Aortic Dissection Group Research Articles

Long-term outcomes of frozen elephant trunk for aortic dissection: a single-center experience

BackgroundTo date a number of papers analysing outcomes of the frozen elephant trunk (FET) in acute aortic dissection has been published. However, there are limited comparative studies on long-term outcomes of FET in acute and chronic aortic dissection. The objective of the study was to analyze the long-term outcomes after FET procedure for aortic dissection (AD).MethodsBetween March 2012 and December 2022, a total of 123 FET had been performed for thoracic aortic disease. Patients with aortic dissection (n = 97) were divided into 2 groups: acute (n = 32, 33%) and chronic aortic dissection (n = 65, 67%). Pre-, intra- and postoperative data were retrospectively collected from electronic patient’s records, including follow-up data of the analyzed patients.ResultsThe incidence of stroke was 3.1%. The delirium rate was up to 9.3% in both groups with a prevalence in chronic aortic dissection (CAD) group without significant differences (P = 0.494). Paraplegia was diagnosed only in CAD patients (n = 2). Respiratory failure and the rate of renal replacement therapy were similar in the studied groups. Re-sternotomy was required in one (3.1%) patient with acute AD and 5 (7.7%) patients with chronic AD (P = 0.416). Overall 30-day mortality in the entire cohort, acute and chronic AD was 13 (13.4%), 7 (21.9%) and 6 (9.2%), respectively (P = 0.097). The overall survival rate at 60 months for the entire cohort, acute and chronic AD was 64.1 ± 5.9%, 62.3 ± 9.1%, 66.5 ± 7%, respectively (P = 0.265). Freedom from unintended distal aortic re-intervention at 60 months for the entire cohort of patients, acute and chronic AD was 74.2 ± 1.5%, 100%, 65.3 ± 2%, respectively (P = 0.355).ConclusionsOur experience showed acceptable long-term outcomes after the FET procedure including mortality and re-intervention rate in patients with aortic dissection regardless of acuity of the dissection.Trial registrationThe study has been registered in Australian and New Zealand Clinical Trial Registry (ACTRN 12618001329257) on August 7, 2018.

Three-dimensional morphometry of the human thoracic aorta using centerline analysis based on least-squares plane fitting

ObjectiveA novel approach to 3-dimensional morphometry of the thoracic aorta was developed by applying centerline analysis based on least-squares plane fitting, and a preliminary study was conducted using computed tomography imaging data. MethodsWe retrospectively compared 3 groups of patients (16 controls without aortic disease, and 16 cases each with acute type B aortic dissection and congenital bicuspid aortic valve). In addition to the standard assessment indices for curvature κ and torsion τ, we conducted coordinate transformation based on the least-squares plane, divided the centerline into 3 representative features (transverse, anterior-posterior, and longitudinal displacements), and analyzed the overall and local displacement in each direction. The transverse displacement, represented by the distance of the centerline from the least-squares plane, was curve-fitted to the damped oscillation waveform. Thereafter, damped oscillation parameters were compared for each group. ResultsCurvature κ exhibited a bimodal distribution, with peaks observed in the ascending aorta and aortic arch, and torsion τ exhibited a transition from positive to negative values in the arch. There were significant differences in the mean displacement between the groups for each direction (transverse P = .0083, anteroposterior P = .010, longitudinal P = 1.32 × 10−6). Furthermore, interval integral analysis revealed that several intervals exhibited significant differences between groups in each direction. The amplitude of damped oscillation parameters was significantly larger in the bicuspid aortic valve group than in the control and type B aortic dissection groups. ConclusionsThe novel analytical approach permitted a quantitative assessment of the 3-dimensional morphological differences between the control, type B aortic dissection, and bicuspid aortic valve groups.

Identifying patients with acute aortic dissection using an electrocardiogram with convolutional neural network

BackgroundThe potential of utilizing artificial intelligence with electrocardiography (ECG) for initial screening of aortic dissection (AD) is promising. However, achieving a high positive predictive rate (PPR) remains challenging. Methods and resultsThis retrospective analysis of a single-center, prospective cohort study (Shinken Database 2010–2017, N = 19,170) used digital 12-lead ECGs from initial patient visits. We assessed a convolutional neural network (CNN) model's performance for AD detection with eight-lead (I, II, and V1-6), single-lead, and double-lead (I, II) ECGs via five-fold cross-validation. The mean age was 63.5 ± 12.5 years for the AD group (n = 147) and 58.1 ± 15.7 years for the non-AD group (n = 19,023). The CNN model achieved an area under the curve (AUC) of 0.936 (standard deviation [SD]: 0.023) for AD detection with eight-lead ECGs. In the entire cohort, the PPR was 7 %, with 126 out of 147 AD cases correctly diagnosed (sensitivity 86 %). When applied to patients with D-dimer levels ≥1 μg/dL and a history of hypertension, the PPR increased to 35 %, with 113 AD cases correctly identified (sensitivity 86 %). The single V1 lead displayed the highest diagnostic performance (AUC: 0.933, SD: 0.03), with PPR improvement from 8 % to 38 % within the same population. ConclusionsOur CNN model using ECG data for AD detection achieved an over 30% PPR when applied to patients with elevated D-dimer levels and hypertension history while maintaining sensitivity. A similar level of performance was observed with a single-lead V1 ECG in the CNN model.

