Recent advances in targeted therapy for inflammatory vascular diseases.

Vascular diseases constitute a significant contributor to worldwide mortality rates, placing a substantial strain on healthcare systems and socio-economic aspects. They are closely associated with inflammatory responses, as sustained inflammation could impact endothelial function, the release of inflammatory mediators, and platelet activation, thus accelerating the progression of vascular diseases. Consequently, directing therapeutic efforts towards mitigating inflammation represents a crucial approach in the management of vascular diseases. Traditional anti-inflammatory medications may have extensive effects on multiple tissues and organs when absorbed through the bloodstream. Conversely, treatments targeting inflammatory vascular diseases, such as monoclonal antibodies, drug-eluting stents, and nano-drugs, can achieve more precise effects, including precise intervention, minimal non-specific effects, and prolonged efficacy. In addition, personalized therapy is an important development trend in targeted therapy for inflammatory vascular diseases. Leveraging advanced simulation algorithms and clinical trial data, treatment strategies are gradually being personalized based on patients' genetic, biomarker, and clinical profiles. It is expected that the application of precision medicine in the field of vascular diseases will have a broader future. In conclusion, targeting therapies offer enhanced safety and efficacy compared to conventional medications; investigating novel targeting therapies and promoting clinical transformation may be a promising direction in improving the prognosis of patients with inflammatory vascular diseases. This article reviews the pathogenesis of inflammatory vascular diseases and presents a comprehensive overview of the potential for targeted therapies in managing this condition.

Triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio predict the prognosis in patients with type B aortic dissection receiving thoracic endovascular aortic repair.

Background: The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio are both reliable surrogate indicator of insulin resistance and have been shown to be valuable in predicting various cardiovascular diseases. However, few studies have explored its association with the prognosis of type B aortic dissection (TBAD) patients receiving thoracic endovascular aortic repair (TEVAR). Methods: A total of 1,425 consecutive patients who underwent TEVAR were included. Data from 935 patients were analyzed in the study. The endpoint was defined as 30-day and 1-year aortic-related adverse events (ARAEs), all-cause mortality, and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: There were 935 patients included during a mean follow-up time of 2.8 years. After adjusting for multiple confounding factors, continuous TG/HDL-c [hazard ratio (HR) =1.07; 95% confidence interval (CI): 1.00-1.15; P=0.041] was independently associated with 1-year all-cause mortality. Both a high (Quintile 5: TG/HDL-c ratio ≥4.11) (HR =4.84; 95% CI: 1.55-15.13; P=0.007) and low TG/HDL-c ratio (Quintile 1: TG/HDL-c ratio <1.44) (HR =4.67; 95% CI: 1.46-14.94; P=0.001) were still independent risk factors for 1-year all-cause mortality. Conclusions: Elevated baseline TG/HDL-c ratio and TG/HDL-c ≥4.11 were significantly related to a higher risk of 1-year all-cause mortality among TBAD patients undergoing TEVAR. At the same time, the low TG/HDL-c ratio was also independently associated with 1-year all-cause mortality. Special attention should be paid to TBAD patients with a higher or an overly low TG/HDL-c ratio.

Selenium Deficiency Promotes Dilatation of the Aorta by Increasing Expression and Activity of Vascular Smooth Muscle Cell Derived Matrix Metalloproteinase-2.

