Genetic and environmental effects on carotid flow velocities: an international twin study.

INTRODUCTION: Altered carotid blood flow velocities (CFV) have a complex background but the underlying genetic contribution is still unclear. We sought to evaluate the influence of genetics, shared and unshared environmental components on individual differences of CFV. METHODS: 193 healthy twin pairs, 126 monozygotic (MZ) and 67 dizygotic (DZ) (mean age 53 ± 14 years) recruited in Italy, in the United States and in Hungary underwent bilateral color-coded Doppler flow assessment of the common carotid artery (CCA) and of the internal carotid artery (ICA) in order to assess the peak systolic (PSV) and end diastolic (EDV) velocities. Means of bilateral CFV values were used in the analysis. RESULTS: Age- and country-adjusted intra-class correlations were higher in monozygotic than in dizygotic pairs for mean PSV of the ICA indicating a heritability of 63%. Unique environmental factors contributed to 37% of ICA PSV. With regards to the mean PSV and EDV of the CCA, and EDV of the ICA, heritability analysis indicated no discernible role for genetic components, while the contributions of shared and unshared environmental factors ranged between 56% and 63%, and between 37% and 44% adjusted for age and country, respectively. Mean ICA/CCA ratio was driven by unique environmental factors (82%) with modest heritability (18%). CONCLUSIONS: Our study showed that the heritability of ICA PSV and ICA/CCA ratio is moderate, while the findings do not support heritability of other investigated CFV values. Environmental effects account for a moderate to major portion of the variance. These findings support the value of early ultrasound screening as well as the prevention of modifiable environmental factors in case of altered carotid flow velocities.

Carotid artery free-floating thrombus caused by paradoxical embolization from greater saphenous vein ascending thrombophlebitis.

Stroke of unknown origin in young patients is seen to be closely correlated with patent foramen ovale (PFO) than stroke in patients with established stroke mechanisms. We report a case of a young woman without cardiovascular risk factors who was admitted to our emergency department with listlessness and altered mental status. The clinical examination revealed right lower limb swelling. Magnetic resonance imaging and contrast-enhanced computed tomographic scans revealed a free floating thrombus of the left internal carotid artery (ICA) with a large bilateral frontal ischemic lesion. The diagnosis of a medium-sized PFO with moderate right-to-left contrast shunting was made after transesophageal echocardiography. No other cardiac sources for embolization were detected, while an ascending thrombophlebitis of the right greater saphenous vein was detected by venous Doppler ultrasonography. These findings support the diagnosis of ICA free-floating thrombus caused by paradoxical embolization (via the PFO) of clot from the greater saphenous vein. The patient underwent emergency saphenofemoral disconnection with femoral vein thrombectomy and subsequently carotid artery thrombectomy under general anesthesia. No carotid atheromatous wall lesions were detected at surgical exploration; no immunologic pathology, hypercoagulable status, or malignancy were recorded. No hemorrhagic cerebral complications were observed in the postoperative period, and the patient had an improvement of her neurologic status (a reduction of the National Institutes of Health Stroke Scale score from 7 to 3). Her recovery was uneventful. The patient was transferred for rehabilitation on postoperative day 5 with oral anticoagulation. Six-month ultrasound follow-up revealed deep and superficial venous system and carotid artery patency. The patient was asymptomatic and anticoagulation was discontinued. Paradoxical cerebral embolization through a PFO is a rare phenomenon that, in our patient, appeared to have resulted in stroke caused by a free-floating thrombus in the ICA. Accurate evaluation of carotid and lower limb veins by duplex scan is mandatory in cases of stroke of unknown origin, and urgent surgical repair can be useful in order to improve the clinical outcome.

Noninvasive imaging of carotid arteries in stroke: emerging value of real-time high-resolution sonography in carotid occlusion due to cardiac embolism.

OBJECTIVE: Comprehension of the pathophysiologic characteristics of atherosclerosis has focused its attention on the study of dynamic and metabolic processes involving the vessel wall as possible causes of stroke. When compared with conventional radiologic techniques, sonography has the main advantage of being a real-time imaging modality. We report 2 acute stroke cases in which carotid sonography showed some dynamic features that could not be identified with computed tomography (CT) and magnetic resonance angiography (MRA). METHODS: Carotid sonography with high-resolution probes (9-14 MHz) was compared with CT and MRA findings showing carotid axis occlusion in 2 patients with acute stroke. RESULTS: In case 1, the internal carotid artery occlusion observed on CT and MRA was interpreted as a dissection on a clinical basis, but sonography showed a mobile embolus originating from the heart in the internal carotid artery. In case 2, the occlusion of the whole carotid axis observed on CT and MRA was instead related to a heart-originating embolus floating in the common carotid artery. CONCLUSIONS: The evaluation of dynamic aspects of atherosclerosis is fundamental to understanding the pathophysiologic characteristics of stroke. Sonography is fundamental in carotid artery imaging for its possibility of showing dynamic processes that could be misdiagnosed with "static" imaging. The correct identification of the pathophysiologic characteristics of stroke in these cases could have led to different diagnostic and therapeutic algorithms.