Biomechanical characterization of normal and pathological human ascending aortic tissues via biaxial testing Experiment, constitutive modeling and finite element analysis

BackgroundAortic dissection and atherosclerosis are two common pathological conditions affecting the aorta. Aortic biomechanics are believed to be closely associated with the pathological development of these diseases. However, the biomechanical environment that predisposes the aortic wall to these pathological conditions remains unclear. MethodsSixteen ascending aortic specimens were harvested from 16 human subjects and further categorized into three groups according to their disease states: aortic dissection group, aortic dissection with accompanied atherosclerosis group and healthy group. Experimental stress-strain data from biaxial tensile testing were used to fit the anisotropic Mooney-Rivlin model to determine material parameters. Computed tomography images or transesophageal echocardiography images were collected to construct computational models to simulate the stress/strain distributions in aortas at the pre-dissection state. Statistical analyses were performed to identify the biomechanical factors to distinguish three groups of aortic tissues. ResultsMaterial parameters of anisotropic Mooney-Rivlin model were fitted with average R2 value 0.9749. The aortic diameter showed no significant difference among three groups. Changes of maximum and average stress values from minimum pressure to maximum pressure (△MaxStress and △AveStress) had significantly difference between dissection group and dissection with accompanied atherosclerosis group (p = 0.0201 and 0.0102). Changes of maximum and average strain values from minimum pressure to maximum pressure (△MaxStrain and △AveStrain) from dissection group were significant different from healthy group (p = 0.0171 and 0.0281). ConclusionChanges of stress and strain values during the cardiac cycle are good biomechanical factors for predicting potential aortic dissection and aortic dissection accompanied with atherosclerosis.

Retrograde type A aortic dissection during or after thoracic endovascular aortic repair: a single center 16-year experience.

This article aims to investigate the incidence rate of retrograde type A aortic dissection (RTAD) and the risk factors of RTAD in relation to thoracic endovascular aortic repair (TEVAR). Patients with thoracic aortic disease who underwent TEVAR at Henan Provincial People's Hospital from January 2004 to December 2019 were enrolled in the present research. The risk factors associated with RTAD following TEVAR using univariate and multiple logistic regression analyses. During the study period, A total of 1,688 TEVAR patients were included in this study, and of these, 1,592 cases were included in the type B aortic dissection (TBAD) group, and 96 cases were included in the non-TBAD group. There were 1,230 cases of aortic dissection and 362 cases of aortic intramural hematoma and/or penetrating ulcer in the TBAD group. The non-TBAD group included 68 cases of thoracic aortic aneurysm, 21 cases of thoracic aortic pseudoaneurysm, and seven cases of congenital aortic coarctation. The overall incidence rate of RTAD was 1.1% (18/1,688) in patients, all of which occurred in the TBAD group. The cohort comprised 18 RTAD patients with an average age of 56.78, consisting of 13 males and 5 females. Among them, 13 individuals exhibited hypertension. Ten instances happened within the TEVAR perioperative period, including two cases during the surgery, six cases occurred within three months, two cases occurred after one year, and the longest interval was 72 months following TEVAR. TEVAR was successfully implemented in 17 patients, while the operation technique was temporarily altered in one case. The new entry position for RTAD was identified as the proximal region of the stent graft (SG) in 13 patients, while in five cases, the entry site was more than 2 cm away from the proximal region of the SG. 17 cases were at the greater curvature of the aorta, and one case was at the lesser curvature. Multivariate logistic regression analysis revealed that the SG oversizing ratio is a relevant risk factor for RTAD. However, ascending aortic diameter, aortic arch type, SG type, and anchored region were not directly related to the occurrence of RTAD. RTAD is a rare yet catastrophic complication. It could occur both during the procedure, early and late postoperative periods. Maintaining an appropriate SG oversizing ratio is crucial to minimize the risk of RTAD.

