Diagnosis of acute aortic dissection patients with normal non-enhanced computed tomography and risk factors of in-hospital mortality of type A acute aortic dissection patients

Diagnosis of acute aortic dissection patients with normal non-enhanced computed tomography and risk factors of in-hospital mortality of type A acute aortic dissection patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Diagnosis of acute aortic dissection patients with normal non-enhanced computed tomography and risk factors of in-hospital mortality of type A acute aortic dissection patients Chuande Zou, Donglin Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5222158/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The non-enhanced computed tomography(CT) of patients with acute aortic dissection(AAD) could be completely normal, which could lead to misdiagnosis of AAD. We aimed to evaluate the diagnosis of AAD patients with normal non-enhanced CT and risk factors of in-hospital mortality of type A AAD patients. Methods: A total of 150 patients with chest pain, back pain, or abdominal pain in emergency center from June 2021 to June 2023 were selected in our study. AAD patients with normal non-enhanced CT were selected as AAD group(56 cases), patients with normal CT angiography were selected as non-AAD group(94 cases).Type A AAD patients in AAD group were divided into death group(14 cases) if died in the hospital before discharge and survival group(29 cases) if lived at discharge. The information of emergency patients were collected anonymously and logistic regression analysis and receiver operator characteristic curve were performed to analyze the figures. Results: D-dimer and pain score have significance in diagnosis of AAD (OR=2.195, 95%CI 1.678 to 2.873 and OR=2.609, 95%CI 1.383 to 4.921, respectively). D-dimer has an overall sensitivity of 92.5% and a specificity of 79.3% for diagnosis of AAD. BMI and entry tear size were independent predictors of in-hospital mortality of type A AAD (OR=1.646, 95%CI 1.246 to 2.175 and OR=1.266, 95%CI 1.073 to 1.492, respectively). AUC of 0.943 combined with BMI and entry tear size were higher than that of single factor (BMI was 0.877, p<0.001 and entry tear size was 0.784, p<0.001). Patients with BMI≥28.57kg/m 2 have higher in-hospital mortality compared to those with lower levels and patients with entry tear size ≥ 7.1mm have higher in-hospital mortality compared to those with lower levels. Conclusions: D-dimer has diagnostic value for AAD patients with normal non-enhanced CT and combination of BMI and entry tear size have prognostic prediction value for in-hospital mortality of type A AAD. Acute aortic dissection D-dimer BMI entry tear size non-enhanced CT Figures Figure 1 Figure 2 Figure 3 Introduction Acute aortic dissection(AAD) caused by the tearing of the intima and subjacent media of aorta and the invasion of blood into the aortic middle layer, resulting in a dissection hematoma, is a life-threatening cardiovascular emergency [1]. The AAD patients have a variety of clinical manifestations according to the location and range ofrupture. The sudden or severe pain, such as chest, back or abdominal pain, is the most common symptom. However, some AAD patients do not show obvious pain in clinical work, which is painless acute aortic dissection. If misdiagnosis was occurred, the life and health of AAD patients will be seriously threatened. Muhammad Hassan[2] presented a case of acute aortic dissection, in which the patient has non-specific complaints of nausea and lightheadedness in the emergency department. Szu-Ju Chen[3] discovered four patients with basilar artery dissection who experienced acute onset of hemiparesis and/or vertigo, in which acute infarct was noted at pons or thalamus. It was previously reported that some patients were admitted to hospital with a preliminary diagnosis of acute myocardial infarction and subsequently diagnosed with acute aortic dissection[4]. The emergency physicians should detect AAD patients early and reduce mortality rate of AAD patients. Computed tomography angiography (CTA), which has broad-spectrum, non-invasive, high sensitivity and high specificity, is the most commonly used diagnostic method for AAD in clinical practice[5, 6]. CTA is not only the preferred means for clinical diagnosis of AAD, but also the preferred approach for regular postoperative follow-up of AAD patients[1, 7]. Dimer, as one of biomarkers in laboratory testing, plays an important role in screening for AAD[8]. When acute aortic dissection occurs, the coagulation system and fibrinolysis system were activated simultaneously and then the D-dimer, degradation products of cross-linked fibrin, was elevated. A recent meta-analysis reported that D-dimer has a pooled sensitivity of 96% for diagnosis of AAD and is a useful tool for detecting suspected AAD[9]. Although CTA can detect suspected AAD patients timely, it is not realistic for all emergency patients to complete CTA examination because the cost of CTA is high and iodine contrast agent is harmful for our body. The non-enhanced computed tomography (CT) could be performed routinely for patients with chest, back or abdominal pain. For some emergency patients, the non-enhanced CT could discover acute aortic dissection (Figure 1).However, non-enhanced CT could be completely normal in clinical practice for some AAD patients, especially in emergency department. How to identify the AAD patients