, whereas lower values were observed in fibrous, collagen-rich plaques. The median strain of the inner plaque layer (1 mm thickness) was significantly higher (P<0.01) for (fibro)atheromatous (n=20, strain=0.27%) than that for fibrous plaques (n=14, strain=-0.75%). Also, a significantly larger area percentage of the inner layer revealed strains above 0.5% for (fibro)atheromatous (45.30%) compared with fibrous plaques (31.59%). (Fibro)atheromatous plaques were detected with a sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 86%, 88%, and 71%, respectively. Strain did not significantly correlate with fibrous cap thickness, smooth muscle cell, or macrophage concentration. CONCLUSIONS: Compound ultrasound strain imaging allows differentiating (fibro)atheromatous from fibrous carotid artery plaques.

Plasma CTGF is independently related to an increased risk of cardiovascular events and mortality in patients with atherosclerotic disease: the SMART study.

AIMS: Connective tissue growth factor (CTGF) plays a key role in tissue fibrogenesis and growing evidence indicates a pathogenic role in cardiovascular disease. Aim of this study is to investigate the association of connective tissue growth factor (CTGF/CCN2) with cardiovascular risk and mortality in patients with manifest vascular disease. METHODS AND RESULTS: Plasma CTGF was measured by ELISA in a prospective cohort study of 1227 patients with manifest vascular disease (mean age 59.0 ± 9.9 years). Linear regression analysis was performed to quantify the association between CTGF and cardiovascular risk factors. Results are expressed as beta (ß) regression coefficients with 95% confidence intervals (CI). The relation between CTGF and the occurrence of new cardiovascular events and mortality was assessed with Cox proportional hazard analysis. Adjustments were made for potential confounding factors. Plasma CTGF was positively related to total cholesterol (ß 0.040;95%CI 0.013-0.067) and LDL cholesterol (ß 0.031;95%CI 0.000-0.062) and inversely to glomerular filtration rate (ß -0.004;95%CI -0.005 to -0.002). CTGF was significantly lower in patients with cerebrovascular disease. During a median follow-up of 6.5 years (IQR 5.3-7.4) 131 subjects died, 92 experienced an ischemic cardiac complication and 45 an ischemic stroke. CTGF was associated with an increased risk of new vascular events (HR 1.21;95%CI 1.04-1.42), ischemic cardiac events (HR 1.41;95%CI 1.18-1.67) and all-cause mortality (HR 1.18;95%CI 1.00-1.38) for every 1 nmol/L increase in CTGF. No relation was observed between CTGF and the occurrence of ischemic stroke. CONCLUSIONS: In patients with manifest vascular disease, elevated plasma CTGF confers an increased risk of new cardiovascular events and all-cause mortality.

The influence of baseline risk on the relation between HbA1c and risk for new cardiovascular events and mortality in patients with type 2 diabetes and symptomatic cardiovascular disease.

BACKGROUND: Strict glycaemic control in patients with type 2 diabetes has proven to have microvascular benefits while the effects on CVD and mortality are less clear, especially in high risk patients. Whether strict glycaemic control would reduce the risk of future CVD or mortality in patients with type 2 diabetes and pre-existing CVD, is unknown. This study aims to evaluate whether the relation between baseline HbA1c and new cardiovascular events or mortality in patients with type 2 diabetes and pre-existing cardiovascular disease (CVD) is modified by baseline vascular risk. METHODS: A cohort of 1096 patients with type 2 diabetes and CVD from the Second Manifestations of ARTerial Disease (SMART) study was followed. The relation between HbA1c at baseline and future vascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality was evaluated with Cox proportional hazard analyses in a population that was stratified for baseline risk for vascular events as calculated with the SMART risk score. The mean follow-up duration was 6.9 years for all-cause mortality and 6.4 years for vascular events, in which period 243 and 223 cases were reported, respectively. RESULTS: A 1 % increase in HbA1c was associated with a higher risk for all-cause mortality (HR 1.18, 95 % CI 1.06-1.31). This association was also found in the highest SMART risk quartile (HR 1.33, 95 % CI 1.11-1.60). There was no relation between HbA1c and the occurrence of cardiovascular events during follow-up (HR 1.03, 95 % CI 0.91-1.16). The interaction term between HbA1c and SMART risk score was not significantly related to any of the outcomes. CONCLUSION: In patients with type 2 diabetes and CVD, HbA1c is related to the risk of all-cause mortality, but not to the risk of cardiovascular events. The relation between HbA1c and all-cause mortality in patients with type 2 diabetes and vascular disease is not dependent on baseline vascular risk.

