Incidence, Predictors, and Implications of Secondary Aortic Intervention Following Thoracic Endovascular Aortic Repair for Type B Dissection.

BACKGROUND: Secondary aortic intervention (SAI) following thoracic endovascular aortic repair (TEVAR) is not uncommon. However, a satisfactory management system has not been established for these patients. We aimed to report our single-center experience with SAI after prior TEVAR for type B aortic dissection (TBAD). METHODS: From January 2010 to May 2017, 860 eligible patients with TBAD underwent TEVAR. One hundred seven (12.4%) patients required SAI, either endovascularly (n=76) or surgically (n=31). The main indications for SAI were entry flow (n=58 [54.2%]), aneurysm expansion of the proximal or remote aorta (n=26 [24.3%]), retrograde type A aortic dissection (n=11 [10.3%]), distal stent-graft-induced new entry tear (n=6 [5.6%]), and stent migration (n=4 [3.7%]). The Kaplan-Meier curves were generated to determine the degree of freedom from SAI and the prognosis. Cox proportional hazards were used to screen for risk factors for SAI and poor prognosis. RESULTS: The overall 30-day mortality rate after SAI was 4.7% (n=5): endovascular (n=2 [2.6%]) vs open surgery (n=3 [9.7%]; p=0.145). The cumulative survival rates with or without SAI were 86.3%±3.6% vs 95.7%±0.8% at 3 years and 82.0%±4.2% vs 92.2%±1.1% at 5 years, respectively (log-rank p<0.001). Although no significant difference in survival was observed, the incidence of SAI was significantly greater in patients who underwent TEVAR during the chronic phase (acute [11.6%] vs subacute [9.6%] vs chronic [27.8]; p<0.001). Multivariate regression analysis revealed that prior TEVAR in the chronic phase (hazard ratio [HR]=1.73, 95% confidence interval [CI]=1.03-2.90; p=0.039), maximum aortic diameter (HR=1.05, 95% CI=1.04-1.07; p<0.001), and arch involvement (HR=1.48, 95% CI=1.01-2.18; p=0.048) were predictors of the incidence of SAI. In addition, the maximum aortic diameter was demonstrated to be the only risk factor for prognosis after adjusting for confounding factors. CONCLUSIONS: Thoracic endovascular aortic repair for chronic TBAD patients should be reconsidered. Open surgery is preferable for those with proximal progression, whereas endovascular treatment is more suitable for distal lesions. Close surveillance and timely reintervention after TEVAR, whether via endovascular techniques or open surgery, are necessary to prevent devastating complications. CLINICAL IMPACT: The management of patients with type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR) is challenging. We summarized our single-center experience regarding secondary aortic intervention after TEVAR for TBAD. We found that TEVAR for chronic TBAD patients should be carefully evaulated, and open surgery is recommended for those with proximal progession, while endovascular treatment is more preferable for distal lesions.

Systemic immune-inflammation index predicts the clinical outcomes in patients with acute uncomplicated type-B aortic dissection undergoing optimal medical therapy.

BACKGROUND: Optimal medical therapy (OMT) for uncomplicated type B aortic dissection (uTBAD) provides excellent short-term outcomes during follow up; however, its long-term therapeutic effectiveness is unsatisfactory. This study evaluated the predictive value of systemic immune-inflammation index (SII) for adverse events among patients with acute uTBAD undergoing OMT. METHODS: We performed a retrospective analysis of a prospectively maintained database between 2013 and 2020. The primary end point in this study was composite outcomes including aortic intervention, all-cause mortality, retrograde type A aortic dissection (rTAAD) and aortic diameter growth > 5 mm. The patients were divided into high and low SII groups according to the optimal cut-off value of SII as determined using the receiver operating characteristic curve. Cox proportional hazards models were constructed to estimate the hazards ratios and identify the predictors of composite outcomes. RESULTS: A total of 124 patients with acute uTBAD who underwent OMT were enrolled. One patient died during hospitalisation. At the end of a mean follow-up duration of 51 ± 23 months, 53 (43.1%) patients experienced composite outcomes, 15 patients (12.2%) died, 31 (25.2%) underwent aortic intervention, 21 (17.1%) exhibited diameter growth of > 5 mm, and 2 developed rTAAD. The patients were divided into low SII group (n = 78, 62.9%) and high SII group (n = 46, 37.1%) as per the optimal cut-off SII value of 1449. The incidence of composite outcomes in high SII group was significantly higher than that in low SII (28 [60.9%] vs. 26[33.3%], p < 0.01). Patients with high SII demonstrated significantly higher mortality rate than those with a low SII (11 [23.9%] vs. 5 [6.4%], respectively; p < 0.01). In addition, the high SII group had significantly higher rate of aortic-related reinterventions than the low SII group (16 [34.8%] vs. 15 [19.2%], p = 0.03). Multivariable Cox analyses showed that a high SII score was independently associated with composite outcomes rate (hazard ratio, 2.15; 95% confidence interval, 1.22-3.78; p < 0.01). CONCLUSIONS: The long-term therapeutic effectiveness of OMT alone in patients with acute uTBAD is unsatisfactory. An SII > 1449 at the time of diagnosis is an independent predictor of OMT failure.

