Paraplegia prevention in aortic aneurysm repair by thoracoabdominal staging with 'minimally invasive staged segmental artery coil embolisation' (MIS²ACE): trial protocol for a randomised controlled multicentre trial.
ABSTRACT: INTRODUCTION:Spinal cord injury (SCI) including permanent paraplegia constitutes a common complication after repair of thoracoabdominal aortic aneurysms. The staged-repair concept promises to provide protection by inducing arteriogenesis so that the collateral network can provide a robust blood supply to the spinal cord after intervention. Minimally invasive staged segmental artery coil embolisation (MIS2ACE) has been proved recently to be a feasible enhanced approach to staged repair. METHODS AND ANALYSIS:This randomised controlled trial uses a multicentre, multinational, parallel group design, where 500 patients will be randomised in a 1:1 ratio to standard aneurysm repair or to MIS2ACE in 1-3 sessions followed by repair. Before randomisation, physicians document whether open or endovascular repair is planned. The primary endpoint is successful aneurysm repair without substantial SCI 30 days after aneurysm repair. Secondary endpoints include any form of SCI, mortality (up to 1 year), length of stay in the intensive care unit, costs and quality-adjusted life years. A generalised linear mixed model will be used with the logit link function and randomisation arm, mode of repair (open or endovascular repair), the Crawford type and the European System for Cardiac Operative Risk Evaluation (euroSCORE) II as fixed effects and the centre as a random effect. Safety endpoints include kidney failure, respiratory failure and embolic events (also from debris). A qualitative study will explore patient perceptions. ETHICS AND DISSEMINATION:This trial has been approved by the lead Ethics Committee from the University of Leipzig (435/17-ek) and will be reviewed by each of the Ethics Committees at the trial sites. A dedicated project is coordinating communication and dissemination of the trial. TRIAL REGISTRATION NUMBER:NCT03434314.
Project description:In patients with large abdominal aortic aneurysm (AAA), open surgical or endovascular aneurysm repair procedures are often used to minimise the risk of aneurysm-related rupture and death; however, aneurysm repair itself carries a high risk. Low cardiopulmonary fitness is associated with an increased risk of early post-operative complications and death following elective AAA repair. Therefore, fitness should be enhanced before aneurysm repair. High-intensity interval exercise training (HIT) is a potent, time-efficient strategy for enhancing cardiopulmonary fitness. Here, we describe a feasibility study for a definitive trial of a pre-operative HIT intervention to improve post-operative outcomes in patients undergoing elective AAA repair.A minimum of 50 patients awaiting elective repair of a 5.5-7.0 cm infrarenal AAA will be allocated by minimisation to HIT or usual care control in a 1:1 ratio. The patients allocated to HIT will complete three hospital-based exercise sessions per week, for 4 weeks. Each session will include 2 or 4 min of high-intensity stationary cycling followed by the same duration of easy cycling or passive recovery, repeated until a total of 16 min of high-intensity exercise is accumulated. Outcomes to be assessed before randomisation and 24-48 h before aneurysm repair include cardiopulmonary fitness, maximum AAA diameter and health-related quality of life. In the post-operative period, we will record destination (ward or critical care unit), organ-specific morbidity, mortality and the durations of critical care and hospital stay. Twelve weeks after the discharge, participants will be interviewed to reassess quality of life and determine post-discharge healthcare utilisation. The costs associated with the exercise intervention and healthcare utilisation will be calculated.Ethics approval was secured through Sunderland Research Ethics Committee. The findings of the trial will be disseminated through peer-reviewed journals, and national and international presentations.Current Controlled Trials ISRCTN09433624.