Misinterpretation of ischaemic infarct location in relationship to the cerebrovascular territories.

PURPOSE: Cerebral perfusion territories are known to vary widely among individuals. This may lead to misinterpretation of the symptomatic artery in patients with ischaemic stroke to a wrong assumption of the underlying aetiology being thromboembolic or hypoperfusion. The aim of the present study was to investigate such potential misinterpretation with territorial arterial spin labelling (T-ASL) by correlating infarct location with imaging of the perfusion territory of the carotid arteries or basilar artery. MATERIALS AND METHODS: 223 patients with subacute stroke underwent MRI including structural imaging scans to determine infarct location, time-of-flight MR angiography (MRA) to determine the morphology of the circle of Willis and T-ASL to identify the perfusion territories of the internal carotid arteries, and basilar artery. Infarct location and the perfusion territory of its feeding artery were classified with standard MRI and MRA according to a perfusion atlas, and were compared to the classification made according to T-ASL. RESULTS: A total of 149 infarctions were detected in 87 of 223 patients. 15 out of 149 (10%) infarcts were erroneously attributed to a single perfusion territory; these infarcts were partly located in the originally determined perfusion territory but proved to be localised in the border zone with the adjacent perfusion territory instead. 12 out of 149 (8%) infarcts were misclassified with standard assessments and were not located in the original perfusion territory. CONCLUSIONS: T-ASL with territorial perfusion imaging may provide important additional information for classifying the symptomatic brain-feeding artery when compared to expert evaluation with MRI and MRA.

Clinical Experience amongst Surgeons in the Asymptomatic Carotid Surgery Trial-1.

INTRODUCTION: Hospital volume may influence the outcomes of carotid revascularization, but in trials the effect of the clinical experience of individual surgeons on procedural outcome is less certain. We assessed perioperative event rates amongst centers with different trial entry volumes and also the effects of individual operator experience in the first Asymptomatic Carotid Surgery Trial-1 (ACST-1). METHODS: In 126 centers participating in ACST-1, surgeons were classified according to their in-trial experience (group A: 50 cases; group B: 51-100 cases; group C: >100 cases), center enrolment volume (group I: <30 patients; group II: 30-75 patients; group III: >75 patients) and center annual hospital volume (group 1: <40 carotid endarterectomies (CEAs); group 2: 40-75 CEAs; group 3: >75 cases). Differences in perioperative event rates were compared using logistic regression analysis. RESULTS: In centers with the most clinical experience compared with those with least experience (groups C vs. A), the number of strokes or deaths was 8 of 275 (2.9%) versus 24 of 810 (3.0%) with OR 0.99 (95% CI 0.44-2.25, p = 0.986). Numbers of strokes or death in high enrolment centers compared with those in low enrolment centers (groups III vs. I) was 20 of 680 (2.9%) versus 21 of 580 (3.6%) with OR 0.81 (95% CI 0.43-1.51, p = 0.921). In centers with a high annual volume compared with those of low annual volume (groups 3 vs. 1), numbers of strokes and death were non-significantly lower, 26 of 823 (3.2%) versus 19 of 422 (4.5%) with OR 0.68 (95% CI 0.37-1.26, p = 0.386). Cumulative stroke risk at 5 and 10 years were similar among different levels of reported clinical experience, enrolment volume and annual hospital volume. CONCLUSION: Although our data did not demonstrate an association between perioperative complications and operators' experience, enrolment volume or annual hospital volume, rates of stroke or death were numerically lower in both high enrolment and high annual volume centers. This lack of association could be explained by an overall low procedural risk in ACST-1.

The Mechanism of Procedural Stroke Following Carotid Endarterectomy within the Asymptomatic Carotid Surgery Trial 1.

