Intramural hemorrhage and hematoma (IMH) refers to intra-aortic wall hemorrhage or limited hematoma formation within the aortic wall [1] and is a specific type of aortic coarctation.IMH was first described by Krukenberg in 1920 as “coarctation without intimal rupture ” [2,3].
Epidemiology: the annual incidence of aortic coarctation is about 5-30 per million population, and about 8-15% of acute aortic syndromes are intermural hematomas of the aorta [4]. Intermural hemorrhage and hematomas are found in about 10-30% of patients with suspected aortic coarctation by various imaging studies [5], and 10% of autopsies in patients diagnosed with aortic coarctation are intermural hematomas [3]. The literature reports that this acute variant of coarctation is most often seen in the elderly (mean age 70 years) with long-term hypertension and hypertensive comorbidities such as stroke and abdominal aortic aneurysm, whereas patients with typical coarctation are younger (mean age 56 years) [3,6]. As with typical clips, there are more men than women [1,2], but there are also reports in the literature of more women with acute intermural hematomas [6].
Etiology and pathogenesis: the most common cause is cystic necrosis of the middle aorta and rupture of the trophoblastic vessels or “aortic wall infarction” [5], with blood spilling into the outer mesenteric layer near the epicardium, and another possible cause is plaque rupture [3]. In addition hypertension, blunt chest trauma [7, 8] and giant cell arteritis [9] are also possible causes. Irrespective of the anatomical location of the onset, chronic hypertension (84%) and Marfan syndrome (12%) are the two main associated factors, and other factors such as diabetes, pregnancy, a large history of continuous smoking or abdominal aortic disease are also common in patients with IMH [1, 4], making its pathogenesis multifactorial.
There are two main views on the mechanism of aortic coarctation: one believes that aortic coarctation originates from endothelial rupture followed by tearing and extension of the mesentery. The hydrodynamic force of the blood flow is generated by pulse wave conduction, and the generation of blood pressure during each systole applies kinetic energy to the aortic wall (the ascending aorta is the largest). Some of this kinetic energy is stored in the wall as potential energy to maintain diastolic blood flow. The intensity of the fluid dynamics of blood flow is related to the mean BP and dP/dt. The combination of these factors eventually leads to aortic intimal tears and the extension of the entrapment into the middle layer of the aortic wall, especially in patients with mesenteric metaplasia.
This is why intimal tears tend to occur in the region of maximum aortic dP/dt and pressure pulsation. Another view is that aortic coarctation originates from intermural hemorrhage and midmembrane hematoma formation, which in turn penetrates the intima and develops into a classic coarctation [4,5]. The literature reports that intermural hematomas occur in approximately 28-47% of acute aortic coarctations during follow-up and are associated with 21-47% of aortic dissections [5,10]. Thus, it has been advocated that intermural aortic hematoma should be considered as a precursor to classical aortic coarctation. Some authors have also suggested that IMH has a similar clinical presentation to classical aortic coarctation, but has a different epidemiology and prognosis and can be considered as a different clinical event or a variant of aortic coarctation [6,8], a view accepted by the European Society of Cardiology in 2001 [10].
Based on literature reports and our own clinical practice, we believe that the occurrence of intermural hematomas can be divided into primary and secondary. The former arises from rupture of a trophoblastic vessel and is confirmed by various imaging studies or surgical/autopsy to have no endothelial fissure or ulcer communicating with the aortic lumen. The latter often occurs secondary to sclerotic plaque rupture [1] or aortic ulceration [3, 4], but can also occur proximal to a typical or limited entrapment [7], and may be formed by leakage of blood components under high pressure in the aortic lumen through the ulcerated or entrapment rupture into the interstitial wall of the aorta, which is lax due to mesenteric lesions [11]. Nienaber et al. reported a case of acute intermural hematoma of the ascending aorta in a descending aortic coarctation with separation that probably belonged to this type [1]; Song JK et al. also reported a case of microfocal coarctation secondary to proximal and ascending aortic intermural hematoma [6]. Cases of ulceration combined with intermural hematoma (Figure 3) and microfocal entrapment combined with intermural hematoma (Figure 4) have also been seen in our clinical practice.
Clinical presentation.
As with typical entrapment, almost all patients present with sudden acute chest or back pain [2,12], some present with abdominal pain [5,10], and individual patients are asymptomatic [12]. Their pain may present as sharp cutting-like, tearing, or dull pain, and the patient’s description of the pain may vary from person to person, but the pain of patients with aortic coarctation is characterized by their metastatic or extended chest pain. A pain-free phase may follow the initial pain, lasting from a few hours to a few days, and then some patients experience pain again. Recurrent pain after this painless interval is an ominous sign and usually signals an imminent rupture [4].
