Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial.

OBJECTIVE: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting. METHODS: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification). RESULTS: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P(interaction) = .008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%). CONCLUSION: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk.

Carotid artery disease: novel pathophysiological mechanisms identified by gene-expression profiling of peripheral blood.

OBJECT: The pathogenesis of carotid artery stenosis (CAS) as well as the mechanisms underlying the different localisation of the atherosclerotic lesions remains poorly understood. We used microarray technology to identify novel systemic mediators that could contribute to CAS pathogenesis. Moreover, we compared gene-expression profile of CAS with that of patients affected by abdominal aortic aneurysm (AAA), previously published by our group. METHODS AND RESULTS: By global gene-expression profiling in a pool of 10 CAS patients and 10 matched controls, we found 82 genes differentially expressed. Validation study in pools used for profiling and replication study in larger numbers of CAS patients (n = 40) and controls (n = 40) of 14 genes by real-time polymerase chain reaction (RT-PCR) confirmed microarray results. Fourteen out of 82 genes were similarly expressed in AAA patients. Gene ontology analysis identified a statistically significant enrichment in CAS of differentially expressed transcripts involved in immune response and oxygen transport. Whereas alteration of oxygen transport is a common tract of the two localisations, alteration of immune response in CAS and of lipid metabolic process in AAA represents distinctive tracts of the two atherosclerotic diseases. CONCLUSIONS: We describe the systemic gene-expression profile of CAS, which provides an extensive list of potential molecular markers.

Gene expression profiling of peripheral blood in patients with abdominal aortic aneurysm.

OBJECT: Abdominal aortic aneurysm (AAA) pathogenesis remains poorly understood. This study investigated the gene expression profile of peripheral blood from patients with AAA using microarray technology. METHODS AND RESULTS: We determined gene expression profiles in pooled RNA from 10 AAA patients and 10 matched controls with arrays representing 14,000 transcripts. Microarray data for selected genes were confirmed by real-time PCR in two different AAA (n=36) and control (n=36) populations and integrated with biochemical data. We identified 91 genes which were differentially expressed in AAA patients. Gene Ontology analysis indicated a significant alteration of oxygen transport (increased hemoglobin gene expression) and lipid metabolism [including monoglyceride lipase and low density lipoprotein receptor-related protein 5 (LRP5) gene]. LRP5 expression was associated inversely with serum lipoprotein(a) [Lp(a)] concentration. CONCLUSIONS: Increased expression of hemoglobin chain genes as well as of genes involved in erythrocyte mechanical stability were observed in the AAA RNA pools. The association between low levels of LRP5 gene expression and increased levels of Lp(a) in AAA patients suggests a potential role of LRP5 in Lp(a) catabolism. Our data underline the power of microarrays in identifying further molecular perturbations associated with AAA.

Dissection of the internal carotid artery. Report of one case.

Spontaneous dissection is a very rare occurrence in the pathology of the carotid artery. The case of a 40 year old male patient affected by dissection of the right carotid artery is described. The patient was admitted to Hospital but was not operated on since he showed progressive improvement of his symptoms under medical treatment and had a favourable outcome. The aetio-pathology and surgical indications of this rare condition is considered with extensive review of the literature on this subject.

Occlusive arterial disease in young patients.

All the young patients (under 40 years) affected by occlusive arterial disease observed at the Istituto di Clinica Chirurgica II, University of Milan, during the last eleven years have been reviewed. About one third of these patients is affected by a form of arteritis; the others demonstrate the typical pattern of early atherosclerosis or an indeterminate condition which may represent an atherosclerotic complication superimposed on a basic arteritic lesion. The available therapeutic procedures are examined. They show that atherosclerotic disease more frequently permits a surgical reconstruction. The average rate of amputation is about the same in the two considered forms, ranging close to 7-8%. The 10 year follow up of these groups of young patients allowed us to analyze the rate of progression and evolution of these morbid conditions and the influence of the most important risk factors.

Influence of the rupture site of abdominal aortic aneurysms with regard to postoperative survival rate.

This study presents an analysis of the influence of the site of rupture of abdominal aortic aneurysms on the postoperative survival rate. A series of 226 patients, who underwent emergency operations for ruptured aneurysms, is examined. The three most important methods of rupture are: (1) Retroperitoneal rupture: this type is associated with a very high mortality (52.8% in our experience), which reaches almost 75% when the posterior parietal peritoneum tears and massive intraperitoneal bleeding occurs. This mortality is related to the amount of blood loss, hypovolemic shock, the number of transfused blood units and, especially, to increasing renal insufficiency. (2) Rupture into the inferior vena cava: in this event the mortality rate it less severe (38.4% in our experience) and it is mostly related to the occurrence of an high output cardiac failure, as well as to oliguria or anuria following renal venous hypertension. (3) Enteric rupture: this is, in our experience, the most uncommon event. It carries a high mortality rate (50%). The copious bleeding, which is unrestricted in hollow organs, explains the dangerous hypovolemic shock, while massive blood reabsorption from the enteric tract leads to a renal insufficiency.

