BACKGROUND:The multicenter, randomized, sham-controlled FAVOR III China trial (Comparison of Quantitative Flow Ratio-Guided and Angiography-Guided Percutaneous Intervention in Patients with Coronary Artery Disease) demonstrated that quantitative flow ratio (QFR)-guided percutaneous coronary intervention (PCI) resulted in better outcomes compared with angiographic guidance at 1-year and 2-year follow-up. Whether these benefits are sustained over long-term follow-up remains uncertain. OBJECTIVES:The purpose of this study was to evaluate the long-term effectiveness and safety of a QFR-guided PCI strategy compared with angiography-guided PCI at 5 years. METHODS:Patients with at least 1 angiographically intermediate coronary lesion (50%-90% diameter stenosis) in a vessel ≥2.5 mm diameter were randomized to a QFR-guided (PCI performed only if QFR ≤0.80) or angiography-guided strategy. The primary endpoint was major adverse cardiac events (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization) at 1 year; 5-year outcomes data are reported herein. RESULTS:At 5 years, major adverse cardiac events composite was lower with QFR guidance than with angiography guidance (17.5% vs 21.1%; HR: 0.80; 95% CI: 0.69-0.92; P = 0.002), driven by fewer myocardial infarctions (5.8% vs 9.0%; HR: 0.63; 95% CI: 0.49-0.80; P < 0.0001) and ischemia-driven revascularizations (9.6% vs 12.0%; HR: 0.78; 95% CI: 0.64-0.95; P = 0.02) in the QFR-guided group. All-cause death did not differ between groups. Landmark analysis showed that the benefit of QFR guidance accrued predominantly within the first 2 years (8.5% vs 12.5%; HR: 0.66; 95% CI: 0.54-0.81; P < 0.0001), with similar outcomes between 2 and 5 years (10.2% vs 11.2%; HR: 0.90; 95% CI: 0.73-1.11; P = 0.32; P for interaction = 0.001). CONCLUSIONS:Compared with angiography guidance, QFR-guided strategy improved 5-year clinical outcomes, with benefits primarily achieved within the first 2 years. (The FAVOR III China Study; NCT03656848).

Magnetocardiography (MCG) provides unrivalled sensitivity to the weak magnetic fields generated by the heart, yet its clinical utility is hindered by two intertwined challenges: severe information loss during conventional channel-wise or spatial-averaging dimensionality reduction and contamination from heterogeneous environmental and physiological noise. We present Edge-Aware Multi-Head Transformer (EA-MHT), a novel spatiotemporal architecture that treats the MCG array as a whole, explicitly preserving both the central cardiac dynamics and the often-neglected edge-field signatures. First, a dedicated multi-head attention block learns rich representations of the peripheral channels, where gradient-rich but low-amplitude signals coexist with dominant noise sources. These edge-aware features are then fused with central-region embeddings through a second multi-head attention layer that jointly encodes global spatial coherence and local temporal structure. Finally, an attention-selection gating mechanism adaptively suppresses noise-related attention heads while amplifying signal-specific ones, yielding a purified, high-fidelity reconstruction of the cardiac magnetic field. Extensive experiments on the publicly released Kiel Cardio Database—containing 128-channel unshielded recordings from 312 subjects—demonstrate that EA-MHT outperforms state-of-the-art CNN, LSTM, and vanilla Transformer baselines in denoising (SNR ↑ 4.7 dB), spatial fidelity (STE ↑ 18 ↑ 6.3

