Thoracic Aorta Aneurysm

Etiology

Male gender, increased age, history of hypertension, chronic obstructive pulmonary disease (COPD), coronary artery disease, smoking, and previous aortic dissection are risk factors of TAA.[7] The distinct demarcation in causes for aortic aneurysms is the ligamentum arteriosum. Above this point, degenerative processes in the elastic media lead to the formation of aneurysms, and below the ligament, atherosclerosis is the perpetrator.[8] This is probably due to the dissimilar embryonic derivation of the smooth muscle cells in these two regions.[5] A family history of thoracic aortic aneurysm is a strong risk factor, as about 20% of cases of TAA are a consequence of genetic conditions.[7] Only 5% of the patients have Marfan syndrome, Loeys-Deitz syndrome, and Ehlers-Danlos syndrome.[9][1][4] About 21% of the patients with a family history are nonsyndromic, and these aneurysms are referred to as “nonsyndromic familial aortic aneurysms” and have no extra-aortic manifestations.[4][10] Left-sided valvular endocarditis can rarely result in an aortic root dilation. Syphilis used to be the leading cause of aortic aneurysms before the advent of antibiotics. Arteritis, including Takayasu, Behçet, giant cell, systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, and ankylosing spondylitis, can involve the aorta in rare instances and result in an aneurysm.[5][11] A bicuspid aortic valve and an isolated sinus of Valsalva aneurysm are also rare causes.[12] There is a TAA association with an abdominal aortic aneurysm, intracranial aneurysm, renal cysts, and bovine aortic arch.[5]

Epidemiology

In the United States, about 13000 patients die because of aortic disease each year, and TAA is the 18 most common causes of death among all individuals.[8][13] TAA has an incidence of 10 cases per 100000 patient years and a prevalence of 0.16 to 0.34%.[9] The incidence of TAA is increasing due to better diagnostic imaging and increased life expectancy in the general population.[9] Patients with familial TAA have an average age of presentation at 56.8 years, while patients with TAA due to other causes present around 64.3 years.[9] More men develop TAA, while more women develop worse clinical outcomes and have an increased risk of dissection.[6][14]

Pathophysiology

Both biochemical and mechanical factors lead to the formation of thoracic aortic aneurysms. The discrepancy between the wall structure elements, including elastin and collagen, proteoglycans, and proteolytic and inflammatory mediators (transforming growth factor-B [TGF-B]), leads to wall weakness and expansion.[11] Matrix metalloproteinases and cathepsins sever the extracellular matrix of the aortic media. This results in cystic medial degeneration. Changes in aortic wall compliance lead to increased stress on the wall as per Laplace’s law (tension= pressure x radius) during a systolic impulse and can further exacerbate wall weakness and lead to the formation of an aneurysm. Intimal atherosclerosis in the descending aorta can further exacerbate medial degeneration.[5] Aortic ulcers, which are disrupted atherosclerotic plaques, and intramural hematoma, a collection of blood within the aortic wall, are also found in the descending aorta and can result in dissection or rupture. A mycotic aneurysm can occur due to an infection damaging an area in the aortic wall.

Histopathology

The ascending aorta contains three layers. The intimal layer consists of a single layer of endothelial cells. The medial layer is composed of elastin, smooth muscle cells, extracellular matrix, and collagen. An external layer of adventitial tissue is present, which also houses the nerves and vasa vasorum. In an aortic aneurysm, the elastic layer breaks up, and the smooth muscle cells become defective. In due course, a cystic appearing mucoid material replaces the contents of the medial layer, leaving behind the intima and adventitia only.[3][11] 

History and Physical

Almost all patients with thoracic aortic aneurysms are asymptomatic.[9] Patients can report chest pain. If this pain radiates to the back with severe hypotension, it may be an alarming feature for dissection.[1] Chest pain can also occur because of compression of adjacent structures. Some patients can present with difficulty breathing due to airway compression or with signs of superior vena cava (SVC) syndrome. Hoarseness of voice can occur due to the compression of the recurrent laryngeal nerve.[11] In rare instances, ascending or root aneurysms can present with signs of heart failure due to rupture in the right atrium or superior vena cava (SVC) or with hemoptysis due to bleeding in the lung. Patients should be questioned about the history of sudden cardiac death in the family. On examination, most aneurysms are silent. In patients with aortic regurgitation, a diastolic murmur with widened pulse pressure would be noted.[9] Patients should also be examined for physical signs of Marfan and Loeys Dietz syndromes to evaluate for the syndromic cause of aortic aneurysm.[11]

