A New Drug-Coated Balloon for the Treatment of Superficial Femoropopliteal Artery Disease: 12-Month Results from the IN-DEPT SFA Trial.

PURPOSE: To report the outcomes of the IN-DEPT trial assessing the feasibility, preliminary safety data, and 12-month outcomes of a new drug-coated balloon (DCB) product for peripheral artery disease (PAD) in Chinese patients. MATERIALS AND METHODS: This is a prospective, multicenter, single-arm clinical trial. A total of 160 patients with superficial femoral artery (SFA) and/or proximal popliteal artery lesions were treated with a new paclitaxel-coated DCB. The preliminary effectiveness end point was 12-month primary patency. The primary safety end point was freedom from device- and procedure-related mortality over 30 days and freedom from major target limb amputation and clinically driven target lesion revascularization (CD-TLR) within 12 months after the index procedure. RESULTS: In total, 160 patients presented with 162 target lesions. A total of 139 lesions (85.8%) were treated with 1 DCB, whereas the other 23 lesions (14.2%) were treated with 2 devices. The device success rate was 100%. A total of 135 subjects reached the preliminary effectiveness end point, with a 12-month primary patency rate of 84.4%. There was no 30-day device- or procedure-related death or unplanned major target limb amputation at 12 months. Five CD-TLRs (3.1%) occurred during the 12-month follow-up period. CONCLUSIONS: Results from the IN-DEPT SFA trial showed satisfactory feasibility and safety of the new DCB over 12 months in Chinese patients with PAD and femoropopliteal de novo lesions, including both stenoses and total occlusions.

Adipose-derived stem cell/FGF19-loaded microfluidic hydrogel microspheres for synergistic restoration of critical ischemic limb.

The efficacy of stem cell therapy is substantially compromised due to low cell survival rate and poor local retention post-delivery. These issues drastically limit the application of stem cells for ischemic limb therapy, which requires effective blood perfusion and skeletal muscle regeneration. Herein, based on microfluidic technology, an integrated stem cell and cytokine co-delivery system designed for functional ischemic limb salvage was constructed by first incorporating the myogenic cytokine, fibroblast growth factor 19 (FGF19), into microspheres composed of methacrylate gelatin (GelMA). Then adipose-derived stem cells (ADSCs) were highly absorbed into the porous structure of the microspheres, overcoming the insufficient loading efficiency and activities by conventional encapsulation strategy. The fabricated ADSCs/FGF19@µsphere system demonstrated a uniform size of about 180 µm and a highly porous structure with pore sizes between 20 and 40 µm. The resultant system allowed high doses of ADSCs to be precisely engrafted in the lesion and to survive, and achieved sustained FGF19 release in the ischemic region to facilitate myoblast recruitment and differentiation and myofibrils growth. Furthermore, the combination of ADSCs and FGF19 exhibited a positive synergistic effect which substantially improved the therapeutic benefit of angiogenesis and myogenesis, both in vitro and in vivo. In summary, a stem cell and cytokine co-delivery system with the properties of easy preparation and minimal invasiveness was designed to ensure highly efficient cell delivery, sustained cytokine release, and ultimately realizes effective treatment of ischemic limb regeneration.

The efficacy and safety of Gore conformable thoracic stent graft and Valiant Captivia thoracic stent graft for acute type B aortic dissection.

