Predicting Preoperative Rupture from Imaging Alone in Acute Type A Aortic Dissection

Objective . To establish risk factors for predicting preoperative ruptures in patients with acute type A aortic dissection (ATAAD) based on computed tomography angiography (CTA) imaging features alone. Methods . We retrospectively reviewed patients with ATAAD treated between January 2017 and December 2021 in Fujian Medical University Union Hospital, China. Te primary outcome was preoperative rupture after admission. Multivariate logistic regression analysis was performed based on basic characteristics and CTA imaging variables selected by the application of the least absolute shrinkage and selection operator. Results . A total of 564 patients were enrolled. Te rate of preoperative rupture was 14.2% ( n � 80). Patients who experienced rupture were signifcantly older ( P � 0.002) and had a higher rate of DeBakey II ( P � 0.016), syncope ( P � 0.003), ventilator-assisted ventilation ( P � 0.008), preoperative shock ( P � 0.040), hypotensive state ( P � 0.009), hepatic insufciency ( P � 0.002), acute kidney injury ( P � 0.045), and moderate or massive pericardial efusion ( P � 0.007). Multivariate analysis identifed the following independent risk factors for preoperative rupture based on CTA imaging features: DeBakey II (odds ratio (OR) � 1.988, 95% confdence interval (CI) 1.211–3.676, P � 0.009), ascending aorta diameter (OR � 2.077, 95% CI 1.335–4.045, P < 0.001), ascending aorta false lumen diameter (OR � 2.988, 95% CI 2.055–4.291, P < 0.001), ascending aorta false lumen/true lumen diameter ratio > 4 :1 (OR � 3.129, 95% CI 2.031–6.225, P < 0.001), and number of branch arteries involved in dissection > 6 (OR � 1.154, 95% CI 1.036–2.006, P � 0.036). Conclusions . CTA imaging features are one of the most convenient indicators for the early prediction of preoperative rupture in patients with ATAAD.


Introduction
Acute type A aortic dissection (ATAAD) is a lethal and emergency condition [1].Timely surgery is efective for most patients.Many patients succumb without an opportunity to receive timely surgical treatment due to acute heart failure, acute myocardial infarction, cerebral infarction, and acute liver and kidney insufciency; however, preoperative dissection rupture is still one of the main reasons for death [2].
In China, most prefecture-level cities do not have hospitals that are adequately equipped to perform surgery for patients with ATAAD.Terefore, it is necessary to transfer such patients to a centralized hospital that has surgical capabilities.Although there is a risk involved in transporting such patients, this approach is efective in improving the success rate of treatment [3,4].Terefore, centralized hospitals often receive several patients with ATAAD at the same time [5].
To address this situation, we performed a risk stratifcation study for patients with ATAAD to efciently identify who is more critical and to prioritize their treatment.Some studies have reported the postoperative mortality and preoperative rupture prediction of patients with ATAAD; however, few studies have evaluated the risk factors for preoperative rupture using computed tomography angiography (CTA) imaging alone in these patients.Tus, the current study aims to identify predictors for in-hospital preoperative rupture in ATAAD patients, especially based on imaging features, to aid physicians in optimal arrangement and management.

Patients and Methods
Tis retrospective, single-center research was approved by Fujian Medical University Union Hospital, China (approval number: 2016KY008), and conducted according to the Declaration of Helsinki, with waived informed consent based on the nature of the retrospective study.
2.1.Patients.Patients with ATAAD treated at our center between January 2017 and December 2021 were enrolled.Te exclusion criteria were as follows: (1) patients with difculty distinguishing the true and false lumen, (2) traumatic aortic dissection, and (3) a history of ascending aortic surgery.

Patient Groups.
Patients were divided into a preoperative rupture group or surgical group based on whether or not the dissection ruptured before surgery.Patients who experienced rupture during transport to the operating room or during anesthesia were placed in the preoperative rupture group.Te criteria for preoperative rupture were as follows: patients with sudden cardiac arrest, disappearance of blood pressure, and electromechanical separation accompanied by a large amount of new pericardial efusion.Te detailed fowchart is shown in Figure 1.

Data Collection
. Demographic characteristics, biochemical indicators, and echocardiography data were recorded at the time of admission and were extracted from the electronic medical records.

