Background: The optimal management strategy for 50-70% chronic coronary artery stenosis in patients undergoing aortic valve surgery for aortic regurgitation (AR) remains controversial. This study evaluates the prognostic impact of chronic coronary obstruction severity on surgical outcomes and mid-term survival. Methods: This retrospective cohort study included 717 patients undergoing aortic valve surgery for AR, grouped by coronary stenosis into <50% (n = 641) and 50-70% (n = 76). Following 1:1 propensity score matching (72 patients per group), the primary outcome of major adverse cardiovascular events (MACE) and the secondary outcome of all-cause death were compared. Results: No intergroup differences emerged in perioperative mortality (1.32% vs. 1.56%, p = 1.000) or complication rate. With a median follow-up of 2.53 years, 50-70% coronary obstruction does not increase MACE (HR = 2.050; 95% CI 0.375-11.197; log-rank p = 0.397) and all-cause mortality (HR = 0.710; 95% CI 0.200-2.522; log-rank p = 0.595). Similar results were obtained in the competing risk regression and multivariable analyses. Conclusions: In patients with AR, 50-70% chronic coronary obstruction does not increase perioperative complications, MACE, and all-cause mortality.

Objective Femoral artery cannulation is commonly used in emergency surgery for type A aortic dissection (TAAD) because of its convenience. However, patients with pre-existing lower limb ischemia undergoing femoral artery cannulation may face additional risks. This study aimed to comprehensively evaluate the short- and long-term outcomes associated with cannulation in ischemic femoral arteries (C-IFA). Methods A retrospective analysis was conducted involving patients with acute type A aortic dissection and lower-limb ischemia who underwent emergency surgery. The primary outcome was overall mortality, while secondary outcomes included permanent limb dysfunction, permanent dialysis, intensive care unit stays exceeding 10 days, and mechanical ventilation duration exceeding 96 h. Patients were stratified into two groups based on whether they underwent cannulation in the ischemic femoral artery in both the original and propensity score (PS)-matched cohorts. Results 92 patients, with a mean age of 53.78 ± 12.58 years, were included. The median follow-up period was 31.0 months. No significant differences were observed in the primary (P = 0.083 and P = 0.100, respectively) and secondary endpoints (P = 0.249 and P = 0.332, respectively) between the two groups in both the original and PS-matched cohorts. Age (hazard ratio [HR]: 1.07) and permanent dialysis (HR: 4.10) were identified as independent risk factors for the primary outcome. Subgroup analysis indicated that male sex, hypertension, and bilateral lower-limb ischemia may derive benefits from avoiding C-IFA. Conclusions Patients may benefit from avoiding C-IFA whenever possible. However, obtaining surgical timing via C-IFA is not entirely unacceptable, particularly in cases where the patient presents with bilateral lower-limb ischemia and requires rescue.