Optimal medical treatment versus endovascular aortic repair in uncomplicated isolated abdominal aortic dissection.

OBJECTIVE: To report the results of optimal medical treatment (OMT) and endovascular aortic repair (EVAR) in patients with uncomplicated isolated abdominal aortic dissection (IAAD). METHODS: A retrospective review of 96 consecutive patients with uncomplicated IAAD (uIAAD) managed at a single tertiary vascular unit between January 2011 and July 2021 was conducted. Standard methods for univariate and survival analyses were used. The primary outcomes were all-cause mortality. Secondary end points included uIAAD progression, interventional complications, and follow-up aortic intervention. RESULTS: Initially, 53.1% of patients (51/96) were managed with OMT. No in-hospital deaths occurred. During follow-up, three patients died, and three and two patients who were initially managed with OMT subsequently required endovascular treatment and surgical management, respectively. Initially, 46.9% of patients (45/96) underwent EVAR. One patient died during hospital admission; nine patients had an endoleak after operation and one needed reintervention. Furthermore, during follow-up, five patients died; four patients needed reoperation, one surgery and three endovascular treatments. The overall long-term mortality was 8.4%, and follow-up aortic intervention rate was 9.5% (median follow-up, 54 months; interquartile range, 33-81 months) with no significant difference between groups. Of note, 12 patients (12.6%) suffered uIAAD progression, which was higher in the OMT group than EVAR group (10 [19.6%] vs 2 [4.5%]; P = .03). CONCLUSIONS: uIAAD may be managed safely by OMT with regular surveillance, despite the risk of disease progression. Compared with OMT, EVAR could significantly prevent uIAAD progression. For anatomically suitable patients with uIAAD progression and who are unresponsive to OMT, pre-emptive EVAR is a safe and feasible option.

Eosinophils Protect Mice From Angiotensin-II Perfusion-Induced Abdominal Aortic Aneurysm.

RATIONALE: Blood eosinophil count and ECP (eosinophil cationic protein) associate with human cardiovascular diseases. Yet, whether eosinophils play a role in cardiovascular disease remains untested. The current study detected eosinophil accumulation in human and murine abdominal aortic aneurysm (AAA) lesions, suggesting eosinophil participation in this aortic disease. OBJECTIVE: To test whether and how eosinophils affect AAA growth. METHODS AND RESULTS: Population-based randomized clinically controlled screening trials revealed higher blood eosinophil count in 579 male patients with AAA than in 5063 non-AAA control (0.236±0.182 versus 0.211±0.154, 109/L, P<0.001). Univariate (odds ratio, 1.381, P<0.001) and multivariate (odds ratio, 1.237, P=0.031) logistic regression analyses indicated that increased blood eosinophil count in patients with AAA served as an independent risk factor of human AAA. Immunostaining and immunoblot analyses detected eosinophil accumulation and eosinophil cationic protein expression in human and murine AAA lesions. Results showed that eosinophil deficiency exacerbated AAA growth with increased lesion inflammatory cell contents, matrix-degrading protease activity, angiogenesis, cell proliferation and apoptosis, and smooth muscle cell loss using angiotensin-II perfusion-induced AAA in Apoe-/- and eosinophil-deficient Apoe-/-ΔdblGATA mice. Eosinophil deficiency increased lesion chemokine expression, muted lesion expression of IL (interleukin) 4 and eosinophil-associated-ribonuclease-1 (mEar1 [mouse EOS-associated-ribonuclease-1], human ECP homolog), and slanted M1 macrophage polarization. In cultured macrophages and monocytes, eosinophil-derived IL4 and mEar1 polarized M2 macrophages, suppressed CD11b+Ly6Chi monocytes, and increased CD11b+Ly6Clo monocytes. mEar1 treatment or adoptive transfer of eosinophil from wild-type and Il13-/- mice, but not eosinophil from Il4-/- mice, blocked AAA growth in Apoe-/-ΔdblGATA mice. Immunofluorescent staining and immunoblot analyses demonstrated a role for eosinophil IL4 and mEar1 in blocking NF-κB (nuclear factor-κB) activation in macrophages, smooth muscle cells, and endothelial cells. CONCLUSIONS: Eosinophils play a protective role in AAA by releasing IL4 and cationic proteins such as mEar1 to regulate macrophage and monocyte polarization and to block NF-κB activation in aortic inflammatory and vascular cells.