Sueyoshi et al. compared 37 cases of type B IMH with 69 cases of typical type B entrapment at follow-up and showed no difference in age, sex, or concomitant disease [2]. Shimizu et al. compared 51 cases of IMH with 45 cases of typical entrapment and showed that IMH was more common distally and typical entrapment was more common proximally (type A), and that systolic blood pressure was somewhat higher in patients with IMH at admission [13]. Most patients with aortic coarctation have hypertension, but 25% have systolic blood pressure <100 mmHg, with hypotension and shock caused by acute severe aortic regurgitation or coarctation rupture, pericardial tamponade, or left ventricular insufficiency [4]. Aortic regurgitation is present in approximately 42% of patients with IMH [1], a diastolic heart murmur can be detected on examination, pericardial leakage is seen in 60% [12] to 100% [3] of patients with ascending aortic involvement, pleural leakage is seen in 47% [3] to 50% [12] of patients, and periaortic or mediastinal leakage can also be present [1].
The diagnosis of IMH is established mainly by imaging.
A CT submural hematoma is defined as a crescentic or circumferential aortic wall thickening >0.7 cm, which may be accompanied by inward migration of intimal calcified plaques. The stratified appearance extends 1-20 cm longitudinally without endothelial sheets or endothelial fissures [1,3,6]. Fresh intermural hematomas are denser than the adjacent aortic wall and usually have CT values of 60-70 HU; when partially or completely thrombosed they show a multi-layered presentation with enhanced density [1]. Enhanced CT can clearly demonstrate crescentic or circumferential thickening of the aortic wall. the sensitivity of CT is 83-94% and the specificity 87-100% [4].
IMH appears on MRI as a crescentic or circumferential area of high density along the aortic wall. t1 images are indistinguishable from T2 images of fresh blood with high signal, whereas IMH on days 1-5 shows low signal intensity. Subacute IMH shows strong T1T2 signal due to methemoglobin formation [1]. the sensitivity and specificity of MRI are 95-100% [4]. yamada et al. noted that MRI may show more hematoma thickness than actual due to slow blood flow at the edge of the vessel [12].
TTE has a diagnostic sensitivity of 35-80% and specificity of 39-96%. The presence or absence of aortic regurgitation can be understood simultaneously [4]. Ultrasound Doppler can identify antegrade, retrograde or delayed flow in the false lumen [5].
The main points of TEE for the diagnosis of IMH include: 1. localized aortic wall thickening; 2. no echogenic lumen between the walls; 3. no intercalated membrane, traffic flow, or Doppler flow signal; and 4. inward migration of intimal calcification. the sensitivity of TEE diagnosis is 98% and specificity 63-96%. the main limitation of TEE is the experience of the examiner, and the examination is limited to the thoracic aorta and proximal abdominal aorta, which is difficult to It is difficult to see below the abdominal trunk. It cannot be done in cases of esophageal varices [4].
Intravascular ultrasound: IMH shows thickening of the aortic wall, including anechoic areas (images that cause delamination of the aortic wall) or structures with inhomogeneous echogenicity within the aortic wall [8].
Aortography: aortography is of little diagnostic significance in IMH because of the absence of endothelial rupture, but a careful and thorough examination helps us to exclude aortic ulceration or intermural hematoma secondary to microscopic confined entrapment [11].
Diagnosis.
The diagnosis of intermural aortic hematoma is mainly based on the imaging data, where the aortic wall shows separated multilayered manifestations due to bleeding or aortic wall thickening >0.5 cm. on tomographic imaging the aortic wall shows crescentic or circumferential thickening changes.
In 2001, the European Society of Cardiology confirmed the classification of aortic coarctation proposed by Svensson et al. and classified the coarctation into five categories, including: category I, which is typical of AD, in which the avulsed endothelial sheet divides the aorta into true and false chambers; category II, which is aortic mesenteric degeneration with subintimal hemorrhage and secondary hematoma. Class III microintima with secondary thrombosis; Class IV aortic wall ulceration formed by aortic plaque rupture; Class V medically or traumatically induced AD. intermural hematoma as a special type of entrapment can be further divided into two subclasses: subclass A shows smooth aortic inner wall, aortic diameter not exceeding 3.5 cm, and aortic wall thickness not exceeding 0.5 cm.
About 1/3 of patients in this category can be found to have a hypoechoic zone in the aortic wall on ultrasonography, with no blood flow signal in the hypoechoic zone and the average length of the hematoma is about 11 cm. Hypoechoic areas can be detected on ultrasonography in this group of patients. This type of lesion is more likely to occur in the descending aorta than in the ascending aorta [10].
