Safety and effectiveness of the sutureless integrated stented graft prosthesis in an animal model.

Background: Prolonged circulatory arrest time is an independent risk factor for postoperative adverse events of type A aortic dissection (TAAD) surgery. Further reduction of the circulatory arrest time is essential to improve surgical outcomes. This study aimed to evaluate the safety and effectiveness of the novel Sutureless Integrated Stented (SIS) graft prosthesis in an animal experiment. Materials and methods: Straight type of the SIS graft prosthesis was implanted into the descending aorta of 10 adult male sheep, and the use of the device was scored on a scale of 1-10. Aortic digital subtraction angiography (DSA) was performed at 4, 14, and 26 weeks to investigate the prostheses. After 26 weeks, the animals were sacrificed for histological analysis. Results: The immediate success rate of the surgery was 100 %, and the overall mean score of the use of the device was 9.65 ± 0.99. Three animals died from non-device-related causes during follow-up. Aortic DSA showed filling defects in 5 animals. Histological analysis revealed that all prostheses were intact. Except for 2 early deaths, the other 8 prostheses were endothelialized with mild inflammation, foreign body reactions, and intimal fibrosis. The mean cross-sectional area of the sutureless region was reduced by 26.4 % (range, 1.3-39.1 %). Conclusions: The safety and effectiveness of the novel SIS graft prosthesis were acceptable, and the delivery system exhibited a promising performance. Using the SIS graft prosthesis in TAAD surgery was expected to simplify the procedures and shorten the circulatory arrest time. Further large-scale clinical trials are required to verify these findings.

HSPB6 Deficiency Promotes the Development of Aortic Dissection and Rupture.

To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples by real-time PCR, western blotting, and immunohistochemical staining techniques. Using an HSPB6-knockout mouse, we investigated the potential role of HSPB6 in ß-aminopropionitrile monofumarate-induced aortic dissection. We found increased mortality and increased probability of ascending aortic dissection after HSPB6 knockout compared with wild-type mice. Mechanistically, our data suggest that HSPB6 deletion promoted vascular smooth muscle cell apoptosis. More importantly, HSPB6 deletion attenuated cofilin activity, leading to excessive smooth muscle cell stiffness and eventually resulting in the development of aortic dissection and rupture. Our data suggest that excessive stiffness of vascular smooth muscle cells caused by HSPB6 deficiency is a new pathogenetic mechanism leading to aortic dissection.

Detection of Various Microplastics in Patients Undergoing Cardiac Surgery.

Microplastics have been detected in human stool, lungs, and placentas, which have direct exposure to the external environment through various body cavities, including the oral/anal cavity and uterine/vaginal cavity. Crucial data on microplastic exposure in completely enclosed human organs are still lacking. Herein, we used a laser direct infrared chemical imaging system and scanning electron microscopy to investigate whether microplastics exist in the human heart and its surrounding tissues. Microplastic specimens were collected from 15 cardiac surgery patients, including 6 pericardia, 6 epicardial adipose tissues, 11 pericardial adipose tissues, 3 myocardia, 5 left atrial appendages, and 7 pairs of pre- and postoperative venous blood samples. Microplastics were not universally present in all tissue samples, but nine types were found across five types of tissue with the largest measuring 469 µm in diameter. Nine types of microplastics were also detected in pre- and postoperative blood samples with a maximum diameter of 184 µm, and the type and diameter distribution of microplastics in the blood showed alterations following the surgical procedure. Moreover, the presence of poly(methyl methacrylate) in the left atrial appendage, epicardial adipose tissue, and pericardial adipose tissue cannot be attributed to accidental exposure during surgery, providing direct evidence of microplastics in patients undergoing cardiac surgery. Further research is needed to examine the impact of surgery on microplastic introduction and the potential effects of microplastics in internal organs on human health.

Small-diameter PCL/PU vascular graft modified with heparin-aspirin compound for preventing the occurrence of acute thrombosis.

