Treatment Outcome Trends for Non-Ruptured Abdominal Aortic Aneurysms: A Nationwide Prospective Cohort Study

a Department of Vascular Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands b Scientific Bureau, Dutch Institute for Clinical Auditing, Leiden, The Netherlands c Department of Surgery, Amsterdam University Medical Centre, Amsterdam, The Netherlands d Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands e Department of Surgery, Hospital Medisch Spectrum Twente, Enschede, The Netherlands Multi-Modality Medical Imaging group, TechMed Centre, University of Twente, Enschede, The Netherlands g Department of Vascular Surgery, Leiden University Medical Centre, Leiden, The Netherlands h Department of Vascular Surgery, Haga Teaching Hospital, The Hague, The Netherlands


INTRODUCTION
As a result of endovascular aneurysm repair (EVAR), the management of intact abdominal aortic aneurysms (iAAA) has changed dramatically in the last decades resulting in improved peri-operative outcomes. 1 Since the first EVAR was performed in the 1990s, many patients with suitable anatomy have received EVAR rather than open surgical repair (OSR) because of the lower peri-operative risks of EVAR, 2 with a subsequent decrease in the number of patients treated by OSR. 2e5 Furthermore, frail patients can receive EVAR rather than conservative treatment. 6 These changes in treatment strategy probably have resulted in fewer OSRs per hospital, which may have negatively influenced the outcomes of OSR. 7 Previous studies have reported trends in the management and outcomes of iAAA repair. A study of an international cohort of vascular registries that described trends in the management and outcomes of iAAA repair from 2005 up to 2013 reported an overall decrease of peri-operative mortality from 3.0% to 2.4% while the peri-operative mortality after OSR increased from 3.9% to 4.4%. 8 Although this international study reported numerous patient outcomes, many of the registries included patients on a voluntary basis. 9 Furthermore, Swedvasc, the Swedish national vascular registry, reported a decrease in 30 day mortality rates following OSR (3.1% in 2006 e 2011, 2.5% in 2012 e 2016). 2 To date however, no studies have examined the most recent trends in the management and outcomes of iAAA repair, reflecting real world nationwide data.
The Dutch Surgical Aneurysm Audit (DSAA) is a mandatory quality registry for all aortic aneurysm repairs performed by vascular surgeons in The Netherlands, established in 2013, to monitor and improve the outcomes of the treatment of abdominal aortic aneurysms (AAAs). In the DSAA, all hospitals that perform AAA repair have insight into their results, using quality indicators, with other hospitals presented anonymously with a 95% confidence interval around the national average for comparison. In this way, internal feedback on the performance of hospitals is provided. 10,11 Although audit and feedback generally lead to small but potentially important improvements in professional practice, 12 it is not known yet whether the outcomes of iAAA repair have improved in The Netherlands since the establishment of the DSAA.
The aim of this study was to evaluate whether national outcomes of iAAA repair have improved since the establishment of the DSAA. Furthermore, changes in patient selection, hospital volumes, and preferred operative technique since 2014 were investigated.

METHODS
This was a retrospective nationwide study of patients who underwent repair of an iAAA in The Netherlands. The study followed the STROBE statement. 13

Data source
The dataset was retrieved from the DSAA, a prospective registered compulsory quality registry for all aortic aneurysm repairs performed by vascular surgeons in The Netherlands. The DSAA was established in 2013 and started by registering all Dutch patients undergoing infrarenal and juxtarenal AAA repair without previous aortic surgery. Since 2016, complex endovascular aneurysm repair, thoracic aortic aneurysm repair, and revision surgery have been registered. Data verification took place over 2015 through a random sample of hospitals showing a case ascertainment of 98.4% and no discrepancies in deaths or re-interventions. 14,15 Data verification will be repeated in the near future.

Participants
All consecutive participants that were registered in the DSAA and underwent primary iAAA repair using either standard EVAR or OSR, between January 2014 and December 2019 were included. Patients with missing data on variables date of birth, date of surgery, sex, and survival status at the time of discharge or 30 days post-operatively, as well as patients aged < 18 or > 110 years were excluded. No ethical approval or informed consent was required for this study according to Dutch law. No distinction exists between private and public healthcare in The Netherlands.

