Clinical experience with the use of bivalirudin in a large population undergoing endovascular abdominal aortic aneurysm repair

PURPOSE: To retrospectively evaluate the safety and effectiveness of the use of bivalirudin, a direct thrombin antagonist, compared with unfractionated heparin in endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: Between March 1994 and September 2007, 740 consecutive patients (mean age, 75.7 y +/- 7.7; 69 women) underwent elective EVAR for infrarenal abdominal aortic aneurysm. Bivalirudin was used in 98 of these 740 (13.2%) and unfractioned heparin was used in the other 642 (86.8%). Complications were classified according to the Society of Vascular Surgery/International Society for Cardiovascular Surgery criteria. Major bleeding was defined as clinically overt blood loss resulting in a decrease of hemoglobin of more than 3 g/dL, any decrease in hemoglobin of more than 4 g/dL, transfusion of 2 U or more of red blood cells, or intracranial or retroperitoneal hemorrhage. RESULTS: Grade 1 major complications were observed in 161 of 642 patients (25.2%) in the heparin group and 12 of 98 patients (12.2%) in the bivalirudin group (P = .0046), whereas the incidences of grade 3 major complications were not significantly different between groups (P = .57). The rate of total complications was higher in the heparin group than in the bivalirudin group (247 of 642 [38.5%] vs 21 of 98 [21.4%]; P = .001). Major bleeding occurred in 10 of 98 patients (10.2%) receiving bivalirudin and in 91 of 642 patients (14.2%) receiving heparin (P = .34). One of 21 major complications (4.76%) in the bivalirudin group and 12 of 247 major complications (4.86%) in the heparin group were attributable to thrombosis (P = 1.0). CONCLUSIONS: Bivalirudin is a safe and feasible alternative to unfractionated heparin in patients undergoing EVAR.

Endoleak detection with CT angiography in an abdominal aortic aneurysm phantom: effect of tube energy, simulated patient size, and physical properties of endoleaks

To analyze the detection of endoleaks with low-tube-voltage computed tomographic (CT) angiography.

True aneurysm of the peripheral pulmonary artery due to necrotizing giant cell arteritis

Pulmonary artery aneurysm in adults is a rare diagnosis. Most cases described in the literature are either associated with congenital heart disease or pulmonal arterial hypertension, respectively, or are not true aneurysms but rather pseudoaneurysms, which are usually iatrogenic. We present the case of a 68-year old female patient with the incidental finding of a true aneurysm of the right peripheral pulmonary artery with a maximum diameter of 4 cm. With increasing aneurysm diameter over time, the decision for a surgical resection was made. Complete resection of the aneurysm including lower lobe resection was performed. Histopathological examination showed necrotizing giant cell arteritis as the underlying cause. The postoperative course was uneventful and no signs of further disease activity were detected. To our knowledge, this is the first reported case of a pulmonary artery aneurysm caused by giant cell arteritis, whereas it should be noted that the distinction between Takayasu arteritis and giant cell arteritis is not clearly defined. Considering the high mortality associated with aneurysm rupture, surveillance is advocated for small aneurysms, whereas for larger aneurysms and those showing signs of progression in size despite medical therapy or even dissection, surgical intervention should be considered.

Sequencing of TGF-beta pathway genes in familial cases of intracranial aneurysm.