Project description:INTRODUCTION:Type II endoleak (EL) is frequently seen after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) and is often considered responsible for aneurysm sac enlargement if it persists. In order to reduce type II EL and consequent sac enlargement, pre-emptive embolisation of the inferior mesenteric artery (IMA), which is a main source for persistent type II EL, has been introduced in many vascular centres. At present, there is a lack of robust evidence to support the efficacy of pre-emptive embolisation of IMA on reduction of persistent type II EL with subsequent sac shrinkage. METHOD AND ANALYSIS:This multicentre, randomised controlled trial will recruit 200 patients who have fusiform AAA ?50?mm/rapidly enlarging fusiform AAA, with patent IMA, and randomly allocate them either to a pre-emptive IMA embolisation group or non-embolisation control group in a ratio of 1:1. The primary endpoint is the difference of aneurysm sac volume change assessed by CT scans between the pre-emptive IMA embolisation group and the control group at 12 months after EVAR. The secondary endpoints are defined as change of aneurysm sac volume in both groups at 6 and 24 months, freedom from sac enlargement at 12 and 24 months after EVAR, prevalence of type II EL at 1, 6, 12 and 24 months evaluated by contrast-enhanced CT, reintervention rate, aneurysm related mortality, overall survival, perioperative morbidity, volume of contrast media used during EVAR and dosage of radiation. ETHICS AND DISSEMINATION:The protocol has been reviewed and approved by the ethics committee of Nara Medical University (No. 2113). The findings of this study will be communicated to healthcare professionals, participants and the public through peer-reviewed publications, scientific conferences and the University Hospital Medical Information Network Clinical Trials Registry home page. TRIAL REGISTRATION NUMBER:UMIN000035502.
Project description:INTRODUCTION:Strict imaging surveillance protocols to detect complications following endovascular aneurysm repair (EVAR) are common practice. However, controversy exists as to whether all EVAR patients need intense surveillance. The 2019 European Society for Vascular Surgery guidelines for management of abdominal aortic aneurysm (AAA) suggest that patients may be considered for limited follow-up with imaging if classified as 'low risk' for complications based on their initial postoperative imaging. The current study aims to investigate the intervention-free survival and overall survival stratified for patients with and without yearly imaging surveillance. METHODS AND ANALYSIS:The Observing a Decade of Yearly Standardised Surveillance in EVAR patients with Ultrasound or CT Scan study comprises a national multicentre retrospective cohort study in 17 medical centres. Consecutive patients with an asymptomatic or symptomatic infrarenal AAA who underwent EVAR between January 2007 and January 2012 will be included in this study with follow-up until December 2018. Clinical variables and all follow-up information will be retrieved in extensive data collection from the patient's medical records. In addition, an e-survey was sent to vascular surgeons at the 17 participating centres to gauge their opinions regarding the possibility of safely reducing the frequency of imaging surveillance. Primary endpoints are intervention after EVAR and aneurysm-related mortality. The initial estimated sample size is 1997 patients. ETHICS AND DISSEMINATION:The study has been approved by the Medical Ethics Review Committee of the Amsterdam UMC, location Academic Medical Centre, Amsterdam, the Netherlands. Study findings will be disseminated via presentations at conferences and publications in peer-reviewed journal. TRIAL REGISTRATION NUMBER:The Netherlands Trial Registry, NL6953 (old: NTR28773).
Project description:Acute kidney injury (AKI) is one of the most common post-operative complications and is closely associated with increased mortality after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Ribonuclease (RNase) 1 belongs to the group of antimicrobial peptides elevated in septic patients and indicates the prediction of two or more organ failures. The role of RNase 1 and its antagonist RNase inhibitor 1 (RNH1) after TAAA repair is unknown. In this study, we analyzed RNase 1 and RNH1 serum levels in patients undergoing open (n = 14) or endovascular (n = 19) TAAA repair to determine their association with post-operative AKI and in-hospital mortality. Increased RNH1 serum levels after open TAAA repair as compared with endovascular TAAA repair immediately after surgery and 12, 48, and 72 h after surgery (all p < 0.05) were observed. Additionally, elevated RNase 1 and RNH1 serum levels 12, 24, and 48 h after surgery were shown to be significantly associated with AKI (all p < 0.05). RNH1 serum levels before and RNase 1 serum levels 12 h after TAAA repair were significantly correlated with in-hospital mortality (both p < 0.05). On the basis of these findings, RNase 1 and RNH1 may be therapeutically relevant and may represent biomarkers for post-operative AKI and in-hospital mortality.