Evaluation

A contrast-enhanced CT scan is the most widely used imaging technique to diagnose thoracic aortic aneurysms. It is readily available and aids in rapid assessment of the size, extent, and location of the aneurysm. Calcifications, dissections, and mural thrombus can also be clearly visualized.[8] When prior CT scans are available, the current scan should be compared to the earliest scan and not the most recent scan.

MRI provides an axial and 3-D reconstruction of the ascending aorta. Contrast-enhanced MR angiography with gadolinium allows more accurate measurements of the aorta and its branches.[11]

Transesophageal echocardiography (TEE) accurately diagnoses aortic aneurysms and dissections and is a reliable technique to measure the annulus, sinus, sinotubular junction, and ascending dimensions.[15] Transthoracic echocardiography (TTE) is a reliable test to check the aortic root and the severity of aortic regurgitation; however, the distal aorta would not be clearly visualized.[1] 

Ascending aortography can demonstrate crisp images of the aortic contour and loss of the typical “waist” of the sinotubular junction during an aneurysm evaluation, although size measurements cannot be made.[8]

PET scans are a newer diagnostic test and can show areas that “light up,” indicating increased metabolic activity depicting inflammation, signifying impending rupture, and should warrant prophylactic surgery.[3][5]

A chest x-ray may show a convex contour of the right superior mediastinum, indicating an aortic aneurysm. In the lateral chest x-ray, there would be an absence of the retrosternal airspace in cases of an ascending aortic aneurysm.

Electrocardiogram (EKG) may demonstrate changes associated with aortic insufficiency, which would show signs of strain and left ventricular hypertrophy. Patients with concomitant coronary artery disease would show ST elevation or depression.

Genetic testing can now be employed to assess for TAA. Whole-exome and genome sequencing are effective in analyzing genes associated with thoracic aortic disease. Patients with high-risk genotypes, including MYLK, ACTA2, and MYH11 mutations, can be diagnosed efficiently.[10]

Treatment / Management

Medical management aims at reducing stress in the aorta, which in turn prevents the growth of the aneurysm. Anti-impulse therapy is essential, and beta-blockers are the first-line drugs as they reduce stress by decreasing blood pressure and contractility. [7] Angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are beneficial for patients with Marfan syndrome as they reduce TGF-B signaling.[11][8][16] Lipid-lowering agents, mainly statins, are also employed as they reduce oxidative stress, rate of rupture, and dissection.[7] Glucocorticoids, indomethacin, and leukocyte-depleting antibody (anti-CD 18) can also be used.[7] Fluoroquinolones should be avoided as they increase wall degeneration in patients with TAA. In asymptomatic patients, reimaging should be performed at 6 months and then annually if there is no expansion to monitor TAA progression. Lifestyle modification, including smoking cessation and diet to control hypertension, is advised.[11][5][17]