Feasibility and safety of Stanford A aortic dissection complete endovascular repair system in a porcine model.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a catastrophic disease with high morbidity and mortality. Although open surgery is still the gold standard for the treatment of ATAAD, some patients, with advanced age and multiple comorbidities, can only receive medical management alone. Nowadays, thoracic aortic endovascular repair (TEVAR) provides a potential treatment option for the patient with ATAAD, but traditional stent grafts (SGs), which are not designed for the ATAAD, are inapplicable to the unique anatomy of the aortic arch. Therefore, we innovatively created the BRIDGE system (Chuangxin Medical, Shenzhen, China), a complete endovascular reconstruction system designed to treat ATAAD. This study aimed to evaluate the feasibility and safety of the novel Stanford A aortic dissection complete endovascular reconstruction system in a porcine model. METHOD: The BRIDGE system consists of the type A stent system and the type C stent system. Between November 2020 and March 2021, three white swine were utilized in the study. The BRIDGE system was deployed via the transcatheter approach under angiographic guidance. The swine(n = 3) treated with our system were evaluated using angiography before sacrifice 1-month after implantation, which was followed by gross specimen evaluation and histological examination of harvested tissues. RESULT: The acute procedure success rate was 100% (3/3). The immediate post-procedural angiography showed that both type A SGs and type C SGs were deployed in satisfactory locations, with patency of the supra-aortic trunk and no endoleak. The cumulative mortality of 30-day was 0% without any adverse events. No device migration or leakage was observed angiographically, before sacrifice. The gross observation confirmed a type A SG covered part of the entry of anonyma. Favorable endothelialization, no thrombogenesis, and slight inflammatory infiltration of the tissues around the device were confirmed by microscopic examinations in all pigs. CONCLUSION: It was feasible and secure to use Stanford A aortic dissection complete endovascular reconstruction system to implement a transcatheter endovascular repair in a porcine model. With this novel system, treating acute type A aortic dissection may be more efficient and secure in human.

Association between the non-HDL-cholesterol to HDL- cholesterol ratio and abdominal aortic aneurysm from a Chinese screening program.

BACKGROUND: Abdominal aortic aneurysms (AAAs) can result in high mortality upon rupture but are usually undiagnosed because of the absence of symptoms in the early stage. Ultrasound screening is regarded as an impactful way to prevent the AAA-related death but cannot be performed efficiently; therefore, a target population, especially in Asia, for this procedure is lacking. Additionally, although dyslipidaemia and atherosclerosis are associated with AAA. However, it remains undetermined whether the non-high-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol ratio (NHHR) is associated with AAA. Therefore, this study was aimed at examining whether NHHR is associated with AAA. METHOD: A total of 9559 participants who underwent AAA screening at Guangdong Provincial People's Hospital and through screening in two communities in Dongguan, from June 2019 to June 2021 joined in this screening program. The diagnosis of AAA was confirmed by the ultrasound examination of the abdominal aorta rather than any known or suspected AAA. Clinical and laboratory data of participants were collected. The participants were separated into a normal group and an AAA group according to the abdominal aortic status. To eliminate confounding factors, a propensity score matching (PSM) approach was utilized. The independent relationship between NHHR and AAA was assessed through the utilization of multivariable logistic regression analysis. In addition, internal consistency was evaluated through subgroup analysis, which controlled for significant risk factors. RESULTS: Of all the participants, 219 (2.29%) participants were diagnosed with AAA. A significant elevation in NHHR was identified in the AAA group when contrasted with that in the normal group (P < 0.001). As demonstrated by the results of the multivariable logistic regression analysis, AAA was independently associated with NHHR before (odds ratio [OR], 1.440, P < 0.001) and after PSM (OR, 1.515, P < 0.001). Significant extension was observed in the areas under the receiver operating characteristic curves (AUROCs) of NHHR compared to those of single lipid parameters before and after PSM. An accordant association between NHHR and AAA in different subgroups was demonstrated by subgroup analysis. CONCLUSION: In the Chinese population, there is an independent association between NHHR and AAA. NHHR might be propitious to distinguish individuals with high risk of AAA.

