917 resultados para Aortic aneurysm


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BACKGROUND: Durability of protection and long-term quality of life (QoL) are critical outcome parameters of abdominal aortic aneurysm (AAA) repair. The aim of the present study was to compare results of endovascular and open aneurysm repair (EVAR and OR) with adjusted standard populations, including stratification for urgency of presentation. METHODS: Retrospective analysis of prospectively collected data of 401 consecutive patients presenting with AAA between January 1998 and December 2002. Cross-sectional follow up was 58 +/- 29 months. Patients were grouped into three cohorts: elective EVAR (n = 68), elective OR (n = 244), and emergency OR (including symptomatic and ruptured AAA, n = 89). Endpoints were perioperative (i.e., 30 days or in-hospital) and late mortality rates, as well as long-term QoL as assessed by the Short Form health survey questionnaire (SF-36). RESULTS: Mean age was lower in the elective OR cohort (66 +/- 10 years) than in the EVAR cohort (72 +/- 7 years; p < .05). Perioperative mortality rates were 4.4%, 0.4%, and 10.1%, for the EVAR, elective OR, and emergency OR cohorts, respectively (p < .05). Corresponding cumulative survival rates after 4 years were 67%, 89%, and 69%, respectively. Long-term QoL SF-36 scores were in all cohorts similar to age- and gender-adjusted standard populations, which score between 85 and 115: 99.6 +/- 35.8 (EVAR), 101.3 +/- 32.4 (elective OR), and 100.4 +/- 36.5 (emergency OR). CONCLUSIONS: Long-term QoL is not permanently impaired after AAA repair, but returns in long-term survivors to what would be expected in a standard population. In this respect, differences were found neither between EVAR and OR, nor between elective and emergency repair. Perioperative mortality rates were highest in patients undergoing emergency OR. The outlook for such patients after the perioperative period, however, was similar to that for patients undergoing elective repair.

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BACKGROUND: Marfan syndrome (MFS) is a heritable disorder of connective tissue, affecting principally skeletal, ocular, and cardiovascular systems. The most life-threatening manifestations are aortic aneurysm and dissection. We investigated changes in the proteome of aortic media in patients with and without MFS to gain insight into molecular mechanisms leading to aortic dilatation. METHODS AND RESULTS: Aortic samples were collected from 46 patients. Twenty-two patients suffered from MFS, 9 patients had bicuspid aortic valve, and 15 patients without connective tissue disorder served as controls. Aortic media was isolated and its proteome was analyzed in 12 patients with the use of 2-dimensional difference gel electrophoresis and mass spectrometry. We found higher amounts of filamin A C-terminal fragment, calponin 1, vinculin, microfibril-associated glycoprotein 4, and myosin-10 heavy chain in aortic media of MFS aneurysm samples than in controls. Regulation of filamin A C-terminal fragmentation was validated in all patient samples by immunoblotting. Cleavage of filamin A and the calpain substrate spectrin was increased in the MFS and bicuspid aortic valve groups. Extent of cleavage correlated positively with calpain 2 expression and negatively with the expression of its endogenous inhibitor calpastatin. CONCLUSIONS: Our observation demonstrates for the first time upregulation of the C-terminal fragment of filamin A in dilated aortic media of MFS and bicuspid aortic valve patients. In addition, our results present evidence that the cleavage of filamin A is highly likely the result of the protease calpain. Increased calpain activity might explain, at least in part, histological alterations in dilated aorta.