Project description:BACKGROUND:Much of the literature describing treatment for thoracoabdominal aortic aneurysm (TAAA) consists of operative series reported by centers of excellence. These studies are limited by referral and selection bias and exclude patients who are not candidates for the reported modality of repair. Little is known about the patients who are not referred or selected for repair. For those undergoing intervention, outcomes such as functional status after surgery are rarely reported. In this study, we address these gaps by reporting two primary end points: 1-year survival and a "good" outcome (defined as successful aneurysm exclusion, freedom from permanent loss of organ system function, and return to preoperative functional status after surgery) in a cohort of TAAA patients, including all nonoperative and operative patients, irrespective of treatment modality. METHODS:A single-institution database was screened by diagnosis codes for TAAA from 2009 to 2017 using the International Classification of Diseases versions 9 and 10. Diagnosis was confirmed by retrospective chart review and computed tomography findings of aneurysmal degeneration ?3.2 cm of the paravisceral aorta in continuity with aneurysmal aorta meeting standard criteria for repair. Patients <18 years of age and those with mycotic aneurysm were excluded. Patients were either managed nonoperatively or by one of four operative strategies: (i) open; (ii) endovascular with branched endografts; (iii) hybrid, defined as iliovisceral debranching followed by endograft placement; or (iv) partial repair in which the paravisceral segment was intentionally left unaddressed. RESULTS:Among the entire cohort of 432 patients with TAAA, significant comorbidities were seen in 143 (33%). Forty-seven percent of the patients were managed nonoperatively. Of these, 65% survived to 1 year. A survival benefit was seen in the open, endovascular, and partial, but not hybrid, operative groups compared with the nonoperative group during a 3-year period. Overall 1-year survival was 81%, but only 65% had a good outcome (P = .0016). CONCLUSIONS:Nearly half of the patients in this inclusive cohort study did not undergo repair despite access to a variety of operative techniques. Many of these patients die in the short term due to high burden of comorbid disease rather than aneurysm rupture. Among those undergoing operation, a notable difference between survival and good outcome was observed. Operation appears to confer a survival advantage among appropriately selected patients with TAAA, but a large proportion are high risk and may not benefit from operative repair due to limited baseline survival and lower probability of good outcome.
Project description:To characterize the inflammatory and coagulopathic response after endovascular thoracoabdominal aortic aneurysm (TAAA) repair and to evaluate the effect of the response on postoperative renal function.From July 2005 to June 2008, 42 patients underwent elective endovascular repair of a TAAA using custom designed multi-branched stent-grafts at a single academic institution. Four patients were excluded from the analysis. White blood cell count (WBC), platelet count, prothrombin time (PT), and creatinine were measured in all patients. In the last nine patients, interleukin-6 (IL-6), protein C, Factor V, d-dimers, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) levels were also measured. Change in lab values were expressed as a percentage of baseline values.The 30-day mortality rate was 5% (2/38). All patients (n = 38) had a higher WBC (mean +/- SD: 139 +/- 80%, P < .0001), lower platelet count (56 +/- 15%, P < .0001), and higher PT (median: 17%, Interquartile range (IQR) 12%-22%, P < .0001) after stent-graft insertion. Twelve of 38 patients (32%) developed postoperative acute renal insufficiency (>50% rise in creatinine). Patients with renal insufficiency had significantly larger changes in WBC (178 +/- 100% vs 121 +/- 64%, P = .04) and platelet count (64 +/- 17% vs 52 +/- 12%, P = .02) compared with those without renal insufficiency. All patients (n = 9) had significant increases in NGAL (182 +/- 115%, P = .008) after stent-graft insertion. Six of nine patients (67%) had increased cystatin C (35 +/- 43%, P = .04) after stent-graft insertion, with a greater rise in those with postoperative renal insufficiency (87 +/- 32% vs 8 +/- 13%, P = .02). IL-6 levels were markedly increased in all patients (n = 9) after repair (9840 +/- 6160%, P = .008). Protein C (35 +/- 10%, P = .008) and Factor V levels (28 +/- 20%, P = .008) were uniformly decreased, while d-dimers were elevated after repair in all patients (310 +/- 213%, P = .008).Leukocytosis and thrombocytopenia were uniform following endovascular TAAA repair, and the severity of the response correlated with post-operative renal dysfunction. Elevation of a sensitive marker of renal injury (NGAL) suggests that renal injury may occur in all patients after stent-graft insertion.
