Background: Postoperative antiplatelet selection after coronary artery bypass grafting (CABG) in adults aged ≥70 years requires balancing ischemic protection against bleeding risk. Methods: We conducted a single-center retrospective cohort study of adults aged ≥70 years who underwent isolated CABG for unstable angina between 2017 and 2021. The exposure was the initial discharge antiplatelet pathway: aspirin 100 mg once daily or indobufen 100 mg twice daily as the cyclooxygenase-inhibitor component, combined with a P2Y12 inhibitor during the first postoperative year and followed by the same cyclooxygenase inhibitor during the second year. Propensity scores were estimated using multivariable logistic regression with 16 prespecified baseline covariates, and stabilized inverse probability of treatment weighting (IPTW) was applied. The primary analyses used IPTW-weighted Cox models. Results: Among 336 screened patients, 79 were included in the final analytic cohort (aspirin-based pathway, n = 49; indobufen-based pathway, n = 30). After weighting, measured covariate balance improved, although residual imbalance remained for prior myocardial infarction and prior percutaneous coronary intervention. At 24 months, no statistically significant association was observed between pathway and MACCE (HR 0.858, 95% CI 0.257–2.866; p = 0.803), BARC grade ≥2 bleeding (HR 0.359, 95% CI 0.093–1.385; p = 0.137), or NACE (HR 0.526, 95% CI 0.204–1.360; p = 0.185). Graft surveillance was evaluable in 77/79 patients at 1 year and 71/79 at 2 years and was analyzed descriptively. Conclusions: In this real-world cohort of older patients undergoing CABG for unstable angina, an initial indobufen-based discharge pathway was not statistically significantly associated with 24-month MACCE, BARC grade ≥2 bleeding, or NACE compared with an aspirin-based pathway after stabilized IPTW. These findings add exploratory CABG-specific data on indobufen in older patients and should be confirmed in larger prospective studies.

BACKGROUND:Septal myectomy is the gold standard treatment for drug-refractory obstructive hypertrophic cardiomyopathy (oHCM). However, conventional septal myectomy (CSM) has been largely confined to specialized centers owing to its technical complexity. Transapical beating-heart septal myectomy (TA-BSM) can simplify CSM, enabling minimally invasive tailored septal resections in the beating heart under real-time echocardiographic guidance. Despite single-institution experience showed favorable efficacy and safety, whether TA-BSM can achieve similar clinical outcomes as CSM remains unknown since randomized controlled trial comparing the 2 approaches was unavailable. METHODS:The TAILOR-HCM trial (Transapical Beating-Heart Septal Myectomy vs Conventional Surgical Myectomy in Patients with Obstructive Hypertrophic Cardiomyopathy) is a multicenter, randomized, controlled, assessor-blinded, noninferiority trial evaluating the safety and efficacy of a novel device-based TA-BSM procedure conducted at 11 experienced CSM centers in China. In total, 216 symptomatic patients with oHCM who meet guideline-directed indications for septal myectomy will be randomly assigned in a 1:1 ratio to TA-BSM or CSM. The primary endpoint is relief of left ventricular outflow tract (LVOT) obstruction at 12 months, defined as a resting LVOT gradient <30 mm Hg and a standardized Valsalva maneuver-provoked LVOT gradient <50 mm Hg. Secondary endpoints include cardiac hemodynamic and structural parameters, procedure-related outcomes, quality of life, and laboratory examinations. The key safety outcome is all-cause mortality within 12 months after surgery. CONCLUSIONS:TAILOR-HCM is the first multicenter randomized controlled trial evaluating both TA-BSM and CSM in oHCM. Through comparative evidence against CSM, this study will inform future clinical decision-making. If noninferior hemodynamic efficacy with favorable safety is confirmed, TA-BSM may represent an alternative surgical approach that expands therapeutic options and improves access to definitive septal reduction therapy for patients with oHCM. CLINICAL TRIAL REGISTRATION:https://www.chictr.org.cn. Unique Identifier: ChiCTR2400087414.