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OBJECTIVE: The aim of this study was to establish and validate a three-dimensional imaging protocol for the assessment of Computed Tomography (CT) scans of abdominal aortic aneurysms in UK EVAR trials patients. Quality control and repeatability of anatomical measurements is important for the validity of any core laboratory. METHODS: Three different observers performed anatomical measurements on 50 preoperative CT scans of aortic aneurysms using the Vitrea 2 three-dimensional post-imaging software in a core laboratory setting. We assessed the accuracy of intra and inter observer repeatability of measurements, the time required for collection of measurements, 3 different levels of automation and 3 different automated criteria for measurement of neck length. RESULTS: None of the automated neck length measurements demonstrated sufficient accuracy and it was necessary to perform checking of the important automated landmarks. Good intra and limited inter observer agreement were achieved with three-dimensional assessment. Complete assessment of the aneurysm and iliacs took an average (SD) of 17.2 (4.1) minutes. CONCLUSIONS: Aortic aneurysm anatomy can be assessed reliably and quickly using three-dimensional assessment but for scans of limited quality, manual checking of important landmarks remains necessary. Using a set protocol, agreement between observers is satisfactory but not as good as within observers.

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The Mendelian inheritance of genetic mutations can lead to adult-onset cardiovascular disease. Several genetic loci have been mapped for the familial form of Thoracic Aortic Aneurysms (TAA), and many causal mutations have been identified for this disease. Intracranial Aneurysms (ICA) also show linkage heterogeneity, but no mutations have been identified causing familial ICA alone. Here, we characterized a large family (TAA288) with an autosomal dominant pattern of inherited aneurysms. It is intriguing that female patients predominantly present with ICA and male patients predominantly with TAA in this family. To identify a causal mutation in this family, a genome-wide linkage analysis was previously performed on nine members of this family using the 50k GenChips Hind array from Affymetrix. This analysis eventually identified a single disease-segregating locus, on chromosome 5p15. We build upon this previous analysis in this study, hypothesizing that a genetic mutation inherited in this locus leads to the sex-specific phenotype of TAA and ICA in this family First we refined the boundaries of the 5p15 disease linked locus down to the genomic coordinates 5p15: 3,424,465- 6,312,925 (GRCh37/hg19 Assembly). This locus was named the TAA288 critical interval. Next, we sequenced candidate genes within the TAA288 critical interval. The selection of genes was simplified by the relatively small number of well-characterized genetic elements within the region. Seeking novel or rare disease-segregating variants, we initially observed a single point alteration in the metalloproteinase gene ADAMTS16 fulfilling this criteria. This variant was later classified as a low-frequency population polymorphism (rs72647757), but we continued to explore the potential role of the ADAMTS16 as the cause of disease in TAA288. We observed that fibroblasts cultured from TAA288 patients consistently upregulated the expression of this gene more strongly compared to matched control fibroblasts when treated with the cytokine TGF-β1, though there was some variation in the exact nature of this expression. We also observed evidence that this protein is expressed at elevated levels in aortic aneurysm tissue from patients with mutations in the gene TGFBR2 and Marfan syndrome, shown by immunohistochemical detection of this protein.

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OBJECTIVE: This study sought to characterize the inflammatory infiltrate in ascending thoracic aortic aneurysm in patients with Marfan syndrome, familial thoracic aortic aneurysm, or nonfamilial thoracic aortic aneurysm. BACKGROUND: Thoracic aortic aneurysms are associated with a pathologic lesion termed "medial degeneration," which is described as a noninflammatory lesion. Thoracic aortic aneurysms are a complication of Marfan syndrome and can be inherited in an autosomal dominant manner of familial thoracic aortic aneurysm. METHODS: Full aortic segments were collected from patients undergoing elective repair with Marfan syndrome (n = 5), familial thoracic aortic aneurysm (n = 6), and thoracic aortic aneurysms (n = 9), along with control aortas (n = 5). Immunohistochemistry staining was performed using antibodies directed against markers of lymphocytes and macrophages. Real-time polymerase chain reaction analysis was performed to quantify the expression level of the T-cell receptor beta-chain variable region gene. RESULTS: Immunohistochemistry of thoracic aortic aneurysm aortas demonstrated that the media and adventitia from Marfan syndrome, familial thoracic aortic aneurysm, and sporadic cases had increased numbers of T lymphocytes and macrophages when compared with control aortas. The number of T cells and macrophages in the aortic media of the aneurysm correlated inversely with the patient's age at the time of prophylactic surgical repair of the aorta. T-cell receptor profiling indicated a similar clonal nature of the T cells in the aortic wall in a majority of aneurysms, whether the patient had Marfan syndrome, familial thoracic aortic aneurysm, or sporadic disease. CONCLUSION: These results indicate that the infiltration of inflammatory cells contributes to the pathogenesis of thoracic aortic aneurysms. Superantigen-driven stimulation of T lymphocytes in the aortic tissues of patients with thoracic aortic aneurysms may contribute to the initial immune response.