BACKGROUND AND PURPOSE: Familial aggregation of intracranial aneurysms (IA) strongly suggests a genetic contribution to pathogenesis. However, genetic risk factors have yet to be defined. For families affected by aortic aneurysms, specific gene variants have been identified, many affecting the receptors to transforming growth factor-beta (TGF-beta). In recent work, we found that aortic and intracranial aneurysms may share a common genetic basis in some families. We hypothesized, therefore, that mutations in TGF-beta receptors might also play a role in IA pathogenesis. METHODS: To identify genetic variants in TGF-beta and its receptors, TGFB1, TGFBR1, TGFBR2, ACVR1, TGFBR3, and ENG were directly sequenced in 44 unrelated patients with familial IA. Novel variants were confirmed by restriction digestion analyses, and allele frequencies were analyzed in cases versus individuals without known intracranial disease. Similarly, allele frequencies of a subset of known SNPs in each gene were also analyzed for association with IA. RESULTS: No mutations were found in TGFB1, TGFBR1, TGFBR2, or ACVR1. Novel variants identified in ENG (p.A60E) and TGFBR3 (p.W112R) were not detected in at least 892 reference chromosomes. ENG p.A60E showed significant association with familial IA in case-control studies (P=0.0080). No association with IA could be found for any of the known polymorphisms tested. CONCLUSIONS: Mutations in TGF-beta receptor genes are not a major cause of IA. However, we identified rare variants in ENG and TGFBR3 that may be important for IA pathogenesis in a subset of families.

State-of-the-art aortic imaging: Part II - applications in transcatheter aortic valve replacement and endovascular aortic aneurysm repair.

Transcatheter aortic valve replacement (TAVR) as well as thoracic and abdominal endovascular aortic repair (TEVAR and EVAR) rely on accurate pre- and postprocedural imaging. This review article discusses the application of imaging, including preprocedural assessment and measurements as well as postprocedural imaging of complications. Furthermore, the exciting perspective of computational fluid dynamics (CFD) based on cross-sectional imaging is presented. TAVR is a minimally invasive alternative for treatment of aortic valve stenosis in patients with high age and multiple comorbidities who cannot undergo traditional open surgical repair. Given the lack of direct visualization during the procedure, pre- and peri-procedural imaging forms an essential part of the intervention. Computed tomography angiography (CTA) is the imaging modality of choice for preprocedural planning. Routine postprocedural follow-up is performed by echocardiography to confirm treatment success and detect complications. EVAR and TEVAR are minimally invasive alternatives to open surgical repair of aortic pathologies. CTA constitutes the preferred imaging modality for both preoperative planning and postoperative follow-up including detection of endoleaks. Magnetic resonance imaging is an excellent alternative to CT for postoperative follow-up, and is especially beneficial for younger patients given the lack of radiation. Ultrasound is applied in screening and postoperative follow-up of abdominal aortic aneurysms, but cross-sectional imaging is required once abnormalities are detected. Contrast-enhanced ultrasound may be as sensitive as CTA in detecting endoleaks.

To see or not to see – Ambiguous findings on post-mortem cross-sectional imaging in a case of ruptured abdominal aortic aneurysm

We present a case of a ruptured abdominal aortic aneurysm (AAA) with ambiguous accessory findings on post-mortem computed-tomography (PMCT), post-mortem magnetic resonance (PMMR) imaging, and PMCT-angiography (PMCTA) suggestive of thoracic aortic dissection. The diagnosis of ruptured AAA was confirmed by autopsy; however, there was no aortic dissection. The imaging findings that mimicked the presence of aortic dissection might have been an atypical presentation of post-mortem clotting or sedimentation. This case is an ideal example to illustrate benefits, limitations, and challenges of post-mortem cross-sectional imaging. It serves as a reminder that both, training as well as correlation of imaging findings with autopsy are fundamental to improve our understanding of radiologic findings on post-mortem cross-sectional imaging.

Outcomes after endovascular or open repair for degenerative descending thoracic aortic aneurysm using linked hospital data.