Imaging of carotid plaque angiogenesis.

Currently, characterization of the vulnerable plaque is a hot research topic as a more adequate strategy for preventing cerebrovascular events is being sought. Histological studies have recognized that plaque inflammation and the presence of adventitial vasa vasorum, intimal angiogenesis and plaque neovascularization are strong predictors of instability in atheromatous lesions of cerebrovascular and cardiovascular patients. The in vivo study of these features has been the focus of development of several new radiological imaging methods. Carotid ultrasound, with ultrasound contrast agents, is not only able to provide an enhanced assessment of the arterial lumen and plaque morphology with an improved resolution of the carotid intima-media thickness, but also to directly visualize adventitial vasa vasorum and plaque neovascularization. This technique and its future clinical implications are discussed in the present review.

Focus on the "unstable" carotid plaque: detection of intraplaque angiogenesis with contrast ultrasound. Present state and future perspectives.

Over the past 20 years, conventional ultrasonography has identified features of the "unstable" carotid plaque. Histological studies have recognized that plaque inflammation and neoangiogenesis play a pivotal role in the developing of the vulnerable plaque. Hence, the growing interest on the biological activities of atherosclerotic lesions leading to cerebrovascular events. The presence of adventitial vasa vasorum and the occurrence of plaque vascularization have been considered as predictors of unstable lesions in cerebrovascular and/or cardiovascular patients. The advent of ultrasound contrast agents has represented a fundamental step in the up-to-date functional evaluation in several fields with minimally invasive procedures. Contrast specific ultrasound modalities are currently used with excellent results in oncology, in cardiology and in vascular diseases. Contrast carotid ultrasound is an emerging imaging technique, able to depict in vivo new functional information on plaque activity and vascularization that may add further new data on the actual condition and future cerebrovascular risk. Further studies will provide a better clarification of the degree of neo-angiogenesis. A future strategy could be represented by the monitoring of plaque neoangiogenesis in order to detect the possible pharmacological effects on plaque remodeling.

Semiquantitative human cerebral perfusion assessment with ultrasound in brain space-occupying lesions: preliminary data.

OBJECTIVE: Transcranial Duplex ultrasound imaging with ultrasound contrast agents is an emerging technique for evaluating brain perfusion. The aim of this study was to evaluate cerebral perfusion with ultrasound in brain space-occupying lesions to identify different perfusion patterns. METHODS: Twenty patients with brain space-occupying lesions underwent ultrasound assessment of brain perfusion with a contrast pulse sequencing nonharmonic ultrasound technique and an ultrasound contrast agent bolus. Data were analyzed with software for semiquantitative analysis. RESULTS: Contrast pulse sequencing imaging with the semiquantitative analysis software allowed identification of qualitative and semiquantitative brain perfusion. Brain hemorrhages showed lower or absent perfusion compared with normal tissue. Meningiomas and glioblastomas without large necrotic areas showed higher perfusion compared with normal tissue. Glioblastomas with large necrotic areas showed overall reduced perfusion compared with normal tissue but higher than that of brain hemorrhages. In glioblastomas with large necrotic areas, it was possible to distinguish between solid and necrotic tissue. CONCLUSIONS: This bedside ultrasound technique, if validated by larger-scale studies, may add helpful information in noninvasive staging of brain tumors. Further potential applications may be in follow-up imaging to evaluate postoperative tumor recurrence or the presence of radionecrosis.

Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent.

BACKGROUND AND PURPOSE: Adventitial vasa vasorum and plaque vascularization have been established as predictors of unstable atheromasic lesions in cerebro- and cardiovascular patients. Ultrasound contrast agents provide reliable information on tissue perfusion and microcirculation. We used contrast ultrasound duplex scanning to identify carotid plaque vascularization. METHODS: Contrast carotid duplex scanning was performed in 23 patients with plaques of different degree of stenosis and echogenicity. RESULTS: Plaque vascularization was detected in the fibrous and fibro-fatty tissue and not observed in the calcific nor in the necrotic and hemorrhagic tissue. Constantly, a small vessel was observed under ulcerations. CONCLUSIONS: Carotid contrast ultrasound imaging appears to be an emerging technique for identifying plaque angiogenesis. Further studies are needed to clarify the role of plaque angiogenesis for assessing cerebrovascular risk and to monitor effects of therapies aimed to plaque remodelling.

Contrast ultrasound imaging: the best method to detect type II endoleak during endovascular aneurysm repair follow-up.

