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.

[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.

Impact of perioperative haemodynamic monitoring on cardiac morbidity after major vascular surgery in low risk patients. A randomised pilot trial.

OBJECTIVE: to evaluate whether perioperative haemodynamic optimisation influences outcome from infrarenal abdominal aortic aneurysm repair. METHODS: a consecutive series of 100 eligible patients were randomised to either haemodynamic optimisation through the use of a pulmonary artery catheter (CI > 3.0 l/min/sqm, PWP > 10 and <18 mmHg, SVR <1450 dyne/sec/cm(-5), DO(2)> 600 ml/min/sqm) or conventional treatment. RESULTS: there were no differences in terms of in-hospital mortality, cardiovascular morbidity, postoperative renal failure or duration of hospital stay between the groups. CONCLUSIONS: in this study perioperative haemodynamic optimisation was not beneficial.

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.

Endoluminal repair of infrarenal abdominal aortic aneurysms using a modular stent-graft: one-year clinical results from a European multicentre trial.

This is a report of a prospective study to evaluate the safety and efficacy of the Medtronic AneuRx stent-graft. Patients with an infrarenal aneurysm with a proximal neck length of greater than 10 mm and a neck diameter not greater than 26 mm and iliac artery diameters of at least 6 mm were accepted for endovascular repair using the Medtronic AneuRx modular stent-graft. A total of 104 patients were included in the study. Transfemoral placement of the bifurcated stent-graft was successful in 102 of 104 patients. Two conversions were performed. The mean operating time was 148 min (range 75-480) and the mean blood loss was 605 ml (range 100-2900). The mean follow-up was 15 months (range 12-21). Complications were rare and no kinking or migration occurred. At follow-up, four endoleaks persisted after 12 months. The Medtronic AneuRx stent-graft is a safe and efficacious alternative to open abdominal aortic aneurysm repair with excellent early results.

Computer analysis of ultrasonic plaque echolucency in identifying high risk carotid bifurcation lesions.

OBJECTIVES: to confirm that plaque echogenicity evaluated by computer analysis, as suggested by preliminary studies, can identify plaques associated with a high incidence of strokes. MATERIALS AND METHODS: a series of 96 patients with carotid stenosis in the range of 50-99% were studied retrospectively (41 with TIAs and 55 asymptomatic). Carotid plaque echogenicity was evaluated using a computerised measurement of the median grey scale value (GSM). All patients had a CT brain scan to determine the presence of infarction in the carotid territory. RESULTS: the incidence of ipsilateral brain CT infarctions was 16% in the asymptomatic and 32% in the symptomatic plaques (p =0.076). It was 20% for <70% stenosis and 25% for >70% stenosis (p =0.52). It was 9% for plaques which had a GSM >50 and 40% in those with GSM <50 (p <0.001) with a relative risk of 4.6 (95% CI 1.8 to 11.6). CONCLUSIONS: the results confirm that computer analysis of plaque echogenicity is better than the degree of stenosis in identifying plaques associated with an increased incidence of CT brain-scan infarction and consequently useful for identifying individuals at high risk of stroke. What is required is a form of image standardisation in order to apply this method to natural history studies with stroke as the endpoint.

[Transluminal treatment in aneurysm of the abdominal aorta. Role of diagnostic imaging]. / Trattamento transluminale degli aneurismi dell'aorta addominale. Ruolo della diagnostica per immagini.

PURPOSE: To emphasize the importance of diagnostic imaging: a) in the selection of patients to be treated with the transluminal approach b) during stent-graft positioning c) in the follow-up of treated patients. MATERIAL AND METHODS: From January 1997 to May 1998, twenty-five patients with abdominal aortic aneurysms (AAA) were treated with transfemoral stent-grafts (AneuRx Medtronic). All patients were submitted to a preoperative study including digital angiography (DSA) and Spiral CT. Intraoperatively they underwent DSA and intravascular ultrasound (IVUS). Follow-up was performed with Spiral CT. RESULTS: Twenty-four bifurcated and one straight device were inserted in twenty-five patients with AAA. In two cases it was impossible to position the endoprosthesis due to narrow or tortuous artery access. Following the intention to treat criteria, the technical success rate was 92.5%. All the stents were patent and no dislodgement was observed at follow-up. Partial thrombosis of the stent was observed in three patients. Owing to incomplete distal covering, early endoleak occurred in one patient with an aortoiliac aneurysm; the positioning of two cuffs allowed a successful outcome. CT examination performed 6 months after positioning revealed the presence of endoleaks in three patients, due to persistence of lumbar and inferior mesenteric artery patency. The AAA was no more appreciable in five of the ten patients submitted to CT follow-up one year after the procedure. In three of ten cases it was reduced in size and in two patients there was no change. DISCUSSION: Spiral CT plays a basic role in the selection of patients because it helps assess the length and diameter of the proximal neck, thus permitting to choose the device to be inserted. Preoperative DSA is mandatory in the evaluation of size and tortuosity of the iliac arteries. IVUS allows to monitor the site of delivery during the maneuver and to make the final measurements while DSA plays a role in checking the correct positioning of the device and excluding the presence of endoleaks at the end of the procedure. Late follow-up with Spiral CT aims at demonstrating possible malfunctioning of the endoprosthesis and confirms the definitive exclusion of AAA. CONCLUSIONS: Diagnostic imaging plays a basic role in the endovascular treatment of AAA, much more than that required for traditional surgical treatment. In particular, pretreatment planning is critical and requires sophisticated imaging including Spiral CT with 3D reconstruction and angiographic evaluation using catheters with calibrated markers.