Late Referral and Patient Transfer is Associated with Worse Outcomes for Patients Presenting with Initially Uncomplicated Type B Aortic Dissections

Acute type B aortic dissections (TBADs) can become complicated at any time point, necessitating surgical repair. We sought to investigate the effect of interhospital transfer on the development of delayed complications in acute type B aortic dissection (dcTBAD). All patients who presented with acute TBAD to a tertiary aortic center from 2015 to 2019 were analyzed. Patients were divided into initially complicated type B aortic dissection (icTBAD) (0-24hours from symptom onset), dcTBAD (25hours to 14days), and uncomplicated type B aortic dissection (ucTBAD) groups. Criteria for complicated dissection were aortic rupture, malperfusion, or rapid aortic growth. Demographics, patient history, the timing of presentation, imaging findings, and clinical outcomes were compared between groups. Of 120 acute TBADs included, 27 (22%) were initially complicated (aortic rupture, n=9; malperfusion, n=18). Twenty-one (18%) developed delayed complications (aortic rupture, n=3; malperfusion, n=14; rapid growth, n=4) at a median of 7.0 [4.0, 9.0] days from symptom onset. Seventy-two (60%) remained uncomplicated. Overall, 111 (93%) presented as transfers from outside hospitals (icTBAD, n=25; dcTBAD, n=21; ucTBAD, n=65). Of those, dcTBADs were more likely to have a prolonged delay between presentation to the outside hospital and referral to the tertiary center compared to ucTBADs (median=1.00 [0.0, 5.0] days delayed vs. 0.00 [0.0, 0.0] days delayed; P<0.001). Initially uncomplicated patients referred for transfer ≥24hours from presentation went on to develop dcTBAD more often than those transferred in <24hours (73% vs 13%; P<0.001). Of dcTBADs, 38% had no high-risk features on initial imaging. Patients with dcTBAD had significantly longer length of stay (median=12 vs 7days; P=0.006). In-hospital mortality was significantly higher in dcTBADs than ucTBADs (9.5% vs 0%; P=0.047). In-hospital mortality was not significantly different between dcTBADs and icTBADs (9.5% vs. 11%; P>0.05). The incidence and consequence of dcTBADsare not insignificant. Late referral and transfer to a tertiary aortic center (≥24hours from initial presentation) was associated with dcTBADsrequiring surgical intervention. The development of dcTBADwas associated with increased length of stay and increased in-hospital mortality.

Comparison of population characteristics and clinical outcomes of patients with type B aortic dissection or aortic intramural hematoma underwent thoracic endovascular aortic repair: a propensity score-matched analysis

BackgroundsSurvival and aortic-related adverse events after thoracic endovascular aortic repair (TEVAR) for aortic intramural hematoma (IMH) and aortic dissection (AD) are controversial. We aimed to assess the preoperative characteristics and to evaluate TEVAR outcomes of acute type B IMH and AD.MethodsBetween June 2002 and May 2021, 83 patients with acute type B IMH and 755 patients with acute type B AD underwent TEVAR at the General Hospital of Northern Theater Command. We retrospectively analyzed data from these patients, including clinical characteristics and follow-up outcomes.ResultsThe patients with IMH were significantly older than the ones with AD (P < 0.001). Diabetes mellitus (P = 0.035) and ischemic cerebrovascular disease (P = 0.017) were more common in the IMH group than in the AD group. The results demonstrated a less long-term aortic-related death-free survival rate in the IMH group than the AD group for all the patients (P = 0.014) and the matched patients (P = 0.027). It also presents a lower long-term overall survival rate (P = 0.047) and aortic-related event-free rate (P = 0.048) in the IMH group than in the matched patients.ConclusionsCompared with AD patients, patients with IMH who underwent TEVAR had a worse long-term outcome of aortic-related survival in all and matched patients.

Clinical characteristics and placental pathology analysis of 14 cases of pregnancy with aortic dissection/aortic aneurysm

Objective: To investigate the pathological changes of placenta in pregnant women with aortic dissection/aneurysm and their relationship with clinical features. Methods: The placental samples of 14 pregnant women with aortic dissection/aneurysm diagnosed from January 2012 to October 2021 and 10 normal placental samples of pregnant women from January 2021 to December 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China were selected. Routine H&E staining and immunohistochemistry were used to analyze the histological features under light microscope. The clinical data were also analyzed. Results: The age of 14 pregnant patients with aortic dissection/aneurysm for placental examination ranged from 22 to 38 years (median, 28 years). The gestational ages ranged from 22 to 39 weeks (median, 34 weeks). The pregnancy of second trimester was noted in 2 cases, and the third trimester in 12 cases. All cases were singleton pregnancy. Seven cases were Stanford type A aortic dissection, 6 cases were Stanford type B aortic dissection, and one case was aortic root aneurysm. Four of the pregnant women underwent aortic dissection surgery after caesarean section, three underwent caesarean section after aortic dissection surgery, and seven underwent both caesarean section and aortic dissection procedures. Among the newborns, 2 cases were full-term birth, and 12 cases were premature birth. Twelve cases had alive newborns, and 2 cases stillbirths. Fetal/placental weight ratio (FPR)<10th percentile was in 5 cases and FPR>90th percentile in one case. Compared with the normal group, accelerated villus maturation and distal villus dysplasia were more frequently found in pregnancy with aortic dissection group (P<0.05). There was no significant difference in villi infarction and decidua vascular lesions between the two groups (P>0.05), nor was there correlation between the type of aortic dissection and distal villus dysplasia and accelerated villus maturation of placentas (P>0.05). The number of villous interstitial blood vessels in the placentas of pregnancy with aortic dissection group was significantly fewer than that in the normal control group (P<0.01). Conclusions: There are considerable pathological changes in the placentas of pregnant women with aortic dissection/aneurysm. The main histological features are accelerated villus maturation and distal villus dysplasia, which are manifestations of villous ischemia and hypoxia, and also a part of the placental pathological manifestations of maternal vascular dysperfusion.

