Buffering Mechanism in Aortic Arch Artery Formation and Congenital Heart Disease.

BACKGROUND: The resiliency of embryonic development to genetic and environmental perturbations has been long appreciated; however, little is known about the mechanisms underlying the robustness of developmental processes. Aberrations resulting in neonatal lethality are exemplified by congenital heart disease arising from defective morphogenesis of pharyngeal arch arteries (PAAs) and their derivatives. METHODS: Mouse genetics, lineage tracing, confocal microscopy, and quantitative image analyses were used to investigate mechanisms of PAA formation and repair. RESULTS: The second heart field (SHF) gives rise to the PAA endothelium. Here, we show that the number of SHF-derived endothelial cells (ECs) is regulated by VEGFR2 (vascular endothelial growth factor receptor 2) and Tbx1. Remarkably, when the SHF-derived EC number is decreased, PAA development can be rescued by the compensatory endothelium. Blocking such compensatory response leads to embryonic demise. To determine the source of compensating ECs and mechanisms regulating their recruitment, we investigated 3-dimensional EC connectivity, EC fate, and gene expression. Our studies demonstrate that the expression of VEGFR2 by the SHF is required for the differentiation of SHF-derived cells into PAA ECs. The deletion of 1 VEGFR2 allele (VEGFR2SHF-HET) reduces SHF contribution to the PAA endothelium, while the deletion of both alleles (VEGFR2SHF-KO) abolishes it. The decrease in SHF-derived ECs in VEGFR2SHF-HET and VEGFR2SHF-KO embryos is complemented by the recruitment of ECs from the nearby veins. Compensatory ECs contribute to PAA derivatives, giving rise to the endothelium of the aortic arch and the ductus in VEGFR2SHF-KO mutants. Blocking the compensatory response in VEGFR2SHF-KO mutants results in embryonic lethality shortly after mid-gestation. The compensatory ECs are absent in Tbx1+/- embryos, a model for 22q11 deletion syndrome, leading to unpredictable arch artery morphogenesis and congenital heart disease. Tbx1 regulates the recruitment of the compensatory endothelium in an SHF-non-cell-autonomous manner. CONCLUSIONS: Our studies uncover a novel buffering mechanism underlying the resiliency of PAA development and remodeling.

ß-Aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice.

BACKGROUND: ß-aminopropionitrile (BAPN) is a pharmacological inhibitor of LOX (lysyl oxidase) and LOXLs (LOX-like proteins). Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to generate pathology. The objective of this study was to define experimental parameters and determine whether equivalent or variable aortopathies were generated throughout the aortic tree during BAPN administration in mice. METHODS: BAPN was administered in drinking water for a period ranging from 1 to 12 weeks. The impacts of BAPN were first assessed with regard to BAPN dose, and mouse strain, age, and sex. BAPN-induced aortic pathological characterization was conducted using histology and immunostaining. To investigate the mechanistic basis of regional heterogeneity, the ascending and descending thoracic aortas were harvested after 1 week of BAPN administration before the appearance of overt pathology. RESULTS: BAPN-induced aortic rupture predominantly occurred or originated in the descending thoracic aorta in young C57BL/6J or N mice. No apparent differences were found between male and female mice. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while there were more heterogeneous changes in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissections with false lumen formation, collagen deposition, and remodeling of the wall surrounding the false lumen. Cells surrounding the false lumen were predominantly positive for α-SMA (α-smooth muscle actin). One week of BAPN administration compromised contractile properties in both regions equivalently, and RNA sequencing did not show obvious differences between the 2 aortic regions in smooth muscle cell markers, cell proliferation markers, and extracellular components. CONCLUSIONS: BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in mice.

Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation.

