Postoperative outcomes in intimal aortic angiosarcoma: a case report and review of the literature.

Intimal angiosarcoma is a most unexpected cause of aortic occlusion. We present the case of a 74-year-old woman with intimal angiosarcoma that manifested with the triad of congestive heart failure, acute renal failure, and abdominal angina. A review of the literature and discussion of postoperative outcomes follows.

Endoluminal intervention for limb salvage after failed lower extremity bypass graft.

BACKGROUND: Lower extremity bypass graft failure in patients with limb-threatening ischemia carries an amputation rate of greater than 50%. Redo bypass is often difficult due to the lack of conduit, adequate target, or increased surgical risk, and resultant limb salvage rates are reduced significantly compared with the index operation. We set forth to investigate whether endovascular treatment in this setting would result in an acceptable limb salvage rate. METHODS: A single-institution, retrospective review from June 2004 to December 2007 of patients with failed grafts who underwent endovascular treatment with percutaneous balloon angioplasty (PTA) of their native circulation was performed. Stents were selectively used in cases of post-PTA residual stenosis or flow-limiting dissection. Technical success was defined as a residual stenosis less than 30%. Percutaneous attempts at bypass graft salvage were excluded. Demographics, comorbidities, procedural data, and follow-up information were recorded. Descriptive, logistic regression and life-table analyses were performed. RESULTS: Twenty-four lower extremities were treated in 23 patients with failed bypass grafts. Average patency of the index graft before failure was 647 days (range 5-2758). Mean age was 68 years (range 51-85), 62% were male and 81% had diabetes mellitus (DM). 87.5% of limbs treated had TransAtlantic InterSociety Consensus (TASC) C and D lesions and 62% had multiple lesions. Technical success was achieved in 100%. Mean follow-up was 25.6 months. At follow-up, there were 17 PTA failures, which resulted in: amputation (4), redo-bypass (3), and redo-PTA (11). Freedom from surgical revision and PTA failure was 89% (+/- 0.07 SE) and 28% (+/- 0.09 SE) respectively. PTA secondary patency was 72% (+/- 0.09 SE) and limb-salvage was 81% (+/- 0.08 SE) at both 12 and 24 months. Overall survival was 83% (+/- 0.07 SE) and 77% (+/- 0.09 SE) at 12 and 24 months, respectively. CONCLUSIONS: Endovascular treatment of patients with previously failed bypass grafts results in a high rate of limb salvage. This is a reasonable option in selected patients and the primary choice in those with poor targets, conduit, or excess surgical risk. Endovascular salvage should be considered before proceeding to primary amputation.

Distal digital embolization from a thrombosed aneurysmal hemodialysis arteriovenous fistula: the benefit of a hybrid approach.

Aneurysmal degeneration of a hemodialysis arteriovenous fistula (AVF) is common; however, distal digital embolization from an AVF is extremely rare. Even though the ultimate fate of all arteriovenous hemodialysis access is thrombosis with minimal consequences, dislodgement of thrombus at the proximal anastomosis could lead to ischemia of the distal arterial circulation. We here present a case of a renal transplant patient with a thrombosed aneurysmal AVF who presented with acute digital ischemia successfully treated with combination catheter-directed thrombolysis and open repair. No similar report was found describing this entity treated with this approach.

Predictors of failure after angioplasty of infrainguinal vein bypass grafts.

