BACKGROUND:Due to the heightened risks and complications associated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in complex high-risk and indicated patients (CHIPs), percutaneous ventricular assist system during PCI might offer a novel alternative. AIMS:We aimed to evaluate the efficacy and safety of the CorVad percutaneous ventricular assist system in CHIPs. METHODS:One hundred and eighteen CHIPs with left ventricular ejection fraction (LVEF) ≤ 40% were enrolled for CorVad support during elective PCI. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) including death, new myocardial infarction, stroke, and target vessel revascularization at 30 days. Performance goal (PG) was set at 22.5%. Additionally, patients underwent CABG in Fuwai Hospital with LVEF ≤ 40% were selected as historical controls. RESULTS:In the intention to treat (ITT) cohort, there were five MACCE (4.2%, 95% CI 1.4%-9.6%) within 30 days, achieving the prespecified PG. The CorVad system was successfully implanted in all patients. Compared with baseline, the LVEF had a significant increase in 48 h (30.95 ± 4.84% vs. 35.96 ± 5.84%, p < 0.001) and 30 days after PCI (30.95 ± 4.84% vs. 39.78 ± 7.82%, p < 0.001). No patient had evidence of hemolysis after PCI. Compared with CABG historical controls, there were no significant differences in the incidence of MACCE at 30 days (after propensity score matching [PSM]: 3.8% vs. 1.3%, p = 0.341) and 90 days (after PSM: 3.8% vs. 1.3%, p = 0.307). CONCLUSIONS:The CorVad percutaneous ventricular assist system is safe and effective in assisting CHIPs-PCI.

Adult human primary cardiomyocytes (hPCMs) is a high-fidelity and informative cardiac model that is expected to advance our knowledge of the human heart. However, currently, no method exists that recovers hPCMs from cryopreservation with high efficiency, limiting their use as a versatile research model. Based on our previous success with isolated hPCMs, we designed a new strategy that cryopreserves myocardial tissue at a specific step during hPCM dissociation, i.e., after sectioning tissue chunks into tissue slices. This method yielded cell viabilities comparable to that of freshly isolated hPCMs, and surpassed the performance of cell isolation from cryopreserved tissue chunk, as well as recovery of frozen isolated cells. We demonstrate cytoskeletal, ultrastructural, transcriptomic, metabolic, electrophysiological recovery of these cells both over short-term (1 week) and long-term (6-12 months) storage. In addition, these cells responded promptly to external stimuli, including adrenergic stimulation and hypoxic stress, suggesting functional integrity. Our study illustrates an optimized cryopreservation protocol for the functional recovery of cardiomyocytes from myocardial tissue, broadening their applications in basic and translational research, and opens up the possibility for cell banking.

BACKGROUND:Functional valve regurgitation (FVR) progression has traditionally been attributed to external anatomic alterations, without consideration of leaflet-intrinsic pathology. Emerging evidence now implicates valvular leaflets as active contributors rather than passive bystanders in FVR pathogenesis. Systematic investigations into leaflet-specific pathomechanisms remain absent for major FVR subtypes, particularly functional mitral regurgitation (FMR) and functional tricuspid regurgitation (FTR).METHODS:The association of FVR with clinical parameters was analyzed in a heart transplantation cohort. Comprehensive microscopic pathology evaluated fibrotic remodeling in mild, moderate, and severe FMR/FTR leaflets, validated in an independent bulk RNA sequencing cohort (FMR/FTR: n=41 each). Single-cell RNA sequencing was performed on 19 FVR leaflets (FMR: 3 mild/2 moderate/3 severe; FTR: 5 mild/3 moderate/3 severe). Subsequent analyses (cluster annotation, cellular proportions, trajectory inference, and cell-cell communication) explored cellular mechanisms of fibrotic remodeling in FVR, focusing on unique and shared changes between FMR and FTR. Histopathology and bulk transcriptomics validated single-cell RNA sequencing findings. Primary valvular endothelial cells and valvular interstitial cells from FVR patients underwent pharmacological intervention. A monocrotaline-induced rat pulmonary hypertension model established FTR, followed by pharmacological treatment to assess leaflet-directed therapy efficacy.RESULTS:Fibrotic leaflet remodeling scores independently predicted FMR/FTR severity with high precision and significantly improved prediction beyond anatomic anomalies. Fibrotic remodeling showed divergent mechanisms between FMR and FTR. In FMR, suppressed retinoic acid metabolism drove antifibrotic-to-neutral valvular interstitial cell transition. In FTR, impaired IFN (interferon) signaling promoted antifibrotic-to-profibrotic valvular interstitial cell transdifferentiation, worsened by endothelial-to-mesenchymal transition-derived profibrotic valvular endothelial cells. Targeted PDK4 (pyruvate dehydrogenase kinase 4) upregulation or IFN signaling activation reduced FTR severity in vitro and in vivo.CONCLUSIONS:Leaflet-specific organic fibrotic remodeling actively involves FVR beyond functional adaptation, with distinct fibrotic mechanisms in FMR versus FTR. PDK4 and IFN modulation demonstrate therapeutic potential for FTR.