Computed Tomography Angiography (CTA).
All CTA data were scanned using a Revolution CT with a scanning thickness of 0.625 mm at our center.Imaging-qualifed DICOM data were passed to the center's imaging two experienced senior radiologists for joint interpretation and analysis.Te total plane diameter and false lumen diameter of the aortic sinus, the mid-section of the ascending aorta, and the proximal aortic arch were measured.(1) Aortic sinus diameter: the maximum diameter of the parallel sinus section; (2) ascending aortic diameter: the plane of the ascending aorta at the midpoint distance from the sinotubular junction to the proximal end of the arch; (3) proximal aortic arch: the diameter of the proximal plane of the innominate artery (Figure 2).

Relevant Defnitions. Relevant defnitions are given as follows:
Shock state: systolic blood pressure was measured to be ≤ 80 mm Hg Hypotensive state: systolic blood pressure was measured to be <90 mm•Hg but >80 mm•Hg Renal insufciency: serum creatinine (Scr) > twice the normal value Hepatic insufciency: alanine aminotransferase >4 times the normal value 2.7.Statistical Analysis.Data distribution was determined by Shapiro-Wilk tests.Categorical and continuous variables are presented as n (%) and mean ± standard deviation or median (interquartile range).Categorical data analyses were performed using chi-square or Fisher exact test.Nonnormally distributed variables were analyzed using the Mann-Whitney U test, whereas normally distributed variables were analyzed using Student's t-test.
Predictors of preoperative rupture selected based on least absolute shrinkage and selection operator (LASSO) regression analysis were included in the multivariate logistic regression analysis.Tis approach could avoid issues of multicollinearity and overftting due to a high number of potential predictors or a small sample size.A graph of statistical OR variable importance was constructed based on the multivariate logistic regression analysis.Te OR variable importance was determined based on the percent of model deviance explained in the model.Data analyses were performed using SPSS 26.0 and R version 4.1.3.P < 0.05 was considered statistically signifcant.

Baseline Data.
A total of 582 patients with acute Stanford type A aortic dissection (ATAAD) were admitted; 8 patients with missing clinical data, 7 with a history of previous aortic surgery, and 3 with unclear images of the true and false lumens of ascending aortic dissection were excluded from this study.Finally, 564 patients were included in the analysis, of whom 80 (14.2%) died of preoperative rupture and 484 (85.8%) did not experience preoperative rupture.Given the lethal nature of ruptured ATAAD, even after a series of rescue measures, none of these ruptured patients survived and they had no opportunity to be operated on.Patients who experienced preoperative rupture had a larger ascending aorta diameter (P � 0.001), ascending aorta false lumen diameter (P < 0.001), ascending aorta false lumen/true lumen diameter ratio (P < 0.001), a higher rate of ascending aorta false lumen/true lumen diameter ratio >4 : 1 (P < 0.001), and the number of branch arteries involved in dissection >6 (P < 0.001) (Table 1).

LASSO Regression Analysis.
Potential risk variables of preoperative rupture selected based on LASSO regression analysis are presented in Figure 3.
A total of 36 variables collected from preoperative data were used in LASSO regression analyses, and 11 predictors including age, DeBakey II type, syncope, preoperative shock, hypotensive state, preoperative hepatic insufciency, moderate or massive pericardial efusion, ascending aorta diameter, ascending aorta false lumen diameter, ascending aorta false lumen/true lumen diameter ratio >4 :1, and the number of branch arteries involved in dissection >6 were selected for a multivariate logistic regression analysis to predict the independent risk of preoperative rupture.