Astragaloside IV inhibits angiotensin II-induced aortic dissection formation by regulating miR-320a/matrix metallopeptidase 9 axis

This study explored the role of miR-320a and Matrix metallopeptidase 9 (MMP-9) in aortic dissection (AD) formation. Aortic tissue diameter (LD) and medial thickness (MT) were measured after the AD model was established. Aortic smooth muscle cells (VSMCs) were assigned into blank group, Astragaloside IV (AS-IV), which was treated with 100, 150 or 200 μg/mL and AngII group. Cells in the AngII group were added with MMP9 inhibitor (MMP9 inhibitor group) and mimics (MMP9 mimics group), followed by analysis of cell proliferation, apoptosis, and target gene for miR-320a. Aortic tissue diameter(LD) from the AD group was significantly higher and MT was lower than in the control group (p&lt;0.05). VSMCs proliferative activity in the AS-IV group and AngII group was increased significantly (p &lt;0.05), with lower activity in the AS-IV group than AngII group (p &lt; 0.05). After transfection, the VSMCs apoptosis in the AngII group was decreased (p &lt;0.05). In addition, cell migration in the AS-IV and AngII groups increased (p &lt;0.05), with lower ability in the AS-IV group than in the AngII group (p &lt;0.05). Alpha smooth muscle Actin (α-SMA) expression was elevated after AngII stimulation and decreased after AS-IV treatment (p &lt;0.05). After AngII stimulation, miR-320a and MMP9 were upregulated (p &lt;0.05) and downregulated by AS-IV (p &lt;0.05). MMP9 is a target gene for miR-320a. miR-320a and MMP9 expressions in the AS-IV group were significantly decreased, with lowest levels in the AS-IV-200 μg/mL group. In addition, MMP9 overexpression reduced the AngII expression. The expression of miR-320a/MMP9 axis was low in the AD, and activity were increased after AngII stimulation. In conclusion, As-IV can relieve the occurrence of AD via regulation of miR-320a/MMP9 axis.

Clinical characteristics and outcomes of Stanford type B aortic intramural hematoma: A single centre experience.

To compare the clinical characteristics of Stanford type B aortic intramural hematoma (IMH) and Stanford type B aortic dissection (AD), and to identify the differences between thoracic endovascular aortic repair (TEVAR) and medical management (MM) in the Stanford type B IMH patients. A retrospective observational study was conducted in patients treated between January 2015 and December 2016. The clinical characteristics and CT images of patients with type B IMH and type B AD were compared, and the clinical characteristics and CT images of patients in the type B IMH group who were treated with TEVAR and MM were compared. A total of 176 patients were included in this study, including 62 patients of type B IMH and 114 patients of type B AD. Five patients died in the IMH group and three in the AD group. The proximal hematoma or entry tear in both groups was mainly located in the descending aorta, and the proportion of the iliac artery involved in the AD group was significantly higher than that in the IMH group (31.6% vs. 8.1% P < 0.05). There were 50 MM patients and 12 TEVAR patients in the IMH group. No death occurred in the TEVAR group, while five patients in the MM group died. Seven patients in the MM group had disease progression vs. 12 in the TEVAR group (P < 0.05). The patients in the TEVAR group had more intima lesions than those in the MM group (83.3% vs. 30.0%, P < 0.05). TEVAR group involved more iliac artery hematoma than MM group (33.3% vs. 2.0%, P < 0.05). The maximum thickness of hematoma in TEVAR group was 14.9 ± 3.4 mm, which was significantly larger than that of MM group (10.2 ± 2.8 mm) (P < 0.05). In the diagnosis of IMH, patients' symptoms and high-risk signs of CTA should be paid attention to. TEVAR therapy should be actively considered on the basis of effective medical management when there are intima lesions (ULP/PAU), increased aortic diameter and hematoma thickness, extensive hematoma involvement, and pleural effusion.