BACKGROUND: To evaluate the safety and efficacy of the conformable thoracic aortic endograft (Conformable TAG Thoracic Endoprosthesis [CTAG]; W. L. Gore & Associates, Flagstaff, Ariz) and Valiant Captivia thoracic stent graft (Medtronic Inc., Santa Rosa, CA) for acute type B aortic dissection (TBAD). METHODS: The early and mid-term outcomes were analyzed for 413 patients undergoing TEVAR using conformable TAG thoracic endoprosthesis and Valiant Captivia thoracic stent graft for acute TBAD. 100 propensity-matched pairs of patients were generated, including 100 patients in the CTAG group and 200 patients in the Valiant Captivia group. RESULTS: Operative mortality were 2.33% (3 of 129) in the CTAG group and 1.76% (5 of 284) in the Valiant Captivia group. The median follow-up was 41.67 (26.00-60.67) months. No significant difference in mortality (9 [7.00%] vs. 36 [12.68%], P = 0.95) or re-intervention rate (3 [2.33%] vs. 20 [7.04%], P = 0.29) was observed between two groups. CTAG group have a lower incidence rate of distal stent graft-induced new entry tear than Valiant Captivia group (2.33% vs. 9.86%, P = 0.045). Lower incidence of type Ia endoleak was identified in the CTAG group (2.22%) than the Valiant Captivia group (14.41%) in patients with type III arch (P = 0.039). CONCLUSIONS: Both Valiant Captivia thoracic stent graft and CTAG thoracic endoprosthesis can be safely performed for acute TBAD with low operative mortality, favorable mid-term survival and freedom from reintervention. CTAG thoracic endoprosthesis had fewer dSINE even with larger oversizing and potentially suitable for type III arch with fewer type Ia endoleaks.

Clinical Results and Aortic Remodeling After Endovascular Treatment for Complicated Type B Aortic Dissection With the "Fabulous" Stent System.

OBJECTIVE: To report the clinical outcomes and aortic remodeling after the implantation of a self-developed, biomechanically optimized, two-stage thoracic stent system named Fabulous. BACKGROUND: Given the efficacy of the PETTICOAT concept, the benefits of Fabulous and the behavior of remodeling in different segments need further investigation. METHODS: This is a prospective and multicenter study. From 2017 to 2019, 145 patients (mean age, 56.6 years; 88.3% male) from 14 centers were included in this cohort. The clinical results and core laboratory results were from a central electronic data capture system. Computed tomographic angiography was performed preoperatively, 1 month, 6 months and yearly thereafter and was used for volumetric analysis by 3mensio (Bilthoven, The Netherlands). After the 1-year follow-up, 97.2 and 87.6% of the clinical and imaging results of the eligible patients were available. RESULTS: Both stent grafts and bare stents were successfully delivered in place in 100% of the patients. The 30-day mortality and 1-year freedom from all-cause mortality were 2.1 and 96.6%, respectively. The incidence of entry flow was 11.7% at 30 days and 6.2% at 365 days. No cases of stent-induced new entry (SINE) or reintervention were observed. After the 1-year follow-up, the true lumen/overall volume ratio reached 88%. The following subdivided segment volume changes were recorded: stent graft segment TL +56%; FL -92%, bare stent segment TL +32%; FL -75%, and there were no significant changes in the visceral segment. CONCLUSIONS: These outcomes indicated that there were favorable clinical benefits of Fabulous stent system. This device achieved a low short-term mortality and a low incidence of reintervention. In addition, patients undergoing Fabulous stent system implantation showed remodeling both on descending aorta and on the distal aorta. The volume changes in the TL and FL varied in the different segments. The long-term follow-up is still ongoing.

Aortic-Related Readmission After Thoracic Endovascular Aortic Repair for Type B Aortic Dissection Patients: A Single-Center Retrospective Study.

OBJECTIVES: This study aimed to investigate the characteristics of and risk factors for aortic-related readmission after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: Data from TBAD patients who underwent TEVAR from 2009-2018 at a Chinese tertiary center were retrospectively collected and analyzed. Enrolled patients were categorized into 2 groups according to whether aortic-related readmission occurred during follow-up, which was defined as hospitalization at least once after the initial procedure due to events that were related to or caused by aortic dissection or the initial procedure. RESULTS: A total of 1 288 TBAD patients were enrolled, and 99 patients experienced aortic-related readmissions (7.7%), among whom chronic patients had the highest readmission rate (9.8%). The yearly proportion of readmission during the first year after initial procedure revealed a decreasing trend with a -9.7% annual percentage change. Seventy-one patients underwent reintervention (71.7%). Distal aneurysmal degeneration (43.7%) and distal stent graft-induced new entries (32.4%) were 2 major causes for reintervention. Fourteen patients in the reintervention subgroup underwent a second reintervention (19.7%). In-hospital mortality was 1.0% during the readmission and 14.3% during the second readmission. The overall survival was comparable between two groups (P = 0.93). CONCLUSIONS: This study highlighted the importance of surveillance after initial procedure for TBAD patients with potential risk factors for aortic-related readmission, and the predisposition of patients with reintervention to multiple readmissions deserves attention.

