Comparative study on clinical efficacy of different methods for the treatment of intramural aortic hematoma

To explore the difference of curative effect between different treatment modalities, in order to provide reference for the treatment of aortic intramural hematoma (IMH). 168 patients with aortic intramural hematoma diagnosed and treated from January 2010 to July 2020 were selected in the Second Affiliated Hospital of Nanchang University. Among them, 48 patients were diagnosed with Stanford A aortic intramural hematoma and 120 were diagnosed with Stanford B aortic intramural hematoma. According to the therapeutic methods, patients were divided into conservative treatment group and endovascular treatment group (TEVAR). For endovascular treatment group, according to the different timing of surgery, can be divided into acute phase group (onset within 72 h) and non-acute phase group (time of onset > 72 h).The clinical data and follow-up data were collected and analyzed by variance analysis and χ2 test. There were 168 patients diagnosed with aortic intramural hematoma 39 of them were (81.25%) Stanford A aortic intramural hematoma patients with pleural or pericardial effusion. For patient with Stanford A aortic intramural hematoma, endovascular treatment was performed in 15 patients (31.2%), and 33 cases (68.8%) for conservative treatment. The average follow-up (24.9 ± 13.9) was months. There were 120 patients with Stanford type B aortic intramural hematoma (71.4%), 60 patients received endovascular treatment (50%), and 60 patients (50%) received conservative treatment, with an average follow-up of (27.8 ± 14.6) months. For Stanford A type aortic intramural hematoma patients when the maximum aortic diameter ≥ 50 mm or hematoma thickness ≥ 11 mm, with high morbidity and mortality, positive endovascular treatment can reduce complications and death. For patients with Stanford type B aortic intramural hematoma, when the maximum aortic diameter ≥ 40 mm or hematoma thickness ≥ 10 mm, with high morbidity and mortality, positive endovascular treatment can reduce complications and death. Both Stanford type A and B aortic intramural hematoma patients could benefit from the endovascular treatment when the initial maximum aortic diameter is ≥ 50 mm or the hematoma thickness is ≥ 11 mm.

selected. The goal of drug therapy is to reduce the rate of systolic blood pressure and intraventricular pressure change (dP/dt), thereby reducing the stress on the aortic wall 21 . The anatomical goal of traditional surgery is to remove the aortic lesions and replace the graft, and reconstruct the layers in the distal anastomosis to block the blood flow to the false lumen 11 . Thoracic endovascular aortic repair (TEVAR) is rapidly promoted clinically with its minimally invasive and safe advantages, especially for elderly patients with poor general condition and intolerance to traditional surgery. It has been reported 18 that the hospital mortality rate for Stanford type A IMH was 39%. Moreover, the mortality rate of surgical treatment and drug-only treatment was 44% and 33%, respectively. While the mortality rate for Stanford type B IMH hospitalization was 8%. Because of its high risk of rupture or progression to AD, especially in Stanford type A IMH patients, Stanford A-type IMH patients with or without ulcers have been surgically treated over the past decade, with a 30-day postoperative mortality report ranging from 10 to 50%, and the risk of observation and medication was much higher than surgery [22][23][24] . In addition, other investigators advocate conservative treatment of type A IMH and report favorable outcomes such as no typical dissection, and pericardial tamponade after conservative treatment [25][26][27][28] . Song et al. 27 recommend that for IMH patients, medical conservative treatment could be performed first, followed by close imaging follow-up, and surgical treatment should be performed when complications occurred. Relative to the risk factors for IMH patients, some researchers suggested 28 that maximal aortic hematoma thickness and enlarged aortic diameter were significant factors leading to complications or death in patients. Besides, some researchers believed that 18,29 for IMH involving the ascending aorta, surgical treatment was advocated. For IMH involving the descending aorta, medication was the best choice. Recurrent or persistent pain, maximum aortic diameter > 50 mm or hematoma thickness > 11 mm, chest or pericardial effusion were regarded as indications for surgical intervention. Others suggested that 27,30 the patient's maximum aortic diameter > 50-55 mm, hematoma thickness > 10-16 mm were regarded as risk factors for death, rupture and progression to the dissection.
The present study aimed to evaluating different treatments of IMH through conducting a single-centre, retrospective study in our hospital.

