Pathophysiology

The pathophysiology of abdominal aortic aneurysms is incompletely understood. It appears to result from medial wall atrophy and degeneration7 that may be triggered by an initial inflammatory response, and neutrophil infiltration at the junction between the media and adventitia. This leads to a reduction in elastin, collagen, glycosaminoglycans, and an imbalance of matrix metalloproteinases, reducing the amount of connective tissue protein content and aortic wall strength.8

Risk factors, prevalence and screening

The strongest modifiable risk factor is cigarette smoking. In a screening and validation study of US veterans, smoking habit increased the odds of having an abdominal aortic aneurysm fivefold9 whereas a healthier lifestyle (weekly exercise, and consumption of fruit and vegetables) reduced the risk.10 Hypertension and atherosclerosis are also associated, but patients with diabetes mellitus appear to be less likely to develop an aneurysm.9 11 This underscores some important differences between the pathophysiology of atherosclerotic and aneurysmal disease. Non-modifiable risk factors include male sex, increasing age, family history, concomitant peripheral artery aneurysms and white ethnicity.11

Prevalence of abdominal aortic aneurysms is extremely low before the age of 55 years but increases thereafter: up to 2.3% in the 75–79 years age group (2275 per 100 000 population).12 Prevalence data in 65-year-old men suggest aneurysms are present in 1.5% of the Swedish (2006–2014)13 and 1.34% of the English (2009–2013) screening programmes.14

In Sweden and the UK, screening programmes only cover men who are invited for an abdominal ultrasound scan at the age of 65 years. In the USA, screening is recommended for men aged 65–74 years with a past or current smoking habit. Screening programmes reduce all-cause mortality and disease-specific mortality due to early detection and treatment.15

Diagnostic imaging

Ultrasound scan is the clinical standard for diagnostic imaging. Its high sensitivity and specificity, and lack of radiation, make it ideal for screening and surveillance.16 CT angiography has a central role in management and intervention planning by visualising the whole aorta to allow accurate anatomical measurements that can be fused with real-time angiography for intraoperative use. CT angiography also defines arterial tributaries, renal vein anatomy and neck morphology, crucial information for planning of either open or endovascular repairs. Ultrasound is not sensitive enough to detect retroperitoneal haemorrhage in an emergency setting and CT angiography is required.

Growth and repair thresholds

Individual patient data meta-analysis of 15 475 individuals with a small aneurysm (30–54 mm diameter)17 showed a growth rate of 2.2 mm/year. This is higher in current smokers (2.6 mm/year) and lower in patients with diabetes (1.7 mm/year). Rupture rate is strongly associated with smoking and female sex. The use of common cardiovascular drugs (beta-blocker, calcium channel blocker, antiplatelet or antihypertensive therapies) does not correlate with growth rates except for statin therapy which is associated with lower growth rates.18 In randomised controlled trials, ACE inhibitor therapy19 and doxycycline20 have no effect on aneurysm growth. Studies exploring the effect of metformin therapy are ongoing (ClinicalTrials.gov numbers NCT04224051 and NCT04500756). Since patients with abdominal aneurysms are also at high risk of all cardiovascular events, 5-year survival rates are higher in those taking antiplatelet, statin or antihypertensive therapies.21

Most aneurysms are considered for repair after a diameter of 55 mm is reached, or when rapid growth occurs (more than 10 mm per year).3–5 A Cochrane review summarised the four trials on which size threshold recommendations are based. The annual risk of rupture comparing surveillance versus repair was found to be less than 1% below 50 mm, 10% between 50–60 mm and 20% above 60 mm. Furthermore, treatment using EVAR for a diameter of 40–55 mm showed no survival advantage.22

Endovascular aneurysm repair

The EVAR stent graft works by excluding the aneurysm from the circulation from the inside of the artery. The proximal and distal aspects of the stent need to provide an adequate seal with the native arterial wall so that blood cannot leak around the endograft and enter the aneurysm sac; this could lead to ongoing expansion and secondary aneurysm rupture. The stent is made of a nitinol (a nickel-titanium alloy) stent covered with polytetrafluoroethylene. It has its own delivery system and is self-expanding. The proximal part of the graft is held in place by barbs or anchors at its proximal end to ensure adequate fixation. The complete endograft is comprised of modular parts of at least two or three separate components including a bifurcate main body and limb components. The modular parts provide a degree of flexibility in size selection, although the overlap between each component must be sufficient to ensure no intervening leaks occur.