Background: Triclosan (TCS), a widely used environmental antimicrobial agent, is associated with cardiovascular risks such as coronary heart disease; however, its effect on post-myocardial infarction (MI) prognosis remains unclear. This study investigated whether TCS exacerbated post-MI outcomes and the underlying mechanisms, with the goal of identifying potential preventive strategies. Methods: MI models were established using mice with left anterior descending coronary artery ligation, alongside hypoxia-treated neonatal rat cardiomyocytes (NRCMs) and human AC16 cardiomyocytes. A comprehensive set of methodologies was employed, including RNA sequencing, echocardiography, Western blotting, co-immunoprecipitation, dual-luciferase reporter assays, molecular docking, quantitative real-time PCR, histological/immunofluorescence staining, and oxidative stress parameter analyses. Mechanistic investigations utilized Nur77 knockout mice, AAV9-based viral vectors targeting Nur77 and NTRK2, adenoviruses, plasmids, and small-molecule inhibitors/activators. Results: Exposure to environmentally relevant TCS concentrations dose-dependently aggravated short- and long-term post-MI cardiac dysfunction and ventricular remodeling in both male and female mice. Mechanistically, TCS induced TRIM13-mediated K48-linked ubiquitination and proteasomal degradation of the nuclear receptor Nur77, leading to reduced transcription of NTRK2. Downregulated NTRK2 suppressed the AKT/mTOR/YY1 signaling cascade, ultimately decreasing PGC-1α expression and impairing mitochondrial function—specifically mitochondrial oxidative phosphorylation. This bioenergetic deficit triggered excessive reactive oxygen species (ROS) production, promoting lipid peroxidation and exacerbating cardiomyocyte ferroptosis, cellular senescence, and the senescence-associated secretory phenotype (SASP). These pathological effects collectively exacerbated acute post-MI injury and facilitated the progression of long-term ventricular remodeling. Validation in NRCMs and human AC16 cardiomyocytes confirmed conserved phenotypes and mechanisms. Pharmacological activation of PGC-1α with ZLN005 mitigated TCS-induced deterioration of short- and long-term post-MI cardiac function and attenuated ventricular remodeling. Conclusions: TCS exacerbates post-MI injury by disrupting the Nur77/NTRK2/PGC-1α axis, triggering mitochondrial dysfunction-mediated ferroptosis and senescence in cardiomyocytes of both male and female mice. Pharmacological activation of PGC-1α represents a potential strategy to counteract TCS-induced adverse outcomes after MI.

AIMS:The long-term impact of left atrial appendage occlusion (LAAO) plus ablation for atrial fibrillation remains controversial. The present study aims to compare the three-year clinical outcomes of LAAO patients with or without one-staged ablation. METHODS AND RESULTS:The RECORD study (NCT03917563) was a prospective registry conducted in 39 participating sites in China between 1 April 2019 and 31 October 2020, which consecutively enrolled 3082 patients who successfully received the WATCHMAN LAAO device. The current study compared patients who received LAAO only to patients who underwent LAAO plus ablation. A 1:1 propensity score matching was performed to attenuate confounding. The primary outcome was a composite endpoint of cardiovascular death, stroke, and systemic embolism at 3-year. 1633/2928 (55.8%) patients received LAAO only and 1295/2928 (44.2%) received LAAO plus ablation. After propensity score matching, 1016/2032 (50.0%) were in the LAAO group and 1016/2032 (50.0%) in the LAAO plus ablation group. The mean ± SD age was 68.8 ± 9.3 years, with 815 (40.1%) participants being female. The mean ± SD CHA2DS2-VASc and HAS-BLED scores at baseline were 3.9 ± 1.8 and 2.4 ± 1.1, respectively. At three-year, compared to LAAO only, LAAO plus ablation was associated with a lower risk of cardiovascular death, stroke, systemic embolism (6.9%vs.10.4%, HRPSM:0.66, 95%CI: 0.49-0.89, P = 0.007), which was driven mainly by the lower risk of cardiovascular death (3.7% vs. 7.3%, HRPSM: 0.50, 95%CI: 0.34-0.74, P = 0.001). No significant between-group differences were noted for BARC-defined bleeding. CONCLUSION:LAAO plus ablation was associated with a lower risk of a composite of cardiovascular death, stroke, and systemic embolism than LAAO only at 3-year. However, given the observational nature of the current study, the results should be considered as hypothesis-generating only.

