A new minimal invasive technique with in-situ stent-graft fenestration for type A aortic dissection.

Background: Aortic surgery successfully improves the prognosis of patients with type A aortic dissection. However, total arch replacement and reconstruction remain challenging. This study presents a new surgical modality, the in-situ stent-graft fenestration (ISSF) technique, for simplifying aortic arch reconstruction and assesses its short-term efficacy and safety in patients with type A aortic dissection. Methods: Data from 177 patients with type A aortic dissection who underwent aortic arch reconstruction were retrospectively analyzed. Sun's procedure was performed in 90 patients and ISSF was performed in the other 87. Results: The in-hospital mortality rate was 7.8% in the Sun's procedure group and 3.4% in the ISSF group (p = 0.357). Compared to the Sun's procedure group, the ISSF group had significantly shorter surgical duration, cardiopulmonary bypass time, circulatory arrest time, mechanical ventilation time, and aortic cross-clamp time (p < 0.05). Additionally, intraoperative blood loss was lower in the ISSF group than in the Sun's procedure group (p < 0.05). Patients who underwent ISSF also had a lower incidence of postoperative complications, including lung injury, renal failure, peripheral nerve injury, and chylothorax, than those who underwent Sun's procedure (p < 0.05). During the 6-month follow-up period after surgery, both groups showed significant improvements in the true lumen diameter of the descending thoracic aorta post-operation compared with the pre-operation measurements; meanwhile, the false lumen diameter decreased (p < 0.05). Conclusions: The ISSF technique appears to be an effective and safe alternative to conventional surgical procedures for patients with type A aortic dissection, with the potential to simplify the procedure, shorten the operation time, and yield satisfactory operative results. However, further investigation is needed to determine its long-term benefits.

Systematic review of the effect of cerebrospinal fluid drainage on outcomes after endovascular type B aortic dissection repair.

OBJECTIVE: The aim of the present systematic review was to determine whether prophylactic use of cerebrospinal fluid drainage (CSFD) contributes to a lower rate of spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched to identify all relevant studies reported before May 7, 2023. A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO registration no. CRD42023441392). The primary outcome was permanent SCI. Secondary outcomes were temporary SCI and 30-day/in-hospital mortality. The data were presented as the pooled event rates (ERs) and 95% confidence intervals (CIs). RESULTS: A total of 1008 studies were screened, of which 34 studies with 2749 patients were included in the present analysis. The mean Downs and Black quality assessment score was 8.71 (range, 5-12). The pooled rate of permanent SCI with prophylactic CSFD was identical to that without prophylactic CSFD (2.0%; 95% CI, 1.0-3.0; P = 0.445). No statistically significant difference was found between the rates of permanent SCI with routine vs. selective prophylactic CSFD (P = 0.596). The pooled rate of temporary SCI was 1.0% (95% CI, 0.00-1.0%). The pooled rate for 30-day or in-hospital mortality was not significantly different (P = 0.525) in patients with prophylactic CSFD (4.0, 95% CI 2.0-6.0) or without prophylactic CSFD (5.0, 95% CI 2.0-7.0). CONCLUSIONS: The systematic review has shown that prophylactic CSFD was not associated with a lower rate of permanent SCI and 30-day or in-hospital mortality after TEVAR for TBAD.

Clinical impact of baseline mitral regurgitation on outcomes after transcatheter aortic valve replacement for severe aortic stenosis.

Objective: The clinical impact of baseline mitral regurgitation (MR) on the outcomes after transcatheter aortic valve replacement (TAVR) is not clear. This study sought to assess the clinical impact of baseline MR on outcomes after TAVR. Methods: The study was a retrospective analysis. Data was from 120 consecutive patients with severe aortic stenosis (AS) undergoing TAVR at our center from June 2018 and July 2020. Clinical outcomes were assessed at 30-day, 1- and 2-year follow-up. Results: The median follow-up was 736.0 (interquartile range, 666.0-965.0) days. Overall survival in patients with nonsignificant and significant baseline MR was not significantly different, while patients from the improved MR group after TAVR demonstrated a significantly higher survival than unchanged or worsened MR group during 2-year follow-up. NYHA functional class had generally improved at 1 year, with only 8.3 % of patients with nonsignificant MR and 17.5 % of patients with significant MR in class III or IV. Patients with improved MR at 1 year after TAVR had a significantly higher LVEF, smaller LVEDD and LVESD than those with unchanged or worsened MR. Among the significant baseline MR group, 70.4 % and 80.0 % of patients had improved to nonsignificant MR at 30-day and 1-year follow-up after TAVR, respectively. Conclusions: Significant baseline MR was not associated with the increased risk of all-cause mortality 2 years after TAVR. Significant baseline MR was improved in most patients at 1 year after TAVR. Patients with unchanged or worsened MR had an increased all-cause mortality.

