A visceral organ function-focused therapeutic strategy using a 6-hour time window for patients with acute type a aortic dissection complicated by mesenteric malperfusion.

BACKGROUND: Acute type A aortic dissection (ATAAD) complicated by mesenteric malperfusion is a critical and complicated condition. The optimal treatment strategy remains controversial, debate exists as to whether aortic dissection or mesenteric malperfusion should be addressed first, and the exact time window for mesenteric ischemia intervention is still unclear. To solve this problem, we developed a new concept based on the pathophysiological mechanism of mesenteric ischemia, using a 6-hour time window to divide newly admitted patients by the time from onset to admission, applying different treatment protocols to improve the clinical outcomes of patients with ATAAD complicated by mesenteric malperfusion. METHODS: This was a retrospective study that covered a five-year period. From July 2018 to December 2020(phase I), all patients underwent emergency open surgery. From January 2021 to June 2023(phase II), patients with an onset within 6 h all underwent open surgical repair, followed by immediately postoperative examination if the malperfusion is suspected, while the restoration of mesenteric perfusion and visceral organ function was performed first, followed by open repair, in patients with an onset beyond 6 h. RESULTS: There were no significant differences in baseline and surgical data. In phase I, eleven patients with mesenteric malperfusion underwent open surgery, while in phase II, our novel strategy was applied, with sixteen patients with an onset greater than 6 h and eleven patients with an onset less than 6 h. During the waiting period, none died of aortic rupture, but four patients died of organ failure, twelve patients had organ function improvement and underwent surgery successfully survived. The overall mortality rate decreased with the use of this novel strategy (54.55% vs. 18.52%, p = 0.047). Furthermore, the surgical mortality rate between the two periods showed even stronger statistical significance (54.55% vs. 4.35%, p = 0.022). Moreover, the proportions of patients with sepsis and multiorgan failure also showed differences. CONCLUSIONS: Our novel strategy for patients with ATAAD complicated by mesenteric malperfusion not only improves the surgical success rate but also reduces the overall mortality rate.

Optimized strategy to improve the outcomes of acute type A aortic dissection with malperfusion syndrome.

BACKGROUND: The mortality of acute type A aortic dissection (ATAAD) with malperfusion syndrome (MPS) is high. However, the management strategy remains controversial. We aimed to evaluate the strategy for MPS at our institution. METHODS: Among 724 patients with ATAAD, 167 patients with MPS were treated with immediate central repair (first stage) or an optimized strategy (second stage). In the second stage, the optimized strategy used was based on 6-hour threshold from symptom onset. For MPS with symptom onset within 6 hours, immediate central repair was performed, followed by endovascular reperfusion if malperfusion persisted. With symptom onset beyond 6 hours, individualized delayed central repair was performed. We compared outcomes between the first and second stages. RESULTS: The in-hospital mortality of ATAAD was significantly decreased when the optimized strategy was used (4.3% in the second stage vs 12.5% in the first stage; P < .01). In the second stage, the in-hospital mortality for MPS was decreased (10.2% vs 33.9%; P < .01). Moreover, the in-hospital mortality for MPS with symptom onset within 6 hours and beyond 6 hours decreased from 24% to 7.5% and from 41.2% to 11.8%, respectively. The operative mortality of MPS in the second stage was comparable to that in patients without MPS (4.0% vs 2.4%; P > .05). CONCLUSIONS: The optimized strategy significantly improved the outcomes of MPS. The 6-hour threshold from symptom onset could be very useful in determining the timing of central repair. For patients with MPS symptom onset within 6 hours, immediate central repair is reasonable; for those with symptom onset beyond 6 hours, individualized delayed central repair should be considered.

Corrigendum: Minimally invasive closure of a progressive pseudoaneurysm of the ascending aorta: a case report.

[This corrects the article DOI: 10.3389/fcvm.2023.1134196.].

A Potential Marker for Prognosis in Giant Left Ventricular Patients Undergoing Valve Surgery.