Importance Acute respiratory distress syndrome (ARDS) represents a frequent and serious complication after cardiovascular surgery. Although sivelestat, a specific neutrophil elastase inhibitor, has demonstrated therapeutic potential in preliminary studies, the evidence remains limited by methodological constraints of observational designs and underpowered studies. Objective To evaluate the efficacy of sivelestat vs placebo in reducing the incidence of postoperative ARDS and associated complications among patients undergoing major cardiovascular procedures. Design, Setting, and Participants This single-center, randomized, placebo-controlled clinical trial conducted at a tertiary care academic medical center om China enrolled 424 participants between February 15, 2024, and April 16, 2025, with a 90-day postoperative follow-up period. Participants were consecutive patients scheduled for cardiovascular surgery, including coronary artery bypass grafting, valve surgeries, ascending aortic reconstruction, combined procedures, congenital heart defect repairs, and cardiac tumor resections. Interventions Participants were randomly allocated (1:1) to receive either continuous intravenous sivelestat (0.2 mg/kg/h), initiated immediately on intensive care unit (ICU) admission postoperatively and continued for up to 7 days or until ICU discharge; or volume-matched 0.9% sodium chloride placebo administered on an identical schedule. Main Outcomes and Measures The primary outcome was the incidence of ARDS. Secondary outcomes included serial measurements of inflammatory biomarkers, including interleukin 6 and interleukin 8, tumor necrosis factor, systemic immune-inflammation index, and serum neutrophil elastase, on postoperative days 1, 3, 5, and 7, along with ARDS-related clinical outcomes including death, pneumonia, and reintubation. Analysis was performed on an intention-to-treat basis. Results Among 424 randomized patients, 382 completed the trial (mean [SD] age, 62.9 [6.2] years; 210 male [55.0%]). Adverse events monitored for safety did not differ between groups. The sivelestat group had significantly lower rates of ARDS (16.8% [32 of 190] vs 31.2% [60 of 192]; P < .001), and 90-day mortality (1.1% [2 of 190] vs 5.2% [10 of 192]; P = .02). Postoperative inflammatory biomarkers, including neutrophil elastase and interleukin 6, were significantly reduced in the sivelestat group. Conclusion and Relevance In this single-center, randomized, placebo-controlled clinical trial of patients undergoing cardiovascular surgery, sivelestat significantly reduced ARDS incidence and 90-day all-cause mortality. Sivelestat attenuated neutrophil-driven inflammation by dynamically suppressing neutrophil elastase and reducing key downstream biomarkers. These preliminary findings suggest sivelestat may be a pharmacologic option to mitigate ARDS in cardiovascular procedures. Trial Registration ClinicalTrials.gov Identifier: NCT06276569

INTRODUCTION:Postoperative delirium (POD) is a common neurological complication following acute type A aortic dissection surgery and is associated with poor clinical outcomes. Identifying reliable biomarkers, particularly those reflecting dynamic perioperative changes, may improve risk stratification and provide insights into POD pathophysiology. METHODS:This was a prospective observational study with a secondary analysis of perioperative serum samples from a registered clinical cohort (ChiCTR2200055980). A total of 128 acute type A aortic dissection patients undergoing open thoracotomy aortic surgery were enrolled, with 52 (40.6%) developing POD. For metabolomic analysis, 30 POD and 30 non-POD patients were matched for age, sex, and body mass index. Serum samples were collected at three time points: preoperatively, on intensive care unit admission, and on postoperative day 3. Untargeted metabolomics using liquid chromatography-mass spectrometry was performed. Differential metabolites were identified using multivariate and univariate analyses with false discovery rate correction. Receiver operating characteristic analysis was used to evaluate exploratory discriminative performance. RESULTS:After false discovery rate correction, no metabolites remained significant in preoperative samples, and only one metabolite, Acetyl-N-formyl-5-methoxykynurenamine, remained significant in postoperative comparisons. In contrast, several metabolites remained significant during the recovery stage. Notably, Acetyl-N-formyl-5-methoxykynurenamine exhibited a consistent temporal pattern, with increased levels in POD patients after surgery and a decline during recovery. Receiver operating characteristic analysis showed promising discriminative ability in postoperative (area under the curve: 0.833) and recovery-stage comparisons (area under the curve: 0.938), while preoperative performance was limited. CONCLUSIONS:Under stringent statistical correction, acetyl-N-formyl-5-methoxykynurenamine emerged as the most robust candidate dynamic biomarker associated with both POD occurrence and recovery. Its temporal pattern highlights the value of longitudinal metabolomic analysis and provides a basis for future validation studies.

