Acute Aortic Syndrome

Etiology

AAS comprises 3 distinct pathologies that can present similarly, with overlapping etiologies and predisposing factors.[6] The etiologies of these conditions are discussed below. 

Acute Aortic Dissection

AAD makes up 70% to 80% of all AAS. This condition arises from a tear in the innermost layer of the aorta and is commonly heralded by existing cystic medial necrosis or medial degeneration.[7] This pathology, combined with continuous exposure to raised blood pressure and shearing forces in a predisposed patient, can lead to a tear in the intimomedial layer, creating a flap. Blood enters this false lumen and, under pressure, causes dissection of the intimomedial layer from the outer wall of the aorta.

Fenestrations can form distal to the initial tear, creating a communicating passage between true and false lumens. The dissection can progress proximally and distally from the site of the initial tear. AAS type A is any dissection involving the ascending aorta. Recently, the Society for Vascular Surgery and the Society of Thoracic Surgeons have defined type B AAS as any dissection where the entry tear occurs distal to the origin of the innominate artery.[8]

Intramural Hematoma 

Discussion regarding the exact cause of IMH is ongoing. The most widely accepted theory is the spontaneous rupture of the vasa vasorum, the blood vessels that supply the outer layers of veins and arteries.[9] Another explanation is thrombosis between aortic wall layers that occurs due to stagnant blood after a dissection or microtear in the intima without a reentrant tear.[10] Both AAD and IMH can develop secondary to trauma from vascular catheter insertion. 

Penetrating Aortic Ulcer

PAU involves atherosclerotic plaque formation, which leads to destruction and inflammation of the intima and penetrates outwardly through the layers of the aortic wall. PAU can either remain stable or progress to AAD or IMH. PAU may result in aortic rupture or visceral ischemia in severe cases.[11]

Common predisposing factors for AAS include:

• Hypertension
• Smoking
• Hyperlipidemia
• Cocaine use
• Connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome, and Turner syndrome
• Congenital cardiovascular anomalies such as bicuspid aortic valve and coarctation of the aorta
• Vascular inflammation from autoimmune causes, eg, giant cell arteritis, or infection, eg, syphilis
• Trauma, particularly from acceleration-deceleration injuries
• Iatrogenic damage, such as from catheter insertion and valvular or aortic surgery [12]

Epidemiology

Existing data sets suggest that the incidence of AAD is between 2.6 and 7.2 per 100,000 patient-years, with data mostly coming from Western countries. Up to 65% of patients are male, with modal presentation in the 7th decade of life.[13][14] Predisposing factors differ between adults older and younger than 70, with the older population more commonly presenting with hypertension, atherosclerosis, and iatrogenic causes such as cardiac catheterization. Younger patients are more likely to have a congenital pathology, including connective tissue disorders such as Marfan Syndrome, bicuspid aortic valves, and prenatal cocaine exposure.

Patients with IMH share the same risk factors as those with AAD, but the typical age at presentation is in the 80s. IMH constitutes 5% to 25% of AAS cases, with studies averaging 1.2 cases per 100,000 patient years. PAU comprises 2% to 7% of AAS cases, with figures averaging 2.1 cases per 100,000 person-years. PAU is most commonly associated with widespread, severe atherosclerosis and often presents multiple ulcerating lesions throughout the aorta. Most patients also suffer from hypertension and coronary artery disease, and some studies show up to 68% of patients also have chronic obstructive pulmonary disease. Between 42% and 61% of patients have concurrent aortic aneurysms.[15]

Pathophysiology

As mentioned, the most common AAS precursors are atherosclerotic disease and hypertension. Besides these conditions, trauma, infective processes, and any media pathology can also lead to AAS. Intimal tearing from blood flow's shearing forces or interference with the media separates the aortic wall layers.[16] This separation can create a true and a false lumen. The true lumen is lined by intima, connects undissected aortic segments, and is separated from the false lumen by an "intimal flap." Blood flowing through a false lumen over time can form an aortic aneurysm.[17]

IMH is traditionally thought to arise from the rupture of the vasa vasorum. However, recent pathological studies suggest the presence of microintimal tears in diagnosed IMH cases, implying that IMH and AAD may have common pathophysiological mechanisms. The difference is the lack of a large enough reentrant tear to preserve the false lumen's patency.