Materials and methods
Research content. Research objects and sources. We retrospectively collected data from 168 patients who met the inclusion criteria and exclusion criteria from the Second affiliated hospital of Nanchang University in China from January 2013 to July 2018 (Fig. 1).
Inclusion criteria (1) patients with IMH; (2) patients with complete CTA examination data. Exclusion criteria (1) admission CTA showed dissection with or other sites; (2) aortic dissection and aortic penetrating ulcer; (3) aortic aneurysm or pseudoaneurysm.  General treatment principles. First of all, in the acute phase of conservative drug treatment, the blood pressure, heart rate, pain should be strictly controlled. After passing the acute stage, CTA was reexamined. If the hematoma was absorbed and there was no clear break, conservative treatment was recommended. If the hematoma is enlarged and there is a clear endometrial break, TEVAR is performed. In TEVAR treatment, the proximal end of the stent should be anchored to the normal artery, the diameter of the stent should be accurately measured, and the low oversize stent should be selected to reduce the probability of stent related new break. The patients with conservative treatment and stent implantation were included in the close follow-up plan to strictly control blood pressure and adjust lifestyle. After 1 month, 3 months, 12 months, follow-up CTA every year, once the patient had complications, leakage and other abnormalities, timely symptomatic treatment.
Research methods. CTA application and related data collection. All patients underwent CTA examination after admission. The vascular surgeon and interventional radiologist who were not aware of the contents of this study were jointly diagnosed on the CT workstation, and the software was used to measure the maximum aortic diameter and intramural hematoma thickness of the IMH patients (maximum aortic diameter: the longest diameter measured by the maximum cross-sectional area of the aorta; the thickness of the hematoma: the thickness measured at the maximum location of the aortic hematoma).
Conservative treatment. All patients were closely monitored to control blood pressure, heart rate, and analgesia was performed. After discharge, the patient continued to control blood pressure and heart rate, and regularly used a series of imaging examinations to monitor, such as CTA. The first review image was taken before discharge, and every 6 months. If the two review images showed stable lesions, then the follow-up period should be extended to 1 year.
Thoracic endovascular aortic repair (TEVAR). All surgical patients were closely monitored and actively treated with medicine after admission. On this basis, surgical treatment was performed. Surgical indications 31 : 1. a type of aortic intramural hematoma patients were recommended for emergency surgery; 2. complex B type aortic intramural hematoma patients were recommended for thoracic aortic endovascular repair; 3. complex B type aorta for intramural hematoma patients. In this study, due to individual differences and the will of the patient's family, some patients were treated conservatively or intracavitally. Surgical method: The patient was placed in the supine position. Routine disinfection and draping were performed, and local anesthesia or general anesthesia was taken. The right/left inguinal oblique incision was performed to expose the common femoral artery. Then, the surgeon preseted the blocking band to block, and punctured the right/left common femoral artery under direct vision (or preseted Proglide vascular closure device after direct percutaneous puncture of the right/left common femoral artery according to Seldinger technique) and placed it into the 12F vascular sheath. Then, the surgeon placed it into the 5F gold-labeled Pigtail catheter through the guide sheath in the abdominal aorta and performed angiography of ascending aorta (speed 20 ml/s, total 30 ml, pressure 900 psi). According to the angiographic results, the relevant data were measured again, and the anatomical relationship and structural morphology of the lesion and the branch vessels were determined. The stent graft system was selected based on the preoperative CTA measurement results. The left upper extremity was used to puncture the brachial artery/radial artery (or the left upper arm/left neck incision exposed the left iliac artery/carotid artery) to place the 4F vascular sheath. The guide sheath was placed into the 4F pigtail catheter to the ascending aorta. Then, the surgeon exchanged superhard guide wire through the guide sheath from right/ left femoral artery (0.035 inches from Lunderquist COOK company), exited from the guide sheath, put it into the stent delivery system along the guide wire, and accurately released the stent through attaching closely to the left subclavian artery open distal edge (e.g., proximal anchoring zone < 15 mm, the main body of the stent was placed close to the distal edge of the left common carotid artery/cephalic artery opening and released, placed the chimney stent from the left subclavian artery/common carotid artery or made a window at the original location). Next, the surgeon exited the coated stent delivery system, performed imaging evaluation again, and determined the presence of various complications. If there were complications which must be dealt with, the surgeon took corresponding measures in a timely manner. Finally, the blood vessel and the surgical wound were sutured, or the puncture site was sutured with a Proglide vascular suturing device. The puncture site and the puncture place were partially pressure-wrapped. In addition, intraoperative patients needed heparinization, and the systolic blood pressure of the patient was controlled to about 100 mmhg before the stent was released. The life signs of the patient were closely monitored during the operation.
Clinical data collection. The patient's general clinical data include name, gender, age, symptoms and signs, smoking history, admission blood pressure, heart rate, blood lipids, conditions of combined underlying disease, diagnosis, time from onset to surgery, time of hospital stay, etc. The CTA data included whether or not the pericardial effusion or pleural effusion was combined and the initial maximum aortic diameter and hematoma Statistical analysis. Statistical analysis was performed using SPSS 21.0 statistical software. The measurement data were expressed as mean and standard deviation (x ± S), and the count data was expressed by the number of cases and percentages. The comparison of measurement data was performed by Kolomogorov-Smirhov Z test. Χ 2 test was used; non-parametric test was used for comparison between groups, and the difference was statistically significant at P < 0.05.
Ethical approval. The  In the remaining 12 patients, hematoma was reduced or absorbed during the follow-up period. In 9 patients admitted to the hospital, CTA showed that the maximum aorta diameter was < 40 mm and the hematoma  www.nature.com/scientificreports/ thickness was < 10 mm. No intraoperative leakage was found, and the hematoma was reduced or absorbed during the follow-up period. 33 patients were in the non-acute surgery group, including 18 patients with CTA maximum aorta diameter ≥ 40 mm or hematoma thickness ≥ 10 mm. The preoperative CTA showed progression to type B aortic dissection, and there was no postoperative endoleak. The hematoma was reduced or absorbed during follow-up period. 60 patients were in the conservative treatment group: 30 patients with CTA maximum aorta diameter ≥ 40 mm or hematoma thickness ≥ 10 mm. There were 30 cases of patients whose CTA showed maximum aortic diameter < 40 mm and hematoma thickness < 10 mm after admitted to hospital, and the hematoma was reduced or absorbed during the follow-up period. The total hospital mortality rate of patients in this group of conservative treatment was 5.0%.