INTRODUCTION: Understanding the pathophysiological mechanism of procedural stroke during carotid intervention may help reduce the risk of stroke in those undergoing surgery. We therefore studied the features of procedural strokes within the first Asymptomatic Carotid Surgery Trial-1 (ACST-1) to identify the underlying pathophysiological mechanism. METHODS: In ACST-1, 3,120 patients with severe asymptomatic carotid stenosis thought suitable for surgery were randomized to CEA or indefinite deferral of surgery. Information on procedural (within 30 days) stroke type, laterality, severity and timing was collected. Eight possible mechanisms were defined: embolism from the carotid artery, haemodynamic, thrombosis or occlusion of the carotid artery, hyperperfusion syndrome, cardioembolic, either carotid embolic or haemodynamic, either carotid embolic or thrombotic occlusion, or undetermined. RESULTS: Procedural strokes occurred in 53 patients (2.7%). Strokes were predominantly ischaemic (n = 43; 81%), ipsilateral to the treated artery (n = 42; 79%), often occurred on the day of the operation (n = 32; 60%) and in over half the patients, were disabling or fatal (n = 27; 51%). The identified stroke mechanism was carotid embolic (n = 7), haemodynamic (n = 5), thrombosis or occlusion of the carotid artery (n = 9), hyperperfusion (n = 7), cardioembolic (n = 3), 'probably carotid embolic or haemodynamic' (n = 7), 'probably carotid embolic or thrombotic occlusion' (n = 3) and undetermined in 12 cases. CONCLUSION: In ACST-1, the risk of procedural stroke was low. Most strokes (60%) occurred on the day of the procedure and were caused by thrombosis or thrombotic occlusion of the ipsilateral carotid artery. These findings emphasize the importance of immediate assessment of the treated carotid artery when a stroke occurs after CEA.

Clinical Risk Factors and Plaque Characteristics Associated with New Development of Contralateral Stenosis in Patients Undergoing Carotid Endarterectomy.

BACKGROUND: Following carotid endarterectomy (CEA), cerebrovascular hemodynamic may be hampered by ipsilateral restenosis or development of contralateral stenosis. It remains to be clarified if these patients need follow-up for identifying development of contralateral stenosis. Identification of risk factors contributing to development of contralateral stenosis could allow more specific follow-up. In this current study, we assessed clinical risk factors and plaque characteristics of patients undergoing CEA with development of new contralateral stenosis during mid-term follow-up. METHODS: Seven hundred and sixty patients undergoing CEA between 2003 and 2011 at UMC Utrecht were included. Atherosclerotic plaques were excised and analyzed for smooth muscle cells (SMCs), collagen, macrophages, lipid core, plaque hemorrhage and vessel density. Patients underwent clinical and duplex ultrasound follow-up at 3 and 12 months and yearly thereafter. Association between plaque- and patient characteristics with development of contralateral stenosis ≥50% was assessed with univariate and multivariate analysis. Clinical outcome during follow-up was associated with development of new contralateral stenosis. RESULTS: After a median follow-up time of 2.5 years, development of contralateral stenosis was observed in 108 patients (20%). Presence of high collagen (p = 0.025) and high SMC (p = 0.027) was associated with development of new contralateral stenosis, whereas large lipid core was negatively associated with new development of contralateral stenosis (p = 0.034). The same plaque characteristics were related to contralateral occlusion. History of coronary artery disease (p = 0.031) and asymptomatic presentation (p = 0.000) were univariably associated with development of contralateral stenosis. Multiple regression analysis indicated that asymptomatic status was independently associated with contralateral stenosis (p = 0.001). Patients with new development of contralateral stenosis more often showed symptoms during follow-up (p = 0.049). CONCLUSION: Dissection of a lipid-poor, collagen-rich or SMC-rich plaque yielded an association with development of new contralateral stenosis during mid-term follow-up after CEA. Asymptomatic patients had a significantly higher risk for development of contralateral stenosis. New contralateral stenosis was related to the presence of new cerebral symptoms. These findings may help to develop individual treatment algorithms for patients with cerebrovascular atherosclerotic burden.

One-Year Mortality, Causes of Death, and Cardiac Interventions in Patients with Postoperative Myocardial Injury.

BACKGROUND: To evaluate the role of routine troponin surveillance in patients undergoing major noncardiac surgery, unblinded screening with cardiac consultation per protocol was implemented at a tertiary care center. In this study, we evaluated 1-year mortality, causes of death, and consequences of cardiac consultation of this protocol. METHODS: This observational cohort included 3224 patients ≥60 years old undergoing major noncardiac surgery. Troponin I was measured routinely on the first 3 postoperative days. Myocardial injury was defined as troponin I >0.06 µg/L. Regression analysis was used to determine the association between myocardial injury and 1-year mortality. The causes of death, the diagnoses of the cardiologists, and interventions were determined for different levels of troponin elevation. RESULTS: Postoperative myocardial injury was detected in 715 patients (22%) and was associated with 1-year all-cause mortality (relative risk [RR] 1.4, P = 0.004; RR 1.6, P < 0.001; and RR 2.2, P < 0.001 for minor, moderate, and major troponin elevation, respectively). Cardiac death within 1 year occurred in 3%, 5%, and 11% of patients, respectively, in comparison with 3% of the patients without myocardial injury (P = 0.059). A cardiac consultation was obtained in 290 of the 715 patients (41%). In 119 (41%) of these patients, the myocardial injury was considered to be attributable to a predisposing cardiac condition, and in 111 patients (38%), an intervention was initiated. CONCLUSIONS: Postoperative myocardial injury was associated with an increased risk of 1-year all-cause but not cardiac mortality. A cardiac consultation with intervention was performed in less than half of these patients. The small number of interventions may be explained by a low suspicion of a cardiac etiology in most patients and lack of consensus for standardized treatment in these patients.

