Thoracic Aneurysm Research Articles

Clinical outcomes of Najuta thoracic stent graft system for arch aneurysms.

We aimed to elucidate the perioperative and short-term clinical outcomes of the Najuta thoracic stent graft system with fenestrations for supra-aortic vessels. We retrospectively investigated the perioperative and short-term clinical outcomes of 20 patients treated for arch or distal arch aneurysms using the Najuta thoracic stent graft system during the period from May 2019 to February 2023. The technical success rate of the Najuta thoracic stent graft system was 95%. Of the 20 patients, 17 patients (85.0%) underwent concomitant extra-anatomical supra-aortic bypass. Postoperative CT revealed type Ia (n = 2) and type II (n = 3) endoleaks which disappeared on follow-up. The postoperative complications were stroke (n = 2, 10.0%), paraplegia (n = 1, 5.0%), and paraparesis (n = 1, 5.0%). In a very old patient, a blood transfusion was performed from the common iliac artery using the retroperitoneal approach. There were no aorta-related complications such as retrograde type A dissection or distal stent graft-induced new entry. We treated arch or distal arch thoracic aneurysms by inserting a tube-type stent graft as a scaffold on the peripheral site and placing the Najuta thoracic stent graft on the proximal site. By extending the landing zone to Zone 0 and using a low radial force, which is a feature of the Najuta thoracic stent graft system, postoperative bird-beak and aorta-related complications were avoided. The treatment of arch and distal arch aortic aneurysms using the Najuta thoracic stent graft system showed acceptable perioperative and short-term clinical outcomes. Thoracic endovascular aortic repair using the Najuta thoracic stent graft system may be a potential treatment option for arch and distal arch aortic aneurysms, warranting further studies.

O071 An assessment of information available online for the public regarding aortic aneurysms

Abstract Introduction Objective - To assess the quality of information provided by open access websites regarding aortic aneurysms (AA) on the World Wide Web. Methods The first 50 results from Yahoo, Bing and Google were collected using the search term ‘aortic aneurysm’ and duplicates removed. Website quality was scored using the University of Michigan Consumer Health Website tool (maximum score 80). Website readability was assessed using the Flesch Reading Ease (FRE)score (maximum score 100) and Simple Measure of Gobbledygook (SMOG) score (years of education needed). Subjective assessment was undertaken to assess the quality of website content. Results 59 of 81 websites were included for analysis after applying the exclusion criteria. 59.3% of websites were targeted at abdominal aortic aneurysms, and only 3.4% specific to thoracic aneurysms. The mean Michigan score for all sources was 48.6 (SD ±5.8), indicating sources were weak globally irrespective of publisher (public, private, independent or non-profit organization). Most sources were rated as requiring standard reading level, with a global average FRE of 62.72 (SD ±10.8). Mean SMOG scores showed that websites published by private organisations required the least educational level to read (mean = 10.5, SD ± 0.1). Conclusion Current online websites providing education to the public and professionals regarding aortic aneuryms are consistently low quality and lack comprehensiveness, with a paucity of information available for thoracic aortic aneurysms specifically. Efforts must be made to improve the quality of sources as well as expanding the scope of content to facilitate patient awareness and decision-making autonomy.

Abstract 284: Pro-Inflammatory Adventitial Fibroblast Contribute To Aortic Aneurysms In Loeys Dietz Syndrome

Introduction: Vascular smooth muscle cell (SMC) phenotype modulation is implicated in thoracic aneurysm formation, however, the role of adventitial fibroblasts (AdvFib) in aneurysm formation remains poorly characterized. Loeys-Dietz Syndrome (LDS), caused by a spectrum of mutations in the TGF-β signaling cascade, leads to aggressive thoracic aneurysms. Given the ubiquitous nature of TGF-β signaling machinery, the exact cell type(s) responsible for initiation of LDS pathogenesis is poorly understood. Methods: We performed single cell transcriptomic characterization of aortic root and ascending aortic samples from LDS patients ((n=6 LDS (harboring TGFB2 , TGFBR1 , TGFBR2 , or SMAD3 mutation); n=2 Donor control)) as well as root/ascending aorta from a murine model of LDS ( Tgfbr2 G357W/+ ) to understand cell-state transitions and transcriptomic alterations in LDS. Results: Single cell RNA sequencing (scRNAseq) of human and mice LDS samples (in total >40,000 cells) revealed a secondary pattern of cellular activation in LDS as compared to Marfan Syndrome. Instead of SMC phenotypic modulation as seen in MFS, LDS appears to preferentially modulate adventitial fibroblasts (AdvFib) phenotype in the Tgfbr2 G357W/+ mouse model. Human LDS patient’s AdvFib turn on high levels of macrophage-recruiting pro-inflammatory cytokines CCL2 and HLA-B, with a corresponding 1.8-fold increase in LDS aortic wall macrophages compared to Donor. A more extreme pattern was observed in the Tgfbr2 G357W/+ LDS mouse model. While Tgfbr2 G357W/+ SMC are transcriptomically similar to wild type counterparts, AdvFib were activated into a pro-inflammatory state associated with increased aortic macrophage recruitment ( Ccl2 , Il6 , Vcam1, and Cxcl2 ) and fibrotic response ( Col1a1 , Col1a2 , Col3a1, and Fn1 ). A 6-fold increase in the number of aortic wall macrophages was identified in Tgfbr2 G357W/+ compared to WT. Conclusions: LDS mouse and human AdvFib undergo phenotypic alterations into a pro-inflammatory state evidenced by increased expression of numerous cytokines, macrophage recruitment, and ECM deposition. AdvFib, in addition to SMCs, are potentially another important pathological cell population in LDS aneurysm formation.

