Mesenteric Ischaemia (Chronic, Suspected)

Chronic mesenteric ischaemia (CMI) is defined as ischaemic bowel symptoms for at least 3 months due to insufficient blood supply to the GI tract 1.

Women are more often affected by CMI than men. Patients are usually >60 years of age.

By far the commonest cause of CMI is mesenteric artery occlusive disease (MAOD) caused by atherosclerosis in the coeliac axis (CA), superior mesenteric artery (SMA) and inferior mesenteric artery (IMA). MAOD is very common in the elderly population but CMI is considerably less common due to the rich collateral supply to the bowel. The bowel is normally richly supplied with blood vessels and a collateral circulation often develops to compensate for hypoperfusion.

Symptoms arise when the collateral circulation becomes inadequate. Patients may present with both CMI and colonic ischaemia. Patients with CMI may also develop an acute-on-chronic episode of acute mesenteric ischaemia – a life-threatening condition.

CMI or “abdominal angina” is due to inadequate blood supply over time. The post-prandial nature of the abdominal pain in CMI is due to the markedly increased blood flow requirement of the bowel after food ingestion.

Less common causes of CMI include dissection, vasculitis, fibromuscular dysplasia, radiation, and cocaine abuse 2.

Median Arcuate Ligament Syndrome (MALS) is a further vascular cause of post-prandial pain and weight loss and is due to coeliac axis compression (see below).

Non-occlusive ischaemia (sometimes known as abdominal migraine 1) is probably due to an insufficient micro-circulation and is related to cardiac failure, pulmonary hypertension, chronic lung disease, severe anaemia and low-flow states 3.

Only the commoner atherosclerotic obstructive CMI will be dealt with in this article.

The extensive collateral circulation to the bowel means that most patients do not develop symptoms of CMI unless there is significant stenosis or occlusion of at least two of the three mesenteric vessels (CA, SMA, IMA) 4.However, it is apparent that single vessel disease (usually the SMA) can cause CMI if collateral networks have been disrupted by previous surgery or radiotherapy 1.

The classic triad of CMI is post-prandial pain (usually lasting 30 minutes to 2 hours after a meal 5), weight loss and abdominal bruit. All three components of the triad  are present in only 20% of patients 6. There is a predictive value of 60% when all three triad components are present. The absence of the triad does not exclude CMI. Cachexia may be absent, possibly due in modern times to earlier diagnosis 3.

Other clinical features include a fear of eating, bowel disturbances, nausea and vomiting (which may be due to ischaemic gastropathy) and occult gastrointestinal bleeding.

Physical examination may show cachexia, presence of abdominal bruits (17–87% of cases), and evidence of atherosclerotic disease in other organs or peripheral vascular disease.

The diagnosis of CMI is made on appropriate symptoms consistent with CMI and imaging evidence of mesenteric stenosis >70%, usually in at least two of the three vessels 5; however, the degree of stenosis that is significant is still debated , with a range of 50-75% being used in the literature 3.

A >70% stenosis of the CA or SMA in single vessel disease may be relevant when accompanied by the appropriate clinical scenario 3, 7. The European guidelines (a joint venture from multiple subspecialty European societies 3) also state that, in symptomatic patients with extensive multivessel disease, a >50% stenosis of the SMA may be significant. However, if single-vessel stenosis is identified, it is important to exclude alternative causes of the patient’s symptoms 3.

The IMA is considered the least significant of the mesenteric vessels in the context of CMI.

Median Arcuate Ligament Syndrome (MALS)

MALS (a.k.a. Coeliac Syndrome or Dunbar Syndrome) is a rare and controversial cause of coeliac artery compression 3, 8, 9, mainly occurring in women of age 20-40 years. It causes post-prandial pain and weight loss due to compression of the coeliac axis and coeliac plexus by the median arcuate ligament during expiration. However, the causal relationship between vascular stenosis and the pathophysiology of MALS is not well established, although it is considered that compression of the CA can lead to intimal hyperplasia and stenosis 9. The diagnosis can be confirmed by Duplex US or CTA or MRA during inspiration and expiration. Evidence is seen of stenosis during expiration with post-stenotic dilatation. A “hook-sign” on CTA may also be seen 10.

MALS will not be dealt with further in this article.

Patients with relevant features to their abdominal pain and those with a low or moderate clinical suspicion of CMI will likely require exclusion of other causes of symptoms; CMI has a wide differential diagnosis which may require investigation - eg. peptic ulcer disease (by upper GI endoscopy), inflammatory bowel disease (by colonoscopy), pancreatic disease (by CT or MRI) or gallstones (by US), GI and other abdominal malignancy (by colonoscopy and CT) and Irritable Bowel Syndrome (IBS) 3. Colonoscopy should be considered in all patients but is considered mandatory in the European Guidelines in patients with diarrhoea 3.

