Chronic Mesenteric Ischemia: Epidemiology, Pathophysiology, Clinical Evaluation, and Management

Introduction

Clinically significant chronic mesenteric ischemia (CMI) is a relatively uncommon disease that was characterized by G.H Goodman in 1918 as “abdominal angina.” In contemporary practice, the term intestinal angina is used to describe the classic symptom of chronic abdominal pain that occurs after meals that eventually leads to food fear and weight loss, which is the hallmark of CMI. Current estimates indicate that CMI accounts for less than 1 per 100,000 hospital admissions in the United States and less than 2% of all admissions for gastrointestinal conditions. Shaw and Maynard described the first successful mesenteric endarterectomy in 1958 and since then, techniques of revascularization have greatly evolved. With the evolution of less invasive endovascular techniques, primary mesenteric stenting has become the most frequently utilized initial treatment for CMI, with open surgery reserved for patients who fail endovascular therapy or have complex lesions not amenable to endovascular intervention. This chapter provides a comprehensive review of the clinical evaluation, treatment options, and results of mesenteric revascularization for patients with CMI.

Pathophysiology

Approximately 20% of the cardiac output goes through the mesenteric arteries under fasting conditions and this can increase to 35% after a meal. Blood flow to the gastrointestinal tract increases drastically shortly after food is ingested and can reach levels approaching 100% to 150% of normal (2000 mL/min) that is sustained over the next 3 to 6 hours. Postprandial intestinal hyperemia is a locally mediated vascular response to the presence of digested food products in the lumen. The degree of response is dependent upon the makeup of the meal as fatty acids and products of protein digestion lead to vasodilation and produce profound and sustained intestinal hyperemia.

Patients with CMI become symptomatic when the combined primary and collateral circulation is inadequate to provide the postprandial hyperemic response that is required to supply oxygen for the metabolic processes of secretion and absorption, and for increased peristaltic activity. Poole et al. showed that when splanchnic blood flow is compromised by 50%, the addition of a fatty meal to the small intestine leads to a significant decrease in pH and when a second meal is added to the stomach, the pH decreases further suggesting that the food in the stomach leads to steal from the rest of the intestines. This sequence of events likely explains the temporal nature of the pain experienced with CMI. A similar phenomenon occurs in the patient with coronary demand ischemia. The symptoms of angina pectoris occur because of an inadequate blood supply to the heart that starves the cardiac muscle of oxygen; similarly, intestinal angina results from the relative imbalance between tissue supply and demand for oxygen and other metabolites. Because the mesenteric circulation has a rich collateral network, most patients only develop symptoms when at least two of the three mesenteric arteries are severely narrowed or occluded ( Fig. 134.1 ). However, this is not an absolute requirement and some patients present with single vessel disease, particularly if the SMA is involved. ^, Ultimately, the degree to which a patient becomes symptomatic from CMI correlates with the extent of disease, timing of progression of stenosis and adequacy of collateral pathways in preventing arterial steal.

Etiology

The most common cause of CMI is arterial obstruction from atherosclerotic disease and this accounts for about 90% of cases of symptomatic CMI. Atherosclerotic lesions usually develop as an extension of plaque from the aorta and thus most are located at the origin of the mesenteric arteries and can extend 2 to 3 cm into the branches. Non-atherosclerotic lesions can also cause CMI and these patients tend to be younger than those with atherosclerotic disease. Non-atherosclerotic pathologies that can affect the mesenteric arteries include vasculitis (including giant cell arteritis, Takayasu disease, and polyarteritis nodosa), systemic lupus, Buerger disease, spontaneous dissections, fibromuscular dysplasia, neurofibromatosis, radiation arteritis, aortic coarctation, mesenteric venous stenosis or occlusion, and drug-induced arteriopathy from cocaine or ergot use.

Natural History

Asymptomatic stenosis of one mesenteric artery is often an incidental finding that has a benign clinical course. However, 15% to 50% of patients who present with mesenteric ischemia with bowel gangrene have developed an acute thrombosis of a preexisting chronic lesion with no antecedent warning signs. ^, As part of a prospective cardiovascular health study, Wilson and associates screened the mesenteric arteries of 553 elderly patients with duplex ultrasound and found that 18% of patients had some degree of SMA or celiac disease but none reported symptoms consistent with CMI. Alternatively, Thomas and associates reviewed 980 aortograms of patients without mesenteric symptoms and found that 82 (8%) had >50% stenosis of at least one mesenteric artery and 15 of the 82 had involvement of all three visceral vessels. The patients were followed for a range of 1–6 years and 86% of patients with three-vessel mesenteric disease developed acute mesenteric ischemia, became symptomatic or died, leading them to conclude that early revascularization should be considered in these patients.