Targeted Proteomic Analysis of Patients with Ascending Thoracic Aortic Aneurysm.

There is a need for clinical markers to aid in the detection of individuals at risk of harboring an ascending thoracic aneurysm (ATAA) or developing one in the future. To our knowledge, ATAA remains without a specific biomarker. This study aims to identify potential biomarkers for ATAA using targeted proteomic analysis. In this study, 52 patients were divided into three groups depending on their ascending aorta diameter: 4.0-4.5 cm (N = 23), 4.6-5.0 cm (N = 20), and >5.0 cm (N = 9). A total of 30 controls were in-house populations ethnically matched to cases without known or visible ATAA-related symptoms and with no ATAA familial history. Before the debut of our study, all patients provided medical history and underwent physical examination. Diagnosis was confirmed by echocardiography and angio-computed tomography (CT) scans. Targeted-proteomic analysis was conducted to identify possible biomarkers for the diagnosis of ATAA. A Kruskal-Wallis test revealed that C-C motif chemokine ligand 5 (CCL5), defensin beta 1 (HBD1), intracellular adhesion molecule-1 (ICAM1), interleukin-8 (IL8), tumor necrosis factor alpha (TNFα) and transforming growth factor-beta 1 (TGFB1) expressions are significantly increased in ATAA patients in comparison to control subjects with physiological aorta diameter (p < 0.0001). The receiver-operating characteristic analysis showed that the area under the curve values for CCL5 (0.84), HBD1 (0.83) and ICAM1 (0.83) were superior to that of the other analyzed proteins. CCL5, HBD1 and ICAM1 are very promising biomarkers with satisfying sensitivity and specificity that could be helpful in stratifying risk for the development of ATAA. These biomarkers may assist in the diagnosis and follow-up of patients at risk of developing ATAA. This retrospective study is very encouraging; however, further in-depth studies may be worthwhile to investigate the role of these biomarkers in the pathogenesis of ATAA.

Value of aortic volumes assessed by automated segmentation of 3D MRI data in patients with thoracic aortic dilatation: A case-control study

PurposeThe purpose of this study was to investigate the benefit of aortic volumes compared to diameters or cross-sectional areas on three-dimensional (3D) magnetic resonance imaging (MRI) in discriminating between patients with dilated aorta and matched controls. Materials and methodsSixty-two patients (47 men and 15 women; median age, 66 years; age range: 33–86 years) with tricuspid aortic valve and ascending thoracic aorta aneurysm (TAV-ATAA) and 43 patients (35 men and 8 women; median age, 51 years; age range: 17–76 years) with bicuspid aortic valve and dilated ascending aorta (BAV) were studied. One group of 54 controls matched for age and sex to patients with TAV-ATAA (39 men and 15 women; median age, 68 years; age range: 33–81 years) and one group of 42 controls matched for age and sex to patients with BAV (34 men and 8 women; median age, 50 years; age range: 17–77 years) were identified. All participants underwent 3D MRI, used for 3D-segmentation for measuring aortic length, maximal diameter, maximal cross-sectional area (CSA) and volume for the ascending aorta. ResultsAn increase in ascending aorta volume (TAV-ATAA: +107%; BAV: +171% vs. controls; P < 0.001) was found, which was three times greater than the increase in diameter (TAV-ATAA: +29%; BAV: +40% vs. controls; P < 0.001). In differentiating patients with TAV-ATAA from their controls, the indexed ascending aorta volume showed better performances (AUC, 0.935 [95% confidence interval (CI): 0.882–0.989]; accuracy, 88.7% [95% CI: 82.9–94.5]) than indexed ascending aorta length (P < 0.001), indexed ascending aorta maximal diameter (P = 0.003) and indexed ascending aorta maximal CSA (P = 0.03). In differentiating patients with BAV from matched controls, indexed ascending aorta volume showed significantly better performances performance (AUC, 0.908 [95% CI: 0.829–0.987]; accuracy, 88.0% [95% CI: 80.9–95.0]) than indexed ascending aorta length (P = 0.02) and not different from indexed ascending aorta maximal diameter (P = 0.07) or from indexed ascending aorta maximal CSA (P = 0.27) ConclusionAortic volume measured by 3D-MRI integrates both elongation and luminal dilatation, resulting in greater classification performance than maximal diameter and length in differentiating patients with dilated ascending aorta or aneurysm from controls.