OBJECTIVES:We evaluated the safety and efficacy of transcatheter aortic valve replacement (TAVR) up to 1-year follow-up for patients with severe pure aortic valve regurgitation (AR) or mixed severe aortic valve regurgitation and aortic valve stenosis (AR+AS) using a novel self-expandable bioprosthesis. METHODS:From 2021 to 2022, transapical TAVR using Ken-Valve (Jenscare Biotechnology Ltd, Ningbo, China) was performed in 142 symptomatic patients (mean age 70.3 ± 5.5 years) with pure AR (n = 109) or AR+AS (n = 33) across 15 hospitals in China. All patients were considered high-risk or inoperable after heart team evaluation, with a mean Society of Thoracic Surgeons score of 5.9 ± 3.0%, and 99.3% in NYHA class III/IV. Procedural characteristics, echocardiography data, and clinical outcomes up to 1-year were analysed. RESULTS:Technical success was achieved in 97.2% of cases. Two (1.4%) patients were converted to open surgery due to unsuitable anatomy or valve migration during the procedure. New permanent pacemakers were implanted in 20 (14.1%) patients. Three (2.1%) patients had stroke, and 3 (2.1%) patients had major bleeding. Thirty-day mortality was 2.1%, and all-cause mortality at 1-year was 5.6% (8/142). Mean aortic valve gradient and effective orifice area (EOA) at 1-year postoperatively were 9.4 ± 5.4 mmHg and 1.9 ± 0.6 cm2, respectively. Significant improvement in clinical symptoms, positive left ventricular remodelling, and quality of life were observed up to 1-year. There was no significant difference in mortality, complications, and haemodynamic performance between patients with pure AR and AR+AS at 1-year. CONCLUSIONS:TAVR using the Ken-Valve was safe and effective in patients with pure AR or mixed AR+AS in mid-term. CLINICAL REGISTRATION NUMBER:NCT03788590.

Aortic dissection (AD) is a catastrophic vascular emergency with high mortality, and current pharmacological interventions to prevent its progression are limited. Vascular smooth muscle cells (VSMCs) undergo a pathological phenotypic switch from a contractile to a synthetic state during AD, compromising aortic wall integrity; however, the underlying metabolic mechanisms remain poorly understood. In this study, we performed integrative transcriptomic analyses and identified glutaminase 1 (GLS1) as a key regulator of VSMC phenotypic switching in AD. GLS1 expression was significantly downregulated in VSMCs from both human AD aortic tissues and mouse models. Functionally, GLS1 deficiency promoted PDGF-BB–induced VSMC dedifferentiation in vitro. Smooth muscle cell–specific Gls1 -knockout ( Gls1 SMKO ) mice exhibited aggravated AD after β-aminopropionitrile treatment, whereas VSMC-specific GLS1 overexpression improved the contractile phenotype and reduced AD incidence. Mechanistically, GLS1 downregulation impaired glutamate metabolism, leading to reduced levels of glutathione and α-ketoglutarate. This metabolic disruption promoted reactive oxygen species accumulation and mitochondrial dysfunction, ultimately triggering VSMC phenotypic switching. Furthermore, we found that GLS1 transcription was repressed by retinoic acid receptor-α (RARα). Pharmacological inhibition of RARα with AR7 restored GLS1 expression, ameliorated VSMC phenotypic switching, and conferred protection against AD. These findings reveal a critical role of GLS1-mediated glutamate metabolism in VSMC phenotypic switching and suggest a promising therapeutic strategy for AD.

BackgroundGastrointestinal bleeding after coronary artery bypass grafting (GIBCG) is a serious postoperative complication linked to increased mortality. The stress hyperglycemia ratio (SHR) has been recognized as a reliable predictor of adverse clinical outcomes, particularly in patients with cardiovascular disease. This study aimed to investigate the association between SHR and both GIBCG and in-hospital mortality.MethodsPatients were recruited from four medical centers and the Medical Information Mart for Intensive Care IV, with a total of 16,440 individuals included in the final analysis. Patients were categorized into four groups based on SHR quartiles. The primary outcomes of interest were the incidence of GIBCG and in-hospital mortality. Restricted cubic splines and logistic regression models were employed to analyze the relationship between SHR and clinical outcomes.ResultsAmong the patients who underwent surgery, 1,158 (7.04%) experienced GIBCG, while 214 (1.3%) died during hospitalization. After adjusting for confounding variables, a U-shaped relationship was observed between SHR and both GIBCG occurrence and in-hospital mortality. The lowest incidence of these outcomes was observed within the SHR range of 0.706–0.792, with inflection points identified at 0.71 for GIBCG and 0.733 for in-hospital mortality.ConclusionA U-shaped relationship was identified between SHR and both GIBCG and in-hospital mortality. Both low and high SHR levels may help identify patients at increased risk of gastrointestinal bleeding and in-hospital mortality following coronary artery bypass grafting.