Effect of initial aortic diameter and hematoma thickness on the efficacy of Stanford type B IMH patients. In
Stanford type B IMH conservative treatment, the therapeutic effect is closely related to the maximum diameter of aorta and the thickness of hematoma. Patients with larger diameter and thicker hematoma are more likely to have complications or death.
For patients with TEVAR, the timing of treatment, aortic diameter, hematoma thickness for the treatment effect were not statistically significant.
TEVAR is superior to conservative treatment for Stanford B IMH patients with aortic diameter ≥ 40 mm or hematoma thickness ≥ 10 mm. See Tables 7, 8

Follow-up.
A total of 168 patients were counted, and follow-up was performed mainly through outpatient, inpatient CTA or telephone. 144 patients had complete data. The overall follow-up rate was 85.7%, including 87.5% for type A and 85.0% for type B. The follow-up period ranged from 3 to 60 months. The mean follow-up Table 5. Comparison of the therapeutic effect of acute and non-acute endovascular treatment for maximal aortic diameter ≥ 50 mm or hematoma thickness ≥ 11 mm. *Progression of aortic dissection, pseudoaneurysm, rupture, visceral arterial perfusion, lower limb ischemia.   By comparing the efficacy of different types of IMH patients, there was no significant difference in the incidence of complications or mortality between the two types of patients (P > 0.05), as shown in Table 14.