BACKGROUND: The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation. METHODS: In this observational study, mass spectrometry imaging (MSI) was applied to identify region-specific metabolic differences between atherosclerotic (n=11) and control (n=11) aortas from low-density lipoprotein receptor-deficient mice, via histology-guided virtual microdissection. Early and advanced plaques were compared within the same atherosclerotic animals. Progression metabolites were further analyzed by MSI in 9 human atherosclerotic carotids and by targeted mass spectrometry in human plasma from subjects with elective coronary artery bypass grafting (cardiovascular risk group, n=27) and a control group (n=27). RESULTS: MSI identified 362 local metabolic alterations in atherosclerotic mice (log2 fold-change ≥1.5; P≤0.05). The lipid composition of cardiac tissue is altered during atherosclerosis development and presents a generalized accumulation of glycerophospholipids, except for lysolipids. Lysolipids (among other glycerophospholipids) were found at elevated levels in all 3 arterial layers of atherosclerotic aortas. LPC(18:0) (lysophosphatidylcholine; P=0.024) and LPA(18:1) (lysophosphatidic acid; P=0.025) were found to be significantly elevated in advanced plaques as compared with mouse-matched early plaques. Higher levels of both lipid species were also observed in fibrosis-rich areas of advanced- versus early-stage human samples. They were found to be significantly reduced in human plasma from subjects with elective coronary artery bypass grafting (P<0.001 and P=0.031, respectively), with LPC(18:0) showing significant association with cardiovascular risk (odds ratio, 0.479 [95% CI, 0.225-0.883]; P=0.032) and diagnostic potential (area under the curve, 0.778 [95% CI, 0.638-0.917]). CONCLUSIONS: An altered phospholipid metabolism occurs in atherosclerosis, affecting both the aorta and the adjacent heart tissue. Plaque-progression lipids LPC(18:0) and LPA(18:1), as identified by MSI on tissue, reflect cardiovascular risk in human plasma.

Blunt traumatic aortic injury in the elderly population.

OBJECTIVE: Blunt thoracic aortic injury (BTAI) is a major cause of morbidity and mortality in trauma patients. Although outcomes for BTAI have been described in younger patient populations, elderly patients may present with different patterns of injury and have unique factors contributing to morbidity and mortality. This study aims to describe patterns of presentation and management in elderly patients presenting with BTAI using a nationwide database. METHODS: Patients aged 65 years and older with BTAI from 2007 through 2016 were identified from the American College of Surgeons Trauma Quality Improvement Program database. Baseline demographics, initial physiologic variables, and clinical outcomes were extracted from the database. Our primary outcome was in-hospital mortality. An adjusted Poisson generalized regression model was used to compare rates of mortality for thoracic endovascular aortic repair (TEVAR), open repair, and nonoperative management. RESULTS: During the study period, 1322 patients aged 65 years and over sustained BTAI and survived past triage. Mean age was 74.7 years, and 60% were male. There were low incidence rates of concomitant major head (9.4%), spine (3.1%), and abdominal (5.7%) injuries. Three hundred fifty (26.5%) underwent TEVAR, 58 (4.4%) open repair, and 914 (69.1%) were managed nonoperatively. Utilization of TEVAR increased from 13.1% to 32.7% from 2007 to 2015, with subsequent decline to 19.9% in 2016 in favor of nonoperative management. Age, gender, and mean Injury Severity Scores (ISS) did not significantly differ by management. In-hospital mortality for the entire cohort was 37.9%. In an adjusted Poisson generalized regression model using inverse probability of treatment weighting controlling for age, race, gender, ISS, and hypotension, TEVAR was associated with the lowest mortality rate (1.31 deaths/100 person-years; 95% confidence interval [CI], 1.17-1.46) compared with open repair (2.53; 95% CI, 2.32-2.75; P < .001) and nonoperative management (3.91; 95% CI, 3.60-4.25; P < .001). There was a higher incidence of acute kidney injury, acute respiratory distress syndrome, and surgical site infection in the TEVAR group. CONCLUSIONS: This study describes the management of and outcomes for BTAI in the elderly population. The majority of patients did not undergo operative repair, which was associated with a higher risk of in-hospital mortality. In an adjusted analysis, TEVAR was associated with the lowest mortality rate, compared with open repair and nonoperative management.

Longitudinal follow-up by MR angiography reveals progressive dilatation of the distal aorta after aortic root replacement in Marfan syndrome.