Backgrounds:Scoring systems are increasingly used for risk stratification in the postoperative management of type A aortic dissection (TAAD), but no consensus exists regarding the optimal tool. Thus, this study aimed to develop and validate a machine learning-based model to predict in-hospital mortality among postoperative patients with TAAD. Methods:Data from postoperative TAAD patients treated at two centers were analyzed retrospectively. The primary outcome was in-hospital all-cause mortality. Clustering methods were implemented for feature selection. A random forest algorithm was selected from a range of machine learning methods to develop a postoperative mortality risk prediction tool. Receiver operating characteristic (ROC) curves were employed to assess predictive accuracy and reliability. Model calibration was evaluated by plotting calibration curves. SHapley Additive exPlanations (SHAP) values were calculated to quantify the contribution of each feature. Model performance was compared with the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). Results:A total of 983 patients who underwent surgical repair for TAAD were included in the study. Eight features were identified as significant predictors of in-hospital mortality. On postoperative day (POD) 1, the final random forest model achieved an area under the receiver operating characteristic curve (AUROC) of 0.8899 (95% confidence interval (CI): 0.7988-0.9469). External validation on POD 1 yielded an AUROC of 0.8331 (95% CI: 0.7722-0.8871). The model demonstrated significantly higher discriminative performance than EuroSCORE II. Conclusions:This study developed and primarily validated an accurate machine learning model to predict the all-cause in-hospital mortality of patients with TAAD undergoing surgical repair.

BACKGROUND:Elderly patients undergoing cardiac surgery are highly susceptible to postoperative pulmonary complications triggered by conventional extracorporeal circulation (CECC)-driven systemic inflammation and subsequent pulmonary endothelial injury. Minimally invasive extracorporeal circulation (MiECC) lowers perioperative hemodilution and systemic inflammatory load, yet the underlying intracellular protective mechanisms in aged populations remain incompletely understood. This study therefore aimed to delineate the C5a-mtDNA-cGAS-STING signaling cascade as the central pathway mediating MiECC's pulmonary protective effect. METHODS:This prospective randomized controlled trial enrolled 94 patients ≥70 years undergoing elective valve or coronary bypass surgery, randomly allocated to MiECC (n = 46) or CECC (n = 48). Perioperative hemoglobin trajectories and 7-day postoperative adverse events were compared using appropriate statistical tests. For mechanistic validation, serum from 5 propensity-matched patient pairs (matched by age, surgery type, and CPB duration) was used to stimulate human pulmonary microvascular endothelial cells (HPMECs). Quantitative phenotypic assays, including fluorometric quantification coupled with high-content screening, were employed to evaluate endothelial barrier integrity, apoptosis, mitochondrial dysfunction, and activation of the cGAS-STING signaling axis. Two targeted pharmacological rescue experiments were conducted using C5a receptor antagonist PMX53 and STING selective inhibitor C-176, to establish the hierarchical causality of this proposed signaling axis. RESULTS:No perioperative mortality was recorded in either cohort. The MiECC group exhibited markedly higher intraoperative hemoglobin levels and a 52.6% relative risk reduction in postoperative pulmonary exudative complications, with no extension of postoperative recovery timelines. Postoperative serum levels of complement C5a, pro-inflammatory cytokines, and endothelial injury biomarkers were significantly lower in the MiECC cohort. Quantitative analyses demonstrated that MiECC serum significantly attenuated endothelial hyperpermeability and reduced apoptosis rates. At the mechanistic level, MiECC serum suppressed mitochondrial superoxide accumulation (38.2% reduction) and preserved mitochondrial membrane potential, resulting in a 46.5% reduction in cytosolic mtDNA leakage. Consequently, MiECC serum downregulated cGAS and STING protein expression and suppressed nuclear translocation of phosphorylated IRF3 (p-IRF3). The dual inhibitor rescue demonstrated that pretreatment with PMX53 fully reversed all CECC serum-induced pathological phenotypes, whereas the STING inhibitor C-176 selectively ameliorated downstream endothelial injury without rescuing upstream mitochondrial dysfunction or cytosolic mtDNA leakage. Dual inhibitor rescue demonstrated that PMX53 completely reversed all pathological phenotypes, whereas C-176 only rescued downstream endothelial injury without correcting upstream mitochondrial damage or mtDNA release. CONCLUSIONS:MiECC is a safe, effective perfusion strategy that mitigates postoperative pulmonary exudation in elderly cardiac surgical recipients. At the mechanistic level, MiECC restricts CPB-induced C5a overproduction, thereby preventing C5a-driven mitochondrial impairment and mtDNA release, which initiates the cGAS-STING inflammatory cascade. Selective C5aR blockade fully interrupts this pathological axis, providing robust translational evidence to support broader adoption of MiECC in high-risk elderly patients and identifying C5aR as a tractable therapeutic target for CPB-associated lung injury.

