Accurate quantification of aortic valve calcification (AVC) on contrast-enhanced computed tomography angiography (CTA) is pivotal for planning surgical and transcatheter aortic valve replacement. The optimal Hounsfield unit (HU) threshold for calcification detection on contrast-enhanced images remains unresolved, and every prior validation study has relied on non-contrast Agatston scoring—itself an imaging estimate—as the reference standard. This study validated two widely used fixed HU thresholds (450 HU and 850 HU) and a self-configuring nnU-Net deep learning model against ex vivo gravimetric calcium weight as an absolute physical ground truth. Four hundred patients were included in a retrospective cohort study with a pre-specified temporal validation split: 300 with CT-confirmed AVC and 100 with normal aortic valves. Fifty chronologically later AVC patients who underwent elective open surgical aortic valve replacement (SAVR) within seven days of clinically indicated pre-operative contrast-enhanced CTA formed the locked surgical validation cohort; their excised native leaflets underwent standardised high-temperature ashing (550 °C, 12 h) and analytical weighing (precision 0.1 mg) to obtain gravimetric calcium mass. The remaining 350 cases served exclusively for nnU-Net development (280 training / 70 internal validation). CT-derived calcium mass-equivalent estimates were quantified on the validation cohort and compared with gravimetric weight using Pearson and Spearman correlation and Bland-Altman analysis. The nnU-Net achieved the strongest observed correlation with gravimetric weight (Pearson r = 0.967; bias + 6.2 mg; RMSE 13.7 mg), significantly outperforming the 450 HU threshold for correlation (r = 0.864; bias + 36.2 mg; RMSE 42.1 mg; Steiger p < 0.001) and showing a non-significant trend toward stronger correlation than 850 HU (r = 0.929; bias + 17.5 mg; RMSE 23.9 mg; Steiger p = 0.085). Compared with 850 HU, nnU-Net provided lower bias and RMSE, although the difference in Pearson r did not reach statistical significance. The 450 HU method exhibited significant proportional bias (p = 0.024), whereas neither 850 HU nor nnU-Net did. The nnU-Net achieved a mean Dice coefficient of 0.873 and intersection-over-union of 0.812. Against physically weighed calcium, nnU-Net deep learning segmentation provided the most favourable overall performance profile on contrast-enhanced CTA, with the lowest bias and RMSE and the strongest observed correlation. The improvement in Pearson correlation over 850 HU represented a non-significant trend, whereas the error and agreement metrics favoured nnU-Net. Among fixed thresholds, 850 HU substantially outperformed 450 HU, offering direct physical-rather than surrogate imaging-evidence to support 850 HU as the preferred fixed threshold in standard contrast-enhanced protocols.

OBJECTIVE:To compare the efficacy and clinical outcomes of flexible band versus rigid ring annuloplasty for the correction of moderate tricuspid regurgitation (TR) or greater. METHODS:In this single-center randomized trial, adult patients with moderate or greater TR were assigned to receive either a flexible band or a rigid ring. The primary outcome was recurrent TR during follow-up. Secondary outcomes included death, permanent pacemaker implantation, and other adverse events. RESULTS:In total, 400 patients were randomized with a 1:1 ratio, and 321 were included in the final analysis (flexible band, n = 156; rigid ring, n = 165). Baseline characteristics were balanced between arms. At discharge, recurrent TR was significantly greater in the flexible band arm than the rigid ring arm (10.1% vs 3.8%, P = .03). However, the significance was no longer significant during follow-up (6.1%/patient-years vs 4.7%/ patient-years, P = .21). Multivariable analysis identified female sex (subdistribution hazard ratio [sHR], 2.16, 95% CI, 1.1-4.22, P = .025), preoperative severe TR (sHR, 2.09; 95% CI, 1.06-4.11, P = .033) and massive TR (sHR, 4.63; 95% CI, 1.29-16.61, P = .019), and preoperative permanent pacemaker implantation (sHR, 3.69; 95% CI, 1.35-10.09, P = .011) as independent risk factors for recurrent TR. Subgroup analyses based on these factors showed no significant between-arm difference in the primary outcome. secondary outcomes were also comparable between the arms during follow-up. CONCLUSIONS:Both annuloplasty devices provided acceptable TR correction with similar adverse event rates over a median 3-year follow-up.