OBJECTIVES: To define and compare growth rates of the distal aorta in Marfan patients with and without aortic root replacement using serial MR angiography (MRA). METHODS: We retrospectively included 136 Marfan patients with a total of 645 MRAs who underwent a median of five MRAs (range: 2-13) at 1.5 T and 3 T in annual intervals. Of these, 41 patients (34.8 ± 12 years) had undergone aortic root replacement. The remaining 95 patients (29.0 ± 17 years) still had a native aorta and served as the control group. Thoracic aortic diameters were independently measured at eleven predefined levels. Estimated growth rates were calculated using a mixed effects model adjusted for sex, age, BMI, and medication. RESULTS: Marfan patients with aortic root replacement revealed the highest mean estimated growth rate in the proximal descending aorta (0.77 mm/year, CI: 0.31-1.21). Mean growth rates at all levels of the distal thoracic aorta were significantly higher in patients with aortic root replacement (0.28-0.77 mm/year) when compared to patients without aortic root replacement (0.03-0.07 mm/year) (all p < 0.001). Antihypertensive medication, gender, and BMI had no significant impact on the distal aortic growth rates. CONCLUSION: Distal thoracic aortic diameters increase at a significantly higher rate in Marfan patients with aortic root replacement compared to Marfan patients without aortic root replacement. Further studies are warranted to investigate if the increased growth rate of the distal thoracic aorta after aortic root replacement is caused by altered hemodynamics due to the rigid aortic root graft or due to the general genetic disposition of post-operative Marfan patients. CLINICAL RELEVANCE STATEMENT: High growth rates of the distal aorta after aortic root replacement underline the need for careful life-long aortic imaging of Marfan patients after aortic root replacement. KEY POINTS: • Aortic growth rates in Marfan patients with aortic root replacement are highest in the mid-aortic arch, the proximal- and mid-descending aorta. • Growth rates of the distal thoracic aorta are significantly higher in Marfan patients with aortic root replacement compared to Marfan patients without aortic root replacement. • Antihypertensive medication, gender, and BMI have no significant impact on distal aortic growth rates in Marfan patients.

Microcalcification and Thoracic Aortopathy: A Window Into Disease Severity.

BACKGROUND: Patients with thoracic aortopathy are at increased risk of catastrophic aortic dissection, carrying with it substantial mortality and morbidity. Although granular medial calcinosis (medial microcalcification) has been associated with thoracic aortopathy, its relationship to disease severity has yet to be established. METHODS: One hundred one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathologic scores, immunohistochemistry, and nanoindentation (tissue elastic modulus) were compared with the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography. RESULTS: Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71-10.39]; P≤0.00010) or moderate histopathologic degeneration (n=30; 3.74 [0.87-11.80]; P<0.042) compared with control samples (n=18; 0.79 [0.36-1.90]). Alkaline phosphatase (n=26; P=0.0019) and OPN (osteopontin; n=26; P=0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathologic degeneration was related to reduced microcalcification (n=82; Spearman ρ, -0.51; P<0.0001)-a process closely linked with elastin loss (n=82; Spearman ρ, -0.43; P<0.0001) and lower tissue elastic modulus (n=28; Spearman ρ, 0.43; P=0.026).18F-sodium fluoride autoradiography demonstrated good correlation with histologically quantified microcalcification (n=66; r=0.76; P<0.001) and identified areas of focal weakness in vivo. CONCLUSIONS: Medial microcalcification is a marker of aortopathy, although progression to severe aortopathy is associated with loss of both elastin fibers and microcalcification.18F-sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible noninvasive imaging modality for identifying aortic wall disruption with major translational promise.

Emergency department visits after acute aortic syndromes.

OBJECTIVE: Recent reports document a high rate of readmission after hospitalization for acute aortic syndromes (AAS) that include acute aortic dissections, intramural hematomas, or penetrating aortic ulcers. We examined the rate of return to the emergency department (ED) to better understand the utilization of emergent health care services after AAS. METHODS: Consecutive patients with AAS admitted to the vascular surgery service from 2004 to 2020 were included. Patients with type A dissections, arch involvement, or chronic aortic pathology were excluded. The primary outcome was ED visits within 90 days of the original hospitalization. RESULTS: The study included 79 subjects (62% men, 38% women; mean age: 64 ± 14 years) with AAS (82% aortic dissections, 11% intramural hematomas, and 6% penetrating aortic ulcers). A total of 54 ED visits related to the AAS occurred within 90 days of the original discharge, each of which incurred a computed tomography angiogram. Twenty-eight (35%) subjects had a mean of 2 ± 2 ED visits, whereas 51 (65%) subjects had no ED visits. Ninety percent (25 of 28) of the first ED visits occurred within 1 month of discharge and 53% (15 of 28) within 1 week. A total of 17 (61%) subjects were readmitted to the hospital from the ED. Four subjects were found to have progression of AAS on imaging studies and underwent thoracic endovascular aortic repair during readmission. Comparing subjects who returned to the ED with those who did not, there were no significant differences in demographics, atherosclerotic risk factors except coronary artery disease, type of AAS, number of antihypertensive medications at admission or discharge, operative intervention, length of initial hospital stay, or discharge status. The chief complaints at the first ED visit were pain (n = 17), uncontrolled hypertension (n = 5), syncope (n = 3), and other (n = 3). CONCLUSIONS: These data show that one in three patients with AAS returned to the ED within 90 days of initial discharge. Although returning subjects had a higher number of readmissions, few had progression of AAS that required intervention. Because the vast majority were readmitted for medical therapy, early and frequent clinic follow-up may help decrease ED visits and readmissions after AAS.