OBJECTIVE: Selenium (Se) is a key part of the body's oxidation defence system. However, it is unclear whether Se affects the development of aortic aneurysm (AA). An animal experiment was conducted to clarify the role of Se in AA development. METHODS: C57BL/6N male mice were fed with a Se deficient (Se-D, < 0.05 mg/kg), Se adequate (Se-A, 0.2 mg/kg), or Se supplemented (Se-S, 1 mg/kg) diet for 8 weeks. Subsequently, an AA murine model (Se-D, n = 11; Se-A, n = 12; Se-S, n = 15) was established using angiotensin II (Ang II, 1 mg/kg/min) for four weeks plus ß-aminopropionitrile (BAPN, 1 mg/mL) for the first two weeks. Saline replaced Ang II, and BAPN was removed during the modelling process for sham mice (Se-A, n = 9). To determine whether Se deficiency promoted aortic dilation via matrix metalloproteinase-2 (MMP-2), the non-specific MMP inhibitor doxycycline (Dox, 100 mg/kg/day) was given to Se-D AA mice (n = 7) for two weeks. RESULTS: The maximum aortic diameter in Se-D AA model mice was significantly increased compared with Se-A AA model mice. MMP-2 expression and activity in the aortic media of Se-D AA model mice was significantly increased compared with Se-A AA model mice. A large number of vascular smooth muscle cells (VSMCs) were found aggregating in the media of the non-dilated aorta of Se-D AA model mice, which was completely inhibited by Dox. The percentage of VSMCs in aortic media of Se-D AA model mice was significantly higher than in Se-A AA model mice. The maximum aortic diameter and occurrence rate of AA in Se-D AA model mice with Dox were significantly reduced compared with Se-D AA model mice. CONCLUSION: Se deficiency promoted dilatation of the aorta in AA model mice by increasing expression and activity of VSMC derived MMP-2, causing abnormal aggregation and proliferation of VSMCs in aortic media.

TEVAR for aortic arch lesions combining physician-modified endograft and in-situ fenestration.

BACKGROUND: The aim of this retrospective study was to investigate the outcomes of combining physician-modified endograft (PMEG) and in-situ fenestration (ISF) for aortic arch repair. METHODS: A retrospective analysis was performed in 12 patients with aortic arch pathologies who underwent thoracic endovascular aortic repair with PMEG and ISF between June 2019 and February 2020. RESULTS: Revascularizations of supra-aortic arteries were successfully performed in 91.7% patients (11/12). One patient with aberrant right subclavian artery was unsuccessful because of tortuosity and sharp angle. One patient received endovascular exclusion by Viabahn due to artery injury of the femoral access. During the follow-up (mean 22.7 months), one patient underwent Bentall surgery because of retrograde type A aortic dissection, and one patient received coils embolization due to occurrence of a type I endoleak. In addition, one patient died of myocardial infarction 13 months after surgery. Results obtained after computed tomography angiography confirmed patency of all the supra-aortic arteries. CONCLUSIONS: Combining PMEG and ISF could be a feasible option for aortic arch lesions in selected patients. Long-term durability concerns require further evaluation.

Thoracic aneurysm and dissection gene variants increase the risk of aortic-related adverse events in early-onset isolated Stanford type B aortic dissection after endovascular aortic repair.

Background: Researches on Marfan syndrome and Ehlers-Danlos syndrome leading to early-onset aortic dissection (AD) emphasize the importance of gene variants, but the genetic pathogenesis, clinical characteristics and outcomes of early-onset isolated Stanford type B aortic dissection (iTBAD) patients remain unclear and need to be further elucidated. Methods: Isolated type B AD patients with an onset age of less than 50 years were enrolled in this study. Whole exome sequencing (WES) was performed to detect 11 known thoracic aortic aneurysm and dissection (TAAD) gene variants. Clinical characteristics and outcomes were compared between patients with and without gene variants. Multivariate Cox regression analysis was performed to identify independent risk factors for aortic-related adverse events (ARAEs) after endovascular aortic repair. Results: A total of 37 patients were included. Ten patients carried 10 variants in five TAAD genes, four of whom carried pathogenic or likely pathogenic variants. Compared to patients without the variants, patients with variants had a lower incidence of hypertension (50.0% vs. 88.9%, P=0.021), a higher incidence of other vascular abnormalities (60.0% vs. 18.5%, P=0.038), all-cause mortality (40.0% vs. 3.7%, P=0.014) and aortic related mortality (30.0% vs. 3.7%, P=0.052). Multivariate analysis confirmed the presence of TAAD gene variants as the only independent risk factor for ARAEs [hazard ratio (HR) =4.00; 95% confidence interval (CI): 1.26-12.74; P=0.019]. Conclusions: Routine genetic testing is necessary for early-onset iTBAD patients. Individuals with a high risk of ARAEs can be identified by detecting TAAD gene variants, which is important for risk stratification and proper management.

Senkyunolide I ameliorates thoracic aortic aneurysm and dissection in mice via inhibiting the oxidative stress and apoptosis of endothelial cells.