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Mutations in smooth muscle cell (SMC)-specific isoforms of α-actin and β-myosin heavy chain, two major components of the SMC contractile unit, cause familial thoracic aortic aneurysms leading to acute aortic dissections (FTAAD). To investigate whether mutations in the kinase that controls SMC contractile function (myosin light chain kinase [MYLK]) cause FTAAD, we sequenced MYLK by using DNA from 193 affected probands from unrelated FTAAD families. One nonsense and four missense variants were identified in MYLK and were not present in matched controls. Two variants, p.R1480X (c.4438C>T) and p.S1759P (c.5275T>C), segregated with aortic dissections in two families with a maximum LOD score of 2.1, providing evidence of linkage of these rare variants to the disease (p = 0.0009). Both families demonstrated a similar phenotype characterized by presentation with an acute aortic dissection with little to no enlargement of the aorta. The p.R1480X mutation leads to a truncated protein lacking the kinase and calmodulin binding domains, and p.S1759P alters amino acids in the α-helix of the calmodulin binding sequence, which disrupts kinase binding to calmodulin and reduces kinase activity in vitro. Furthermore, mice with SMC-specific knockdown of Mylk demonstrate altered gene expression and pathology consistent with medial degeneration of the aorta. Thus, genetic and functional studies support the conclusion that heterozygous loss-of-function mutations in MYLK are associated with aortic dissections.

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Tuberous sclerosis complex (TSC) is a genetic disorder with pleiotropic manifestations caused by heterozygous mutations in either TSC1 or TSC2. One of the less investigated complications of TSC is the formation of aneurysms of the descending aorta, which are characterized on pathologic examination by smooth muscle cell (SMC) proliferation in the aortic media. SMCs were explanted from Tsc2(+/-) mice to investigate the pathogenesis of aortic aneurysms caused by TSC2 mutations. Tsc2(+/-) SMCs demonstrated increased phosphorylation of mammalian target of rapamycin (mTOR), S6 and p70S6K and increased proliferation rates compared with wild-type (WT) SMCs. Tsc2(+/-) SMCs also had reduced expression of SMC contractile proteins compared with WT SMCs. An inhibitor of mTOR signaling, rapamycin, decreased SMC proliferation and increased contractile protein expression in the Tsc2(+/-) SMCs to levels similar to WT SMCs. Exposure to alpha-elastin fragments also decreased proliferation of Tsc2(+/-) SMCs and increased levels of p27(kip1), but failed to increase expression of contractile proteins. In response to artery injury using a carotid artery ligation model, Tsc2(+/-) mice significantly increased neointima formation compared with the control mice, and the neointima formation was inhibited by treatment with rapamycin. These results demonstrate that Tsc2 haploinsufficiency in SMCs increases proliferation and decreases contractile protein expression and suggest that the increased proliferative potential of the mutant cells may be suppressed in vivo by interaction with elastin. These findings provide insights into the molecular pathogenesis of aortic disease in TSC patients and identify a potential therapeutic target for treatment of this complication of the disease.