Endothelial Rap1 (Ras-Association Proximate 1) Restricts Inflammatory Signaling to Protect From the Progression of Atherosclerosis.

OBJECTIVE: Small GTPase Rap1 (Ras-association proximate 1) is a novel, positive regulator of NO release and endothelial function with a potentially key role in mechanosensing of atheroprotective, laminar flow. Our objective was to delineate the role of Rap1 in the progression of atherosclerosis and its specific functions in the presence and absence of laminar flow, to better define its role in endothelial mechanisms contributing to plaque formation and atherogenesis. Approach and Results: In a mouse atherosclerosis model, endothelial Rap1B deletion exacerbates atherosclerotic plaque formation. In the thoracic aorta, where laminar shear stress-induced NO is otherwise atheroprotective, plaque area is increased in Athero-Rap1BiΔEC (atherogenic endothelial cell-specific, tamoxifen-inducible Rap1A+Rap1B knockout) mice. Endothelial Rap1 deficiency also leads to increased plaque size, leukocyte accumulation, and increased CAM (cell adhesion molecule) expression in atheroprone areas, whereas vascular permeability is unchanged. In endothelial cells, in the absence of protective laminar flow, Rap1 deficiency leads to an increased proinflammatory TNF-α (tumor necrosis factor alpha) signaling and increased NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and elevated inflammatory receptor expression. Interestingly, this increased signaling to NF-κB activation is corrected by AKTVIII-an inhibitor of Akt (protein kinase B) translocation to the membrane. Together, these data implicate Rap1 in restricting Akt-dependent signaling, preventing excessive cytokine receptor signaling and proinflammatory NF-κB activation. CONCLUSIONS: Via 2 distinct mechanisms, endothelial Rap1 protects from the atherosclerosis progression in the presence and absence of laminar flow; Rap1-stimulated NO release predominates in laminar flow, and restriction of proinflammatory signaling predominates in the absence of laminar flow. Our studies provide novel insights into the mechanisms underlying endothelial homeostasis and reveal the importance of Rap1 signaling in cardiovascular disease.

Authentication of In Situ Measurements for Thoracic Aortic Aneurysms in Mice.

[Figure: see text].

Critical Appraisal on the Quality of Reporting on Safety and Efficacy of Transcarotid Artery Stenting With Flow Reversal.

Transcarotid revascularization is an alternative to transfemoral carotid artery stenting, designed to avoid aortic arch manipulation and concomitant periprocedural stroke. This article aims to perform a detailed analysis on the quality of the currently available evidence on safety and efficacy of transcarotid artery revascularization. Although current evidence is promising, independent randomized controlled studies comparing transcarotid artery revascularization with carotid endarterectomy in recently symptomatic patients are lacking and will be necessary to establish the true value of transcarotid artery revascularization in carotid artery revascularization.

A smaller heart-aorta-angle associates with ascending aortic dilatation and increases wall shear stress.