BACKGROUND: Thoracic aortic aneurysm and aortic dissection (TAAD) is one of the most fatal cardiovascular diseases. Senkyunolide I (SEI) is a component of traditional Chinese medicine with remarkable anti-inflammatory properties and exhibits remarkable protective effects, but its impact on TAAD remains unclear. Our study aimed to explore the role of SEI in a murine model of TAAD and further explore the immunopharmacological mechanism. METHODS AND MATERIALS: The in vivo model were assessed using echocardiography, gross anatomy, and tissue staining. Western blot and immunofluorescence were performed to evaluate the effects of SEI in vivo and in vitro. A SEI solution injection containing 1 % dimethyl sulfoxide (DMSO) was administered intraperitoneally to the TAAD model group, while a normal saline injection comprising 1 % DMSO was administered to the sham group. RESULTS: SEI prevented TAAD formation induced by BAPN/Ang II and reduced the TAAD incidence in mice. SEI treatment significantly inhibited the degradation of collagen and elastin fibers in the extracellular matrix. Furthermore, it reduced the expression of inflammatory factors in the aortic intima. Western blot analysis revealed that SEI-treated mice showed a significant decrease in apoptosis-related protein levels in the aorta compared with the TAAD group. PI3K, Akt, and mTOR in the SEI treatment group were significantly lower than in the model group. SEI could also attenuate H2O2-induced Human umbilical vein endothelial cells (HUVECs) damage and reverse the decline in migrant cells. The apoptosis of HUVECs was considerably reduced by the SEI treatment. CONCLUSIONS: Conclusively, SEI may alleviate the progression of TAAD by suppressing the PI3K/Akt/NF-κB signaling pathway. The SEI's ability to inhibit inflammation and oxidative stress opens the way to restore the function of endothelial cells and vascular homeostasis, and thus to provide novel and promising options for the treatment of TAAD patients.

Pristimerin protects against pathological cardiac hypertrophy through improvement of PPARα pathway.

Pristimerin (PM), serving as a biological component mainly obtained from Celastraceae and Hippocrateaceae families, has been extensively explored for its numerous pharmacological activities, especially anti-cancer activity. However, the function of PM on pathological cardiac hypertrophy is poorly understood. This work was intended to investigate the effects of PM on pressure-overload induced myocardial hypertrophy and its potential pathways. Mouse model of pathological cardiac hypertrophy was generated by transverse aortic constriction (TAC) or minipump administration of the ß-adrenergic agonist ISO for 4 weeks, and PM (0.5 mg/Kg/d, i.p.) was treated for 2 weeks. PPARα-/- mice received TAC surgery were used for mechanism exploration. Moreover, neonatal rat cardiomyocytes (NRCMs) were utilized to explore the effect of PM following Angiotensin II (Ang II, 1.0 µM) administration. We found that PM attenuated pressure-overload induced cardiac dysfunction, myocardial hypertrophy and fibrosis in mice. Likewise, PM incubation dramatically reversed Ang II-mediated cardiomyocytes hypertrophy in NRCMs. RNA-Sequence showed that PM selectively contributed to improvement of PPARα/PGC1 signaling, while silencing PPARα abrogated the beneficial effects of PM on Ang II-treated NRCMs. Importantly, PM ameliorated Ang II-induced mitochondrial dysfunction and decrease in metabolic genes, whereas knockdown of PPARα eliminated these alterations in NRCMs. Similarly, PM presented limited protective effects on pressure-overload induced systolic dysfunction and myocardial hypertrophy in PPARα deficient mice. Overall, this study revealed that PM exerted protective activity against pathological cardiac hypertrophy through improvement of PPARα/PGC1 pathway.

Serum Ionized Calcium as a Prognostic Biomarker in Type B Aortic Dissection After Endovascular Treatment.

