Aortic dissection (AD), penetrating atherosclerotic ulcer (PAU), and intramural hematomas (IMH) are a group of aortic lesions with similar clinical symptoms, and in recent years it has been proposed to describe this group of pathological changes in the aorta by the term acute aortic syndrome (AAS) [1]. Each of these lesions has a different pathophysiology, but some patients present with the coexistence of 2 or 3 of them, demonstrating that they are somehow related to each other. Their clinical presentation is similar, with the typical clinical manifestation being chest pain, also known as aortic pain, which presents as sharp, tearing chest and back pain that peaks rapidly after the onset of pain. When the lesion involves the ascending aorta, the pain may radiate to the anterior chest or neck; when the descending aorta is involved, the pain may radiate to the posterior back. Currently, AAS is classified into type A and type B according to the Stanford staging of aortic coarctation: type A involves the ascending aorta and aortic arch, and type B involves the descending aorta distal to the opening of the left subclavian artery. Recent rapid advances in imaging techniques have led to a better understanding of AAS, which predicts acute aortic dissection, a new term that highlights the critical nature of aortic lesions. At the same time, with the development of endovenous aortic therapy (TEVER), the treatment of this type of disease has changed from the original drug-based treatment to the increasing use of surgical treatment. Feng Xiang, Department of Vascular Surgery, Shanghai Changhai Hospital
1. Pathological mechanism of AAS [2]
AD is caused by degenerative lesions or cystic necrosis of the middle layer of the aorta, resulting in the tearing of the intima and the perfusion of blood through the tear into the arterial wall, resulting in the formation of a pseudocavity between the intima and the middle and outer membranes, which can extend to each branch of the aorta in either a downward or a reverse direction, resulting in syndromes such as underperfusion and occlusion of the corresponding organs or incomplete closure of the valve leaflets. The most important factor is uncontrolled moderate to severe hypertension, which accelerates hypertrophy, fibrosis, calcification, deposition of extracellular fatty acids, and degenerative lesions of the extracellular matrix in the aortic intima, eventually causing rupture at the edge of the plaque. Congenital factors, such as Marfan syndrome, often affect the differentiation of vascular smooth muscle cells, resulting in increased dissociation of elastic tissue. Cystic necrosis of the mesothelium. This eventually also leads to entrapment formation and endothelial rupture.
IMH accounts for 10-30% of AAS. The hematoma is located in the middle layer without intimal tear sheet formation.IMH is often caused by rupture of the trophoblastic artery in the middle layer of the artery or bleeding within the AS plaque. Unlike AD, IMH often occurs in the proximal epicardium, which may explain the higher rate of aortic dissection in IMH compared to AD. IMH can also be self-resorbing. When aortic wall permeability is increased, accumulation of blood in the thoracic and pericardial cavities can occur, thus leading to unpredictable consequences if the lesion progresses rapidly.
PAU occurs in atherosclerotic plaques (AS) at the site of intimal defect and is common in elderly patients with cardiovascular disease.PAU most commonly occurs in the descending aorta. Further injury to the intima allows blood flow to enter the middle layer leading to hemorrhage in the middle layer and the formation of IMH (due to ulcerated trophoblastic artery) or AD. further penetration of the lesion into the epicardium can lead to the formation of a pseudoaneurysm and even arterial rupture can occur. The rate of aortic dissection is higher in PAU compared to IMH and AD.
2 Clinical presentation
Typical AD clinically presents with sudden and intense chest stabbing pain, dull pain in the posterior back, and sometimes radiation to the lower extremities. Chest pain is more common in type A lesions compared to type B lesions. The clinical manifestations of AD vary widely, with most patients having sudden onset of intense chest pain as the main symptom, but a significant number of patients have atypical symptoms. Changes in blood pressure and pulse before and after the course of the disease, these are helpful in the diagnosis of AD. When combined with syncope, it often indicates that the patient has developed serious complications, such as pericardial tamponade or inadequate perfusion of the cerebral circulation. The prognosis is aggressive.
Clinically IMH is difficult to distinguish from typical AD. Unlike AD: the incidence of IMH is essentially similar in men and women, and risk factors for AD such as aortic diastasis, Marfan syndrome, and collagen system disease are not commonly associated with IMH.