The etiology, clinical features, and treatment options of hemifacial microsomia.

The second most frequent craniomaxillofacial congenital deformity is hemifacial microsomia (HFM). Patients often accompany short mandible, ear dysplasia, facial nerve, and soft tissue dysplasia. The etiology of HFM is not fully understood. To organize the possible up-to-date information on the etiology, craniofacial phenotypes, and therapeutic alternatives in order to fully comprehend the HFM. Reviewing the potential causes, exploring the clinical features of HFM and summarizing the available treatment options. Vascular malformation, Meckel's cartilage abnormalities, and cranial neural crest cells (CNCCs) abnormalities are three potential etiology hypotheses. The commonly used clinical classification for HFM is OMENS, OMENS-plus, and SAT. Other craniofacial anomalies, like dental defects, and zygomatic deformities, are still not precisely documented in the classification. Patients with moderate phenotypes may not need any treatment from infancy through adulthood. However, patients with severe HFM require to undergo multiple surgeries to address facial asymmetries, such as mandibular distraction osteogenesis (MDO), autologous costochondral rib graft (CCG), orthodontic and orthognathic treatment, and facial soft tissue reconstruction. It is anticipated that etiology research will examine the pathogenic mechanism of HFM. A precise treatment for HFM may be possible with thoroughly documented phenotypes and a pathogenic diagnosis.

IgE Contributes to Atherosclerosis and Obesity by Affecting Macrophage Polarization, Macrophage Protein Network, and Foam Cell Formation.

OBJECTIVE: By binding to its high-affinity receptor FcεR1, IgE activates mast cells, macrophages, and other inflammatory and vascular cells. Recent studies support an essential role of IgE in cardiometabolic diseases. Plasma IgE level is an independent predictor of human coronary heart disease. Yet, a direct role of IgE and its mechanisms in cardiometabolic diseases remain incompletely understood. Approach and Results: Using atherosclerosis prone Apoe-/- mice and IgE-deficient Ige-/- mice, we demonstrated that IgE deficiency reduced atherosclerosis lesion burden, lesion lipid deposition, smooth muscle cell and endothelial cell contents, chemokine MCP (monocyte chemoattractant protein)-1 expression and macrophage accumulation. IgE deficiency also reduced bodyweight gain and increased glucose and insulin sensitivities with significantly reduced plasma cholesterol, triglyceride, insulin, and inflammatory cytokines and chemokines, including IL (interleukin)-6, IFN (interferon)-γ, and MCP-1. From atherosclerotic lesions and peritoneal macrophages from Apoe-/-Ige-/- mice that consumed an atherogenic diet, we detected reduced expression of M1 macrophage markers (CD68, MCP-1, TNF [tumor necrosis factor]-α, IL-6, and iNOS [inducible nitric oxide synthase]) but increased expression of M2 macrophage markers (Arg [arginase]-1 and IL-10) and macrophage-sterol-responsive-network molecules (complement C3, lipoprotein lipase, LDLR [low-density lipoprotein receptor]-related protein 1, and TFR [transferrin]) that suppress macrophage foam cell formation. These IgE activities can be reproduced in bone marrow-derived macrophages from wild-type mice, but muted in cells from FcεR1-deficient mice, or blocked by anti-IgE antibody or complement C3 deficiency. CONCLUSIONS: IgE deficiency protects mice from diet-induced atherosclerosis, obesity, glucose tolerance, and insulin resistance by regulating macrophage polarization, macrophage-sterol-responsive-network gene expression, and foam cell formation.

Adipocytes promote interleukin-18 binding to its receptors during abdominal aortic aneurysm formation in mice.