OBJECTIVE: Lower serum ionized calcium (iCa2+) was reported to be associated with a higher risk of adverse events in patients with cardiovascular diseases. This study aimed to investigate the associations between preoperative serum iCa2+ and outcomes of type B aortic dissection (TBAD) patients receiving thoracic endovascular aortic repair (TEVAR). METHODS: Between January 2016 and December 2019, 491 TBAD patients received TEVAR in a single center. Patients with acute or subacute TBAD were included. Serum iCa2+ (pH 7.4) was obtained from the arterial blood gas analysis before TEVAR. The study population was grouped into the hi-Ca group (1.11 mmol/L ≤ iCa2+ < 1.35 mmol/L) and lo-Ca group (iCa2+ < 1.11 mmol/L). The primary outcomes were all-cause mortality. The secondary outcomes were any major adverse clinical events (MACEs), which included all-cause mortality and aortic-related severe complications. To eliminate bias, 1:1 propensity score matching (PSM) was conducted. RESULTS: Overall, 396 TBAD patients were included in this study. In the total population, there were 119 (30.1%) patients in the lo-Ca group. After PSM, 77 matched pairs were obtained for further analysis. In the matched population, the 30-day mortality and 30-day MACEs between the two groups presented significant differences (p=0.023 and 0.029, respectively). At 5 years, cumulative incidences of mortality (log-rank p<0.001) and MACEs (log-rank p=0.016) were significantly higher in the lo-Ca group than that of the hi-Ca group. Multivariate cox regression analysis indicated that lower preoperative iCa2+ (hazard ratio for per 0.1 mmol/L decrease, 2.191; 95% confidence interval, 1.487-3.228, p<0.001) was an independent risk factor for 5-year mortality after PSM. CONCLUSIONS: Lower preoperative serum iCa2+ might have an association with 5-year mortality in TBAD patients after TEVAR. Serum iCa2+ monitoring in this population may facilitate the identification of critical conditions. CLINICAL IMPACT: Our present study found that the cutoff value of preoperative serum iCa2+ 1.11 mmol/L, which is slightly lower than the lower limit of the normal range of 1.15-1.35 mmol/L, worked relatively well for discerning the high-risk and low-risk TBAD patients at 5 years. Serum iCa2+ monitoring in TBAD patients receiving TEVAR may facilitate the identification of critical conditions.

The intervention seasons of thoracic endovascular aortic repair impacted the outcomes for patients with type B aortic dissection.

Purpose: The objective of this research was to investigate whether seasonal variations influence the outcomes of type B aortic dissection (TBAD) patients with thoracic endovascular aortic repair (TEVAR). Patients and methods: From 2003 to 2020, a retrospective cohort study was performed, which included 1,123 TBAD patients who received TEVAR. Medical records were used to gather data on baseline characteristics. Outcomes including all-cause mortality and aortic-related adverse events (ARAEs) were tracked and analyzed. Results: Of the 1,123 TBAD patients in this study, 308 received TEVAR in spring (27.4%), 240 cases in summer (21.4%), 260 cases in autumn (23.2%), and 315 cases in winter (28.0%). Patients in the autumn group had a significantly lower risk of 1-year mortality than those in the spring group (hazard ratio: 2.66, 95% confidence interval: 1.06-6.67, p = 0.037). Kaplan-Meier curves revealed that patients who underwent TEVAR in autumn had a lower risk of 30-day ARAEs (p = 0.049) and 1-year mortality (p = 0.03) than those in spring. Conclusion: This study confirmed that TEVAR operated in autumn for TBAD was associated with a lower risk of 30-day ARAEs and 1-year mortality than in spring.

Peripheral Eosinophil Count Is Associated With the Prognosis of Patients With Type B Aortic Dissection Undergoing Endovascular Aortic Repair: A Retrospective Cohort Study.

Background Eosinophil count (EOS) has been proposed to provide prognostic information in multiple cardiovascular disorders. However, few researchers have investigated the predictive value of EOS for patients with type B aortic dissection who had thoracic endovascular repair. Methods and Results The authors reviewed the records of 912 patients with type B aortic dissection who were treated with thoracic endovascular repair in Changhai Hospital, Shanghai. By using receiver operating characteristic curve analysis, patients were divided into 2 groups based on the admission EOS cutoff value (<7.4×106/L [n=505] and ≥7.4×106/L [n=407]). To reduce selection bias, propensity score matching was applied. Multivariable regression analysis and Kaplan-Meier curves were performed to assess the association between EOS and long-term outcomes. Furthermore, we investigated nonlinear correlations between EOS and outcomes using general additive models with restricted cubic splines. In the matched population, lower EOS was associated with significantly higher 30-day mortality (4.1% vs 0%, P=0.007). There was no statistically difference in 30-day adverse events between the 2 groups (all P>0.05). Kaplan-Meier analysis revealed that patients with an EOS <7.4×106/L had a higher incidence of 1-year all-cause death (7.95% vs. 2.34%, P=0.008) and aortic-related death (5.98% vs 1.81%, P=0.023) than those with higher EOS. Multivariable Cox analysis showed that continuous EOS was independently associated with 1-year mortality (hazard ratio, 3.23 [95% CI, 1.20-8.33], P=0.019). In addition, we discovered a nonlinear association between EOS and 1-year outcomes. Conclusions Lower admission EOS values predict higher short- and long-term mortality after thoracic endovascular repair.