Chronic pancreatitis should be considered, since the symptoms and risk factors (e.g. smoking, hypertriglyceridaemia) of chronic pancreatitis are similar to those for CMI. For patients with weight loss, coeliac serology should be considered. In patients with diarrhoea, colonoscopy should be performed to exclude colorectal carcinoma and other ileal and colonic causes of diarrhoea, and considered as well in elderly patients with symptoms indicating colonic disease or ischaemia.3

The North American Society for Vascular Surgery (SVS) guidelines recommend expedited workup in patients with abdominal pain, weight loss and food fear. This may include an esophagogastroduodenoscopy, a colonoscopy, an abdominal computed tomography scan and an abdominal ultrasound 7.

Underlying exacerbating conditions (eg anaemia) should be excluded by full blood count and lipid profile.

Other laboratory and diagnostic tests will be determined by the patient’s symptoms – patients with significant diarrhoea or evidence of GI blood loss may require consideration for colonoscopy.

An “expedited work-up” of patients with symptoms of abdominal pain, weight loss and food fear is recommended by the North American Society for Vascular Surgery (SVS) guidelines, emphasising the urgency of the condition 7. These guidelines as well as the European Society of Vascular Surgery (ESVS) guidelines recommend that duplex ultrasound (DUS) should be used for screening, and computed tomography angiography (CTA) to map the anatomy of the lesions 11. Further European guidelines 3, jointly developed by multiple European sub-specialty societies, recommend CT angiography (or, if this is contraindicated, contrast-enhanced MR angiography [CE-MRA]) as the preferred examination, but also state that DUS, when performed by an experienced operator, might be used as a screening method to exclude significant proximal mesenteric artery stenosis, and that when DUS is positive, CTA or CE-MRA is required to confirm the presence of a significant stenosis and to guide treatment planning 3. These guidelines point out that there is a paucity of comparative studies among DUS, CTA and CE-MRA showing superiority of one technique over another; all are considered appropriate.

The American College of Radiology (ACR) Appropriateness Criteria, on the other hand, recommends CTA or MRA as the initial imaging examination in patients with suspected chronic mesenteric ischaemia 12.

Diagnostic strategy

In view of the high negative predictive value of a technically satisfactory negative DUS, and thus its value as a screening test, the following strategy would seem to be reasonable:

• Especially for patients with a low clinical suspicion for CMI, it is important to exclude other non-CMI causes of their symptoms. Appropriate investigations may include upper and/or lower GI endoscopy, US, or CT scan.

• If alternative diagnoses are excluded in these patients and in patients presenting with a low or moderate clinical probability of CMI, DUS or CTA are appropriate first-line imaging tests.

• DUS is a good screening test - a technically adequate negative DUS makes CMI very unlikely.

• Therefore, if DUS is negative, further investigation for alternative diagnoses may be indicated.

• If DUS is positive or technically unsuccessful, CT angiogram is appropriate – in the former case to demonstrate detailed anatomy to facilitate treatment.

• In patients with a high clinical suspicion of CMI, CTA is the appropriate first-line investigation.

• DSA should be reserved as the initial step in intravascular intervention rather than be performed as a diagnostic test, unless non-invasive imaging requires clarification.

A mesenteric artery calcium score (MACS) obtained in coeliac artery and superior mesenteric artery has a high negative predictive value for chronic mesenteric ischemia and could serve as a screening tool 13. A further study has suggested a symptom-based score chart 14 combined with a MACS 15 can stratify risk of CMI in patients with symptoms consistent with CMI, to enable appropriate investigation and treatment.

DUS is cost-effective and free of the risks of ionising radiation and contrast media. It is a good screening test for CMI, but it is technically demanding, requires a high level of skill, and is observer-dependent, and is thus best performed in a high-volume centre with highly trained operators. It may result in an unsatisfactory examination due to the patient’s body habitus, overlying bowel gas, variant anatomy, etc.

The technique is described by Aly et al. 16 and van Dijk et al. 17; further details including pitfalls are provided in a recent review 18.

In one 1993 study, 83% of CAs and 93% of SMAs were visualised on the initial DUS, compared with 100% of CAs and 99% of SMAs visualised on Digital Subtraction Angiography (DSA).  A 1998 study reported a technically adequate examination of the SMA and CA in 98% and 96%, respectively 19. A 2014 study found the interpretability of duplex imaging was much better in women than in men, with good interpretability obtained in 81% of women compared with 53% in men 20. DUS can only demonstrate the proximal aspects of the mesenteric vessels.