Numerical simulation in the abdominal aorta and the visceral arteries with or without stenosis based on 2D PCMRI.

It is important to obtain accurate boundary conditions (BCs) in hemodynamic simulations. This article aimed to improve the accuracy of BCs in computational fluid dynamics (CFD) simulation and analyze the differences in hemodynamics between healthy volunteers and patients with visceral arterial stenosis (VAS). The geometric models of seven cases were reconstructed using the magnetic resonance angiogram (MRA) or computed tomography angiogram (CTA) imaging data. The physiological flow waveforms obtained from 2D Phase Contrast Magnetic Resonance Imaging (PCMRI) were imposed on the aortic inlet and the visceral arteries' outlets. The individualized RCR values of the three-element Windkessel model were imposed on the aortic outlet. CFD simulations were run in the open-source software: svSolver. Two specific time points were selected to compare the hemodynamics of healthy volunteers and patients with VAS. The results suggested that blood in the stenotic visceral arteries flowed at high speed throughout the cardiac cycle. The low pressure is distributed at stenotic lesions. The wall shear stress (WSS) reached 4 Pa near stenotic locations. The low time average wall shear stress (TAWSS), high oscillatory shear index (OSI), and high relative residence time (RRT) concentrated in the abdominal aorta. Besides, the ratios of the areas with low TAWSS, high OSI, and high RRT to the computational domain were higher in patients with VAS than which in the healthy volunteers. The individualized BCs were used for hemodynamic simulations and results suggest that patients with stenosis have a higher risk of blood retention and atherosclerosis formation in the abdominal aorta.

A modified method of computed fluid dynamics simulation in abdominal aorta and visceral arteries.

PURPOSE: The flow velocity of visceral arteries was measured by 2D PCMRI to produce the patient-specific flow BC imposed on the outlets of visceral arteries in CFD simulation. This modified method aimed to improve the CFD accuracy in the abdominal aorta and visceral arteries. METHODS: A volunteer underwent non-contrast-enhanced MRA to scan the abdominal aorta and visceral arteries, and 2D PCMRI to obtain the flow velocity of the aforementioned vessels. The three-dimensional geometric model was reconstructed using the MRI scan data of the abdominal aorta and visceral arteries. The flow waveforms measured by 2D PCMRI were processed and then imposed on the aortic inlet and the outlets of all visceral arteries as the flow BC. The RCR parameters of the three elements Windkessel model were modulated and imposed on the aortic outlet. CFD simulation was run in the open-source software: svSolver. The same volunteer underwent 4D flow MRI to compare the flow field with those extracted from CFD results. RESULTS: Four specific time points in a cardiac cycle and three cross-sectional planes of aorta were selected to analyze the flow field, pressure and wall shear stress (WSS) from CFD. The flow waveforms and streamlines of CFD agreed with those of 4D flow MRI. The pressure waveforms, pressure distribution and WSS distribution from CFD conformed with the physiological condition of human body. CONCLUSION: These results suggest this modified CFD method may yield reasonable flow field, pressure and WSS in the abdominal aorta and visceral arteries.