Effect of transcatheter aortic valve replacement on ascending aorta dilatation rate in patients with tricuspid and bicuspid aortic stenosis.

Objectives: The aim of the present study was to assess the differences between BAV and TAV patients with chronic moderate to severe or severe AS regarding presentation, incidence of TAVR, survival, ascending aorta diameter and dilatation rate before and after TAVR. Methods: The study included 667 consecutive patients with chronic moderate to severe or severe AS from January 2012 and December 2022. Outcomes included all-cause mortality, incidence of TAVR, and ascending aorta diameter and dilatation rate. Results: There were 185 BAV-AS and 482 TAV-AS patients, and BAV-AS patients were younger (67 vs 78 years, P = 0.027). Total follow-up was 4.5 years (IQR: 2.7-8.9 years), 290 patients underwent TAVR, and 165 patients died. The 8-year TAVR incidence was higher in BAV-AS (55% ± 4%) vs TAV-AS (41% ± 5%; P = 0.02). The 8-year survival was higher in BAV-AS (85% ± 6%) vs TAV-AS (71% ± 6%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). The dilatation rate of ascending aorta was significantly faster in BAV-AS patients compared with TAV-AS patients before TAVR. However, the ascending aorta dilatation rate for BAV-AS and TAV-AS patients was not significantly different after TAVR. Conclusions: Compared with TAV-AS, BAV-AS patients were younger and underwent TAVR more frequently, resulting in a considerable survival advantage. After TAVR, ascending aorta dilatation rates were similar in BAV-AS and TAV-AS patients, suggesting an important role of hemodynamics on ascending aorta dilatation in BAV-AS.

Early outcome of simplified total arch reconstruction under mild hypothermia (30-32 °C) with distal aortic perfusion.

OBJECTIVE: We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30-32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). METHODS: We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25-28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30-32 °C) with distal aortic perfusion (s-TAR group). RESULTS: The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. CONCLUSIONS: s-TAR under mild hypothermia (30-32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR.

A modified prosthesis eversion technique for proximal anastomosis in ascending aorta replacement.

Background: One of the crucial aspects of ascending aorta replacement is to achieve hemostasis of the proximal anastomosis. This study aimed to describe a modified prosthesis eversion technique for proximal anastomosis in ascending aorta replacement and compare its operative outcomes with the conventional prosthesis eversion technique. Methods: We conducted a retrospective analysis of all consecutive patients who had ascending aortic aneurysm and underwent ascending aorta replacement with the modified or conventional prosthesis eversion technique between January 2019 and December 2022 in our center. Results: A total of 108 patients were included: 55 in the modified group and 53 in the conventional group. The durations of cardiopulmonary bypass, aortic cross-clamping and total operation in the conventional group were longer than those in the modified group. Furthermore, perioperative blood loss and the incidence of re-exploration for bleeding were significantly lower in the modified group. Accordingly, patients in the conventional group accepted more blood transfusion. The modified group had a shorter duration in intensive care unit (ICU) and hospital, and lower total hospitalization costs than those in the conventional group. Conclusions: The modified prosthesis eversion technique is an effective alternative for proximal anastomosis in ascending aorta replacement, with less blood loss, shorter operation time, and lower rate of postoperative complications compared with the conventional technique.