BACKGROUND: Although many clinicians have made efforts to improve the prognosis for giant left ventricular with valve disease patients, potential markers to judge the prognosis of giant left ventricular patients undergoing valve surgery are still unknown. The purpose of this study was to explore the possible impact factors for giant left ventricle prognosis. METHODS: From September 2019 to September 2022, 75 patients with preoperative valvular disease with a giant left ventricle (left ventricular end diastolic diameter (LVEDD) >65 mm) underwent cardiac valve surgery. The changes in cardiac function one year after surgery were used to describe prognosis and analyze the potential independent factors affecting surgical prognosis. The left ventricular ejection fraction (LVEF) was considered to be recovered if it was ≥50% on follow-up echocardiography at least 6 months after the diagnosis. RESULTS: The cardiac function of patients with a giant left ventricular and valve disease improved. Compared with preoperation, the left ventricular end diastolic diameter (LVEDD), left ventricular end-systolic dimension (LVESD), pulmonary artery systolic pressure (PASP), NT-proBNP, and cardio thoracic ratio (CTR) were significantly decreased (p < 0.05), and the ratio of severe heart failure was decreased from 60% to 37.33%. In the univariate analyses, the preoperative NT-proBNP levels and PASP were significantly associated with the cardiac function recovery (odds ratio [OR] = 1.001, 95% CI 1.000-1.002, p = 0.027; OR = 1.092, 95% CI 1.015-1.175, p = 0.018). However, during the diagnostic test, PASP did not account for cardiac function recovery (AUROC = 0.505, 95% CI = 0.387-0.713, p = 0.531). Based on the cutoff value in the experiment, we found that a NT-proBNP >753 pg/mL (AUROC = 0.851, 95% CI = 0.757-0.946, p < 0.0001) was a potential prognostic marker for patients with a giant left ventricular valve disease. CONCLUSIONS: We have demonstrated that an elevated preoperative NT-proBNP level is an independent predictor of cardiac function recovery in a cohort of giant left ventricular patients undergoing valve surgery, and this is the first study about this specific cohort of patients.

A Label-Free and Antibody-Free Molecularly Imprinted Polymer-Based Impedimetric Sensor for NSCLC-Cells-Derived Exosomes Detection.

In this study, a label-free and antibody-free impedimetric biosensor based on molecularly imprinting technology for exosomes derived from non-small-cell lung cancer (NSCLC) cells was established. Involved preparation parameters were systematically investigated. In this design, with template exosomes anchored on a glassy carbon electrode (GCE) by decorated cholesterol molecules, the subsequent electro-polymerization of APBA and elution procedure afforded a selective adsorption membrane for template A549 exosomes. The adsorption of exosomes caused a rise in the impedance of the sensor, so the concentration of template exosomes can be quantified by monitoring the impedance of GCEs. Each procedure in the establishment of the sensor was monitored with a corresponding method. Methodological verification showed great sensitivity and selectivity of this method with an LOD = 2.03 × 103 and an LOQ = 4.10 × 104 particles/mL. By introducing normal cells and other cancer cells derived exosomes as interference, high selectivity was proved. Accuracy and precision were measured, with an obtained average recovery ratio of 100.76% and a resulting RSD of 1.86%. Additionally, the sensors' performance was retained at 4 °C for a week or after undergoing elution and re-adsorption cycles seven times. In summary, the sensor is competitive for clinical translational application and improving the prognosis and survival for NSCLC patients.

Minimally invasive closure of a progressive pseudoaneurysm of the ascending aorta: A case report.

Ascending aortic pseudoaneurysm (AAP) is rare but may cause life-threatening complications. Although the placement of a stent graft and the use of occluder devices and vascular plugs to exclude pseudoaneurysm are adopted for some patients, the management of progressive pseudoaneurysms that may rupture at any time remains a challenge that needs to be addressed. In this study, we present the case of a patient with an AAP that was caused by aortic and mitral valve replacement for the giant left ventricle. Aortic pseudoaneurysm was suspected on the basis of a spherical cystic echo (70 × 80 mm) of the ascending aorta; this pseudoaneurysm was detected by an ultrasonic cardiogram, and the diagnosis was confirmed by an aortic computed tomography angiography (CTA) examination. To prevent the unexpected rupture of a progressive pseudoaneurysm, our patient was treated with a 28- mm ASD occluder without any procedural complications. Our patient has a good prognosis, which will inspire clinicians to choose minimally invasive procedures when dealing with such high-risk cases in emergency situations.