The diagnostic significance of integrating m6A modification and immune microenvironment features based on bioinformatic investigation in aortic dissection.

PurposeThe aim of this study was to investigate the role of m6A modification and the immune microenvironment (IME) features in aortic dissection (AD) and establish a clinical diagnostic model for AD based on m6A and IME factors.MethodsGSE52093, GSE98770, GSE147026, GSE153434, and GSE107844 datasets were downloaded from the GEO database. The expression of 21 m6A genes including m6A writers, erasers, readers, and immune cell infiltrates was analyzed in AD and healthy samples by differential analysis and ssGSEA method, respectively. Both correlation analyses between m6A genes and immune cells were conducted by Pearson and Spearman analysis. XGboost was used to dissect the major m6A genes with significant influences on AD. AD samples were classified into two subgroups via consensus cluster and principal component analysis (PCA) analysis, respectively. Among each subgroup, paramount IME features were evaluated. Random forest (RF) was used to figure out key genes from AD and healthy shared differentially expressed genes (DEGs) and two AD subgroups after gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, we constructed an AD diagnostic model combining important m6A regulatory genes and assessed its efficacy.ResultsAmong 21 m6A genes, WTAP, HNRNPC, and FTO were upregulated in AD samples, while IGF2BP1 was downregulated compared with healthy samples. Immune cell infiltrating analysis revealed that YTHDF1 was positively correlated with γδT cell level, while FTO was negatively correlated with activated CD4+ T cell abundance. FTO and IGF2BP1 were identified to be crucial genes that facilitate AD development according to the XGboost algorithm. Notably, patients with AD could be classified into two subgroups among which 21 m6A gene expression profiles and IME features differ from each other via consensus cluster analysis. The RF identified SYNC and MAPK1IP1L as the crucial genes from common 657 shared common genes in 1,141 DEGs between high and low m6A scores of AD groups. Interestingly, the AD diagnostic model coordinating SYNC and MAPK1IP1L with FTO and IGF2BP1 performed well in distinguishing AD samples.ConclusionThis study indicated that FTO and IGF2BP1 were involved in the IME of AD. Integrating FTO and IGF2BP1 and MAPK1IP1L key genes in AD with a high m6A level context would provide clues for forthcoming AD diagnosis and therapy.

Identification and validation of differentially expressed chromatin regulators for diagnosis of aortic dissection using integrated bioinformatics analysis and machine-learning algorithms

Background: Aortic dissection (AD) is a life-threatening disease. Chromatin regulators (CRs) are indispensable epigenetic regulators. We aimed to identify differentially expressed chromatin regulators (DECRs) for AD diagnosis. Methods: We downloaded the GSE52093 and GSE190635 datasets from the Gene Expression Omnibus database. Following the merging and processing of datasets, bioinformatics analysis was applied to select candidate DECRs for AD diagnosis: CRs exertion; DECR identification using the “Limma” package; analyses of enrichment of function and signaling pathways; construction of protein–protein interaction (PPI) networks; application of machine-learning algorithms; evaluation of receiver operating characteristic (ROC) curves. GSE98770 served as the validation dataset to filter DECRs. Moreover, we collected peripheral-blood samples to further validate expression of DECRs by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, a nomogram was built for clinical use. Results: A total of 841 CRs were extracted from the merged dataset. Analyses of functional enrichment of 23 DECRs identified using Limma showed that DECRs were enriched mainly in epigenetic-regulation processes. From the PPI network, 17 DECRs were selected as node DECRs. After machine-learning calculations, eight DECRs were chosen from the intersection of 13 DECRs identified using support vector machine recursive feature elimination (SVM-RFE) and the top-10 DECRs selected using random forest. DECR expression between the control group and AD group were considerably different. Moreover, the area under the ROC curve (AUC) of each DECR was >0.75, and four DECRs (tumor protein 53 (TP53), chromobox protein homolog 7 (CBX7), Janus kinase 2 (JAK2) and cyclin-dependent kinase 5 (CDK5)) were selected as candidate biomarkers after validation using the external dataset and clinical samples. Furthermore, a nomogram with robust diagnostic value was established (AUC = 0.960). Conclusion: TP53, CBX7, JAK2, and CDK5 might serve as diagnostic DECRs for AD diagnosis. These DECRs were enriched predominantly in regulating epigenetic processes.

Diagnostic Value of Aortic Dissection Risk Score, Coagulation Function, and Laboratory Indexes in Acute Aortic Dissection.