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways.

Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.

Outcomes of Zone 1 Thoracic Endovascular Aortic Repair With Fenestrated Surgeon-Modified Stent-Graft for Aortic Arch Pathologies.

OBJECTIVES: This study evaluated the feasibility and safety of zone 1 thoracic endovascular aortic repair (TEVAR) with fenestrated surgeon-modified stent-graft (SMSG) for aortic arch pathologies. METHODS: Between March 2016 and November 2020, 34 consecutive patients underwent zone 1 TEVAR with fenestrated SMSG for aortic arch pathologies. Outcomes included technical success, perioperative, and follow-up morbidity and mortality. RESULTS: During the study period, 34 patients were treated with zone 1 TEVAR with fenestrated SMSG. Twenty-four (70.6%) patients presented with type B aortic dissections, 9 (26.5%) patients presented with aneurysms (7 located on the lesser curvature side of aortic arch), 1 (2.9%) patient presented with type Ia endoleak after previous TEVAR owing to traumatic aortic dissection. The proximal landing zone for all patients were in zone 1, and all supra-aortic trunks were reconstructed, except for one left subclavian artery. Technical success was achieved in all cases. The 30-day estimated survival (±SE) was 90.9% ± 5.0% [95% confidence interval (CI): 77.0%-97.0%]. The 30-day estimated freedom from reintervention (±SE) was 87.9% ± 5.7% (95% CI: 73.4%-95.3%). At a median follow-up of 48 months (range, 12-68 months), 2 patients died, including 1 aortic-related death and 1 non-aortic-related death. One patient had reintervention 13 months after the operation owing to type Ia endoleak. All supra-aortic trunks were patent. The estimated survival (±SE) during follow-up was 85.1% ± 6.2% (95% CI: 69.9%-93.6%). One (2.7%) patient had stroke. The estimated freedom from reintervention (±SE) during follow-up was 84.2% ± 6.5% (95% CI: 69.9%-93.5%). CONCLUSIONS: Zone 1 TEVAR with fenestrated SMSG is an alternate option for treatment of aortic arch pathologies in experienced centers.

Elevated Admission Cardiac Troponin I Predicts Adverse Outcomes of Acute Type B Aortic Dissection after Endovascular Treatment.

Background: There is a lack of evidence about the predictive role of serum cardiac troponin I (cTnI) on the long-term adverse outcomes of acute type B aortic dissection (aTBAD) patients after thoracic endovascular aortic repair (TEVAR). In this study, we identified whether cTnI was an independent risk factor of 5-year adverse outcomes for aTBAD patients after TEVAR. Methods: We reviewed consecutive aTBAD patients without previous heart disease who were admitted for TEVAR. The total study population was divided into the cTnI(+) group (≥0.03 ng/mL) and the cTnI(-) group (<0.03 ng/mL) according to the time-dependent receiver operating characteristic curve analysis. The differences in clinical characteristics, operative details and clinical outcomes were compared between the two groups. Results: There was no difference in age and male prevalence between the two groups. Compared with the cTnI(-) group, the incidence of chronic kidney disease was higher in patients with cTnI ≥0.03 ng/mL. In addition, the cTnI(+) group presented with more frequent premature beats and non-myocardial-infarction ST-T segment changes. In terms of laboratory examinations, white blood cell counts, neutrophil counts, serum D-dimer and serum fibrin degradation products showed an increase in the cTnI(+) group, while lymphocyte and platelet counts showed a decrease in these patients. Patients with elevated cTnI suffered from increased risks of 5-year aortic-related adverse events (hazard ratio, HR = 1.822, 95% confidence interval, CI: 1.094-3.035; p = 0.021) and all-cause mortality (HR = 4.009, 95% CI: 2.175-7.388; p < 0.001). Conclusion: Among aTBAD patients without previous heart disease, preoperative elevated cTnI identified patients at an increased risk of long-term adverse outcomes after TEVAR.