PAU occurs most often in older men over 60 years of age with hypertension and extensive atherosclerosis and calcification [3].The vast majority of PAU occurs in the descending aorta. Rarely, it occurs in the ascending aorta. Early symptoms are chest pain and back pain similar to typical AD, and other less common symptoms include pleural effusion, hoarseness, and syncope. the natural course of PAU is ulcer penetration of the internal elastic lamina to form a hematoma in the middle layer, which can cause aortic dilatation and aneurysm formation, and in severe cases, AD, aortic dissection, or aortic pseudoaneurysm.
3 Diagnostic and imaging examinations
General electrocardiography, X-ray chest radiography, and serum myocardial enzymology are still routinely used in the diagnosis of AAS, and can differentially diagnose whether the chest pain is caused by acute coronary syndrome (ACS), and occasionally both can coexist. Imaging methods are the most important means to confirm the diagnosis of AAS, mainly including transesophageal echocardiography (TEE), aortic CTA, MRA, DSA, and so on. Among them, CTA is the most widely used because of its high sensitivity and specificity and non-invasive. Transthoracic echocardiography (TTE) can detect lesions distal to the aorta, but its diagnostic value is limited for type A lesions and is mainly used to evaluate cardiac complications of type A lesions, such as aortic valve closure insufficiency, pericardial tamponade, and abnormal ventricular wall motion. Aortography not only determines the extent of the entrapment lesion including the involved branch vessels, but also helps in the detection of complications such as aortic valve insufficiency and is a necessary test before surgical and vascular interventional treatment. The current imaging requirements in the diagnosis of AAS are not only qualitative but also quantitative, to clarify the severity of the lesion, the presence or absence of AAS, the localization of the ruptured population and outlet, the size, extent, and staging of the entrapment (type A or type B lesion), and the indication for emergency surgery (pericardial, mediastinal, and intrapleural hemorrhage).
Imaging of AD is characterized by a double-lumen aorta or visible intimal lamellae [4].IMH imaging shows thickened annular or crescentic areas of high density within the aortic wall, which can change shape dynamically over time, with aortic wall thickening >7 mm. without intimal tears and pseudolumella. The thickened aortic wall cannot be seen by aortography and enhanced CT because there is no endothelial tear, no blood flow in the intramural hematoma, and no direct communication with the aorta. The best way to diagnose IMH is by CT scan, which shows a continuous crescentic high-density area along the aortic wall, and no enhancement of the intramural hematoma shadow is seen on contrast-enhanced scans, thus excluding its communication with the aorta .The TEE imaging of patients with IMH is characterized by localized thickening of the aortic wall. MRI can identify not only intramural hematoma but also pathologic changes within the hematoma, which can help in the determination of hematoma regression and progression. Aortography is the “gold standard” for confirming the diagnosis of PAU and shows a contrast-filled niche in the aortic wall without endothelial slices or aortic biluminal manifestations. Enhanced CT and MRI show a prominent localized ulcerative niche in the aortic wall, and MRI is more suitable for those with contraindications to contrast. As with the diagnosis of ACS, research to develop convenient serologic markers for the diagnosis of AAS is a rather tempting project, and one that is currently quite promising is circulating smooth muscle myosin heavy chain, which is released into human blood after aortic intimal rupture and damage to smooth muscle, resulting in increased serum concentrations that persist for approximately 3 hours. Other serum markers, such as white blood cell count, c-reactive protein, fibrinogen, and D-dimer, which reflect the acute inflammatory response, are being investigated in relation to AAS. To date, no serum markers are available for clinical confirmation of AAS.
4 Treatment principles and methods
Once AAS is diagnosed, the first step is to reduce the patient’s pain and control the systolic blood pressure to 100-120 mmHg as much as possible to avoid lesion progression or arterial rupture. The most commonly used drugs are beta-blockers. If the blood pressure is not well controlled, a vasodilator, such as sodium nitroprusside, may be added. Further management is made depending on the location of the lesion, whether the patient remains symptomatic (e.g., persistent chest and back pain or symptoms of end-organ ischemia), and whether there is evidence of lesion progression on imaging.
4.1 Treatment of type A AAS
When AD, IMH or PAU is located in the ascending aorta, the lesion is prone to progression. Acute type A AD has a morbidity and mortality rate of 1 to 2% per hour in the first 24 to 48 h after the onset of symptoms. Type A IMH, PAU, and aortic aneurysm have similar risks as AD, and a single conservative medical treatment for type AAS is not effective. Although attempts have been made both nationally and internationally to select appropriate patients with acute type A AD for treatment with TEVER, most patients with AAS are not suitable for TEVER, due to the proximity of the lesion to the sinotubular junction. Therefore, surgical open surgery is still the mainstream method for the treatment of type A AAS.