Time-dependent changes in atherosclerotic plaque composition in patients undergoing carotid surgery.

BACKGROUND: Time-dependent trends in the incidence of cardiovascular disease have been reported in high-income countries. Because atherosclerosis underlies the majority of cardiovascular diseases, we investigated temporal changes in the composition of atherosclerotic plaques removed from patients undergoing carotid endarterectomy. METHODS AND RESULTS: The Athero-Express study is an ongoing, longitudinal, vascular biobank study that includes the collection of atherosclerotic plaques of patients undergoing primary carotid endarterectomy in the province of Utrecht from 2002 to 2011. Histopathologic features of plaques of 1583 patients were analyzed in intervals of 2 years. The analysis included quantification of collagen, calcifications, lipid cores, plaque thrombosis, macrophages, smooth muscle cells, and microvessels. Large atheroma, plaque thrombosis, macrophages, and calcifications were less frequently observed over time, with adjusted odds ratios of 0.72 (95% confidence interval, 0.650-0.789), 0.62 (95% confidence interval, 0.569-0.679), 0.87 (95% confidence interval, 0.800-0.940), and 0.75 (95% confidence interval, 0.692-0.816) per 2-year increase in time, respectively. These changes in plaque characteristics were consistently observed in patient subgroups presenting with stroke, transient ischemic attack, ocular symptoms, and asymptomatic patients. Concomitantly, risk factor management and secondary prevention strategies among vascular patients scheduled for carotid endarterectomy significantly improved over the past decade. CONCLUSIONS: In conclusion, over the past decade, atherosclerotic plaques harvested during carotid endarterectomy show a time-dependent change in plaque composition characterized by a decrease in features currently believed to be causal for plaque instability. This appears to go hand in hand with improvements in risk factor management.

Symptomatic carotid atherosclerotic disease: correlations between plaque composition and ipsilateral stroke risk.

BACKGROUND AND PURPOSE: For symptomatic patients with carotid artery stenosis, the risk benefit for surgical intervention may vary among patient groups. Various modalities of plaque imaging have been promoted as potential tools for additional risk stratification, particularly in patients with moderate stenosis. However, it remains uncertain to what extent carotid plaque components predict risk of future ipsilateral ischemic stroke. METHODS: In 2 large atherosclerotic carotid plaque biobank studies, we related histological characteristics of 1640 carotid plaques with a validated risk model for the prediction of individual 1- and 5-year stroke risk. RESULTS: No significant heterogeneity between the studies was found. Predicted 5-year stroke risk (top versus bottom quartile) was related to plaque thrombus (odds ratio, 1.42; 95% confidence interval, 1.11-1.89; P=0.02), fibrous content (0.65; 0.49-0.87; P=0.004), macrophage infiltration (1.41; 1.05-1.90; P=0.02), high microvessel density (1.49; 1.05-2.11; P=0.03), and overall plaque instability (1.40; 1.05-1.87; P=0.02). This association was not observed for cap thickness, calcification, intraplaque hemorrhage, or lymphocyte infiltration. Plaques removed within 30 days of most recent symptomatic event were most strongly correlated with predicted stroke risk. CONCLUSIONS: Features of the vulnerable carotid plaque, including plaque thrombus, low fibrous content, macrophage infiltration, and microvessel density, correlate with predicted stroke risk. This study provides a basis for plaque imaging studies focused on stroke risk stratification.

Plaque components in symptomatic moderately stenosed carotid arteries related to cerebral infarcts: the plaque at RISK study.