The occurrence of acute thrombosis, directly related to platelet aggregation and coagulant system, is a considerable reason for the failure of small-diameter vascular grafts. Heparin is commonly used as a functional molecule for graft modification due to the strong anticoagulant effect. Unfortunately, heparin cannot directly resist the adhesion and aggregation of platelets. Therefore, we have prepared a heparin-aspirin compound by coupling heparin with aspirin, an antiplatelet drug, and covalently grafted it onto the surface of polycaprolactone/polyurethane composite tube. In this way, the graft not only showed a dual function of both anticoagulation and antiplatelet, but also effectively avoided the rapid drug release and excessive toxicity to other organs caused by simple blending the medicine with material matrix. The compound retained the original function of heparin, showing good hydrophilicity and biocompatibility, which could promote the adhesion and proliferation of endothelial cells (ECs) and facilitate the process of tissue regeneration. What's more, the compound showed more effective than heparin in reducing platelet activation and preventing thrombosis. The graft modified by this compound maintained completely unobstructed for one month of implantation, while severe obstruction or stenosis occurred in PCL/PU and PCL/PU-Hep lumen at the first week, verifying the effect of the compound on preventing acute thrombosis. In general, this study proposed a designing method for small-diameter vascular graft which could prevent acute thrombosis and promote intimal construction.

Calcium promotes vascular smooth muscle cell phenotypic switching in Marfan syndrome.

Fibrillin 1 (Fbn1) mutations cause Marfan syndrome (MFS), with aortic root dilatation, dissection, and rupture. Few studies reported the blood calcium and lipid profile of MFS, and the effect of vascular smooth muscle cell (VSMC) phenotypic switching on MFS aortic aneurysm is unclear. Here, we aimed to investigate the role of calcium-related VSMC phenotypic switching in MFS. We retrospectively collected MFS patients' clinical data, performed bioinformatics analysis to screen the enriched biological process in MFS patients and mice, and detected markers of VSMC phenotypic switching on Fbn1C1039G/+ mice and primary aortic vascular smooth muscle cells. We found that patients with MFS have elevated blood calcium levels and dyslipidemia. Furthermore, the calcium concentration levels were increased with age in MFS mice, accompanied by the promoted VSMC phenotypic switching, and SERCA2 contributed to maintaining the contractile phenotype of VSMCs. This study provides the first evidence that the increased calcium is associated with the promoted VSMC phenotype switching in MFS. SERCA may become a novel therapeutic target for suppressing aneurysm progression in MFS.

It Is Advisable to Control the Duration of Hypothermia Circulatory Arrest During Aortic Dissection Surgery: Single-Center Experience.

Objective: The duration of hypothermic circulatory arrest (HCA) is one of the important factors affecting the prognosis of arch surgery, which is still controversial. The purpose of this study was to investigate the effect of HCA duration on early prognosis in type A aortic dissection (TAAD) patients who underwent arch surgery in our center. Methods: All consecutive patients who underwent surgical treatment for TAAD in Fuwai Hospital from January 2013 to December 2018 were included in this study and divided into four quartile groups based on HCA time. Baseline characteristics, perioperative indicators, and early mortality were statistically analyzed by propensity score matching (PSM) and restricted cubic spline (RCS) method. Perioperative adverse events were confirmed according to the American STS database and Penn classification. Results: About 1,018 consecutive patients (mean age 49.11 ± 1.4 years, male 74.7%) with TAAD treated surgically were eventually included in this study. After PSM, with the prolongation of HCA time, the surgical mortality rates of group [2,15], (15,18], (18,22], and (22,73] were 4.1, 6.6, 7.8, and 10.9% with p = 0.041, respectively. As shown in RCS, the mortality rate increased sharply after the HCA time exceeded 22 min. And from the subgroup analysis, the HCA time of 22 min or less was associated with better clinical outcomes (OR 2.09, 95%CI 1.25-3.45, p = 0.004). Conclusions: The early mortality increases significantly with the duration of HCA time when arch surgery was performed. And multiple systems throughout the body can be adversely affected.

Surgical Interventions Are Effective for Treating Unruptured Sinus of Valsalva Aneurysms.