Multivariate logistic regression analyses
Excluding: Difficult to distinguish true and false lumen (n=3) A history of ascending aortic surgery (n=7) Lack of some clinical data (n=8)   Journal of Cardiac Surgery However, there were no signifcant diferences with respect to the diameter of the aortic sinus, the diameter of the proximal end of the arch, and the diameter of the false lumen at the proximal end of the arch (all P > 0.05).Te average false lumen/true lumen ratio of the ascending aorta was 2.96 ± 2.03, and the diferences between the rupture and surgical groups were signifcant (3.55 ± 2.05 vs. 2.66 ± 2.06, P < 0.001).Te proportion of false lumen/true lumen ratio greater than 4 : 1 between the rupture group and the surgical group was statistically signifcantly diferent (36.3% (29/80) vs. 11.2%(54/ 484), adjusted P < 0.001, adjusted by Bonferroni method) (Table 1).6 Journal of Cardiac Surgery 3.5.Treshold Analysis for Dissection Rupture.Te preoperative rupture risk for ATAAD also rose with increasing false lumen diameter.Te lower 95% CI of OR tended to be >1 and gradually increased when the false lumen diameter of the ascending aorta was up to 36.3 mm (Figure 5(a)).Te smallest false lumen diameter in the rupture group was 13.57mm, and the largest was 53.07.When the false lumen diameter of the ascending aorta was up to 41.65 mm and above, 90% (72/80) of patients sufer rupture in the rupture group.Change in the false lumen/true lumen diameter ratio was also associated with preoperative rupture.When it was up to 2.76, the lower 95% CI of OR reached 1 and increased gradually (Figure 5(b)).Te smallest false lumen/true lumen diameter ratio in the rupture group was 0.04, and the largest was 8.31.When the false lumen/true lumen diameter ratio was up to 5.38 and above, 90% (72/80) of patients sufer rupture in the rupture group.

Treshold Analysis for Dissection Rupture in Diferent
States of False Lumen Trombosed.When patent thrombosed in the false lumen, the lower 95% CI of OR was >1 when the diameter of the false lumen of the ascending aorta was between 22.9 and 26.7 mm (Figure 6(a)).When partial or complete thrombosed in the false lumen, the lower 95% CI of OR was >1 when the diameter of the false lumen of the ascending aorta started greater than 26.7 mm, and the maximum value of OR was attained when the false lumen of the ascending aorta was up to 37.9 mm, which was significantly greater than that when the OR reached its maximum value in the patent thrombosed state (Figure 6(b)).