Myocardial ischemia/reperfusion (I/R) injury undermines the clinical benefit of percutaneous coronary intervention, with cardiac macrophages playing critical roles. Here, using spatial transcriptomics and flow cytometry, we identified adenylyl cyclase 7 (ADCY7) as a macrophage-specific regulator and potential therapeutic target in myocardial I/R injury, and validated its expression in patient samples. By establishing a macrophage depletion/reconstitution model, we demonstrate that macrophage Adcy7 deficiency significantly exacerbates myocardial I/R injury and cardiac dysfunction in male mice, whereas Adcy7 overexpression attenuates these effects. Macrophage Adcy7 deficiency also increases leukocyte infiltration and pro-inflammatory cytokine production. Mechanistically, transcriptomic and phosphoproteomic analyses reveal that ADCY7 activates cAMP-protein kinase A signaling, thereby inhibiting nuclear translocation of NF-κB and restraining the pro-inflammatory response. Combined with the macrophage depletion/reconstitution approach, we developed a photoactivated adenylyl cyclase system that alleviated cardiac inflammation and I/R injury. Our study identifies ADCY7 as a macrophage-intrinsic anti-inflammatory regulator and a promising therapeutic target for myocardial I/R injury.

BackgroundStent implantation in vessels with moderate/severe coronary tortuosity is associated with increased rates of target vessel failure due to higher rates of target vessel-related myocardial infarction or ischemia-driven target vessel revascularization. Local wall shear stress (WSS) changes might contribute to this phenomenon. This study investigates the impact of stenting on the hemodynamic environment of tortuous coronary arteries in a numerical simulation model.Materials and methodsA numerical simulation model was established to explore the characteristics of hemodynamic parameters before and after simulated stent implantation in tortuous coronary vessels. The numerical simulation model is composed of four tortuous arcs. By controlling the curvature of these arcs, three groups with different tortuosity were formed. Four different stenosis degrees (40%, 50%, 60%, and 70%) were formed by changing the diameter of the third arc in each group. Finally, 12 models with different degrees of stenosis and tortuosity were analyzed.ResultsThe velocity and WSS were reduced in proportion to increased stenosis after stent implantation in tortuous segments mimicking tortuous coronary vessels with low, medium, and high tortuosity.ConclusionOur results indicate that further reduced WSS in tortuous coronary vessels post stenting might lead to increased endothelial dysfunction, vascular inflammation, and neointimal hyperplasia, all of which facilitate the formation of in-stent restenosis, especially in tortuous coronary vessels with severe stenosis.

BackgroundGuidewire fracture during percutaneous coronary intervention (PCI) is rare but serious, with management dependent on fracture characteristics. We report an innovative minimally invasive hybrid approach for this complication.Case summaryA 59-year-old male with diabetes/hypertension developed Sion guidewire fracture during LAD PCI. Percutaneous retrieval failed; conservative therapy was initially given. A minimally invasive hybrid “trans-brachial arteriotomy with endoluminal traction” retrieved the fragment 34 days post-fracture, with uneventful recovery.DiscussionGuidewire fracture occurs in 0.2%–0.8% of PCI cases. Histopathological evidence suggests that at 34 days, incomplete endothelialization facilitates rather than hinders retrieval. Although no standard retrieval window exists, delayed elective retrieval can achieve high success rates in stable patients. Traditional open surgery is traumatic; our hybrid approach avoids sternotomy, offering a novel salvage strategy valuable for interventional cardiologists and surgeons.Take home messagesMinimally invasive hybrid retrieval is safe and effective for PCI guidewire fractures refractory to percutaneous methods, emphasizing the value of multidisciplinary collaboration.

Magnetocardiography (MCG) provides high-resolution spatiotemporal insights into cardiac electrophysiology but remains underutilized for left ventricular hypertrophy (LVH) diagnosis due to a lack of interpretable analytical tools. We propose a novel interpretable machine learning framework that systematically decodes MCG signals across four complementary domains: temporal waves, spatial waves, current source imaging, and dynamic characterization. To address class imbalance, we integrated Focal Loss into the XGBoost objective function. In a dataset of 481 subjects, our model achieved an AUC of 0.902 in cross-validation and 0.837 in independent validation, significantly outperforming conventional baselines. Notably, SHapley Additive exPlanations (SHAP) identified T-wave magnetic polarity as the most influential predictor, offering new perspectives on the electrophysiological remodeling of hypertrophied myocardium. This framework bridges the gap between raw sensor data and clinical decision-making, providing a robust tool for automated LVH detection.