BACKGROUND The population-based effectiveness of thoracic endovascular aortic repair (TEVAR) versus open surgery for descending thoracic aortic aneurysm remains in doubt. METHODS Patients aged over 50 years, without a history of aortic dissection, undergoing repair of a thoracic aortic aneurysm between 2006 and 2011 were assessed using mortality-linked individual patient data from Hospital Episode Statistics (England). The principal outcomes were 30-day operative mortality, long-term survival (5 years) and aortic-related reinterventions. TEVAR and open repair were compared using crude and multivariable models that adjusted for age and sex. RESULTS Overall, 759 patients underwent thoracic aortic aneurysm repair, mainly for intact aneurysms (618, 81·4 per cent). Median ages of TEVAR and open cohorts were 73 and 71 years respectively (P < 0·001), with more men undergoing TEVAR (P = 0·004). For intact aneurysms, the operative mortality rate was similar for TEVAR and open repair (6·5 versus 7·6 per cent; odds ratio 0·79, 95 per cent confidence interval (c.i.) 0·41 to 1·49), but the 5-year survival rate was significantly worse after TEVAR (54·2 versus 65·6 per cent; adjusted hazard ratio 1·45, 95 per cent c.i. 1·08 to 1·94). After 5 years, aortic-related mortality was similar in the two groups, but cardiopulmonary mortality was higher after TEVAR. TEVAR was associated with more aortic-related reinterventions (23·1 versus 14·3 per cent; adjusted HR 1·70, 95 per cent c.i. 1·11 to 2·60). There were 141 procedures for ruptured thoracic aneurysm (97 TEVAR, 44 open), with TEVAR showing no significant advantage in terms of operative mortality. CONCLUSION In England, operative mortality for degenerative descending thoracic aneurysm was similar after either TEVAR or open repair. Patients who had TEVAR appeared to have a higher reintervention rate and worse long-term survival, possibly owing to cardiopulmonary morbidity and other selection bias.

Intracranial Aneurysm Rupture Is Predicted by Measures of Solar Activity.

OBJECTIVE The cause precipitating intracranial aneurysm rupture remains unknown in many cases. It has been observed that aneurysm ruptures are clustered in time, but the trigger mechanism remains obscure. Because solar activity has been associated with cardiovascular mortality and morbidity, we decided to study its association to aneurysm rupture in the Swiss population. METHODS Patient data were extracted from the Swiss SOS database, at time of analysis covering 918 consecutive patients with angiography-proven aneurysmal subarachnoid hemorrhage treated at 7 Swiss neurovascular centers between January 1, 2009, and December 31, 2011. The daily rupture frequency (RF) was correlated to the absolute amount and the change in various parameters of interest representing continuous measurements of solar activity (radioflux [F10.7 index], solar proton flux, solar flare occurrence, planetary K-index/planetary A-index, Space Environment Services Center [SESC] sunspot number and sunspot area) using Poisson regression analysis. RESULTS During the period of interest, there were 517 days without recorded aneurysm rupture. There were 398, 139, 27, 12, 1, and 1 days with 1, 2, 3, 4, 5, and 6 ruptures per day. Poisson regression analysis demonstrated a significant correlation of F10.7 index and RF (incidence rate ratio [IRR] = 1.006303; standard error (SE) 0.0013201; 95% confidence interval (CI) 1.003719-1.008894; P < 0.001), according to which every 1-unit increase of the F10.7 index increased the count for an aneurysm to rupture by 0.63%. A likewise statistically significant relationship of both the SESC sunspot number (IRR 1.003413; SE 0.0007913; 95% CI 1.001864-1.004965; P < 0.001) and the sunspot area (IRR 1.000419; SE 0.0000866; 95% CI 1.000249-1.000589; P < 0.001) emerged. All other variables analyzed showed no significant correlation with RF. CONCLUSIONS We found greater radioflux, SESC sunspot number, and sunspot area to be associated with an increased count of aneurysm rupture. The clinical meaningfulness of this statistical association must be interpreted carefully and future studies are warranted to rule out a type-1 error.

Is intracranial aneurysm rupture related to solar activity?

