Philip J. Walker

Transluminal Placement of Endovascular Stent-Grafts for the Treatment of Descending Thoracic Aortic Aneurysms

BACKGROUND The usual treatment for thoracic aortic aneurysms is surgical replacement with a prosthetic graft, but the associated morbidity and mortality are considerable. We studied the use of transluminally placed endovascular stent-graft devices as an alternative to surgical repair. METHODS We evaluated the feasibility, safety, and effectiveness of transluminally placed stent-graft to treat descending thoracic aortic aneurysms in 13 patients over a 24-month period. Atherosclerotic, anastomotic, and post-traumatic true or false aneurysms and aortic dissections were treated. The mean diameter of the aneurysms was 6.1 cm (range, 5 to 8). The endovascular stent-grafts were custom-designed for each patient and were constructed of self-expanding stainless-steel stents covered with woven Dacron grafts. RESULTS Endovascular placement of the stent-graft prosthesis was successful in all patients. There was complete thrombosis of the thoracic aortic aneurysm surrounding the stent-graft in 12 patients, and partial thrombosis in 1. Two patients initially had small, residual patent proximal tracts into the aneurysm sac, but both tracts thrombosed within two months after the procedure. In four patients, two prostheses were required to bridge the aneurysm adequately. There have been no deaths or instances of paraplegia, stroke, distal embolization, or infection during an average follow-up of 11.6 months. One patient with an extensive chronic aortic dissection required open surgical graft replacement four months later because of progressive dilatation of the arch. CONCLUSIONS These preliminary results demonstrate that endovascular stent-graft repair is safe in highly selected patients with descending thoracic aortic aneurysms. This new method of treatment will, however, require careful long-term evaluation.

Abnormal Extracellular Matrix Protein Transport Associated With Increased Apoptosis of Vascular Smooth Muscle Cells in Marfan Syndrome and Bicuspid Aortic Valve Thoracic Aortic Aneurysm

Background—Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)-2 in VSMC apoptosis was studied in MS aneurysm. Methods and Results—Aneurysm tissue was obtained from patients undergoing surgery (MS: 4 M, 1 F, age 27–45 years; BAV: 3 M, 2 F, age 28–65 years). Normal aorta from subjects with nonaneurysm disease was also collected (4 M, 1 F, age 23–93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs.There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS (27±8%) and BAV (32±14%) compared with control (7±5%). Conclusions—In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.

Three-dimensional spiral computed tomographic angiography: An alternative imaging modality for the abdominal aorta and its branches

PURPOSE We sought to apply a new technique of computed tomographic angiography (CTA) to the preoperative and postoperative assessment of the abdominal aorta and its branches. METHODS After a peripheral intravenous contrast injection, the patient is continuously advanced through a spiral CT scanner, while maintaining a 30-second breath-hold. Thirty-five patients with abdominal aortic, renal, and visceral arterial disease have undergone CTA. RESULTS Diagnostic three-dimensional images were obtained in patients with aortic aneurysms (n = 9), aortic dissections (n = 4), and mesenteric artery stenoses (n = 4). The technique has also been used to assess vessels after operative reconstruction or endovascular intervention in 18 patients. These preliminary studies have correlated well with conventional arteriographic findings. In aneurysmal disease both the lumen and mural thrombus and associated renal artery stenoses are visualized. The true and false channels of aortic dissections and the perfusion source of the visceral vessels are clearly shown; patency of visceral and renal reconstruction or stent placement are confirmed. CTA is relatively noninvasive and can be completed in less time than conventional angiography with less radiation exposure. CONCLUSIONS This initial experience suggests that CTA may be a valuable alternative to conventional arteriography in the evaluation of the aorta and its branches.

Clinical experience with a bifurcated endovascular graft for abdominal aortic aneurysm repair

PURPOSE The purpose of this study was to test a transfemoral system of bifurcated endovascular graft insertion for aortic aneurysm repair. METHODS Bifurcated endovascular grafts were inserted through bilateral femoral artery cutdowns in 41 patients. The results were assessed by completion angiography and follow-up computed tomography. RESULTS The second half of the study included more aneurysms 6 cm or larger (p < 0.05) and more instances of short proximal neck (p < 0.05), proximal neck angulation (p < 0.05), and iliac angulation (p < 0.05). Despite the increasingly challenging anatomy, the results were better in the second half of the study as illustrated by the lower overall combined morbidity/mortality rate (15% vs 50%) and higher overall success rate (85% versus 65%). The mortality rate for the series as a whole was 7.5%. Mean follow-up was 18.8 months for the first 20 patients and 10.9 months for the second 20. The commonest complication in the first half of the study was graft thrombosis (n = 5). This complication was absent from the second half of the study because of routine adjunctive stenting. Two patients died of complications of endovascular repair. In both cases aneurysm rupture on the third postoperative day was associated with coagulopathy and angiographic signs of perigraft leak. CONCLUSION Aneurysm exclusion with a bifurcated endovascular graft was feasible in a wide range of patients, but when the aneurysm was not entirely excluded from the circulation, the risk of rupture persisted.