OBJECTIVES:This study aims to compare intraoperative blood transfusion and perioperative outcomes for patients undergoing left ventricular assist device (LVAD) implantation before and after the implementation of a blood conservation protocol. METHODS:This retrospective cohort study included patients who underwent LVAD implantation from June 2017 to October 2024 at our Hospital. The primary outcome was total intraoperative transfusion volume, and secondary outcomes included intraoperative transfusion volume and rates of red blood cells (RBC), fresh frozen plasma (FFP), platelets, and reoperation due to bleeding. Exploratory outcomes included mortality and serious complications before hospital discharge. RESULTS:In total, 120 patients were included, with 62 receiving traditional care and 58 treated with blood conservation protocol. After protocol implementation, total intraoperative transfusion volume decreased from 3.23 ± 3.24 units to 1.74 ± 1.56 units (P = 0.002). The intraoperative RBC transfusion rate dropped from 30.6% to 8.6% (P = 0.003), and the transfusion volume fell from 1.00 ± 1.71 units to 0.31 ± 1.05 units (P = 0.009). In multivariate analysis, the protocol was significantly associated with reduced total intraoperative transfusion volume, lower RBC transfusion volume and rate, and shorter ICU and hospital stays, while not correlated with perioperative mortality or serious complications. CONCLUSIONS:The blood conservation protocol significantly reduced intraoperative transfusion in LVAD patients and expedited recovery.

Vascular smooth muscle cell (VSMC) migration is the key event in the pathogenesis of atherosclerosis (AS) and plaque instability. Trimethylamine-N-oxide (TMAO) induces VSMC migration to promote the progression of AS. However, the effects of the N6-methyladenosine (m6A) modification on this process remain unclear. Here, TMAO increased total m6A levels in human aortic smooth muscle cells (HASMCs) and decreased fat mass and obesity-associated protein (FTO) and YTH domain-containing family protein 2 (YTHDF2) protein expression. FTO or YTHDF2 overexpression significantly inhibited HASMC migration induced by TMAO. Mechanistically, the COL3A1 gene was shown to be critical for the regulation of HASMC migration by FTO or YTHDF2. Furthermore, methylated RNA immunoprecipitation and RNA stability assays demonstrated that FTO bound to the COL3A1 mRNA and altered its m6A modification, resulting in its decay. In vivo, VSMC-specific FTO or YTHDF2 deletion aggravated AS and plaque instability, whereas adeno-associated virus serotype 9 (AAV9)-mediated VSMC-specific YTHDF2 overexpression or COL3A1 knockdown exerted protective effects on AS and/or plaque instability. Notably, VSMC-specific FTO deletion promoted VSMC migration in atherosclerotic lesions in ApoE−/− AS model mice, whereas VSMC-specific YTHDF2 overexpression had the opposite effect. Overall, the in vitro and in vivo evidence highlights the critical role of the FTO/YTHDF2/COL3A1 axis in VSMC migration, AS, and plaque instability, suggesting that targeting the FTO/YTHDF2/COL3A1 axis in VSMCs may be a novel and promising therapeutic strategy for the treatment and prevention of AS and plaque instability.