Discussion
Analysis of IMH clinical characteristics, treatment and efficacy. Pathologically, unlike typical aortic dissection, IMH does not have a decompression mechanism, but shows that non-communicating blood with intimal thickening or no echo. These differences also explain the risk of higher rupture or progression to AD in patients with IMH 16,17,[31][32][33] , or possibility of hematoma regression and absorption 34 . The most common clinical manifestation is "aortic pain". Chest pain often indicates that the lesion is located in the ascending aorta. Pain in the upper or lower back often indicates that the lesion is located in the descending aorta. Some patients have a combination of pericardium, pleural effusion or mediastinal effusion, and related studies 35 believe that its occurrence was related to increased permeability of the aortic wall. In this study, IMH patients were more common in the elderly, 58.9% were male. 92.9% of the patients had symptoms on admission, which showed "aortic pain", and the pain site was associated with the lesion. 82.1% had a history of hypertension; 90% patients with Stanford type A IMH had pleural effusion or pericardial effusion, and their formation mechanism and impact on patient prognosis needed to be further studied.
According to the onset time, the acute phase is within 14 days of onset, the subacute phase is from 14 to 60 days, and the chronic phase is after 60 days 5 . In terms of treatment, because IMH has a higher risk of rupture or progression to AD, early detection and active treatment are essential, and it can be treated with drugs, traditional surgery, TEVAR. Good drug therapy should be used throughout the whole process of the treatment. Since Dake et al. 36 had successfully applied TEVAR to aortic dissection in 1994, TEVAR has been rapidly promoted clinically due to its minimally invasive and safe advantages, especially suitable for the elderly and those with poor systemic conditions who cannot tolerate traditional surgery. And it has a good near-and medium-term efficacy, the goal of which includes covering the vulnerable segment of the aorta, preventing the intimal tear, forming aortic dissection or rupture, and promoting complete thrombosis of the pseudo-cavity. TEVAR surgery was performed in all patients undergoing surgery in this study. There is still debate at home and abroad about the choice and criteria for IMH treatment options. For patients with Stanford type A IMH, because of the high mortality rate due to drug therapy alone, Evangelista et al. 37 advocated active surgical treatment to avoid rupture or progression of the aorta dissection. For the treatment of Stanford type B IMH, studies have concluded Table 9. Comparison of the maximum aortic diameter and hematoma thickness for the treatment of Stanford B IMH. *Progression of aortic dissection, pseudoaneurysm, rupture, visceral arterial perfusion, lower limb ischemia.

Items
Total Complications* or death (n) No complications (n) Chi-square value P    www.nature.com/scientificreports/ were with all-cause death. Univariate analysis found that maximal aortic diameter and hematoma thickness were significant factors leading to complications and death. Stanford type A IMH patients were more prone to complications or death when the maximum aortic diameter was ≥ 50 mm or hematoma thickness was ≥ 11 mm, and the therapeutic effect of intraluminal treatment was better than conservative treatment. Patients with Stanford type B IMH had a greater maximum aortic diameter ≥ 40 mm or a hematoma thickness ≥ 10 mm, which was more prone to complications or death, and the efficacy of intraluminal treatment is better than conservative treatment. By comparing and analyzing the efficacy of different types of IMH patients, it was found that there was no significant difference between the two types, and there was a deviation from the domestic and international reports. Considering that the number of cases in this center is small, and there is selective bias in treatment, it needs to be confirmed by a large number of clinical data. For IMH patients involving ascending aorta, especially the patients whose initial maximum aortic diameter is ≥ 50 mm or hematoma thickness is ≥ 11 mm, the complication rate and mortality are greater, and the efficacy of intracavitary treatment is better than conservative treatment. It is recommended to actively perform TEVAR.
Compared with traditional open surgery, TEVAR will be the beneficial treatment options, especially for those who are unable to tolerate traditional open surgery. When initial maximum aortic diameter is < 50 mm or hematoma thickness is < 11 mm, medical therapy, traditional surgery or TEVAR can be performed. For patients with IMH involving the descending aorta, especially when the maximum aortic diameter is ≥ 40 mm or the hematoma thickness is ≥ 10 mm, the complication rate and mortality are higher. The efficacy of TEVAR is better than conservative treatment. When the initial maximum aortic diameter is < 40 mm and the hematoma thickness is < 10 mm, active drug therapy can be given at the early stage, and regular follow-up review should be performed, for complications such as persistent or recurrent pain, aortic dilation, anatomical progression, terminal organs poor perfusion syndrome, surgery or interventional therapy are advocated. Compared with traditional open surgery, TEVAR has significantly improved surgery-related complications and mortality, and it has a good short-term effect. However, the long-term efficacy needs further follow-up observation. The number