The porcine model of myocardial infarction (MI) has been widely used to assess the feasibility, safety, and efficacy of prototype products in preclinical research. The heterogeneity of the left coronary artery (LCA) among pigs led to relatively low stability and repeatability, likely diminishing the accuracy of the preclinical research. Herein, we proposed a comprehensive strategy for establishing stable and reproducible porcine MI model based on LCA anatomical classification. Through precise analysis of coronary anatomical features via coronary angiography, we categorized the LCA into a nine‐type classification system and identified candidate subtypes for construction of porcine MI model. Utilizing a new embolic composite, we proposed subtype‐specific occlusion protocols to achieve stable vessel embolization within 3 s, effectively preventing blood flow from recanalization. This strategy significantly improved the efficiency, accuracy, and reproducibility in porcine MI induction, providing a more reliable experimental platform for preclinical research of prototype products.

ABSTRACT Repairing anisotropic tissues such as the myocardium requires implanted cells to organize into highly ordered structures. However, achieving controlled cell alignment remains a major challenge for current cell delivery patches. Here, we develop a magnetically aligned, fiber‐reinforced extracellular matrix (ECM) patch that directs anisotropic cell organization and supports stem cell implantation. Poly‐lactic acid fibers containing Fe 3 O 4 are fabricated via electrospinning and controlled hydrolysis, and are aligned uniaxially within ECM hydrogels using an external magnetic field prior to gelation. The resulting ECM–fiber patches exhibit enhanced mechanical strength and reliably guide the alignment of cardiomyocytes, fibroblasts, and endothelial cells. A beating patch is also created by seeding human induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CMs). In a nude mouse myocardial infarction (MI) model, implantation of iPSC‐CMs@ECM–fiber patches preserves cardiac function, reduces apoptosis, limits fibrosis, and enhances vascularization. Implanted iPSC‐CMs demonstrate high viability and low immunogenicity. Molecular profiling reveals transient modulation of early inflammatory responses post‐MI, probably mediated through IL‐17, IL‐3, and IL‐1β pathways. Overall, the ECM–fiber patch provides a versatile platform for delivering highly organized cells for in vivo tissue repair.

BACKGROUND:For patients undergoing surgical valve procedures with concomitant coronary artery disease, current guidelines recommend that coronary artery bypass grafting (CABG) should be anatomically guided on the basis of stenosis severity, as assessed by coronary angiography. We aimed to test whether a physiologically guided strategy using angiography-derived fractional flow reserve (FFR) could improve clinical outcomes in this population. METHODS:FAVOR IV-QVAS is an investigator-initiated, multicentre, randomised, triple-blind trial done at 12 tertiary hospitals in China. Eligible patients were aged 18 years or older and were scheduled for valve surgery, with at least one clinically significant stenosis in a major coronary artery. Patients were randomly assigned (1:1) to undergo physiologically guided CABG (for lesions with an angiography-derived FFR value ≤0·80) or anatomically guided CABG (for lesions with a stenosis diameter ≥50% on coronary angiography). Randomisation was done using a web-based program and stratified by site with fixed blocks of four. Patients, surgeons, follow-up physicians, and outcome assessors were masked to treatment allocation. The primary outcome was a composite of death, myocardial infarction, stroke, unplanned coronary revascularisation, and new renal failure requiring dialysis within 30 days after surgery. The key secondary outcome was a composite of death, myocardial infarction, stroke, unplanned coronary revascularisation, and hospitalisation for unstable angina or heart failure at a minimum follow-up of 1 year. The primary analysis of the primary and key secondary outcomes was done in a modified intention-to-treat population that included all randomly assigned patients who underwent surgery and had available data for the primary outcome. Missing data for the primary outcome were planned to be analysed using complete-case analysis or multiple imputation, with a proportion of missing data of 2% as the threshold. This trial is registered at ClinicalTrials.gov (NCT03977129); extended follow-up is ongoing. FINDINGS:Between Aug 4, 2019, and Aug 13, 2024, 793 patients were enrolled. 396 were randomly assigned to the angiography-derived FFR group and 397 to the coronary angiography group; one patient in the coronary angiography group declined surgery and was excluded from the modified intention-to-treat population. The median age was 65 years (IQR 59-70), 221 (28%) patients were female, and 571 (72%) were male. Concomitant CABG was done in 223 (56%) patients in the angiography-derived FFR group and in 388 (98%) patients in the coronary angiography group. The primary outcome occurred in 31 (7·8%) patients in the angiography-derived FFR group and 53 (13·4%) in the coronary angiography group (absolute difference -5·6 percentage points [95% CI -9·9 to -1·3]; risk ratio 0·58 [95% CI 0·38 to 0·89]; p=0·011). Death within 30 days occurred in 11 (2·8%) patients in the angiography-derived FFR group and 17 (4·3%) patients in the coronary angiography group. At a median follow-up of 27 months (28 months [IQR 18-44] in the angiography-derived FFR group and 27 months [18-42] in the coronary angiography group), the key secondary outcome occurred in 82 (20·7%) patients in the angiography-derived FFR group and in 106 (26·8%) patients in the coronary angiography group (hazard ratio 0·74 [95% CI 0·55-0·98]; p=0·036). INTERPRETATION:Among patients undergoing valve surgery with concomitant coronary artery disease, physiologically guided CABG using angiography-derived FFR reduced the incidence of the composite perioperative outcome compared with anatomically guided CABG. These findings support a selective approach to surgical coronary revascularisation guided by physiological assessment in patients undergoing valve procedures. FUNDING:Shanghai Hospital Development Center, Shanghai Municipal Science and Technology Commission, and Ministry of Science and Technology of the People's Republic of China.