Project description:Randomized trials and observational studies have shown that perioperative morbidity and mortality are lower with endovascular repair of abdominal aortic aneurysm than with open repair, but the survival benefit is not sustained. In addition, concerns have been raised about the long-term risk of aneurysm rupture or the need for reintervention after endovascular repair.We assessed perioperative and long-term survival, reinterventions, and complications after endovascular repair as compared with open repair of abdominal aortic aneurysm in propensity-score-matched cohorts of Medicare beneficiaries who underwent repair during the period from 2001 through 2008 and were followed through 2009.We identified 39,966 matched pairs of patients who had undergone either open repair or endovascular repair. The overall perioperative mortality was 1.6% with endovascular repair versus 5.2% with open repair (P<0.001). From 2001 through 2008, perioperative mortality decreased by 0.8 percentage points among patients who underwent endovascular repair (P=0.001) and by 0.6 percentage points among patients who underwent open repair (P=0.01). The rate of conversion from endovascular to open repair decreased from 2.2% in 2001 to 0.3% in 2008 (P<0.001). The rate of survival was significantly higher after endovascular repair than after open repair through the first 3 years of follow-up, after which time the rates of survival were similar. Through 8 years of follow-up, interventions related to the management of the aneurysm or its complications were more common after endovascular repair, whereas interventions for complications related to laparotomy were more common after open repair. Aneurysm rupture occurred in 5.4% of patients after endovascular repair versus 1.4% of patients after open repair through 8 years of follow-up (P<0.001). The rate of total reinterventions at 2 years after endovascular repair decreased over time (from 10.4% among patients who underwent procedures in 2001 to 9.1% among patients who underwent procedures in 2007).Endovascular repair, as compared with open repair, of abdominal aortic aneurysm was associated with a substantial early survival advantage that gradually decreased over time. The rate of late rupture was significantly higher after endovascular repair than after open repair. The outcomes of endovascular repair have been improving over time. (Funded by the National Institutes of Health.).
Project description:BACKGROUND:The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. METHODS:An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. RESULTS:The analysis included 2783 patients, with 14?245 person-years of follow-up (median 5·5?years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P?=?0·022) in the period from 6 months to 4 years after randomization. CONCLUSION:The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5?years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle?:?brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM?(Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.
Project description:Objectives:The primary aim of this study was to investigate the rate of sac enlargement and secondary procedures after 5 years when instructions for use are strictly applied with endovascular aortic repair. The secondary aim was to investigate if strict indications with endovascular aortic repair, rendering more open operations, would change the general outcome of patients with abdominal aortic aneurysm. Materials and methods:Patients having their abdominal aortic aneurysm procedure in a single institution between 01 January 2002 and 31 December 2006 were included. Indications for endovascular aortic repair were as follows: aortic neck: length 15 mm or more, diameter 32 mm or less and straight configuration; iliac arteries: length > 10 mm, 7.5-20 mm in diameter. Sac enlargement was defined as an increase in diameter of 5 mm or more. Results:A total of 123 patients were intended to be treated electively with endovascular aortic repair from 2002 to 2007 using Cook Zenith stent grafts. In the same period, 147 patients were treated with elective open repair. At 5 years, 7.3% (N = 9) of the elective intended-to-treat patients with endovascular aortic repair had a sac enlargement. Thirty-five percent of the patients were registered with endoleaks, 13% of the patients had secondary procedures, 12.2% of the patients had early and 6.5% late complications during the follow-up period. Aneurysm rupture was seen in 1.6% of the patients. During the 5-year follow-up period, 34 (27.6%) of the endovascular aortic repair patients died. Five-year mortality for open repair was 23.8%, and 12.2% of the open repair patients had secondary procedures. Conclusion:Endovascular aortic repair for abdominal aortic aneurysm in accordance with instructions for use gives a low long-term risk for increased diameter and low rate of secondary procedures. There was similar mortality after elective endovascular aortic repair and open repair for abdominal aortic aneurysm. Applying endovascular aortic repair according to instructions for use does not seem to change the general outcome of patients with abdominal aortic aneurysm but improves the outcome with the method.
Project description:Hybrid visceral-renal debranching procedures with endovascular repair have been proposed as an appealing technique to treat conventional thoracoabdominal aortic aneurysm (TAAA). This approach, however, still remained controversial because of the non-physiological blood flow direction of its retrograde visceral revascularization (RVR) which is generally constructed from the aortic bifurcation or common iliac artery. The current study carried out the numerical simulation to investigate the effect of RVR on the hemodynamics of abdominal aorta. The results indicated that the inflow sites for the RVR have great impact on the hemodynamic performance. When RVR was from the distal aorta, the perfusion to visceral organs were adequate but the flow flux to the iliac artery significantly decreased and a complex disturbed flow field developed at the distal aorta, which endangered the aorta at high risk of aneurysm development. When RVR was from the right iliac artery, the abdominal aorta was not troubled with low WSS or disturbed flow, but the inadequate perfusion to the visceral organs reached up to 40% and low WSS and flow velocity predominated appeared at the right iliac artery and the grafts, which may result in the stenosis in grafts and aneurysm growth on the host iliac artery.