Objective:Conventional large mitral bioprostheses may cause left ventricular outflow tract obstruction. A dual-orifice mitral bioprosthesis was designed for both surgical and transcatheter valve replacement. Methods:Pulsatile flow testing was used to measure the effective orifice area (EOA). Computational fluid dynamics analysis was conducted to assess thrombogenic and hemolysis risk. An ovine model was used to evaluate procedural safety, hemodynamic performance, and leaflet calcification. Results:Pulsatile flow testing showed that the EOAs of surgical dual-orifice valve (17K, 18K, 19K, 20K, 21K) were 2.0 ± 0.2, 2.1 ± 0.3, 2.4 ± 0.4, 2.5 ± 0.1, and 2.7 ± 0.3 cm2 under 5 L/min cardiac output, respectively. The mean hemolysis index and platelet activation state of 19K surgical dual-orifice valve under 7 L/min cardiac output were 1.3 × 10-8 and 2.2 × 10-8 in the computational fluid dynamics analysis, respectively. Six ovine underwent implantation of the 19K surgical dual-orifice valve and were followed for 20 weeks. The mean pressure gradient and EOA were 3.7 ± 0.8 mm Hg and 2.7 ± 0.3 cm2 immediately after implantation and 5.0 ± 2.3 mm Hg and 2.5 ± 0.2 cm2 at 20 weeks, respectively. One ovine was implanted the 19K transcatheter dual-orifice valve and followed up for 125 days. The mean pressure gradient was 5.0 mm Hg immediately after implantation and 3.0 mm Hg at the end point. Conclusions:The dual-orifice mitral bioprosthesis may represent an alternative design for mitral valve replacement, especially for patients with large mitral annuli. This findings also show the potential of this design in transcatheter mitral valve replacement.

Purpose:To compare the safety and efficacy of indobufen-based versus aspirin-based sequential antiplatelet therapy in septuagenarians undergoing coronary artery bypass grafting (CABG). Patients and Methods:Patients aged 70-79 years who underwent CABG between 2020 and 2022 received either indobufen- or aspirin-based dual antiplatelet therapy (DAPT) (with clopidogrel) for 12 months, followed by monotherapy with their respective baseline agent (indobufen or aspirin) for an additional year. Propensity score matching (1:2, caliper 0.25 SD) balanced the baseline characteristics. The primary outcomes were 2-year major adverse cardiac and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding. Results:Among 296 patients (indobufen, 46; aspirin, 250), 104 (indobufen, 36; aspirin, 68) were well matched. Before matching, indobufen showed similar 2-year MACCE risk to aspirin (6.5% vs 6.8%; subdistribution hazard ratio [sHR] 0.96, 95% CI 0.28-3.28; p = 0.95) and lower BARC type 2, 3, or 5 bleeding (2.2% vs 6.8%; sHR 0.32, 95% CI 0.04-2.38; p = 0.23). After matching, results remained consistent (MACCE 8.3% vs 10.3%; sHR 0.81, 95% CI 0.21-3.10; p = 0.76; bleeding 2.8% vs 11.8%; sHR 0.24, 95% CI 0.03-1.87; p = 0.14). Indobufen reduced clinically relevant bleeding by 9.0% (number needed to treat [NNT] ≈ 11) without compromising ischemic outcomes. Conclusion:Indobufen-based sequential therapy provided ischemic protection similar to that of aspirin, while showing a favorable bleeding profile in septuagenarians undergoing CABG. For individuals with a high bleeding risk or aspirin intolerance, indobufen may represent a practical alternative. Larger prospective studies focusing on geriatric outcomes are warranted.

Heart transplantation offers the only life-saving option for patients with terminal heart failure; yet, the sequential "innate-adaptive" avalanche initiated by ischemia-reperfusion injury (IRI) remains the Achilles' heel of long-term graft acceptance. Current regimens overwhelmingly focus on either the adaptive or the IRI-triggered innate arm, failing to interrupt the positive-feedback loop that amplifies allo-rejection. To address this unmet need, we herein present a single ROS-responsive nanoplatform that weds dual immunosuppression with on-demand oxygenation Fe3O4@CaO2@Tac@HA. The core-shell Fe3O4@CaO2 carrier simultaneously loads hyaluronic acid (HA), which is a potent dampener of innate inflammatory signaling, and tacrolimus (Tac), which is a calcineurin inhibitor that arrests adaptive T-cell activation. Upon exposure to the ROS-rich milieu of the reperfused graft, CaO2 undergoes conversion to O2, promptly relieving tissue hypoxia while reducing oxidative stress. In vitro, the nanocomposite exhibits rapid ROS scavenging, sustained oxygen release and inhibit T cell activation; in vivo, it markedly prolongs cardiac-allograft survival by synchronously suppressing innate immune cells infiltration and CD8+ T-cell cytotoxicity. Collectively, Fe3O4@CaO2@Tac@HA offers a translatable "one-two punch" strategy that unites innate and adaptive immunomodulation, setting the stage for precision nanotherapy in cardiac transplantation.