The use of endovascular techniques for the treatment of complications of aortic dissection

Intravascular ultrasonography, balloon angioplasty, stent placement, and endovascular septal fenestration have been used in the evaluation and treatment of vascular complications of acute and chronic aortic dissection in five patients. There were three men and two women with an average age of 52 years (range 39 to 64 years). There were three chronic type A dissections, one acute type B, and one subacute type B dissection. Intravascular ultrasonography was used in all five cases. The three patients with chronic type A dissections underwent unilateral renal artery angioplasty (RA PTA) and stent placement; one patient with an acute type B dissection and associated fibromuscular dysplasia underwent bilateral RA PTA without stent placement. These procedures were performed to ameliorate severe hypertension. The final patient, with a subacute type B dissection, underwent iliac artery stenting to correct severe lower extremity ischemia. During a second intervention, this patient, who also had bowel ischemia and nonresolving acute renal failure, underwent balloon dilatation of a preexisting septal fenestration to augment visceral blood supply and bilateral RA PTA and stent placement in an effort to improve renal function. This patient eventually died of gut ischemia. After RA PTA and stent placement, one patient had a major intrarenal hemorrhage that required coil embolization and transfusion. In the four survivors, RA PTA and stent placement resulted in immediate improvement in blood pressure control. This response has been sustained during follow-up intervals ranging from 8 to 18 months (average 10 months). Intravascular ultrasonography can clearly demonstrate the pathologic anatomy associated with aortic dissection (even when angiography is ambiguous) and is essential for guiding therapeutic endovascular interventions. Further exploration of the efficacy of these endovascular techniques is warranted in this high-risk group of patients with aortic dissection who have appropriate clinical indications.

Effect of Ramipril on Walking Times and Quality of Life Among Patients With Peripheral Artery Disease and Intermittent Claudication: A Randomized Controlled Trial

IMPORTANCE Approximately one-third of patients with peripheral artery disease experience intermittent claudication, with consequent loss of quality of life. OBJECTIVE To determine the efficacy of ramipril for improving walking ability, patient-perceived walking performance, and quality of life in patients with claudication. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, placebo-controlled trial conducted among 212 patients with peripheral artery disease (mean age, 65.5 [SD, 6.2] years), initiated in May 2008 and completed in August 2011 and conducted at 3 hospitals in Australia. INTERVENTION Patients were randomized to receive 10 mg/d of ramipril (n = 106) or matching placebo (n = 106) for 24 weeks. MAIN OUTCOME MEASURES Maximum and pain-free walking times were recorded during a standard treadmill test. The Walking Impairment Questionnaire (WIQ) and Short-Form 36 Health Survey (SF-36) were used to assess walking ability and quality of life, respectively. RESULTS At 6 months, relative to placebo, ramipril was associated with a 75-second (95% CI, 60-89 seconds) increase in mean pain-free walking time (P < .001) and a 255-second (95% CI, 215-295 seconds) increase in maximum walking time (P < .001). Relative to placebo, ramipril improved the WIQ median distance score by 13.8 (Hodges-Lehmann 95% CI, 12.2-15.5), speed score by 13.3 (95% CI, 11.9-15.2), and stair climbing score by 25.2 (95% CI, 25.1-29.4) (P < .001 for all). The overall SF-36 median Physical Component Summary score improved by 8.2 (Hodges-Lehmann 95% CI, 3.6-11.4; P = .02) in the ramipril group relative to placebo. Ramipril did not affect the overall SF-36 median Mental Component Summary score. CONCLUSIONS AND RELEVANCE Among patients with intermittent claudication, 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo. This was associated with a significant increase in the physical functioning component of the SF-36 score. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00681226.

Early experience with cryopreserved saphenous vein allografts as a conduit for complex limb-salvage procedures