AIMS: Obesity is a risk factor of abdominal aortic aneurysm (AAA). Inflammatory cytokine interleukin-18 (IL18) has two receptors: IL18 receptor (IL18r) and Na-Cl co-transporter (NCC). In human and mouse AAA lesions, IL18 colocalizes to its receptors at regions rich in adipocytes, suggesting a role of adipocytes in promoting IL18 actions in AAA development. METHODS AND RESULTS: We localized both IL18r and NCC in human and mouse AAA lesions. Murine AAA development required both receptors. In mouse AAA lesions, IL18 binding to these receptors increased at regions enriched in adipocytes or adjacent to perivascular adipose tissue. 3T3-L1 adipocytes enhanced IL18 binding to macrophages, aortic smooth muscle cells (SMCs), and endothelial cells by inducing the expression of both IL18 receptors on these cells. Adipocytes also enhanced IL18r and IL18 expression from T cells and macrophages, AAA-pertinent protease expression from macrophages, and SMC apoptosis. Perivascular implantation of adipose tissue from either diet-induced obese mice or lean mice but not that from leptin-deficient ob/ob mice exacerbated AAA development in recipient mice. Further experiments established an essential role of adipocyte leptin and fatty acid-binding protein 4 (FABP4) in promoting IL18 binding to macrophages and possibly other inflammatory and vascular cells by inducing their expression of IL18, IL18r, and NCC. CONCLUSION: Interleukin-18 uses both IL18r and NCC to promote AAA formation. Lesion adipocyte and perivascular adipose tissue contribute to AAA pathogenesis by releasing leptin and FABP4 that induce IL18, IL18r, and NCC expression and promote IL18 actions.

Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice.

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe-/- ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe-/- mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe-/- mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.

Outcomes of Evolut R Versus CoreValve After Transcatheter Aortic Valve Implantation: A Meta-Analysis.

BACKGROUND: Superiority of the new-generation, self-expanding Evolut R compared with the first-generation CoreValve on outcomes after transcatheter aortic valve implantation (TAVI) is unclear. This meta-analysis sought to investigate the outcomes of Evolut R vs CoreValve after TAVI. METHODS: A systematic review of studies comparing outcomes of Evolut R and CoreValve after TAVI was performed through PubMed, EMBASE and Cochrane Library. Crude risk ratios (RRs) were calculated with 95% confidence intervals using a random effects model. Outcomes of interest were mortality, myocardial infarction (MI), stroke or transient ischaemic attack (TIA), severe bleeding, acute kidney injury (AKI), major vascular complications (MVC), permanent pacemaker implantation (PPI), moderate or severe paravalvular regurgitation (PVR), and device failure. RESULTS: Six studies involving 11,530 patients (4,597 receiving Evolut R and 6,933 receiving CoreValve) were included. There was no significant difference in 30-day all-cause mortality between Evolut R and CoreValve (3.4% vs 5.0%, p = 0.10). The incidence of MI (0.2% vs 0.5%, p = 0.02), AKI (6.0% vs 9.2%, p = 0.001), moderate or severe PVR (6.4% vs 8.0%, p = 0.04), and device failure (3.5% vs 5.2%, p = 0.04) were significantly lower in Evolut R than CoreValve. There were trends toward less severe bleeding (7.2% vs 8.8%, p = 0.05) and PPI (18.6% vs 20.8%, p = 0.05) in Evolut R. The rates of stroke or TIA and MVC were similar between the two prostheses. CONCLUSIONS: Compared with CoreValve, Evolut R did not reduce 30-day all-cause mortality, but significantly improved periprocedural complications after TAVI.

Management of type B aortic dissection with an isolated left vertebral artery.

OBJECTIVE: The objective of this study was to report our single-center experience of thoracic endovascular aortic repair (TEVAR) and concomitant procedures in patients with type B aortic dissection (TBAD) with an isolated left vertebral artery (ILVA) and the early to midterm outcomes in these patients. METHODS: Between March 2011 and June 2018, there were 31 patients (27 men; median age, 55 years; range, 31-66 years) with TBAD and an ILVA who received TEVAR and concomitant procedures in our center. Demographics, coexisting medical conditions, imaging features, operation details, and follow-up outcomes in these patients were retrospectively collected and analyzed. RESULTS: All patients received aortic stent grafts; nine patients also received chimney stents, and 10 patients received aortic arch bypasses. The technical success rate was 96.8% (30/31), with only one patient (3.2%) showing immediate type IA endoleak. One patient experienced transient neurologic deficit, and a puncture-related femoral artery pseudoaneurysm was observed in one patient; both recovered completely before their hospital discharge. There was no death in the early term. The median duration of follow-up was 33 months (range, 2-90 months). Reintervention for a type II endoleak by using coils to seal the origin of the left subclavian artery was performed in one (3.1%) case 72 months postoperatively. One (3.2%) death occurred 42 months after operation as a result of rectal cancer. No neurologic deficits, chimney stent occlusions, or bypass occlusions were observed during the follow-up period. CONCLUSIONS: Our limited experience reveals that TEVAR and concomitant procedures are relatively safe and viable for treatment of TBAD with an ILVA. Further studies with larger samples of patients and longer follow-ups are needed to confirm these findings.

Outcomes of Chimney Technique for Preservation of the Left Subclavian Artery in Type B Aortic Dissection.