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.

Ambient air pollution is a major public health concern, and while PM2.5 is a known risk factor for cardiovascular disease, its specific role in aortic dissection (AD) remains unclear. This study investigated how PM2.5 exposure promotes AD by focusing on endoplasmic reticulum (ER) stress and apoptosis in vascular smooth muscle cells (SMCs). Using in vitro PM2.5-treated SMCs and an in vivo murine AD model with real-world PM2.5 exposure, we employed transcriptomic profiling, lentiviral overexpression, AAV-mediated knockdown, Western blot, immunofluorescence, Seahorse analysis, and electron microscopy. Results showed significant enrichment of ER stress and mitochondrial dysfunction pathways, with upregulation of the PERK–eIF2α axis. PM2.5 induced mitochondrial damage, which was alleviated by PERK inhibition but worsened by eIF2α activation. PM2.5 downregulated NDUFA3, a complex I subunit, an effect reversed by PERK inhibition. Overexpression of NDUFA3 attenuated mitochondrial dysfunction and apoptosis. Furthermore, SMC-specific PERK knockdown in mice reduced the incidence and mortality of AD, mitigated mitochondrial defects, and ameliorated aortic pathology. These findings demonstrate that PM2.5 exposure promotes AD via the PERK–eIF2α–NDUFA3 pathway, inducing mitochondrial dysfunction and SMC apoptosis, thereby identifying a potential therapeutic target for reducing environmental risk of AD.

Aims Vascular smooth muscle cell (VSMC) apoptosis plays a key role in the development of thoracic aortic aneurysm and dissection (TAAD), a lethal cardiovascular disease with high mortality rates but limited pharmacological therapy. BMAL1 dysregulation is associated with apoptosis. However, it remains elusive whether BMAL1 dysregulation may aggravate VSMC apoptosis to participate in the development of TAAD. Methods and results Transcriptomic analysis and molecular assays were performed to analyse BMAL1 level in the TAAD patients and 3-aminopropionitrile fumarate (BAPN)-induced TAAD mice. Global and VSMC-specific BMAL1 haploinsufficient mice were used to determine the role of BMAL1 in BAPN-induced TAAD murine model. Transcriptomics, spatial transcriptomics, histological, and in vitro experiments were performed to examine the underlying mechanisms. BMAL1 level was reduced in the thoracic aorta from TAAD patients and BAPN-challenged mice. Global and VSMC-specific BMAL1 haploinsufficiency significantly increased the risk of BAPN-induced TAAD in mice. BMAL1 dysregulation induced VSMC apoptosis during challenge-induced TAAD formation. Moreover, BMAL1 transcriptionally regulated REV-ERBα by binding to the E-box in its promoter region. Overexpression of REV-ERBα alleviated the detrimental effect of BMAL1 dysregulation on the formation of TAAD and VSMC apoptosis. Conversely, REV-ERBα dysregulation aggravated TAAD and VSMC apoptosis. Mechanistically, VSMC apoptosis inducer c-MYC was regulated by BMAL1/REV-ERBα axis and was proven as a direct target of REV-ERBα. Importantly, BMAL1 activator ISX-9 and REV-ERBα agonist SR9009 reduced the risk of BAPN-induced TAAD in both BMAL1 haploinsufficient and control mice, even when they were administered from 14 days after BAPN modeling. Conclusion BMAL1 insufficiency increases the risk of TAAD by inducing VSMC apoptosis via down-regulation of REV-ERBα. BMAL1 and REV-ERBα may serve as pharmacological targets for TAAD prevention and therapy.