Background: This study investigates the optimal management for unruptured sinus of Valsalva aneurysms (USVAs) combined with other cardiovascular lesions. Methods: This retrospective study examined 33 USVA patients who underwent surgical repair from February 1, 2007 to January 31, 2012. We analyzed the surgical procedures and the patients' quality of life after surgery. Additionally, echocardiography follow-up was performed before and after the operation. Results: Most USVAs (87.8%) originated in the right coronary sinus. Aside from one patient who was preoperatively misdiagnosed as having a ruptured sinus of Valsalva aneurysm (SVA). USVAs of the right coronary sinus were addressed by reinforcing this sinus with a Dacron patch through the right ventricle. USVAs were corrected by aortotomy using an autogenous pericardium patch when they originated in the non-coronary or left coronary sinus. Thirty patients (90.9%) were followed up for 22-119 months. No early death, residual fistula or SVA recurrence were found during the follow-up period. They all had a good quality of life and good heart function (New York Heart Association class I-II). Conclusions: Active surgical repair of an USVA can be achieved with satisfactory results in patients combined with other cardiovascular lesions.

Early Outcomes of Three Total Arch Replacement Strategies for DeBakey Type I Aortic Dissection.

Background: This study employed three surgical techniques: total arch replacement (TAR) with frozen elephant trunk (FET), aortic balloon occlusion technique (ABO) and hybrid aortic arch repair (HAR) on patients with type I aortic dissection in Fuwai Hospital, aiming to compare the early outcomes of these surgical armamentariums. Methods: From January 2016 to December 2018, an overall 633 patients (431 of TAR+FET, 122 of HAR, and 80 of ABO) with type I aortic dissection were included in the study. Thirty-day mortality, stroke, paraplegia, re-exploration for bleeding, and renal replacement therapy were compared using the matching weight method (MWM). Results: After MWM process, the baseline characteristics were comparable among three TAR groups. It showed that ABO group had the longest cardiopulmonary bypass (p < 0.001) and aortic cross-clamp time (p < 0.001), while the operation time was longest in the HAR group (p = 0.039). There was no significant difference in 30-day mortality among groups (p = 0.783). Furthermore, the incidence of stroke (p = 0.679), paraplegia (p = 0.104), re-exploration for bleeding (p = 0.313), and CRRT (p = 0.834) demonstrated no significant difference. Of note, no significant differences were found regarding these outcomes even before using MWM. Conclusions: Based on the early outcomes, the three TAR approaches were equally applicable to type I aortic dissection. We may choose the specific procedure relatively flexibly according to patient status and surgeon's expertise. Importantly, long-term investigations are warranted to determine whether above approaches remain to be of equivalent efficacy and safety.

A Novel Sutureless Integrated Stented (SIS) Graft Prosthesis for Type A Aortic Dissection: A Pilot Study for a Prospective, Multicenter Clinical Trial.

AIMS: Various kinds of surgical strategies and prostheses have been advocated to improve short-term and long-term outcomes in type A aortic dissection (TAAD). Large-scale repair of the pathological aorta is hard to generalize due to complex procedures. We aimed to investigate the performance, effectiveness and safety of a novel Sutureless Integrated Stented (SIS) graft prosthesis in TAAD patients undergoing total arch replacement (TAR) and frozen elephant trunk (FET) implantation surgery. METHODS: All patients admitted to Fuwai Hospital were prospectively screened. Urgent or scheduled surgery was arranged for eligible patients. The primary endpoint was operative mortality. Key secondary endpoints included stroke, spinal cord injury, unexpected aortic reoperation, and 1-year survival. Discharged patients were followed up with computed tomography angiography and transthoracic echocardiography at 3 months, 6 months, and 1 year after surgery. Performance, effectiveness and safety analyses were performed in those patients. RESULTS: Between August 1 and September 3, 2020, ten TAAD patients were enrolled in this study and successfully implanted with the SIS graft prosthesis. The median (IQR) age was 56.50 (43.75, 66.75) years (range from 31 to 75), and seven patients were male (70.0%). All patients underwent ascending aorta replacement + TAR + FET and additional procedures when necessary. The median (IQR) operation time, cardiopulmonary bypass time and cross clamp time were 270.50 (218.50, 312.50), 110.00 (88.00, 125.75), 69.50 (51.25, 82.75) min, respectively. Of note, the median (IQR) circulatory arrest time was 9.00 (8.00, 9.00) min (range from 4 to 12). The median (IQR) lowest nasopharyngeal temperature was 26.75 (25.98, 27.67) °C. Follow-up was 100% completed. During the 1-year follow-up, no patients died, no severe adverse events occurred, and rate of freedom from aortic reintervention was 100%. CONCLUSIONS: The SIS graft prosthesis was implanted in a novel sutureless way, which simplified the surgical procedure, shortened the circulatory arrest time and avoided deep hypothermia. The preliminary clinical outcomes and follow-up outcomes demonstrated the effectiveness and safety of this prosthesis. A large-scale trial is being conducted to further assess these findings.