Thoracic aortic dissection (TAD) is a life-threatening disorder with limited therapeutic options, critically linked to vascular smooth muscle cell (VSMC) phenotypic switching. Neuronal PAS Domain Protein 2 (NPAS2), a circadian rhythm-related transcription factor, regulates diverse physiological processes. However, the biological functions and underlying regulatory mechanisms of NPAS2 in VSMCs during TAD pathogenesis remain to be elucidated. NPAS2 expression decreased in TAD tissue samples, PDGF-BB-treated HASMCs and BAPN-administrated mice. NPAS2 depletion facilitated VSMC phenotype switching. VSMC-specific NPAS2 knockout (NPAS2SMKO) mice exhibited aggravated TAD. Mechanistically, NPAS2 depletion attenuates its transcriptional repression of LPCAT3, subsequently elevating the accumulation of phosphatidylcholines with two polyunsaturated fatty acyl chains (PC-PUFA2S), thereby promoting ferroptosis-induced VSMC phenotype switching and accelerating TAD progression. Targeting NPAS2 represents a potential therapeutic strategy for TAD treatment.

Introduction and objectivesLeft ventricular reverse remodeling (LVRR) after transcatheter aortic valve replacement (TAVR) is associated with outcomes, but the relevance of aortic-root geometry remains uncertain. We examined whether the annular eccentricity index (EI) and sinus of Valsalva height on computed tomography angiography (CTA) were associated with 1-year LVRR.MethodsThis retrospective secondary analysis included 115 patients with severe aortic stenosis from an 11-center cohort who underwent successful TAVR and survived to undergo evaluable preprocedural CTA and 1-year echocardiography. EI was calculated as the difference between maximum and minimum annular diameters divided by the maximum diameter. Sinus height was the mean perpendicular distance from the annular plane to the sinus tip across the three sinuses. LVRR was defined as an increase in left ventricular ejection fraction of at least 5 percentage points or a decrease in indexed left ventricular end-diastolic volume of at least 15%. A fixed multivariable logistic model adjusted for baseline ventricular function and clinical covariates; Firth bias-reduced logistic regression was used for primary inference because the smaller outcome group contained 37 patients, with conventional maximum-likelihood estimation as a sensitivity analysis.ResultsLVRR occurred in 78 patients (67.8%). In the primary Firth analysis, each 1-standard deviation (SD) decrease in EI was associated with higher odds of LVRR (adjusted odds ratio, 2.40; 95% confidence interval, 1.52–3.92; P < 0.001), as was each 1-SD increase in sinus height (adjusted odds ratio, 1.84; 95% confidence interval, 1.23–2.74; P = 0.003). Conventional maximum-likelihood estimates were directionally consistent. Model performance was lower after bootstrap optimism correction (area under the curve, 0.77 vs. 0.81 apparent).ConclusionsAmong patients who survived to undergo evaluable 1-year echocardiography, a lower EI and greater sinus height were associated with LVRR after TAVR. These hypothesis-generating associations require external validation before clinical application.

INTRODUCTION:Trans-thoracoscopic atrial fibrillation (AF) ablation combined with left atrial appendage excision (LAAE) is an alternative treatment approach for nonvalvular AF patients with a history of thromboembolic events. The primary objective of this research was to investigate the electrophysiological characteristics of recurrent atrial tachyarrhythmias and rhythm outcome in patients receiving repeat catheter ablation after surgical AF ablation plus LAAE. METHODS:Nonvalvular AF patients with previous thromboembolic events who underwent trans-thoracoscopic AF ablation plus LAAE and then received radiofrequency catheter ablation were enrolled. During the procedure, the reconnection of the left atrium (LA) and pulmonary veins (PVs) was investigated, and three-dimensional activation mapping of the LA and/or right atrium during atrial tachyarrhythmias was performed. RESULTS:From January 2014 to December 2021, 173 patients without a history of prior ablation underwent concurrent trans-thoracoscopic AF ablation and LAAE. A total of 74 patients experienced recurrent atrial tachyarrhythmias during a median follow-up period of 3.5 years (interquartile range [IQR]: 2.0 to 5.0 years) after the surgical procedure. A total of 22 patients with atrial tachyarrhythmias recurrence (11 males, aged 60 ± 9 years) underwent radiofrequency catheter ablation. Among them, 10 patients with recurrent AF were identified, and in two of them, non-PV triggers originated from the interatrial septum and the superior vena cava. Reconnected LA-PV conduction was detected in 12 patients, with a total of 27 PV gaps. Eighteen of these PV gaps were located at the roof or the bottom. Thirteen sustained atrial tachycardias (ATs) were mapped in 12 patients, including peri-mitral AT (n = 7), cavotricuspid isthmus-dependent AT (n = 3), remnant LAA-related micro-reentrant AT (n = 1), roof-dependent reentry AT (n = 1), and focal AT (n = 1). At a median follow-up of 9 months (IQR: 3-20 months) after the ablation procedure, the freedom rate from atrial tachyarrhythmias was 77%. CONCLUSION:Reconnection of LA-PVs and macro-reentry ATs are common in repeat catheter ablation after surgical treatment for AF, with peri-mitral AT being the most frequently observed AT. PV gaps are most often located at the roof or bottom. Additionally, LAAE may contribute to arrhythmogenesis in certain patients. Catheter ablation targeting these mechanisms resulted in a favorable short- to mid-term rhythm outcome.