Background: Early postoperative mortality remains a major clinical challenge in left ventricular assist device implantation. Accurate preoperative identification of high-risk patients could optimize candidate selection and improve perioperative management. Methods: From February 2021 to March 2025, 60 patients who underwent LVAD implantation at Zhongshan Hospital, Fudan University were included in the present study. Early mortality was defined as death within 2 months postoperatively, a threshold derived from survival analysis showing a distinct early hazard phase. Preoperative demographic, echocardiographic, hemodynamic, and laboratory variables were evaluated. Predictor selection used least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross-validation, followed by multivariable Firth logistic regression. Internal validation employed bootstrap resampling (1,000 iterations). Results: The mean age was 55 ± 10 years, and 50 (83%) patients had dilated cardiomyopathy. Kaplan–Meier analysis indicated an early hazard phase, with all deaths occurring by ~ 1.7 months after implantation. LASSO selected age, MELD-XI, passive cardiac index (PasCI), and mixed venous oxygen saturation (SvO₂) for multivariable modeling. In the final Firth model, lower SvO₂ (odds ratio [OR] 0.92; 95% CI 0.83–1.00; p = 0.048) and older age (OR 1.13; 95% CI 1.00–1.35; p = 0.059) were associated with higher early mortality. Internal validation yielded an optimism-adjusted AUC of 0.84. Conclusions: In this exploratory study, lower preoperative SvO₂ and older age were the principal predictors of early mortality after LVAD implantation. Our internally validated risk assessment model supports preoperative risk prediction and stratification; however, confirmation in larger, multicenter cohorts is warranted before broader adoption. (246/250)

Background Right ventricular (RV) function is closely associated with prognosis in isolated tricuspid regurgitation. Beyond conventional longitudinal indexes, nonlongitudinal RV deformation may provide additional prognostic information. Objectives The authors aimed to evaluate whether 3-dimensional (3D) RV circumferential strain (RV-CS) provides incremental prognostic value in patients undergoing isolated tricuspid valve surgery (ITVS). Methods Patients scheduled for ITVS were prospectively enrolled and underwent 3D echocardiography 1 day before surgery. 3D RV longitudinal strain, CS, and area strain were derived using commercially available software. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization. Results From April 2018 to December 2024, 251 patients were enrolled; 171/251 (68.1%) were women, and the mean age was 57 ± 14 years. During a median follow-up of 495 days, 48/251 patients (19.1%) reached the primary endpoint. Baseline 3D right ventricular circumferential strain (3D RV-CS) was lower in patients with events than in those without events (P < 0.001) and showed modest but had the highest Harrell’s C-index for adverse events discrimination (0.695; 95% CI: 0.618-0.774; P < 0.001) among all tested RV function parameters. Patients with impaired 3D RV-CS, defined as |3D RV-CS| < 14%, had lower 1-year event-free survival than those with preserved 3D RV-CS (54.2% vs 92.5%; log-rank P < 0.001). After multivariable adjustment, impaired 3D RV-CS remained independently associated with adverse events. Adding 3D RV-CS improved risk reclassification beyond European System for Cardiac Operative Risk Evaluation II, TRI-SCORE, and Society of Thoracic Surgeons score models. Conclusions 3D RV-CS provides complementary prognostic information in patients undergoing ITVS and may improve preoperative risk stratification.

OBJECTIVE:To evaluate the mid-term outcomes of aortic root preservation in patients with acute type A aortic dissection (ATAAD) and significant preoperative aortic regurgitation (AR). METHODS:The study included patients who underwent surgical repair for ATAAD with aortic root preservation from 2005 to 2024. Root preservation was preferred unless limited by severely damaged root intima, significant AR with cusp lesions, dilated sinus, or connective tissue disorder. Patients were stratified into an AR group (moderate or severe AR) and a non-AR group (less than moderate AR). Primary outcomes included overall survival and freedom from recurrent AR. RESULTS:Totally 1,333 patients were included into AR group (n = 369) and non-AR group (n = 964). Overall 30-day mortality was 11.3% (15.2% AR group vs 9.9% non-AR group; P = .006); however, preoperative AR was not associated with early mortality after multivariate adjustment. Overall survival at 10 years was comparable between groups (93.6% vs 92.3%). Freedom from recurrent AR at 10 years was 88% in the AR group compared to 97.1% in the non-AR group (P < .001). In multivariable analysis, intraoperative residual mild AR (Hazard ratio [HR] 4.08, P = .001) and connective tissue disorders (HR 4.36, P = .018) were the strongest predictors of recurrence. Without presence of intraoperative residual mild AR, preoperative moderate/severe AR did not increase risk or late recurrence. CONCLUSIONS:Aortic root preservation demonstrated satisfactory mid-term outcomes and may represent a safe and durable strategy for ATAAD with significant preoperative AR. Intraoperative residual mild AR increases risk of recurrence, warranting closer monitoring.

