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Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to 'phenotype switching' and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Quimiocina CCL2 , Células Endoteliais , SARS-CoV-2 , Humanos , COVID-19/metabolismo , COVID-19/complicações , Animais , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Células Endoteliais/patologia , Camundongos Transgênicos , Camundongos , Masculino , Feminino , Células-Tronco Pluripotentes Induzidas/metabolismo , Estresse Oxidativo , Síndrome de COVID-19 Pós-Aguda , Pessoa de Meia-Idade , Idoso , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/virologia , Miócitos Cardíacos/patologia , Organoides/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/virologia , Cardiopatias/etiologiaRESUMO
OBJECTIVE: As a result of conflicting, inadequate or controversial data in the literature, several issues concerning the management of patients with abdominal aortic aneurysms (AAAs) remain unanswered. The aim of this international, expert-based Delphi consensus document was to provide some guidance for clinicians on these controversial topics. METHODS: A three-round Delphi consensus document was produced with 44 experts on 6 prespecified topics regarding the management of AAAs. All answers were provided anonymously. The response rate for each round was 100%. RESULTS: Most participants (42 of 44 [95.4%]) agreed that a minimum case volume per year is essential (or probably essential) for a center to offer open or endovascular AAA repair (EVAR). Furthermore, 33 of 44 (75.0%) believed that AAA screening programs are (probably) still clinically effective and cost effective. Additionally, most panelists (36 of 44 [81.9%]) voted that surveillance after EVAR should be (or should probably be) lifelong. Finally, 35 of 44 participants (79.7%) thought that women smokers should (or should probably/possibly) be considered for screening at 65 years of age, similar to men. No consensus was achieved regarding lowering the threshold for AAA repair and the need for deep venous thrombosis prophylaxis in patients undergoing EVAR. CONCLUSIONS: This expert-based Delphi consensus document provides guidance for clinicians regarding specific unresolved issues. Consensus could not be achieved on some topics, highlighting the need for further research in those areas.
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OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.
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Objective: Metformin treatment attenuates experimental abdominal aortic aneurysm (AAA) formation, as well as reduces clinical AAA diameter enlargement in patients with diabetes. The mechanisms of metformin-mediated aneurysm suppression, and its efficacy in suppressing established experimental aneurysms, remain uncertain. Methods: Experimental AAAs were created in male C57BL/6J mice via intra-aortic infusion of porcine pancreatic elastase. Metformin alone (250 mg/kg), or metformin combined with the 5' AMP-activated protein kinase (AMPK) antagonist Compound C (10 mg/kg), were administered to respective mouse cohorts daily beginning 4 days following AAA induction. Further AAA cohorts received either the AMPK agonist AICA riboside (500 mg/kg) as positive, or vehicle (saline) as negative, controls. AAA progression in all groups was assessed via serial in vivo ultrasonography and histopathology at sacrifice. Cytokine-producing T cells and myeloid cellularity were determined by flow cytometric analyses. Results: Metformin limited established experimental AAA progression at 3 (-85%) and 10 (-68%) days following treatment initiation compared with saline control. Concurrent Compound C treatment reduced this effect by approximately 50%. In metformin-treated mice, reduced AAA progression was associated with relative elastin preservation, smooth muscle cell preservation, and reduced mural leukocyte infiltration and neoangiogenesis compared with vehicle control group. Metformin also resulted in reduced interferon-γ-, but not interleukin-10 or -17, producing splenic T cells in aneurysmal mice. Additionally, metformin therapy increased circulating and splenic inflammatory monocytes (CD11b+Ly-6Chigh), but not neutrophils (CD11b+Ly-6G+), with no effect on respective bone marrow cell populations. Conclusions: Metformin treatment suppresses existing experimental AAA progression in part via AMPK agonist activity, limiting interferon-γ-producing T cell differentiation while enhancing circulating and splenic inflammatory monocyte retention.