Reconstruction of functional microvascular networks, particularly at the capillary scale, remains a critical bottleneck for the integration of tissue-engineered grafts with host tissues. Here, we report a photothermal ablation blotting (PAB) strategy for engineering perfusable, robust, and hierarchically branched microvascular network within a hydrogel matrix. This approach leverages bioresorbable photothermal fibers (PTF) that act as a sculpting template, enabling multiple diameters of controlled microchannel formation upon sequential near-infrared (NIR) and UV activation while simultaneously enhancing the mechanical toughness of the hydrogel via fiber reinforcement. The resulting photothermal microchannel hydrogel (PMH) supports efficient perfusion and cellular infiltration in vitro, and facilitates vascular integration and tissue remodeling in vivo through both rat subcutaneous and myocardial infarction (MI) models. This PAB platform offers a scalable and adaptable method for capillary-scale microvasculature engineering, with broad applicability across regenerative medicine and soft tissue reconstruction.

BACKGROUND:The prognostic value of Murray's law-based quantitative flow ratio (μFR) in multi-arterial coronary artery bypass grafting (CABG) remains unclear. OBJECTIVES:This study aims to investigate whether grafting strategies meeting μFR guidance improve mid-term outcomes following multi-arterial CABG. METHODS:This prospective secondary analysis included patients with available μFR analysis, clinical follow-up, and protocol-driven imaging from the ASRAB-Pilot (Different Anti-Spastic Strategy After CABG Using Radial Artery Grafts) trial. Patients were classified into μFR-guidance-met (all coronary lesions with μFR ≤0.80 were revascularized and all lesions with μFR >0.80 were not revascularized) or μFR-guidance-not-met groups. Outcomes included major adverse cardiac events (composite of death, myocardial infarction, stroke, or revascularization) and graft failure (Fitzgibbon grade B/S/O). Stabilized inverse probability weighting was applied to control confounding. RESULTS:Among 141 patients analyzed, 77 (54.6%) met μFR guidance. At a median follow-up of 29.9 (Q1-Q3: 23.4-36.6) months, no significant difference in major adverse cardiac events was observed (μFR-guidance-met group: 16.0% [9.4%-26.5%] vs μFR-guidance-not-met group: 14.5% [7.8%-26.1%]; adjusted HR: 1.12, 95% CI: 0.47-2.66; P = 0.793). Graft-level analysis showed a significantly lower failure rate of arterial grafts with the μFR-guidance-met group (9.4% [n = 25 of 265] vs 34.9% [n = 15 of 43]; adjusted RR: 0.28; 95% CI: 0.16-0.50; P < 0.001) but not venous grafts (18.8% [n = 32 of 170] vs 22.2% [n = 6 of 27]; adjusted RR: 1.50; 95% CI: 0.61-3.68; P = 0.378). CONCLUSIONS:In patients undergoing multi-arterial CABG, grafting strategies meeting μFR guidance were associated with a significantly lower failure rate of arterial grafts but not venous grafts. However, no improvement in mid-term clinical outcomes was observed, and larger trials are warranted in the future (Quantitative Flow Ratio on Radial Artery Graft Outcome After Coronary Artery Bypass Grafting [ASRAB-QUARGO]; NCT05556590).