Objective: A number of intrinsic and extrinsic risk factors for the rupture of intracranial aneurysms have been identified. Still, the cause precipitating aneurysm rupture remains unknown in many cases. In addition, it has been observed that aneurysm ruptures are clustered in time but the trigger mechanism remains obscure. As solar activity has been associated with cardiovascular mortality and morbidity we decided to study ist association to aneurysm rupture in the Swiss population. Method: Patient data was extracted from the Swiss SOS database, at time of analysis covering 918 patients with angiography-proven aSAH treated at seven Swiss neurovascular centers between 01/01/2009 – 12/31/2011. The number of aneurysm rupture per day, week, month (Daily/Weekly/Monthly Rupture Frequency = RF) was measured and correlated to the absolute amount and the change in various parameters of interest representing continuous measurements of solar activity (radioflux (F10.7 index), solar proton flux, solar flare occurrence, planetary K-index/planetary A-index) using Poisson regression analysis. Results: Of a consecutive series of 918 cases of SAH, precise determination of the date of symptom onset was possible in 816 (88.9%). During the period of interest there were 517 days without recorded aneurysm rupture. There were 398, 139, 27 and 12 days with 1, 2, 3, and 4 ruptures per day. Five or 6 ruptures were only noted on a single day each. Poisson regression analysis demonstrated a significant correlation of F10.7 index and aneurysm rupture (incidence rate ratio (IRR) = 1.006303; standard error (SE) 0.0013201; 95% confidence interval (CI) 1.003719 – 1.008894; p<0.001), according to which every 1-unit increase of the F10.7 index increased the count for an aneurysm to rupture by 0.63%. As the F10.7 index is known to correlate well with the Space Environment Services Center (SESC) sunspot number, we performed additional analyses on SESC sunspot number and sunspot area. Here, a likewise statistically significant relationship of both the SESC sunspot number (IRR 1.003413; SE 0.0007913; 95%CI 1.001864 – 1.004965; p<0.001) and the sunspot area (IRR 1.000419; SE 0.0000866; 95%CI 1.000249 – 1.000589; p<0.001) emerged. All other variables analyzed showed no correlation with RF. Conclusions: Using valid methods, we found higher radioflux, sunspot number and sunspot area to be associated with an increased count of aneurysm rupture. Since we were using rupture frequencies rather than incidences and because we cannot explain the physiological basis of this statistical association, the clinical meaningfulness of this statistical association must be interpreted carefully. Future studies are warranted to rule out a type-1 error.

Dissecting abdominal aortic aneurysm in Ang II-infused mice: suprarenal branch ruptures and apparent luminal dilatation.

AIMS In this work, we provide novel insight into the morphology of dissecting abdominal aortic aneurysms in angiotensin II-infused mice. We demonstrate why they exhibit a large variation in shape and, unlike their human counterparts, are located suprarenally rather than infrarenally. METHODS AND RESULTS We combined synchrotron-based, ultra-high resolution ex vivo imaging (phase contrast X-Ray tomographic microscopy) with in vivo imaging (high-frequency ultrasound and contrast-enhanced micro-CT) and image-guided histology. In all mice, we observed a tear in the tunica media of the abdominal aorta near the ostium of the celiac artery. Independently we found that, unlike the gradual luminal expansion typical for human aneurysms, the outer diameter increase of angiotensin II-induced dissecting aneurysms in mice was related to one or several intramural haematomas. These were caused by ruptures of the tunica media near the ostium of small suprarenal side branches, which had never been detected by the established small animal imaging techniques. The tear near the celiac artery led to apparent luminal dilatation, while the intramural haematoma led to a dissection of the tunica adventitia on the left suprarenal side of the aorta. The number of ruptured branches was higher in those aneurysms that extended into the thoracic aorta, which explained the observed variability in aneurysm shape. CONCLUSION Our results are the first to describe apparent luminal dilatation, suprarenal branch ruptures, and intramural haematoma formation in dissecting abdominal aortic aneurysms in mice. Moreover, we validate and demonstrate the vast potential of phase contrast X-ray tomographic microscopy in cardiovascular small animal applications.

High-flow venous pouch aneurysm in the rabbit carotid artery: A model for large aneurysms.