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BACKGROUND: Renal failure after thoracoabdominal aortic repair is a significant clinical problem. Distal aortic perfusion for organ and spinal cord protection requires cannulation of the left femoral artery. In 2006, we reported the finding that direct cannulation led to leg ischemia in some patients and was associated with increased renal failure. After this finding, we modified our perfusion technique to eliminate leg ischemia from cannulation. In this article, we present the effects of this change on postoperative renal function. METHODS: Between February 1991 and July 2008, we repaired 1464 thoracoabdominal aortic aneurysms. Distal aortic perfusion was used in 1088, and these were studied. Median patient age was 68 years, and 378 (35%) were women. In September 2006, we began to adopt a sidearm femoral cannulation technique that provides distal aortic perfusion while maintaining downstream flow to the leg. This was used in 167 patients (15%). We measured the joint effects of preoperative glomerular filtration rate (GFR) and cannulation technique on the highest postoperative creatinine level, postoperative renal failure, and death. Analysis was by multiple linear or logistic regression with interaction. RESULTS: The preoperative GFR was the strongest predictor of postoperative renal dysfunction and death. No significant main effects of sidearm cannulation were noted. For peak creatinine level and postoperative renal failure, however, strong interactions between preoperative GFR and sidearm cannulation were present, resulting in reductions of postoperative renal complications of 15% to 20% when GFR was <60 mL>/min/1.73 m(2). For normal GFR, the effect was negated or even reversed at very high levels of GFR. Mortality, although not significantly affected by sidearm cannulation, showed a similar trend to the renal outcomes. CONCLUSION: Use of sidearm cannulation is associated with a clinically important and highly statistically significant reduction in postoperative renal complications in patients with a low GFR. Reduced renal effect of skeletal muscle ischemia is the proposed mechanism. Effects among patients with good preoperative renal function are less clear. A randomized trial is needed.

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BACKGROUND: A 24-year-old man presented with previously diagnosed Marfan's syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment. INVESTIGATIONS: CT scans, arteriogram, genetic mutation screening of transforming growth factor beta receptors 1 and 2. DIAGNOSIS: Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfan's syndrome, but was later rediagnosed with Loeys-Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor beta receptor 2. MANAGEMENT: Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease.

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OBJECTIVES To report the mid-term results of aortic root replacement using a self-assembled biological composite graft, consisting of a vascular tube graft and a stented tissue valve. METHODS Between January 2005 and December 2011, 201 consecutive patients [median age 66 (interquartile range, IQR, 55-77) years, 31 female patients (15.4%), median logistic EuroSCORE 10 (IQR 6.8-23.2)] underwent aortic root replacement using a stented tissue valve for the following indications: annulo-aortic ectasia or ascending aortic aneurysm with aortic valve disease in 162 (76.8%) patients, active infective endocarditis in 18 (9.0%) and acute aortic dissection Stanford type A in 21 (10.4%). All patients underwent clinical and echocardiographic follow-up. We analysed survival and valve-related events. RESULTS The overall in-hospital mortality rate was 4.5%. One- and 5-year cardiac-related mortality rates were 3 and 6%, and overall survival was 95 ± 1.5 and 75 ± 3.6%, respectively. The rate of freedom from structural valve failure was 99% and 97 ± 0.4% at the 1- and 5-year follow-up, respectively. The incidence rates of prosthetic valve endocarditis were 3 and 4%, respectively. During a median follow-up of 28 (IQR 14-51) months, only 2 (1%) patients required valve-related redo surgery due to prosthetic valvular endocarditis and none suffered from thromboembolic events. One percent of patients showed structural valve deterioration without any clinical symptoms; none of the patients suffered greater than mild aortic regurgitation. CONCLUSIONS Aortic root replacement using a self-assembled biological composite graft is an interesting option. Haemodynamic results are excellent, with freedom from structured valve failure. Need for reoperation is extremely low, but long-term results are necessary to prove the durability of this concept.