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Background Although diabetes attenuates abdominal aortic aneurysms (AAAs), the mechanisms by which diabetes suppresses AAAs remain incompletely understood. Accumulation of advanced glycation end- (AGEs) reduces extracellular matrix (ECM) degradation in diabetes. Because ECM degradation is critical for AAA pathogenesis, we investigated whether AGEs mediate experimental AAA suppression in diabetes by blocking AGE formation or disrupting AGE-ECM cross-linking using small molecule inhibitors. Methods and Results Male C57BL/6J mice were treated with streptozotocin and intra-aortic elastase infusion to induce diabetes and experimental AAAs, respectively. Aminoguanidine (AGE formation inhibitor, 200 mg/kg), alagebrium (AGE-ECM cross-linking disrupter, 20 mg/kg), or vehicle was administered daily to mice from the last day following streptozotocin injection. AAAs were assessed via serial aortic diameter measurements, histopathology, and in vitro medial elastolysis assays. Treatment with aminoguanidine, not alagebrium, diminished AGEs in diabetic AAAs. Treatment with both inhibitors enhanced aortic enlargement in diabetic mice as compared with vehicle treatment. Neither enhanced AAA enlargement in nondiabetic mice. AAA enhancement in diabetic mice by aminoguanidine or alagebrium treatment promoted elastin degradation, smooth muscle cell depletion, mural macrophage accumulation, and neoangiogenesis without affecting matrix metalloproteinases, C-C motif chemokine ligand 2, or serum glucose concentration. Additionally, treatment with both inhibitors reversed suppression of diabetic aortic medial elastolysis by porcine pancreatic elastase in vitro. Conclusions Inhibiting AGE formation or AGE-ECM cross-linking enhances experimental AAAs in diabetes. These findings support the hypothesis that AGEs attenuate experimental AAAs in diabetes. These findings underscore the potential translational value of enhanced ECM cross-linking as an inhibitory strategy for early AAA disease.
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Aneurisma da Aorta Abdominal , Diabetes Mellitus Experimental , Camundongos , Masculino , Animais , Suínos , Aorta Abdominal/patologia , Produtos Finais de Glicação Avançada/metabolismo , Diabetes Mellitus Experimental/metabolismo , Reação de Maillard , Estreptozocina/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/prevenção & controle , Aneurisma da Aorta Abdominal/metabolismo , Colágeno/metabolismoRESUMO
BACKGROUND: The Global Vascular Guidelines (GVG) recommend selecting an endovascular versus open-surgical approach to revascularization for chronic limb-threatening ischemia (CLTI), based on the Global Limb Anatomic Staging System (GLASS) and wound, ischemia, and foot infection (WIfI) classification systems. We assessed the utility of GVG-recommended strategies in predicting clinical outcomes. METHODS: We conducted a single-center, retrospective review of first-time lower-extremity revascularizations within a comprehensive limb-preservation program from 2010 to 2018. Procedures were stratified by (1) treatment concordance with GVG-recommended strategy (concordant versus nonconcordant groups), (2) GLASS stages I-III, and (3) endovascular versus open strategies. The primary outcome was 5-year freedom from major adverse limb events (FF-MALE), defined as freedom from reintervention or major amputation, and secondary outcomes included 5-year overall survival, freedom from major amputation, freedom from reintervention, and immediate technical failure (ITF) during initial revascularization. Kaplan-Meier (KM) survival analysis and multivariate analysis with Cox proportional hazard models were performed on the primary and secondary outcomes. RESULTS: Of 281 first-time revascularizations for CLTI, 251 (89.3%) were endovascular and 186 (66.2%) were in the concordant group, with a mean clinical follow-up of 3.02 ± 2.40 years. Within the concordant group alone, 167 (89.8%) of revascularizations were endovascular. The concordant group had a higher rate of chronic kidney disease (60.8% vs. 45.3%, P = 0.02), WIfI foot infection grade (0.81 ± 1.1 vs. 0.56 ± 0.80, P = 0.03), and WIfI stage (3.1 ± 0.79 vs. 2.8 ± 1.2, P < 0.01) compared to the non-concordant group. After both KM and multivariate analyses, there were no significant differences in 5-year FF-MALE or overall survival between concordant and non-concordant groups. There was higher freedom from major amputation in the non-concordant group on KM analysis (83.9% vs. 74.2%, P = 0.025), though this difference was non-significant on multivariate analysis (hazard ratio [HR]: 0.49, 95% confidence interval [CI]: 0.21-1.15, P = 0.10). The open group had lower MALE compared to the endovascular group (HR: 0.39, 95% CI: 0.17-0.91, P = 0.029) attributed to a lower reintervention rate in the open group (HR: 0.31, 95% CI: 0.11-0.87, P = 0.026). GLASS stage was not associated with significant differences in outcomes, but the severity of GLASS stage was associated with ITF (2.1% in stage 1, 6.4% in stage 2, and 11.7% in stage 3, P = 0.01). CONCLUSIONS: In this study, CLTI treatment outcomes did not differ significantly based on whether treatment was received in concordance with GVG-recommended strategy. There was no difference in overall survival between the endovascular and open groups, though there was a higher reintervention rate in the endovascular group. The GVG guidelines are an important resource to help guide the management of CLTI patients. However, in this study, both concordance with GVG guidelines and GLASS staging were found to be indeterminate in differentiating outcomes between complex CLTI patients treated primarily with an endovascular-first approach. The revascularization approach for a CLTI patient is a nuanced decision that must take into account patient anatomy and clinical status, as well as physician skill and experience and institutional resources.