Evaluation for the safety and effectiveness of the in situ fenestration system in TEVAR for aortic arch pathologies: protocol for a prospective, multicentre and single-arm study.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) has gradually become the mainstream therapy for aortic arch pathologies (AAP). Our centre developed the in situ fenestration (ISF) system according to years of clinical experience and technological innovation. This study aims to evaluate the safety and effectiveness of the innovative, self-developed ISF system in TEVAR for AAP. METHODS AND ANALYSIS: The study is a prospective, multicentre and single-arm study. Patients diagnosed with AAPs in five centres on 1 January 2021 will be recruited and general TEVAR with ISF system will be performed. Clinical information and CT angiography images will be collected and recorded. Patients will be followed up for 5 years. Safety and efficacy endpoints are planned to be reported to evaluate this self-developed ISF system. ETHICS AND DISSEMINATION: The study is a registry. We have registered the study on the Chinese Clinical Trial Registry website (http://www.chictr.org.cn/). This study has been approved by the Ethics Committee of Zhongshan Hospital Fudan University (B2020-371) and individual consents will be signed at the time of enrolment. We anticipate that this self-developed ISF system will result in favourable social and economic benefits. Findings will be disseminated in peer-reviewed journals to provide reference for future clinical practice. TRIAL REGISTRATION NUMBER: ChiCTR1900026696.

Ten-Year Clinical Characteristics and Early Outcomes of Type B Aortic Dissection Patients With Thoracic Endovascular Aortic Repair.

OBJECTIVE/BACKGROUND: This study examined the 10-year hospitalization characteristics, economic patterns and early clinical outcomes of type B aortic dissection (TBAD) patients that underwent thoracic endovascular aortic repair (TEVAR) in one high-volume hospital in China. METHODS: We performed a population-based retrospective analysis based on electronic medical record system data provided by Zhongshan Hospital Fudan University from 2009 to 2018. RESULTS: We identified 1,367 cases of TBAD patients with TEVAR over the past decade. The total incidence of in-hospital complications was 7.6% (104 of 1,367), among which acute kidney injury (AKI) had the highest incidence (3.1%, 42 of 1,367). Aortic-related reintervention was performed in 7 patients (0.5%). The overall aortic-related in-hospital mortality rate was 2.7% (37 of 1,367) and had no significant time-varying trend (P = 0.2). Among these, 27% of in-hospital deaths were caused by retrograde type A dissection (RTAD). Chronic TBAD had a higher risk of in-hospital death versus acute TBAD, with a risk ratio of 2.69 (95% confidence interval [CI]: 1.19-6.09). Patients with hypertension (risk ratio 4.63, 95% CI: 1.38, 15.54) also had a higher in-hospital death risk. These 2 factors were also the predictive factors for the composite endpoint of in-hospital adverse events (risk ratio 2.17, 95% CI: 1.43, 3.29 and risk ratio 4.83, 95% CI: 1.90, 12.28, respectively), in addition to Marfan syndrome (risk ratio 4.05, 95% CI: 1.61, 10.19). The average length of hospitalization significantly declined during the past decade (annual percentage change -6.3%, 95% CI -8.2 to -4.3), and the stent-grafts (SGs) cost was the main expenditure of the total hospitalization costs. CONCLUSION: Our study showed a favorable early outcome of TEVAR over the past decade. Greater attention should be paid to certain risk factors in order to reduce the in-hospital adverse events. SG expenditure is still the primary economic burden on Chinese TBAD patients.

Low Dose Rivaroxaban for Atherosclerotic Cardiovascular Diseases: A Systematic Review and Meta-analysis.

