AIMS/BACKGROUND:In-hospital progressive stroke in patients with pre-existing large artery occlusion presents a therapeutic dilemma, particularly when standard reperfusion strategies are unsuitable. This case report aims to illustrate a mechanism-guided medical approach in this complex scenario. CASE PRESENTATION:We report the case of a 65-year-old male patient with chronic left vertebral artery occlusion, hospitalised for dizziness, who experienced acute neurological deterioration with a National Institutes of Health Stroke Scale (NIHSS) score ranging from 2 to 14. Magnetic resonance imaging confirmed a new pontine infarction. Endovascular therapy was deferred due to suspected artery-to-artery embolism from an unstable plaque. Instead, argatroban infusion combined with antiplatelet therapy was initiated within 5 h. RESULTS:The patient showed gradual improvement, and follow-up imaging demonstrated complete thrombus resolution. The NIHSS score was reduced to 4 at discharge. CONCLUSION:This case highlights the successful use of a mechanism-guided approach with argatroban for thrombolysis-naïve posterior circulation stroke, effectively balancing the thrombotic and haemorrhagic risks. This suggests that personalised anticoagulation may optimise outcomes in similar complex scenarios in which standard reperfusion is unsuitable.

Background and Objective: Brief paired 12-lead calibration may supply patient-specific information unavailable to population models for missing-lead reconstruction. We quantified its contribution relative to nonlinear architecture and tested transfer across recordings from the same patient.,Methods: From I, II and V2, we reconstructed V1 and V3-V6. We compared a population linear mapping (GL), a patient-calibrated linear mapping (PCM), four uncalibrated neural architectures, and CaLiNet-E, which combines a quality-gated patient-calibrated anchor with a FiLM-conditioned residual U-Net. Evaluation used patient-disjoint PTB-XL development and locked test folds plus CPSC2018 and CODE-test. Cross-record transfer used 189 patients with multiple PTB-XL recordings.,Results: On development, calibration increased Eq. (6) by 0.155 within linear models (GL 0.441; PCM 0.596) and by 0.167 within matched nonlinear models (forced rho=0 0.513; CaLiNet-E 0.680); corresponding nonlinear contributions were 0.072 and 0.084. On locked fold 10, CaLiNet-E achieved PCC 0.969 and nRMSE 0.213 versus 0.944 and 0.295 for PCM; diagnostic macro F1 was 0.664 versus 0.675 for the original signal. CPSC2018 agreed; on CODE-test, PCM had higher PCC but CaLiNet-E lower nRMSE. Cross-record coefficients without shrinkage did not improve on GL (-0.001; 95% CI -0.019 to 0.018) but exceeded mismatched-patient coefficients by 0.124 (0.105 to 0.144). Half-weight shrinkage toward GL recovered 0.033 (0.015 to 0.051), while cross-record CaLiNet-E exceeded its matched forced-rho=0 control by 0.064 (0.044 to 0.090). On a common GL reference, it retained 21.4% (16.8% to 26.1%) of fresh-calibration gain. Same-patient coefficient pairs were closer than different-patient pairs in 81.5% of comparisons; nearest-neighbour identification was 18.5% versus 0.53% chance.,Conclusions: Calibration contributed more than the architectural differences examined. The coefficients carry a detectable patient-specific ECG signature, but most within-record benefit is recording-specific. Shrinkage improves transfer; recalibration remains preferable after measurement-geometry changes.