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Procedimentos Endovasculares , Doença Arterial Periférica , Humanos , Resultado do Tratamento , Salvamento de Membro/efeitos adversos , Fatores de Risco , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Fatores de Tempo , Isquemia/diagnóstico por imagem , Isquemia/cirurgia , Isquemia Crônica Crítica de Membro , Doença Crônica , Estudos RetrospectivosRESUMO
OBJECTIVE: Since 2005, the United States Preventative Services Task Force has recommended abdominal aortic aneurysm (AAA) ultrasound screening for 65- to 75-year-old male ever-smokers. Integrated health systems such as Kaiser Permanente and the Veterans Affairs (VA) health care system report 74% to 79% adherence, but compliance rates in the private sector are unknown. METHODS: The IBM Marketscan Commercial and Medicare Supplemental databases (2006-2017) were queried for male ever-smokers continuously enrolled from age 65 to 75 years. Exclusion criteria were previous history of AAA, connective tissue disorder, and aortic surgery. Patients with abdominal computed tomographic or magnetic resonance imaging from ages 65 to 75 years were also excluded. Screening was defined as a complete abdominal, retroperitoneal, or aortic ultrasound. A logistic mixed-effects model utilizing state as a random intercept was used to identify patient characteristics associated with screening. RESULTS: Of 35,154 eligible patients, 13,612 (38.7%) underwent screening. Compliance varied by state, ranging from 24.4% in Minnesota to 51.6% in Montana (P < .05). Screening activity increased yearly, with 0.7% of screening activity occurring in 2008 vs 22.2% in 2016 (P <.05). In a logistic mixed-effects model adjusting for state as a random intercept, history of hypertension (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03-1.13), coronary artery disease (OR, 1.17; 95% CI, 1.10-1.22), congestive heart failure (OR, 1.14; 95% CI, 1.01-1.22), diabetes (OR, 1.1; 95% CI, 1.06-1.16), and chronic kidney disease (OR, 1.4; 95% CI, 1.24-1.53) were associated with screening. Living outside of a census-designated metropolitan area was negatively associated with screening (OR, 0.92; 95% CI, 0.87-0.97). CONCLUSIONS: In a private claims database representing 250 million claimants, 38.7% of eligible patients received United States Preventative Services Task Force-recommended AAA screening. Compliance was nearly one-half that of integrated health systems and was significantly lower for patients living outside of metropolitan areas. Efforts to improve early detection of AAA should include targeting non-metropolitan areas and modifying Medicare reimbursement and incentivization strategies to improve guideline adherence.