Management Strategies for Acute Type A Aortic Dissection Complicated By Limb Malperfusion.

BACKGROUND: Acute type A aortic dissection complicated by limb malperfusion presents a risk of mortality to the patients. Debates exist regarding management, whether focused on reperfusion first or immediate repair. Here, we aimed to describe our experience with the management of acute type A aortic dissection (ATAAD) complicated by limb malperfusion. METHODS: From January 1, 2020 to December 31, 2021, 22 consecutive patients were admitted to Xiamen Cardiovascular Hospital, due to acute type A aortic dissection complicated by limb malperfusion. All perioperative variables were recorded and analyzed. Limb malperfusion was diagnosed, according to the clinical symptoms, computed tomography angiography, and laboratory test. We adopted the clinical categories of acute limb ischemia to stratify severity of limb ischemia. Surgery strategies are as follows: Reperfusion first followed by central repair, immediate central repair, and immediate central repair followed by stenting. RESULTS: There were 21 males and one female with an average of 53.3±11.7 years. Management strategies were as follows: immediate central repair using total arch replacement with frozen elephant trunk in 15 patients, endovascular stenting followed by central repair in four patients, and endovascular stenting after central repair in two patients. The average extracorporeal circulation time was 258.8 ± 70.5 min; the average aortic cross-clamp time was 177.9 ± 54.2 min; and the average circulatory arrest time was 45.5 ± 13.1 min. The early mortality rate was 13.6% (3/22). Two patients left the hospital voluntarily, due to cerebral infarction and bleeding. One patient underwent fasciotomy for osteofascial compartment syndrome and uneventfully was discharged. Six patients underwent continuous renal replacement therapy and hemoperfusion. CONCLUSION: Central repair is safe and feasible for ATAAD complicated with limb malperfusion. For serious limb malperfusion, endovascular stenting followed by central repair is a good choice with continuous renal replacement therapy (CRRT) and hemoperfusion. Hospital mortality rate is high in cases with multiple organ malperfusion.

Postoperative Myocardial Infarction in Acute Type A Aortic Dissection: A Case Report.

Postoperative myocardial infarction (POMI) in acute type A aortic dissection rarely has been reported, we report a case of postoperative myocardial infarction in acute type A aortic dissection, and the clinical presentation and possible mechanisms are described. This case illustrates that postoperative myocardial infarction in acute type A aortic dissection is a rare fatal complication in patients without coronary lesions or coronary malperfusion before aortic repair. Type 2 myocardial infarction may account for POMI. Effective treatment may include anticoagulation therapy, volume adjustment, blood pressure support, administration of blood products, heart rate control, and individualized respiratory support.

Crispr-Cas9 mediated complete deletion of glucagon receptor in mice display hyperglucagonemia and α-cell hyperplasia.

Glucagon receptor plays an important role in the regulation of glucose metabolism. Studies have revealed that glucagon receptor antagonism is a potential effective treatment for diabetes. However, the functions of GCGR have not been fully illustrated. Although two Gcgr truncation knockout mice models have been widely used for GCGR function studies, truncated gene may remain neomorphic and/or dominant-negative function. In this study, we took the advantages of Crispr-Cas9 technique and generated a novel allele of GCGR in the mouse that yields complete loss of GCGR protein. Our studies reveal that complete deletion of Gcgr results in hyperglucagonemia, α-cell hyperplasia, improvement of glucose tolerance. These results are similar to the Gcgr-truncated mutation in mice. Hence, we provide a novel strain of GCGR knockout mice for the GCGR function studies.

Potential metabolomic biomarkers for the identification and diagnosis of type A acute aortic dissection in patients with hypertension.