Continuous-flow left ventricular assist devices (CF-LVAD) have been increasingly implemented in China as a vital life-support strategy for patients with end-stage heart failure. Non-pulsatile blood flow is a defining physiological characteristic of CF-LVAD. Although an association between reduced pulsatility and adverse outcomes continues to be proposed, robust clinical evidence remains lacking. Retrospective study of adults (>18 years) receiving CF-LVAD at four Chinese centers (Jan 2019 - Jul 2024) was conducted. Systemic pulsatility index (SPI, calculated as pulse pressure divided by the mean arterial pressure) was derived from blood pressure measurements pre-LVAD and serially post-LVAD (days 1,7,14,21,28). Latent Class Trajectory Modeling (LCTM) identified distinct population groups based on SPI trajectories. The primary outcome of this study was major adverse events (MAE) within 90 days, including all-cause mortality and complication events. The secondary outcome was the evaluation of each complication event, mortality, ICU and hospital-free days. Among 115 LVAD patients (mean age 49.4 years, 87.8

OBJECTIVE:To investigate the associations of oxidative balance score (OBS) with all-cause mortality, cardiovascular mortality and cardiovascular disease (CVD) incidence in two large, population-based cohorts. DESIGN:Cohort study and cross-sectional study were used. SETTING:The US National Health and Nutrition Examination Survey (NHANES) and the UK Biobank. PARTICIPANTS:A total of 33 566 adults from NHANES (1998-2018) and 55 760 adults from the UK Biobank were included. MAIN OUTCOME MEASURES:All-cause mortality, cardiovascular mortality and CVD. Mortality outcomes were ascertained through national death registries. Prevalent CVD was identified in NHANES through questionnaire, and incident CVD events were identified in the UK Biobank using linked hospital admission and death registry data. RESULTS:Higher OBS was consistently associated with lower all-cause and cardiovascular mortality in both cohorts. In NHANES, participants in the highest OBS quartile (Q4) had a 39% lower risk of all-cause mortality (adjusted HR: 0.61, 95% CI 0.52 to 0.72) and a 45% lower risk of cardiovascular mortality (adjusted HR: 0.55, 95% CI 0.41 to 0.74) compared with those in Q1. Similarly, in the UK Biobank, Q4 was associated with an 18% lower risk of all-cause mortality (adjusted HR: 0.82, 95% CI 0.74 to 0.91) and a 41% lower risk of cardiovascular mortality (adjusted HR: 0.59, 95% CI 0.4 to 0.87). In NHANES, Q4 was associated with lower odds of prevalent CVD (adjusted OR: 0.56, 95% CI 0.46 to 0.67), whereas in the UK Biobank, Q4 was associated with a 19% lower risk of incident CVD during follow-up (adjusted HR: 0.81, 95% CI 0.74 to 0.9). Subgroup analyses in NHANES indicated heterogeneity by ethnicity and socioeconomic status, whereas associations in the UK Biobank followed an L-shaped pattern with a flattening of estimated risk at moderate OBS levels. CONCLUSION:Higher OBS was associated with more favourable mortality and cardiovascular outcomes. These findings indicate that OBS is a composite indicator associated with cardiovascular health at the population level.

BACKGROUND:The routine implementation of heart teams for patients with complex coronary artery disease (CAD) is challenging due to the insufficient multidisciplinary specialist resources for face-to-face discussion. A real-time heart team during the angiography, based on an online meeting, offers the potential to efficiently integrate resources. OBJECTIVES:In this study, we sought to evaluate the implementation value and safety of a "real-time heart team" decision making approach. METHODS:This noninferiority randomized controlled trial enrolled patients with de novo left main or 3-vessel CAD at 3 cardiac centers. Patients were randomly assigned to the conventional heart team group (discussed by a face-to-face meeting after the angiography) or the real-time heart team group (discussed by an online meeting during the angiography). Implementation value outcomes included care efficiency (waiting time for treatment, recatheterization, specialist workload, and economic outcomes) and process evaluation metrics (discussion adequacy, surgeon participation, and shared decision making). The safety outcomes were a composite of 1-year major adverse cardiovascular and cerebrovascular events (MACCE) (including all-cause mortality, myocardial infarction, stroke, unplanned revascularization, and readmission due to reangina) and revascularization decision making. RESULTS:Overall, 490 complex CAD patients were included, with 245 patients in each group. Waiting time for final therapy (median: 2 days [Q1-Q3: 0-7 days] vs 5 days [Q1-Q3: 2-10 days]; P < 0.001), recatheterization rate (12.5% vs 98.9%; P < 0.001), specialist high workload rate (5.3% vs 29.0%; P < 0.001), and percutaneous coronary intervention (PCI) hospitalization cost (percentage of decrease: 18.0%; P < 0.001) were significantly reduced in the real-time group. More discussion time spent (4.0 ± 1.8 min vs 3.4 ± 1.6 min), better specialist satisfaction (based on NASA Task Load Index scale), more chief surgeon participation (26.5% vs 18.8%), but less multidisciplinary synchronous shared decision making (2.0% vs 11.5%) were found in the real-time group. The real-time heart team group was noninferior to the conventional group in 1-year MACCE (8.2% vs 10.6%; risk difference: -2.45%; 95% CI: -7.61%-2.71%; P for noninferiority < 0.001). The proportions of PCI, coronary artery bypass grafting, and medical therapy were similar between the 2 groups (P = 0.892). CONCLUSIONS:Compared with the conventional heart team, the real-time heart team significantly improved care efficiency and process evaluation metrics, with similar clinical outcomes and decision making. However, insufficient shared decision making and intercenter generalizability should be optimized before widespread implementation of this approach. (Feasibility and Effectiveness of a Real-Time Heart Team Approach in Complex CAD [EHEART; NCT05514210]).