BACKGROUND:Metabolic disturbances are key contributors to myocardial ischemia-reperfusion (I/R) injury, yet the underlying molecular mechanisms remain largely unclear. Rho family GTPase 3 (RND3), a cytosolic small guanosine triphosphatase (GTPase) known to antagonize ROCK1 (Rho-associated coiled-coil kinase 1), has been implicated in several cardiovascular disorders. However, its mitochondrial localization and functional role in cardiac energy metabolism and I/R injury remain unknown. METHODS:A murine model of myocardial I/R injury was established through left anterior descending coronary artery ligation. Mice with cardiomyocyte-specific knockout and overexpression of Rnd3 were generated. To investigate the role of RND3 in cardiac metabolism and I/R injury, we used 13C-nuclear magnetic resonance, 18F-fluorodeoxyglucose positron emission tomography/computed tomography scanning, seahorse mitochondrial energy metabolism assays, and 13C-metabolic flux tracing. Mechanistic studies were conducted using RNA sequencing, coimmunoprecipitation, mass spectrometry, and glutathione S-transferase (GST) pulldown assays. RESULTS:Cardiomyocyte-specific deletion of Rnd3 (Rnd3 conditional knockout, Rnd3cKO) resulted in impaired glucose oxidation and compensatory upregulation of fatty acid oxidation, leading to pronounced cardiac dysfunction and increased mortality. Rnd3cKO hearts exhibited reduced pyruvate/malate-driven complex I respiration and marked uncoupling between glycolysis and the tricarboxylic acid cycle. Mechanistically, RND3 was identified as a novel mitochondrial matrix-localized small GTPase that directly binds to ACAT1 (acetyl-coenzyme A [CoA] acetyltransferase), disrupting its interaction with PDHA1 (pyruvate dehydrogenase E1α subunit) and thereby promoting PDHA1 acetylation and glucose oxidation. It is important to note that RND3 expression was significantly downregulated in both human and murine hearts after I/R insult. Loss of RND3 sensitized the hearts to I/R injury, as evidenced by reduced levels of phosphocreatine and ATP. Conversely, cardiac-specific overexpression of Rnd3 conferred protection against I/R injury, an effect that was abolished upon Pdha1 knockdown. CONCLUSIONS:Our results identify RND3 as a novel mitochondria-localized regulator of glucose oxidation that safeguards the heart against I/R injury. Therapeutic reconstitution of Rnd3 may represent a promising strategy to restore metabolic homeostasis and mitigate myocardial damage in the context of I/R.

Glycolysis-derived lactate serves as a substrate for lysine lactylation, an epigenetic modification playing critical transcriptional regulatory roles in inflammatory diseases. Endothelial inflammation, characterized by upregulated glycolysis, initiates atherosclerosis, yet the contribution of histone lactylation remains undefined. Although narciclasine exhibits anti-inflammatory and antioxidant properties, its impact on endothelial inflammation in atherosclerosis is unknown. Connectivity Map (CMap) analysis predicted narciclasine as an inhibitor of oscillatory shear stress and TNF-α-induced endothelial inflammation. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with 20 nM narciclasine significantly suppressed ox-LDL-induced expression of VCAM1, ICAM1, SELE, and CCL2, reduced reactive oxygen species (ROS) production, and inhibited monocyte adhesion and migration. In vivo, administration of narciclasine (0.02 mg/kg) attenuated carotid artery endothelial inflammation and macrophage infiltration, consequently reducing early atherogenesis in partial carotid ligation model in ApoE−/− mice. Mechanistically, ox-LDL upregulated GLUT1 and PFKFB3 expression, enhancing endothelial glycolysis and lactate production. Increased lactate accumulation promoted histone H3 lysine 18 lactylation (H3K18la). Both pharmacological (2-DG, DCA) suppression of lactate production or genetic (LDHA, P300 silencing) suppression reduced H3K18la levels and inhibited ox-LDL-induced endothelial inflammation. Reanalysis of public CUT Tag data (GEO: GSE267661) and chromatin immunoprecipitation (ChIP) validation revealed ox-LDL-induced enrichment of H3K18la at key promoters of NF-κB pathway genes (TRAF2, TRAF6, RIP1, cIAP1, RELA). Narciclasine treatment suppressed GLUT1 and PFKFB3 expression, thereby reducing H3K18la enrichment and inhibiting NF-κB pathway activation. Our findings provide novel insights into the functional role of lactylation-mediated epigenetic regulation in glycolysis-driven endothelial inflammation. Collectively, this study identifies narciclasine as a potential therapeutic candidate, which mitigates endothelial inflammation and early atherosclerosis by targeting a glycolysis-H3K18la network linked to NF-κB activation.