Objectives: Most patients with acute aortic dissection (AAD) have a history of hypertension. Diagnosis of AAD in patients with hypertension at an early stage is complicated and challenging. This study aimed to explore the distinctive metabolic changes in plasma samples of AAD patients with hypertension and patients with hypertension only and provide early identification and diagnosis of AAD in patients with hypertension. Materials and methods: We collected blood samples from 20 patients with type A AAD and hypertension admitted to the emergency department and physically examined other 20 patients with hypertension as controls. The plasma metabolomic profiles of these patients were determined using untargeted metabolomics with ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Results: A total of 38 metabolites that differed between the AAD and hypertension groups were screened. In the positive ion mode, 12 metabolites were different between the two groups, and in the negative ion mode, 26 metabolites were different. Among the 26 different metabolites detected by the negative ion mode, 21 were significantly upregulated and five were downregulated in patients with AAD compared to patients with hypertension. Moreover, five metabolites were upregulated and seven were significantly downregulated in patients with AAD compared to those with hypertension, as detected by the positive ion mode. The metabolites differentially expressed in AAD were mainly involved in lipid metabolism (fatty acid biosynthesis, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism), carbohydrate metabolism (galactose, fructose, and mannose metabolisms), and membrane transport (ATP-binding cassette transporters). Interestingly, plasma hydrocortisone and dimethylglycine concentrations were significantly increased in patients with type A AAD, with the highest area under the curve value (AUC = 0.9325 or 0.9200, respectively) tested by the receiver operating characteristic curve analysis. Conclusion: This study provides possible metabolic markers for the early clinical diagnosis of AAD in patients with hypertension.

IL-38 in modulating hyperlipidemia and its related cardiovascular diseases.

Hyperlipidemia is confirmed to be associated with several health problems that include the combination of diabetes mellitus, obesity, and hypertension, ie, metabolic syndrome. Although the lipid-lowering therapy is an effective treatment in hyperlipidemia and its related cardiovascular diseases (CVDs), the persistence of high atherosclerotic risk is notable which could not be simply explained as a phenomenon of hyperlipidemia. Concerning on this notion, it is imperative to identify novel biomarkers which could monitor treatment and predict adverse cardiovascular events. It is demonstrated that the chronic inflammatory response caused by immune cells is a characteristic of hyperlipidemia and atherosclerosis. Notably, among several inflammatory related cytokines, interleukin 38 (IL-38), as a member of the IL-1 family, plays an important role in anti-inflammatory response by binding with its receptor which inhibits the downstream signaling pathways. In addition, IL-38 suppresses the expression of inflammatory factors mainly through the mitogen-activated protein kinase (MAPK). At the cellular level, IL-38 could inhibit the CD4 positive T lymphocyte into T-helper 17 (Th-17) lymphocyte which further enhances the immunosuppressive activity of the T-regulatory lymphocyte (T-reg) to inhibit the inflammatory response. Consistently, IL-38 is shown to be strongly correlated to development of hyperlipidemic related CVDs. In this review, the roles of IL-38 in the development of hyperlipidemia are fully summarized. Furthermore, a theoretical basis for further in-depth research of IL-38 for treatment of hyperlipidemia is also provided.

Antepartum acute Stanford type A aortic dissection: a case report and literature review.

BACKGROUND: Aortic dissection in pregnancy is a life-threatening event that is associated with high maternal and foetal mortality. Most cases occur during the third trimester of pregnancy, Herein, we describe a case of a pregnant woman with acute type A aortic dissection at 28 weeks of gestation. CASE PRESENTATION: A previously healthy, 24-year-old gravida 2 para 1 woman was brought to the emergency department during at the 28 weeks of gestation and diagnosed with acute type A aortic dissection. Cesarean section was performed with the cardiac surgical team on standby for cardiopulmonary bypass and the patient delivered a baby weighing 1000 g. After the operation, we performed the Beatall procedure and total arch replacement with FET using the deep hypothermic circulatory arrest technique. Both the mother and child survived and recovered well. A review of the literature on antepartum acute aortic dissection during pregnancy is also presented. CONCLUSION: Women should have a comprehensive, systematic physical examination before getting pregnant. Women at high risks of aortic dissection must undergo multidisciplinary evaluation and be counseled before pregnancy, once they become pregnant, their consistent aortic root diameter should be consistently monitored, and their blood pressure strictly controlled.