OBJECTIVE: Percutaneous transluminal angioplasty (PTA) has had an expanding role as primary therapy for vein graft stenosis with variable results. The aim of this study is to identify patient and graft characteristics predictive of failure after PTA of infrainguinal vein grafts. METHODS: Retrospective review from Jan 2004 to Mar 2007 of patients undergoing angioplasty for failing grafts. Demographics, comorbidities, procedural data, and follow-up information were recorded. PTA failure was defined as first significant event including restenosis by duplex scan (>3.5 x velocity ratio), occlusion, redo-PTA, surgical revision, or amputation. Descriptive, logistic regression and life-table analyses were performed. RESULTS: Eighty-seven grafts in 79 patients underwent PTA. Mean age was 70 years (median 70; range, 39-89 years), 71% were male and 52% were symptomatic (40% with limb-threat). Mean follow-up was 17 months (median 17.4; range, 0.03-39.8 months). Freedom from PTA failure was 58% (standard error [SE] 0.0574) at 12 months. Predictors of PTA failure by multivariate analysis were: time from bypass <3 months (hazard ratio [HR] 5.8; 95% confidence interval [CI] 1.91-18.0; P = .002), stenosis length >2 cm (HR 2.7; 95% CI 1.33-5.83; P = .007) and multiple stenoses (HR 2.5; 95% CI 1.29-5.1; P = .007). PTA patency for grafts with favorable lesions (single, less than 2 cm lesions in grafts older than 3 months) was 71% vs 35% for unfavorable lesions at 12 months. Limb-salvage was 95% and 90% and overall survival was 92% and 81% at 12 and 24 months, respectively. CONCLUSION: PTA of failing infrainguinal vein grafts is a reasonable primary therapy for favorable lesions. Early graft stenosis, long, and multiple stenoses are markers for procedural failure and are better served with surgical revision.

Regulation of vascular smooth muscle cell growth by survivin.

The inhibitor of apoptosis protein survivin has long been of interest in the cancer literature for its role in both the regulation of cell proliferation and the inhibition of apoptosis. A growing body of literature has implicated survivin in the maladaptive pathways following vascular injury and, in particular, in the growth of vascular smooth muscle cells that comprise the hyperplastic neointimal lesions that characterize midterm vein bypass graft failure and restenosis following angioplasty and stenting. This review focuses on the emerging role of survivin in the regulation of smooth muscle cell growth and its implications for the prevention of restenosis following revascularization procedures. The expression, regulation, and function of survivin are addressed, as well as the current state of understanding regarding the effects of survivin inhibition in vitro and in vivo.

Increased risk of deep venous thrombosis with endovascular cooling in patients with traumatic head injury.

Endovascular therapeutic hypothermia has been shown to preserve neurological function and improve outcomes; however, its use and potential complications have not been fully described in patients with traumatic head injuries. We believe that the use of endovascular cooling leads to deep venous thrombosis (DVT) in this high-risk population. We performed a retrospective review of 11 patients with severe head injuries admitted to our Level I trauma center surgical intensive care unit who underwent intravascular cooling. Duplex sonograms were obtained after 4 days at catheter removal or with clinical symptoms that were suspicious for DVT. Patients had a mean age of 23.2 (range, 16-42) years and an Injury Severity Score of 31.9 (range, 25-43). The overall incidence of DVT was 50 per cent. The DVT rate was 33 per cent if catheters were removed in 4 days or less and 75 per cent if removed after 4 days (risk ratio = 2.25; odds ratio = 6; P = ns). An elevated international normalized ratio upon admission was protective against DVT (no DVT = 1.26 vs DVT = 1.09; P = 0.02). Inferior vena cava filters were placed in most patients with DVT. The use of endovascular cooling catheters is associated with increased risk of DVT in patients with traumatic head injuries. Therefore, we discourage the use of endovascular cooling devices in this patient population.

Regulation of vein graft hyperplasia by survivin, an inhibitor of apoptosis protein.

OBJECTIVE: Survivin (SVV) is an inhibitor of apoptosis protein (IAP) that is upregulated in cancer and has recently been implicated in vascular injury. We sought to investigate the role of SVV in vein graft hyperplasia. METHODS AND RESULTS: Adenoviral constructs expressing a dominant-negative (AdT34A) and wild-type (AdWT) SVV were used. Proliferation and apoptosis were assayed on endothelial cells (ECs) and smooth muscle cells (SMCs) from human saphenous vein. A rabbit carotid interposition vein graft model (N=31) was used, with adventitial gene transfer of SVV constructs. In vitro, overexpression of SVV was associated with protection from cytokine-induced apoptosis in ECs and SMCs; conversely, AdT34A directly induced apoptosis in these cells. SMC proliferation was increased by AdWT infection, whereas AdT34A reduced proliferation; both effects were serum-dependent. Expression of platelet-derived growth factor (PDGF) in SMCs was regulated by functional SVV expression in analogous fashion. In vivo, proliferation and apoptosis (7 days), as well as wall thickness (30 days), were modified by adenoviral-mediated SVV expression. Adventitial angiogenesis was regulated by the SVV-expressing constructs in a fashion parallel to wall thickness changes. CONCLUSIONS: SVV is a critical regulator of multiple processes, including proliferation, apoptosis, and angiogenesis, that determine the remodeling response of vein grafts following arterialization.