P208 PET-CT scanning of GCA patients: the additive role of opportunistic screening for cardiovascular disease in a high-risk population

Abstract Background/Aims Cardiovascular disease (CVD) is well-recognised in giant cell arteritis (GCA) and thoracic aortic aneurysms (TAAs) are a late complication. Although the British Society for Rheumatology acknowledge the increased risk of CVD and TAAs, guidance for the management of GCA does not recommend antithrombotic agents or vascular screening due to lack of evidence. Positron emission topography (PET-CT) is commonly used for evaluation of large vessel vasculitis (LVV) in GCA. Although not routinely reported, additional measurements including aortic calibre and presence of coronary and aortic calcification can be assessed. LVV is known to be a risk factor for TAA. Therefore, this cohort represents an enriched population to evaluate for cardiovascular abnormalities. Our aims were to: estimate the prevalence of CV abnormalities on PET-CT scans in GCA; develop a standard operating procedure of CV parameters to improve the management of cardiovascular complications in conjunction with radiology and cardiology. Methods A retrospective review of PET-CT scans in GCA patients between 2016-2022 was undertaken. We determined the prevalence of CV abnormalities. Maximum diameter of the thoracic aorta and the presence of coronary and aortic calcification were reviewed by a PET-CT radiologist. Clinical characteristics and CV risk factors were evaluated. A standardised reporting protocol was developed for GCA PET-CT scans. A local guideline for the management of CV abnormalities was formulated. Results Fifty-two consecutive patients with GCA who had undergone PET-CT were identified. Most were female (40/51; 80%). Median age at diagnosis was 71 years (interquartile range [IQR] 63-75). Median time from GCA diagnosis to PET-CT scan was 20 months (IQR 4-38). Nine patients were diagnosed with GCA by PET-CT scan. Most GCA patients (32/51; 63%) were known to have CVRFs. 17/32 (53%) took an antithrombotic and/or anticoagulant, and 10/32 (31%) had a lipid lowering therapy. Original PET-CT scans reported coronary artery and/or aortic calcification in 6/51 (12%) GCA patients. Re-examination of PET-CT scans found coronary artery calcification in 38/51 (74%) and aortic calcification in 14/51 (27%) of all GCA patients. Coronary artery calcification was found in 27/32 (84%) of GCA patients known to have CVRFs, and 12/32 (38%) had evidence of aortic calcification. For GCA patients without CVRFs, 11/19 (58%) had evidence of coronary artery calcification and 2/19 (10%) had aortic calcification. Conclusion We observed a significant burden of cardiovascular abnormalities on PET-CT in GCA patients. Ten percent of patients with aortic dilation required follow up. A significant proportion of those with coronary calcification were not on primary prevention therapy. Importantly, 58% of patients without known CV risk factors were found to have coronary artery calcification. Given the burden of abnormalities identified we have now instituted a standardised reporting policy on CV abnormalities on PET-CT for GCA indications. Local policies have been developed for the management of thoracic aneurysms in GCA. Disclosure B. Mulhearn: None. J. Ellis: None. R. Foley: None. S. Gunawardana: None. R. Wickramarachchi: None. J. Rodrigues: None. O. Watkinson: None. S. Tansley: None. R. Graham: None. S. Skeoch: None.