Hyperlipidemia and hypothyroidism.

Hypothyroidism is closely associated with increased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). The thyroid gland plays an important role in this process because thyroid hormones (THs) modulate cholesterol production, transformation and clearance. Although recent evidence suggests that thyroid-stimulating hormone (TSH) itself also participates in hyperlipidemia, the underlying mechanism remains unclear. Others demonstrated that the pathologic development of hypothyroidism-related hyperlipidemia was associated with down-regulated THs and up-regulated TSH in serum. This finding suggests a role for hypothyroidism in hyperlipidemia and potentially in related cardio-metabolic disease. Multiple newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play a role in modulating the risk of hyperlipidemia induced by hypothyroidism. Moreover, hypothyroidism also contributes to the production of dysfunctional high-density lipoprotein (HDL) particles. In the present review, we examine the relationship between hypothyroidism with the risk and pathologic development of hyperlipidemia. We explore mechanisms by which hypothyroidism promotes hyperlipidemia in general and its contribution to cardio-metabolic disease specifically.

Novel insights into the pathological development of dyslipidemia in patients with hypothyroidism.

According to the previous reports, hypothyroidism has been shown to be strongly correlated with increased circulating concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Notably, thyroid hormones  are confirmed to modulate the production, clearance, and transformation process of cholesterol within circulation of mammals. Moreover, emerging evidence suggests that the thyroid-stimulating hormone could also participate in modulating serum lipid metabolism independently of thyroid hormones, which further induces the pathological development of dyslipidemia. However, the underlying mechanism is still not fully elucidated. Recently, several research studies have demonstrated that the pathogenic progression of hypothyroidism-related dyslipidemia might be correlated with the decreased serum concentrations of thyroid hormones and the increased serum concentrations of thyroid-stimulating hormones. Thus, this indicates that hypothyroidism could induce dyslipidemia and its related cardio-metabolic disorder diseases. In addition, several newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play an important role in the regulation of dyslipidemia induced by hypothyroidism. Furthermore, under the status of hypothyroidism, significantly dysfunctional HDL particles could also be observed. In the current review, we summarized the recent knowledge of the relationship between the development of hypothyroidism with dyslipidemia. We also discussed the updated understanding of the mechanisms whereby hypothyroidism induces the risk and the development of dyslipidemia and cardio-metabolic diseases.

A modified frozen elephant trunk technique for acute Stanford type A aortic dissection.

BACKGROUND: Acute Stanford type A aortic dissection is often fatal, with a high mortality rate and requiring emergency intervention. Salvage surgery aims to keep the patient alive by addressing severe aortic regurgitation, tamponade, primary tear, and organ malperfusion and, if possible, prevent the late dissection-related complications in the proximal and downstream aorta. Unfortunately, no optimal standard treatment or technique to treat this disease exists. Total arch replacement with frozen elephant trunk technique plays an important role in treating acute type A aortic dissection. We aim to describe a modified elephant trunk technique and report its short-term outcomes. METHODS: From February 2018 to August 2019, 16 patients diagnosed with acute Stanford type A aortic dissection underwent surgery with the modified frozen elephant trunk technique at Xiamen Heart Center (male/female: 9/7; average age: 56.1 ± 7.6 years). All perioperative variables were recorded and analyzed. We measured the diameters of the ascending aorta, aortic arch, and descending aorta on the bifurcation of the pulmonary and abdominal aortas and compared the diameters at admission, before discharge, and 3 months after discharge. RESULTS: Fifteen patients (93.8%) had hypertension. The primary tears were located in the lesser curvature of the aortic arch and ascending aorta in 5 (31.3%) and 9 patients (56.3%), respectively, and no entry was found in 2 patients (12.5%). The dissection extended to the iliac artery and distal descending aorta in 14 (87.6%) and 2 patients (12.5%), respectively. The duration of cardiopulmonary bypass (CPB), cross-clamping, and antegrade cerebral perfusion were 215.8 ± 40.5, 140.8 ± 32.3, and 55.1 ± 15.2 min, respectively. Aortic valve repair was performed in 15 patients (93.8%). Bentall procedure was performed in one patient (6.3%). Another patient received coronary artery repair (6.3%). The diameters at all levels were greater on discharge than those on admission, except the aortic arch. After 3 months, the true lumen diameter distal to the frozen elephant trunk increased, indicating false lumen thrombosis and/or aortic remodeling. CONCLUSIONS: The modified frozen elephant trunk technique for acute Stanford type A aortic dissection is safe and feasible and could be used for organ malperfusion. Short-term outcomes are encouraging, but long-term outcomes require further investigation.

