Development and Validation of Medical Decision Tools in Detection and Treatment of Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a permanent dilatation of the infrarenal segment of the abdominal aorta which can be fatal if the aneurysm ruptures. Ruptured AAA is the second leading cause of global surgical mortality, and prophylactic AAA repair can decrease mortality by a tenfold if surgery is performed as an elective procedure. While screening and repair of AAA could potentially reduce AAA-related mortality, selecting patients that are likely to benefit from repair remains a complex medical decision process which has been compounded by an improved life expectancy of the general population, minimal invasive treatment methods and the increased prevalence of AAA in the elderly. The overall aim of this thesis was to improve detection and management of AAA and to develop a predictive decision tool that can assist in clinical management. This thesis has been conducted, to shed some light into issues highlighted above using New Zealand and international data. The format of this thesis was categorized into three main domains: First, the prevalence of AAA and the influence of aortic size on late survival was documented in a large cohort of individuals undergoing CT colonography for gastrointestinal symptoms in Canterbury, New Zealand; Second, a systematic review and meta-analysis of prognostic factors that might influence late survival following AAA repair were performed, and the national clinical and administrative AAA repair databases were interrogated to provide epidemiological and outcome data; Third, the factors identified from this review were applied into developing a discrete event-simulation model to predict survival following AAA repair. The model developed has been externally validated against existing national databases of patients undergoing AAA repair and it appears sufficiently accurate to predict five- year survival. The results and conclusions presented throughout this thesis fill some of the gap in AAA knowledge, and such predictive decision-making tools might help improve AAA management

The impact of COVID-19 pandemic on vascular registries and clinical trials.

Quality improvement programs and clinical trial research experienced disruption due to the coronavirus disease 2019 (COVID-19) pandemic. Vascular registries showed an immediate impact with significant declines in second-quarter vascular procedure volumes witnessed across Europe and the United States. To better understand the magnitude and impact of the pandemic, organizations and study groups sent grass roots surveys to vascular specialists for needs assessment. Several vascular registries responded quickly by insertion of COVID-19 variables into their data collection forms. More than 80% of clinical trials have been reported delayed or not started due to factors that included loss of enrollment from patient concerns or mandated institutional shutdowns, weighing the risk of trial participation on patient safety. Preliminary data of patients undergoing vascular surgery with active COVID-19 infection show inferior outcomes (morbidity) and increased mortality. Disease-specific vascular surgery study collaboratives about COVID-19 were created for the desire to study the disease in a more focused manner than possible through registry outcomes. This review describes the pandemic effect on multiple VASCUNET registries including Germany (GermanVasc), Sweden (SwedVasc), United Kingdom (UK National Vascular Registry), Australia and New Zealand (bi-national Australasian Vascular Audit), as well as the United States (Society for Vascular Surgery Vascular Quality Initiative). We will highlight the continued collaboration of VASCUNET with the Vascular Quality Initiative in the International Consortium of Vascular Registries as part of the Medical Device Epidemiology Network coordinated registry network. Vascular registries must remain flexible and responsive to new and future real-world problems affecting vascular patients

Editor's Choice - The Impact of Centralisation and Endovascular Aneurysm Repair on Treatment of Ruptured Abdominal Aortic Aneurysms Based on International Registries

Objectives: Current management of ruptured abdominal aortic aneurysms (RAAA) varies among centres and countries, particularly in the degree of implementation of endovascular aneurysm repair (EVAR) and levels of vascular surgery centralisation. This study assesses these variations and the impact they have on outcomes. Materials and methods: RAAA repairs from vascular surgical registries in 11 countries, 2010-2013, were investigated. Data were analysed overall, per country, per treatment modality (EVAR or open aortic repair [OAR]), centre volume (quintiles IV), and whether centres were predominantly EVAR (>= 50% of RAAA performed with EVAR [EVAR(p)]) or predominantly OAR [OAR(p)]. Primary outcome was peri-operative mortality. Data are presented as either mean values or percentages with 95% CI within parentheses, and compared with chi-square tests, as well as with adjusted OR. Results: There were 9273 patients included. Mean age was 74.7 (74.5-74.9) years, and 82.7% of patients were men (81.9-83.6). Mean AAA diameter at rupture was 7.6 cm (7.5-7.6). Of these aneurysms, 10.7% (10.0-11.4) were less than 5.5 cm. EVAR was performed in 23.1% (22.3-24.0). There were 6817 procedures performed in OAR(p) centres and 1217 performed in EVAR(p) centres. Overall peri-operative mortality was 28.8% (27.9-29.8). Peri-operative mortality for OAR was 32.1% (31.0-33.2) and for EVAR 17.9% (16.3-19.6), p 22 repairs per year), 23.3% (21.2-25.4) than in QII-V, 30.0% (28.9-31.1), p <.001. Peri-operative mortality after OAR was lower in high volume centres compared with the other centres, 25.3% (23.0-27.6) and 34.0% (32.7-35.4), respectively, p <.001. There was no significant difference in peri-operative mortality after EVAR between centres based on volume. Conclusions: Peri-operative mortality is lower in centres with a primary EVAR approach or with high case volume. Most repairs, however, are still performed in low volume centres and in centres with a primary OAR strategy. Reorganisation of acute vascular surgical services may improve outcomes of RAAA repair. (C) 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms

Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs). Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single- or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality. Results: A total of 1947 patients (65% male; mean age, 71 ± 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9±1.3% vs 79.6±1.7%) and 3 years (72.7±2.1% vs 64.2±2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach. Conclusions: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years

Documenting the Recovery of Vascular Services in European Centres Following the Initial COVID-19 Pandemic Peak: Results from a Multicentre Collaborative Study

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March – May 2020, “period 1”), and then again between May and June (“period 2”) and June and July 2020 (“period 3”). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries’ first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic “normal” by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries

The UK EndoVascular Aneurysm Repair (EVAR) randomised controlled trials: long-term follow-up and cost-effectiveness analysis.