The effectiveness of EVAR is dependent on achieving a good seal with the native arteries at the proximal and distal sealing zones, that is, the infrarenal aortic neck and (usually) the common iliac arteries. Manufacturers’ ‘Instructions for Use’ refer to the endograft-specific anatomical requirements which aneurysm anatomy must adhere to, in order to reduce the risk of stent migration, endoleak formation and late aneurysm rupture. Instructions for use give recommended morphological features at the sealing zones and outline the hostile neck features that are incompatible with the use of a specific endograft (box 1). Additionally, there must be adequate femoral access, and no substantial or circumferential calcification or thrombus in the landing zones.3 When one of the iliac seal zones is of insufficient quality, an aorto-uni-iliac stent graft can be used. Here, the iliac artery is occluded with a plug and a surgical femorofemoral cross-over graft is fashioned to perfuse the leg in question. If one of the common iliac arteries is also aneurysmal, an iliac branch device may be used. This involves inserting a further bifurcated endograft into the common iliac artery, with limbs into the internal and external iliac arteries.

The stent graft is delivered into the aneurysm under fluoroscopic guidance through sheaths inserted into the femoral arteries (figure 1). Open cutdown onto the femoral arteries may be required, although percutaneous EVAR with sheath insertion using ultrasound and fluoroscopic guidance is increasingly performed. This requires predeploying closure devices into the common femoral artery before sheath insertion and fully deploying them on sheath removal to close the arterial puncture site. This approach is less invasive and allows EVAR to be performed under local anaesthesia. A systematic review found that percutaneous access is associated with a lower frequency of postoperative groin infection and lymphocoele formation, and a reduction in procedure time and hospital stay. There was no additional risk of haematoma formation, pseudoaneurysm or arterial thrombosis.26

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Figure 1

(A) Intraoperative fluoroscopy showing digital subtraction angiography of the non-deployed stent graft within the abdominal aorta and aneurysm. Contrast can be seen within the aortic branches and the aneurysm sac. (B) Digital subtraction angiography after the stent graft was deployed demonstrating correct position and absence of endoleaks. (C) Three-dimensional reconstruction of a postoperative CT angiography showing a stent graft in place.

Endoleak and long-term EVAR outcomes

Long-term EVAR durability is compromised by endoleak formation. Endoleak is the presence of persistent blood flow within the aneurysm sac but outside of the stent graft. It can be observed either immediately following stent graft delivery (early) or it can develop months or years after the procedure (late). There are five types of endoleaks, classified by their origin (figure 2).

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Figure 2

(A) Type I endoleak: This results from loss of seal at the proximal or distal sealing zones. It is further categorised depending on the location of seal loss. IA, proximal seal loss; IB, distal seal loss; IC, an iliac plug (not shown). (B) Type II endoleak: Blood flow within the sac from the patent collateral arteries arising from the aneurysm itself, such as the inferior mesenteric artery (type IIA) or lumbar arteries (type IIB). (C) Type III endoleak: Loss of seal arising either from around the junctions of the different modular parts (type IIIA) or due to holes in the graft fabric (type IIIB). (D) Type IV endoleak: This occurs due to graft porosity, and used to be more common with older generation stent grafts. (E) Type V endoleak: Sometimes described as endotension, this refers to sac enlargement on serial imaging, in the absence of a visualised endoleak. Other types of endoleaks should be completely excluded first. Black arrows indicate direction of blood and white arrows indicate pressure within the sac.

Inflow of blood around the stent graft can result in a pressurised aneurysm sac which may lead to rupture.27 Therefore, types Ia and type III endoleaks noted either on completion angiography or follow-up imaging require urgent management. Type Ia endoleak occurs more frequently when hostile neck features are present (box 1).4 In contrast, around half of early type II endoleaks appear to follow a more benign course and tend to be managed conservatively unless there is aneurysm sac growth. Surveillance of type II endoleaks without intervention is rarely associated with an increased risk of aneurysm-related mortality, all-cause mortality, sac expansion or type I endoleak development.28

Stent graft migration is defined as a >10 mm movement of the graft or stent resulting in symptoms or the need for re-intervention.29 Stent migration can result in a type I endoleak, separation of modular components or graft occlusion. Similar to type Ia endoleak, stent migration is more likely to occur when hostile neck features are present.30 Device adjuncts have been developed with the aim of reducing the risk of type I endoleak and migration, especially in short necks. These include circumferentially deploying helically shaped anchors to tack the endograft to the wall of the aortic neck.31

Most endoleaks are asymptomatic, mandating lifelong surveillance in order to detect and prevent subsequent complications. Cost, and the risks of contrast nephropathy and ionising radiation from serial CT scans preclude the use of just CT angiography for EVAR surveillance. Duplex ultrasound or contrast-enhanced duplex ultrasound also form part of current surveillance strategies. Duplex ultrasound-based surveillance may be used if CT angiography performed within the first postoperative year is reassuring. However, while duplex ultrasound reliably detects the presence of type I endoleaks, it is less sensitive in detecting type II endoleaks. A surveillance programme could therefore take the form of a CT angiogram at 30 days postoperatively proceeding to annual ultrasound surveillance. An increase in aneurysm sac diameter or an endoleak would trigger early cross-sectional imaging, otherwise a CT angiogram could be repeated after 5 years (figure 3).3