Definitions
Intact AAA repairs included both electively treated aneurysms and aneurysms that caused symptoms. Aneurysm treatments were categorised by intention to treat; attempts at endovascular treatment for aneurysms that were converted from EVAR to OSR during surgery were categorised as EVAR. The variables "pulmonary comorbidity" and "cardiac comorbidity" were dichotomised per patient into categories "present" or "absent". From 2014 to 2018, the variables regarding pulmonary and cardiac comorbidities were based on parameters from the V-POSSUM, 16 while from 2019, "pulmonary comorbidity" and "cardiac comorbidity" were based on ICD-10 codes (Supplementary Table  S1). During the study period, some hospitals have been merged. When hospitals have been merged during the study, the hospitals were classified as one hospital in the years before the merger.
Outcomes. The primary outcome was the peri-operative mortality trend per year (30 day mortality and in hospital mortality). Secondary outcomes were trends per year in the outcomes major complications and textbook outcome (TbO), and trends per year in patient characteristics, hospital volume, and applied surgical technique (OSR or EVAR). As described before, 17,18 major complications were defined as either intra-operative complications or peri-operative complications within 30 days that caused a prolonged stay (length of hospital stay above the 75th percentile of living patients registered in the DSAA, stratified by OSR, EVAR, elective, or symptomatic [thresholds: EVAR, elective > 3 days; EVAR, symptomatic > 7 days; OSR, elective > 12 days; OSR, symptomatic > 14 days]), intra-operative complications or peri-operative complications that caused a re-intervention or death. The specific complications included in the categories of peri-operative complications that were included in the DSAA are shown in the Supplementary Table  S3. TbO is a desirable composite outcome measure that provides information on the overall quality of care that can be used for internal quality improvement, 19e22 and could be valuable in shared decision making processes. As described by Karthaus et al., 21 TbO is achieved in the elective setting if no intra-operative or post-operative surgical complications, no re-interventions, no prolonged stay ( 4 days for EVAR, 10 days for OSR), no re-admissions and no peri-operative mortality occur within 30 days.

Statistical methods
Firstly, descriptive statistics of outcomes per year were shown for both EVAR and OSR patients together, as well as separately. To examine the linear time trends per year for outcomes, univariable as well as multivariable logistic regression analyses, using known confounders "sex", "age", "pulmonary comorbidity", "cardiac comorbidity", "haemoglobin", "creatinine", "urgency", "aneurysm diameter", and "aneurysm location" were performed. For these multivariable analyses, the missing values of categorical variables were included in the models as separate categories. Missing values of continuous variables were not included in the multivariable analyses as these were < 5%. Because of the low missing value rate, it was decided not to impute these using multiple imputation. Secondly, linear time trends per year of patient characteristics were examined from 2014 to 2019 using univariable logistic and linear regression analyses for dichotomous variables and continuous variables, respectively. Trends per year regarding hospitals that treated fewer than 30 patients per year and number of hospitals were examined using univariable linear regression analyses. Additionally, the trends regarding hospital volume were shown using boxplots. For linear regression analyses,  the beta coefficients, including 95% confidence intervals, were reported. For logistic regression analyses, the odds ratios, the exponent of the beta coefficient, including 95% confidence intervals, were reported. All analyses were performed using R version 4.0.1.

RESULTS
A total of 23 063 patients (2 587 -4 176 patients per year) were registered in the DSAA between January 2014 and December 2019. Of these, 15 562 patients treated in 61 hospitals underwent EVAR or OSR for a primary iAAA, of whom 15 532 (99.8%) were eligible (2 445 -2 753 patients per year) and 30 (0.2%) were excluded (Fig. 1). The 7 501 patients who were not included in this study underwent ruptured AAA repair, thoracic aortic aneurysm repair, secondary AAA repair, or complex endovascular repair.
Time trends in peri-operative outcomes All patients. Table 1 shows that the peri-operative mortality of all patients included in this study remained stable (aOR 0.95; 95% CI 0.89 e 1.02). In 2019, the crude peri-operative mortality of all patients was 2.2%. The crude percentage of major complications decreased after correction for confounders, from 14.7% in 2014 up to 11.8% in 2019. Details of the peri-operative complications that are defined as a major complication are shown in Table 2.
Open surgical repair patients and endovascular aneurysm repair patients. In Table 3 Open surgical repair patients and endovascular aneurysm repair patients.  Table 4).  Table 4).

Time trends in the application of surgical techniques
Hospital volume. The number of patients treated per hospital (hospital volume) did not change statistically over the years (b coefficient 0.59, 95% CI -0.75 e 1.94). As shown in Figure 3A, in 2014, the median hospital volume was 40 (IQR 26, 58), while in 2019, the median hospital volume was 42 (IQR 34, 56.5). The number of hospitals that treated fewer than 30 patients per year decreased from 20 in 2014, to 10 in 2019 (Table 5). Figure 3B shows the median hospital volume and IQR, including complex EVAR stratified by OSR and EVAR. The median hospital volume per year of OSR was stable, around 11 patients per hospital per year.