Background: This study aims to explore the role of low-dose rivaroxaban (≤10 mg daily) for the treatment of atherosclerotic cardiovascular disease (ASCVD). Methods: PubMed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) of low-dose rivaroxaban in patients with ASCVD including coronary artery disease (CAD) and peripheral artery disease (PAD). Literature screening, data extraction, and risk of bias assessment were carried out independently by two researchers. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effect models to determine risks of outcomes in ASCVD patients treated with rivaroxaban and comparators, and meta-analysis was conducted via Review Manager 5.3.5 software. Results: 3,768 records were obtained through literature search, and 9 articles representing 6 RCTs ultimately qualified for this study. The meta-analysis indicated that for patients with CAD, the addition of rivaroxaban (5 mg daily) to aspirin could significantly reduce the risk of major adverse cardiovascular events (MACEs) compared with aspirin alone (HR 0.81, 95% CI, 0.72 to 0.91, p = 0.0004, I2 = 60%, 4 studies). For PAD patients receiving rivaroxaban (5 mg daily) plus aspirin, there was no significant reduction in the risk of MACEs (HR 0.84, 95% CI, 0.63 to 1.13, p = 0.25, I2 = 74%, 2 studies); however, there was significant reduction in major adverse limb events (MALEs) (HR 0.54, 95% CI, 0.35 to 0.83, p = 0.005, one studies) and in the composite of MACEs or MALEs (HR 0.78, 95% CI, 0.64 to 0.95, p = 0.02, I2 = 66%, 2 studies) when compared with patients receiving aspirin alone. Meanwhile, rivaroxaban combined with aspirin significantly increased the risk of International Society on Thrombosis and Haemostasis (ISTH) major bleeding compared with aspirin alone in patients with CAD (HR 1.74, 95% CI, 1.43 to 2.13, p < 0.00001, I2 = 0%, 2 studies) and PAD (HR 1.47, 95% CI, 1.19 to 1.83, p = 0.0004, I2 = 0%, 2 studies). Conclusions: Compared with standard antiplatelet therapy, the addition of a 5 mg daily dose of rivaroxaban to standard antiplatelet therapy may improve cardiovascular or limb outcomes of patients with ASCVD, with an increase in major bleeding. Patients who would benefit from the addition of low-dose rivaroxaban to antiplatelet agents and appropriate dual-pathway antithrombotic strategies should be identified in clinical practice to individualize antithrombotic therapy.

High-risk factors related to the occurrence and development of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a common and potentially dangerous vascular disease with many risk factors related to its occurrence and development. This review collects the results from recent studies of different comorbidities including hypertension, diabetes, and hyperlipidemia and summarizes their connections with AAA development and its underlying mechanisms. We believe that hypertension, diabetes, and hyperlipidemia can affect AAA occurrence and development, but more studies are needed to further explore the mechanisms.

Temporal modulation of host aerobic glycolysis determines the outcome of Mycobacterium marinum infection.

Macrophages are the first-line host defense that the invading Mycobacterium tuberculosis (Mtb) encounters. It has been recently reported that host aerobic glycolysis was elevated post the infection by a couple of virulent mycobacterial species. However, whether this metabolic transition is required for host defense against intracellular pathogens and the underlying mechanisms remain to be further investigated. A pathogenic mycobacterial species, M. marinum, is genetically close to Mtb and was utilized in this study. Through analyzing cellular carbon metabolism of RAW 264.7 (a murine macrophage-like cell line) post M. marinum infection, a strong elevation of glycolysis was observed. Next, three glycolysis inhibitors were examined for their ability to inhibit mycobacterial proliferation inside RAW264.7 macrophages. Among them, a glucose analog, 2-deoxyglucose (2-DG) displayed a protective role against mycobacterial infection. Treatment with 2-DG at concentrations of 0.5 or 1 mM significantly induced autophagy and decreased the phagocytosis of M. marinum by macrophages. Moreover, 2-DG pre-treatment exerted a significantly protective effect on zebrafish larvae by limiting the proliferation of M. marinum, and such effect was correlated to tumor necrosis factor alpha (TNF-α) as the 2-DG pre-treatment increased the expression of TNF-α in both mouse peritoneal macrophages and zebrafish. On the contrary, the 2-DG treatment post infection did not restrain proliferation of M. marinum in WT zebrafish, and even accelerated bacterial replication in TNF-α-/- zebrafish. Together, modulation of glycolysis prior to infection boosts host immunity against M. marinum infection, indicating a potential intervention strategy to control mycobacterial infection.