Chyle leak after transposition of the aberrant left vertebral artery via 1-debranching thoracic endovascular aortic repair: a case report

BackgroundAlthough the transposition of the aberrant left vertebral artery (ALVA) in 1-debranching thoracic endovascular aortic repair requiring zone 2 coverage for thoracic aneurysm with ALVA is reported to be an effective option, there are few reports of complications associated with the transposition of the ALVA.Case presentationAn 87-year-old man underwent 1-debranching thoracic endovascular repair for a saccular thoracic aortic aneurysm with the aberrant left vertebral artery. Simultaneously, the transposition of the ALVA was performed to prevent cerebral complications because the left vertebral artery was dominant. Postoperative computed tomography revealed the reconstructed vertebral artery and no endoleak. However, a postoperative chyle leak occurred and was treated with lymphangiography.ConclusionAlthough the ALVA transposition is one of the better options, a chyle leak should be considered a serious complication of the procedure.

Mid-term outcomes of left subclavian artery revascularization with Castor stent graft in treatment of type B aortic dissection in left subclavian artery

BackgroundHere we analyzed mid-term data of thoracic endovascular aneurysm repair (TEVAR) surgery with Castor single-branched stent graft placement for the management of Stanford type B aortic dissection (STBAD) involving the left subclavian artery (LSA). MethodsBetween April 2014 and February 2019, 32 patients with STBAD involving a Castor single-branched stent graft were included. We analyzed their outcomes, including technical success rate (TSR), surgical duration (SD), presence of ischemia, perioperative complications, LSA patency, and survival rate (SR), using computed tomography angiography and clinical evaluation during mid-term follow-up. ResultsThe mean patient age was 54.63 ​± ​12.37 years (range, 36–83 years). The TSR was 96.88% (n ​= ​31/32). The mean SD was 87.44 ​± ​10.89 with a mean contrast volume of 125.31 ​± ​19.30 ​mL. No neurological complications or deaths occurred during the study period. The patients had a mean hospital stay of 7.84 ​± ​3.20 days. At a mean follow-up of 68.78 ​± ​11.26 months, four non-aortic deaths (12.5%) were observed. The LSA patency rate was 100% (n ​= ​28/28). There was only one case of type I endoleak immediately after surgery (3.12%) (type I from LSA). However, none of the patients experienced type II endoleaks, and there were no cases of retrograde type A aortic dissection or stent graft-driven new distal entry. Finally, all patients exhibited good LSA patency. ConclusionTEVAR using a Castor single-branched stent graft may be a highly feasible and efficient procedure for the management of STBAD involving the LSA.

Race and Socioeconomic Disparities in Proximal Aortic Surgery

BackgroundSubstantial socioeconomics-based disparities exist in cardiac surgery. Although there are robust data for revascularization and valve procedures, the effect of race and socioeconomic status on proximal aortic surgery is not well studied. This study analyzed the impact of race and socioeconomic status on in-hospital outcomes after proximal aortic surgery. MethodsAll adult patients who underwent proximal aortic surgery for aortic dissection or thoracic aneurysm from the 2016 to 2018 National Inpatient Sample were included. Primary outcomes included in-hospital mortality and in-hospital composite morbidity (stroke, pulmonary embolus, major bleeding, acute kidney injury, or permanent pacemaker insertion). Adjusted outcomes were assessed with multivariable analysis. ResultsA weighted total of 32,895 patients were included; 25,461 (77.4%) classified as White, 3224 (9.8%) Black, 2039 (6.2%) Hispanic, and 2171 (6.6%) other. Black and Hispanic patients had significantly lower median household income, higher proportion of self-pay insurance status, younger age, higher comorbidity burden, and a higher proportion of urgent or emergency procedures compared with White patients. There was no significant difference in observed in-hospital mortality by patient race, but non-White patients had significantly higher composite morbidity. On adjusted analysis, there was no difference in in-hospital mortality, but non-White race was an independent predictor of in-hospital morbidity (adjusted odds ratio, 1.6; 95% CI, 1.4-1.8; P < .001). ConclusionsPatients of non-White race who undergo proximal aortic surgery have less insurance coverage, more urgent procedures, and a higher comorbidity burden than White patients, disparities that translate to significantly higher morbidity in non-White. A greater focus on nonfatal outcome differentials and improving access to care likely will improve aortic surgery disparities.