PAU develops as atherosclerotic plaque invades through the intimal layer toward the adventitia. PAU may progress to IMH, AAD, or a pseudoaneurysm. 

Histopathology

The most common histopathological feature in AAD is the degeneration of the medial layer. Fundamental degenerative changes include fragmentation, thinning of elastic fibers, and accumulation of mucoid extracellular matrix. Additionally, a notably thin intimal layer and a dissection plane often found at the level of the vasa vasorum network in the outer media have been observed.[18] Patients with connective tissue disorders or aortic aneurysms tend to exhibit more severe medial degeneration. However, medial degeneration is considered the final common pathway for various forms of AAS.

The discussion surrounding the pathophysiology of IMH should not detract from its key feature: the restricted blood flow within the aortic wall, leading to its distinctive morphology and progression over time. IMH can resolve spontaneously or progress to AAD. Histologically, the hematoma extends within the media. Between AAD and IMH, the latter is more strongly associated with atherosclerotic lesions. While AAD typically results from an intimal tear, IMH is thought to arise from the rupture of the vasa vasorum, leading to intramural hemorrhage.[19] However, both conditions share a common mechanism in some cases, with IMH potentially representing an AAD with an acutely thrombosed false lumen. Studies showing a high incidence of tears or communicating points in presumed IMH cases support this shared mechanism theory.[20]

PAUs typically develop in the context of severe, widespread atherosclerotic disease and are most often found in the descending thoracic aorta. PAUs are frequently accompanied by localized intramedial bleeding, which may spread locally or, in rare cases, lead to an aortic dissection, with the ulcer's "crater" acting as the entry tear. Wall calcification and inflammation are believed to limit the extent of hemorrhage, resulting in a more localized form of AAD. PAUs penetrate the adventitia in some cases, causing either an aortic rupture or pseudoaneurysm formation, leading to aortic wall bulging.

History and Physical

A classic symptom of AAS is severe aortic pain, which is a chest or back pain commonly described as "tearing," "ripping," "migrating," or "pulsating."[21] The International Registry of Acute Aortic Dissection (IRAD), the largest single dataset on the subject, has sharp, severe pain as the most common presenting complaint. About 4.5% of patients deny pain, and AAS is incidentally detected through screening programs in these individuals.

Neurological signs such as syncope can copresent with pain, suggesting reduced blood flow to the central or peripheral nervous system. This cooccurrence results from the aortic wall pathology's disruption of spinal and aortic outflow, affecting both central and peripheral blood flow.[22] Dissection in the ascending aorta may be associated with myocardial ischemia, aortic regurgitation from the involvement of the aortic valve, or pericardial effusion.

Chronic severe hypertension is the most common risk factor associated with AAS. In a large prospective study conducted by Landenhed et al, hypertension was observed in 86% of individuals who later developed aortic dissection and showed a strong correlation with its incidence.[23] However, hypertension is not highlighted as a significant predisposing factor in the Aortic Dissection Detection Risk Score based on 12 risk factors organized into 3 categories (see Image. Aortic Dissection Detection Risk Score).[24]

Evaluation

Besides taking the clinical history and performing a physical examination, patients must be further investigated with imaging and non-imaging-based examinations when AAS is suspected. The modalities that may be included in the workup are discussed below.

Non-Imaging Based Examinations

This set of tests consists of electrocardiography (ECG) and blood tests. An ECG allows for separating cardiac sources of chest pain, such as myocardial infarction. AAS and myocardial infarction can present concomitantly, though further investigation and careful management are required. Data from IRAD show that 31% in a group of 464 patients had type A dissection with normal ECG tracing, with the rest showing an array of ECG changes from nonspecific ST- and T-wave changes to features consistent with acute myocardial infarction.[25]

Blood tests that can help diagnose AAS or provide evidence for other differential diagnoses include:

• Complete blood count
• Blood urea nitrogen and electrolytes
• C-reactive protein
• Liver function tests
• D-dimer
• Troponin
• Creatinine kinase
• Arterial blood gas analysis, including lactate and glucose levels

The selection of non–imaging-based diagnostic tests should be guided by the clinical presentation, especially if patient or facility resources are limited.