Clinical Presentation

Patients who present with clinically significant CMI secondary to atherosclerosis are usually in their 60s but the age can range from 40 to 90 years old and the female to male ratio is 3:1. ^, The main symptoms associated with CMI include abdominal pain, weight loss, and “food fear.” The classic abdominal pain is postprandial and begins within 10–15 minutes of ingestion of a meal. The pain can persist for as long as 5 to 6 hours. It is usually located in the mid-abdominal location, and its character can range from sharp and debilitating to cramping or a dull ache. Patients often describe intolerance to certain types of food, and consequently they alter their eating habits to avoid foods that precipitate symptoms. In some cases, patients will not endorse postprandial pain because they have adapted their eating habits to prevent the pain from occurring, but careful questioning will reveal minimal caloric intake. Patients may also present with complaints of postprandial nausea, vomiting or diarrhea. Unintentional weight loss is the result of the altered eating patterns, progressing to malnutrition and cachexia, which is then an indication for intervention. Indeed, patients who endorse post-prandial pain but have experienced no weight loss may not benefit from revascularization. A recent review of experience with CMI at the Massachusetts General Hospital showed that over 90% of patients presented with abdominal pain and 65% had significant weight loss prior to intervention. In addition, the average time from onset of symptoms to revascularization was 18 months. The pattern of symptoms varies as symptoms can occur intermittently, occur consistently after every meal or progress in severity. CMI may present in a form of sub-acute mesenteric ischemia that is characterized by progression of pain from intermittent to unremitting or continuous over days to weeks. Sub-acute mesenteric ischemia may be an ominous presentation that warrants immediate revascularization. Physical examination is often nonspecific and does not commonly reveal any pathognomonic findings, but can point to the diagnosis. Many individuals are thin at the onset of their symptoms and progress to cachexia. These patients have physical signs of malnutrition including muscle wasting, and a flat or scaphoid abdomen. Pain may be present but not localized or aggravated by abdominal palpation; the finding of pain out of proportion to physical findings is more consistent with acute mesenteric ischemia (AMI) than CMI (see Ch. 133 , Acute Mesenteric Ischemia: Epidemiology, Pathophysiology, Clinical Evaluation, and Management). An abdominal bruit may be noted in up to 50% of patients, and differs from the bruit caused by compression of the celiac axis (CA) by the median arcuate ligament, which is elicited by deep expiration and elevation of the diaphragm. A complete vascular examination may document diminished peripheral pulses and bruit. Laboratory tests are nonspecific or unremarkable in the absence of acute symptoms but may demonstrate malnutrition.

The clinical presentation can be ambiguous in some patients. Vague abdominal pain, nausea, vomiting, or a change in bowel habits such as diarrhea or constipation, without the classic postprandial component to the pain, may be subtle complaints that coupled with weight loss could support the diagnosis of CMI. If upper or lower endoscopy is performed, diffuse small ulcerations in the stomach or proximal duodenum or patchy areas of ischemia in the colon are not uncommon and some patients will present with abnormal liver function tests. Other common risk factors include hypertension, hyperlipidemia, and a history of smoking. ^{, ,} Indeed, atherosclerosis can affect multiple vascular beds and patients often have disease in the coronary (50%–70%), cerebrovascular (20%–45%), and peripheral arteries (20%–35%). Concomitant renal artery disease with difficult to control hypertension or ischemic nephropathy is present in about 20% of patients. ^,

Diagnostic Imaging

It is not infrequent for patients with CMI to undergo an extensive evaluation to rule out other causes of chronic abdominal pain and weight loss. The differential diagnosis is extensive, including inflammatory, infectious, and malignant disease. The investigation often includes upper and lower gastrointestinal endoscopy and cross-sectional studies of the abdomen. Often the finding of mesenteric artery stenosis in an imaging study is the first clue to the diagnosis.

Multidetector Computed Tomography

Cross-sectional imaging of the abdomen provides an anatomic analysis to plan revascularization. ^, The choice of CTA or MRA can be driven by individual expertise or institutional preference. Multidetector computed tomography (MD-CT) technology is readily available in most centers, has the highest spatial resolution and finest image detail, and is considered by most surgeons to be the best study to evaluate anatomic characteristics (calcification, thrombus, diameters, and lengths) that are important to plan mesenteric interventions ( Fig. 134.2 ). In patients with classic symptoms, CTA may supplement or even replace duplex ultrasound, and is often the only imaging study that is obtained prior to intervention. It is also useful to objectively assess patency of grafts and stents.

Treatment Strategies

The goal of treatment in patients with chronic mesenteric ischemia should be to resolve abdominal symptoms, promote weight gain and prevent deterioration to AMI. The timing and type of intervention is dependent upon the severity of patient symptoms and the patient’s overall surgical risk. There may be a role for medical therapy with bowel rest and parenteral nutrition in select patients with symptomatic CMI as a short-term bridge to revascularization. However, there is no role for a prolonged treatment with chronic parenteral nutrition and noninterventional therapy in these patients. Indeed, excessive delays in proceeding with definitive revascularization or use of parenteral nutrition alone have been associated with clinical deterioration, bowel infarction, and risk of sepsis from catheter-related complications. ^, In addition, a recent study that looked at the quality of life of patients who were treated with long-term parenteral nutrition found that it was significantly worse in patients with CMI when compared to those with Crohn’s disease.