BACKGROUND AND AIMS:While surgical left atrial appendage occlusion (SLAAO) reduces stroke in atrial fibrillation (AF) patients, its efficacy in patients without pre-operative AF but with CHA₂DS₂-VASc ≥2 remains uncertain despite their high post-operative AF risk (15-54%). The aim of this study was to evaluate whether prophylactic SLAAO reduces post-operative thrombo-embolic events in valvular surgery patients. METHODS:The OPINION was a multicentre, open-label, randomized, superiority trial conducted at three cardiac surgery centres in China. Eligible non-AF patients with CHA₂DS₂-VASc ≥2 and an indication for valve repair or replacement due to mitral or aortic valve lesions were randomly assigned (1:1) to undergo SLAAO (intervention arm) or not undergo SLAAO (control arm) during surgery. The primary outcome was a composite of ischaemic stroke, transient ischaemic attack (TIA), or cardiovascular mortality assessed at 1 year. The primary analysis was done in the intention-to-treat population. RESULTS:Between April 2021 and June 2024, a total of 2157 patients were enrolled and randomized. After exclusion of 39 patients who withdrew informed consent, 2118 participants were included in the intention-to-treat population (1062 in the SLAAO group and 1056 in the control group). Baseline characteristics were well-balanced between the SLAAO group and control group (mean age 55.5 [11.4] vs 55.6 [11.5] years, P = .65; female 32.9% vs 32.3%, P = .78; CHA2DS2-VASc score 2.88 [0.98] vs 2.87 [0.96], P = .83; median EuroSCORE II 1.58% [1.42%] vs 1.56% [1.28%], P = .74). The 1-year primary endpoint occurred in 73 (6.9%) patients in the SLAAO group and in 87 (8.2%) patients in the control group (hazard ratio 0.83; 95% confidence interval 0.61-1.14; P = .25). CONCLUSIONS:For valvular surgery patients with CHA₂DS₂-VASc scores ≥2 but no pre-operative AF, routine prophylactic left atrial appendage closure did not significantly reduce the incidence of the primary composite endpoint (ischaemic stroke, TIA, and cardiovascular mortality) at 1-year follow-up. TRIAL REGISTRATION:ChiCTR.org registry ChiCTR2100042238.

OBJECTIVES:Left Ventricular Assist Devices have become an important therapy for advanced heart failure. We present 2-year results of the prospective, multicentre clinical trial in China, showing long-term efficacy and safety of a novel miniaturized magnetically levitated, continuous-flow left ventricular assist system. METHODS:Patients were adults with a left ventricular ejection fraction <30% and a cardiac index < 2.0 L/min/m2 without inotropic, or dependence on continuous intravenous inotropes. Clinical data, including survival status, laboratory parameters, adverse events, and functional status, were collected at baseline and at 3, 6, 12, and 24 months and analysed. The primary end-point was the composite of survival at 2 years (on device support, transplant, or recovery), free of disabling stroke or device replacement. RESULTS:A total of 50 patients were enrolled in 12 centres between January 2022 and July 2022. At the 2-year follow-up, 39 patients (78%) remained on device support, 3 patients (6%) received heart transplants, and 1 patient (2%) had the device explanted due to cardiac recovery. The 2-year event-free survival was 86% (95% Confidence Interval [CI]: 73.3% - 94.2%). Major adverse events included right heart failure (n = 2, 4%), stroke (n = 3, 6%), driveline infection (n = 6, 12%), and gastrointestinal bleeding (n = 2, 4%). No haemolysis or device malfunction occurred. CONCLUSIONS:This study demonstrates promising long-term effectiveness and safety of the Corheart 6 left ventricular assist system for circulatory support in patients with advanced heart failure.ClinicalTrials.gov: NCT05353816.

