Section 8 -

Aortic Atherosclerosis - Aneurysms and Other Complications Jagdish Butany John Veinot

Case 7 - Aortic Atherosclerosis - Aneurysms and Other Complications This 82-year-old man was known to have severe atherosclerosis with prior abdominal aortic aneurysm (AAA) surgery with patch placement. He had been a smoker prior to his AAA surgery. He was otherwise thought to be well. He died unexpectedly after severe hemoptysis. Findings at complete autopsy: Penetrating aortic ulcer with ruptured dissection Severe aortic atherosclerosis with multiple complicated plaques Penetrating atherosclerotic aortic ulcers of the proximal descending aorta and abdominal aorta Upper aortic ulcer associated with underlying chronic aortic dissection extending from subclavian artery to abdominal aorta Aortic dissection false lumen aneurysm penetration into left lung with hemorrhage - lung filled with blood Lower aorta penetrating ulcer - early recent localized dissection, not ruptured or otherwise complicated AAA graft uncomplicated - no evidence of thrombosis, anastomotic leak, anastomotic stenosis or fistula Aortic Aneurysms and Peripheral Vascular Disease Aortic Aneurysms - Pathoetiology An aneurysm is defined as a localized dilatation of a vessel or the aorta. Aneurysmal dilatation contrasts to vascular ectasia in which the dilatation is more diffuse, usually due to high flow. Aortic aneurysms are most common below the renal arteries above the aortic bifurcation. The most common aneurysm etiology and predisposing cause is atherosclerosis, which is more common in the abdominal aorta compared to the rest of the aorta. All the stages of atherosclerotic plaque development can be observed in the aorta. The number of plaques increases from the ascending to abdominal aorta. The number of plaques is usually most marked below the renal arteries. It is common to find ulcerated and complicated plaques covered by thrombus and exposed to blood flow. The aorta is the largest elastic artery. It acts as a conduit for blood distribution and absorbs energy as blood is ejected from the heart. The strength of the aortic wall depends upon the balance between the blood pressure (the dilating force) and the strength of the aortic wall. The wall has collagen fibers, important for strength, and elastic fibers important for viscoelasticity. Between the elastic lamellae there are smooth muscle cells and fibroblasts. Increased smooth muscle cell apoptosis and cell death are thought to be contributors to aneurysm development. A recent study has demonstrated smooth muscle cell hyperplasia as an early event in aneurysm development. [1] Aneurysms have altered extracellular matrix including collagen, and fragmented elastic lamellae thus allowing the vessel to dilate. [2, 3] The pathogenesis of an aneurysm may be multifactorial with several factors playing a role including atherosclerosis, familial clustering, genetic tendency, biochemical alterations of the vascular wall and hemodynamic and mechanical factors. There is evidence that matrix metalloproteinases (MMPs), especially MMP2 and MMP9, enzymes that degrade extracellular matrix, may contribute to aneurysm formation. [4] For the most part, these enzymes are released in an inactive form and are activated in the tissues (some membrane activated forms also exist). Inhibitors and activators exist and the state of the MMP enzyme ultimately depends upon the balance between these factors. Transforming growth factor (TGF) beta and its receptors are thought to have a major influence on vascular extracellular matrix. This mediator is increasingly believed to play a central role in aortic wall matrix metabolism and aneurysm pathoetiology. [3, 5] This is true in atherosclerotic abdominal aortic aneurysms and in heritable disorders of connective tissue including Marfan's syndrome. Interventions to influence the state of TGF activation and its effect on the vascular matrix proteins are now being investigated. [6] Inflammation in the adventitial outer layer and media may play a role by releasing proteolytic enzymes or inducing aortic wall mesenchymal cells to do so by way of cytokines. [2] These medial and adventitial cells are a mixture of B and T lymphocytes, mast cells and macrophages. They may be a response to the atheromatous plaque with oxidized lipid. [4] Inflammation also activates the MMPs. Aneurysms are thus influenced not only by the intimal atherosclerosis, but also by the medial degeneration and proteolysis from the adventitial and medial inflammation. Some aortic aneurysms have been shown to be familial, beyond the familial and genetic pre-disposition to atherosclerosis and systemic arterial hypertension. Family studies suggest a risk figure of 14.5 % for offspring and 13 - 32 % for siblings compared with the general population risk of 2 - 5 %. [4] Abnormalities in the genes regulating matrix proteins such as collagen and elastin, similar to Ehlers Danlos or Marfan syndrome, are being implicated in sporadic and familial cases. Mutations in TGF beta and its receptor family also are important. [5] Aneurysm Classification Aneurysms can be divided into categories depending upon shape, structure of their walls, etiology and location. Aneurysms of the aorta may be saccular (S) or fusiform (F). Aneurysms may also be true or false types. Saccular or fusiform refers to the shape of the aneurysm. Saccular aneurysms are made up of a portion of the circumference of