Transcatheter aortic valve replacement (TAVR), also known as transcatheter aortic valve implantation (TAVI), is an interventional technology in which an artificial aortic valve is compressed and assembled outside the body, then delivered through a catheter and implanted at the site of the diseased aortic valve, thereby functionally replacing the native valve. Two versions of the Chinese expert consensus on TAVR were issued in China in 2015 and 2020, respectively. To promptly update the field's understanding of TAVR and to promote its broader, more standardized, and higher-quality application in China, an expert panel has developed this new version of the consensus. This consensus includes substantial updates compared with the previous version, covering topics such as the epidemiology of aortic valve disease, recent advances in TAVR research, indications, procedural standards, post-procedural antithrombotic therapy, prevention and management of complications, management of special cases, and future development trends. This consensus integrates international research evidence and references international guidelines to ensure rigor and evidence-based recommendations, while also incorporating domestic research findings and clinical practice in China, thereby enhancing both its forward-looking perspective and practical applicability.

Assessing ventricular aneurysm (VA) after myocardial infarction (MI) with Cardiopulmonary Exercise Testing (CPET) are lack of evidence. This study aimed to evaluate the safety and characteristics of CPET in patients with post-MI VA. A total of 803 CPET were completed. The patients were divided into VA and non-VA groups according to echocardiography results (60 vs 743). The primary endpoint events about safety were set as blood pressure (BP) drops, exercise-related myocardial ischemia, and severe arrhythmias, while secondary endpoint events were set as abnormal BP response and frequent ventricular premature beats. The differences about CPET parameters were compared by propensity score matching analysis. No fatal adverse events were observed during or within 2 h post-CPET, while endpoint adverse events were observed in 15 cases (1.87%) which all occurred in the non-VA group. The maximum voluntary ventilation and left ventricular ejection fraction were statistically lower in the VA group, while left ventricular end-diastolic diameter was larger. A logistic regression analysis suggested that development of VA or not was not the risk factor for the occurrence of the primary endpoint events during CPET. No increase in the incidence of adverse events during CPET was observed in the VA versus non-VA group.

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).

BACKGROUND AND AIMS:To evaluate the real-world impact of early in-hospital Proprotein Convertase Subtilisin-Kexin Type 9 (PCSK9) inhibitor initiation on clinical outcomes in Chinese acute coronary syndrome (ACS) patients. METHODS:This retrospective study analyzed ACS patients (2021-2023) from the CCA Database-Chest Pain Center, comparing alirocumab-treated (n = 6414) and control (n = 25,656) groups after propensity score matching. Outcomes included 1-year major adverse cardiovascular events (MACE) (defined as the composite of non-fatal myocardial infarction, non-fatal ischemic stroke, all-cause mortality, or any coronary revascularization) via Kaplan-Meier analysis and low-density lipoprotein cholesterol (LDL-C) goal attainment (<1.4 mmol/L) at 1/3/6 months. Logistic regression was performed to identify predictors. RESULTS:The alirocumab group showed a significantly lower MACE incidence rate during 1-year of follow-up (2.76 vs 3.95 per 100 person-years, p = 0.003). At follow-up, LDL-C measurements were available in 293, 123, and 33 patients in the alirocumab group and 1759, 984, and 424 patients in the control group at 1, 3, and 6 months, respectively. More patients in the alirocumab group reached the LDL-C goal at 1-month (58.02% vs. 24.33%, p < 0.001). This trend remained consistent during the subsequent 3-month (52.85% vs. 23.88%, p < 0.001) and 6-month follow-up (51.52% vs. 26.18%, p = 0.002). Participation in the ACS Pathway Optimization project (OR = 0.49; 95% CI 0.29, 0.77; p = 0.004), in-hospital initiation of alirocumab (OR = 0.62; 95% CI 0.48, 0.78; p < 0.001), male (OR = 0.71; 95% CI 0.58, 0.87; p < 0.001) were significantly negatively associated with the occurrence of MACE event, and in-hospital initiation of alirocumab (OR = 4.29; 95% CI 3.23, 5.71; p < 0.001), male (OR = 1.47; 95% CI 1.09, 2.00; p = 0.014), hypertension (OR = 1.31; 95% CI 1.06, 1.63; p = 0.012) and lipid lowering treatment statin and ezetimibe (OR = 2.20; 95% CI 1.58, 3.07; p < 0.001) were significantly positively associated with 1-month LDL-C goal attainment. CONCLUSION:In-hospital initiation of alirocumab was associated with a lower risk of MACE and with higher LDL-C goal attainment in China real-world ACS patients.