OBJECTIVES: The aim of this study was to evaluate whether the orientation of the heart, measured as an angle between the long axis of the heart and ascending aorta midline (heart-aorta-angle, HAA), associates with ascending aortic (AA) dilatation. Furthermore, the association between HAA and wall shear stress (WSS) was studied. METHODS: HAA was retrospectively measured in 1000 consecutive coronary artery computed tomographic angiography (CCTA) images in patients with low-to-moderate pretest probability for coronary artery disease (CAD). To evaluate the effects of HAA on AA flow, 4D flow MRI was performed for 28 patients with AA dilatation (> 40 mm) and WSS was analyzed. RESULTS: The mean age of patients undergoing CCTA was 52.9 ± 9.8 years; 66.5% were women. Their median HAA was 128.7° and interquartile range 123.3-134.1°. HAA was significantly smaller in patients with dilated AA (median 126.7° [121.3-130.8°]) compared with the patients with normal AA (median 129.5° [124.3-135.3°], p < 0.001). HAA was smaller in males (p < 0.001) and in patients with diabetes (p = 0.016), hypertension (p = 0.001), CAD (p = 0.003), hypercholesterolemia (p < 0.001), and bicuspid aortic valve (p = 0.025) than without these factors. In a subpopulation without any of these underlying diseases (n = 233), HAA was still significantly smaller in the patients with dilated AA (median 127.9° [124.3-134.3°]) compared with patients with normal AA (median 131.9° [127.6-136.9°], p = 0.013). In 4D flow MRI, a smaller HAA correlated with increased total WSS in the outer curvature of the proximal AA (r = - 0.510, p = 0.006). CONCLUSION: A smaller HAA associates with AA dilatation and affects the blood flow in the proximal AA. KEY POINTS: • A smaller angle between the long axis of the heart and ascending aorta midline associated with ascending aortic dilatation. • A smaller heart-aorta-angle correlated with increased total wall shear stress in the outer curvature of the proximal ascending aorta.

[Surgical treatment for type Stanford A aortic dissection with Kommerell's diverticulum].

Objective: To examine the outcomes of surgical treatment in patients of type Stanford A aortic dissection with Kommerell's diverticulum. Methods: From January 2009 to August 2017, patients of type Stanford A aortic dissection with Kommerell's diverticulum who underwent the Sun procedure were enrolled. Patient demographic, preoperative, intraoperative, early morbidity and mortality data were collected from medical and electronic patient records. Clinical follow-up data, including late morbidity and mortality, were obtained by telephone interview with the patient. Results: A total of 13 patients (11 males and 2 females; mean age 47 years) were included. The mean maximum diameter of Kommerell's diverticulum was (21.8±7.7) mm. The Kommerell's diverticulum was repaired by direct suture of the orifice in 3 patients, ligation of the aberrant right subclavian artery in 9 patients, and suture and ligation in 1 patient, respectively. No perioperative death occurred. One patient underwent a reexploration for bleeding. There were 2 late deaths: unknown reason in 1 patient and septic shock secondary to renal abscess in 1 patient. Reintervention was performed in one patient for a persistent type Ⅱ endoleak. Conclusions: The Sun procedure with femoral artery cannulation for cardiopulmonary bypass, unilateral carotid artery cannulation for selective cerebral perfusion and ligation of aberrant right subclavian artery on the right side of the trachea is an appropriate therapeutic strategy for patients of type Stanford A aortic dissection with Kommerell's diverticulum.

Clinical significance of acute and chronic ischaemic lesions in multiple cerebral vascular territories.