Feasibility of aortic aneurysm sac embolization using a novel shape memory polymer embolic device

BackgroundWe investigated the feasibility of aneurysm sac embolization using a novel self-expanding porous shape memory polymer (SMP) device during endovascular aortic abdominal or thoracic aneurysm repair (EVAR).MethodsRetrospective analysis of consecutive patients treated at 2 centers in Germany. Patients were treated from January 2019 to July 2021 with follow-up at 7 days and 3, 6, and 12 months. Aneurysm sacs were implanted with SMP devices immediately following endograft placement during the same procedure. Primary endpoint was technically successful SMP-device deployment into the aneurysm sac outside the endograft. Secondary endpoints were changes in aneurysm volume and associated complications (e.g., endoleaks).ResultsWe included 18 patients (16 males), aged 72 ± 9 years, achieving 100% technical success. Mean preprocedure aortic aneurysm sac volume was 195 ± 117 mL with a perfused aneurysm volume of 97 ± 60 mL. A mean of 24 ± 12 SMP devices per patient were used (range 5–45, corresponding to 6.25–56.25 mL expanded embolic material volume). All evaluable patients exhibited sac regression except 2 patients yet to reach 3-month follow-up. At mean 11 ± 7 months (range 3–24), change in aneurysm volume from baseline was -30 ± 21 mL (p < 0.001). In 8 patients, aneurysm regression was observed despite type 2 endoleaks in 6 and type 1A endoleaks in 2, none of them requiring further intervention to date. No morbidity or mortality related to this treatment occurred.ConclusionsSMP devices for aortic aneurysm sac embolization during endovascular repair appear feasible and safe in this small case series. Prospective studies are needed.Key points• Shape memory polymer is a novel, self-expanding, porous, and radiolucent embolic device material.• Aortic aneurysm sacs were treated with polymer devices immediately following endograft placement.• Aortic aneurysm sac regression was observed in all patients with over 3-month follow-up.• Aortic aneurysm sac regression was observed even in the presence of endoleaks.

The association between diabetes mellitus and its management with outcomes following endovascular repair for descending thoracic aortic aneurysm

ObjectivePrior literature is conflicted regarding the effect of diabetes mellitus (DM) on outcomes after endovascular repair of aortic aneurysms. In this study, we aimed to examine the association between DM and outcomes after thoracic endovascular aneurysm repair (TEVAR) for thoracic aortic aneurysm (TAA). MethodsWe identified patients who underwent TEVAR for TAA of the descending thoracic aorta in the Vascular Quality Initiative between 2014 and 2022. We created two cohorts, DM and nonDM, based on the patient’s preoperative DM status, and secondarily substratified patients with DM by management strategy: dietary management, noninsulin medications, and insulin therapy cohorts. Outcomes included perioperative and 5-year mortality, in-hospital complications, indications for repair, and 1-year sac dynamics, which were analyzed with multivariable cox regression, multivariable logistic regression, and χ2 tests, respectively. ResultsWe identified 2637 patients, of which 473 (18%) had DM preoperatively. Among patients with DM, 25% were diet controlled, 54% noninsulin medications, and 21% insulin therapy. Within patients who underwent TEVAR for TAA, the proportions of ruptured presentation were higher in the dietary-managed (11.1%) and insulin-managed (14.3%) cohorts relative to noninsulin therapy (6.6%) and those without DM (6.9%). After multivariable regression analysis, we found that DM was associated with similar perioperative mortality (odds ratio, 1.14; 95% confidence interval [CI], 0.70-1.81) and 5-year mortality compared with patients without DM (hazard ratio, 1.15; 95% CI, 0.91-1.48). Furthermore, all in-hospital complications were comparable between patients with DM and patients without DM. Compared with patients without DM, dietary management of DM was significantly associated with higher adjusted perioperative mortality (OR, 2.16; 95% CI, 1.03-4.19) and higher 5-year mortality (hazad ratio, 1.50; 95% CI, 1.03-2.20), although this was not the case for other DM subgroups. All cohorts displayed similar 1-year sac dynamics, with sac regression occurring in 47% of patients without DM vs 46% of patients with DM (P = .27). ConclusionsPreoperatively, patients with DM who underwent TEVAR had a higher proportion of ruptured presentation when treated with diet or insulin medications than when treated with noninsulin medications. After TEVAR for descending TAA, DM was associated with a similar risk of perioperative and 5-year mortality as nonDM. In contrast, dietary therapy for DM was associated with significantly higher perioperative mortality and 5-year mortality.

Komplex endovascularis rekonstrukciók az aortaíven.