the aortic wall with lateral sac-like protrusion. Fusiform aneurysms involve almost the entire circumference of the aorta and are shaped like a sausage. In true aortic aneurysms, the wall of the aneurysm is derived from all the constituents of the aortic wall. In false aneurysms, the aneurysm wall is due to organization of a hematoma due to organization of a local rupture. In the aorta, both true and false types of aneurysms have a propensity to rupture (indeed the false aneurysm already has). Abdominal Aortic Aneurysms Abdominal aortic aneurysms (AAA) are commonly fusiform, involving the entire circumference of the aorta, but there may be some asymmetry with localized protrusion. The aneurysm wall consists of dense fibrous tissue with laminated old and recent thrombus adherent to the inner sac. This aneurysm is complicated atherosclerosis with very little residual media. Small abdominal aortic aneurysms may be clinically silent for a long period of time. Complications of aortic aneurysms local mass effect with distortion of intra-abdominal structures including the ureters thrombosis vascular stenosis and claudication infarction of viscera atheroemboli to the viscera or the peripheral limbs rupture and hemorrhage infection Aneurysms of the abdominal aorta may be diagnosed by CT or ultrasound. The natural history is gradual expansion with ultimate rupture into the peritoneal cavity or retroperitoneal tissues. The timing of surgical intervention, if necessary, is a complex decision that must be made with each individual. [7, 8] This depends upon the size of the aneurysm (observe the aneurysm if it is 4 to 5.4 cm diameter on imaging; operate if greater than 5.5 cm diameter), the presence of complications such as peripheral ischemia and emboli, the rate of aneurysm expansion and the presence of symptoms. Gender may play a role in the progression of an aneurysm and its risk of serious complication. AAA in females may rupture earlier and require earlier intervention, as compared to males. [9, 10, 11] Female patients also do worse after surgery. The morphology of the aneurysms may differ between the sexes. Some investigators state that women's aneurysms are shorter and more angulated, thus possibly more difficult to treat. Risk factors for rupture of an asymptomatic aneurysm include a large aneurysm diameter, systemic arterial hypertension, and chronic obstructive pulmonary disease (COPD). [7] It is impossible to predict which aneurysms will rupture or complicate. Some are silent for years then rapidly expand with no apparent reason. Rupture of the aneurysm may be the presenting event at the time the aneurysm is diagnosed and treated. Aneurysms often rupture into the left retroperitoneum. The patient may have hypovolemic shock and rapid surgery is usually indicated. The classic clinical triad of a rupturing AAA is hypotension, back pain and a pulsatile abdominal mass. Aneurysms are usually surgically bypassed with prosthetic grafts. The actual aneurysm is often left in situ with the graft sewn into the lumen. The excised surgical specimen often is solely laminated thrombus with only a small amount of atheroma at the periphery of the specimen. If neutrophils are prominent a Gram and a silver stain are necessary to rule out an infection that has caused the AAA to rupture. Early post-operative complications include cardiac events (ischemia, arrhythmia, heart failure), respiratory insufficiency, renal injury, bleeding, thromboembolism, and wound infection. Stroke, paralysis or ischemic viscera are rare. At autopsy attention to the anastomoses and to the integrity of the visceral vessels is needed. Branches may inadvertently be ligated with severe ischemia of the organs including visceral infarction or insufficiency. Chronic complications include graft infection, aorto-enteric fistula, graft occlusion and thrombosis, and anastomotic aneurysms. Mortality associated with repair of an uncomplicated aneurysm is much less than that associated with a ruptured aneurysm. Stents with prosthetic graft material may also be deployed in the vessel. This type of intervention is usually done by an interventional radiologist and sometimes a surgeon and may be useful if the individual is not a good surgical candidate. It is important to remember that if the patient has an atherosclerotic abdominal aortic aneurysm they also likely have coronary artery disease. This is important for pre-operative planning for the surgical procedure and also is prognostic as many individuals die from CAD after a successful AAA repair. [7] Abdominal aortic aneurysm with prosthetic bypass graft placed. Thoracic and Ascending Aortic Aneurysms Atherosclerotic thoracic and ascending aortic aneurysms also exist. Thoracic aneurysms may present with chest or back pain. Vertebral column erosion may occur if the aneurysms are large. Stridor or dysphagia may result from local compression effects. Angina and peripheral emboli may occur. In ascending aortic aneurysms there may be congestive heart failure due to compression of the right ventricle outflow tract, secondary dilatation of the aortic annulus causing aortic insufficiency or rupture of the aneurysm into a cardiac chamber or vessel with shunting. If rupture occurs in the pericardial sac or pleural space, hemopericardium/ tamponade or hemothorax may result. These thoracic, arch, and ascending aortic aneurysms are usually excised or grafted with prosthetic graft