4.2 Treatment of type B AAS
Conservative medical treatment is desirable in patients with type B AD without significant symptoms and manifestations such as end-organ ischemia, and when there is no evidence of lesion progression on imaging. Recently this treatment strategy has also been used in the management of IMH and PAU . It is generally accepted that the following factors are often indicative of progressive aortic disease: persistent pain despite aggressive medical therapy; increasing aortic diameter; PAU lesions greater than 20 mm in diameter and 10 mm in depth; increased volume or extent of IMH; IMH bulge; increasing pleural effusion; and coexistence of IMH and PAU. Because the development of lesions is often intricate, even with close monitoring of these indicators of lesion progression, most patients still have the potential for aortic dissection. Therefore, early TEVER should be performed when a patient presents as described above.
The outcome of open surgical treatment of type B AAS is not satisfactory. The risk of aortic dissection is high in many patients, especially in elderly patients with complex complications, and the risk of aortic replacement surgery is high. aortic replacement surgery in the acute phase of type B aortic coarctation has a mortality rate of 10-20%, with a higher rate of death when complicated by renal or mesenteric ischemia, and a high incidence of serious complications such as renal failure and paraplegia. Therefore, although surgery can be used to manage patients who are not suitable for conservative medical treatment, it does not improve patient prognosis and its efficacy is not superior to that of medical therapy.
The TEVAR technique for type B AD was first reported in 1994 by Dake et al. The basic principle is to implant an intraluminal graft into the aortic lesion through a femoral artery incision to effectively cover the aortic lesion segment. After stent graft placement, it can seal the proximal endothelial tear of AD (population, which can reduce the pressure of the false lumen, leading to blood clotting or thrombus formation in the false lumen, and eventually the volume of the false lumen becomes smaller due to the mechanized absorption of the thrombus; it can also modify the broken true lumen, which can reduce the risk of aortic aneurysm formation, and it can restore blood flow to the obstructed arterial branches, thus reversing end-organ ischemia, and now TEVAR is also applied to IMH and PAU [5]. Since PAU and IMH often occur in the descending aorta, patients are older, often with AS, and a distinguishing feature is the higher rate of aortic dissection in PAU and IMH compared to AD. TEVER in these lesions reduces aortic wall tension and therefore prevents progression of the lesion to aneurysm formation or to aortic dissection. In a large study including 120 type B AD, 4 IMH and 15 PAU, the stenting success rate was 98% with a 1.7% mortality rate at 1 year in the AD group and 100% in the IMH and PAU groups, with no deaths or neurological complications at 1 year. reported a 1-year survival rate of 85% and a 5-year survival rate of 75% in 26 elderly patients with type B PAU after TEVAR; in the Nesser et al. study, all patients with type B IMH underwent emergency TEVAR and were followed up for 18 months after successful stent placement, and all patients were free of symptoms and endoleaks.Nienbar et al. divided patients with subacute type B AD into a TEVAR group (12 patients In the study of Doss et al, 54 patients (including thoracic aortic aneurysm, type B AD, and traumatic aortic dissection) were divided into TEVAR group (26 patients) and surgical group (28 patients), and the difference between the two groups was statistically significant. TEVAR is a minimally invasive technique that allows the use of local anesthesia and also facilitates the monitoring of the patient’s peripheral nervous system function. Compared to surgical repair, TEVAR takes less time and the patient loses less blood. One study showed that TEVAR takes about 1.6 h compared to about 8 h for surgical repair. TEVAR also avoids open chest, single lung ventilation, heparinization, and aortic block, which are important factors associated with high morbidity and mortality rates in surgery. Because TEVAR is less invasive, patients recover more quickly after TEVAR.
5 Outlook
Patients with AAS are in critical condition and must be diagnosed and treated promptly. TEVAR is an effective treatment for patients with type B AAS who are at high risk for surgical intervention. Short- and mid-term follow-up studies have shown that TEVAR significantly reduces the rate of death and complications in patients. The development of new stents, ideal stent delivery systems and release devices will make TEVAR safer. Given that most studies are currently limited to case reports and small single-center studies that provide only short-term or intermediate follow-up results, the long-term efficacy of TEVAR for AAS needs to be further investigated.