with normal non-enhanced CT quickly? The aim of our study was to mainly analyze the diagnostic value of D-dimerfor AAD patients with normal non-enhanced CTand explore the predictive factors of in-hospital mortality of type A AAD patients. Subjects and methods Subjects From June 2021 to June 2023, 340 patients with chest, back, or abdominal pain in emergency center were selected, and the total number of patients included was 150 according to the exclusion criteria. AAD patients with normal non-enhanced CT were selected as AAD group(56 cases), patients with normal computed tomography angiography were selected as non-AAD group(94 cases). Type A AAD patients in AAD group were divided into death group (14 cases) if died in the hospital before discharge and survival group (29 cases) if lived at discharge. Aorta bentall operation and total arch replacement with elephant trunk were performed for type A AAD patients in our study. Inclusion criteria included the aortic dissection detection risk score (ADD-RS) =0 and the time interval from the onset of symptoms to hospital admission ≤24h. Exclusion criteria included: (1) AAD patients with abnormal non-enhanced CT, (2) presence of congenital aortic disease, (3) presence of symptoms for >24h, (4) presence of intramural hematoma, (5) aortic dissection after operation. The specific inclusion and exclusion process is shown in Figure2. The study was approved by the hospital institutional review board, and as a retrospective study, informed consent was waived. Data collection The information of patients in emergency room, including gender, age, history, symptoms, blood pressure, heart rate, pain score and D-dimer, were collected through outpatient electronic medical record system. The information of type A AAD patients in AAD group, such as BMI, entry tear size, renal inadequacy, hydropericardium and operation time, were collected through inpatient electronic medical record system. Statistical analysis SPSS 26.0 statistical software was used for statistical analyses. Continuous variable was presented as the mean±standard deviation. Independent samples t-test was used to assess data conforming to normal distribution and non-parametric rank sum test was used to assess data conforming to skewed distribution. Categorical variable was expressed as a percentage and chi-squared test was used to compare count variables between two groups. Univariate and multivariate logistic regression analyses and receiver operating characteristic curve (ROC) were performed to analyze the diagnostic value of D-dimer for AAD patients with normal non-enhanced CT and identify independent factors related to prognostic prediction value of in-hospital mortality of type A AAD patients. Odds ratio (OR) and 95% confidence interval (CI) were also calculated. A value of P <0.05 was considered statistically significant. Results Clinical features of all patients Based on the inclusion and exclusion criteria, a total of 150 patients were enrolled and divided into AAD group (n=56) and non-AAD group (n=94). Baseline characteristics of these selected participants were presented inTable 1. There was no statistically significant difference in baseline data between the two groups, including gender, age, symptoms, history of diabetes, history of coronary heart disease ( P > 0.05). D-dimer and pain score have great significance in diagnosis of AAD patients with normal non-enhanced CT To explore the influencing factors of diagnosis of AAD patients with normal non-enhanced CT, we used univariable logistic regression analysis firstly, which showed that systolic pressure, heart rate, D-dimer and pain score have certain significance in diagnosis of AAD patients with normal non-enhanced CT (Table 2). And then results of multivariate logistic regression analysis showed that D-dimer and pain score were helpful in diagnosis of AAD patients with normal non-enhanced CT (OR=2.195, 95%CI 1.678 to 2.873 and OR=2.609, 95%CI 1.383 to 4.921,respectively, Table2). We used the ROC curve analytical method to explore the diagnostic value of D-dimer for AAD patients with non-enhanced CT, which showed that the area under ROC curve (AUC) was 0.961, the sensitivity was 92.5%, and the specificity was 79.3% (Figure 3A). Logistic regression analysis of in-hospital mortality of type A AAD patients To explore the risk factors of in-hospital mortality of type A AAD patients, we used univariable logistic regression analysis firstly, which showed that BMI, entry tear size and renal inadequacy have prognostic prediction value for type A AAD patients (Table 3). And then the results of multivariate logistic regression analysis showed that BMI and entry tear size were independent predictors of in-hospital mortality of type A AADpatients(OR=1.646, 95%CI 1.246 to 2.175 and OR=1.266, 95%CI 1.073 to 1.492, respectively, Table 3). ROC curve analysis of in-hospital mortality of type A AAD patients Afterwards, we used the ROC curve analytical method to explore the prognostic prediction value of BMI and entry tear size for type A AAD patients, which showed that the AUC of BMI was 0.877, the cutoff value of BMI was 28.57kg/m 2 , and the AUC of entry tear size was 0.784, the cutoff value of entry tear size was 7.1mm. The AUC of 0.943 combined with BMI and entry tear size were higher than that of single factor (Figure 3B). Patients with BMI≥28.57kg/m 2 have significantly higher in-hospital mortality compared to those with lower