Imaging

Imaging is the mainstay of the diagnostic process, and it may include chest radiography, computed tomography (CT), ultrasound, or magnetic resonance imaging (MRI). Simple chest radiography has shown a sensitivity of up to 64% and a specificity of 86% in identifying AAS. Chest radiographic features indicative of AAS include mediastinal or aortic notch widening, aortic kinking, tracheal shifting, and the aortic shadow demonstrating a double density.[26] The current gold standard in AAS imaging is CT angiography, which is available in most emergency departments. This modality is also noninvasive, less operator-dependent than ultrasound, and less time-consuming. The CT scan's average sensitivity in detecting AAS is upward of 95%. Recorded specificities are anywhere between 87% and 100%.[27][28]

Transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) may also be used in the diagnosis of AAS. However, the effectiveness of each varies greatly. TTE can help diagnose proximal dissection and its complications in an acute setting. However, views can be limited in many other regions along the aorta's entirety. TEE brings the ultrasound probe closer to the aorta than TTE. Thus, TEE's sensitivity for AAS is 99% and specificity is 89%.[29] However, TEE is operator-dependent and far less readily available in an emergency setting. Further, an investigation requiring intubation of the esophagus is much more invasive than CT or MRI.

MRI is seldom used as a primary mode of acute investigation due to the limited availability of this modality in emergency settings and the life-threatening nature of AAS. However, as the most sensitive and specific modality for identifying all AAS types, MRI may be used when primary investigations prove inconclusive.

Treatment / Management

AAS can be categorized based on whether the ascending or descending aorta is involved. Conditions affecting the ascending aorta are surgical emergencies. Static AAS involving the descending aorta are often managed conservatively, but cases that actively progress, cause organ or limb malperfusion and unmanageable pain, or pose a risk of rupture require urgent surgical management.[30] Immediate AAS management focuses on reducing systolic blood pressure below 120 mm Hg and slowing the rate of blood pressure change (dP/dt) to halt dissection or prevent rupture. Intravenous β-blockers, such as labetalol, are the mainstay of medical management, with nondihydropyridine calcium channel blockers as alternatives for patients intolerant of β-blockers. Vasodilators may be used alongside these treatments.

AAD involving the ascending aorta is a surgical emergency traditionally managed with an open approach. Treatment aims to eliminate the false lumen by closing or excising the initial intimal tear and any subsequent tears. Alternatively, synthetic grafts can reinforce the aortic wall. Proximal extension into the aortic valve may lead to aortic valve insufficiency and damage to the coronary arteries, which can be corrected by resuspending or replacing the valve. Endovascular repair has been attempted for type A dissections. However, literature on the topic is scarce, with only 92 published cases over the last 2 decades. A significant limitation of the endovascular approach is the difficulty in addressing dissection involving the aortic valve and root.

Acute type B dissection is divided into complicated and uncomplicated cases. Complicated dissection of the descending aorta affects 25% of patients with acute type B aortic dissection who are either hemodynamically unstable or present with malperfusion to organ systems or limbs. Other symptoms include unrelenting chest pain, uncontrollable hypertension, or imaging findings indicating progression.[31] Endovascular stenting with synthetic grafts and aggressive medical therapy yields the most favorable outcomes for this pathology.(A1)

Uncomplicated type B aortic dissection has been traditionally managed with medical therapy alone. However, a case can be made for prophylactic endovascular treatment to prevent disease progression. Data remains inconclusive due to the lack of large-scale, long-term, randomized controlled trials. IMH, despite having a lower mortality than AAD, receives similar treatment due to the risk of progression to dissection, aneurysm formation, or aortic rupture. Aneurysms affecting the ascending aorta are stented with an endovascular approach when possible. In contrast, lesions in the descending aorta may be managed by watch-and-wait therapy, optimal medical therapy, or surgery.[32] 

IMH of the descending aorta can either progress or regress over time. Stable, regressive IMH can be managed with medical treatment, while unstable, progressive IMH requires endovascular management. The expansion and contraction of IMH complicate stent graft sizing and increase the risk of a type 1 endoleak. The hematoma expands during the acute phase, but over time, it thromboses and retracts, increasing the aortic lumen. Isolated asymptomatic PAU can be safely treated with medical therapy. Symptomatic PAU is more likely to progress to aneurysm, pseudoaneurysm, or aortic rupture, necessitating surgical management. Given the comorbidities and advanced age of patients with PAU, endovascular repair with stent grafts significantly reduces mortality.