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OBJECTIVES Long-term follow-up reports after implantation of the Shelhigh® (Shelhigh, Inc., NJ, USA) No-React® aortic valved conduit used for aortic root replacement do not exist. METHODS Between November 1998 and December 2007, the Shelhigh® No-React® aortic valved conduit was implanted in 291 consecutive patients with a mean age of 69.6 ± 9.1 years, and 33.7% were female (n = 98). Indications were annulo-aortic ectasia (n = 202), aortic valve stenosis combined with ascending aortic aneurysm (n = 67), acute type A aortic dissection (n = 29), endocarditis (n = 26) and other related pathologies (n = 48) including 62 patients with previous cardiac surgery. Data from two cardiac institutions were analysed retrospectively using SPSS (SPSS Software IBM, Inc., 2014, NY, USA). RESULTS Operative mortality was 10% (n = 29). Main cause of death was cardiac failure in 15 patients (51.8%), neurological events in 6 patients (20.7%), respiratory failure in 4 patients (13.8%), bleeding complications in 2 patients (6.9%) and gastrointestinal ischaemia in 2 cases (6.9%). There were 262 hospital survivors and all were entered in the follow-up study (100% complete). During the long-term follow-up (mean 70.3 ± 53.1 in months), a total of 126/262 patients (44.3%) died. Main causes of death in patients after discharge were cardiac (n = 37, 14.1%), neurological (n = 15, 5.7%) respiratory (n = 12, 4.6%), endocarditis (n = 12, 4.6%) and peripheral vascular disease (n = 5, 1.9%). In 29 (11.1%) patients, the cause of death could not be determined. Reoperation was required in 25 (8.6%) patients due to infection of the conduit (n = 9), aortoventricular disconnection (n = 4), pseudoaneurysm formation (n = 4) and structural valve degeneration (n = 8). Reoperations were performed 5.0 ± 3.8 (range 0.1-11.7) years after index surgery. CONCLUSIONS The Shelhigh® No-React® aortic valved conduit showed satisfactory short-term operative results. However, the long-term follow-up revealed a relatively high rate of deaths, which may be explained by the epidemiology of the patient group, but a substantial proportion of deaths could not be clarified. The overall rate of reoperation (8.6%) during the mid-term follow-up is worrisome and the failures due to aortoventricular disconnection, endocarditis and pseudoaneurysm formation remain unexplained. The redo-procedures were technically demanding. We recommend close follow-up of patients with the Shelhigh® No-React® aortic valved conduit, because besides classical structural valve degeneration, unexpected findings may be observed.

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PURPOSE The purpose of this study was to identify morphologic factors affecting type I endoleak formation and bird-beak configuration after thoracic endovascular aortic repair (TEVAR). METHODS Computed tomography (CT) data of 57 patients (40 males; median age, 66 years) undergoing TEVAR for thoracic aortic aneurysm (34 TAA, 19 TAAA) or penetrating aortic ulcer (n = 4) between 2001 and 2010 were retrospectively reviewed. In 28 patients, the Gore TAG® stent-graft was used, followed by the Medtronic Valiant® in 16 cases, the Medtronic Talent® in 8, and the Cook Zenith® in 5 cases. Proximal landing zone (PLZ) was in zone 1 in 13, zone 2 in 13, zone 3 in 23, and zone 4 in 8 patients. In 14 patients (25%), the procedure was urgent or emergent. In each case, pre- and postoperative CT angiography was analyzed using a dedicated image processing workstation and complimentary in-house developed software based on a 3D cylindrical intensity model to calculate aortic arch angulation and conicity of the landing zones (LZ). RESULTS Primary type Ia endoleak rate was 12% (7/57) and subsequent re-intervention rate was 86% (6/7). Left subclavian artery (LSA) coverage (p = 0.036) and conicity of the PLZ (5.9 vs. 2.6 mm; p = 0.016) were significantly associated with an increased type Ia endoleak rate. Bird-beak configuration was observed in 16 patients (28%) and was associated with a smaller radius of the aortic arch curvature (42 vs. 65 mm; p = 0.049). Type Ia endoleak was not associated with a bird-beak configuration (p = 0.388). Primary type Ib endoleak rate was 7% (4/57) and subsequent re-intervention rate was 100%. Conicity of the distal LZ was associated with an increased type Ib endoleak rate (8.3 vs. 2.6 mm; p = 0.038). CONCLUSIONS CT-based 3D aortic morphometry helps to identify risk factors of type I endoleak formation and bird-beak configuration during TEVAR. These factors were LSA coverage and conicity within the landing zones for type I endoleak formation and steep aortic angulation for bird-beak configuration.