BACKGROUND AND PURPOSE Currently one of the most widely used models for the development of endovascular techniques and coiling devices for treatment of aneurysm is the elastase-induced aneurysm model in the rabbit carotid artery. Microsurgical techniques for creating an aneurysm with a venous pouch have also been established, although both techniques usually result in aneurysms less than 1 cm in diameter. We investigated whether an increase in blood flow toward the neck would produce larger aneurysms in a microsurgical venous pouch model. MATERIALS AND METHODS Microsurgical operations were performed on 11 New Zealand white rabbits. Both carotid arteries and the right jugular vein were dissected, and the right carotid artery was temporarily clipped followed by an arteriotomy. The left carotid artery was also clipped proximally, ligated distally, and sutured onto the proximal half of the arteriotomy in the right carotid artery. The venous graft was sutured onto the distal half of the arteriotomy. Digital subtraction angiography was also performed. RESULTS Angiography showed patent anastomosed vessels and aneurysms in the seven surviving rabbits. Mean aneurysm measurements among surviving rabbits with patent vessels were: 13.9 mm length, 9.3 mm width, and neck diameter 4.7 mm. The resulting mean aspect ratio was 3.35 and the mean bottleneck ratio was 3.05. CONCLUSION A large venous graft and increased blood flow toward the base of the aneurysm seem to be key factors in the creation of large venous pouch aneurysms. These large aneurysms allow testing of endovascular devices designed for large and giant aneurysms.

Dissecting abdominal aortic aneurysm in Angiotensin II-infused mice: the importance of imaging

INTRODUCTION Since the initial publication in 2000, Angiotensin II-infused mice have become one of the most popular models to study abdominal aortic aneurysm in a pre-clinical setting. We recently used phase contrast X-ray based computed tomography to demonstrate that these animals develop an apparent luminal dilatation and an intramural hematoma, both related to mural ruptures in the tunica media in the vicinity of suprarenal side branches. AIMS The aim of this narrative review was to provide an extensive overview of small animal applicable techniques that have provided relevant insight into the pathogenesis and morphology of dissecting AAA in mice, and to relate findings from these techniques to each other and to our recent PCXTM-based results. Combining insights from recent and consolidated publications we aimed to enhance our understanding of dissecting AAA morphology and anatomy. RESULTS AND CONCLUSION We analyzed in vivo and ex vivo images of aortas obtained from macroscopic anatomy, histology, high-frequency ultrasound, contrast-enhanced micro-CT, micro-MRI and PCXTM. We demonstrate how in almost all publications the aorta has been subdivided into a part in which an intact lumen lies adjacent to a remodeled wall/hematoma, and a part in which elastic lamellae are ruptured and the lumen appears to be dilated. We show how the novel paradigm fits within the existing one, and how 3D images can explain and connect previously published 2D structures. We conclude that PCXTM-based findings are in line with previous results, and all evidence points towards the fact that dissecting AAAs in Angiotensin II-infused mice are actually caused by ruptures of the tunica media in the immediate vicinity of small side branches.

Clipping techniques in cerebral aneurysm surgery

The history of cerebral aneurysm surgery owes a great tribute to the tenacity of pioneering neurosurgeons who designed and developed the clips used to close the aneurysms neck. However, until the beginning of the past century, surgery of complex and challenging aneurysms was impossible due to the lack of surgical microscope and commercially available sophisticated clips. The modern era of the spring clips began in the second half of last century. Until then, only malleable metal clips and other non-metallic materials were available for intracranial aneurysms. Indeed, the earliest clips were hazardous and difficult to handle. Several neurosurgeons put their effort in developing new clip models, based on their personal experience in the treatment of cerebral aneurysms. Finally, the introduction of the surgical microscope, together with the availability of more sophisticated clips, has allowed the treatment of complex and challenging aneurysms. However, today none of the new instruments or tools for surgical therapy of aneurysms could be used safely and effectively without keeping in mind the lessons on innovative surgical techniques provided by great neurovascular surgeons. Thanks to their legacy, we can now treat many types of aneurysms that had always been considered inoperable. In this article, we review the basic principles of surgical clipping and illustrate some more advanced techniques to be used for complex aneurysms.