Valvular heart disease imposes a heavy global clinical burden, and conventional mechanical and bioprosthetic valves struggle to achieve an optimal balance between long-term durability and in vivo biocompatibility. Siloxane polyurethane urea (SiPUU) serves as a commonly used polymer matrix for heart valve research owing to its intrinsic favorable cytocompatibility. Nevertheless, its insufficient tear resistance and inferior cyclic fatigue properties render it incompatible with the surgical suturing and forming procedures of prosthetic heart valves. To overcome the mechanical bottlenecks of existing polyurethane valve materials, we engineered a library of polyurethane-urea thermoplastic elastomers (Fuwai Material (J), FWJ series) by embedding abundant N-H moieties along the polymer backbone to amplify intermolecular hydrogen-bonding interactions. The top-performing variant 2NO-FWJ delivers a suite of valve-matching superior mechanical properties: a tear strength of 158.64 N/mm (55.07% higher than conventional polyurethane matrices), an elongation at break of 1686.80%, and a Young's modulus of 15.74 MPa. Under simulated physiological circulation, the material maintains robust structural integrity beyond 200 million fatigue cycles while presenting ideal hemodynamic metrics (effective orifice area ≥1.99 cm2 and transvalve pressure differential ≤11.6 mmHg). Distinct from prior polymer biocompatibility assessments relying on immortalized cell lines, this work pioneers biocompatibility characterization utilizing multiple types of primary human cardiac cells. In vitro biological characterizations suggest that 2NO-FWJ displays mild cellular toxicity, limited protein adhesion, moderate antidegradation ability against enzymes, and favorable hemocompatibility. Benefiting from hydrogen-bond-reinforced intermolecular networks, the developed FWJ elastomers simultaneously resolve the insufficient tear resistance and poor long-term fatigue durability of prevailing polymeric valve substrates and display immense translational potential for surgical suturable artificial heart valve fabrication.

Evidence from the fully magnetically levitated HeartMate 3 has suggested that aspirin omission may be safe and potentially beneficial. CH-VAD, a novel fully magnetically levitated ventricular assist device, has historically used standard anticoagulation protocols. This multicenter, retrospective study aimed to assess the impact of aspirin omission on hemocompatibility-related adverse events (HRAE) in CH-VAD patients. Among 274 patients implanted with the CH-VAD across 13 centers in China, 220 met the inclusion criteria; 155 received aspirin plus warfarin, and 65 received warfarin alone. The primary endpoint was survival free from major nonsurgical HRAEs, defined as stroke, pump thrombosis, major bleeding, or peripheral arterial thromboembolism beyond 14 days postimplantation. During a median follow-up of 368 days (interquartile range [IQR], 173-597), 186 patients (84.5%) met the primary endpoint. Twelve month survival free from major nonsurgical HRAEs was 85.7% in patients treated with warfarin alone and 82.6% in those treated with warfarin and aspirin (log-rank p = 0.8771). Rates of thrombotic and hemorrhagic complications were not significantly different. In multivariable Cox modeling, baseline estimated glomerular filtration rate was the only independent predictor of HRAEs. In clinically stable CH-VAD recipients, warfarin monotherapy was not associated with a higher rate of HRAEs.