Whole-Exome Sequencing Identified Genes Responsible for Thoracic Aortic Aneurysms and Dissections in three Chinese Families.

Thoracic aortic aneurysms and dissections are precarious conditions that often cannot be diagnosed with fatal outcomes. Over the last few years, pathogenic variants in numerous genes have been identified that predispose to heritable presentations of TAAD. An evidence-based strategy for the selection of genes to test in familial TAAD helps inform family screening and intervention to prevent life-threatening events. Using whole-exome sequencing, four members of three unrelated families clinically diagnosed with TAAD were used to identify the genetic origin of the disorder. Variant evaluation was carried out to detect the pathogenic mutation. Our studies suggest that mutations of COL3A1 and ACTA2 are responsible for familial TAAD. In addition, we highlight FBLN5, FBN1, SLC2A10, FBN2, and NOTCH1 as candidate genes. Future studies of crosstalk among the pathways may provide us a step toward understanding the pathogenic mechanism. This finding indicates the necessity of obtaining family medical history and screening of extended relatives of patients with TAAD for the early identification and treatment of TAAD.

Anatomical Feasibility Study on Novel Ascending Aortic Endograft With More Proximal Landing Zone for Treatment of Type A Aortic Dissection.

Objective: Type A aortic dissection (TAAD) is associated with high morbidity and mortality, and open surgery is the best treatment option. Development of endovascular repair devices for TAAD will benefit patients deemed unfit for open surgery. In this study, we performed a thorough investigation of anatomical features in Asian patients with TAAD to learn about the patient eligibility of a novel ascending aortic endograft technique. Methods: Computed tomography angiography (CTA) images of TAAD cases in our institution from January 2015 to November 2021 were reviewed, and three-dimensional reconstructions were performed with the Endosize software (Therenva, Rennes, France). Anatomic structures including length measured along centerline and greater/lesser curvature, ascending aorta/aortic root dimensions, as well as location of entry tear and extent of dissection were analyzed. Results: A total of 158 patients were included [median age 58 years, interquartile range (IQR), 30-76 years; 115 males, 72.8%]. In 99 (62.7%) of the cases, entry tear was distal to the sinotubular junction (STJ). In 106 (67.1%) of the cases, the pathology proximally extended into the aortic root, which was intramural hematoma in 37 (23.4%) of the cases, and the aortic root was free from the pathology in 52 (32.9%) of the cases. The median distance from the STJ to the proximal edge of the ostium of the innominate artery (IA) measured along the centerline was 65 mm (IQR 58-74 mm). The median distance from the distal edge of the higher coronary ostium to the STJ was 7.95 mm (IQR 5.625-10.9 mm). The bare metal stent part was set between the edge of the higher coronary ostium and the STJ. In our series, 63 (39.9%) of the cases had this distance >10 mm. The relative difference was <20% between the STJ and the proximal edge of the ostium of the IA in 92 (58.2%) of the cases. Ascending aorta radius of curvature was 52.2 mm (IQR 43.7-63.7 mm). Conclusions: Our study demonstrates that 56.3% of the TAAD cases would be amenable to endovascular repair by the novel ascending aortic endograft, with sufficient landing zone free of the dissected aorta.

A methylprednisolone-loaded and core-shell nanofiber-covered stent-graft to prevent inflammation and reduce degradation in aortic dissection.