Survivin expression is up-regulated in vascular injury and identifies a distinct cellular phenotype.

OBJECTIVES: The healing response to vascular injury is characterized by neointimal thickening. Proliferation and phenotypic transformation of vascular smooth muscle cells (SMCs) have been implicated in this process. We sought to investigate the role of survivin, a dual regulator of cell proliferation and apoptosis, in lesion formation after diverse forms of vascular injury. METHODS: Rabbits underwent either carotid interposition vein grafting (n = 17) or bilateral femoral balloon injury (BI; n = 29); some in the BI group were placed on a high-cholesterol diet. A subset of BI arteries were treated with local adenoviral gene delivery of a survivin dominant negative-mutant (AdT34A) versus vector or saline controls. Survivin expression in vessels was analyzed by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry (IHC), which also included markers of SMC differentiation. Specimens of human tissue including failed lower extremity bypass grafts and carotid plaque were also examined. RESULTS: RT-PCR and IHC demonstrated increased survivin expression in all experimental models, colocalizing at early times with proliferating and alpha-actin-expressing cells but was largely absent in mature, contractile SMCs. Delivery of AdT34A after BI attenuated neointimal hyperplasia. CONCLUSION: These studies provide strong evidence supporting a role for survivin in the cellular response to vascular injury. CLINICAL RELEVANCE: The regulation of cell proliferation, death, and phenotype after vascular interventions remains incompletely understood. We investigated the role of the inhibitor of apoptosis protein survivin in diverse models of vascular injury. The results suggest that survivin is an important modulator of the generalized vascular injury response and may represent a relevant target for therapies targeting intimal hyperplasia.

Genetic therapy for vein bypass graft disease: current perspectives.

Although continued progress in endovascular technology holds promise for less invasive approaches to arterial diseases, surgical bypass grafting remains the mainstay of therapy for patients with advanced coronary and peripheral ischemia. In the United States, nearly 400,000 coronary and 100,000 lower extremity bypass procedures are performed annually. The autogenous vein, particularly the greater saphenous vein, has proven to be a durable and versatile arterial substitute, with secondary patency rates at 5 years of 70 to 80% in the extremity. However, vein graft failure is a common occurrence that incurs significant morbidity and mortality, and, to date, pharmacologic approaches to prolong vein graft patency have produced limited results. Dramatic advances in genetics, coupled with a rapidly expanding knowledge of the molecular basis of vascular diseases, have set the stage for genetic interventions. The attraction of a genetic approach to vein graft failure is based on the notion that the tissue at risk is readily accessible to the clinician prior to the onset of the pathologic process and the premise that genetic reprogramming of cells in the wall of the vein can lead to an improved healing response. Although the pathophysiology of vein graft failure is incompletely understood, numerous relevant molecular targets have been elucidated. Interventions designed to influence cell proliferation, thrombosis, inflammation, and matrix remodeling at the genetic level have been described, and many have been tested in animal models. Both gene delivery and gene blockade strategies have been investigated, with the latter reaching the stage of advanced clinical trials.

Genetic interventions for vein bypass graft disease: a review.

The failure of vein bypass grafting in the coronary or lower extremity circulation is a common clinical occurrence that incurs significant morbidity, mortality, and cost. Vein grafts are uniquely amenable to intraoperative genetic modification because of the ability to manipulate the tissue ex vivo with controlled conditions. Although the pathophysiology of vein graft failure is incompletely understood, numerous relevant molecular targets have been elucidated. Interventions designed to influence cell proliferation, thrombosis, inflammation, and matrix remodeling at the genetic level have been described, and many have been tested in animal models. Both gene delivery and gene blockade strategies have been investigated, with the latter now reaching the stage of advanced clinical trials. This review describes the basic and translational science of genetic interventions for vein graft disease and the current state of application in the clinic.