Discussion
Rupture of acute aortic dissection is a catastrophic clinical event, which has become the leading cause of prehospital death in ATAAD patients [6].Mehta et al. retrospectively analyzed 574 cases of ATAAD and found that during conservative medical treatment, 33.3% died of dissection rupture [7].Hagan et al. also reported that up to 41.6% of ATAAD patients died of dissection rupture [8].ATAAD often involves the aortic sinus, ascending aorta, and proximal arch in the pericardial cavity.However, Rylski et al. [9] found that all of the aortic morphology did not change signifcantly after the occurrence of dissection, especially changes in the aortic sinus, which was possibly related to the fxation efect of the valve annulus.In contrast, the ascending aortic morphology changed signifcantly [9].In this study, although the geometry of the aorta changed in both the preoperative rupture group and the surgical group, there were no signifcant diferences in the mean diameter of the aortic sinus, the proximal end of the aortic arch, and the false lumen at the proximal end of the aortic arch between both groups.Te geometric diference was mainly found in the ascending aorta (50.14 ± 4.68 mm vs. 48.11± 6.08 mm, P � 0.001); thus, the ascending aorta may be the target location of dissection lesions causing disastrous preoperative rupture.Based on autopsies, Mészáros et al. [10] confrmed that the rupture site in preoperative rupture ATAAD patients was mainly in the ascending aorta.Newly increased blood of the pericardial cavity confrmed by bedside ultrasound also proved that the ascending aorta was the location of preoperative aortic dissection rupture [10,11].Rupture of ascending aortic dissection also obeyed the law that the rupture rate increased with an increase in diameter; however, it was not completely equivalent to the pattern that with the gradual expansion of true aneurysms beyond the critical line, rupture events increased suddenly.Recent studies [12,13] reported that the diameter of the ascending aorta was <50 mm after dissection in approximately half of the patients.Terefore, diferent from aneurysm, the pathological characteristics of the false lumen are an important reason for the preoperative rupture of aortic dissection in addition to the infuence of the total diameter [7].
Te false lumen of aortic dissection is only covered by the adventitia and a part of the media, which is prone to rupture [14,15].We found that the diameter of the false lumen in the rupture group was signifcantly larger than that in the surgical group (35.09 ± 9.96 mm vs. 25.99 ± 4.34 mm, P < 0.001); moreover, the preoperative rupture risk rose with an increase in false lumen diameter.Te lower 95% CI of OR tended to be >1 and gradually increased when the false lumen diameter of the ascending aorta was up to 36.3 mm.Te false lumen/true lumen ratio was also used to describe the relationship between the two groups in our study.Te ratio of false lumen/true lumen in the rupture group was signifcantly diferent from that in the operation group (3.55 ± 2.05 vs. 2.66 ± 2.06, P < 0.001), and patients with severe true lumen compression (false lumen/true lumen ≥4 : 1) accounted for 36.3% vs. 11.2%, also with diferent rupture rates among diferent ratios of false lumen/true lumen (36.3% (≥4 : 1) vs. 12.5% (≥3 : 1) vs. 20.0%(≥2 : 1) vs. 21.3%(≥1 : 1) vs. 10.0%(<1 : 1)).An increase in the false lumen/true lumen ratio is a manifestation of increased false lumen pressure, which may be due to a limited extent of aortic dissection (such as DeBakey II type), the lack of a distal breach, or a reverse tear of ATAAD.As the diameter of the false lumen increases, the external tension in the false lumen increases according to Laplace's law and rupture is more likely to occur.Meanwhile, the high pressure in the larger false lumen can cause compression or even a complete block of the true lumen, leading to organ tissue ischemia called "malperfusion syndrome," which is defned as compromised blood fow in 1 or more organs resulting in ischemia and organ dysfunction, such as myocardial infarction, cerebral infarction, lower extremity ischemia, or renal insufciency, and it remains a severe condition associated with adverse outcomes in patients with ATAAD [16].
Many studies have shown that age is a risk factor for inhospital mortality in ATAAD [17,18].Increased vascular wall stifness in elderly patients is a cause of susceptibility to rupture [19,20].However, multivariate analysis indicated that age was not an independent risk factor for preoperative rupture.Tis may be because the average age of patients in this study (53.8 ± 11.4 vs. 49.6 ± 9.7) was lower than that in Western countries.We found that an increase in the diameter of the ascending aorta and the diameter of the false lumen was the main reason for rupture.Lesion on the aortic wall itself is the main reason determining whether dissection is prone to Journal of Cardiac Surgery occur, which is diferent from whether it is prone to rupture after the occurrence of dissection.Similarly, lesions of the middle tissue in patients with Marfan syndrome are prone to aortic dissection [11] but do not increase the preoperative rupture risk itself in patients with acute dissection.Patients with Marfan syndrome mainly present with dilation of the aortic sinus.In our study, the diameter of the aortic sinus was not directly an independent risk factor for aortic dissection rupture.Moreover, some studies show that Marfan syndrome may even slow down the rupture in patients with aortic dissection due to increased tissue compliance caused by the medial lesion, which is more resistant to vasodilation and reduces vascular wall tension [21].Aortic dissection rupture is afected by a combination of factors such as emergency window, uncontrolled blood pressure, persistent pain, and disease of the media aortic layer [22,23].Anagnopoulos et al. [24] found that treatment time and clinical events were closely related.In this study, most patients were transported to our center in a timely manner after onset.Te average time interval from onset to the clinical event (including Time 1: time from onset to admission; Time 2: time from admission to surgery or rupture; Time 3: time from the onset to surgery or rupture) between both groups did not difer signifcantly (with all P > 0.05, Table 1), reducing the interference with the study results due to discrepancies in the emergency window.Although with the improvement of medical equipment nowadays, diagnosis of acute aortic syndromes (AAS) may be challenging particularly in physicians who are inexperienced with AAS, misdiagnosis of AAS does not uncommonly occur in patients transferred to by nonexperienced referring facilities.Te nearly 10% frequency of misdiagnosis was observed in two separate geographic institutional aortic center, and all of the misdiagnosis was due to imaging misinterpretation including imaging artifacts and expected postsurgical changes [25].However, we reduce the impact of misdiagnosis on this study through the following ways: in the case of suboptimal outside imaging, most of the referred patients in this study experienced repeat imaging, and the diagnosis was reviewed by two experienced board-certifed imaging specialists.In addition, we also excluded the patients with difculty to distinguish the true and false lumen and with a history of ascending aortic surgery.By doing this, none received unnecessary surgery as the misdiagnosis was detected beforehand.Even so, the high rupture rate of 14.2% still surprised us.We analyzed that it was possibly due to the uneven levels of care during transport and less early experience of the operative facility despite expedited care of the aortic dissection patients.In particular, there are quite a few patients with an aura rupture occurred rupture shortly after admission to our hospital.Besides, 3 patients sufered rupture during anesthesia and 5 patients ruptured in route to the operating room who were characterized by sudden confusion, a sharp drop in blood pressure, or a slowdown in heart rate and pulse, without the opportunity to be operated on, indicating again the lethality and urgency of ATAAD [1].What is more, some patients were frst referred to the relevant department for suspected acute coronary syndrome or acute pulmonary embolism, leading to delays in diagnosis and treatment.Te above reasons may have resulted in a higher preoperative rupture rate.Blood pressure control is also a key factor in the occurrence of preoperative rupture.In this study, the blood pressure of patients in both groups was well controlled after admission.Tere were no signifcant diferences in the systolic blood pressure between both groups of patients (120.1 ± 29.5 mm•Hg vs. 122.4± 23.6 mm•Hg, P = 0.509), but more patients in the preoperative rupture group experienced preoperative shock (7.8% vs. 2.7%, P = 0.040) and had hypotensive state (10.0% vs. 3.1%, P = 0.009) mainly due to moderate and large pericardial efusions.Terefore, a new or sudden increase in pericardial efusion is usually a warning sign for dissection rupture.
After thrombus formation in the false lumen, blood fow in the false lumen gradually decreases, weakening the shear force on the vascular wall.Tus, the false lumen gradually shrinks and the risk of rupture decreases.We found no discrepancy in false lumen thrombosed between the groups (P � 0.177), but when the false lumen was partial or complete thrombosed, the diameter threshold for maximum risk of preoperative rupture (37.9 mm) was signifcantly greater than that when the false lumen was patent (22.9 to 26.7 mm).It is likely because thrombosis greatly increases the diameter threshold of the false lumen to cause dissection rupture.
Moreover, we found DeBakey II type aortic dissection is an independent risk factor for ATAAD.Tis type of aortic dissection is characterized by a location of origin break and the limited extent of dissection in the ascending aorta.As the initial site of dissection is limited at the junction of the heart and aorta and there is no reentry tear in the descending aorta, the false lumen remains pressurized due to lack of decompression resulting from reentry tear and is at higher risk for rupture.
Tus, our center is applying the results of this study to current practice: the cardiopulmonary circulation team and the anesthesia team of our unit have specially scheduled emergency classes for of-shift time.When the independent risk factors analyzed above are met, we will immediately perform emergency surgery; otherwise, we will delay the operation to the shift time under the premise of drug treatment.