OBJECTIVES:To evaluate the efficacy of dual antiplatelet therapy (DAPT) for three months versus 12 months in saphenous vein graft occlusion while reducing bleeding risk. DESIGN:Multicentre, non-inferiority, double blind, randomised controlled trial. SETTING:13 cardiac surgery centres in China, with enrolment between February 2023 and July 2024. PARTICIPANTS:2300 participants aged 18 to 80 years who underwent elective primary coronary artery bypass grafting with ≥1 saphenous vein graft. INTERVENTIONS:Participants were randomly assigned (1:1) to receive DAPT (ticagrelor 90 mg twice daily plus aspirin 100 mg once daily) for 12 months or the same dual antiplatelet regimen for the first three months, followed by placebo plus aspirin for nine months. MAIN OUTCOME MEASURES:The primary outcomes were saphenous vein graft occlusion at one year (non-inferiority) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (superiority). Secondary outcomes were major adverse cardiovascular events (MACCE), saphenous vein graft failure, venous or arterial graft stenosis, and venous or arterial graft occlusion. RESULTS:2290 patients (mean age 61.5 (standard deviation (SD) 8.4) years, 20.6% (n=472) women) were included in the modified intention-to-treat set. The mean number of saphenous vein graft segments was 2.5 (SD 0.8). 2070 patients (90.4%) with a total of 5125 saphenous vein graft segments were assessed at one year. Saphenous vein graft occlusion occurred in 280 of 2596 (10.8%) in the three month DAPT group and 283 of 2529 (11.2%) in the 12 month DAPT group (absolute difference -0.31%, 95% confidence interval (CI) -3.13% to 2.52%; P=0.008 for non-inferiority). During a median follow-up of 368 (interquartile range 358-382) days, BARC type 2, 3, or 5 bleeding occurred in 95 patients (8.3%) in the three month DAPT group and 149 patients (13.2%) in the 12 month DAPT group (absolute difference -4.67%, 95% CI -7.18% to -2.16%; P<0.001). The number needed to treat to prevent one bleeding event was 21 (95% CI 13 to 46). MACCE occurred in 26 (2.3%) patients in the three month DAPT group and 27 (2.7%) in the 12 month DAPT group (absolute difference -0.11%, 95% CI -1.48% to 1.26%). The findings for other secondary outcomes were also similar between the two groups. CONCLUSIONS:A three month DAPT strategy was non-inferior to the 12 month DAPT strategy in saphenous vein graft occlusion and was superior in reducing bleeding risk. TRIAL REGISTRATION:ClinicalTrials.gov NCT05380063.

Drug-induced mitochondrial toxicity is a major contributing factor to cardiotoxicity, which can cause drug attrition and adverse cardiac events. To assess the toxicity of anti-inflammatory agents, we used adult human primary cardiomyocytes (hPCMs) to screen 18 clinically available anti-inflammatory drugs in a high-content manner, and revealed widespread mitochondrial dysfunction without affecting cell viability. Nabumetone, a representative nonsteroidal anti-inflammatory drug with profound mitochondrial toxicity, induced mitochondrial fission, inhibited mitophagy, and impaired both electrophysiological and metabolic functions in adult hPCMs. Mechanistically, we uncovered that nabumetone (Nab) exerted its toxic effects through the prostaglandin E2- E-type prostanoid receptor 4 (PGE2-EP4) pathway, which was essential for its anti-inflammatory functions. To find an alternative route to ameliorate mitochondrial damage, we identified SIRT3 as a downstream target of nabumetone. Its mRNA, protein, and activity levels were significantly reduced upon nabumetone treatment. SIRT3 activator honokiol exhibited protective potential against NSAID-induced mitochondrial toxicity both in hPCMs and in nabumetone-treated mice. Finally, through screening mitochondrial liability in various common cardiomyocyte models, we identified mitochondrial abundance as an important determinant of the sensitivity of cells towards mitochondrial toxicants. Our study demonstrates the vast presence of mitochondrial dysfunction in human adult cardiomyocytes imposed by clinically used anti-inflammatory drugs, and identified both toxicity and protective pathways that may serve future therapeutic purposes.