The most widely accepted criteria for stenosis >70% are Peak Systolic Velocity (PSV) >275 cm/s for the SMA, and 200 cm/s for both the celiac and inferior mesenteric arteries in the fasting state 16, 18, 21. In addition to raised PSV, a “tardus-parvus” wave form distal to the site of a stenosis provides supportive evidence. It should be noted that there is significant variation in PSV between inspiration and expiration 3.

These parameters generally provide high sensitivities and specificities – mostly around 90% for ≥ 70% stenosis 18. In a study comparing DUS evaluation to DSA, a diagnostic accuracy of 85-90% was confirmed for the detection of >70% mesenteric artery stenosis 19.

There is a negative predictive value of 99% for SMA and 94% for CA 22. Importantly, a negative study essentially rules out a significant stenosis of the SMA 7.

DUS is performed in the fasting state, but a post-prandial vascular response within the mesenteric vessels can also be detected and may be useful 11. The normal maximum response occurs within 30 to 90 minutes and is seen as increased blood flow in the SMA and on DUS imaging during a meal challenge 23. In patients with CMI, the postprandial hyperaemic response is blunted. The widespread use of post-prandial DUS is hindered by the lack of standardisation of the post-challenge response. The use of postprandial DUS imaging has not been shown to improve the overall accuracy for the evaluation of either SMA or CA stenoses 7. A similar increase in post-prandial SMA flow can be measured using MRI. MR Angiography (MRA)

It is apparent, therefore, that when a technically adequate DUS examination is achieved, a negative DUS result is highly predictive of the absence of a significant stenosis (i.e. in excluding CMI). DUS is therefore a good screening test. However, a positive result requires further imaging to confirm the findings and assess detailed anatomy.

CTA is recommended by the American College of Radiology (ACR) Appropriateness Criteria as the first-line study 12. Similarly the European Society of Vascular Surgery (EVS) 11 and the joint European Society guidelines 3 recommend CTA as the investigation of choice.

The technique is described by Horton et al 24 among others. Multidetector CT angiography with 3D reformatting is the gold standard of the non-invasive imaging examinations for mesenteric artery stenosis. It can detect alternative causes of abdominal pain as well as provide anatomical detail of the mesenteric circulation.

The sensitivity and specificity of CTA for detecting significant SMA and CA stenoses are reported as 100% and 95-100% respectively 3 with a diagnostic accuracy of 96-98% 25  (Digital Subtraction Angiography being the reference standard).

A mesenteric artery calcium score (MACS) obtained in coeliac artery and superior mesenteric artery has a high negative predictive value for chronic mesenteric ischemia and could serve as a screening tool 13. A further study has suggested a symptom-based score chart 14 combined with a MACS 15 can stratify risk of CMI in patients with symptoms consistent with CMI, to enable appropriate investigation and treatment.

MR Angiography (MRA) may be used as an alternative to CTA where there are contra-indications to CT or iodinated contrast agents.

Several studies suggest that contrast-enhanced MR angiography (CE-MRA) is a good alternative for the detection of CA and SMA stenoses as it shows 92-100% sensitivity, 84–100% specificity 25-28 3 and a high degree of interobserver agreement 27.

However, MRA is less good at visualising and assessing the IMA 3, 27 and peripheral mesenteric vessels. Because of the latter, it has a limited role in diagnosing distal disease. Also, MRI cannot assess vessel calcification (important for risk assessment and treatment planning). Supplementing MRA with non-contrast CT may be necessary 7.

Other disadvantages of MR are its contraindication in patients with pacemakers and its inability to assess patients with intravascular stents. Caution is advised in patients with chronic renal disease or on dialysis in view of the risk of nephrogenic systemic fibrosis with some gadolinium contrast agents. The use of Group II and Group III agents (rather than Group I) is advised to minimise the risk 29.

Acquisition times for MRA are considerably longer than for CTA, making movement artifact and reduced spatial resolution a problem in some patients.

MRA techniques can also be applied to assess the flow response to a caloric challenge (see also Duplex US section). This has shown promise in demonstrating the significantly lower increase in post-prandial mesenteric blood flow in CMI patients compared to normal 30, 31

Digital Subtraction Angiography (DSA) is the reference standard for imaging of the mesenteric vessels. It is an invasive test involving selective catheterisation of the coeliac and mesenteric arteries.

DSA involves some risks, including - complications at the arterial access site (usually femoral artery at the groin, but otherwise in the [preferably left] upper limb); damage (dissection or thrombosis) to the access or selected mesenteric vessels; and distal embolization to the bowel.

In view of the diagnostic accuracy of non-invasive CTA and MRA, the use of DSA is now largely reserved for patients where there is an intent to undertake endovascular intervention Treatment, or where CTA/MRA are non-diagnostic.

The origins of the CA, SMA and IMA are visualised on early phase imaging. Later imaging identifies any retrograde flow, delayed peripheral filling and collateral pathways.