Limitations.
Our study has several limitations.First, a single-center study may have introduced bias.Second, information on some important clinical risk factors for aortic dissection rupture was not prospectively collected, which may have under-or overestimated the efects of certain risk factors.Tird, previous comorbidity data and biochemical data were incomplete in some patients who ruptured shortly after admission.Last, there was a lack of analysis of in-transit rupture patients due to the absence of their medical information.

Conclusions
Collectively, CTA is one of the most convenient tools for the early prediction of preoperative rupture in patients with ATAAD.

Figure 1 :
Figure 1: A detailed fowchart of patient selection.

Figure 2 :
Figure 2: Schematic diagram of the measurement of 2A the proximal aortic arch; 2B the middle part of the ascending aorta; 2C the aortic sinus (black arrows refer to intimal patch; T refers to true lumen; F refers to false lumen).

Figure 3 :
Figure 3: Potential risk variables of preoperative rupture selected based on least absolute shrinkage and selection operator (LASSO) regression analysis.

Figure 5 :Figure 6 :
Figure 5: Treshold analysis of ascending aortic false lumen diameter (a) and false lumen/true lumen diameter ratio (b) for aortic dissection rupture.

Table 1 :
Te clinical characteristics and computed tomography angiography (CTA) features of two groups.
Data are presented as mean ± SD or median (interquartile range), and categorical variables are presented as number (%).* Te proportion of patients was signifcantly diferent between the two groups by Bonferroni method.# Time 1: time from onset to admission; Time 2: time from admission to surgery or rupture; Time 3: time from the onset to surgery/rupture.Q1, frst quartile; Q3, third quartile; BMI, body mass index; CAD, coronary artery disease; MFS, Marfan syndrome; LVEF, left ventricular ejection fraction; AR, aortic regurgitation.