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Aneurisma da Aorta Abdominal , Doença da Artéria Coronariana , Humanos , Masculino , Estados Unidos , Idoso , Medicare , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , United States Department of Veterans Affairs , Programas de Rastreamento/métodosRESUMO
OBJECTIVE: Practice patterns and durability of parallel stent graft techniques in complex endovascular aneurysm repair (EVAR) remain poorly defined. We aimed to quantify and compare the impact of renal chimney intra-aortic stent length (IASL) on geometric deformations of renal arteries in complex EVAR. METHODS: Thirty-eight nonconsecutive patients underwent EVAR utilizing parallel stent graft techniques (chimney EVAR [chEVAR], n = 28; chimney endovascular aneurysm sealing [chEVAS], n = 10) between 2010 and 2016. A total of 59 renal chimney stent grafts were used. Geometric quantification was derived from three-dimensional model-based centerline extraction. Renal chimney intra-aortic stent length (IASL) was defined as the length of chimney stent that extended from the proximal edge of the chimney stent to the ostium of the corresponding renal artery. RESULTS: Mean IASL for both left and right renal arteries in the cohort was 35.7 mm. Renal arteries containing chimney IASL <30 mm trended toward a greater branch angle (135.4 vs. 127.8°, p = .06). Left renal arteries showed significantly greater branch angle among those with IASL <40 mm (135.5 vs. 121.7°, p = .045). Mean IASL for renal arteries in chEVAR was significantly longer compared to chEVAS (39.2 vs. 26.3 mm, p = .003). No difference was noted in overall branch angle or end-stent angle based on procedure type. ChEVAR with IASL <30 mm had significantly greater end-stent angle (48.2 vs. 33.5°, p = .03). In contrast, chEVAS patients showed no difference in end-stent angle based on IASL thresholds, but did have significantly greater branch angle among those with IASL <30 mm when grouped by both all renal arteries (133.5 vs. 113.5°, p = .004) and right renal arteries (134.3 vs. 111.6°, p = .02). CONCLUSIONS: Renal chimney stents with longer IASL appear to exhibit less renal artery deformation, suggesting a more gradual and perpendicular transition of the chimney stent across the renal ostium.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Correção Endovascular de Aneurisma , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Aortografia/métodos , Stents , Desenho de PróteseRESUMO
OBJECTIVE: Type I interferon receptor signaling contributes to several autoimmune and vascular diseases such as lupus, atherosclerosis and stroke. The purpose of this study was to assess the influence of type I interferon receptor deficiency on the formation and progression of experimental abdominal aortic aneurysms (AAAs). METHODS: AAAs were induced in type I interferon receptor subunit 1 (IFNAR1)-deficient and wild type control male mice via intra-infrarenal aortic infusion of porcine pancreatic elastase. Immunostaining for IFNAR1 was evaluated in experimental and clinical aneurysmal abdominal aortae. The initiation and progression of experimental AAAs were assessed via ultrasound imaging prior to (day 0) and days 3, 7 and 14 following elastase infusion. Aneurysmal histopathology was analyzed at sacrifice. RESULTS: Increased aortic medial and adventitial IFNAR1 expression was present in both clinical AAAs harvested at surgery and experimental AAAs. Following AAA induction, wild type mice experienced progressive, time-dependent infrarenal aortic enlargement. This progression was substantially attenuated in IFNAR1-deficient mice. On histological analyses, medial elastin degradation, smooth muscle cell depletion, leukocyte accumulation and neoangiogenesis were markedly diminished in IFNAR1-deficient mice in comparison to wild type mice. CONCLUSION: IFNAR1 deficiency limited experimental AAA progression in response to intra-aortic elastase infusion. Combined with clinical observations, these results suggest an important role for IFNAR1 activity in AAA pathogenesis.
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Aneurisma da Aorta Abdominal , Camundongos , Masculino , Suínos , Animais , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/metabolismo , Camundongos Endogâmicos C57BL , Receptor de Interferon alfa e beta/genética , Elastina , Modelos Animais de Doenças , Elastase PancreáticaRESUMO
OBJECTIVE: This study was an unplanned exploratory analysis of a subset of participants from the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. It aimed to assess the efficacy of the angiotensin 1 receptor blocker telmisartan in reducing abdominal aortic aneurysm (AAA) peak wall stress (PWS) and peak wall rupture index (PWRI) among individuals with small AAAs. METHODS: Participants with AAAs measuring 35 - 49 mm in maximum diameter were randomised to receive telmisartan 40 mg or identical placebo in the TEDY trial. Participants who had computed tomography angiography performed at entry and at least one other time point during the trial (12 or 24 months) were included in the current study. Orthogonal AAA diameter, PWS, and PWRI were measured using previously validated methods. The annual change in PWS and PWRI from baseline was compared between participants allocated telmisartan or placebo using linear mixed effects models. These models were either unadjusted or adjusted for risk factors that were different in the groups at entry (p < .100) or systolic blood pressure (SBP) at one year. RESULTS: Of the 207 participants recruited to TEDY, 124 were eligible for inclusion in this study. This study included 65 and 59 participants from the telmisartan and placebo groups, respectively. The PWS and PWRI were not significantly different in the two groups at baseline. Participants allocated telmisartan had a slower annual increase in PWS (-4.19; 95% CI -8.24, -0.14 kPa/year; p = .043) and PWRI (-0.014; 95% CI -0.026, -0.001; p = .032) compared with those allocated placebo after adjusting for risk factors. After adjustment for SBP at one year, telmisartan did not significantly reduce annual increases in PWS or PWRI. CONCLUSION: The findings of this study suggest that telmisartan limits the rate of increase in PWS and PWRI of small AAAs by reducing blood pressure.