Thoracic endovascular aneurysm repair (TEVAR) of the aortic arch has started to spread in recent years. We present our initial experience with TEVAR involving supra-aortic branches using parallel and branched grafts. Parallel grafts are typically used in emergency cases. In the case of Z0 proximal fixation, we can perform a combined hybrid surgery with Z1 debranching and securing of the innominate artery with chimney graft, which can also be used instead of Z0 debranching when the patient is unfit for sternotomy. In the case of TEVAR with planned Z2 position with inadvertent covering of the left common carotid artery, we can perform chimney conversion to rapidly recover the circulation of the left common carotid artery (LCCA). Instead of prior revascularization of the left subclavian artery, chimney graft can be used to recover the lumen, in the case of left upper limb ischemia after Z2 TEVAR. Exclusion of penetrating aortic ulcers located in the lesser curvature can be facilitated by use of a custom-made graft, where a scallop is placed around the origin of the supra-aortic vessel, thus increasing the length of the proximal neck. For elective interventions, custom-made branching grafts can be allowed to save all three branches with Z0 fixation. Technical success was obtained in all cases. Orv Hetil. 2023; 164(11): 426-431.

The C-terminal domains of ADAMTS1 contain exosites involved in its proteoglycanase activity

A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS1) is a protease involved in fertilization, cancer, cardiovascular development, and thoracic aneurysms. Proteoglycans such as versican and aggrecan have been identified as ADAMTS1 substrates, and Adamts1 ablation in mice typically results in versican accumulation; however, previous qualitative studies have suggested that ADAMTS1 proteoglycanase activity is weaker than that of other family members such as ADAMTS4 and ADAMTS5. Here, we investigated the functional determinants of ADAMTS1 proteoglycanase activity. We found that ADAMTS1 versicanase activity is approximately 1000-fold lower than ADAMTS5 and 50-fold lower than ADAMTS4 with a kinetic constant (kcat/Km) of 3.6× 103M-1s-1 against full-length versican. Studies on domain-deletion variants identified the spacer and cysteine-rich domains as major determinants of ADAMTS1 versicanase activity. Additionally, we confirmed that these C-terminal domains are involved in the proteolysis of aggrecan as well as biglycan, a small leucine-rich proteoglycan. Glutamine scanning mutagenesis of exposed positively charged residues on the spacer domain loops and loop substitution with ADAMTS4 identified clusters of substrate-binding residues (exosites) in β3-β4 (R756Q/R759Q/R762Q), β9-β10 (residues 828-835), and β6-β7 (K795Q) loops. This study provides a mechanistic foundation for understanding the interactions between ADAMTS1 and its proteoglycan substrates and paves the way for development of selective exosite modulators of ADAMTS1 proteoglycanase activity.

Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms

ObjectiveArterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM).MethodsThis study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms.ResultsPheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc (‘ntreeA’) was associated with both AAA (β = −0.36, P = 6.75e−10) and ICA (β = −0.11, P = 5.51e−06). In addition, the mean angles between each artery branch (‘curveangle_mean_a’) were commonly associated with 4 MFS genes (FBN1: β = −0.10, P = 1.63e−12; COL16A1: β = −0.07, P = 3.14e−09; LOC105373592: β = −0.06, P = 1.89e−05; C8orf81/LOC441376: β = 0.07, P = 1.02e−05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780–0.838], which was similar to the clinical risk model (0.806 [0.778–0.834]) but higher than the baseline model (0.739 [0.733–0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727–0.869) for the aneurysm-RVF model, 0.795 (0.718–0.871) for the clinical risk model and 0.719 (0.620–0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5–48.8], P = 1.02e−05).ConclusionWe identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system.Graphical abstract

Accuracy of aortic annulus measurements by three-dimensional transesophageal echocardiography and predictive value for thoracic aorta aneurysm in patients with aortic regurgitation.

Accurate assessment of the aortic annulus (AA) dimension and judgment of thoracic aorta aneurysm is crucial for patients with aortic regurgitation (AR) before surgery. The aim of this study was to evaluate the accuracy and reproducibility of three-dimensional transesophageal echocardiography (3D-TEE) methods for AA measurement and explore the predictive value of the AA dimensions obtained by 3D-TEE for high-risk thoracic aorta aneurysms using the gold standard of multi-slice computed tomography (MSCT). 3D-TEE was performed on 111 patients with pure moderate-to-severe AR, and MSCT examination was conducted simultaneously. AA dimensions were obtained using reconstruction software for these two imaging techniques. Thoracic aortic diameters at standard anatomic landmarks were also measured by MSCT. All patients were divided into two groups depending on the presence of high-risk thoracic aorta aneurysms. Compared to MSCT, 3D-TEE overestimated all AA parameters. However, no statistically significant differences were found in the average bias between methods (minimum diameter: 26.07±3.57 vs. 25.88±3.68 mm, P=0.52; maximum diameter: 32.30±2.68 vs. 31.78±4.06 mm, P=0.11; area: 669.76±155.19 vs. 660.05±168.28 mm2, P=0.44; perimeter: 93.52±10.42 vs. 92.26±11.71 mm, P=0.12). 3D-TEE demonstrated good correlations with MSCT measurement for AA minimum diameter, maximum diameter, area, and perimeter (r=0.63, 0.64, 0.74, 0.69, P<0.05 for all). According to the multivariate logistic regression analysis, the AA minimum diameter obtained by 3D-TEE was the best predictor for the presence of high-risk thoracic aorta aneurysms. The sensitivity and specificity for prediction were 84.6% and 63.9%, respectively, for an AA minimum diameter ≥25.74 mm (AUC: 0.759, 95% CI: 0.668-0.850). AA measurements obtained by the 3D-TEE method are feasible and reliable for patients with pure AR. The AA minimum diameter measured by 3D-TEE can effectively predict the presence of high-risk thoracic aorta aneurysms.