Nineteen year experience on the treatment of aneurysms of the abdominal aorta: a survey of 832 consecutive cases.

832 patients with abdominal aortic aneurysm were admitted to our Hospital, at the University of Milan, from 1965 to 1983. 238 patients were operated on as an emergency for rupture of the aneurysm while 541 underwent elective surgery. The overall postoperative mortality was 7% for the patients operated on electively and 54.3% for the ruptured aneurysm operated on as an emergency.

Intracavitary heart fibroma. A case of successful total excision.

Tumors of the heart are relatively rare events and fibromas represent no more than 5% of these. A central source of peripheral embolization suggests the possibility to kept in mind in the absence of other causes and is therefore worthy of closer investigation.

Pathological patterns and surgical treatment of renal artery stenosis in renovascular hypertension.

Atherosclerosis and dysplasia are the most common lesions affecting the renal artery, causing stenosis and renovascular hypertension. Surgical revascularization of the ischemic kidney in properly selected patients has proved to be the treatment of choice. The different pathological characters of dysplastic lesions are examined and compared with the ones of atherosclerotic disease, in surgically treated patients. Correlations between angiographic and histological aspects are also considered. The recognition of these different pathological patterns is important for the selection of the most suitable surgical procedures. The results of a personal technique of arterial reconstruction and angioplasty are reported.

Aneurysms of the renal artery.

The detection of renal artery aneurysms has greatly increased in the last years with the use of angiographic procedures and nowadays thanks to digital subtraction angiography routinely adopted in the diagnostic evaluation of patients affected by lesions at the renal artery level. This study reports the data of 31 renal artery aneurysms observed in 30 patients admitted to our Institute from 1970 to 1986. All the aneurysms were demonstrated by means of selective renal angiographies. Twenty-two patients out of 30 presented hypertension. In order to establish the possible role of the aneurysm in the genesis of hypertension, in all these cases the PRA was determined. In 27 patients a surgical procedure was adopted. This paper reviews our series of patients, analyzing the diagnostic procedures, the symptomatology presented with particular regard to the presence and the type of the associated hypertensive condition, the adopted therapeutic procedures and the results.

Ultrastructural (SEM and TEM) observations on arterial lesions of the human aorto-iliac area obtained at surgery from donors.

Ultrastructural observations on arterial lesions of the human aorto-iliac area obtained at surgery from donors after bilateral nephrectomy for kidney transplantation have revealed the presence of intimal fibro-muscular lesions, very similar to the "early lesions" of experimental animal models in the younger people of this group.

Ultramicroscopic observations on the pseudointimal coating in implanted dacron vascular grafts.

The common use of Dacron arterial prostheses produced enormous improvement in vascular surgery, yet some serious complications such as thrombosis or infection persist, which are connected to the utilization of this material. Light and electron microscopic studies may allow a better understanding of such complications. Scanning electron microscopy and semithick sections were used to examine dacron arterial prostheses removed for failure after long-term implantation. Semithick sections showed periprosthetic inflammatory reaction and the neointimal surface never exhibited a regular endothelial layer (at S.E.M.).

European multicentre experience with modular device (Medtronic Aneurx) for the endoluminal repair of infrarenal abdominal aortic aneurysms.

OBJECTIVE: Transfemoral endoluminal repair of AAA, introduced for the first time in the early 90's, has become a very promising alternative to conventional open repair and more and more centers are reporting satisfactory postoperative results in a high percentage of cases. Straight and bifurcated grafts represent the devices available on the market at present and aortic, as well as iliac aneurysmal lesions can be safely treated through a transfemoral approach. The possibility to indicate an endovascular AAA repair is related to the configuration (length and size) of the proximal and distal necks, tortuosity and calcification of the access arteries and to vascular and non-vascular comorbidities, which afflict the patients. The objective of our study was to evaluate the early and late postoperative results in a series of patients affected by infrarenal AAA, who underwent endoluminal repair. MATERIALS AND METHODS: From December 1996 to 31 October 1997 in 5 different European Centers, 100 Medtronic AneuRx bifurcated stent grafts were implanted for infrarenal abdominal aortic aneurysms. The diameter of the AAA varied from 33 to 77 mm (average 64 mm) and the mean age of the patients was 70.8 years (51-87 years). In one patient with a 33 mm diameter of the aneurysm, the surgical procedure was indicated because the size of the aneurysm had increased by 5 mm, compared to the previous control made 2 months before. In addition the aneurysm became symptomatic. There were 92 male and 8 female patients. The average time of the surgical procedure was 150 minutes (75-480 minutes) with an average blood loss of 570 ml (100-2,600 ml).