BACKGROUND: Short-term survival benefits of endovascular aneurysm repair (EVAR) compared with open repair (OR) of intact abdominal aortic aneurysms have been shown in randomised trials, but this early survival benefit is soon lost. Survival benefit of EVAR was unclear at follow-up to 10 years. OBJECTIVE: To assess the long-term efficacy of EVAR against OR in patients deemed fit and suitable for both procedures (EVAR trial 1; EVAR-1); and against no intervention in patients unfit for OR (EVAR trial 2; EVAR-2). To appraise the long-term significance of type II endoleak and define criteria for intervention. DESIGN: Two national, multicentre randomised controlled trials: EVAR-1 and EVAR-2. SETTING: Patients were recruited from 37 hospitals in the UK between 1 September 1999 and 31 August 2004. PARTICIPANTS: Men and women aged ≥ 60 years with an aneurysm of ≥ 5.5 cm (as identified by computed tomography scanning), anatomically suitable and fit for OR were randomly assigned 1 : 1 to either EVAR (n = 626) or OR (n = 626) in EVAR-1 using computer-generated sequences at the trial hub. Patients considered unfit were randomly assigned to EVAR (n = 197) or no intervention (n = 207) in EVAR-2. There was no blinding. INTERVENTIONS: EVAR, OR or no intervention. MAIN OUTCOME MEASURES: The primary end points were total and aneurysm-related mortality until mid-2015 for both trials. Secondary outcomes for EVAR-1 were reinterventions, costs and cost-effectiveness. RESULTS: In EVAR-1, over a mean of 12.7 years (standard deviation 1.5 years; maximum 15.8 years), we recorded 9.3 deaths per 100 person-years in the EVAR group and 8.9 deaths per 100 person-years in the OR group [adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.97 to 1.27;p = 0.14]. At 0-6 months after randomisation, patients in the EVAR group had a lower mortality (adjusted HR 0.61, 95% CI 0.37 to 1.02 for total mortality; HR 0.47, 95% CI 0.23 to 0.93 for aneurysm-related mortality;p = 0.031), but beyond 8 years of follow-up patients in the OR group had a significantly lower mortality (adjusted HR 1.25, 95% CI 1.00 to 1.56,p = 0.048 for total mortality; HR 5.82, 95% CI 1.64 to 20.65,p = 0.0064 for aneurysm-related mortality). The increased aneurysm-related mortality in the EVAR group after 8 years was mainly attributable to secondary aneurysm sac rupture, with increased cancer mortality also observed in the EVAR group. Overall, aneurysm reintervention rates were higher in the EVAR group than in the OR group, 4.1 and 1.7 per 100 person-years, respectively (p < 0.001), with reinterventions occurring throughout follow-up. The mean difference in costs over 14 years was £3798 (95% CI £2338 to £5258). Economic modelling based on the outcomes of the EVAR-1 trial showed that the cost per quality-adjusted life-year gained over the patient's lifetime exceeds conventional thresholds used in the UK. In EVAR-2, patients died at the same rate in both groups, but there was suggestion of lower aneurysm mortality in those who actually underwent EVAR. Type II endoleak itself is not associated with a higher rate of mortality. LIMITATIONS: Devices used were implanted between 1999 and 2004. Newer devices might have better results. Later follow-up imaging declined, particularly for OR patients. Methodology to capture reinterventions changed mainly to record linkage through the Hospital Episode Statistics administrative data set from 2009. CONCLUSIONS: EVAR has an early survival benefit but an inferior late survival benefit compared with OR, which needs to be addressed by lifelong surveillance of EVAR and reintervention if necessary. EVAR does not prolong life in patients unfit for OR. Type II endoleak alone is relatively benign. FUTURE WORK: To find easier ways to monitor sac expansion to trigger timely reintervention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55703451. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the results will be published in full inHealth Technology Assessment; Vol. 22, No. 5. See the NIHR Journals Library website for further project information.Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research

Development and Validation of Medical Decision Tools in Detection and Treatment of Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a permanent dilatation of the infrarenal segment of the abdominal aorta which can be fatal if the aneurysm ruptures. Ruptured AAA is the second leading cause of global surgical mortality, and prophylactic AAA repair can decrease mortality by a tenfold if surgery is performed as an elective procedure. While screening and repair of AAA could potentially reduce AAA-related mortality, selecting patients that are likely to benefit from repair remains a complex medical decision process which has been compounded by an improved life expectancy of the general population, minimal invasive treatment methods and the increased prevalence of AAA in the elderly. The overall aim of this thesis was to improve detection and management of AAA and to develop a predictive decision tool that can assist in clinical management. This thesis has been conducted, to shed some light into issues highlighted above using New Zealand and international data. The format of this thesis was categorized into three main domains: First, the prevalence of AAA and the influence of aortic size on late survival was documented in a large cohort of individuals undergoing CT colonography for gastrointestinal symptoms in Canterbury, New Zealand; Second, a systematic review and meta-analysis of prognostic factors that might influence late survival following AAA repair were performed, and the national clinical and administrative AAA repair databases were interrogated to provide epidemiological and outcome data; Third, the factors identified from this review were applied into developing a discrete event-simulation model to predict survival following AAA repair. The model developed has been externally validated against existing national databases of patients undergoing AAA repair and it appears sufficiently accurate to predict five- year survival. The results and conclusions presented throughout this thesis fill some of the gap in AAA knowledge, and such predictive decision-making tools might help improve AAA management