Surgery in patients with TAA aims to prevent dissection or rupture of the aneurysm.[8] Patients with acute dissection, rupture, or intramural hematoma need immediate surgical correction. There is an increased risk of rupture when the ascending aorta reaches 6 cm, and the descending aorta is at 7 cm. Therefore, elective surgery is advised for patients with a 5.5 cm ascending aorta and 6.5 cm descending aorta; the cut-off for ascending aneurysm is 5 cm in an asymptomatic patient with Marfan syndrome.[8][5] Body size is also taken into account while planning surgery where an aortic size index (aortic diameter divided by body surface area) less than 27.5 cm/m necessitates surgery.[5] In TAA of the ascending aorta, an open surgical approach with aorta replacement is performed.[5] The extent of resection depends on the location of aneurysmal disease: some patients may be sufficiently treated with supracoronary ascending aorta replacement alone, while others may need more extensive surgery, which may include the aortic root or aortic arch. For patients with connective tissue disorders, bicuspid aortic valve, or strong family history of aortic dissection or rupture, replacing the sinus segment, ascending aorta, and proximal arch may be beneficial. For a bicuspid aortic valve, the valve can be replaced or repaired at the time of aortic surgery. Open repair generally entails median sternotomy, cardiopulmonary bypass, and ischemic arrest with or without deep hypothermic circulatory arrest (DHCA). For ascending aorta replacement alone, it is preferred to utilize DHCA with open distal anastomosis. After aortic cross-clamping and achieving cardioplegic arrest, the aorta is transected 1 cm below the clamp and resected to the sinotubular junction. Once the goal temperature is reached, a circulatory arrest is initiated, and the cross-clamp is released. The remainder of the ascending aorta is excised up to the base of the innominate artery takeoff. An appropriately sized polyester or polyethylene terephthalate tube graft is then anastomosed to the open aorta. Cardiopulmonary bypass is reinitiated, and the proximal anastomosis is then performed to the sinotubular junction. Cerebral protection techniques, including antegrade or retrograde perfusion, can be employed.[11] Branched arch grafts or debranching grafts can be used after the aortic arch is opened. Descending TAA is repaired with open repair, endovascular approach, or a hybrid procedure.[5] These aneurysms are accessed via a thoracotomy in open repair and usually do not involve cardiopulmonary bypass or cardioplegia. Thoracic endovascular aortic repair (TEVAR) repairs TAA between the left subclavian and the celiac arteries with endovascular grafts. During the procedure, a carotid-subclavian bypass may be performed when the stent edge covers the left subclavian artery.[11] Special care is taken in TEVAR to prevent spinal cord ischemia. Custom made branched and fenestrated grafts can be ordered for elective cases.[18]

Differential Diagnosis

Aortic dissection presents with severe tearing chest pain radiating to the back. It is one of the complications of TAA because of increased stress and aortic wall weakness. A tear develops in the intima leading to the creation of true and false lumens. Patients can also present with hypotension, nausea, shortness of breath with a difference in blood pressure between the right and left arm.[1] On chest X-ray, widening of the cardiac silhouette could be seen. A CT scan will clearly show the intimal flap and the lumens in the aortic wall. Emergent surgery is needed to fix the defect.

Thoracic aortic pseudoaneurysm is an aortic rupture contained by the thin layer of adventitia. They develop following trauma or due to erosion of an atherosclerotic ulcerated plaque. Patients can present with chest pain or deficits due to embolization. CT scanning and angiography can visualize this anomaly. Surgical repair is necessary to prevent aortic rupture.

Aortic intramural hematoma is a hematoma located in the medial layer of the aorta. Usually, no intimal tears are present. They can occur because of a penetrating atherosclerotic ulcer or by thrombosis of the false lumen after a dissection. Surgical correction is required to restore the architecture of the aortic wall as the hematoma is also a precursor for aortic dissection.

Prognosis

Each year the ascending aortic aneurysm increases in size by 1 mm while the descending aortic aneurysm grows up to 3 mm.[5] As the size of the aorta reaches 6 cm, its distensibility declines, and it becomes a rigid tube where increased pressure results in increased stress on the aortic wall.[9][17][19] Surgery should be planned for all symptomatic patients and asymptomatic patients with an increased size aneurysm. Among the patients who undergo elective surgical correction for TAA, the 5-year survival is 85%, while those who undergo emergency surgery have a 5-year survival 0f 37%.[9]

Complications

Aortic dissection and rupture can happen as a result of an enlarging aortic aneurysm.[5] The incidence of these complications is similar, at 3.5 per 100000 patient-years. [9] The chance of rupture is 34% when the ascending aortic aneurysm reaches 6 cm. [8] Acute emotion and high-intensity weight lifting can lead to acute aortic dissection or rupture due to high blood pressure levels up to 300 mmHg.[17][19] Aortic dissection also reflects patterns of circadian and diurnal rhythm with increased incidence in winter and morning time, depicting times when blood pressure is the highest.[17]

Surgical complications include bleeding, stroke, pulmonary dysfunction, myocardial dysfunction, and perioperative mortality. Patients have perioperative mortality of 28.6% during the repair of the descending aorta and 23.4% during the endovascular repair.[9]

In an autopsy study in patients with sudden cardiac death, the TAA complications of dissection and rupture occur between 2 to 7.3%.[4]