levels (80.0% vs 7.1%, Table 4) and patients with entry tear size ≥ 7.1mm have significantly higher in-hospital mortality compared to those with lower levels (52.0% vs 5.6%, Table 4). Discussion Acute aortic dissection is a grievous and fatal cardiovascular disease and the mortality of AAD patients in hospital within 24 hours is approximately 30%[10]. Some studies have shown that the overall annual incidence rate of AAD was 2.6-3.5/100000 people[1, 11, 12]. With the increase of morbidity of diverse cardiovascular emergencies, the incidence of AAD is increasing year by year, and it tends to occur younger[13]. The result of International Registry of Acute Aortic Dissection (IRAD) indicated that the mean age of AAD patients was 62 years and two-thirds of patients were men[14]. Our study discovered that the mean age of AAD patients was 55.2 years, which is lower than IRAD (62 years). This situation may be related to poor blood pressure control in hypertensive patients in China[15]. Moreover, our study also discovered that 75% of patients were men, which is similar with IRAD. A ruptured AAD could lead to sudden death, and clinical manifestations of AAD patients were diversified, leading to high misdiagnosis rate of 14-39%%[16, 17]. We discovered a total of 86 AAD patients in our study, in which 56 AAD patients have normal non-enhanced CT, accounting for 65.12%. Emergency doctors usually do not pay attention to patients with normal non-enhanced CT, which could lead to misdiagnosis or delayed diagnosis of AAD. To explore how to improve diagnosis rate of AAD with normal non-enhanced CT rapidly, a total of 150 patients with chest, back, or abdominal pain were selected and we discovered D-dimer and pain score have significance in diagnosis of AAD patients with normal non-enhanced CT through univariable and multivariate logistic regression analysis. Abrupt in onset, sever in intensity and tearing or sharp quality were described as pain features for patients with chest, back, or abdominal pain and emergency doctors should arrange reasonable examination to diagnose or rule out AAD. Previous studies have discovered that some AAD patients probably have head and neck pain[18], leg pain[19, 20], shoulder pain[21]. Besides, some studies have reported the presence of painless AAD in clinical practice[2, 3]. It is inadequacy that our study only collected patients with chest, back , or abdominal pain as research subjects. Dimer, as an important serum biomarker, exhibits excellent performance in diagnosis of AAD, with a sensitivity of 96% and specificity of 70%[9]. We discovered that D-dimer has an overall sensitivity of 92.5% and a specificity of 79.3% for diagnosis of AAD through ROC curve analytical method, which is similar with aforementioned study. We suggested that if patients with chest, back, or abdominal pain have significantly elevated serum D-dimer levels, CTA examination could be arranged to diagnose or rule out aortic dissection. Some studies have demonstrated that negative D-dimer result (<0.5mg/L) could help rule out AAD in low-risk patients[22, 23], but results of some studies have reported that D-dimer levels in minority of AAD patients were normal completely[24, 25], which could lead to misdiagnosis or delayed diagnosis of AAD. Adam M Rogers[26] discovered that aortic dissection detection risk score (ADD-RS) is a highly sensitive clinical tool for the detection of AAD. We suggested that if emergency patients were classified as intermediate or high risk of AAD according to ADD-RS, CTA examination could be arranged directly with consent of patients and their family members. A study has reported that in-hospital mortality of AAD is as high as 30% [27]. We discovered that a total of 14 (32.5%) type A AAD patients in AAD group died in the hospital before discharge. The results of both studies were close, but it is inadequacy that the sample size of our study is a little less. Previous studies have analyzed the risk factors of in-hospital mortality of AAD. Jun Liu [28] reported that low fibrinogen level on admission is an independent predictor of in-hospital mortality in AAD patients. Cihan Bedel[29] also demonstrated that admission neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were important risk factors of in-hospital mortality of AAD patients. Our study discovered that BMI and entry tear size were independent predictors of in-hospital mortality of AADpatients through univariable and multivariate logistic regression analysis. Some studies have confirmed that a high admission D-dimer level might be a powerful predictor of in-hospital mortality of AAD patients[30, 31]. But our study discovered that admission D-dimer level was not a risk factor of in-hospital mortality of AAD patients (OR=1.063, 95%CI 0.991 to 1.140, p>0.05). With the improvement of people's living standards, obesity has become a serious public health problem. One study had shown that severe obesity is consistently related with higher risk of cardiovascular disease incidence and mortality[32]. A retrospective observational study demonstrated that BMI was positively correlated with in-hospital mortality of AAD patients through multivariate cox regression analysis[33]. Our study demonstrated that patients with BMI≥28.57kg/m 2 have significantly higher in-hospital mortality compared to those with lower levels (80.0% vs 7.1%). Artur Evangelista[34] has revealed that a large entry tear located in the proximal