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Dissecting aortic aneurysm is the hallmark of Marfan syndrome (MFS) and the result of mutations in fibrillin-1, the major constituent of elastin-associated extracellular microfibrils. It is yet to be established whether dysfunction of fibrillin-1 perturbs the ability of the elastic vessel wall to sustain hemodynamic stress by disrupting microfibrillar assembly, by impairing the homeostasis of established elastic fibers, or by a combination of both mechanisms. The pathogenic sequence responsible for the mechanical collapse of the elastic lamellae in the aortic wall is also unknown. Targeted mutation of the mouse fibrillin-1 gene has recently suggested that deficiency of fibrillin-1 reduces tissue homeostasis rather than elastic fiber formation. Here we describe another gene-targeting mutation, mgR, which shows that underexpression of fibrillin-1 similarly leads to MFS-like manifestations. Histopathological analysis of mgR/mgR specimens implicates medial calcification, the inflammatory–fibroproliferative response, and inflammation-mediated elastolysis in the natural history of dissecting aneurysm. More generally, the phenotypic severity associated with various combinations of normal and mutant fibrillin-1 alleles suggests a threshold phenomenon for the functional collapse of the vessel wall that is based on the level and the integrity of microfibrils.

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BACKGROUND AND AIMS: Although it has become clear that aneurysmal and occlusive arterial disease represent two distinct etiologic entities, it is still unknown whether the two vascular pathologies are prognostically different. We aim to assess the long-term vital prognosis of patients with abdominal aortic aneurysmal disease (AAA) or peripheral artery disease (PAD), focusing on possible differences in survival, prognostic risk profiles and causes of death. METHODS: Patients undergoing elective surgery for isolated AAA or PAD between 2003 and 2011 were retrospectively included. Differences in postoperative survival were determined using Kaplan-Meier and Cox regression analysis. Prognostic risk profiles were also established with Cox regression analysis. RESULTS: 429 and 338 patients were included in the AAA and PAD groups, respectively. AAA patients were older (71.7 vs. 63.3 years, p < 0.001), yet overall survival following surgery did not differ (HR: 1.16, 95% CI: 0.87-1.54). Neither was type of vascular disease associated with postoperative cardiovascular nor cancer-related death. However, in comparison with age- and gender-matched general populations, cardiovascular mortality was higher in PAD than AAA patients (48.3% vs. 17.3%). Survival of AAA and PAD patients was negatively affected by age, history of cancer and renal insufficiency. Additional determinants in the PAD group were diabetes and ischemic heart disease. CONCLUSIONS: Long-term survival after surgery for PAD and AAA is similar. However, overall life expectancy is significantly worse among PAD patients. The contribution of cardiovascular disease towards mortality in PAD patients warrants more aggressive secondary prevention to reduce cardiovascular mortality and improve longevity.

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On 6 May 2001, a 67-year-old Australian born, Caucasian male presented to the Emergency Department of the Austin and Repatriation Medical Centre (A&RMC) with a 3 day history of fever, lethargy and confusion. This occurred one week after returning from a trip to the Northern Territory. His previous medical problems included ischaemic heart disease, a repaired abdominal aortic aneurysm, hypertension, hyperlipidaemia and congestive cardiac failure. He smoked 20 cigarettes per day and had a history of heavy alcohol consumption. He had no history of diabetes. His medications were aspirin, frusemide, lisinopril, simvastatin, and a nitroglycerol patch. Fifty years ago, he had an adverse reaction to penicillin with angioedema and an urticarial rash. Four weeks before admission he went on a fishing trip in the Northern Territory. He travelled by road, through outback regions of Victoria, New South Wales, Queensland, the Northern Territory and South Australia, spending time in Daly River, Coolum, Darwin, Dunmarra, Avon Downs, Innaminka and Mataranka. He was away for 3 weeks and camped in tents or outside in a swag throughout the trip. He recalls numerous times where he was exposed to mosquitoes with large numbers of bites at Dunmarra. During the time away, he remained well as did his 5 travelling companions. There was...