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.

Tissue mechanical properties are spatially heterogeneous and tightly coupled to cellular function, developmental patterning, and disease progression, yet spatially resolved characterization of viscoelastic and microrheological behavior across intact tissues remains limited. Here we introduce spatial mechanomics, a framework for tissue-wide acquisition, quantitative extraction, and computational representation of location-resolved mechanical states. Using BioAFM-based spatial sampling with multi-protocol microrheology, we acquire force responses at defined tissue coordinates and fit physically interpretable viscoelastic models to extract elastic, viscous, and frequency-dependent parameters at each position. These parameters are assembled into per-niche mechanomic feature vectors and reconstructed into tissue-scale mechanomic atlases that resolve heterogeneous mechanical organization. We implement these capabilities in MechScape, an open-source computational platform that supports force curve fitting, spatial feature matrix construction, unsupervised domain discovery, and cross-modal alignment with histological and molecular measurements. Application to murine myocardial tissue reveals that spatial mechanomics identifies distinct mechanical states, quantifies condition-dependent remodeling across all measured parameters, and resolves spatially coherent mechanical domains. This work establishes spatial mechanomics as a quantitative approach for tissue-scale biomechanical mapping and provides a generalizable framework for integrating mechanics as an omics layer in multi-modal tissue analysis.

Hypertrophic cardiomyopathy (HCM) is a condition where approximately 65% of patients exhibit myocardial fibrosis, indicated by late gadolinium enhancement, with the severity and extent of fibrosis being positively correlated with the risk of sudden cardiac death. While fibroblast activation in HCM has been noted in previous studies, the underlying regulatory mechanisms have not been thoroughly explored. In this study, we analyzed the latest single-nucleus sequencing (snRNA-seq) datasets related to HCM caused by the two most common mutations. We also examined the largest existing snRNA-seq and spatial transcriptomics datasets of HCM for external validation. Additionally, we conducted preliminary histopathological and molecular biology experiments to validate our findings and explore potential mechanisms. Our analysis revealed a phenotypic transformation of macrophages in both cases of HCM. These pro-inflammatory macrophages, driven by the high expression of ENPP2, mediated intercellular interactions that influenced fibroblast activation. The resulting increase in lysophosphatidic acid appeared to act as a plausible intermediary. Activated fibroblasts secreted substantial amounts of COL14A1, which is a critical component of myocardial fibrosis. These findings were consistent across different genetic backgrounds, suggesting their universal applicability in most HCM cases. Our study provides valuable insights into the mechanisms underlying myocardial fibrosis in HCM, highlighting the role of macrophage transformation and fibroblast activation. These findings offer potential for the identification of novel diagnostic or prognostic biomarkers and the development of targeted therapies with clinical translational potential.

Myocardial infarction (MI) induces critical trace element imbalances that exacerbate adverse ventricular remodeling. Here, we comprehensively map the spatiotemporal dynamics of zinc (Zn) and copper (Cu) ions post-MI and design a sequential Zn-Cu therapeutic regimen tailored to match staged physiological demands. This temporally controlled administration effectively modulates ion levels and significantly improves overall cardiac function, attenuating post-infarction heart failure. Mechanistically, we demonstrate that therapeutic efficacy inherently relies on the precise modulation of the core circadian rhythm gene, period circadian protein homolog 2 (PER2), which controls cellular metabolic homeostasis. To autonomously sustain this molecular regulatory mechanism and further optimize cardiomyocyte repair, we engineer a perfusable epicardial device (PerMed) that maintains stable, localized ion concentrations, thereby minimizing off-target systemic effects. Ultimately, this Zn-Cu sequential therapy offers a highly targeted intervention strategy strictly aligned with the dynamic pathological microenvironment alterations emerging immediately following myocardial infarction.