The pathogenic mechanism underlying diseases caused by mitochondrial DNA (mtDNA) mutation, including hypertension, persists as an unresolved global challenge. Although mutation-induced mitochondrial defects have been well characterized, how these mito-perturbations are converted into critical intermediary signaling cascades and contribute to diseases remain unknown. Here, using human induced pluripotent stem cell (hiPSC)-derived vascular organoids (VOs) and vascular cells, the hypertensive mt. tRNAIle4263A > G mutation was identified to induce vascular senescence, apoptosis and vascular-specific dysfunction through mitochondria-endoplasmic reticulum (ER) interaction. For the first time, this study mapped the transcriptional reprogramming landscape of human VOs carrying this mutation. Through systematic screening and functional validation, ER stress was screened out, together with downstream mitochondria-associated ER membranes-mitochondrial Ca2+ overload resulting in vascular abnormality. Pathological reactive oxygen species (ROS) elevation, driven by tRNAIle destabilization and bioenergetic failure, acts as the primary instigator of maladaptive ER stress activation in this cascade. Pharmacological targeting of this axis-using mito-Tempol (a mitochondria-targeted ROS scavenger), Tauro Ursodeoxycholic Acid (an ER stress inhibitor), or RU265 (a highly-selective mitochondrial calcium uniporter inhibitor)-rescues vascular abnormality. This study highlights mt. tRNAIle4263A > G mutation orchestrates vascular pathology through ROS induced activation of inter-organelle communication, resolving a long-standing knowledge gap between mtDNA mutations and diseases and establishing therapeutic nexuses for mtDNA mutation-related cardiovascular diseases.

BACKGROUND:This study investigated the ability of coronary computed tomography angiography (CCTA)-derived computational fluid dynamics (CFD) parameters to identify lesions associated with subsequent acute coronary syndrome (ACS). METHODS AND RESULTS:The study included 37 patients with well-documented ACS and available CCTA performed at least 1 week before the event. Lesions identified on CCTA were classified as culprit (n=37) or non-culprit (n=42). Information on clinical characteristics and anatomical features was collected. CFD analysis was performed to compute wall shear stress (WSS) and axial plaque stress (APS) at both the segment (seg) and arc levels, with minimum (min) and maximum (max) values recorded. Univariate and multivariate logistic regression analyses were used to identify predictors of ACS. Significant stenosis was more frequent in culprit than non-culprit lesions (P=0.033). Compared with non-culprit lesions, culprit lesions had lower min(APSseg) values but higher max(|APS|seg) and max(WSSseg), although the differences were not statistically significant. In multivariate analysis, vessel location, min(APSseg) (odds ratio [OR] 3.17, P=0.047), and max(WSSseg) (OR 6.99, P=0.020) were independently associated with the occurrence of ACS events. Incorporating CFD parameters max(|APS|seg), min(APSseg) and max(WSSseg) into a model containing clinical and anatomical variables significantly improved ACS prediction (area under the curve 0.862 vs. 0.781; P=0.044). CONCLUSIONS:CCTA-derived CFD parameters are independently associated with the development of ACS. Integrating multiple CFD metrics enhances the predictive performance beyond traditional clinical and anatomical characteristics, supporting their potential role in risk stratification.