OBJECTIVE: To report outcomes of the chimney technique for preservation of the left subclavian artery (LSA) in patients with type B aortic dissection (TBAD). METHODS: A retrospective analysis was performed of a prospectively maintained database from August 2012 to October 2017. Primary endpoints were 30 day and overall mortality. Secondary endpoints were technical success, type Ia endoleak, chimney stent occlusion, aortic rupture, stroke, spinal cord ischaemia, and re-intervention rate. RESULTS: A total of 159 patients (mean age 54 ± 11 years; 141 men) with TBAD were treated using the chimney technique for LSA revascularisation. Acute, subacute, and chronic TBAD accounted for 64%, 28%, and 8% of cases, respectively. One hundred and six cases (67%) were complicated TBAD. One hundred and fifty-six patients (98%) were treated electively, while three (2%) were treated urgently because of intestinal or lower extremity ischaemia. The 30 day mortality and morbidity rates were 2% (3/159) and 4% (7/159), respectively. The technical success rate was 81% (129/159) and immediate type Ia endoleak occurred in 30 (19%) patients. Three major strokes, two spinal cord ischaemia and one aortic rupture, occurred early on. During a mean follow up of 23 ± 16 months (range 1-65 months), three more patients died: from aortic rupture, cerebral haemorrhage, and rectal cancer, respectively. Chimney stent occlusions were observed in four patients and all these chimney stents were self expanding. During follow up, two major strokes, one late type Ia endoleak and one re-intervention, occurred. According to the Kaplan-Meier curve, the estimated one and three year survival rates were 98.1 ± 1.1% and 94.4 ± 2.4%, respectively. CONCLUSION: Short and mid-term outcomes in the present study demonstrate that the chimney technique is safe and feasible for preservation of the LSA in patients with TBAD, but the durability of chimney stent needs to be evaluated carefully and immediate type Ia endoleak is a concern.

Upregulation of miR-146a-5p is associated with increased proliferation and migration of vascular smooth muscle cells in aortic dissection.

BACKGROUND: This study aimed to investigate whether miR-146a-5p was involved in the pathogenesis of thoracic aortic dissection (AD) via regulating the biological function of vascular smooth muscle cells (VSMCs). METHODS: Circulating miR-146a-5p level was measured by quantitative polymerase chain reaction (qPCR) in AD patients and healthy controls. Human dissected aortic samples were obtained from patients with thoracic AD Stanford type A undergoing surgical repair, and normal control samples were from organ donors who died from nonvascular diseases. The expression level of miR-146a-5p was detected using qPCR in each sample. The expression of SMAD4, which is involved in the TGF-ß pathway and indicated as the target gene of miR-146a-5p, was measured by qPCR and Western blot analysis at the mRNA level and protein level, respectively. Subsequently, VSMCs were transfected with miR-146a-5p mimics or inhibitors in vitro. VSMC proliferation and migration were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay, respectively. Flow cytometry was used to identify apoptosis. The expression of SMAD4 in VSMCs was determined using qPCR and Western blot analysis. RESULTS: Plasma level of miR-146a-5p is significantly higher in the AD group as compared with the control group. The expression of miR-146a-5p was significantly upregulated in dissected aorta compared with controls (P < 0.05). The overexpression of miR-146a-5p significantly induced VSMC proliferation and migration in vitro. CONCLUSIONS: The expression of SMAD4 was modulated by miR-146a-5p. miR-146a-5p induced VSMC proliferation and migration through targeting SMAD4 and hence might be potentially involved in the development of AD.

Outcomes of hybrid procedure for type B aortic dissection with an aberrant right subclavian artery.