Prognostic impact of new permanent pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: Conduction disturbances requiring permanent pacemaker implantation (PPI) are common following transcatheter aortic valve replacement (TAVR). There were conflicting data regarding the impact of new PPI on clinical outcomes after TAVR. OBJECTIVES: The study sought to evaluate the impact of new PPI on clinical outcomes in patients undergoing TAVR. METHODS: This study was a retrospective analysis of prospectively collected data. Data were from 210 consecutive patients without prior PPI who underwent TAVR due to severe symptomatic aortic stenosis at our center between June 2018 and July 2020. Clinical, echocardiographic, and pacing data were assessed at 30-day, 1- and 2-year follow-up. RESULTS: New PPI was required in 35 (16.7%) patients within 30 days after TAVR. The median time from TAVR to PPI was 3 days. The most common indication for PPI was high-degree or complete atrioventricular block. The median follow-up was 798.0 (interquartile range, 669.0-1115.0) days. There were no differences in all-cause mortality (adjusted hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.85-2.36; p = 0.415) and cardiovascular mortality (adjusted HR: 0.92; 95% CI: 0.57-1.89; p = 0.609) between groups. However, PPI group had a higher risk of heart failure (HF) rehospitalization (adjusted HR: 1.53; 95% CI: 1.26-2.28; p = 0.027). Echocardiography showed no significant improvement of LVEF over time in patients with PPI. At the latest follow-up, 31.3% of patients exhibited low (≤10%) pacing burdens, whereas 28.1% of patients had near constant (>90%) right ventricular pacing. CONCLUSIONS: New PPI within 30 days following TAVR was not associated with an increased risk of all-cause or cardiovascular mortality. However, patients with PPI had a higher risk of HF rehospitalization and lack of LVEF improvement.

Transfemoral transcatheter aortic valve replacement for pure native aortic regurgitation: one-year outcomes of a single-center study.

BACKGROUND: Evidence about safety and efficacy of transcatheter aortic valve replacement (TAVR) with the Venus A-Valve system (Venus Medtech, Hangzhou, China) remains limited for patients with pure native aortic regurgitation (PNAR). OBJECTIVES: The single-center study sought to report the one-year clinical outcomes of the Venus A-Valve in the treatment of PNAR. METHODS: This study was a retrospective analysis of prospectively collected data. Data was from all consecutive patients who had PNAR and underwent TAVR with the Venus A-Valve system at our center from July 2020 and June 2021. Procedural and clinical outcomes up to one year were analyzed using Valve Academic Research Consortium-2 criteria. RESULTS: A total of 45 consecutive patients with PNAR underwent transfemoral TAVR with the Venus A-Valve system. The Mean age was 73.5 ± 5.5 years and 26.7% were female. All the TAVR procedures were performed via transfemoral access. Implantations were successful in 44 cases (97.8%). Only one patient was converted to surgical aortic valve replacement. No patient died intraoperatively. No second valve was implanted. In-hospital mortality rate was 2.3%. The one-year all-cause mortality rate was 4.7% without cardiovascular related death. No patient had moderate or severe paravalvular leakage during follow-up. At one year, the mean pressure gradient was 8.8 ± 0.9 mmHg, and left ventricular ejection fraction increased to 61.5 ± 3.6%. CONCLUSIONS: This single-center study demonstrated the safety and efficacy of transfemoral TAVR with the Venus A-Valve in the treatment of patients with PNAR.

Simplified total arch reconstruction with a stented graft for extended aortic arch dilation.

Background: Reconstruction of the aortic arch and its three supra-aortic vessels remains a great surgical challenge with postoperative complications. We present a simplified total arch reconstruction with a modified stent graft (s-TAR) and compared its operative outcomes with conventional total arch replacement (c-TAR). Methods: This retrospective analysis of prospectively collected data from all consecutive patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and aortic arch reconstruction with the s-TAR or c-TAR between 2018 and 2021. The indication for intervention was maximum diameter of ascending aorta >55 mm and aortic arch in zone II >35 mm. Results: A total of 84 patients were analyzed: 43 in the s-TAR group and 41 in the c-TAR group. No inter-group differences were found for sex, age, comorbidities, or EuroSCORE II results. All patients were successfully treated with s-TAR or c-TAR, and none died intraoperatively. Cardiopulmonary bypass, selective cerebral perfusion, and lower-body circulatory arrest time were significantly shorter in the s-TAR group, which also had a lower incidence of prolonged ventilation and transient neurologic dysfunction. No patient in either group experienced permanent neurologic dysfunction. The incidence of recurrent laryngeal nerve injury and paraplegia was markedly increased in the c-TAR group; however, no such events were observed in the s-TAR group. Both perioperative blood loss and the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The in-hospital mortality rate was 0% in the s-TAR group and 4.9% in the c-TAR group. The s-TAR group had significantly shorter intensive care unit (ICU) stay and lower total hospitalization costs. Conclusions: The s-TAR technique is a safe and effective alternative for total arch reconstruction with shorter operation time, lower rate of postoperative complications and lower total hospitalization costs compared with c-TAR.