BACKGROUND: Stent-graft-induced inflammation is an independent risk factor for adverse aortic remodeling in aortic dissection. In this context, we asked that whether a methylprednisolone-loaded stent-graft could reduce inflammation and degradation. METHODS: First, a coaxial electrospinning technique was used to create a core-shell film with methylprednisolone encapsulated in the inner of poly (L-lactide-co-caprolactone) nanofibers for controllable drug release. Second, an in vitro study was conducted to evaluate the biocompatibility of the nanofiber meshes. Third, the porcine aortic dissection model was developed to investigate the therapeutic effects of the methylprednisolone-loaded stent-graft. RESULTS: The results demonstrated that the nanofiber-coated film with a methylprednisolone-poly-caprolactone core layer and a poly (L-lactide-co-caprolactone) shell layer could effectively sustain drug release in vitro. In vivo study showed that the methylprednisolone-loaded stent-graft could reduce degradtion of aortic dissection by regulating inflammation. CONCLUSIONS: Overall, the controllable drug release by coaxial nanofiber is a promising approach to alleviate aortic inflammation and promote aortic remodeling after stent-graft implantation.

Mid-term Comparison of One-Piece Branched Stent-Graft and Chimney Technique Treating Aortic Arch Pathologies.

PURPOSE: We compared the mid-term outcomes of a one-piece branched stent-graft with the chimney technique in the treatment of aortic arch pathologies. METHODS: Between August 2012 and December 2017, a retrospective analysis of 279 patients with thoracic aortic dissection (TAD) or aneurysm (TAA) who underwent thoracic endovascular aortic repair with b-TEVAR (n = 69, 58 TAD and 11 TAA) or c-TEVAR (n = 210, 151 TAD and 59 TAA) was performed. RESULTS: Forty-five double-chimney for the left subclavian artery (LSA) and left common carotid artery LCCA and 165 single-chimney for the LSA were performed in chimney-TEVAR (c-TEVAR) and 69 branched-TEVAR (b-TEVAR) with 36 single-branched stent-grafts and 33 branched stent-grafts combined with fenestration technique. The c-TEVAR group experienced more in-hospital complications than the b-TEVAR group (19.5 vs. 7.2%, p = 0.017), primarily because the c-TEVAR group experienced more in-hospital cerebral ischemia events (6.2 vs. 0%, p = 0.043) and intra-operative type I endoleaks (31.9 vs. 5.8%, p < 0.01). There were significantly more follow-up type I endoleaks (21.9 vs. 4.3%, p = 0.002), cerebral ischemia events (11.0 vs. 2.9%, p = 0.042), and re-interventions (12.9 vs. 4.3%, p = 0.048) in the c-TEVAR group than in the b-TEVAR group. However, follow-up mortality was not significantly different between the c-TEVAR and b-TEVAR groups (5.2 vs. 2.9%, p = 0.638). CONCLUSION: In patients with aortic pathologies involving the arch branches, customized b-TEVAR may result in fewer cerebral ischemia events and endoleaks than c-TEVAR. However, c-TEVAR should be considered an off-the-shelf treatment option for patients in need of emergency treatment. LEVEL OF EVIDENCE: Level 4, Case Series.

A Novel Solution for Distal Dilation of Chronic Dissection After Repair Involving Visceral Branches: The Road Block Strategy.

Aim: Notwithstanding that unprecedented endovascular progress has been achieved in recent years, it remains unclear what is the best strategy to preserve the blood perfusion of abdominal visceral arteries and promote positive aortic remodeling in patients with distal dilatation of chronic aortic dissection in abdominal visceral part (CADAV) after aortic repair. The present study developed a Road Block Strategy (RBS) to solve this conundrum. Methods and Results: This prospective single-center clinical study included patients suffering from symptomatic distal dilatation of CADAV after aortic repair treated with RBS from January 2015 to December 2019 and followed up regularly for at least 2 years. Stent grafts were implanted first to cover distal tears and expand the true lumen. Device embolization was performed to induce proximal and distal segmental false lumen thrombosis (FLT) apart from the level of the ostia of vital branches. Successful RBS was performed in 13 patients. Significant differences were found in maximum true lumen diameter (p < 0.05), blood flow area in false lumen (FL) (p < 0.001), and the ratio of blood lumen to FL area (p < 0.05) between the pre-procedure and the latest follow-up results. No aortic rupture, vital branches occlusion, thoracic and abdominal pain, or death occurred during hospitalization and follow-up. Conclusions: Our findings suggest that RBS is feasible in treating distal dilatation of chronic aortic dissection after prior proximal repair, inducing false lumen thrombosis, preventing deterioration of aortic dissection, and maintaining the patency of abdominal visceral arteries.