PURPOSE The lack of a suitable alternative to autogenous vein is often the limiting factor for complex lower extremity vascular reconstruction, especially when previously placed grafts have failed. Cryopreserved saphenous vein allografts have been used as an alternative conduit. This report reviews our early experience with this conduit in a series of complex redo revascularization procedures for limb salvage when no suitable autogenous vein was available. METHODS Thirty-five patients underwent 39 lower extremity bypass grafts on 36 limbs. These patients had undergone a combined total of 72 prior revascularization procedures on the symptomatic limb, an average of two procedures per patient. Only five bypasses were performed as a primary procedure. There were 18 men and 17 women with a mean age of 71 years. Sixteen of the patients had diabetes. Thirty-four bypasses were performed for rest pain or ulceration, four for disabling claudication, and one for replacement of an aneurysmal vein graft. There were 35 femorotibial, three below-knee femoropopliteal, and one femoropedal reconstruction. Twenty-five grafts were constructed with cryopreserved vein only, whereas 14 were composite grafts; 10 were constructed with polytetrafluoroethylene, one with Dacron, and three with spliced native saphenous vein. The mean follow-up was 9 months (range 1 to 25 months). RESULTS There was one early death (< 30 days) and two late deaths. Two patients died with a patent graft. There have been 12 early graft closures and an additional 17 late failures, resulting in primary cumulative graft patency rates of 67%, 56%, 43%, 28%, and 14% at 1, 3, 6, 12, and 18 months, respectively. Surgically correctable causes, including technical error and anastomotic stenosis, could be identified in 13 of the 29 graft failures. Salvage of failed grafts resulted in secondary cumulative graft patency rates of 87%, 77%, 61%, 46%, and 37% at these same intervals. There was no significant difference in primary or secondary graft patency rates related to diabetes, ABO graft compatibility, graft composition or orientation, indication for surgery, state of the outflow tract, or site of distal anastomosis. Limb salvage was attained in 24 (67%) of the 36 limbs. Two amputations were necessary despite patent grafts. CONCLUSIONS Because of the poor overall graft patency rates, cryopreserved saphenous vein allografts should be used only as a last resort when no alternative autogenous conduit is available. Unless patency rates superior to those achievable with currently available prosthetic or biologic conduits can be attained by adjunctive measures such as routine anticoagulation or immunosuppressive therapy, the use of cryopreserved saphenous vein allografts for lower extremity revascularization should be deferred until improved preparation techniques provide a more durable conduit.

Characterization of heat shock protein-specific T cells in atherosclerosis.

ABSTRACT A role for infection and inflammation in atherogenesis is widely accepted. Arterial endothelium has been shown to express heat shock protein 60 (HSP60) and, since human (hHSP60) and bacterial (GroEL) HSP60s are highly conserved, the immune response to bacteria may result in cross-reactivity, leading to endothelial damage and thus contribute to the pathogenesis of atherosclerosis. In this study, GroEL-specific T-cell lines from peripheral blood and GroEL-, hHSP60-, and Porphyromonas gingivalis-specific T-cell lines from atherosclerotic plaques were established and characterized in terms of their cross-reactive proliferative responses, cytokine and chemokine profiles, and T-cell receptor (TCR) Vβ expression by flow cytometry. The cross-reactivity of several lines was demonstrated. The cytokine profiles of the artery T-cell lines specific for GroEL, hHSP60, and P. gingivalis demonstrated Th2 phenotype predominance in the CD4 subset and Tc0 phenotype predominance in the CD8 subset. A higher proportion of CD4 cells were positive for interferon-inducible protein 10 and RANTES, with low percentages of cells positive for monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α, whereas a high percentage of CD8 cells expressed all four chemokines. Finally, there was overexpression of the TCR Vβ5.2 family in all lines. These cytokine, chemokine, and Vβ profiles are similar to those demonstrated previously for P. gingivalis-specific lines established from periodontal disease patients. These results support the hypothesis that in some patients cross-reactivity of the immune response to bacterial HSPs, including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may explain the apparent association between atherosclerosis and periodontal infection.

Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms

Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA.

The value of screening in siblings of patients with abdominal aortic aneurysm.

OBJECTIVES This study aimed to determine the incidence of abdominal aortic aneurysm (AAA) in a large group of siblings of Australian AAA patients to determine if screening in this group is justified. METHODS 1254 siblings of 400 index AAA patients were identified and offered aortic ultrasound screening. An age and sex matched control group was recruited from patients having abdominal CT scans for non-vascular indications. AAA was defined by an infrarenal aortic diameter of > or =3 cm or a ratio of the infrarenal to suprarenal aortic diameter of > or =2.0. A ratio of 1.0-1.5 was considered normal, and a ratio of >1.5 to <2.0 was considered ectatic. Aortic enlargement was defined as ectasia or aneurysm. RESULTS 276 (22%) siblings could be contacted and agreed to screening or had previously been diagnosed with AAA. All 118 controls had normal diameter aortas. 55/276 siblings had previously been diagnosed with AAA. The remaining 221 siblings underwent ultrasound screening. Overall, 30% (84/276) had enlarged aortas (5% ectasia, 25% aneurysmal); 43% of male siblings (64/150) and 16% of females siblings (20/126). The incidence was 45% in brothers of female index patients, 42% in brothers of male patients, 23% in sisters of female patients, and 14% in sisters of male index patients. CONCLUSIONS The overall incidence of aortic enlargement of 30% found in this study warrants a targeted screening approach with ultrasound for all siblings of patients with AAA. A similar targeted approach for screening of the children of AAA patients would also seem advisable.