Aortic aneurysm and dissection (AAD) are life-threatening vascular diseases for which effective pharmacological therapies remain limited. Smooth muscle cell phenotypic switching plays a central role in AAD development and progression. Orforglipron, a novel orally active non-peptide glucagon-like peptide-1 receptor agonist, has shown potential cardiovascular benefits; however, its role in AAD remains unclear. In this study, male B6 humanized GLP-1R mice were treated with orforglipron by oral gavage for 28 consecutive days and subjected to beta-aminopropionitrile combined with angiotensin II infusion to induce AAD. Orforglipron treatment protected mice from smooth muscle cell phenotypic switching, medial degeneration, and AAD formation. RNA sequencing of human aortic smooth muscle cells identified Wnt5a as a key downstream target regulated by orforglipron. Mechanistically, orforglipron inhibited ERK phosphorylation, reduced EGR1 expression, and thereby suppressed EGR1-mediated Wnt5a transcription. Conditional deletion of Wnt5a in smooth muscle cells significantly attenuated AAD progression, whereas activation of JNK signaling aggravated vascular remodeling and AAD development. These findings demonstrate that orforglipron attenuates smooth muscle cell phenotypic switching and AAD progression by modulating the ERK/EGR1/Wnt5a/JNK signaling axis, supporting orforglipron as a promising therapeutic candidate for aortic diseases.

Objective: This study aimed to assess how the time interval between onset of symptoms and hospital admission associates with postoperative outcomes after type A acute aortic dissection (TAAD) repair. Methods: From January 2011 to January 2020, 1406 consecutive patients underwent TAAD repair at our center. We included 1228 patients who were admitted within 72 hours of symptom onset and divided them into 2 groups: 867 patients in the early (≤12 hours) and 361 in the late (>12 hours and <72 hours) admission group. Results: Hypotension (11% vs 7.6%, P = .06) and bradycardia on admission (11% vs 1.9%, P < .01) were more common in the early group. This group also had a greater incidence of preoperative limb ischemia (17% vs 11%, P < .01) and greater rates of rescue surgeries (16% vs 11%, P = .05). Despite prompt intervention, the postoperative mortality rate (15% vs 9.4%, P = .01), stroke rates (5.8% vs 2.8%, P = .03), and postoperative kidney failure (29% vs 21%, P < .01) were greater in the early group. Conclusions: Our analysis indicates that the timing of surgery in patients with TAAD is primarily driven by the presence of more severe symptoms and signs of ischemia and, despite early treatment, these patients have increased rates of complications and mortality. This emphasizes the importance of the clinical status on admission, rather than the time, as the main driver for postoperative complications.

BACKGROUND:This study aimed to evaluate the predictive value of C1q (complement activation regulatory factor) for the occurrence of postoperative delirium (POD) following surgery for acute aortic dissection. METHODS:We prospectively included patients undergoing surgery for aortic dissection. Serum levels of C1q were measured preoperatively and on the first postoperative day. POD was assessed daily postoperatively using the confusion assessment method (CAM) or the confusion assessment method for the intensive care unit (CAM-ICU) for patients in the intensive care unit (ICU). Statistical analyses included the Pearson correlation coefficient and multivariate logistic regression to evaluate the association between C1q levels and POD. RESULTS:A total of 67 patients were enrolled in the study. Serum C1q levels were significantly higher in the Delirium group compared to the non-Delirium group both preoperatively and postoperatively. Univariate logistic analysis revealed that preoperative serum C1q levels were predictive of POD (OR = 1.379, 95% CI = 1.176-1.683, p < 0.001). The area under the curve (AUC) for preoperative serum C1q was 0.788 (95% CI = 0.671-0.880). CONCLUSIONS:C1q is a potential biomarker for predicting POD in patients undergoing aortic dissection surgery. These findings suggest that C1q may be valuable for early diagnose and intervention strategies for POD.