OBJECTIVE: To report our single-center experience of the hybrid procedure for type B aortic dissection (TBAD) with an aberrant right subclavian artery (ARSA) and the early to midterm outcomes in these patients. METHODS: From December 2011 to February 2016, 16 patients (12 males; median age, 51 years; range, 40-66 years) underwent thoracic endovascular aortic repair and extraanatomic bypass hybrid procedure for TBAD with an ARSA in our center. Demographics, coexisting medical conditions, imaging features, operation details, and follow-up outcomes of these patients were collected retrospectively and analyzed. RESULTS: Duration from onset to hybrid procedure ranged from 5 to 57 days, with a median duration of 17 days. The median duration of stay in the intensive care unit and duration of in-hospital stay was 126 hours (range, 14-450 hours) and 21 days (range, 11-31 days), respectively. The overall technique success rate was 100%. No perioperative death, major stroke, or spinal cord ischemia was registered. Immediate type Ia endoleak was detected in three patients (18.8%) and immediate type II endoleak was detected in one patient (6.3%). One access-related complication occurred, which was a femoral artery pseudoaneurysm requiring compression bandage. Brachial plexus injury was observed in two patients (12.5%) with weakness of the upper extremity. The median follow-up was 33 months (range, 11-59 months). During follow-up, a retrograde type A aortic dissection was found in one patient (6.3%) 3 months after procedure. The occlusion of left common carotid artery to left subclavian artery bypasses were confirmed by computed tomography angiography in two patients (12.5%). They were left untreated for no symptoms. Reintervention was required in one patient (6.3%) for persistent type II endoleak by using Amplatzer plugs to seal the origin of the ARSA 20 months after the operation. There was no recorded death or stroke during the study period. CONCLUSIONS: Our limited experience demonstrates that a hybrid procedure is a viable and relatively safe treatment strategy for patients with TBAD and an ARSA. A larger series of cases with a longer follow-up is needed to substantiate these results.

Outcomes and morphologic changes of immediate type Ia endoleak following endovascular repair of acute type B aortic dissection.

BACKGROUND: The clinical significance of immediate type Ia endoleaks after thoracic endovascular aortic repair (TEVAR) for aneurysms has been described in detail. However, this phenomenon is still controversial in TEVAR patients treated for acute type B aortic dissection. METHODS: A single-institution study was conducted in 81 prospectively evaluated patients treated between January 2012 and June 2012 for acute type B aortic dissection. Preoperative and postoperative computed tomography angiography (CTA) images were analyzed using 3-dimensional reconstruction to measure the areas and indices of the true lumen, false lumen, and total aorta in the proximal, middle, and distal descending thoracic aorta. Data were analyzed and compared between the 2 groups of patients, with and without immediate type Ia endoleaks. RESULTS: The average follow-up period was 12 months (range 10-13 months) after the procedure. TEVAR was successfully performed in all patients (mean age 53 years; 86% men). Thirty-six of the 81 patients were diagnosed with complicated type B dissection, including persistent pain (19/36, 52.7%), refractory hypertension (4/36, 11.1%), and end-organ ischemia (13/36, 36.1%). Of all the patients, 37 (45.7%) were diagnosed with immediate type Ia endoleaks. The differences between the 30-day and 1-year all-cause mortality rates between the 2 groups were nonsignificant (13.5% vs. 2.2%, P = 0.08; 16.2% vs. 4.5%, P = 0.13). No stroke or paraplegia occurred during the follow-up. Reintervention was performed in 2 patients for delayed type I endoleaks in the group without immediate type Ia endoleaks. Pre- and postoperative CTA images were available for analysis in 54 patients. Among them, 24 patients had type Ia endoleaks. Patients with immediate type Ia endoleaks had a significantly larger preoperative distal false lumen area (498 ± 274 vs. 284 ± 213 mm(2), P = 0.02) and a larger distal aortic area (759 ± 275 vs. 624 ± 185 mm(2), P = 0.03). The 1-year follow-up CTA demonstrated significantly smaller true lumen indices and larger false lumen areas and false lumen indices in the proximal, middle, and distal sections in patients with immediate type Ia endoleaks. Differences in the postoperative morphological changes of the whole descending thoracic aorta were significant between the 2 groups, with the maximum area and the proximal, middle, and distal regions involved. The occurrence of endoleaks and the rates of postoperative false lumen thrombosis throughout the length of stent grafts were not significant at 1-year follow-up. CONCLUSIONS: The majority of immediate type Ia endoleaks following TEVAR in acute type B aortic dissections could seal spontaneously, without additional procedures needed. However, the appearance of such complications could be a risk factor of poorer aortic remodeling. Careful surveillance is recommended more frequently in patients with immediate type Ia endoleaks.

CIRC_0033530 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY MODEL OF HUMAN LUNG FIBROBLASTS BY MIR-1184/TLR4 AXIS.