BACKGROUND AND PURPOSE: Carotid plaque composition is a major determinant of cerebrovascular events. In the present analysis, we evaluated the relationship between intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (TRFC) in moderately stenosed carotid arteries and cerebral infarcts on MRI in the ipsilateral hemisphere. METHODS: A total of 101 patients with a symptomatic 30% to 69% carotid artery stenosis underwent MRI of the carotid arteries and the brain, within a median time of 45 days from onset of symptoms. The presence of ipsilateral infarcts in patients with and without IPH and TRFC was evaluated. RESULTS: IPH was seen in 40 of 101 plaques. TRFC was seen in 49 of 86 plaques (postcontrast series were not obtained in 15 patients). In total, 51 infarcts in the flow territory of the symptomatic carotid artery were found in 47 patients. Twenty nine of these infarcts, found in 24 patients, were cortical infarcts. No significant relationship was found between IPH or TRFC and the presence of ipsilateral infarcts. CONCLUSIONS: MRI detected IPH and TRFC are not related to the presence of old and recent cortical and subcortical infarcts ipsilateral to a symptomatic carotid artery stenosis of 30% to 69%. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01208025.

Stenting versus endarterectomy for restenosis following prior ipsilateral carotid endarterectomy: an individual patient data meta-analysis.

OBJECTIVE: To study perioperative results and restenosis during follow-up of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) for restenosis after prior ipsilateral CEA in an individual patient data (IPD) meta-analysis. BACKGROUND: The optimal treatment strategy for patients with restenosis after CEA remains unknown. METHODS: A comprehensive search of electronic databases (Medline, Embase) until July 1, 2013, was performed, supplemented by a review of references. Studies were considered for inclusion if they reported procedural outcome of CAS or CEA after prior ipsilateral CEA of a minimum of 5 patients. IPD were combined into 1 data set and an IPD meta-analysis was performed. The primary endpoint was perioperative stroke or death and the secondary endpoint was restenosis greater than 50% during follow-up, comparing CAS and CEA. RESULTS: In total, 13 studies were included, contributing to 1132 unique patients treated by CAS (10 studies, n = 653) or CEA (7 studies; n = 479). Among CAS and CEA patients, 30% versus 40% were symptomatic, respectively (P < 0.01). After adjusting for potential confounders, the primary endpoint did not differ between CAS and CEA groups (2.3% vs 2.7%, adjusted odds ratio 0.8, 95% confidence interval (CI): 0.4-1.8). Also, the risk of restenosis during a median follow-up of 13 months was similar for both groups (hazard ratio 1.4, 95% (CI): 0.9-2.2). Cranial nerve injury (CNI) was 5.5% in the CEA group, while CAS was in 5% associated with other procedural related complications. CONCLUSIONS: In patients with restenosis after CEA, CAS and CEA showed similar low rates of stroke, death, and restenosis at short-term follow-up. Still, the risk of CNI and other procedure-related complications should be taken into account.

The relation between the presence of cardiovascular disease and vascular risk factors in offspring and the occurrence of new vascular events in their parents already at high vascular risk.

BACKGROUND: For parents at high risk for cardiovascular events, presence of cardiovascular disease or risk factors in their offspring may be an indicator of their genetic load or exposure to (unknown) risk factors and might be related to the development of new or recurrent vascular events. METHODS: In 4,267 patients with vascular disease, hypertension, diabetes, or hypercholesterolemia enrolled in the SMART cohort, the presence of cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking, or overweight) and cardiovascular disease (coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysm) was assessed in their 10,564 children. The relation between presence of cardiovascular disease or cardiovascular risk factors in their offspring and new or recurrent vascular events was determined by Cox proportional hazard analyses. RESULTS: Of the patients, 506 (12%) had offspring with cardiovascular disease, hypertension, hypercholesterolemia, or diabetes. Smoking in offspring was present in 1,972 patients (46%), and overweight in 845 patients (20%). During a median follow-up of 7.0 years (interquartile range 3.7-10.4), the composite outcome of myocardial infarction (MI), stroke, or vascular mortality occurred in 251 patients. Patients with offspring with cardiovascular disease, hypertension, hypercholesterolemia, or diabetes had an increased risk of vascular mortality (hazard ratio [HR] 2.9, 95% CI 1.2-7.1), MI (HR 1.6, 95% CI 1.1-2.5), and the composite outcome (HR 1.5, 95% CI 1.1-2.2). Diabetes in offspring was related to an increased risk of the composite outcome (HR 2.7, 95% CI 1.5-5.0), MI (HR 3.3, 95% CI 1.7-6.6), and vascular mortality (HR 3.4, 95% CI 0.8-14.8). Smoking and overweight in offspring were not related to increased vascular risk in parents. CONCLUSIONS: Presence of cardiovascular disease, hypertension, hypercholesterolemia, and diabetes in offspring, with diabetes mellitus being the most contributing cardiovascular risk factor, is related to an increased risk of developing new or subsequent vascular events in patients already at high vascular risk.