Coronary heart disease (CAD) is the leading cause of death worldwide, and coronary angiography (CAG) serves as the gold standard for its assessment. Valvular heart diseases, such as severe aortic stenosis (AS) and severe mitral regurgitation (MR), frequently coexist with CAD yet are often underdiagnosed. Opportunistic screening for these conditions at the time of CAG could influence therapeutic strategies and improve prognosis. This study developed and validated a foundation model for the automated screening of severe AS and severe MR from CAG videos. The study presents CAGFound, a video-based foundation model that was self-supervised pre-trained on CAG sequences from seven medical centers and subsequently adapted to two downstream tasks: screening for severe AS and severe MR. Two internal and external validation datasets were retrospectively enrolled from the First Medical Center and the Sixth Medical Center of Chinese PLA General Hospital, respectively. A total of 117,383 unlabeled CAG sequences were used to build CAGFound. For the detection of severe AS, CAGFound achieved an area under the receiver operating characteristic curve (AUROC) of 0.932 (sensitivity 0.767, specificity 0.921) on the internal test dataset and maintained robust performance on the external validation dataset, with an AUROC of 0.879 (sensitivity 0.800, specificity 0.955). For the detection of severe MR, the model demonstrated an AUROC of 0.933 (sensitivity 0.738, specificity 0.938) on the internal dataset and an AUROC of 0.896 (sensitivity 0.754, specificity 0.855) on the external cohort. The performance of CAGFound was also compared with other video-based foundation models, VideoMAEv2 and Video Swin. CAGFound achieved the highest AUROC and demonstrated the best calibration performance (Brier score 0.122, R2 0.478) compared with VideoMAEv2 (Brier score 0.159, R2 0.306) and Video Swin (Brier score 0.162, R2 0.306). CAGFound enables accurate, automated screening for severe AS and severe MR during CAG. It has the potential to increase detection rates, facilitate timely clinical referral, and improve prognosis without requiring additional contrast administration or procedures.

BACKGROUND AND AIMS:Atherosclerosis preferentially develops at disturbed flow sites, where macrophage polarization critically determines plaque vulnerability. PlexinD1 may regulate this process by mediating M1 macrophage polarization under low and oscillatory shear stress (OSS). This study aims to investigate the role of macrophage PlexinD1 in OSS-induced atherosclerotic progression. METHODS:Plasma PlexinD1 was quantified in 72 patients with acute coronary syndrome (ACS) stratified by coronary bifurcation lesion involvement. Plaques in carotid bifurcations (exposed to OSS) and those in proximal common carotid arteries (exposed to laminar shear stress, LSS) were compared to investigate the differential effects of OSS vs LSS. Myeloid-PlexinD1 knockout mice were generated to investigate its role in atherosclerosis, which was induced by exposure to a high-fat, high-cholesterol diet on an apolipoprotein E-deficient background. PlexinD1-targeted multi-modal nanoparticles were developed for imaging. PlexinD1-centric regulatory mechanisms were explored through proteomic and molecular analyses of co-cultured endothelial cells and macrophages subjected to OSS or LSS. RESULTS:Patients with coronary bifurcation lesions exhibited 1.32-fold higher plasma PlexinD1 levels. Human carotid bifurcation lesions demonstrated concurrently increased PlexinD1 expression, M1 macrophage polarization, and plaque vulnerability compared with plaques in common carotid arteries. In atherosclerotic mice, myeloid-PlexinD1 deletion attenuated lesions by suppressing M1 macrophage polarization. OSS down-regulated PTGS2/PGE2, thereby promoting PlexinD1/NF-κB-dependent M1 macrophage polarization. PlexinD1-targeted multi-modal imaging nanoparticles enabled in vivo identification and monitoring of bifurcation lesions. CONCLUSIONS:OSS drives atherosclerotic progression by suppressing endothelial PTGS2/PGE2 to promote PlexinD1/NF-κB-mediated M1 macrophage polarization. PlexinD1 represents a promising target to identify and stabilize atherosclerotic lesions.