Effect of heated humidified ventilation on intraoperative core temperature and prognosis in normothermic thoraco-abdominal aortic aneurysm repair.

BACKGROUND: To evaluate whether the heated humidified ventilation can effectively maintain core temperature and improve prognosis in normothermic thoraco-abdominal aortic aneurysm repair surgery. METHODS: Patients who were scheduled for normothermic thoraco-abdominal aortic aneurysm repair surgery were randomized into the group using heated humidified ventilation combined with water blanket and the group using water blanket only. During the operation, the core temperature will be measured every 30 minutes. We analyzed intraoperative core-temperature, coagulation function and in-hospital mortality. RESULTS: HHV&WB group showed lesser decrease in core temperature than WB groups in the first two hours, while WB group had a higher body temperature at the third to fifth hour (2-hour: 35.45±0.47 vs. 35.24±0.59 °C, P=0.284; 5-hour: 35.38±0.70 vs. 35.51±0.88 °C, P=0.664). There was less blood loss, dosage of coagulation drugs and in-hospital mortality (13.33% vs. 20.00%, P=1) in the HHV&WB group. CONCLUSIONS: Heated humidified ventilation can improve the prognosis of normothermic thoraco-abdominal aortic aneurysm repair surgery to some extent, but it can only maintain the core temperature during the first 2 hours.

Subacute/chronic type A aortic dissection: a retrospective cohort study.

OBJECTIVES: Our goal was to outline the clinical presentations, surgical treatment and outcomes of subacute/chronic type A aortic dissection (TAAD). METHODS: A total of 1092 patients with TAAD were enrolled retrospectively and divided into 2 groups based on acuity of TAAD (181 subacute/chronic vs 911 acute cases of TAAD). Early and late outcomes were investigated and compared using propensity score matching. RESULTS: The top 3 symptoms for subacute/chronic TAAD were chest tightness (80/181, 44.2%), mild pain (65/181, 35.9%) and sweating (58/181, 32.0). Fifteen (15/181, 8.3%) patients were symptom-free. Typical symptoms of acute TAAD were less common in patients with subacute/chronic TAAD such as intense/sharp pain (48/181, 26.5%), tear-like pain (35/181, 19.3%) and radiating pain (30/181, 16.6%). Patients with subacute/chronic TAAD had better early and late survival rates, with an early mortality rate of 6.1% (11/181) compared to 11.6% (106/911) of those with acute TAAD (P = 0.038). Before propensity score matching, survival at 1, 3 and 5 years was 93.1% [95% confidence interval (CI) 89.4-96.9%], 88.4% (95% CI 83.1-93.9%) and 86.4% (95% CI 80.1-93.1%) for subacute/chronic TAAD and 86.9% (95% CI 84.7-89.2%), 82.6% (95% CI 79.9-85.3%) and 79.0% (95% CI 75.5-82.7%) for acute TAAD, respectively (P = 0.039). The propensity score matching analysis substantiated the foregoing results. CONCLUSIONS: Subacute/chronic TAAD was clearly distinct from acute TAAD in terms of clinical presentations and had better early and late survival rates. Current surgical strategies for acute TAAD are applicable to subacute/chronic TAAD with excellent outcomes.

Surgical Management and Outcomes of the Aortic Root in Acute Type A Aortic Dissection.