material, sometimes with aortic valve replacement (Bentall procedure) or CABG if warranted. They may also be bypassed with graft material and the aneurysm excised. Surgical complications are similar to those encountered with abdominal aortic aneurysms - anastomotic complications, and compromise of the visceral arterial branches and the spinal cord, in the case of thoracic aneurysms. Inflammatory Aortic Aneurysms "Inflammatory" aortic aneurysms are also related to atherosclerosis. These aneurysms have a clinical triad of chronic abdominal pain, weight loss and an increased ESR. They have a florid chronic inflammatory and fibrotic response in the adventitial layer. The fibro-inflammatory response, which may include lymphoid follicles, surrounds nerves and may encroach upon the ureters, or the vena cava. The duodenum is at risk of adhesion to the aorta. These aneurysms have a reduced risk of rupture and exsanguination, but increased local complications from distortion of the abdominal viscera. Pathological examination shows an aneurysm with an extremely thickened wall due to lymphoplasmocytic aortitis with severe adventitial fibrosis. The media and adventitia are severely inflamed with chronic mononuclear inflammatory cells associated with adventitial fibrosis. Elastic stain shows that the majority of the aneurysm wall thickness is actually due to the fibro-inflammatory adventitia layer and the media is thin, as is typical of a usual aneurysm. Endarteritis of the vasa vasora, phlebitis and nerves entrapped in the adventitia are all seen. These changes pathologically mimic retroperitoneal fibrosis. The cause of these aneurysms is not known but possibilities implicated include:(a) that the aneurysm is part of a systemic inflammatory disorder, (b) an autoimmune response to altered atherosclerotic plaque constituents, or (c) chronic leakage of the aneurysm with inflammatory and myofibroblastic reaction. [12] Penetrating Aortic Ulcer This is a relatively recently recognized type of aortic aneurysm. The typical patient is a middle aged or elderly individual with atherosclerosis or systemic arterial hypertension who presents with chest or back pain without evidence of stroke, aortic insufficiency, pulse deficit or peripheral or visceral vascular compromise (in contrast to aortic dissection). [13] This type of aneurysm is a localized saccular aneurysm due to complicated atherosclerosis. The ulcerated atheroma penetrates the internal elastic lamina and allows hematoma formation in the media of the aorta. There may be variable amounts of intramural hemorrhage, dissection, aneurysmal dilatation, pseudoaneurysm or even aortic rupture. [14] Calcification is common and there is usually no intimal flap. The most common location is in the proximal descending aorta, but these aneurysms may also be found in the ascending aorta. These penetrating ulcer aneurysms have a propensity for complication with rupture and dissection. There is continuing debate as to whether they all should be operated upon or whether some may be observed. If they are symptomatic or deeply penetrating there is little debate that they should be treated. Some clinicians group the penetrating ulcer group with intramural hematoma. If recognized, ulcers have a worse prognosis than the hematoma (some suggest medical management for hematoma). If surgically excised and received intact, they have a distinct appearance with an intimal ulcer leading to a flask-like underlying saccular aneurysm. However, they are more commonly received in fragments. They may be confused with the more routinely encountered aortic dissection unless the atherosclerotic ulcer is noted. Clinical information and imaging results are often useful to sort out the difference in these circumstances. Peripheral Vascular Disease Arterial stenosis and chronic occlusion of the peripheral vessels arise from the same mechanisms of atherogenesis described in the coronary arteries. The morphology of the atherosclerotic plaques encountered is similar to those seen in the aorta, but the effect of the plaque is different since the vessels are a different size, the limbs have a different demand, and the degree of collaterals may be more developed in the limbs. The majority of individuals with lower limb ischemia have proximal atherosclerosis in the aorta, iliac and femoral arteries. Diabetics may have particularly severe distal small vessel disease. These plaques may cause leg pain (claudication with exercise or at rest), ischemic ulcers, or gangrene of the limbs. Bypass procedures with vascular prosthetic grafts or vein grafts, endarterectomy of the plaque at open operation or atherectomy via catheter devices may be used - similar to what is possible in coronary arteries. Stenting of the peripheral arteries is increasingly performed and these vessels may undergo restenosis, similar to coronary artery stented vessels. References Tang PCY, Coady MA, Lovoulos C, Dardik A, Aslan M, Elefteriades JA, et al. Hyperplastic Cellular Remodeling of the Media in Ascending Thoracic Aortic Aneurysms. Circulation 2005;112(8):1098-105. Rehm JP, Grange JJ, Baxter BT. The formation of aneurysms. Semin Vasc Surg 1998;11(3):193-202. Baxter BT. Heritable diseases of the blood vessels. Cardiovasc Pathol 2005;14(4):185-8. Davies MJ. Aortic aneurysm formation: lessons from human studies and experimental models. Circulation 1998;98(3):193-5. 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