[Endovascular treatment of pararenal aortic aneurysms]. / Il trattamento endovascolare degli aneurismi dell'aorta pararenale.

Endovascular procedures have emerged as an attractive alternative technique for the repair of abdominal aortic aneurysms with an increasing popularity and diffusion. Even if technology progresses are developing more and more efficient grafts and devices, at the moment the endovascular treatment is still not applicable to all patients. The most common reason for patient exclusion remains an unsuitable proximal implantation site. Endografts with suprarenal fixation were studied for solving the problem of the proximal neck but results seem to be not so encouraging. At the moment pararenal aortic aneurysms, involving ostia of renal or visceral arteries, are usually excluded from endovascular treatment. The solution could be a custom-made graft for each single patient, with fenestrations or branches for renal and visceral arteries. The first clinical use of a fenestrated graft was by Park in 1996 and some groups are now studying different kinds of grafts, both in experimental and clinical studies, which are opening attractive new possibilities. At present results are only preliminary but this would be the first step towards the potential substitution of the entire aorta through endovascular techniques.

Processed bovine pericardium as patch angioplasty for carotid endarterectomy: a preliminary report.

Although the routine use of a patch for closure of the arteriotomy after carotid endarterectomy is still debated, patch angioplasty is frequently used to avoid residual stenosis and to lower the incidence of later restenosis. Several materials are widely used for carotid patching, notably, autologous vein, Dacron and polytetrafluorethylene (PTFE). During recent years a heterologous stabilized graft made from bovine pericardium has been introduced. This paper reports the authors' experience of 52 carotid endarterectomies in which a patch of bovine pericardium was used to close the arteriotomy. The patients were followed with colour-duplex scanning over 12-30 months. This biograft did not require preclotting and proved to be easy to suture. Follow-up did not uncover any complications related to graft use. Although this is a preliminary report, it is concluded that bovine pericardium is a promising material for carotid patch angioplasty.

Processed bovine pericardium as patch angioplasty for carotid endarterectomy: a preliminary report.

Although the routine use of a patch for closure of the arteriotomy after carotid endarterectomy is still debated, patch angioplasty is frequently used to avoid residual stenosis and to lower the incidence of later restenosis. Several materials are widely used for carotid patching, notably, autologous vein, Dacron and polytetrafluorethylene (PTFE). During recent years a heterologous stabilized graft made from bovine pericardium has been introduced. This paper reports the authors' experience of 52 carotid endarterectomies in which a patch of bovine pericardium was used to close the arteriotomy. The patients were followed with colour-duplex scanning over 12-30 months. This biograft did not require preclotting and proved to be easy to suture. Follow-up did not uncover any complications related to graft use. Although this is a preliminary report, it is concluded that bovine pericardium is a promising material for carotid patch angioplasty.

The ICAROS registry of carotid artery stenting. Imaging in Carotid Angioplasties and Risk of Stroke.

ICAROS (Imaging in Carotid Angioplasties and Risk Of Stroke) is a multicenter international registry of carotid artery stenting designed to determine the criteria for identifying patients at higher or lower risk of periprocedural stroke and restenosis at 1 year. The aim of the registry is to improve patient selection and consequently reduce the risk of cerebral embolization during carotid stenting. The registry is open to all interventionists performing carotid stenting, and the participants are free to apply their own endovascular techniques and devices, including cerebral protection mechanisms. All cerebral ischemic events following the procedure will be reported. Follow-up surveillance to 1 year will include periodic duplex scanning and neurological examinations. Echographic plaque images will be standardized for comparison, processed for echodensity, and analyzed by computer at the Registry Center. Correlation will be investigated between the echographic index (gray-scale median) and the risk of embolism and outcome of carotid stenting.

Spontaneous aorto-caval fistulas from ruptured abdominal aortic aneurysms.

Thirty-six cases of abdominal aortic aneurysms rupturing into the vena cava and two iliac aneurysms rupturing into iliac veins are reported. This group represents 10% of the total number of observed ruptured abdominal aortic aneurysms (388). Such a condition is therefore quite rare but should be considered positively because the reported mortality rate is less than with ruptured aneurysms in general. Nevertheless, a spontaneous aorto-caval fistula is responsible for a critical haemodynamic deterioration and sudden worsening of the general condition of the patient and therefore prompt surgical repair is mandatory. The overall mortality rate in our series was 21% (8 cases).