Reported outcomes after aortic valve resuspension for acute type A aortic dissection: a systematic review and meta-analysis.

In the majority of patients presenting with acute type A aortic dissection (AAD) complicated by aortic valve insufficiency, the aortic valve (AV) can be preserved by AV resuspension. A meta-analysis was performed to investigate the outcomes following AV resuspension for AAD. A systematic literature search for publications reporting outcomes after AV resuspension in AAD published between January 1998 and June 2018 was conducted. Early outcome events and linearized occurrence rates for late outcome events were derived. The retrieval process yielded 18 unique studies involving 3295 patients with a total of 17 532 patient-years (pt-yrs). Pooled early mortality was 15.5% [95% confidence interval (95% CI) 11.5-19.4%, I2 = 91.9%], and the linearized late mortality rate was 3.21%/pt-yrs (95% CI 2.49-3.77, I2 = 29%). The linearized occurrence rates for aortic root reintervention was 1.4%/pt-yrs (95% CI 0.88-1.79, I2 = 48%); for recurrent significant aortic valve insufficiency (>2+), it was 1.12%/pt-yrs (95% CI 0.79-1.45, I2 = 68%); and for endocarditis, it was 0.01%/pt-yrs (95% CI 0-0.04, I2 = 7%). The composite rate of thromboembolism and bleeding was 1.41%/pt-yrs (95% CI 0.18-2.63, I2 = 82%). A more recent surgical period was associated with a decreased hazard of reoperation on the aortic root (P < 0.001). Requirement of AV resuspension alone in AAD is a risk factor for mortality. The long-term durability of AV resuspension is excellent, with low rates of endocarditis and thromboembolism and bleeding. Root reoperation hazard has become acceptable in recent years. Preoperative aortic valve insufficiency grade exceeding 2+ is a predictor for root reoperation.

Is it justified to apply a modified Cabrol fistula in surgical repair of acute type A aortic dissection?

OBJECTIVE: Open repair of acute type A aortic dissection frequently results in oozing from the suture lines. A modified fistula technique was developed to rapidly control oozing and allow closing the chest immediately and safely. The efficiency of this modified fistula technique in surgical repair of acute type A aortic dissection was evaluated. METHODS: This was a retrospective study. From January 2015 to December 2016, 172 patients with acute type A aortic dissection underwent emergency surgical repair in our center. Among them, 76 were treated with the modified Cabrol fistula technique (fistula group), and the others did not receive this modified technique (nonfistula group). The clinical data of all patients were retrospectively reviewed and analyzed. RESULTS: The preoperative data, cardiopulmonary bypass time, aortic crossclamp time, selective cerebral perfusion, and lower body arrest time of the 2 groups were similar. The chest closure time was shorter in the fistula group. The postoperative drainage, amount of red blood cell transfusion, incidence of reopening for hemostasis, mechanical ventilation support time, duration of intensive care unit stay, incidence of postoperative dialysis, and 30-day mortality were significantly lower in the fistula group than in the nonfistula group. CONCLUSIONS: During surgical repair of acute type A aortic dissection, a modified Cabral fistula technique can rapidly control oozing and effectively improve the short-term outcomes.