OBJECTIVES: To investigate the association between acute and chronic ischaemic lesions in a multiple territory lesion pattern (MTLP) detected by 3-Tesla MRI and stroke aetiology, specifically atrial fibrillation-associated stroke. METHODS: We analysed data from the 1000+ study - a prospective, observational 3-Tesla MRI cohort study of consecutively included acute stroke patients. Acute and chronic lesions were detected by DWI and fluid-attenuated inversion recovery, respectively. Observers blinded to clinical data allocated lesions to the right anterior, left anterior or posterior circulation. Lesion pattern was categorised as MTLPa/c when more than one territory was affected by either acute or chronic lesions or as MTLPa when more than one territory was affected by acute lesions alone. RESULTS: Of the 1,000 included patients, an MTLPa/c was found in 43% and MTLPa in 24%. Advanced age (aOR=1.21 per 10 years, 95% CI 1.06-1.39), atrial fibrillation (aOR=1.44, 95% CI 1.06-1.94), aortic arch atherosclerosis (aOR=2.52, 95% CI 1.10-5.77), malignant disease (aOR=1.99, 95% CI 1.25-3.16) and lower estimated glomerular filtration rate (eGFR) (aOR=0.90 per 10 ml, 95% CI 0.84-0.97) were associated with MTLPa/c. Only malignant disease (aOR=2.03, 95% CI 1.27-3.23) and lower eGFR (aOR=0.91 per 10 ml, 95% CI 0.85-0.97) were associated with MTLPa. CONCLUSIONS: An MRI-detected multiple territory lesion pattern of acute and chronic ischaemic lesions is frequent and more often present in older patients and patients with atrial fibrillation, aortic arch atherosclerosis, malignant disease and lower eGFR. Considering not only acute but also chronic ischaemic lesions may facilitate identifying atrial fibrillation-associated or aorto-embolic stroke. KEY POINTS: • Brain imaging with MRI may help to determine the aetiology of stroke. • Of 1,000 stroke patients undergoing 3-Tesla MRI, 43% had acute and chronic ischaemic lesions in multiple cerebral vascular territories. • Atrial fibrillation, aortic arch atherosclerosis and malignant disease were associated with a multiple territory lesion pattern.

Aortic stiffness in aortic stenosis assessed by cardiovascular MRI: a comparison between bicuspid and tricuspid valves.

OBJECTIVES: To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). METHODS: MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57 ± 0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. RESULTS: The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p < 0.001), but there were no significant differences in AA distensibility (p = 0.099), DA distensibility (p = 0.498) or PWV (p = 0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. CONCLUSIONS: In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. KEY POINTS: • Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). • We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. • Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I.

Thoracic Aorta Calcification and Noncardiovascular Disease-Related Mortality.

Objective- Arterial calcification is highly correlated with underlying atherosclerosis. Arterial calcification of the thoracic aorta is evident in many older individuals at high susceptibility to aging-related diseases and non-cardiovascular disease (CVD)-related mortality. In this study, we evaluated the association of thoracic aorta calcification (TAC) with non-CVD morbidity and mortality. Approach and Results- We analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study of subclinical atherosclerosis, in which participants underwent cardiac computed tomography at baseline and were followed longitudinally for incident CVD events and non-CVD events. Using modified proportional hazards models accounting for the competing risk of CVD death and controlling for demographics, CVD risk factors, coronary artery calcium, and CVD events, we evaluated whether TAC was independently associated with non-CVD morbidity and mortality. Among 6765 participants (mean age, 62 years), 704 non-CVD deaths occurred for a median follow-up of 12.2 years. Compared with no TAC, the highest tertile of TAC volume was associated with a higher risk of non-CVD mortality (hazard ratio, 1.56; 95% confidence interval, 1.23-1.97), as well as several non-CVD diagnoses, including hip fracture (2.14; 1.03-4.46), chronic obstructive pulmonary disease (2.06; 1.29-3.29), and pneumonia (1.79; 1.30-2.45), with magnitudes of association that were larger than for those of coronary artery calcium. Conclusions- TAC is associated with non-CVD morbidity and non-CVD mortality, potentially through a pathway that is unrelated to atherosclerosis. TAC may be a general marker of biological aging and an indicator of increased risk of non-CVD and death.

Experts' Results in Blunt Thoracic Aortic Injury are Reproducible in Lower Volume Tertiary Institutions. Early and Mid-term Results of an Observational Study.

OBJECTIVES: The aim of this study was to evaluate the early and mid-term clinical results, the device performance, and the mid-term re-intervention rates of patients suffering blunt thoracic aortic injury (BTAI) managed by a multidisciplinary team in a low-volume BTAI centre. METHODS: This was a retrospective observational study in a tertiary hospital setting. From December 2005 to March 2016, all patients over 18 years old admitted with BTAI were included in the study. No exclusion criteria were applied. The study data were collected and analysed retrospectively. Follow-up of survivors included computed tomography imaging 3 and 9 months post-procedure, then annually. RESULTS: Twenty-eight patients were included in the study. Their mean age was 42 ± 16 years and 89% were male. A contained aortic rupture was diagnosed in 20 patients, a Stanford type B dissection in six, and intramural haematoma in two patients. Multidisciplinary evaluations were performed and an intervention was indicated in 25 patients (89%), four of whom died before the intervention. Nineteen patients underwent thoracic endovascular aortic repair of the descending thoracic aorta and two patients underwent a frozen elephant trunk procedure. The procedures were performed 0.7 ± 1.2 days after injury. All procedures were successful. There were no device related complications. The post-operative 30 day mortality was 5%, with one patient dying on the day of operation from other vascular injuries. The 30 day mortality of all patients was 18%. The median mid-term follow-up period was 786 days. All 30 day survivors survived the follow-up period. The mid-term imaging showed stable results in 19 patients. Two patients required frozen elephant trunk procedures after 240 and 681 days and both procedures were successful. CONCLUSIONS: In a low volume centre, a multidisciplinary team using a standardised protocol with the endovascular first approach demonstrated excellent outcomes, similar to those of large centres. If the aortic trauma is adequately managed, the patient's outcome is closely related to the additional trauma.