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Aneurisma da Aorta Abdominal , Ruptura Aórtica , Humanos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/complicações , Ruptura Aórtica/etiologia , Telmisartan/uso terapêutico , Aortografia/métodos , Medição de Risco , Estresse Mecânico , Análise de Elementos Finitos , Aorta Abdominal/diagnóstico por imagemRESUMO
BACKGROUND: The need for multidisciplinary care of patients with advanced limb threat is well established. We examined patient reported outcomes and health-related quality of life (HR-QoL) for those who completed a multidisciplinary extremity preservation program (EPP) at our institution. METHODS: Patients with advanced limb threat, who had previously failed standard management at a tertiary-care center, were referred to EPP for evaluation by a multidisciplinary panel of vascular, plastic, orthopedic and podiatric surgeons, along with infectious disease, prosthetics, orthotics, imaging, palliative care, social work and wound nursing specialists. HR-QoL was quantified before and after EPP participation with the RAND-36 questionnaire. The validated RAND-36 assesses physical function, role limitations caused by physical and emotional health problems, social functioning, emotional well-being, energy, pain and general health perceptions. RESULTS: From 2018 to 2020, 185 patients were referred to EPP. After review by the multidisciplinary panel, 120 were accepted into the program, 63 of whom completed their course of care; 9 were one-time consultations. The median number of EPP in-person care visits was 23 (13-54) per participant; 87.3% of patients received one or more surgical procedure, including operative debridement (73%), revascularization (44%), soft-tissue reconstruction or transplantation (46%), as well as hyperbaric oxygen therapy (11%) during their course of treatment. 85.7% of patients achieved complete wound healing, 41.5% occurring within 6 months. Ultimately, 14.3% required a major amputation. Graduates noted improvement in all categories of the HR-QoL upon completion, including those undergoing major amputation. On adjusted multivariate regression analysis, patients with immunocompromised status were more likely to show greater improvement in their social function (OR: 10.1; P < 0.044) and emotional role limitation (OR: 8.1; P = 0.042), while, patients with larger wound volume at presentation were more likely to have greater improvement in their general health (OR: 1.1; P < 0.049). Conversely, patients with a smoking history had less improvement in energy level (OR: 0.4; P = 0.044) and patients with dialysis-dependence had less improvement in social function (OR: 0.2; P = 0.034). CONCLUSIONS: Coordinated, multidisciplinary extremity preservation program improves HR-QoL of patients with complex limb threat, including those who are immunocompromised with impaired social function and emotional role limitations. Furthermore, study is warranted to better characterize the generalizability of this approach, including considerations of cost-effectiveness, wound recidivism, and limiting the number of in-person visits required to achieve complete healing.
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Salvamento de Membro , Qualidade de Vida , Humanos , Salvamento de Membro/efeitos adversos , Isquemia , Resultado do Tratamento , Fatores de Tempo , Amputação Cirúrgica/efeitos adversos , Extremidade Inferior/irrigação sanguínea , Estudos RetrospectivosRESUMO
OBJECTIVE: Fenestrated endovascular aneurysm repair (FEVAR) is increasingly used in the treatment of juxtarenal aortic aneurysms and short-neck infrarenal aneurysms. Reinterventions (REIs) occur frequently, contributing to patient morbidity and resource utilization. We sought to determine whether REI affects long-term survival after FEVAR. METHODS: A single-institution retrospective review of all Cook Zenith fenestrated (ZFEN; Cook Medical, Inc, Bloomington, IN) repairs was performed. Patients with ≥6 months of follow-up and without adjunctive branch modifications were included. REI was defined as any aneurysm, device, target branch, or access-related intervention after the index procedure. REIs were categorized as early (<30 days) or late (≥30 days), by indication (ie, branch, endoleak, limb related, access related, other), and by target branch or device components. Patients were stratified into REI vs no REI groups and branch REI vs non-branch REI groups. RESULTS: Of 219 consecutive ZFEN repairs from 2012 to 2021, 158 patients met the inclusion criteria. Of these 158 patients, 41 (26%) required a total of 51 REIs (10 early and 41 late) during a mean follow-up of 33.9 months. The most common indication for REI was branch-related (31 of 51; 61%), with the renal arteries the most frequently affected (26 of 51; 51%). The only