Objective This study was aimed at studying the diagnostic value of aortic dissection (AD) risk score, coagulation function, and laboratory indicators in acute aortic dissection (AAD). Methods In this retrospective study, 57 patients with AAD and 57 with an acute coronary syndrome (ACS). During the same period, 50 healthy subjects were selected as the control group admitted to our institution which were assessed for eligibility and recruited. They were assigned to an AD group (AAD patients) and an ACS group (ACS patients). The AD risk scores, coagulation function indexes, and laboratory indexes of the two groups were compared. With digital subtraction angiography- (DSA-) based diagnosis result as the gold standard, the receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of various indexes for AD, and the sensitivity, specificity, and optimal diagnostic value (Youden index) of the diagnostic indexes were calculated. Additionally, the overall blood clot formation strength (MA), clotting factor function (R), platelet function (MAp), and functional fibrinogen (MAf) levels were evaluated. Results AAD risk, AD screening, early diagnosis of AAD, fibrinogen degradation products (FDP), fibrinogen (Fib), prothrombin time (PT), activated partial thromboplastin time (APTT), tenascin C (TN-C), D-dimer (D-D), and N-terminal B-type natriuretic peptide precursor (NT-proBNP) in the three groups were statistically different (P < 0.05). Further pairwise comparisons showed that the AD patients got higher scores of AAD risk, AD screening, and early diagnosis of AAD versus ACS patients (P < 0.05). AD was associated with lower levels of fibrinogen degradation products (FDP) and fibrinogen (Fib), shorter prothrombin time (PT), and activated partial thromboplastin time (APTT) versus ACS (P < 0.05). AD also resulted in higher levels of tenascin C (TN-C), D-dimer (D-D), and N-terminal B-type natriuretic peptide precursor (NT-proBNP) versus ACS (P < 0.05). The three risk scores, various laboratory indicators, and various coagulation function indicators were of high diagnostic values for the diagnosis of AAD (AUC > 0.9, P < 0.05). The sensitivity of the AD screening scale and TN-C expression level to the diagnosis of AAD was up to 100%, and the specificity of TN-C expression level was up to 98.25%. The influencing factors of AAD included Fib, FDP, PT, APTT, D-D, TN-C, and NT-proBNP. MA, MAf, and MAp displayed the same trend and reached the lowest point at T2. R was the opposite and reached the highest point at T2. At T4, a higher Map and a lower MAf were found than before surgery, and R and MA returned to preoperative levels. The positive detection rate of ACS by CT scan was positively correlated with the degree of stenosis (r = 0.814, P < 0.05). Conclusion AD screening scale, TN-C, and FDP are of the highest diagnostic value in the risk score of AD, laboratory indicators, and coagulation function. It has implications for the diagnosis of ADD.

Hemodynamic Study of Stanford Type B Aortic Dissection Based on Ex Vivo Porcine Aorta Models

Background: In this study, we aimed to evaluate hemodynamic influence of the dissected aortic system via various ex vivo type B aortic dissection (AD) models. Methods: Twenty-four raw porcine aortas were harvested and randomly divided into 4 groups to create various aortic models. Model A was the control group, while models B to D indicated the AD group, where models B and C presented a proximal primary entry with the false lumen (FL) lengths of 15 and 20 cm, respectively, and model D presented a 20 cm FL with a proximal primary entry and a distal reentry. All the aortic models were connected to a mock circulation loop to attain the realistic flow and pressure status. The flow distribution rate (FDR) of the aortic branches was calculated. Doppler ultrasound was applied to visualize the AD structure and to attain the velocity of flow in both the true and false lumens. Several sections of the AD were stained with hematoxylin and eosin for histologic evaluation after the experiment. Results: This study demonstrated that higher pressures were found for the AD group compared with the control group. The mean systolic pressures at the inlet of models A to D were 113.34±0.81, 120.58±0.52, 117.76±0.82, and 115.87±0.42 mm Hg, respectively. The FDRs of the celiac artery in models A to D were 8.65%, 8.32%±0.15%, 7.87%±0.13%, and 8.03%±0.21%, respectively. By ultrasound visualization, the velocity of the flow at the entry to the FL in the AD group ranged in 10 to 92 cm/s. The dissection flap presented pulsatile movement, especially in the models B and C which contained 1 primary entry without distal reentries. Histological examinations indicated that AD was located between the intimal and medial layers. Conclusions: Our ex vivo models demonstrated that the configuration of the dissected aorta influenced the pressure distribution. Moreover, the dissection flap affected the FDR of the aortic branches that possibly inducing malperfusion syndrome.

Pharmacologic IRE1α kinase inhibition alleviates aortic dissection by decreasing vascular smooth muscle cells apoptosis.