Differential Diagnosis

The differential diagnoses for acute aortic syndrome include the following:

• AAD
• IMH
• PAU
• Thoracic aortic aneurysm
• Abdominal aortic aneurysm
• Traumatic aortic injury
• Myocardial infarction
• Pulmonary embolism

A thorough clinical examination and judicious diagnostic testing can help differentiate AAS from similarly presenting conditions, guiding management.

Staging

Classification

The 2 most widely used classification systems for AAD are the Debakey and Stanford Classifications. IMH is also classified in the same way. 

DeBakey classification

• Type 1 – Starts in the ascending aorta and progresses to the arch and, sometimes, beyond this point 
• Type 2 – Involves the ascending aorta only
• Type 3 – Involves the descending aorta only

Stanford classification

• Type A – Any dissection involving the ascending aorta
• Type B – Any dissection not involving the ascending aorta

Prognosis

AAD carries a high mortality rate that varies by dissection location. Ascending aorta dissections treated medically have an overall mortality of 24% within 24 hours, 44% at 7 days, and up to 49% at 14 days. Surgically managed type A dissections show lower mortality rates of 10% in the first 24 hours, 16% at 7 days, and up to 20% at 14 days. Type B dissections have a lower fatality rate, with 30-day mortality of up to 10%. In patients experiencing complications, mortality can exceed 25% by day 30.

Separating IMH from coexisting AAS is challenging, as studies indicate that up to 30% of patients present with both AAD and IMH at diagnosis.[33] IMH can either undergo reabsorption in up to 10% of cases or progress to aortic dissection in up to 47% of patients. Surgical management of type A IMH produces better outcomes, with mortality rates of 14% compared to 36% for medical management. Treatment approaches for type B IMH yield comparable mortality rates, with 14% for medical therapy and 20% for surgical intervention.[34]

Complications

The complications that can develop from AAS include:

• Aortic aneurysm formation
• Aortic rupture
• End organ ischemia
• Limb ischemia
• Aortic valve
• Haemoperidardium
• Pleural effusion
• Coronary artery dissection
• Death
• Stroke
• Myocardial infarction

Endoleaks following endovascular stenting are classified into 5 types based on the source of leakage (see Image. Endoleak Types). These types are as follows:

• Type I: Leakage occurs at the attachment site due to insufficient sealing. This type is subdivided as:
  • IA: Leakage at the proximal attachment
  • IB: Leakage at the distal attachment
  • IC: Involves aorto-mono-iliac grafts and femoro-femoral bypass from the contralateral nongrafted iliac artery.
• Type II: Leakage occurs through collateral vessels, such as the lumbar, inferior mesenteric., and internal iliac arteries.
• Type III: Leakage results from defects in the graft, such as fractures or holes, indicating mechanical failure of the graft.
• Type IV: Leakage occurs without a specific source but is typically due to graft porosity.
• Type V: The aneurysm sac expands without visible leakage, a phenomenon known as endotension.

Endoleak management mainly depends on the type, as well as the presence of sac expansion. Types I and III require prompt intervention, while type II can be monitored and treated selectively if significant sac enlargement occurs. Since endoleaks can develop at any time after endovascular aneurysm repair, conducting a contrast-enhanced CT angiogram or duplex ultrasound every 5 years in a specialized laboratory is recommended. Types I and III pose the highest risk of rupture (7.5% within 2 years for type I and 8.9% within 1 year for type III) and should be addressed immediately.

Current guidelines indicate that intervention is warranted for other endoleak types if the aneurysm sac grows by more than 5 mm. Type II endoleaks are the most frequent, comprising 50% of cases. Up to 90% of type II endoleaks resolve spontaneously or do not cause sac expansion, requiring only observation. The risk of rupture is below 1%, but cases needing reintervention are complex, with a high recurrence rate and potential rupture even without sac growth. Types IV endoleaks and endotension are rare, usually benign, and best managed with observation.[35]