part of the dissection has been associated with adverse event of AAD patients. Our study discovered that patients with entry tear size ≥ 7.1mm have significantly higher in-hospital mortality compared to those with lower levels (52.0% vs 5.6%). And we also discovered that the combination of BMI and entry tear size could better predict in-hospital mortality of AAD patients through ROC curve analysis. Conclusions The present study demonstrated that D-dimer has diagnostic value for AAD patients with normal non-enhanced CT and the combination of BMI and entry tear size have prognostic prediction valuefor in-hospital mortality of type A AAD. Declarations Funding Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors’ contributions CDZ and DLW conceived and designed the study, collected and analyzed data, drafted manuscript. All authors read and approved the manuscript. Ethics approval and consent to participate The study was approved by the hospital institutional review board, and as a retrospective study, informed consent was waived. Consent for publication Not applicable. Competing interests The authors have no conflict of interest. Acknowledgements Not applicable. Authors' information 1 Department of Emergency, Second Affiliated Hospital of Anhui Medical University, Hefei, China. 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Supplementary Files Table1.docx Table2.docx Table3.docx Table4.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5222158","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":379806431,"identity":"e94103a7-d7da-4969-a9e4-06f79078249c","order_by":0,"name":"Chuande Zou","email":"","orcid":"","institution":"Second Affiliated Hospital of Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chuande","middleName":"","lastName":"Zou","suffix":""},{"id":379806432,"identity":"6535a15a-5d50-46a5-9e44-23636e672df0","order_by":1,"name":"Donglin Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIie2RMWrDMBSGJQya1HgrzwTsoRdQMIQOobmKhcFTKZQumVoZg7O0u0Mv0SPICNTFtKvBQ1NyAeUCpTJ0CdhNu2XQNz7ex8//HkIOx0mSCrn/ggc/2snasIWdeAIh+ZvC87oil0kgMr6DVYYQwUeVQlGySpi8vmC0UccV9spFXVG4QbIhEJTvIfvI861pUOSfD3us+RTSANzh/EnDbdnFTONiVrVotnlOBpV526cwwIU3yWxKx180LqfUoIR144qiCeCS0DmclW9/VSTwR0pjW1/+KO24srRd6o2AGID0R07jQHPbpYHRLsE6VWYv7sNl6/WvvAonStVboxeRPx1WRoH/rTscDofjgG9IgW8DtMiMAAAAAABJRU5ErkJggg==","orcid":"","institution":"Second Affiliated Hospital of Anhui Medical University","correspondingAuthor":true,"prefix":"","firstName":"Donglin","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-10-08 05:38:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5222158/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5222158/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70287786,"identity":"c8859b7c-d50f-4714-a192-4f44c5ed20bf","added_by":"auto","created_at":"2024-12-01 16:53:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3001323,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003erepresentative images of non-enhanced CT and CTA images obtained at the same level.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Left, abnormal aortic contour in the aortic arch. Right, CTA shows the presence of intimal flap and thickening aortic contour in the aortic arch.\u003c/p\u003e\n\u003cp\u003e(B) Left, positive intimal flap in the descending aorta (white arrow). Right, CTA shows the presence of intimal flap with partial thrombosis of the false lumen.\u003c/p\u003e\n\u003cp\u003e(C) Left, deviation of aortic calcification in the descending aorta (white arrow). Right, CTA shows the presence of intimal flap in aortic dissection patient.\u003c/p\u003e\n\u003cp\u003e(D) Left, hydropericardium and abnormal aortic contour in the ascending aorta (white arrow). Right, CTA shows the presence of thickening aortic contour in the ascending aorta with partial thrombosis of the false lumen.\u003c/p\u003e\n\u003cp\u003e(E) Left, high-density area in the descending aorta (white arrow). Right, CTA shows aortic dissection with partial thrombosis of the false lumen.\u003c/p\u003e","description":"","filename":"Binder51.png","url":"https://assets-eu.researchsquare.com/files/rs-5222158/v1/13a528aab598e8e9cf1456a7.png"},{"id":70287782,"identity":"27b372f4-eeec-4e79-b6b4-a9843c2a2c61","added_by":"auto","created_at":"2024-12-01 16:53:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42586,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow chart of the inclusion and exclusion process of patients with with chest, back, or abdominal pain.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Binder52.png","url":"https://assets-eu.researchsquare.com/files/rs-5222158/v1/e7f9764adf6b32c011d58855.png"},{"id":70288203,"identity":"d814d8c1-2b8a-42a2-99cb-a0e102f8736c","added_by":"auto","created_at":"2024-12-01 17:17:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":263350,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ethe diagnostic value of D-dimer and the prognostic prediction value of BMI and entry tear size.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) The diagnostic value of D-dimer for AAD patients with normal non-enhanced CT, ROC curve AUC=0.961.\u003c/p\u003e\n\u003cp\u003e(B) The prognostic prediction value of BMI and entry tear size, ROC curve AUC of 0.943 combined with BMI and entry tear size is higher than that of single factor (BMI was 0.877 and entry tear size was 0.784).