DISCUSSION
The present study aimed to evaluate whether iAAA repair outcomes have improved since the establishment of the DSAA, a mandatory registry of all AAAs operated on in The Netherlands. The study demonstrated that several important iAAA repair outcomes in The Netherlands improved from 2014 up to 2019, while patient characteristics showed that patients with similar or more comorbidities underwent surgery. The number of patients per hospital remained stable; however, the number of hospitals that treated fewer than 30 patients decreased, which is a sign of regionalisation of vascular services.  The present study shows that during the study period, patients who received EVAR became slightly older, and more patients had cardiac comorbidities. In contrast to OSR, the peri-operative mortality rate following EVAR did not decrease and remained between 0.7% and 1.3%, consistent with rates described in contemporary literature. 8 Although mortality did not change, the major complications after EVAR declined, and the TbO rate increased remarkably. The decrease in major complications and the increase in TbO suggest that the peri-operative care quality for patients that underwent EVAR has increased. The exact cause of this improvement is hard to determine and is probably multifactorial, including better patient selection, increased experience, and further regionalisation of services. It is likely that the audit itself also plays an important role, as described previously. 12 Furthermore, this study shows that all examined patient outcomes following OSR for iAAA repair improved over time, while more patients had cardiac comorbidities but were of similar age during the study period. An important finding from this study is that the peri-operative mortality following OSR improved, from 6.1% in 2014 to 4.7% in 2019, in line with rates described in international registries. 8 However, some of these registries might be biased by voluntary data contributions, 24 while the DSAA is a compulsory registry. Additionally, the percentage of major complications following OSR declined, and the percentage of TbO increased. Altogether, this suggests that the outcomes of patients who received OSR have improved. As for after EVAR, the exact cause of this is likely to be multifactorial, for example a result of stricter case selection. Several studies have suggested that lower hospital volume is associated with increased mortality. 7,25 The present study described the trends in hospital volume and the number of hospitals that performed iAAA repair. For OSR, the median hospital volume of 11 per year raises some concern, 26 and should be investigated in the near future. Although the hospital volume of all iAAA repairs per year and the median hospital volume of OSR patients did not increase, the number of hospitals that treated patients decreased, and the number of hospitals that treated fewer than 30 patients per year decreased. This regionalisation of aneurysm care is probably a result of the European Society for Vascular Surgery (ESVS) guideline, 23 which suggests that a minimum of 30 AAA repairs should be performed per hospital per year or could be related to the clinical auditing process of the DSAA. 10 The DSAA monitors and  provides feedback about the number and outcomes of patients that underwent elective AAA repair per hospital, as well as the total number of aortic aneurysm repairs per hospital. Finally, this study examined the proportion of OSR vs. EVAR per year, including the total number of patients. It was noted that the total number of patients per year has declined since 2016. Interestingly, the proportion of patients with an AAA diameter below the guideline threshold remained stable, while the mean diameter of iAAAs decreased; however, this decrease was small (0.3 mm per year). The National Vascular Registry reported a decrease in the number of elective infrarenal AAA repairs in the UK, and it was stated that this could indicate a more conservative approach in the management of sicker patients. 27 Furthermore, including patients that were treated by complex endovascular means for AAA, the applied surgical technique slightly changed with an increase of OSR and decrease of standard EVAR. The increase in OSR might be a result of the recent discussion regarding preferred treatment for specific patients 23,28e30 or published findings indicating inferior long term survival and more secondary interventions after EVAR. 31,32 A decrease in the number of standard EVAR was also reported in the UK in 2018. 27 In 2019, the percentage of patients that received standard EVAR in the present study was 65.3% of all patients, which was similar to the overall proportion of EVAR in international registries from 2010 to 2013 but far lower compared with the USA (79%), as reported by Vascunet. 33 To the present authors' knowledge, this is the first study reporting treatment trends for iAAAs based on data from a compulsory national quality registry for all aortic aneurysm repairs and therefore represents real world data. One important limitation of this study is that the DSAA was initially designed for quality measurement and not for scientific purposes, which may result in some missing variables. The possible influence of these missing variables was considered in the present study and attempts were made to deal accurately with the missing values. Another limitation is that the DSAA does not contain anatomical morphological details, and only patients who underwent aneurysm repair were included in the DSAA. Therefore, selection and confounding bias cannot be excluded. Finally, the DSAA does not include information on surgeon volumes, and therefore, it was not possible to describe surgeon volume, in contrast to other countries. 34,35 In conclusion, since the establishment of this nationwide quality improvement initiative (DSAA), all iAAA repair outcomes following standard EVAR and OSR have improved except for peri-operative mortality following standard EVAR which remained unchanged, although the proportion of patients with cardiac comorbidity increased over time in this group. The number of major complications after both OSR and EVAR decreased, and the proportion of TbO increased. The peri-operative survival after OSR increased, despite a higher proportion of patients with cardiac comorbidity. This nationwide audit provides real world data on aneurysm care and can be seen as an important tool for further quality improvement initiatives.