BACKGROUND:Vascular smooth muscle cell (VSMC) phenotype switching plays a significant role in the pathogenesis of atherosclerosis (AS). However, the subtypes of VSMC transdifferentiation and their impact on AS progression and atherosclerotic plaque instability remains unclear. METHODS:We reanalysed scRNA-seq datasets of GSE155513 and GSE253903 and performed single-sample gene set enrichment analysis (ssGSEA) in three transcriptome datasets from unstable plaques to determine the major subtypes contributing the most to plaque instability. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA), we identified hub genes in macrophage (MP)-like smooth muscle cells (SMCs) of unstable plaques. We conducted cell communication analysis according to tensin1 (TNS1) gene levels in VSMCs. TNS1 expression was analysed in human AS plaques. Finally, an AS model was established in VSMC-specific Tns1 knockout ApoE-/- mice to validate the causative role of TNS1 on atherosclerotic lesions. RESULTS:MP-like SMC was identified as the key subtype for plaque instability. hdWGCNA analysis for MP-like SMC identified blue module as the key gene module involved in unstable plaques. Decreased TNS1 expression in VSMCs was positively correlated with the down-regulation of contractile VSMC marker genes, SRF and MYCOD genes, negatively correlated with the up-regulation of CD68 and KLF4 genes, and activated VCAM, PDGF, THBS and CXCL signalling pathways. TNS1 mRNA expression levels were lower in human atherosclerotic arteries than in healthy arteries, and even lower in unstable plaques than in early and stable plaques. TNS1 protein levels in VSMCs were lower in human atherosclerotic plaques than in healthy arteries, and even lower in advanced plaques than in early plaques. VSMC-specific Tns1 gene deficiency aggravated AS progression and enhanced plaque instability with increased MP-like SMC transdifferentiation. CONCLUSION:The reduction of TNS1 gene in VSMCs might drive contractile VSMC transdifferentiation into MP-like SMC, the major subtype contributing to plaque instability. In vivo experimental results confirmed the role of Tns1 gene in contractile VSMC transdifferentiation into MP-like SMC and plaque instability.

BackgroundCardiac surgery-associated acute kidney injury (CSA-AKI) is driven partly by venous congestion, yet no single bedside measure fully captures volume status: central venous pressure (CVP) reflects venous pressure, not plasma-volume expansion. Whether dynamic estimated plasma volume status (ePVS), a non-invasive marker derived from routine hemoglobin and hematocrit, conveys AKI-relevant information independent of and complementary to CVP is unknown.MethodsIn 4,818 adult patients with coronary artery bypass grafting (CABG) from Medical Information Mart for Intensive Care IV, version 3.0 (MIMIC-IV v3.0), serial ePVS over the first 48 h after admission to the intensive care unit (ICU) was modeled by latent-class linear mixed modeling to identify dynamic phenotypes. The primary outcome was Kidney Disease: Improving Global Outcomes (KDIGO) acute kidney injury (AKI) stage ≥ 2 within 72 h. Independence from CVP was tested by the ePVS-CVP correlation, progressive adjustment for admission CVP, CVP-stratified analysis with a trajectory by CVP interaction term, and parallel multiple-mediator analysis (24-h ΔHgb, peak CVP, net fluid balance). Forward-time landmark analyses and incremental-value metrics [Δ area under the curve (ΔAUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision-curve analysis] were also performed.ResultsFour phenotypes emerged: Low-stable (58.5%), Gradually-increasing (6.9%), Rapid-decline (8.7%), and High-stable (25.9%). Admission ePVS and CVP were essentially uncorrelated (Spearman r = 0.04), indicating non-redundant axes. Only the Gradually-increasing phenotype was independently associated with AKI (Model 3 OR 1.47, 95% CI 1.14 to 1.89), and this was barely changed by adjustment for admission CVP (from 1.58 in Model 1 to 1.49 in Model 2); peak CVP mediated only 9.9% of the total effect, the majority not being attributable to any single measured pathway. Forward-time landmarking amplified the association (OR 2.10 at 24 h; 2.26 at 48 h), arguing against reverse causation. The trajectory-by-CVP interaction was not significant (p = 0.20); the phenotype effect was numerically larger at low than high admission CVP (OR 1.76 versus 1.20), an exploratory pattern. Adding trajectory class to a static model produced modest gains (NRI 9.9%, IDI 0.4%, ΔAUC 0.003).ConclusionFour distinct ePVS trajectories within 48 h after CABG carry differential AKI risk. A Gradually-increasing ePVS trajectory after CABG signifies AKI risk that is largely independent of and complementary to CVP, providing a non-invasive volume axis not captured by pressure-based monitoring.