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Figure 3

An approach to elective management of patients with abdominal aortic aneurysm. Following diagnosis, the patient should be reviewed by a member of the clinical team. If obvious contraindications to treatment are present, for example, active malignancy with a reduced life expectancy, it may be more prudent for the patient to be managed conservatively from the outset. If not, cross-sectional imaging in the form of a CT angiogram should be sought to provide anatomical details on the aneurysm morphology. Preoperative investigations which assess the patient’s aerobic capacity may be performed at this point. The case should be discussed at a multidisciplinary team (MDT) level, this is usually comprised of vascular surgeons, interventional radiologists and vascular anaesthetists. The outcome of the meeting would then be discussed with the patient and a treatment decision reached. If conventional endovascular aneurysm repair (EVAR) is performed, a normal postoperative CT angiogram would lead to enrolment within an EVAR surveillance programme. While not yet standard practice, one example of an EVAR surveillance programme would be an ultrasound scan annually and a CT angiogram at 5 years. An abnormal ultrasound scan would trigger more detailed and earlier imaging (CT angiogram) which would also be discussed at an MDT. Interventions can then be planned depending on what abnormality is identified.

Surgical repair

Open surgical repair is performed through either a midline vertical or a transverse abdominal incision. A textile polyester graft such as Dacron is used to replace the diseased aorta. The proximal anastomosis is sutured as close to the renal arteries as possible to prevent later aneurysm formation in the remaining infrarenal aortic neck. Aneurysm anatomy dictates whether the graft is a simple tube or bifurcated ‘trouser’ graft. The distal anastomoses are completed at either the common iliac, external iliac or femoral arteries as necessary.

Abdominal aortic aneurysm repairs are high-risk interventions. Mortality with open repair has been reported as high as 10%,32 but it is greatly reduced (2.3%) in higher-volume centres.25 Morbidity with both types of interventions can also be serious and certain long-term complications can occur in both open repair and EVAR (table 1).

EVAR trials and clinical practice guidelines

Four major randomised controlled trials have compared EVAR and open surgical repair (table 2). A meta-analysis of the individual patient data (2783 patients) at 5 years confirmed the original trial findings. The early (0–6 months) reduction in EVAR group mortality (pooled HR 0.61; 95% CI 0.42 to 0.89; p=0.010) changed within 3 years and the survival rates converged. Beyond this, aneurysm-related mortality was higher in the EVAR group (pooled HR 5.16; 95% CI 1.49 to 17.89; p=0.010). There was no early survival advantage with EVAR in patients with moderate renal dysfunction or coronary artery disease.33 Long-term follow-up of these trials has shown that EVAR is not associated with a higher risk of death due to cancer, but a greater need for re-intervention (HR 2.13; 95% CI 1.69 to 2.68; p=<0.001).34 The increasing re-interventions with EVAR highlight concerns over endograft durability and the need for ongoing postoperative surveillance. These contrasting findings of early benefit with endovascular treatments but later benefits from open surgery strike a chord with the experience of coronary revascularisation where percutaneous coronary intervention is associated with better short-term outcomes but coronary artery bypass surgery reduces longer-term mortality.35

These EVAR trials have informed the recommendations in clinical practice guidelines published by the Society for Vascular Surgery, the European Society for Vascular Surgery and the National Institute for Health and Care Excellence. However, each has come to different conclusions. The Society for Vascular Surgery recommends an assessment of operative risk and life expectancy when contemplating repair, arguing that a patient who is at high risk for open surgery may be at lower risk for EVAR. The European Society for Vascular Surgery recommends EVAR as the preferred treatment modality where anatomically suitable, but open repair in patients with longer life expectancies (more than 10–15 years). The National Institute for Health and Care Excellence recommends open surgical repair unless contraindicated due to a hostile abdomen, anaesthetic risks or comorbidities when EVAR is recommended but notes that this needs balancing with the uncertainty benefit of EVAR in these patients.

There are many critics of the differences in the recommendations. Some argue that the quoted trials were performed with either older generation endografts or ones which are not commercially available anymore. Newer generation grafts appear to have fewer re-intervention rates than their older counterparts in more recent studies.36 Endovascular experience among clinicians has also continued to increase and imaging technology and devices have continued to develop. In contrast, the surgical technique for open repair has remained more or less unchanged since the 1950s. Similar arguments have previously been advanced for percutaneous and open surgical approaches for coronary revascularisation and yet open surgery continues to have the best long-term outcomes.35

The European Society for Vascular Surgery took into consideration more contemporary population-based registries, some of which reported improved short-term outcomes that are sustained for at least 5 years.24 Others would argue that the conclusions by the National Institute for Health and Care Excellence are more valid since they only considered higher quality evidence (in the form of randomised controlled trials). They also looked at cost-effectiveness in more detail and used UK-specific economic modelling. It concluded that despite the short-term benefit, the higher net costs and lower net benefits of EVAR than open repair, put it above the range normally considered to be a cost-effective use of National Health Service resources. This lack of consensus has even led some to suggest that new randomised controlled trials are required.37