A case report of a sudden adolescent death from a rare cause: rupture of a saccular thoracic aneurysm complicating undiagnosed coarctation of the aorta

Introduction: Coarctation of the aorta is one of the most commonly encountered congenital heart diseases accounting for about 7% of the cases. With early childhood diagnosis and the development of corrective surgical intervention, undiagnosed aortic coarctation presenting as sudden and unexpected death is today a rarity. Fatal complications such as aortic rupture or dissection, endocarditis and ruptured cerebral aneurysm can arise when left untreated. We report a rare case of sudden death involving an adolescent female found to have an undiagnosed aortic coarctation at autopsy with a saccular thoracic aneurysm and hemothorax. Case description: A healthy 17-year-old girl was dead on arrival at the Emergency Department of a district hospital after collapsing at home following a short history of breathing difficulties. A forensic autopsy revealed massive left-sided hemothorax and a heretofore undiagnosed aortic coarctation with a pre-coarctation saccular thoracic aneurysm that has ruptured. On histology, the aneurysm wall was found to be deficient in tunica media with no evidence of dissection. Discussion and conclusion: The clinicopathology of coarctation-associated aneurysms will be discussed. Despite their rarity, the forensic pathologist should consider the likelihood of aortic coarctation when confronted with the unexpected finding of a ruptured thoracic aortic aneurysm in the young.

Concurrent validity of radiography and ultrasound examination for the diagnosis of aortic aneurisms in Albanian patients

Aim: The aim of our study was to assess the concurrent validity of radiography and ultrasound examination among patients diagnosed with aortic aneurisms in Albania, a transitional country in South Eastern Europe. Methods: This study included 75 consecutive patients diagnosed with aortic aneurisms (thoracic and/or abdominal) admitted at the University Hospital Centre “Mother Teresa” in Tirana during 2012-2014 (56 men and 19 women). For each patient, computerized tomography (CT) scan with contrast was used to confirm the diagnosis of aortic aneurisms. In addition to the CT scan (“gold standard” for the diagnosis of aneurisms), in 37 patients, radiography and ultrasound examination were simultaneously performed in order to assess the validity of these techniques. Furthermore, demographic data and other relevant clinical information were collected for each study participant. Results: In 18 patients with thoracic aneurisms pertinent to ascendant aorta where radiography and ultrasound were simultaneously performed, ultrasound was able to diagnose 5 (27.8%) cases which were not detected through radiography (P=0.038). Conversely, in 16 patients with abdominal aneurisms where radiography and ultrasound were simultaneously performed, ultrasound was able to diagnose 4 (25.0%) cases which were not detected through radiography (P=0.034). The remaining three patients diagnosed with thoracic-abdominal aneurisms were not detected either by ultrasound examination or radiography. Conclusions: In this sample of Albanian patients diagnosed with aortic aneurisms (N=75), overall, 9 (24.3%) subjects were detected through ultrasound examination but not radiography (P&lt;0.001). Findings from this study provide valuable clues about the concurrent validity and predictive value of these two key examinations for the diagnosis of aortic aneurisms.

Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.