differences found in baseline, aneurysm, and device characteristics were a higher mean Society for Vascular Surgery comorbidity score (9.6 vs 7.9; P = .04) and larger suprarenal neck angle (23.3° vs 17.1°; P = .04) in the no REI group. In contrast, the REI group had a larger mean proximal seal zone diameter (26.3 mm vs 25.1 mm; P = .03) and device diameter (31.9 mm vs 30.0 mm; P = .002) compared with the no REI group. Technical success and operative characteristics were similar between the groups, except for a longer mean fluoroscopy time (74.9 minutes vs 60.8 minutes; P = .01) and longer median length of stay (2 vs 2 days; P = .006) for the REI group. Although the rate of early (<30 days) major adverse events was greater for the REI group (24.4% vs 6.0%; P = .001), the difference in 30-day mortality was not statistically significant (4.9% vs 0.9%; P = .10). On Kaplan-Meier analysis, freedom from REI at 1 and 5 years was 85.7% and 62.6%, respectively, for the overall cohort. No difference was found in the estimated 5-year survival between the REI and no REI groups (62.8% vs 63.5%; log-rank, P = .87) and branch REI and non-branch REI groups (71.8% vs 49.9%; log-rank, P = .16). On multivariate analysis, REI was not an independent predictor for mortality. However, age, Society for Vascular Surgery comorbidity score, and preoperative maximum aneurysm diameter each increased the hazard of death (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12 [P = .007]; HR, 1.10; 95% CI, 1.01-1.18 [P = .02]; HR, 1.05; 95% CI, 1.02-1.08 [P = .003], respectively). CONCLUSIONS: After ZFEN, 41 patients (26%) had required a total of 51 REIs, with most occurring ≥30 days after the index procedure, and 61% were branch related, with no influence on 5-year survival. Age, comorbidity, and baseline aneurysm diameter independently predicted mortality. The use of FEVAR mandates lifelong surveillance and protocols to maintain branch patency. Despite their relative frequency, REIs did not influence 5-year postprocedural survival.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/etiologia , Prótese Vascular , Desenho de Prótese , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , Estudos RetrospectivosRESUMO
Background: The durability of fenestrated endovascular aneurysm repair (fEVAR) has been threatened by thrombotic complications. In the present study, we used patient-specific computational fluid dynamic (CFD) simulation to investigate the effect of the endograft diameter on hemodynamics after fEVAR and explore the hypothesis that diameter-dependent alterations in aortic hemodynamics can predict for thrombotic events. Methods: A single-institutional retrospective study was performed of patients who had undergone fEVAR for juxtarenal aortic aneurysms. The patients were stratified into large diameter (34-36 mm) and small diameter (24-26 mm) endograft groups. Patient-specific CFD simulations were performed using three-dimensional paravisceral aortic models created from computed tomographic images with allometrically scaled boundary conditions. Aortic time-averaged wall shear stress (TAWSS) and residence time (RT) were computed and correlated with future thrombotic complications (eg, renal stent occlusion, development of significant intraluminal graft thrombus). Results: A total of 36 patients (14 with a small endograft and 22 with a large endograft) were included in the present study. The patients treated with large endografts had experienced a higher incidence of thrombotic complications compared with small endografts (45.5% vs 7.1%; P = .016). Large endografts were associated with a lower postoperative aortic TAWSS (1.45 ± 0.76 dynes/cm2 vs 3.16 ± 1.24 dynes/cm2; P < .001) and longer aortic RT (0.78 ± 0.30 second vs 0.34 ± 0.08 second; P < .001). In the large endograft group, a reduction >0.39 dynes/cm2 in aortic TAWSS demonstrated discriminatory power for thrombotic complications (area under the receiver operating characteristic curve, 0.77). An increased aortic RT of ≥0.05 second had similar accuracy for predicting thrombotic complications (area under the receiver operating characteristic curve, 0.78). The odds of thrombotic complications were significantly higher if patients had met the hemodynamic threshold changes in aortic TAWSS (odds ratio, 7.0; 95% confidence interval, 1.1-45.9) and RT (odds ratio, 8.0; 95% confidence interval, 1.13-56.8). Conclusions: Patient-specific CFD simulation of fEVAR in juxtarenal aortic aneurysms demonstrated significant endograft diameter-dependent differences in aortic hemodynamics. A postoperative reduction in TAWSS and an increased RT correlated with future thrombotic events after large-diameter endograft implantation. Patient-specific simulation of hemodynamics provides a novel method for thrombotic risk stratification after fEVAR.