Low expression level of low-density lipoprotein receptor (LDLR) in hepatocytes leads to hypercholesterolemia and eventually contributes to atherosclerotic cardiovascular disease (ASCVD). Here, we report that inhibition of hepatocyte ABCC4, identified as a top hit from large-scale CRISPR/Cas9 screens, significantly increases hepatic LDLR abundance and enhances LDL cholesterol clearance. As a hepatic transporter for cAMP efflux, ABCC4 silencing alters its intracellular distribution and activates the downstream Epac2/Rap1a signaling pathway, which ultimately blocks PCSK9 protein expression, thereby preventing lysosomal degradation of LDLR. Furthermore, in both male mice and cell models, we demonstrate that liver-specific disruption and pharmacological inhibition of ABCC4 elevate hepatic plasma membrane LDLR levels and reduce plasma LDL cholesterol through ABCC4-cAMP-PCSK9 pathway. Collectively, our genome-wide CRISPR screening offers a valuable resource for identifying LDLR modifiers, providing potential insights for therapeutic strategies in hypercholesterolemia and atherosclerosis.

Background:The benefits of physiology-guided management in acute coronary syndrome (ACS) remain inconclusive due to limited evidence. In our FAVOR III China trial, a quantitative flow ratio (QFR)-based physiology-guided strategy versus standard angiography guidance improved the 1-year primary outcome among participants with coronary artery disease (CAD). We aimed to investigate, in a prespecified analysis, the outcomes of QFR-based physiological guidance in the FAVOR III China participants with low-risk ACS. Methods:This pre-specified secondary analysis included patients diagnosed with low-risk ACS who were enrolled in the FAVOR III China trial. The trial was a prospective, randomised study that assigned 3825 CAD patients to receive QFR-guided or angiography-guided percutaneous coronary intervention (PCI) at 26 hospitals in China between December, 2018 and January, 2020. The primary outcome of interest for this study was major adverse cardiac events (MACE), defined as a composite of all-cause death, myocardial infarction, and ischaemia-driven revascularisation, at 1-year (primary outcome of FAVOR III China) and 2-year follow-up. Secondary outcomes included PCI strategy change and the procedural characteristics. FAVOR III China is registered with ClinicalTrials.gov, NCT03656848. Findings:Of the 2371 participants with low-risk ACS (93.7% unstable angina and 6.3% non-ST elevation myocardial infarction [NSTEMI]) in the FAVOR III China trial, the QFR-guided strategy changed the original intended treatment plan in 23.6% of the low-risk ACS patients, resulting in more PCI deferrals (19.0% vs 3.8%; P < 0.001), less stenting (1.5 ± 1.1 vs 1.6 ± 1.0 per participant; P = 0.034), and shorter fluoroscopy time (13.7 ± 7.7 min vs 14.6 ± 7.1 min; P = 0.01) compared with the angiography-guided strategy. During follow-up, there was some evidence that the QFR guided strategy is superior to the angiography-guided approach at reducing the risk of MACE at 1-year follow-up (6.1% vs 8.2%; HR, 0.74; 95% CI, 0.54-1.01, P = 0.055), with a significant risk reduction at 2-year follow-up (8.3% vs 11.7%; HR, 0.70; 95% CI, 0.54-0.91, P = 0.009). The landmark analysis indicated consistent patterns both before and after 1 year (P interaction = 0.35). Interpretation:Our findings favoured the superiority of QFR-guided lesion selection strategy over standard angiography guidance in reducing long-term MACE for the low-risk ACS population. The benefits associated with QFR need to be confirmed by future studies with extended follow-up. Funding:The National High Level Hospital Clinical Research Funding, the Capital's Funds for Health Improvement and Research, the Chinese Academy of Medical Sciences, the Noncommunicable Chronic Diseases National Science and Technology Major Project, Shanghai Municipal Health Commission "Top Priority Research Centre", and Shanghai Shenkang Hospital Development Centre.