ABSTRACT: Background: Circular RNAs have been reported to be involved in regulating the progression of sepsis and sepsis-associated damage. Herein, this work investigated whether circ_0033530 had roles in the process of septic acute lung injury (sepsis-ALI) and its associated mechanism. Methods: Lipopolysaccharide (LPS)-stimulated human lung fibroblasts MRC-5 were used to mimic the cell model of sepsis-ALI in vitro . Levels of genes and proteins were detected by quantitative real-time polymerase chain reaction and Western blotting. Functional experiments were conducted using 5-ethynyl-2'-deoxyuridine assay, Cell Counting Kit-8 assay, flow cytometry, and enzyme-linked immunosorbent assay. The interaction between miR-1184 and circ_0033530 or toll-like receptor 4 (TLR4) was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0033530 expression was lower in sepsis patients and LPS-induced fibroblasts than those in healthy control and untreated cells. Functionally, knockdown of circ_0033530 protected fibroblasts against LPS-induced proliferation arrest, apoptosis, and inflammatory response. Mechanistically, circ_0033530 acted as a sponge for miR-1184, and TLR4 RNA was targeted by miR-1184, indicating the circ_0033530/miR-1184/TLR4 axis. Further rescue experiments showed that circ_0033530 silencing-mediated growth inhibition and inflammation on fibroblasts were attenuated by miR-1184 downregulation or TLR4 upregulation. Conclusion: Circ_0033530 knockdown alleviated LPS-induced proliferation arrest, apoptosis, and inflammation in lung fibroblasts by miR-1184/TLR4 axis, and provided molecular theoretical basis for circ_0033530 on the pathogenesis of sepsis-ALI.

Positive additive interaction effects of age, sex, obesity, and metabolic syndrome on left ventricular dysfunction.

OBJECTIVE: This study aims to explore the association between metabolic syndrome (MetS) and left ventricular diastolic dysfunction (LVDD) and systolic dysfunction (LVSD), defined by impaired global longitudinal strain (GLS), and assess additive and multiplicative interactions among age, sex, obesity, and MetS regarding LVDD and LVSD. METHODS: We prospectively recruited 5503 participants from the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project with complete echocardiography exam. Multivariable logistic models were used to calculate adjusted odds ratios to evaluate both additive and multiplicative interactions. RESULTS: The mean age was 56.59 years; 59.4% were women, 46.7% had MetS, 26.6% had left ventricular hypertrophy, 46.3% had LVDD, and 12.50% had impaired GLS. Compared to the non-MetS, the odds ratio (OR) of LVDD and impaired GLS in MetS were 1.40 (1.20-1.64) and 1.26 (1.03-1.54), respectively. For LVDD, relative excess risk due to additive interaction (RERI) for women and MetS, elderly and MetS, obesity and MetS were 0.76 (0.02-1.50), 35.65 (17.51-53.79), and 2.14 (0.66-3.62), respectively, thus suggesting additive interactions. For impaired GLS, RERI for obesity and MetS was 3.37 (0.50-6.24), thus suggesting additive interactions. CONCLUSIONS: The MetS is independently associated with LVDD and impaired GLS. From the public health implications, prevention of MetS in women, elderly, and obese individuals might result in a greater reduction of LVDD and LVSD risk in cardiovascular high-risk population.

Efficacy and safety of sacubitril/valsartan in chronic Type B aortic dissection combined with mild hypertension.

BACKGROUND: Optimal antihypertensive medication for chronic Type B aortic dissection remains undecided. This study compared the efficacy and safety of sacubitril/valsartan with valsartan to determine suitable antihypertensive drug combinations. METHODS: In this single-center, open-label, randomized, controlled trial, patients with chronic Stanford type B aortic dissection and mild hypertension were randomized to receive sacubitril/valsartan 100/200 mg or valsartan 80/160 mg. The primary endpoint was the reduction in mean sitting systolic blood pressure (msSBP) at Week 8 in patients with sacubitril/valsartan versus valsartan. Key secondary endpoints included changes in 1) mean sitting diastolic blood pressure (msDBP); 2) pulse pressure; and 3) mean ambulatory blood pressure for 24-hour, daytime, and nighttime. Safety assessments included adverse events and serious adverse events. This trial was registered with the Chinese Clinical Trial Registry, identifier: ChiCTR2300073399. RESULTS: A total of 315 patients completed the study. Sacubitril/valsartan provided a significantly greater reduction in msSBP than valsartan at Week 8 (between-treatment difference: -5.1 mm Hg [95% confidence interval (CI) -5.8 to -4.5], P < 0.001). Reductions in msSBP, msDBP, and pulse pressure as well as the mean ambulatory blood pressure for 24-hour, daytime, and nighttime, were significantly greater in sacubitril/valsartan compared with valsartan (all P < 0.001). No excessive episodes of adverse events occurred in the sacubitril/valsartan group. CONCLUSION: Sacubitril/valsartan and valsartan reduced BP compared with baseline values. However, sacubitril/valsartan improved blood pressure control to a greater extent than valsartan. It may offer a new treatment option for patients with mild hypertension and chronic Type B aortic dissection.