BACKGROUND:Patients with coronavirus disease 2019 (COVID-19) infection prior to cardiac surgery are at a higher risk of contracting the virus and worse outcomes. Administration of ursodeoxycholic acid (UDCA) may be effective in reducing the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, it remains unclear whether prophylactic use of UDCA could prevent complications in cardiac surgical patients with previous COVID-19 infection. METHODS:In one comparison from a 2 × 2 factorial trial, we randomly assigned patients with COVID-19 infection prior to cardiac surgery to UDCA or control in a 1:1 ratio. The randomization process was initiated 2 days before surgery by a central randomization system. The participants in the UDCA group received UDCA (15 mg/kg of body weight) on the day of randomization, administered orally twice a day during breakfast and dinner for 5 days. The primary outcome was a composite endpoint of all-cause death, myocardial infarction, stroke, moderate or severe acute kidney injury, and COVID-19 pneumonia within 30 days after surgery. RESULTS:From January 2023 through March 2023, a total of 500 participants were randomized, and all the participants (UDCA: 250 and control: 250; mean [standard deviation] age, 57.1 [11.5] years; 25.4% female) were included in the primary analysis. The primary outcome event occurred in 37 (14.8%) participants in the UDCA group and 35 (14.0%) participants in the control group (risk difference, 0.8% [97.5% confidence interval [CI], - 6.2% to 7.8%]; risk ratio, 1.08 [97.5% CI, 0.63 to 1.85]). The results were consistent in subgroups. Additionally, the incidence of COVID-19 pneumonia within 30 days was similar between the UDCA group and the control group (10.4% vs. 7.6%; risk difference, 2.8 [95% CI -2.2 to 7.8]; risk ratio, 1.35 [95% CI 0.75 to 2.44]). Serious adverse events occurred in 94 (37.6%) participants in the UDCA group and 94 (37.6%) participants in the control group (P>0.05). There were also no significant between-group differences in the incidence of the other secondary outcomes. CONCLUSION:Among patients who underwent cardiac surgery following a recent COVID-19 infection, prophylactic use of UDCA for a 5-day course was not associated with better postoperative outcomes, including major complications and COVID-19 reinfection.

While biventricular assist devices (BiVADs) remain underutilized in Western countries for biventricular heart failure (BHF), their application is expanding in China. This consensus synthesizes international guidelines, medical evidence, and Chinese clinical expertise to establish standardized protocols for BiVAD management. Key recommendations include: (1) Preoperative right heart catheterization and echocardiography for central venous pressure (CVP): pulmonary capillary wedge pressure (PCWP) ratio and pulmonary artery pulsatility index (PAPi) assessment (Class I); (2) BiVAD indication in refractory BHF or high-risk right heart failure post-left ventricular assist device (LVAD) implantation (Class IIa); (3) Right atrial implantation as the preferred surgical approach (Class IIa); (4) Warfarin-based anticoagulation (INR 2.0-2.5) with aspirin, avoiding direct oral anticoagulants (DOACs) (Class III). The guidance addresses critical gaps in patient selection, pump speed titration, and complication management, positioning integrated BiVAD systems as a promising solution for complex BHF.

Graft restenosis remains a significant challenge in coronary artery bypass grafting (CABG). Traditional function assessments, primarily relying on blood flow rate, often fail to capture the geometric and hemodynamic influences on graft patency. To address these limitations, this retrospective study aimed to establish a comprehensive risk prediction model that incorporates both flow dynamics and geometric features, facilitating clinically applicable evaluations. A total of 110 patient-specific CABG geometries were reconstructed from coronary computed tomography angiography (CCTA) images to extract key geometric parameters for subsequent statistical analysis. An additional 28 cases were analyzed for statistical and hemodynamic validation. Three logistic regression models were built and validated for restenosis risk prediction. Computational fluid dynamics (CFD) simulations were performed to investigate the hemodynamic characteristics of high-risk grafts. A MATLAB-based software tool was also developed to automate the analysis workflow. Among the three prediction models, the one combining graft flow and geometric factors balanced sensitivity and specificity, and performed best in the validation cohort (area under curve = 0.758, sensitivity = 89.1 %). CFD simulations on the validation cohort confirmed that grafts with high predicted risk exhibited poor hemodynamic conditions, including low time-averaged wall shear stress, high oscillatory shear index, and high relative residence time. Further statistical analysis revealed complex context-dependent interactions between graft flow and geometry. This study presents an integrated approach to restenosis risk prediction by combining patient-specific flow and geometric features. These findings are expected to enhance clinical decision-making and support more individualized postoperative management strategies in CABG.