Endovascular treatment of complicated aortic aneurysms using a modified flow-diverting strategy: Mid- to long-term outcome from a multicenter cohort study.

OBJECTIVES: Frequently reported adverse events following flow-diverting stents' treatment of aortic aneurysms indicate further refinements of this technique are required. This study aims at evaluating the clinical efficacy of an improved flow-diverting strategy. METHODS: A modified flow-diverting procedure was utilized in selected patients, in which stent-grafts were used to cover the non-branched segment of the aneurysmal lesion while flow-diverting multilayered bare metal stents were applied to cover the reno-visceral segment. The safety and efficacy of this joint procedure were assessed by regular follow-up. RESULTS: We screened 497 patients and included 67 cases (mean age: 67.07 ± 12.14 years; 53 males) between February 2012 and March 2018. The median number of stent-grafts and bare metal stents used in the procedure were 1 (range: 1 to 3) and 3 (range: 2 to 4), respectively. During a mean follow-up period of 34.54 ± 20.28 months, aneurysm maximum diameter decreased from 64.79 ± 10.31 to 59.32 ± 10.20 mm (p = 0.002), while sac thrombosis ratio increased from 26.01±10.99% to 98.46±4.84% (p<0.001). Aneurysm-related death or conversion to open repair was documented in three patients. The majority side-branches (198/201) remained patent during follow-up. Overall clinical success rate reached 91.04% (61/67). CONCLUSIONS: The joint procedure is characterized by significant aneurysm thrombosis along with high aneurysm stabilization/shrinkage and side-branches' patency rate. It might represent a potential improvement of the flow-diverting strategy in treating complex aortic lesions, yet large-scale, prospective, and randomized trials are anticipated to draw a robust conclusion. ADVANCES IN KNOWLEDGE: The joint procedure could potentially exclude complex aortic aneurysms from circulation while maintaining the collateral branches.

Outcomes of Total Endovascular Aortic Arch Repair with Surgeon-Modified Fenestrated Stent-Grafts on Zone 0 Landing for Aortic Arch Pathologies.

OBJECTIVES: This study evaluated the feasibility and safety of total endovascular aortic arch repair with surgeon-modified fenestrated stent-graft on zone 0 landing for aortic arch pathologies. METHODS: Between June 2016 and October 2019, 37 consecutive patients underwent total endovascular arch repair with surgeon-modified fenestrated stent-grafts on zone 0 landing. Outcomes included technical success, perioperative and follow-up morbidity and mortality, and branch artery patency. RESULTS: During the study period, 37 patients were treated with total endovascular aortic arch repair with surgeon-modified fenestrated stent-graft. Twenty-one (56.8%) patients were diagnosed with aortic dissections, 15 (40.5%) patients with aneurysms, and 1 (2.7%) patient required reintervention due to endoleak and sac expansion from previous thoracic endovascular aortic repair for thoracoabdominal aneurysm. The proximal landing zone for all patients were in zone 0, and all branch arteries of aortic arch were reconstructed. Technical success was achieved in 34 cases (91.9%). Three (8.1%) patients had fenestrations misaligned with target arteries, and the chimney technique was applied as a complementary measure. Thirty-day mortality rate was 5.4% (n=2). Thirty-day stroke rate was 5.4% (n=2). Thirty-day reintervention rate was 2.7% (n=1). At a median follow-up of 20 months (range, 3-49 months), 5 (13.5%) patients died, including 2 aortic-related deaths, 1 nonaortic-related death, and 2 deaths of unknown reason. One (2.7%) patient had stroke. Four patients (10.8%) had reintervention during the follow-up, including 2 cases of left subclavian artery occlusion and 2 cases of type II endoleak. The estimated survival (±SE) at 2 years was 72.4%±9.7% (95% CI 53.4%-91.4%). The estimated freedom from reintervention (±SE) at 2 years was 87.4%±5.9% (95% CI 75.84%-98.96%). CONCLUSIONS: Total endovascular aortic arch repair with surgeon-modified fenestrated stent-grafts on zone 0 landing is an alternate option for the treatment of aortic arch pathologies in experienced centers.