\u003c/p\u003e","description":"","filename":"Binder53.png","url":"https://assets-eu.researchsquare.com/files/rs-5222158/v1/589484c926122fb574f58103.png"},{"id":85101670,"identity":"2ec070a8-e47a-461a-a30d-368a54daa8a2","added_by":"auto","created_at":"2025-06-21 07:01:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5562085,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5222158/v1/b4e7d135-f6b0-42c8-ada4-17b2b56f9cd3.pdf"},{"id":70287830,"identity":"c841bc40-1876-4b98-afe8-c1b7654aca2c","added_by":"auto","created_at":"2024-12-01 17:01:45","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13832,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5222158/v1/599374607adbbf0159caaf79.docx"},{"id":70287784,"identity":"268d865f-f72b-4070-beab-5986e1230ba5","added_by":"auto","created_at":"2024-12-01 16:53:45","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":12842,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-5222158/v1/afa0837445cb6e2f29e8ee32.docx"},{"id":70288129,"identity":"440e5690-71f6-48c2-a1c6-afef9d89cf6a","added_by":"auto","created_at":"2024-12-01 17:09:45","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":14784,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-5222158/v1/78949ad4f2307a5ab7866d93.docx"},{"id":70287831,"identity":"03075d2e-d09c-41b1-8926-0c58607edc9c","added_by":"auto","created_at":"2024-12-01 17:01:45","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":12273,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.docx","url":"https://assets-eu.researchsquare.com/files/rs-5222158/v1/04e41ec2359a39c99b5b2eb9.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnosis of acute aortic dissection patients with normal non-enhanced computed tomography and risk factors of in-hospital mortality of type A acute aortic dissection patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute aortic dissection(AAD) caused by the tearing of the intima and subjacent media of aorta and the invasion of blood into the aortic middle layer, resulting in a dissection hematoma, is a life-threatening cardiovascular emergency [1]. The AAD patients have a variety of clinical manifestations according to the location and range ofrupture. The sudden or severe pain, such as chest, back or abdominal pain, is the most common symptom. However, some AAD patients do not show obvious pain in clinical work, which is painless acute aortic dissection. If misdiagnosis was occurred, the life and health of AAD patients will be seriously threatened. Muhammad Hassan[2] presented a case of acute aortic dissection, in which the patient has non-specific complaints of nausea and lightheadedness in the emergency department. Szu-Ju Chen[3] discovered four patients with basilar artery dissection who experienced acute onset of hemiparesis and/or vertigo, in which acute infarct was noted at pons or thalamus. It was previously reported that some patients were admitted to hospital with a preliminary diagnosis of acute myocardial infarction and subsequently diagnosed with acute aortic dissection[4]. The emergency physicians should detect AAD patients early and reduce mortality rate of AAD patients.\u003c/p\u003e\n\u003cp\u003eComputed tomography angiography (CTA), which has broad-spectrum, non-invasive, high sensitivity and high specificity, is the most commonly used diagnostic method for AAD in clinical practice[5, 6]. CTA is not only the preferred means for clinical diagnosis of AAD, but also the preferred approach for regular postoperative follow-up of AAD patients[1, 7]. Dimer, as one of biomarkers in laboratory testing, plays an important role in screening for AAD[8]. When acute aortic dissection occurs, the coagulation system and fibrinolysis system were activated simultaneously and then the D-dimer, degradation products of cross-linked fibrin, was elevated. A recent meta-analysis reported that D-dimer has a pooled sensitivity of 96% for diagnosis of AAD and is a useful tool for detecting suspected AAD[9]. Although CTA can detect suspected AAD patients timely, it is not realistic for all emergency patients to complete CTA examination because the cost of CTA is high and iodine contrast agent is harmful for our body. The non-enhanced computed tomography (CT) could be performed routinely for patients with chest, back or abdominal pain. For some emergency patients, the non-enhanced CT could discover acute aortic dissection (Figure 1).However, non-enhanced CT could be completely normal in clinical practice for some AAD patients, especially in emergency department. How to identify the AAD patients with normal non-enhanced CT quickly? The aim of our study was to mainly analyze the diagnostic value of D-dimerfor AAD patients with normal non-enhanced CTand explore the predictive factors of in-hospital mortality of type A AAD patients.