Ulinastatin is a protease-inhibiting drug with anti-inflammatory and other pharmacological properties. Little is known regarding its role following acute type A aortic dissection (ATAAD) surgery. We perform a randomized controlled trial to investigate the protective effect of ulinastatin against negative inflammatory response and organ dysfunction in ATAAD surgery (PANDA). The primary outcome of mean daily Sequential Organ Failure Assessment (SOFA) score from baseline to 7 days of surgery is 8.80 (SD, 4.11) in the ulinastatin group and 8.61 (SD, 4.47) in the control group (mean difference between groups was 0.04; 95% confidence interval [CI], -0.24 to 0.33; p = 0.765). Systemic inflammatory response syndrome (SIRS) within 7 days of surgery is lower in the ulinastatin group than in the control group (p < 0.001). Additional ulinastatin to standard treatment is likely to reduce SIRS rates instead of preventing organ dysfunction, highlighting the potential importance of the benefits of anti-inflammatory pharmacotherapeutics. The trial is registered on clinicaltrials.org (NCT04711889).

Background: Acute type A aortic dissection (TAAD) is a life-threatening cardiovascular emergency with a high mortality rate. The peri-operative factors influencing in-hospital mortality among surgically treated TAAD patients remain unclear. This study aimed to identify key peri-operative risk factors associated with in-hospital mortality. Methods: Peri-operative laboratory data, surgical strategies, and TAAD-related risk factors, associated with mortality, were collected. Machine learning techniques were applied to evaluate the impact of various parameters on in-hospital mortality. Based on the findings, a nomogram model was developed and validated using area under the receiver operating characteristic curve (AUC) analysis, calibration plots, and internal validation methods. Results: A total of 199 patients with TAAD were included in the study cohort, which was divided into derivation and validation cohorts. Using the least absolute shrinkage and selection operator (LASSO) regression method, 66 features were narrowed down to six key predictors. These included age, lymphocyte count, use of continuous renal replacement therapy (CRRT), cardiopulmonary bypass (CPB) time, duration of mechanical ventilation, and postoperative interleukin-10 (IL-10) levels, all of which were identified as significant risk factors for in-hospital mortality following TAAD surgery. Conclusions: We developed and validated a predictive model, presented as a nomogram, to estimate in-hospital survival in patients with TAAD. Post-operative IL-10 was identified as an independent prognostic factor for patients with TAAD. The combination of IL-10 with five additional indicators significantly improved the predictive accuracy, demonstrating superiority over the use of any single variable alone. Clinical Trial Registration: This study protocol was registered at ClinicalTrials.gov (NCT04711889). https://clinicaltrials.gov/study/NCT04711889.