BACKGROUND Intravenous leiomyomatosis (IVL) is a rare smooth muscle neoplasm that, although histologically benign, can exhibit clinically progressive behavior with extension into great vessels and even the heart. This study aimed to evaluate the surgical outcomes of single-stage en bloc resection using cardiopulmonary bypass (CPB) in IVL patients presenting with intracardiac or major vascular extension. METHODS A retrospective study was conducted on patients with IVL treated at a single institution from 2019 to 2025. Demographic characteristics, operative techniques, and surgical outcomes were collected and analyzed. RESULTS The cohort consisted of 12 female patients with a mean age of 45.5 years. Among them, 7 patients diagnosed with IVL ultimately underwent surgical resection at our center. Tumor extension most involved the inferior vena cava and right atrium. Complete surgical resection was achieved in all operative cases through a single-stage en-bloc resection under CPB, with no perioperative mortality or major complications During a median follow-up of 28.3 months, no tumor-related deaths were observed, and one patient experienced recurrence (14.3%, 1/7). CONCLUSIONS Single-stage en-bloc resection with CPB for IVL extending into the heart or great vessels may be a safe and effective approach, with favorable short- and mid-term outcomes.

Background and objectives Cardiovascular diseases, particularly those involving valvular and coronary conditions, lead to significant global mortality. Current strategies combine surgeries like valve replacement and coronary artery bypass grafting, which can increase perioperative risks. Research indicates that physiology-guided strategies such as fractional flow reserve and quantitative flow ratio improve outcomes by guiding more precise surgical interventions. This study aims to compare physiology-guided and angiography-guided surgical strategies, focusing on evaluating their efficacy and safety in treating patients with combined valvular and coronary pathologies.Methods and analysis We will search PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform for studies comparing outcomes of physiology-guided and angiography-guided strategies for patients with valvular diseases combined with coronary heart disease. All English articles published before 31 May 2024 will be considered. The primary outcomes will be major adverse cardiovascular events and graft occlusion rate. The secondary outcomes will be cardiac death, myocardial infarction, stroke, repeat revascularisation, and so on. The Jadad score and Newcastle-Ottawa Scale will be used to assess the quality of randomised controlled trials (RCTs) and non-RCTs, respectively. The Q-test and I² statistic will be used to assess the heterogeneity. For the primary outcome, we will perform the subgroup analysis if sufficient studies are available. We will also conduct leave-one-out sensitivity analysis to assess the impact of each individual study on the overall results. The protocol follows the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines.Ethics and dissemination This study is a secondary analysis of previous studies and therefore does not require ethical approval. Our research will be disseminated in peer-reviewed publications.PROSPERO registration number CRD42024542876.

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.

BACKGROUND:Coronary artery anomalies resulting from Kawasaki disease in pediatric patients can lead to significant myocardial ischemia, necessitating surgical intervention such as coronary artery bypass grafting (CABG). Total arterial CABG in children is rarely reported. METHODS:A single-center retrospective cohort study was conducted in patients who underwent CABG for Kawasaki disease-related coronary artery disease between January 2015 and January 2024. Outcomes were assessed through major adverse cardiac events, graft patency, and cardiac function. RESULTS:CABG was performed on 46 patients using 72 grafts including 44 internal thoracic arteries and 28 radial arteries. Sixteen patients (34.8%) received off-pump CABG, with a significantly older median age (P < .05) and shorter median operation duration (P = .019) compared with the on-pump CABG group. The outcomes of off-pump group were comparable to on-pump group in terms of perioperative morbidity and postoperative recovery. The median follow-up was 31.5 (range, 7-108) months, and all patients survived. Major adverse cardiac events occurred in only 1 patient, with the incidences of freedom from major adverse cardiac events 100%, 96.7%, and 96.7% at 1 year, 3 years, and 5 years, respectively. No nonfatal myocardial infarction, angina pectoris, or ventricular tachyarrhythmias was recorded in all other patients. The median left ventricular ejection fraction at last follow-up was 0.68 (range, 0.48-0.78). All grafts remained patent during follow-up except 1 with distal anastomosis stenosis. CONCLUSIONS:Total arterial CABG is a safe and effective surgical approach for Kawasaki disease-related coronary artery anomalies in pediatric patients. Off-pump CABG may be a viable option for selected cases. Further research is warranted to establish long-term outcomes and optimal surgical strategies.