\u003c/p\u003e\n"},{"header":"Subjects and methods","content":"\u003cp\u003e\u003cstrong\u003eSubjects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom June 2021 to June 2023, 340 patients with chest, back, or abdominal pain in emergency center were selected, and the total number of patients included was 150 according to the exclusion criteria. AAD patients with normal non-enhanced CT were selected as\u0026nbsp;AAD group(56 cases), patients with normal computed tomography angiography were selected as\u0026nbsp;non-AAD group(94 cases). Type A AAD patients in AAD group were divided into death group (14 cases) if died in the hospital before discharge and survival group (29 cases) if lived at discharge. Aorta bentall operation and total arch replacement with elephant trunk were performed for type A AAD patients in our study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInclusion criteria included the aortic dissection detection risk score (ADD-RS) =0 and the time interval from the onset of symptoms to hospital admission ≤24h. Exclusion criteria included: (1) AAD patients with abnormal non-enhanced CT, (2) presence of congenital aortic disease, (3) presence of symptoms for \u0026gt;24h, (4) presence of intramural hematoma, (5) aortic dissection after operation. The specific inclusion and exclusion process is shown in Figure2. The study was approved by the hospital institutional review board, and as a retrospective study, informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe information of patients in emergency room, including gender, age, history, symptoms, blood pressure, heart rate, pain score and D-dimer, were collected through outpatient electronic medical record system. The information of type A AAD patients in AAD group, such as BMI, entry tear size, renal inadequacy, hydropericardium and operation time, were collected through inpatient electronic medical record system.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS 26.0 statistical software was used for statistical analyses.\u0026nbsp;Continuous variable was presented as the mean±standard deviation. Independent samples t-test was used to assess data conforming to normal distribution and non-parametric rank sum test was used to assess data conforming to skewed distribution. Categorical variable was expressed as a percentage and chi-squared test was used to compare count variables between two groups. Univariate and multivariate logistic regression analyses and receiver operating characteristic curve (ROC) were performed to analyze the diagnostic value of D-dimer for AAD patients with normal non-enhanced CT and identify independent factors related to prognostic prediction value of in-hospital mortality of type A AAD patients. Odds ratio (OR) and 95% confidence interval (CI) were also calculated. A value of \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical features of all patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on the inclusion and exclusion criteria, a total of 150 patients were enrolled and divided into AAD group (n=56) and non-AAD group (n=94). Baseline characteristics of these selected participants were presented inTable 1. There was no statistically significant difference in baseline data between the two groups, including gender, age, symptoms, history of diabetes, history of coronary heart disease (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD-dimer and pain score have great significance in diagnosis of AAD patients with normal non-enhanced CT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo explore the influencing factors of diagnosis of AAD patients with normal non-enhanced CT, we used univariable logistic regression analysis firstly, which showed that systolic pressure, heart rate, D-dimer and pain score have certain significance in diagnosis of AAD patients with normal non-enhanced CT (Table 2). And then results of multivariate logistic regression analysis showed that D-dimer and pain score were helpful in diagnosis of AAD patients with normal non-enhanced CT (OR=2.195, 95%CI 1.678 to 2.873 and OR=2.609, 95%CI 1.383 to 4.921,respectively, Table2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe used the ROC curve analytical method to explore the diagnostic value of D-dimer for AAD patients with non-enhanced CT, which showed that the area under ROC curve (AUC) was 0.961, the sensitivity was 92.5%, and the specificity was 79.3% (Figure 3A).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLogistic regression analysis of in-hospital mortality of type A AAD patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo explore the risk factors of in-hospital mortality of type A AAD patients, we used univariable logistic regression analysis firstly, which showed that BMI, entry tear size and renal inadequacy have prognostic prediction value for type A AAD patients (Table 3). And then the results of multivariate logistic regression analysis showed that BMI and entry tear size were\u0026nbsp;independent predictors of in-hospital mortality of type A AADpatients(OR=1.646, 95%CI 1.246 to 2.175 and OR=1.266, 95%CI 1.073 to 1.492, respectively, Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROC curve analysis of in-hospital mortality of type A AAD patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfterwards, we used the ROC curve analytical method to explore the prognostic prediction value of BMI and entry tear size for type A AAD patients, which showed that the AUC of BMI was 0.877, the cutoff value of BMI was 28.57kg/m\u003csup\u003e2\u003c/sup\u003e, and the AUC of entry tear size was 0.784, the cutoff value of entry tear size was 7.1mm. The AUC of 0.943 combined with BMI and entry tear size were higher than that of single factor (Figure 3B). Patients with BMI≥28.57kg/m\u003csup\u003e2\u003c/sup\u003e have significantly higher in-hospital mortality compared to those with lower levels (80.0% vs 7.1%, Table 4) and patients with entry tear size ≥ 7.1mm have significantly higher in-hospital mortality compared to those with lower levels (52.0% vs 5.6%, Table 4).