Thoracic aortic disease affects people of all ages and the majority of those aged &lt;60 years have an underlying genetic cause. There is presently no effective medical therapy for thoracic aneurysm and surgery remains the principal intervention. Unlike abdominal aortic aneurysm, for which the inflammatory/atherosclerotic pathogenesis is well established, the mechanism of thoracic aneurysm is less understood. This paper examines the key cell signaling systems responsible for the growth and development of the aorta, homeostasis of endothelial and vascular smooth muscle cells and interactions between pathways. The evidence supporting a role for individual signaling pathways in pathogenesis of thoracic aortic aneurysm is examined and potential novel therapeutic approaches are reviewed. Several key signaling pathways, notably TGF-β, WNT, NOTCH, PI3K/AKT and ANGII contribute to growth, proliferation, cell phenotype and survival for both vascular smooth muscle and endothelial cells. There is crosstalk between pathways, and between vascular smooth muscle and endothelial cells, with both synergistic and antagonistic interactions. A common feature of the activation of each is response to injury or abnormal cell stress. Considerable experimental evidence supports a contribution of each of these pathways to aneurysm formation. Although human information is less, there is sufficient data to implicate each pathway in the pathogenesis of human thoracic aneurysm. As some pathways i.e., WNT and NOTCH, play key roles in tissue growth and organogenesis in early life, it is possible that dysregulation of these pathways results in an abnormal aortic architecture even in infancy, thereby setting the stage for aneurysm development in later life. Given the fine tuning of these signaling systems, functional polymorphisms in key signaling elements may set up a future risk of thoracic aneurysm. Multiple novel therapeutic agents have been developed, targeting cell signaling pathways, predominantly in cancer medicine. Future investigations addressing cell specific targeting, reduced toxicity and also less intense treatment effects may hold promise for effective new medical treatments of thoracic aortic aneurysm.

Bicolor K-edge spectral photon-counting CT imaging for the diagnosis of thoracic endoleaks: A dynamic phantom study

PurposeThe purpose of this study was to investigate the feasibility of identifying and characterizing the three most common types of endoleaks within a thoracic aorta aneurysm model using bicolor K-edge imaging with a spectral photon-counting computing tomography (SPCCT) system in combination with a biphasic contrast agent injection. Materials and methodsThree types of thoracic endoleaks (type 1, 2 and 3) were created in a dynamic anthropomorphic thoracic aorta phantom. Protocol consisted in an injection of an iodinated contrast material followed 80 seconds after an injection of a gadolinium-based contrast agent (GBCA). The phantom was scanned using a clinical prototype SPCCT during bicolor phase imaging consisting in an early distribution of GBCA and a late distribution of iodine. Conventional and spectral images were reconstructed for differentiating between the contrast agents and measuring their respective attenuation values and concentrations inside and outside the stent graft. ResultsConventional images failed to provide specific dynamic imaging contrast agents in the aneurysmal sac and outside the stent graft while spectral images differentiated their specific distribution. In type 1 and 3 thoracic endoleaks, GBCA concentration was measured outside the stent graft at 6.1 ± 3.7 (standard deviation [SD]) mg/mL and 6.0 ± 4.0 (SD) mg/mL, respectively, in favor of an early blood flow. In type 2 thoracic endoleak, iodine was measured outside the stent graft at 24.3 ± 5.5 (SD) mg/mL in favor of a late blood flow in the aneurysmal sac. ConclusionBicolor K-edge imaging enabled SPCCT allows a bicolor characterization of thoracic aorta endoleaks in a single acquisition in combination with a biphasic contrast agent injection.

Thoracic aortic aneurysm and atrial fibrillation: clinical associations with the risk of stroke from a global federated health network analysis

BackgroundAn association with aortic aneurysm has been reported among patients with atrial fibrillation (AF). The aims of this study were to investigate the prevalence of thoracic aorta aneurysm (TAA) among patients with AF and to assess whether the co-presence of TAA is associated with a higher risk of adverse clinical outcomes.Methods and resultsUsing TriNetX, a global federated health research network of anonymised electronic medical records, all adult patients with AF, were categorised into two groups based on the presence of AF and TAA or AF alone. Between 1 January 2017 and 1 January 2019, 874,212 people aged ≥ 18 years with AF were identified. Of these 17,806 (2.04%) had a TAA. After propensity score matching (PSM), 17,805 patients were included in each of the two cohorts. During the 3 years of follow-up, 3079 (17.3%) AF patients with TAA and 2772 (15.6%) patients with AF alone, developed an ischemic stroke or transient ischemic attack (TIA). The risk of ischemic stroke/TIA was significantly higher in patients with AF and TAA (HR 1.09, 95% CI 1.04–1.15; log-rank p value < 0.001)The risk of major bleeding was higher in patients with AF and TAA (OR 1.07, 95% CI 1.01–1.14), but not significant in time-dependent analysis (HR 1.04, 95% CI 0.98–1.10; log-rank p value = 0.187),ConclusionThis retrospective analysis reports a clinical concomitance of the two medical conditions, and shows in a PSM analysis an increased risk of ischemic events in patients affected by TAA and AF compared to AF alone.