Carotid plaque characterization using digital image processing and its potential in future studies of carotid endarterectomy and angioplasty.

PURPOSE: To corroborate the validity of a computerized methodology for evaluating carotid lesions at risk for stroke based on plaque echogenicity. METHODS: The records of 96 carotid endarterectomy patients (59 men; median age 69.5 years, range 52 to 83) with stenoses > 50% were studied retrospectively. Forty-one patients (43%) had been symptomatic preoperatively. All patients had undergone computed tomography (CT) to detect infarction in the carotid territory and a duplex scan to measure carotid stenosis. Plaque echogenicity was analyzed by computer, expressing the echodensity in terms of the gray scale median (GSM). The incidence of CT-documented cerebral infarction was analyzed in relation to symptomatology, percent stenosis, and echodensity. RESULTS: Symptoms correlated well with CT evidence of brain infarction: 32% of symptomatic patients had a positive CT scan versus 16% for asymptomatic plaques (p = 0.076). The mean GSM value was 56 +/- 14 for plaques associated with negative CT scans and 38 +/- 13 for plaques from patients with positive scans (p < 0.0001). However, there was no difference in the GSM value between plaques with > or < 70% stenosis. Furthermore, the incidence of CT infarction was 40% in the cerebral territory of carotid plaques with a GSM value < 50 and only 9% in those with a GSM > 50 (p < 0.001). CONCLUSIONS: Computerized analysis of plaque echogenicity appears to provide clinically useful data that correlates with the incidence of cerebral infarction and symptoms. This method of analyzing plaque echolucency could be used as a screening tool for carotid stent studies to identify high-risk lesions better suited to conventional surgical treatment.

Fresh and cryopreserved arterial homografts in the treatment of prosthetic graft infections: experience of the Italian Collaborative Vascular Homograft Group.

Following the experience of cardiac surgeons with homografts in the treatment of infective aortic valve endocarditis, cardiovascular surgeons have investigated in situ revascularization by means of homografts in the management of vascular prosthetic graft infections. Preliminary results are encouraging, but their late fate in long-term follow-up and the influence of preservation techniques are still under investigation. This article reports the experience of the Italian Collaborative Vascular Homograft Group, with the use of fresh and cryopreserved arterial homografts for the treatment of prosthetic graft infections. Between March 1994 and December 1996, 44 patients with prosthetic graft infection were treated with homografts (13 preserved at 4 degrees C, 31 cryopreserved). The mean age of the patients was 65 years. Emergency surgical procedures were performed in eight patients (18%). Sepsis was diagnosed in 11 patients, aortoenteric fistula in 13, and false aneurysms in 10. Staphylococcus was the main cause of infection. The types of vascular reconstruction with homograft were: 32 aortobifemoral, 3 aortoaortic, 2 iliofemoral, 4 peripheral, and 3 axillobifemoral. Human lymphocyte antigen (HLA) and antibody (ABO) blood group system compatibility between donors and recipients was not respected. The mean duration of follow-up was 15 months (range 1-33). Clinical and duplex scanning evaluations were routinely performed. Computed tomography (CT) or magnetic resonance (MR) scanning or arteriography were performed on the basis of duplex scanning results. There were six deaths during the early postoperative period (30 days) with a mortality rate of 13.6%. During the follow-up there were five late deaths with a mortality rate of 11.4%. Eight patients had graft occlusion. Three cases were successfully treated with thrombectomy. Two cases were successfully treated with femoropopliteal bypass with autologous vein. In three cases leg amputation was necessary. The results of fresh and cryopreserved homograft were compared. No significative differences of early postoperative mortality, late mortality, homograft related mortality, and graft occlusion were observed. We have evaluated the actuarial survival of the patients and the actuarial patency of the homografts on the aortoiliac reconstructions. Twelve months after the surgery the actuarial survival of the patients was 73% and the actuarial patency of the homografts was 56%. In our preliminary experience, we have not observed any significant difference in terms of clinical outcome by using fresh rather than cryopreserved homografts. In the near future it will be our policy to employ only cryopreserved homografts. Moreover, we will extend vessel harvesting to nonheart-beating donors, thus maximizing retrieval. The aforementioned solutions will supply the best graft availability to obtain dimensional and ABO compatibility between donors and recipients.

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).

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.

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).