Background:Early prediction of heart failure (HF) after acute myocardial infarction (AMI) remains a clinical challenge. There is a lack of studies investigating Thymosin α1 expression levels in AMI patients and its relationship with cardiac function post-AMI. Methods:This retrospective analysis included patients with AMI from December 2019 to February 2022. The baseline data of two groups were collected. Thymosin α1 expression level of peripheral blood plasma in AMI patients was examined by ELISA. Logistic regression analysis was applied to evaluate risk factors in-hospital cardiac dysfunction after emergency PCI in AMI patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of the biomarker. Results:A total of 307 hospitalized patients were enrolled in this study, divided into AMI group (n = 274) and non-AMI group (n = 33). The expression level of thymosin α1 in the AMI group was significantly higher than in the non-AMI group. The AMI patients were divided into two subgroups based on the EF values. The sample size was 64 (EF < 50%) and 210 (EF ≥ 50%), respectively. The expression of thymosin α1 in the EF ≥ 50% group was significantly higher than EF < 50% group. Spearman's correlation analysis demonstrated that thymosin α1 was positively correlated with the EF value. Logistic multivariate analysis suggested that thymosin α1, NT-proBNP, and creatine kinase were independent predictors of cardiac function after AMI. The AUC of thymosin α1, NT-proBNP, and creatine kinase was 0.614, 0.714, and 0.724, respectively. Conclusion:Thymosin α1 may serve as a potential biomarker to predict cardiac function following AMI. This study may provide novel insights into the potential therapeutic targets for HF following AMI.

Background:Quantitative flow ratio (QFR) based lesion selection for percutaneous coronary intervention (PCI) treatment has shown clinical benefits in terms of reduced risk for myocardial infarction and repeat revascularization. Whether this benefit is consistent across different age groups still needs further investigation. Methods:In this prespecified subgroup study of FAVOR III China trial, we compared long-term clinical outcomes between QFR-guided and angiography-guided PCI among different age groups among 3825 enrolled subjects. The primary endpoint was major adverse cardiac events (MACEs), a composite of all-cause death, myocardial infarction, and ischemia-driven revascularization. Results:Of the 3825 patients, 1717 (44.9%) were aged ≥ 65 years. At baseline, patients ≥ 65 had higher rates of hypertension, hyperlipidaemia, stroke history (P < 0.0001), and peripheral vascular disease (P = 0.024) and had higher SYNTAX scores (P = 0.0095). Compared with standard angiography guidance, the QFR-guided strategy consistently reduced the 1-year (≥ 65 years, 6.04% vs. 9.19%, HR = 0.65, 95% CI: 0.46-0.92; < 65 years, 5.53% vs. 8.43%, HR = 0.65, 95% CI: 0.47-0.91) and 3-year MACE rates in both age groups (≥ 65 years, 11.8% vs. 15.2%, HR: 0.75, 95% CI: 0.58-0.98; < 65 years, 9.5% vs. 14.6%, HR = 0.63; 95% CI: 0.49-0.81), without a significant interaction (P interaction = 0.99). Within the QFR-guided group, the 3-year MACE rate in patients with deferred vessels was numerically greater in patients aged ≥ 65 years than in those aged < 65 years (8.3% vs. 3.0%, P = 0.10). Conclusions:Although with higher rate of comorbidities and more complex coronary anatomy, the long-term benefit of the QFR-guided PCI strategy remained consistent in patients ≥ 65 years, compared with those < 65 years.

Early diagnosis and localization of myocardial ischemia (MS) and coronary artery stenosis (CAS) play a crucial role in the effective prevention and management of ischemic heart disease (IHD). Magnetocardiography (MCG) has emerged as a promising approach for non-invasive, non-contact, and high-sensitivity assessment of cardiac dysfunction. This study presents a multi-center, AI-enabled diagnosis and localization of myocardial ischemia and coronary artery stenosis from MCG data. To this end, we collected a large-scale dataset consisting of 2,158 MCG recordings from eight clinical centers. We then proposed a multiscale vision transformer-based network for extracting spatio-temporal information from multichannel MCG recordings. Anatomical prior knowledge of the coronary artery and the irrigated left ventricular regions was incorporated by a carefully designed graph convolutional network (GCN)-based feature fusion module. The proposed approach achieved an accuracy of 84.7%, a sensitivity of 83.8%, and a specificity of 85.6% in diagnosing IHD, an average accuracy of 78.4% in localization of five MS regions, and an average accuracy of 65.3% in localization of stenosis in three coronary arteries. Subsequent validation on an independent validation dataset consisting of 268 MCG recordings collected from four clinical centers demonstrated an accuracy of 82.3%, a sensitivity of 83.8%, and a specificity of 81.3% in diagnosing IHD, an average accuracy of 77.3% in localization of five myocardial ischemic regions, and an average accuracy of 65.6% in localization of stenosis in three coronary arteries. The proposed approach can be used as a fast and accurate diagnosis tool, boosting the integration of MCG examination into clinical routine.