The diosgenin prodrug nanoparticles with pH-responsive as a drug delivery system uniquely prevents thrombosis without increased bleeding risk.

Thrombosis is the leading cause of death in patients with cardiovascular disease in the world. Current antithrombotic agent aspirin has serious side effects such as higher bleeding risk and serious gastrointestinal ulcers. Diosgenin reported in clinical research could prevent thrombosis without side effects. However, poor bioavailability and low knowledge on its molecular targets limit its clinical application. A novel prodrug with antithrombotic effect was prepared based on conjugating diosgenin derivatives to PEG with Schiff-base bond. The prodrug with long blood circulation time and satisfying safety could self-assemble into micelles in water. The prodrug micelles with pH-responsibility could targetedly release diosgenin in position of thrombus in vivo. The results indicate that the prodrug micelles without bleeding risk and histological damages prevent thrombosis by inhibiting platelet activation and apoptosis. Our studies demonstrate that the prodrug micelles could obviously enhance the efficacy in the prevention of arterial thrombus and venous thrombus than aspirin.

Physiochemical Properties and Probiotic Survivability of Symbiotic Corn-Based Yogurt-Like Product.

Corn is a major grain produced in northern China. Corn-based functional food products are very limited. In this study, a symbiotic corn-based yogurt-like product was developed. Corn milk was prepared through grinding, extrusion and milling, and hydration processes. Corn extrudate was prepared under the optimized conditions of corn flour particle size <180 µm, moisture content of 15% and extrusion temperature at 130 °C. The corn milk was prepared from 8% corn extrudate suspension and then milled twice with 0.1% glyceryl monostearate and 0.1% sucrose ester as emulsifiers. The corn milk was mixed with sugar (5%), glucose (2%), soy protein isolate (0.75%), inulin (1%), polymerized whey protein (0.3%) and xanthan gum (0.09%) as thickening agents. The mixture was fermented at 35 °C for 6 h using a probiotic starter culture containing L. plantarum. Chemical composition (%) of the symbiotic corn-based yogurt-like product was: total solids (17.13 ± 0.31), protein (1.12 ± 0.03), fat (0.30 ± 0.05), carbohydrates (15.14 ± 0.19), and ash (0.16 ± 0.02), respectively. pH value of this symbiotic product decreased from 4.50 ± 0.03 to 3.88 ± 0.13 and the population of L. plantarum declined from 7.8 ± 0.09 to 7.1 ± 0.14 log CFU/mL during storage at 4 °C. SDS-PAGE analysis showed that there were no changes in protein profile during storage. Texture and consistency were also stable during the period of this study. It can be concluded that a set-type corn-based symbiotic yogurt-like product with good texture and stability was successfully developed that would be a good alternative to the dairy yogurt.

Mitochondria targeting and near-infrared fluorescence imaging of a novel heptamethine cyanine anticancer agent.

The future of personalized cancer treatments relies on the development of functional agents that have tumor-targeted anticancer activities and can be detected in tumors using imaging. However, application of these functional agents in the clinic has been limited due to inefficient drug delivery, low specificity for tumor imaging, development of drug resistance, low signal-to-noise ratio and safety concerns regarding potential toxicity. Currently, the most common strategy to develop these functional agents is to conjugate therapeutic agents with the appropriate fluorescent probe. The present study synthesized a novel mitochondria-targeted heptamethine cyanine (Cy) derivative Cy­triphenylphosphonium. The newly developed compound exhibited stronger near infrared (NIR) fluorescence and reacted with bovine serum albumin. In addition, it preferentially accumulated in the mitochondria of cancer cells, as observed using confocal microscopy, and efficiently reduced cancer cell viability (IC50=3.04 µM). This novel multifunctional heptamethine Cy derivative, with cancer mitochondria targeting and NIR fluorescence imaging, may be promising as an alternative anticancer agent.