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion ","content":"\u003cp\u003eAcute aortic dissection is a grievous and fatal cardiovascular disease and the mortality of AAD patients in hospital within 24 hours is approximately 30%[10]. Some studies have shown that the overall annual incidence rate of AAD was 2.6-3.5/100000 people[1, 11, 12]. With the increase of morbidity of diverse cardiovascular emergencies, the incidence of AAD is increasing year by year, and it tends to occur younger[13]. The result of International Registry of Acute Aortic Dissection (IRAD) indicated that the mean age of AAD patients was 62 years and two-thirds of patients were men[14]. Our study discovered that the mean age of AAD patients was 55.2 years, which is lower than IRAD (62 years). This situation may be related to poor blood pressure control in hypertensive patients in China[15]. Moreover, our study also discovered that 75% of patients were men, which is similar with IRAD.\u003c/p\u003e\n\u003cp\u003eA ruptured AAD could lead to sudden death, and clinical manifestations of AAD patients were diversified, leading to high misdiagnosis rate of 14-39%%[16, 17]. We discovered a total of 86 AAD patients in our study, in which 56 AAD patients have normal non-enhanced CT, accounting for 65.12%. Emergency doctors usually do not pay attention to patients with normal non-enhanced CT, which could lead to misdiagnosis or delayed diagnosis of AAD. To explore how to improve diagnosis rate of AAD with normal non-enhanced CT rapidly, a total of 150 patients with chest, back, or abdominal pain were selected and we discovered D-dimer and pain score have significance in diagnosis of AAD patients with normal non-enhanced CT through univariable and multivariate logistic regression analysis. \u003c/p\u003e\n\u003cp\u003eAbrupt in onset, sever in intensity and tearing or sharp quality were described as pain features for patients with chest, back, or abdominal pain and emergency doctors should arrange reasonable examination to diagnose or rule out AAD. Previous studies have discovered that some AAD patients probably have head and neck pain[18], leg pain[19, 20], shoulder pain[21]. Besides, some studies have reported the presence of painless AAD in clinical practice[2, 3]. It is inadequacy that our study only collected patients with chest, back , or abdominal pain as research subjects. \u003c/p\u003e\n\u003cp\u003eDimer, as an important serum biomarker, exhibits excellent performance in diagnosis of AAD, with a sensitivity of 96% and specificity of 70%[9]. We discovered that D-dimer has an overall sensitivity of 92.5% and a specificity of 79.3% for diagnosis of AAD through ROC curve analytical method, which is similar with aforementioned study. We suggested that if patients with chest, back, or abdominal pain have significantly elevated serum D-dimer levels, CTA examination could be arranged to diagnose or rule out aortic dissection. Some studies have demonstrated that negative D-dimer result (\u0026lt;0.5mg/L) could help rule out AAD in low-risk patients[22, 23], but results of some studies have reported that D-dimer levels in minority of AAD patients were normal completely[24, 25], which could lead to misdiagnosis or delayed diagnosis of AAD. Adam M Rogers[26] discovered that aortic dissection detection risk score (ADD-RS) is a highly sensitive clinical tool for the detection of AAD. We suggested that if emergency patients were classified as intermediate or high risk of AAD according to ADD-RS, CTA examination could be arranged directly with consent of patients and their family members. \u003c/p\u003e\n\u003cp\u003eA study has reported that in-hospital mortality of AAD is as high as 30% [27]. We discovered that a total of 14 (32.5%) type A AAD patients in AAD group died in the hospital before discharge. The results of both studies were close, but it is inadequacy that the sample size of our study is a little less. Previous studies have analyzed the risk factors of in-hospital mortality of AAD. Jun Liu [28] reported that low fibrinogen level on admission is an independent predictor of in-hospital mortality in AAD patients. Cihan Bedel[29] also demonstrated that admission neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were important risk factors of in-hospital mortality of AAD patients. Our study discovered that BMI and entry tear size were independent predictors of in-hospital mortality of AADpatients through univariable and multivariate logistic regression analysis. Some studies have confirmed that a high admission D-dimer level might be a powerful predictor of in-hospital mortality of AAD patients[30, 31]. But our study discovered that admission D-dimer level was not a risk factor of in-hospital mortality of AAD patients (OR=1.063, 95%CI 0.991 to 1.140, p\u0026gt;0.05). \u003c/p\u003e\n\u003cp\u003eWith the improvement of people's living standards, obesity has become a serious public health problem. One study had shown that severe obesity is consistently related with higher risk of cardiovascular disease incidence and mortality[32]. A retrospective observational study demonstrated that BMI was positively correlated with in-hospital mortality of AAD patients through multivariate cox regression analysis[33]. Our study demonstrated that patients with BMI≥28.57kg/m\u003csup\u003e2\u003c/sup\u003e have significantly higher in-hospital mortality compared to those with lower levels (80.0% vs 7.1%). Artur Evangelista[34] has revealed that a large entry tear located in the proximal part of the dissection has been associated with adverse event of AAD patients. Our study discovered that patients with entry tear size ≥ 7.1mm have significantly higher in-hospital mortality compared to those with lower levels (52.0% vs 5.6%). And we also discovered that the combination of BMI and entry tear size could better predict in-hospital mortality of AAD patients through ROC curve analysis. \u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe present study demonstrated that D-dimer has diagnostic value for AAD patients with normal non-enhanced CT and the combination of BMI and entry tear size have prognostic prediction valuefor in-hospital mortality of type A AAD.