Aortic dissection (AD) is a rare but catastrophic disorder, and associated with significant morbidity among survivors. This study aimed to target IRE1α-XBP1s pathway pharmacologically, and evaluate its therapeutic potential in the occurrence and progression of AD. Western Blot and immunohistochemistry results showed that expression of XBP1s was significantly increased in the human aorta samples of AD group in compared with the control group, and exclusively in aortic vascular smooth muscle cells (VSMCs). Further in vitro study revealed that Angiotensin II (Ang II) could increase the expression of XBP1s and promote its nuclear translocation in cultured VSMCs, which leads to numerous gene transcription, including gp91phox, Chop, Cleaved-caspase 3, Bax, and Bcl-2. These genes contribute to the production of reactive oxygen species (ROS), VMSCs phenotypic switch and apoptosis. Whereas an IRE1α endoribonuclease domain inhibitor MKC-3946 could reverse it. Finally, the efficacy of MKC-3946 was tested in a mouse AD model. As shown in vitro, MKC-3946 could reduce the expression of XBP1s and protect against AD by suppressing XBP1s associated ROS production and apoptosis in VSMCs in vivo. The current study revealed the relevant role of IRE1α-XBP1s signaling pathway in AD occurrence and progression. MKC-3946 could be of great potential in clinical application.

Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in human aortic dissection

BackgroundMany studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in aortic dissection (AD) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in aortic dissection on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network.MethodsThis study collected the lncRNAs (GSE52093), mRNAs (GSE52093) and miRNAs (GSE92427) expression data within human tissue samples with aortic dissection group and normal group based on Gene Expression Omnibus (GEO) database.ResultsThis study identified three differentially expressed lncRNAs (DELs), 19 differentially expressed miRNAs (DEmiRs) and 1046 differentially expressed mRNAs (DEGs) identified regarding aortic dissection. Furthermore, we constructed a lncRNA-miRNA-mRNA network through three lncRNAs (including two with up-regulation and one with down-regulation), five miRNAs (five with up-regulation), as well as 211 mRNAs (including 103 with up-regulation and 108 with down-regulation). Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, four critical genes were found (E2F2, IGF1R, BDNF and PPP2R1B). In addition, E2F2 level was possibly modulated via lncRNA FAM87A-hsa-miR-31-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. The expression of IGF1R may be regulated by lncRNA FAM87A-hsa-miR-16-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p.ConclusionIn conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating AD. Our results shed more lights on the possible pathogenic mechanism in AD using a lncRNA-associated ceRNA network.

299 The Diagnostic Value of D-dimer Levels for the Exclusion of Aortic Dissection

Acute aortic dissection is a highly fatal disorder if not diagnosed promptly. The current gold standard for diagnosis of aortic dissection is with CT angiogram, MRI, or transesophageal echocardiogram. These advanced imaging techniques are expensive, time-consuming, and carry risks, so they are not ideal, especially for low risk patients. A universal, rapid-screening biomarker could reduce the need for advanced imaging tests to exclude the diagnosis of acute aortic dissection. Some prior studies have suggested that serum d-dimer levels are elevated in patients with aortic dissection, but the diagnostic value of d-dimer levels for ruling out aortic dissection remains uncertain. Thus, we sought to further assess the diagnostic usefulness of d-dimer levels as a means to rule out aortic dissection in emergency department patients. This was a retrospective analysis of emergency department patients from the Hospital Corporation of America (HCA) database. We queried the database to find patients who had a diagnosis of acute aortic dissection and who had a d-dimer test result within 24 hours of arrival to the emergency department. We also identified patients who had a diagnosis of (nonspecific) chest pain and who had a d-dimer test result within 24 hours of arrival to the emergency department. The median d-dimer value was compared in the aortic dissection group and the chest pain group using the Wilcoxon Rank Sum Test. We determined the sensitivity and specificity of d-dimer for aortic dissection using the standard cutoff value of 500 ng/mL, and we formulated a receiver operating characteristic (ROC) curve. Finally, we sought to determine if there is a different d-dimer cutoff value with better test characteristics than the standard 500 ng/mL. D-dimer values are reported in fibrinogen equivalent units (FEUs). A total of 48,902 patients’ records were analyzed for this study. This sample included 572 aortic dissection patients and 48,330 chest pain patients. The median d-dimer value for the aortic dissection group was 2455 ng/mL, and for the chest pain group, it was 385 ng/mL. The difference between the median values of each group of 2070 ng/mL was statistically significant (p-value <0.0001). Using a standard cutoff of 500 ng/mL, we found the sensitivity of the d-dimer to be 91.1% and the specificity to be 71.4%. To achieve a sensitivity greater than 95% for aortic dissection, the d-dimer cutoff had to be reduced to 375 ng/mL, at which point the sensitivity was 95.1% and the specificity was 48.5%. The Youden index maximized at 835 ng/mL, at which point the sensitivity was 82.9% and the specificity was 86.3%. The area under the ROC curve was 0.91 (95% CI 0.89 to 0.92). In general, serum d-dimer values are higher in patients with an aortic dissection than in those with nonspecific chest pain. At the standard cutoff of 500 ng/mL, the serum d-dimer seems to have a high sensitivity for aortic dissection, but it is likely not high enough such that d-dimer levels alone can be used to exclude aortic dissection.