Background: Neurologic complications represented by stroke are one of the most terrible complications of coronary artery bypass grafting (CABG). We aimed to investigate the association between concomitant carotid-cerebral artery disease and major neurologic complications after CABG. Methods: A cohort study of consecutive patients undergoing CABG from March 2020 to November 2022 in our single center was registered (NCT05036044) and conducted. Preoperative computed tomography angiography was used to identify carotid-cerebral artery disease, defined as any carotid, vertebral, or intracranial artery with stenosis ≥50%. The primary outcome was early major neurologic complications within 7 days after CABG, a composite of stroke, delayed awakening (≥48 hours after withdrawal of sedative), and severe delirium (Confusion Assessment Method of Intensive Care Unit II score ≥2). Results: A total of 1002 patients were enrolled (mean age, 65.0 ± 9.6 years; 19.7% female). Early major neurologic complications occurred in 104 patients (10.4%), including 16 (1.6%) with stroke, 45 (4.5%) with delayed awakening, and 60 (6.0%) with severe delirium. Patients with carotid-cerebral artery disease had a higher risk of early major neurologic complications (adjusted risk ratio [RR], 1.66; 95% CI, 1.10-2.51; P = .015), represented by stroke (RR, 2.78; 95% CI, 0.78-9.90), delayed awakening (RR, 1.67; 95% CI, 0.96-2.89), and severe delirium (RR, 1.44; 95% CI, 0.76-2.70). A stepwise increase in the incidence of all neurologic complications was observed with increasing severity of arterial stenosis (P < .05 for all). Conclusions: Concomitant carotid-cerebral artery disease was associated with higher risk of early major neurologic complications after CABG, including stroke, delayed awakening, and severe delirium.

Cardiovascular disease remains a leading cause of mortality, highlighting the critical need for novel therapeutic strategies. RNA-based therapeutics, including siRNA and mRNA, offer promising approaches for cardiac diseases, yet their clinical application is limited by low heart specificity and suboptimal delivery methods. Lipid nanoparticles (LNPs) are widely used for RNA delivery but often accumulate in non-cardiac tissues, reducing their effectiveness. To address this, an extracellular matrix (ECM)-LNP composite is developed for targeted RNA delivery to the myocardium. The LNPs are conjugated to the ECM scaffold to enhance RNA retention. In vivo experiments demonstrate effective mRNA delivery and expression within the heart, with preferential targeting towards immune cells. Epidermal growth factor receptor (EGFR), a key regulator of cell proliferation and inflammation, is found to affect macrophage polarization in this study. The therapeutic potential of EGFR siRNA delivered via ECM-LNP composite is further explored in a mouse model of myocardial infarction (MI). Results indicate that ECM-siEGFR@LNP reduces cardiac fibrosis and promotes M2 macrophage polarization. This effect is associated with down-regulation of the EGFR-AKT signaling pathway. In conclusion, this study presents an injectable platform for heart-specific RNA delivery and sheds light on the role of EGFR signaling in the cardiac repair process.

To clarify the fat attenuation index (FAI) change trend of peri-saphenous vein graft (SVG) and determine the association between FAI and graft disease progression based on CCTA images. Patients with venous coronary artery bypass grafts (CABGs) were consecutively enrolled in this retrospective study. In study 1, 72 patients who had undergone 1, 3, and 5 years of CCTA examinations without graft occlusion were recruited, and generalized estimation equation was used to analyze the peri-SVG FAI change trend over time. In study 2, 42 patients with graft disease progression and 84 patients as controls were propensity score-matched. Generalized linear mixed model and continuous net reclassification improvement (NRI) were used for assessing the associations with graft disease progression. Multivariable Cox regression analysis was used for assessing risk factors predicting cardiac events. In study 1, both the FAI of proximal right coronary artery and SVG decreased over time. In study 2, the 1-year CTA-derived FAI of grafts and graft anastomosis were independent indicators of graft disease progression at the 3-year CCTA follow-up (graft: odds ratio [OR] = 1.106; 95