Background To compare short-term computed tomography angiography (CTA) findings after frozen elephant trunk (FET) for type A aortic dissection (TAAD) using a single-branched stent graft (Fontus) versus a straight stent graft (Cronus). Methods A single-center retrospective study (July 1, 2021 – August 31, 2024) included 189 TAAD patients (Fontus, n = 111; Cronus, n = 78) after excluding anatomical contraindications. Postoperative CTA assessed branch endoleak, stented-segment false lumen thrombosis, and distal stent-induced new entry (dSINE). Inverse probability of treatment weighting balanced baseline differences. Results Stented-segment false lumen thrombosis was comparable between Fontus and Cronus, indicating non-inferior performance of the branched design. In the Fontus cohort, branch-related endoleak occurred in 11 patients (10%) and was independently associated with left subclavian artery (LSA) involvement by dissection (odds ratio, 11.24; P = 0.003). Branch endoleak delayed complete thrombosis but did not alter mid-term remodeling. dSINE incidence did not differ by stent type but was independently driven by distal stent angulation (hazard ratio, 2.27 per 10°; P < 0.01); angles exceeding 30° were particularly hazardous. Conclusions Short-term CTA outcomes after FET for TAAD are comparable between Fontus and Cronus. Branch endoleak (10%) is the principal imaging limitation of the single-branched strategy and is predicted by LSA dissection involvement; thus, careful preoperative LSA assessment is advised. Across both stent types, distal angulation > 30° independently predicts dSINE, emphasizing the need for intraoperative geometric alignment and rigorous postoperative CTA surveillance.

Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with increased mortality. Amino acids may improve renal perfusion, but their effect in patients undergoing aortic surgery remains unclear. We used the Aortic Surgery Database of the Shanghai Hospital Development Center to emulate a target trial. Patients were classified to one of two exposure strategies: receiving a daily amino acid dose of > 21 g during the first 2 postoperative days, or not receiving amino acid therapy above this threshold. Overlap weighting was used to balance covariates and emulate randomized assignment. The primary outcome was the incidence of AKI. Secondary outcomes included AKI stage, renal replacement therapy, hospital stay, in-hospital mortality, and 30-day mortality. Overall, 1,816 patients were included in the study. The incidence of AKI and 30-day mortality was 37.8% (n = 686) and 1.6% (n = 29), respectively. No significant association was observed between low-dose postoperative amino acid exposure and the incidence of AKI (OR = 0.96, 95% CI: 0.79-1.17, p = 0.70) or 30-day mortality (OR = 1.54, 95% CI: 0.68-3.50, p = 0.30). In subgroup analysis, amino acid exposure was associated with a lower risk of AKI in patients aged ≥ 65 years (OR = 0.71, 95% CI: 0.53-0.95, p = 0.02). The subgroup finding in older patients should be considered exploratory and requires confirmation in future studies.

BACKGROUND:Prolonged cold myocardial ischemia/reperfusion injury-driven by mitochondrial dysfunction, oxidative stress, and ferroptosis-limits cardiac transplantation success. Dihydroorotate dehydrogenase (DHODH), a key mitochondrial enzyme for redox homeostasis and ferroptosis suppression, has short ischemic half-life and poor targeting, restricting clinical use. We aimed to engineer cardiomyocyte-targeted mitochondria (DHODH-CT-Mito) for sustained DHODH delivery to mitigate prolonged cold myocardial ischemia/reperfusion. METHODS:Using a Langendorff model, we validated DHODH's transient protective role. DHODH-CT-Mito was designed by fusing translocase of the outer mitochondrial membrane 20 with an ischemic myocardium-targeting peptide. Efficacy/safety were tested in a 2-mo rat allogeneic heart transplant model, assessing homing, membrane potential, immunogenicity, biodistribution, and sustained DHODH activity. RESULTS:DHODH-CT-Mito showed robust myocardial homing, preserved membrane potential, and sustained DHODH activity. Treated grafts had improved long-term function, less fibrosis, and reduced apoptosis. It displayed low immunogenicity (transient inflammation, balanced macrophages) and minimal off-target accumulation. Acute DHODH delivery primed grafts for sustained redox balance. CONCLUSIONS:DHODH-CT-Mito overcomes exogenous DHODH limits, providing durable mitochondrial activity, suppressing ferroptosis, and preserving graft function with low risk-offering a translatable strategy for donor heart preservation.

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.