In class III IV coarctation can also be associated with intermural hematoma of the aorta, hence the need for total aortography [11] or enhanced CT. nevertheless, reliance on various clinical examinations to arrive at a diagnosis may overestimate the proportion of intermural hematoma of the aorta, as the presence of an intimal fissure is often found during surgery or autopsy [11].
Treatment.
All patients, except those with low blood pressure, should be started on sedative antihypertensive medication as soon as the diagnosis of acute aortic coarctation is considered. The goal of drug therapy is to reduce left ventricular systolic force and thus the dP/dt of the aortic pulse wave , the lower the blood pressure the better without compromising the perfusion of vital organs. The current standard pharmacological treatment for aortic coarctation is a combination of β-blockers and vasodilators (e.g. sodium nitroprusside). β-blockers should be started before sodium nitroprusside, otherwise vasodilation causes an increase in reflex catecholamine release, leading to increased left ventricular contractility and increased aortic dP/dt, which in turn accelerates coarctation. Labetalol is an α- and β-receptor antagonist and can replace the regimen of β-blockers in combination with sodium nitroprusside [4].
Once the diagnosis of aortic coarctation is considered the patient should be transferred to a medical center with interventional or surgical support. Aggressive surgical intervention is indicated if: 1. pain does not decrease or recurs despite aggressive medical therapy; 2. there is rapid local dilatation of the aorta; 3. there is leakage or risk of rupture, especially in the presence of a pre-existing aortic aneurysm; 4. large branch vessel compression; and 5. pre-existing connective tissue abnormalities [14].
Ascending aortic involvement is usually considered an indication for surgery because of its intrinsic risk of rupture, pericardial tamponade, and coronary sinus compression. In contrast, data from Asia suggest that conservative treatment of proximal IMH is more effective. Distal IMH is recommended for close observation and elective or emergency stent-based prosthetic vessel implantation [5].
Mohr-Kahaly S, et al. reported that TEE can see contradictory motion between the wall layers of intermural hematoma with the cardiac cycle [3]. We believe that this paradoxical motion is not conducive to hemostasis of the trophoblastic vessels in the intermural rupture, and the stimulation of the aortic epicardium by such fluctuations is not conducive to pain relief and thus affects blood pressure control.
The overlying stent can effectively inhibit this paradoxical movement of the endothelium, reduce the direct impact of blood flow on the wall, and form a certain compression on the intermural hematoma, thus stopping the development of the intermural hematoma and gradually absorbing it. To date, none of the distal interstitial hematomas treated with stenting has resulted in perioperative death, and the interstitial hematoma has been rapidly resolved. Therefore, we advocate aggressive intraluminal stenting of type B aortic interstitial hematomas that are painful, have uncontrollable blood pressure, have some compression of the true lumen by the false lumen, or have various precursors of rupture.
Prognosis.
The natural history of aortic intermural hematoma is similar to that of a typical entrapment, with complication rates and mortality related to the site of involvement. In addition to endothelial rupture that transforms into a typical entrapment, it can also penetrate the aortic wall deeper leading to rupture or pseudoaneurysm formation [4].In 25 patients with aortic intermural hematoma reported by Nienaber et al, 8 progressed to typical entrapment rupture and/or acute pericardial tamponade within 24 to 72 hours (32%) [1]. Pericardial, thoracic or mediastinal exudates are very important, predicting impending rupture and should be intervened aggressively. The percentage of spontaneous remission is about 6% in the ascending aorta and 45% in the descending aorta [15]. European guidelines for aortic coarctation state that follow-up data confirm that 28% to 47% of patients with intra-aortic wall hemorrhage and hematoma formation will develop class I AD, with 10% of patients resolving spontaneously [10]. Ascending aortic intermural hematoma had a 30-day mortality rate of 80% with conservative treatment and no death within 30 days after surgical replacement of the artificial vessel; at 1-year follow-up, the survival rate was 71.4% in the surgical group compared with 20% in the medically treated group. The early mortality rate of conservative treatment of intermural hematoma of the arch was 50%.
There was one death in the conservative treatment group for descending aortic intermural hematoma and no death in the surgical treatment group, but there was no statistical difference in the 1-year survival rate between surgical and pharmacological treatment [1].Shimizu et al. reported that aortic intermural hematoma is not uncommon in acute aortic coarctation (53%), with a mortality rate of 13% in the surgical group compared with 42% in typical coarctation, and in-hospital mortality in the conservative group was 9% for intermural hematoma and was 39% [13]. Their mortality rates were higher for open-heart surgery or conservative treatment than for our endoluminal treatment. Endoluminal stenting of the aorta is an important method widely used in recent years to treat aortic coarctation, especially type B coarctation. Therefore, we advocate that endoluminal stenting should be actively performed for B-type aortic intermural hematoma with potential rupture risk.