Identification of transfer RNA-derived fragments and their potential roles in aortic dissection

Emerging evidence suggests that majority of the transfer RNA (tRNA)-derived small RNA, including tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), play a significant role in the molecular mechanisms underlying some human diseases. However, expression of tRFs/tiRNAs and their potential roles in aortic dissection (AD) remain unclear. This study examined the expression characteristics and explored the functional roles of tRFs/tiRNAs in AD using RNA-sequencing, bioinformatics, real-time quantitative reverse transcription polymerase chain reaction, and loss- and gain-of-function analysis. Results revealed that a total of 41 tRFs/tiRNAs were dysregulated in the AD group compared to the control group. Among them, 12 were upregulated and 29 were downregulated (fold change≥1.5 and p < 0.05). RT-qPCR results revealed that expressions of tRF-1:30-chrM.Met-CAT was significantly upregulated, while that of tRF-54:71-chrM.Trp-TCA and tRF-1:32-chrM.Cys-GCA were notably downregulated; expression patterns were consistent with the RNA sequencing data. Bioinformatic analysis showed that a variety of related pathways might be involved in the pathogenesis of AD. Functionally, tRF-1:30-chrM.Met-CAT could facilitate proliferation, migration, and phenotype switching in vascular smooth muscle cells (VSMCs), which might serve as a significant regulator in the progression of AD. In summary, the study illustrated that tRFs/tiRNAs expressed in AD tissues have potential biological functions and may act as promising biomarkers or therapeutic targets for AD.

Association between single nucleotide polymorphisms of tropoelastin gene and aortic dissection.

To evaluate the relation between single nucleotide polymorphisms (SNPs) of tropoelastin gene and aortic dissection (AD) via identifying SNPs in the tropoelastin gene, and to detect the level of tropoelastin mRNA, elastin and elastic fibers. The specimens of the AD group (n=96) and the control group (n=95), including their blood and aortic wall tissues, were collected. DNA was extracted from the blood samples in the 2 groups, and the SNPs in the tropoelastin gene were examined by the MassARRAY genotyping technique, and their haplotypes were constructed by PHASE software. The expression of tropoelastin mRNA and elastin in the aortic tunica media was respectively detected by real-time PCR or Western blotting. Elastin Van Gieson (EVG) staining was used to observe the shape of aortic tunica media and clarify the distribution of elastic fibers. The frequency of genotypes and haplotypes of SNP loci in the tropoelastin gene was analyzed and compared between the 2 groups, and the expression of tropoelastin mRNA, elastin and elastic fibers were also compared. Seven SNP loci of the tropoelastin gene were detected in these samples. Among them, 5 SNP loci were polymorphic. The frequency of 3 SNP loci[rs2071307 (G/A), rs34945509 (C/T) and rs17855988 (G/C)] was significantly different between the AD group and the control group (all P<0.05). There were significantly different in the haplotypes frequency of rs2071307 (G/A), rs34945509 (C/T) and rs17855988 (G/C) between the 2 groups (all P<0.01). Real-time PCR and Western blotting showed that the relative expression of tropoelastin mRNA and elastin in the aortic tunica media in the AD group was significantly lower than that in the control group (P<0.05). EVG staining showed that the aortic tunica media was torn, the morphology and structure of elastic fibers were broken, cracked, and disordered in the AD group, while the aortic tunica media was in complete structure and well arrangement.The elastic fibers were presented closely and orderly in the control group. The polymorphisms of rs2071307 (G/A), rs34945509 (C/T), and rs17855988(G/C) in the tropoelastin gene may eventually affect the synthesis of elastic fibers and they may play an important role in the occurrence of AD.

The role of the aortic area in type A aortic dissection

Aortic dissection (AD) is a cardiovascular disease with a high mortality rate. At present, there is no practical guidance for predicting and preventing aortic dissection, which is usually guided by clinicians' experience. The purpose of this study was to analyze the correlation between the maximum true lumen area of ascending aorta and the severity of type A aortic dissection in Stanford type A dissection. Fifteen patients were divided into the aortic rupture group, aortic dissection group, and healthy control group. The hemodynamic analysis of CTA data of two cases before and after the operation was used for experimental verification. The results showed that the maximum true lumen area of ascending aorta was negatively correlated with the risk degree. We suggest that the maximum true lumen area of the ascending aorta should be considered a predictor of rupture risk in Stanford A aortic dissection.