[Experience of Sun's procedure for chronic type B dissection with aortic arch involvement].

Objective: To study the surgical treatment of chronic type B dissection with aortic arch involvement using Sun's procedure. Methods: Between February 2009 and December 2015, 29 patients [20 males, 9 females, with a mean age of (41±12) years, range 24-64 years] with type B dissection with aortic arch involvement underwent Sun's procedure. Sixteen patient had a history of hypertension. Marfan syndrome was observed in 9 cases, coronary artery disease in 3 cases, mitral regurgitation in 3 patients, cerebrovascular disease in one patient. Twenty-two patients suffered proximal aortic arch disease, 4 cases experienced history of aortic root procedure and 2 subjects had history of pregnancy. Four patients had aortic arch malformation. Results: One case suffered from massive cerebral infarction after surgery and died in another hospital. Concomitant procedures included mitral valve replacement in 3 cases, coronary artery bypass grafting in 3 patients, reconstruction of the right aberrant subclavian artery in one patient. Ventilator support exceeding 24 hours obseved in 2 patients. One of them recieved continuous renal replacement therapy and recovered before discharge. Spinal cord injury was obseved in one case, brain infarction in one patient and pericardial drainage in one case. Two patients required tracheotomy. During 12-94 (43±23) months' follow-up, thoracoabdominal aortic replacment was performed in 4 patients, thoracic endovascular aortic repair (TEVAR) in 2 subjects and repair of perivalvular leakage in one patient. Conclusions: Sun's procedure obtained satisfactory results in patients with chronic type B dissection with aortic arch involvement. Concomitant repair of proximal aortic arch lesions and distal type B dissection can be adopted using Sun's procedure.

[Progress and challenge of Stanford type A aortic dissection in China].

In recent 20 years, the rapid development of acute Stanford type A aortic dissection in China has been mainly due to three aspects: (1) the refined classification of aortic dissection based on Stanford classification, (2) right axillary artery canal and selective cerebral perfusion technology become basic cardiopulmonary bypass strategy for Stanford type A aortic dissection, and (3) total aortic arch replacement and descending aortic stent graft surgery (Sun's surgery) become the standard treatment of Stanford type A aortic dissection. However, there are still many problems in the diagnosis and treatment of aortic dissection in China, such as: (1) unstandardized, lack of comprehensive guidelines of aortic dissection, (2) immature, perioperative organ protection and intraoperative blood protection technology remains a big flaw, and (3) it takes a long time to get patient prepared for surgery. In conclusion, as to the issue of the management of acute Stanford type A aortic dissection, there will be a long way for Chinese doctors to go. Peers should pay more attention to this problem and take more efforts, so that the outcome of acute Stanford type A aortic dissection surgical patients can be improved.

[Progress of problems related to the reconstruction of aortic arch in acute type A aortic dissection].

Aortic arch reconstruction is one of the most challenging operations in aortic surgery. Anatomical abnormalities of the aortic arch, including bovine aortic arch, aberrant right subclavian artery, and single vertebral artery have direct impact on the choice of surgical procedures and methods of brain protection.The risk of aortic arch reconstruction and the difficulty of operation, it is possible to avoid the injury of patients by strictly grasping the indication of operation. Intraoperative arterial cannulation and brain protection strategies are directly related to the success of the operation. This article makes a brief review of the above problems in the reconstruction of the aortic arch, hoping to be helpful to the cardiovascular surgeon.