Xanthohumol isolated from Humulus lupulus prevents thrombosis without increased bleeding risk by inhibiting platelet activation and mtDNA release.

AIM: As the global population has reached 7 billion and the baby boom generation reaches old age, thrombosis has become the major contributor to the global disease burden. It has been reported that, in moderate doses, beer may protect against thrombosis. Xanthohumol (XN), an antioxidant, is found at high concentrations in hop cones (Humulus lupulus L.) and is a common ingredient of beer. Here, the aim of the present work was to investigate the effects of XN on antithrombotic and antiplatelet activities, and study its mechanism. APPROACH AND RESULTS: Using ferric chloride-induced carotid artery injury, inferior vena cava ligation model, and platelet function tests, we demonstrated that XN uniquely prevents both venous and arterial thrombosis by inhibiting platelet activation. Interestingly, in tail bleeding time studies, XN did not increase bleeding risk, which is recognized as a major limitation of current antithrombotic therapies. We also demonstrated that XN induces Sirt1 expression and thereby decreases reactive oxygen species (ROS) overload, prevents mitochondrial dysfunction, and reduces activated platelet-induced mitochondrial hyperpolarization, respiratory disorders, and associated membrane damage at low concentrations. In mitochondrial function assays designed to detect amounts of extracellular mitochondrial DNA (mtDNA), we found that XN prevents mtDNA release, which induces platelet activation in a DC-SIGN-dependent manner. CONCLUSIONS: XN exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing ROS accumulation and platelet mtDNA release without incurring a bleeding risk. This study has also provided novel insights into mechanisms of thrombotic diseases with possible therapeutic implications.

Synthesis, characterization, and biological studies of diosgenyl analogs.

A series of diosgenyl analogs were prepared from diosgenin to evaluate their anticancer activity and antithrombotic property. Analog 4, which had a spiroketal structure with a 6-aminohexanoic acid residue, exhibited the highest potency against all five tumor cell lines. It significantly blocked tumor growth, induced cell apoptosis and autophagy, and regulated cellular calcium concentration, mitochondrial membrane potential, adenosine triphosphate, and cell cycle. In addition, fluorescence-tagged compounds indicated that the analogs could rapidly accumulate in the cytoplasm, but no specific localization in the nucleus of cancer cells was observed. Furthermore, preliminary structure-activity relationship studies demonstrated that spiroketal analogs exhibit better antithrombotic activity than furostanic analogs, which exhibit the opposite effect by promoting thrombosis. Our study indicates that compound 4 may be a promising anticancer drug candidate for cancer patients with thromboembolism.

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release.

Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.

Preventive effect of a novel diosgenin derivative on arterial and venous thrombosis in vivo.

Current therapy for blood vessel thrombosis has the risk of leading to gastrointestinal bleeding and thrombocytopenia. We previously reported that a new derivative of diosgenin, compound 5, had significant anti-inflammatory activity superior to that of aspirin, prolonged bleeding time, and inhibited platelet aggregation in vitro. In the present study, we investigated the in vivo efficacy and safety of compound 5 using the ferric chloride (FeCl3)-induced arterial and venous thrombosis models in rats as well as its toxicity in mice. Compared with the control rats, those treated with compound 5 showed significantly less adenosine diphosphate (ADP)-induced platelet aggregation and a prolonged activated partial thromboplastin time mediated by the specific regulation of factor VIII. Furthermore, compound 5 significantly reduced the average length and weight of thrombi in both arteries and veins. These findings were similar to those of aspirin at the same dose. The safety evaluation revealed a much lower risk of bleeding and lesser gastric mucosal damage with compound 5 than with the same dose of aspirin. An oral dose of up to 575.5mg/kg showed no toxicity in mice. In conclusion, consistent with our in vitro findings, compound 5 exhibited an in vivo antithrombotic activity that was comparable to aspirin mainly by reducing platelet aggregation and regulating factor VIII, but with fewer side effects.