Magnetocardiography (MCG) is a highly sensitive, non-invasive, and functional imaging technique that records and examines magnetic fields generated by the electrical activity of the heart to reflect cardiac electrophysiological changes, including the first superconducting quantum interference device and optically pumped magnetometers-MCG. The 60-year research process yields new understanding in the areas of signal extraction, processing, and clinical application for the detection and treatment of cardiac diseases. Especially, the significant advancements in magnetic sensor technology, preprocessing methods and denoising methods have promoted the development of MCG. This article systematically reviews 83 studies to provide the latest and general overview of MCG in acute chest pain (6 studies), acute coronary syndrome (10 studies), ischemic heart disease (13 studies), non-ischemic cardiomyopathies (3 studies), arrhythmia (9 studies), and fetal congenital arrhythmia (11 studies). We highlight its incremental value in the triage of acute chest pain, diagnosis and prognosis prediction of chronic and acute coronary syndromes. We also discuss the limitations of this field and directions of future development.

Myocardial infarction (MI) is the leading cause of death globally, often resulting to significant loss of cardiac function. A key factor in the pathological progression of MI is the excessive generation of reactive oxygen species (ROS) by dysfunctional mitochondria. However, no antioxidant therapy has been approved for clinical treatment of MI to date. In this study, selenium-loaded porous silica nanospheres (Se@PSN) are synthesized as a novel therapeutic approach for MI. These nanospheres are capable of neutralizing various ROS, thereby reducing hypoxia-induced myocardial cell damage. Additionally, Se@PSN promote the upregulation of antioxidant proteins, providing sustained intracellular ROS scavenging, which helps reduce infarct size and preserve cardiac function post-MI. The sustained antioxidant effects of Se@PSN are attributed to their ability to safeguard mitochondrial function by modulating oxidative phosphorylation, mitochondrial dynamics, and mitophagy. The activation of mitophagy by Se@PSN is achieved through the upregulation of HIF-1α expression. In conclusion, Se@PSN show significant potential for clinical translation as a novel therapeutic strategy for MI.

Magnetocardiogram is a promising technology for future heart disease diagnosis and prognosis. However, there is no unified standard of magnetocardiogram in the normal population for further study and comparison. This study aimed to establish the magnetocardiogromics platform that could provide a well-acknowledged parameter library and its reference range in the normal population for future study. 93 cases were enrolled in study set for parameter reference range determination. Another 111 cases were used as validation. We built a library with 246 parameters with their reference range in the normal population. In addition, we established a standard process for future magnetocardiogram study. This is the first time that we proposed the concept of magnetocardiogromics, which standardized the parameter library and its reference range as well as establishing a unified analysis platform. Not applicable.

Carotid atherosclerosis is a common vascular disease characterized by lipid deposition and plaque formation within the carotid artery walls, which may lead to restricted blood flow and even severe complications such as stroke. This study aims to develop an automated evaluation system based on the ResNet and transformer framework to diagnose carotid atherosclerosis and grade its severity using bilateral ultrasound images of the neck at different time points along with related metadata. Given the complexity and multifactorial nature of carotid atherosclerosis, we designed a cross-time-point image fusion strategy to capture the dynamic changes and spatial distribution characteristics of lesions. Additionally, a masked cross-time-point attention mechanism was employed to optimize information interaction between images at different time points, reducing noise interference. Furthermore, a multilayer perceptron was utilized to extract metadata features, further enhancing the model’s expressive capabilities. Extensive comparative and ablation experiments conducted on a self-constructed dataset demonstrated the effectiveness and robustness of the proposed method, providing new technical support for the early screening and precise treatment of carotid atherosclerosis.