BACKGROUND: This study evaluated the short- and middle-term outcomes of different aortic root managements in the setting of acute type A aortic dissection (ATAAD): aortic root repair (ARR group), untouched aortic root (UAR group), and Bentall procedure (Bentall group). METHODS: The study enrolled 673 patients (512 men; age 48.8 ± 11.2 years) between 2010 and 2015. Survival, aortic growth, reintervention, and valve function were compared between the 3 groups. RESULTS: The ages were 50.6 ± 9.9, 49.8 ± 12.2, and 44.0 ± 12.0 years for ARR, UAR, and Bentall groups, respectively (P < .01). The mean follow-up time was 3.0 years (range, 0.5-6.8 years). The aortic root diameters in the groups were 39.0 ± 5.1 mm in ARR, 38.2 ± 4.4 mm in UAR, and 50.3 ± 6.2 mm in Bentall (P < .01). The overall 30-day mortality was 11.7% (79 of 673). There was no difference in 30-day mortality between the 3 groups (P = .58). The estimated aortic root growth rate was 0.60 ± 0.17 mm/y for ARR and 0.50 ± 0.14 mm/y for UAR. During follow-up, 28 patients (4.1%) died. Differences in 5-year survival between the 3 groups did not reach statistical significance (P = .82). Aortic insufficiency greater than grade 2+ developed in 15 patients (2.2%). There was no significant difference between ARR and UAR in freedom from aortic insufficiency greater than grade 2+ (P = .56). None of the patients experienced new dissection or underwent proximal reoperation during the follow-up period. CONCLUSIONS: Conservative techniques (ARR and UAR) and aggressive root replacement can both be performed with excellent short- and middle-term outcomes in ATAAD. Thus, an individualized approach in managing the aortic root for ATAAD is recommended based on the patient's general condition, root pathology, and the surgeon's preference.

Alliin alleviates myocardial ischemia-reperfusion injury by promoting autophagy.

Alliin is an important organosulfur compound derived from garlic. In this study, the role of alliin in myocardial ischemia-reperfusion (I/R) injury and its underlying mechanisms were investigated. Treatment with alliin significantly reduced the area at risk and the infarct area in a mouse model of I/R injury. Besides, compared with I/R group, the cardiac function was significantly improved in I/R + alliin group. Treatment with alliin attenuated hypoxia/reoxygenation (H/R) induced apoptosis of cardiomyocytes. The results of the following high throughput RNA-sequencing revealed that autophagy participates in the myocardial protection role of alliin. Treatment with alliin decreased apoptosis and increased the autophagy activity in vivo. Autophagic flux in primary mouse cardiomyocytes was monitored using mRFP-GFP-LC3 adenovirus, and the results indicated that alliin could increase the autophagic flux. Moreover, the myocardial protective effect of alliin could be reversed by administration of autophagy inhibitor 3-MA. In conclusion, all the results indicated that alliin alleviates myocardial ischemia-reperfusion injury by promoting autophagy.

Predicting in-hospital rupture of type A aortic dissection using Random Forest.

BACKGROUND: This study is to establish prediction tools for in-hospital rupture of type A aortic dissection (TAAD) patients, to better guide emergency surgical triage and patient counselling. METHODS: We retrospectively evaluated 1,133 consecutive patients with TAAD from January 2010 to December 2016. The study population was divided into training and testing datasets in a 70:30 ratio for further analysis using Random Forest. RESULTS: The Random Forest classification model was developed with the training dataset and 16 variables were confirmed as 'important': age, BMI, gender, syncope, lower limb numbness/pain, acute phase of the TAAD, BP >160 mmHg at admission; acute liver dysfunction, WBC >15×109/L, aortic size, aortic height index (AHI), periaortic hematoma, pleural effusion, brachiocephalic artery involvement, renal artery involvement, and hemopericardium. Validation of the model showed good discrimination with an AUC, sensitivity, specificity, positive predictive value and negative predictive value of 0.994, 1.000, 0.987, 0.998 and 1.000, respectively, in the training dataset, and 0.752, 0.990, 0.514, 0.945 and 0.857, respectively, in the testing dataset. CONCLUSIONS: An easy-to-use tool to predict in-hospital rupture for TAAD patients was developed and validated (http://47.107.228.109/). Periaortic hematoma is the strongest predictor. Simple clinical information such as syncope can be very useful in in-hospital rupture risk stratification.