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCDZ and DLW conceived and designed the study, collected and analyzed data, drafted manuscript. All authors read and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the hospital institutional review board, and as a retrospective study, informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Emergency, Second Affiliated Hospital of Anhui Medical University, Hefei, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eErbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H, Evangelista A, Falk V, Frank H, Gaemperli O\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: \u003cstrong\u003e2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. 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\u003cstrong\u003eTG/HDL-C ratio predicts in-hospital mortality in patients with acute type A aortic dissection\u003c/strong\u003e. \u003cem\u003eBMC cardiovascular disorders\u0026nbsp;\u003c/em\u003e2022, \u003cstrong\u003e22\u003c/strong\u003e(1):346.\u003c/li\u003e\n \u003cli\u003eEvangelista A, Salas A, Ribera A, Ferreira-Gonz\u0026aacute;lez I, Cuellar H, Pineda V, Gonz\u0026aacute;lez-Alujas T, Bijnens B, Permanyer-Miralda G, Garcia-Dorado D: \u003cstrong\u003eLong-term outcome of aortic dissection with patent false lumen: predictive role of entry tear size and location\u003c/strong\u003e. \u003cem\u003eCirculation\u0026nbsp;\u003c/em\u003e2012, \u003cstrong\u003e125\u003c/strong\u003e(25):3133-3141.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acute aortic dissection, D-dimer, BMI, entry tear size, non-enhanced CT","lastPublishedDoi":"10.21203/rs.3.rs-5222158/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5222158/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003cem\u003e \u003c/em\u003eThe non-enhanced computed tomography(CT) of patients with acute aortic dissection(AAD) could be completely normal, which could lead to misdiagnosis of AAD. We aimed to evaluate the diagnosis of AAD patients with normal non-enhanced CT and risk factors of in-hospital mortality of type A AAD patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cem\u003e \u003c/em\u003eA total of 150 patients with chest pain, back pain, or abdominal pain in emergency center from June 2021 to June 2023 were selected in our study. AAD patients with normal non-enhanced CT were selected as AAD group(56 cases), patients with normal CT angiography were selected as non-AAD group(94 cases).Type A AAD patients in AAD group were divided into death group(14 cases) if died in the hospital before discharge and survival group(29 cases) if lived at discharge. The information of emergency patients were collected anonymously and logistic regression analysis and receiver operator characteristic curve were performed to analyze the figures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cem\u003e \u003c/em\u003eD-dimer and pain score have significance in diagnosis of AAD (OR=2.195, 95%CI 1.678 to 2.873 and OR=2.609, 95%CI 1.383 to 4.921, respectively). D-dimer has an overall sensitivity of 92.5% and a specificity of 79.3% for diagnosis of AAD. BMI and entry tear size were\u003cstrong\u003e \u003c/strong\u003eindependent predictors of in-hospital mortality of type A AAD (OR=1.646, 95%CI 1.246 to 2.175 and OR=1.266, 95%CI 1.073 to 1.492, respectively). AUC of 0.943 combined with BMI and entry tear size were higher than that of single factor (BMI was 0.877, p\u0026lt;0.001 and entry tear size was 0.784, p\u0026lt;0.001). Patients with BMI≥28.57kg/m\u003csup\u003e2\u003c/sup\u003e have higher in-hospital mortality compared to those with lower levels and patients with entry tear size ≥ 7.1mm have higher in-hospital mortality compared to those with lower levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003cem\u003e \u003c/em\u003eD-dimer has diagnostic value for AAD patients with normal non-enhanced CT and combination of BMI and entry tear size have prognostic prediction value\u003cstrong\u003e \u003c/strong\u003efor in-hospital mortality of type A AAD.\u003c/p\u003e","manuscriptTitle":"Diagnosis of acute aortic dissection patients with normal non-enhanced computed tomography and risk factors of in-hospital mortality of type A acute aortic dissection patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-01 16:53:40","doi":"10.21203/rs.3.rs-5222158/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fb30977b-f3d0-449e-8e97-c1b788fe2130","owner":[],"postedDate":"December 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-21T06:53:36+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-01 16:53:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5222158","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5222158","identity":"rs-5222158","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}