Selective catheterisation also allows for the measurement of the pressure gradient proximal and distal to any stenosis to assess its significance.

In addition, intravascular ultrasound can be used during selective catheter angiography to detail the degree of arterial stenosis and to aid in intervention 7, 32, 33.

The management of individual patients with symptoms and imaging consistent with CMI should be discussed at multidisciplinary meetings attended by, at a minimum, an interventional radiologist, a vascular surgeon and a gastroenterologist.

Current therapeutic options include:

1. Endovascular therapy 

   Techniques include angioplasty and endovascular stent placement. Angioplasty and stent placement have become the primary treatment in many patients who have suitable lesions, largely due to reduced peri-operative complication rate, and reduced hospital stay compared to surgical intervention 7, 34, 35. The 30-day mortality rate is not significantly different 7. However, the rate of recurrent symptoms and need for reintervention are both higher 7. Currently > 70% of patients with CMI are treated by endovascular techniques. Endovascular therapy is associated with high technical success ranging from 85% to 100% in the setting of stent placement 36.

2. Open Surgery

   Open surgical revascularisation procedures include vascular bypass, open stenting and endarterectomy.

   Indications for open surgical revascularization should be reserved for patients who are not endovascular candidates and those who have failed prior endovascular interventions. Open revascularization may also be appropriate as the initial procedure for selected younger, healthier patients with longer life expectancies, assuming that the improved long-term patency offsets the increased peri-operative risks 7.

Atherosclerotic disease of mesenteric vessels is very common, whereas CMI is much less common. Therefore, in selected patients it may be necessary to determine, by functional testing, the significance of a stenotic lesion seen on imaging prior to treatment. This is especially relevant when there is single-vessel stenosis 37, since single-vessel disease is an uncommon cause of CMI.

However, the European guidelines 3 state that CMI is likely in patients with unexplained abdominal symptoms and significant stenoses (>70% in single vessel disease of CA or SMA; >50% in SMA with extensive multivessel disease) - further functional testing (while preferable) is not required for the presumptive diagnosis of chronic mesenteric ischaemia in these patients. These guidelines recognise the limitation of lack of availability of functional tests.

Determining the significance of a stenosis can be achieved by measurement of the pressure gradient proximal and distal to the stenosis by selective catheterisation of the vessel in question, but this, of course, is invasive and not without risk. Similarly, a “therapeutic trial” of revascularisation by endovascular or surgical means would usually entail unacceptable risk to the patient.

Attempts have been made to assess the functional significance of mesenteric stenoses non-invasively, using the methods below, but unfortunately none has yet proven sufficiently reliable or gained widespread acceptance 7:

• Normal response to a caloric challenge results in a marked increase in SMA blood flow which can be seen on Duplex ultrasound (DUS) 23. In patients with CMI, the post-prandial hyperaemic response on DUS is decreased. The widespread use of this test is hindered by the lack of standardisation of the post-challenge response.The use of postprandial DUS imaging has not been shown to improve the overall accuracy for the evaluation of either SMA or CA stenoses 7.

• MRA techniques can also be applied to assess the flow response to a caloric challenge. Earlier studies and one recent study 30 using 2-dimensional time-resolved phase-contrast magnetic resonance imaging (2D PC-MRI) have shown promise in non-invasively assessing patients with suspected CMI by measuring volumetric blood flow rates in mesenteric vasculature to evaluate post-prandial haemodynamic responses, but it is cumbersome and requires separate MR or CT angiography to delineate anatomy. However, a recent study using 4D-Flow MRI 31 showed increased flow in response to a caloric challenge in the SMA, SMV and PV in controls and a lack of response in patients with CMI. 4D-Flow MRI with large volumetric coverage is a promising non-invasive diagnostic technique that can functionally and anatomically evaluate mesenteric vasculature at the same examination. However, both of these recent studies have been small and further studies on larger cohorts of patients are required.

• PCO₂ tonometry and Visible Light Spectroscopy (VLS) - both these tests have serious limitations and are not widely available 3:

• PCO₂ tonometry measures the PCO₂ within the lumen of the bowel 37. This is raised when there is ischaemia of the bowel mucosa. While tonometry performed either as an exercise test or after standard test meals has good accuracy for diagnosing CMI, the current technique is “complicated, time-consuming, and error-prone” 11. This test is not widely available.

• Visible Light Spectroscopy (VLS) - Mucosal oxygen saturation can be measured endoscopically by combining a light source and external spectrometer. Limited studies have shown potential for this technique. A study published in 2019, for example, reported the sensitivity of O₂ saturation measured by VLS for diagnosing CMI was 94% and the specificity 72% 38. The level of specificity may not be high enough for patient selection. The inter- and intra-observer reliability is “fair to good” 39. There is no additional discriminatory value in CMI in measuring post-prandial VLS40.