Ascending thoracic aortic aneurysm (ATAA) is a life-threatening disorder with limited therapeutic options, critically linked to vascular smooth muscle cell (VSMC) phenotypic switching. Neuronal PAS Domain Protein 2 (NPAS2), a circadian rhythm-related transcription factor, regulates diverse physiological processes. However, the biological functions and underlying regulatory mechanisms of NPAS2 in VSMCs during ATAA pathogenesis remain to be elucidated. NPAS2 expression decreased in ATAA patients, PDGF-BB-treated HASMCs and BAPN-administrated mice. NPAS2 depletion facilitated VSMC phenotype switching. VSMC-specific NPAS2 knockout (NPAS2SMKO) mice exhibited aggravated ATAA. Mechanistically, NPAS2 depletion attenuates its transcriptional repression of LPCAT3, subsequently elevating the accumulation of phosphatidylcholines with two polyunsaturated fatty acyl chains (PC-PUFA2S), thereby promoting ferroptosis-induced VSMC phenotype switching and accelerating ATAA progression. Targeting NPAS2 represents a potential therapeutic strategy for ATAA treatment. ### Competing Interest Statement The authors have declared no competing interest. National Natural Science Foundation of China, 82370376 National Science and Technology Major Project, 2024ZD0527202 Jiangsu Province Capability Improvement Project through Science, Technology and Education, ZDXK202230

It remains controversial as to which optimal cannulation strategy ought to be employed in surgery for type A aortic dissection (TAAD). The aim of this study was to make a comparison of the clinical outcomes between single and double arterial cannulation. From January 2018 to December 2022, 403 individuals with TAAD were recruited for the study and were divided into two groups based on the cannulation approach. A total of 206 patients underwent single arterial cannulation, while 197 patients underwent double arterial cannulation. In order to balance the data encompassing specific pathological traits, stabilized inverse probability weighting (IPTW) was utilized. Confounding variables that could potentially be associated with the outcomes were adjusted by means of multivariate logistic regression analysis with IPTW. There was a significant difference in in-hospital mortality (19.9% versus 9.1% for single versus double arterial cannulation, respectively, P < 0.01). The incidence of stroke and acute kidney injury requiring dialysis was lower in the double arterial cannulation group than in the single artery cannulation group, but there was no statistical difference. Compared with the single arterial cannulation cohort, the IPTW adjusted odds ratios for in-hospital mortality and stroke in the double arterial cannulation cohort were 0.436 (95% CI, 0.211-0.903, P < 0.01) and 0.52 (95% CI, 0.3-0.89, P = 0.017), respectively. Double arterial cannulation served as a protective factor for in-hospital mortality and stroke. Consistent findings were noted upon stratification based on age, sex, BMI, and the duration of cardiopulmonary bypass. By providing stable systemic organ perfusion, the establishment of CPB with DAC can constitute a safe technique for TAAD repair.

This study evaluated the impact of atrial fibrillation (AF) recurrence during the “blanking period” following thoracoscopic ablation on long-term AF recurrence. This prospective observational study enrolled consecutive patients who underwent thoracoscopic AF ablation at our center between 2013 and 2020. Patients were grouped based on AF recurrence during the 3-month blanking period: no recurrence (Group A), early recurrence only (0–7 days, Group B), late recurrence only (8 days-3 months, Group C), or both early and late recurrence (Group D). The primary endpoint was long-term AF recurrence. We finally analyzed 171 patients (mean age 62.5 ± 8.4 years, 34.5

OBJECTIVE:Aortic dissection (AD) is a life-threatening disease. Tankyrase1 (TNKS1), a PARylating ADP-ribosyl transferase, plays a major role in myogenesis, a vital process known to drive muscle fiber formation and regeneration.This study explores the impact of TNKS1 on the transformation of human aortic smooth muscle cells (HASMCs) in AD. METHODS AND RESULTS:Single-cell RNA sequencing was performed and clusters were used for between-disease differential gene expression analyses. In the AD aorta, WB, immunofluorescence and RT-q-PCR revealed that TNKS1 expression was elevated, accompanied by a disorganized cell phenotype. Further examination like WB，immunofluorescence,Scratch-Wound Assay confirmed the upregulation of TNKS1 triggers phenotypic switching.Subsequent studies revealed that ferroptosis played a key role in TNKS1-induced phenotypic switching. Increased ferroptosis markers, such as elevated iron content,ROS and lipid peroxidation, were observed in HASMCs overexpressing TNKS1, while inhibition of ferroptosis restored the contractile phenotype.Co-IP assay demonstrated a direct protein-protein interaction between TNKS1 and SLC7A11 at the molecular level. In vivo, the upregulation of TNKS1 not only activated ferroptosis but also triggered phenotypic transformation. CONCLUSION:This study demonstrates that TNKS1 is a key regulator of AD pathogenesis, driving HASMC phenotypic switching through ferroptosis activation, ultimately leading to aortic wall destabilization and dissection. Targeting TNKS1 or the ferroptosis pathway may offer novel therapeutic strategies for AD prevention and treatment.