The transcription factor ZEB2 has been implicated in cardiovascular disease, but its role and post-translational regulation in cardiac fibroblast-to-myofibroblast transition (FMT) and fibrosis after myocardial infarction (MI) are not fully understood. ZEB2 protein expression was significantly increased in infarcted murine hearts, activated cardiac fibroblasts, and human fibrotic myocardium. Myofibroblast-specific ZEB2 knockout alleviates cardiac dysfunction and adverse remodeling post-MI. Mechanistically, SENP1 regulated SUMO-1 modification of ZEB2 at K462, K479, K611, and K774. Reconstituting ZEB2-deficient systems with wild-type ZEB2 (ZEB2-WT) restored pathological fibrosis and FMT, whereas the SUMOylation-deficient mutant (ZEB2-4KR) conferred cardioprotective effects. ZEB2 SUMOylation activated the pro-fibrotic PI3K/AKT-mTORC1 signaling pathway. ZEB2-4KR weakens CtBP1 binding and enhances ZEB2 occupancy at the Nr4a1 promoter. Importantly, Nr4a1 knockdown abolished the protective effects of ZEB2-4KR. These findings identify SUMO-1 modification of ZEB2 as a central driver and molecular switch of pathological cardiac remodeling after MI and suggest that targeting ZEB2 SUMOylation may represent a promising therapeutic strategy.

Background Type A Aortic Dissection (TAAD) is a life-threatening disease that requires emergency surgical treatment. With a mortality rate reported as high as 2% per hour, the time to admission to hospital represent a crucial point in the management of these patients. This study aimed to assess how the time interval between onset of symptoms and hospital admission influences postoperative outcomes after TAAD repair. Methods From January 2011 to January 2020, 1406 consecutive patients underwent TAAD repair at our center. We included 1,228 patients who were admitted within 72 hours of symptom onset, and divided into two groups: 867 patients in the early (≤ 12 hours) and 361 in the late (> 12 hours and < 72 hours) admission group. Results Hypotension (11% vs 7.6%, p = 0.06) and bradycardia on admission (11% vs 1.9%, p < 0.01) were more common in the early group. This group also had a higher incidence of preoperative limb ischemia (17% vs 11%, p < 0.01) and higher rates of rescue surgeries (16% vs 11%, p = 0.05). Despite prompt intervention, the postoperative mortality rate (15% vs 9.4%, p = 0.01), stroke rates (5.8% vs 2.8%, p = 0.03) and postoperative kidney failure (29% vs 21%, p < 0.01) were higher in the early group. Conclusions Our analysis indicates that the timing of surgery in TAAD patients is primarily driven by the presence of more severe symptoms and signs of ischemia and, despite early treatment, these patients have increased rates of complications and mortality. This emphasizes the importance of the clinical status on admission, rather than the time, as the main driver for postoperative complications.