OBJECTIVES: Type II endoleak is the most common complication after endovascular aneurysm repair and require close surveillance. Hence, the need to validate new techniques as alternative to helical CT-scan, the reference standard. The aim of this study is to evaluate the efficacy of Cadence Contrast Pulse Sequencing ultrasound technique with second generation contrast agents in detecting endoleaks, and to compare the results with data obtained from CTA. METHODS: 30 patients with endovascular stent grafts, during their regular follow-up consisting in serial CT and ultrasound exams performed at discharge, at one and six months and at one year thereafter, previous informed consent, were enrolled in a prospectic double blind study design in order to compare triphasic helical CT-scan to another adjunctive ultrasound investigation (Cadence CPS technique with Sono Vue). No more than 15 days occurred between the two examinations. In the study were evaluated only data obtained from the comparison of the two concomitant investigations, independently from the follow-up. Variables analysed were changes in the maximum diameter of the aneurysmal sac, presence and type of endoleak, if detected. In the case of disagreement between the two diagnostic tools angiography was performed. RESULTS: One patient dropped out because of violation of the study protocol (a stroke occurred in the time interval between the two investigations). Both exams visualised patency and proper graft placement in all the remaining patients. Aneurysmal diameters with both investigations overlapped (r(s):0.98). In 21 patients no endoleak was detected with a significant aneurysmal sac shrinkage (P<0.001). In seven patients both methods confirmed presence of endoleak. Ultrasonography detected all type of endoleaks, while CT-scan was uncertain in one. Moreover, in one patient CT-angiography showed an increased aneurysmal diameter without other evidence, while a contrast ultrasound investigation disclosed a type II low-flow endoleak, confirmed by angiography. CONCLUSIONS: The Cadence Contrast Pulse Sequencing with echo contrast agent is an ultrasound technique that substantially improves the ultrasound diagnostic reliability.

Endovascular graft infection: preliminary results of an international enquiry.

PURPOSE: To investigate the frequency of aortoiliac endovascular graft infections and seek the main factors influencing their development. METHODS: To augment personal experience (1 case), a questionnaire was sent to 40 international centers of vascular and endovascular surgery. The literature was also reviewed to collect data on infections developing in endovascular grafts. RESULTS: The survey (85% response rate) and literature review identified 62 cases of infected endovascular grafts (0.4% frequency of endograft infection). In 22 (35%) patients, the infection manifested initially with vague symptoms only, but 41 (65%) patients eventually presented with abdominal abscess, groin fistula, and septic embolization. Common bacteria, such as Staphylococcus aureus, were identified as the cause of most infections (54.5%). The majority (49, 79%) of the 62 patients were treated surgically; 11 (17.7%) patients received conservative therapy (no therapeutic data in 2 patients). Overall mortality was 27.4% (17/62), and operative mortality was 16.3% (8/49). Conservative treatment led to a mortality rate of 36.4% (4/11). The mean follow-up for all patients was 47.8 weeks. Possible factors influencing the development of an infection were secondary adjunctive procedures, immunosuppression, treatment of false aneurysms, and infected central lines. CONCLUSIONS: Infected endovascular grafts are an urgent problem that has been heretofore underestimated and will probably increase as follow-up lengthens. New techniques should be sought to expedite the diagnosis, and an international registry should be set up to provide validated data.

Contrast-enhanced ultrasound imaging for aortic stent-graft surveillance.

PURPOSE: To compare unenhanced and enhanced ultrasound imaging to computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) for surveillance of aortic endografts. METHODS: Thirty consecutive patients (29 men; mean age 69 years, range 50-82) who underwent endovascular aortic aneurysm repair agreed to participate in a follow-up program. Patients underwent CTA (26/30) or MRA (4/30), plain abdominal radiography, and unenhanced and enhanced ultrasound examinations at 3, 12, and 24 months to evaluate aneurysm diameter, endoleaks, and graft patency. The accuracy of ultrasound was compared with CTA or MRA as the reference standards. RESULTS: Twenty-six patients reached the 24-month assessment (mean follow-up 30 months, range 6-60). All endoleaks detected by CTA or MRA were confirmed by enhanced ultrasound; the aneurysm diameter in these patients remained unchanged or increased. In patients without endoleaks on any imaging method, the sac diameter remained unchanged or decreased. Endoleaks disclosed by enhanced ultrasound alone, all type II, numbered 16 at 3 months, 6 at 12 months, and 3 at 24 months. In this group, the aneurysm diameter remained unchanged or increased. Enhanced ultrasound yielded 100% sensitivity in detecting endoleaks, but compared with CTA and MRA, all endoleaks detected by enhanced ultrasound alone were false positives (mean specificity 65%). Nevertheless, because changes in the postoperative aneurysm diameter were similar in patients with endoleaks detectable on CTA/MRA and on enhanced ultrasound ("true positives") and in those with endoleaks detectable only on enhanced ultrasound ("false positives"), some endoleaks were possibly "true positive" results. CONCLUSIONS: Enhanced ultrasound is a useful method in the long-term surveillance of endovascular aortic aneurysm repairs, possibly in association with CTA or MRA. Enhanced ultrasound also seems able to identify endoleaks missed by other imaging techniques, but this conclusion awaits further investigation.