BACKGROUND:To evaluate the clinical outcomes and the validity of the in situ needle fenestration (ISNF) technique during thoracic endovascular aortic repair (TEVAR) for patients with aortic arch conditions. METHODS:A total of 115 patients with aortic arch conditions treated with ISNF during TEVAR between January 2018 and December 2021 were incorporated. RESULTS:The median age of the patients was 62.0 years, and 10.4% (12/115) were female. The median follow-up time was 31.0 months. A total of 175 supra-arch branches were reconstructed. A single branch was fenestrated in 80 patients, while the left subclavian artery (LSA) and left common carotid artery (LCCA) were fenestrated simultaneously in 11 patients, and all supra-arch branches were fenestrated in 24 patients. The rate of technical success was 100%, 30-day mortality was 3.5% (4/115), overall mortality was 8.7% (10/115), and aortic-related mortality was 2.6% (3/115). Aortic-related reintervention was required in 7.8% (9/115) of patients. Among the major postoperative complications, four patients developed retrograde type A dissection requiring emergent open surgery, three patients had cerebrovascular accidents, and one patient had an endoleak. No occlusions or stenoses of the main or branch aortic stents were observed. CONCLUSIONS:The mid-term results of the ISNF technique during TEVAR for aortic arch conditions were within the acceptable range; however, further follow-up results are needed and long-term stability and durability needs to be assessed. Related fenestration devices also require further development.

Calcific aortic valve disease (CAVD) is a progressive cardiovascular disorder involving multiple pathogenesis. Effective pharmacological therapies are currently unavailable. Sirtuin6 (SIRT6) has been shown to protect against aortic valve calcification in CAVD. The exact regulatory mechanism of SIRT6 in osteoblastic differentiation remains to be determined, although it inhibits osteogenic differentiation of aortic valve interstitial cells. We demonstrated that SIRT6 was markedly downregulated in calcific human aortic valves. Mechanistically, SIRT6 suppressed osteogenic differentiation in human aortic valve interstitial cells (HAVICs), as confirmed by loss- and gain-of-function experiments. SIRT6 directly interacted with Runx2, decreased Runx2 acetylation levels, and facilitated Runx2 nuclear export to inhibit the osteoblastic phenotype transition of HAVICs. In addition, the AKT signaling pathway acted upstream of SIRT6. Together, these findings elucidate that SIRT6-mediated Runx2 downregulation inhibits aortic valve calcification and provide novel insights into therapeutic strategies for CAVD.

Objective: Calcific aortic valve disease (CAVD) is a prevalent condition in the elderly population, lacking effective medical treatments. Nesfatin-1, a hypothalamic peptide generated from Nucleobindin 2 processing, has been implicated in both physiological and pathological calcification. In this study, we aimed to investigate the role of Nesfatin-1 in facilitating the transformation of aortic valve interstitial cells (AVICs) in relation to CAVD. Methods and Results: In vitro experiments demonstrated that Nesfatin-1 treatment attenuated osteogenic differentiation of AVICs, while in vivo studies showed that it slowed down CAVD progression. RNA-sequencing analysis of AVICs treated with or without Nesfatin-1 revealed enrichment of the Ferroptosis pathway among the top 15 Kyoto Encyclopedia of Genes and Genomes pathways. Further investigations confirmed increased ferroptosis in calcified valves and osteoblast-like AVICs, with Nesfatin-1 treatment reducing ferroptosis in AVICs. Among the genes involved in the Ferroptosis pathway, ZIP8 exhibited the most significant change upon Nesfatin-1 treatment. Silencing ZIP8 enhanced ferroptosis and osteogenic differentiation in AVICs. Additionally, silencing ZIP8 reduced intracellular Mn2+ concentration, as well as the expression and activity of superoxide dismutase (SOD2). Concordantly, silencing SOD2 further enhanced ferroptosis and osteogenic differentiation in AVICs. Moreover, Nesfatin-1 treatment increased glutathione peroxidase 4 (GPX4) expression and glutathione (GSH) levels in AVICs, as confirmed by Western blotting and GSH concentration estimation. Conclusion: In summary, Nesfatin-1 inhibits osteogenic differentiation of AVICs by attenuating ferroptosis. This reduction in ferroptosis levels is mediated by the GSH/GPX4 and ZIP8/SOD2 axes.