Objective Despite effective mechanical unloading, myocardial recovery after left ventricular assist device (LVAD) implantation remains highly heterogeneous. The determinants of this variable response, particularly the role of metabolic dysregulation during support, are incompletely understood. Methods In this multicenter, prospective cohort study, 54 consecutive patients (28 with type 2 diabetes mellitus (T2DM), 26 non-diabetic controls) undergoing LVAD implantation were followed longitudinally for up to 24 months. Serial assessments included the Triglyceride-Glucose (TyG) index (insulin resistance), soluble suppression of tumorigenicity-2 (sST2, fibrotic signaling), and left ventricular global longitudinal strain (LV-GLS, myocardial deformation). A surrogate composite fibrosis phenotype was defined by persistent elevation of sST2 (> 100 ng/mL at 6 and 12 months) combined with severely impaired LV-GLS (< 10% at 12 months). Results TyG remained elevated in T2DM during LVAD support (P<.001). No preoperative TyG-sST2 correlation, but significant positive association emerged from 6 months (all r > 0.50, P<.01) and persisted. LV-GLS recovery attenuated in T2DM vs. non-diabetics from 12 months. The surrogate composite fibrosis phenotype exclusively in T2DM (21.4% vs. 0%, P= .018). Conclusion Persistent insulin resistance during LVAD support is strongly associated with adverse remodeling, as characterized by delayed functional recovery and a surrogate fibrosis phenotype. These findings suggest that insulin resistance may represent a key therapeutic target beyond glycemic control in unloading-responsive myocardium, a hypothesis that warrants further investigation in prospective trials

To investigate surgical outcomes and prognostic factors in elderly patients (≥ 60 years) with valvular heart disease (VHD) undergoing surgery, and to provide evidence for optimizing clinical decision-making. A retrospective analysis was conducted on 347 elderly VHD patients who underwent valve surgery across three Chinese centers from December 2021 to June 2025. Baseline characteristics, comorbidities, preoperative cardiac function, surgical details, complications, and follow-up data were collected. Cumulative survival was estimated using Kaplan–Meier method, with subgroup comparisons by log-rank test. Independent prognostic factors were identified using multivariable Cox regression. Among 347 patients (53.9

BACKGROUND:End-stage heart failure (HF) remains a major global health challenge, and left ventricular assist devices (LVADs) represent an important therapeutic option. LVAD-mediated mechanical unloading improves cardiac function and promotes myocardial recovery in many patients with HF; however, this recovery response is suboptimal in obese patients. The mechanisms by which LVAD-mediated unloading induces myocardial recovery, and how obesity alters these processes to blunt myocardial recovery, remain poorly understood. METHODS:Patients with HF receiving LVAD support were recruited to investigate the correlation between patients' body mass index and the myocardial recovery response following LVAD implantation. In parallel, a mouse model of heterotopic cervical heart transplantation was used to simulate LVAD-mediated cardiac unloading. Single-nucleus RNA sequencing and stable-isotope tracing metabolomics were performed to explore the changes of signaling pathways and metabolic processes in unloaded hearts. In vitro cyclic stretch assays were used to evaluate how reduced mechanical load regulates cardiomyocyte metabolic pathways. Unloaded hearts from HF mice were used to determine whether the identified metabolic processes contribute to unloading-induced myocardial recovery. Furthermore, the unloaded hearts from obese HF mice were used to evaluate whether these metabolic adaptations are attenuated by obesity. RESULTS:HF patients with a higher body mass index (≥28.0) and greater insulin resistance tended to have poorer LVAD-mediated myocardial recovery. Single-nucleus RNA sequencing showed that mechanical unloading activated myocardial insulin signaling and increased glucose uptake. Stable-isotope tracing metabolomics further revealed that glucose taken up by unloaded hearts was preferentially shunted into the pentose phosphate pathway. Mechanistically, reduced mechanical stress attenuated Hippo pathway activation in cardiomyocytes, facilitating insulin signaling and enhancing pentose phosphate pathway flux. In unloaded hearts from HF mice, increased pentose phosphate pathway flux could reduce oxidative stress and exert cardioprotective effects. However, these benefits were blunted by insulin resistance in obese mice, whereas treatment with insulin sensitizers alleviated insulin resistance and restored unloading-mediated cardioprotection. CONCLUSIONS:In failing hearts, mechanical unloading leads to activation of insulin signaling, resulting in increased glucose uptake and enhanced pentose phosphate pathway flux to protect cardiomyocytes against oxidative stress. However, this cardioprotective effect is attenuated by obesity-induced insulin resistance. Administration of insulin sensitizers has the potential to improve LVAD-mediated myocardial recovery in obese patients with HF.