OBJECTIVE:To investigate the effects of early in-hospital intensive lipid-lowering therapy (LLT) with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on lipid dynamics and clinical outcomes in Chinese acute coronary syndrome (ACS) patients, providing robust real-world evidence for its long-term benefits and optimal implementation timing to address the evidence gap in optimal lipid management for secondary prevention. METHODS & RESULTS:This multicenter prospective real-world study (http://www.clinicaltrials.gov, NCT number: NCT06738758), which building upon the ELEGANT pilot registry (ChiCTR2200065861), will enroll 6000 consecutively hospitalized ACS patients with uncontrolled dyslipidemia across more than 30 Chinese centers. Participants are enrolled based on recommended stratified proportions [(1) diagnostic categories: ST-segment elevation myocardial infarction : non-ST-segment elevation myocardial infarction : intermediate-high-risk unstable angina = 1:1:3; and (2) lipid-lowering strategies: PCSK9 inhibitor ± statin : statin+ezetimibe/hybutimibe : statin = 2:1:2). Treatment assignment reflects real-world clinical decisions guided by low-density lipoprotein cholesterol levels and patient preference. Twelve-month follow-up assessments were conducted at predefined intervals: baseline hospitalization, discharge, and 1, 3, 6, 12 months post-discharge. Primary endpoints were the goal attainment (low-density lipoprotein cholesterol < 1.4 mmol/L) rates across treatment arms. Key secondary endpoints were the major adverse cardiovascular events (including myocardial infarction, ischemic stroke, cardiovascular mortality, coronary revascularization) and all-cause death, and other secondary endpoints encompassed time-to-lipid-goal, longitudinal changes in lipids profiles and inflammatory biomarkers, and perivascular fat attenuation index evolution quantified by coronary computed tomographic angiography. Propensity score matching and inverse probability treatment weighting will address confounding bias. CONCLUSIONS:This study will pioneer evidence clarifying the optimal therapeutic window and clinical benefits of in-hospital intensive LLT for Chinese ACS patients. By establishing the first Chinese population-derived evidence for the "early intensive and rapid target attainment" strategy, our findings may challenge stepwise LLT paradigms. These results may guide international guideline updates for high-risk ACS populations, particularly in East Asian cohorts with distinct lipid profiles.

BACKGROUND:Vulnerable plaque rupture is a major mechanism underlying acute coronary events, but imaging-based risk assessment using individual plaque features remains limited. The histology-derived vulnerability index (VI) integrates multiple plaque components and is associated with adverse cardiovascular outcomes but requires ex vivo assessment. Optical coherence tomography (OCT) enables high-resolution in vivo plaque characterization, and the OCT-derived index of plaque attenuation (IPA) may provide a quantitative measure of integrated plaque vulnerability. AIMS:This study aimed to determine the association between OCT-derived IPA and histological VI and to identify the histological plaque components contributing to IPA. METHODS:In 240 coronary blocks from 10 human cadaveric hearts, co-registered OCT and histology were performed. IPA was calculated from attenuation images. Histology quantified necrotic core, collagen, α-SMA+ area, and macrophages (CD68+, CD206+). Associations were assessed using correlation and multivariable regression. RESULTS:IPA at a 9 mm-1 threshold (IPA9) correlated with VI (r = 0.714, p < 0.001) and discriminated high-VI blocks (AUC = 0.852). CD68+ macrophage area (β = 17.20, p < 0.001) and necrotic core (β = 1.39, p = 0.013) predicted higher IPA, whereas collagen and α-SMA+ area were inversely associated. CD206+ areas were not independently related with IPA, but the CD206+/CD68+ ratio significantly improved IPA model performance (ΔR2 = 0.023, p = 0.004). CONCLUSIONS:OCT-derived IPA closely corresponds to histological VI and is primarily driven by necrotic core and pro-inflammatory macrophage infiltration. IPA may serve as a clinically obtainable quantitative OCT marker for integrated assessment of inflammation-weighted plaque vulnerability.

BACKGROUND:The novel thin-strut sirolimus-eluting iron bioresorbable scaffold (IBS) demonstrated safety and efficacy in a nonrandomized first-in-human study. OBJECTIVES:The objective of this study was to compare the IBS with contemporary metallic cobalt chromium everolimus-eluting stents (CoCr-EES) in patients with coronary artery disease. METHODS:IRONMAN-II was a prospective, multicenter, single-blinded, noninferiority randomized trial across 36 centers in China. Eligible patients had myocardial ischemia and 1 or 2 de novo target lesions. Patients were randomly assigned (1:1) to IBS or CoCr-EES, with allocation masked. Optical coherence tomography (OCT) was performed in the first 25 participant pairs. Clinical follow-up was scheduled at 1, 6, and 12 months, and annually to 5 years, with angiographic and OCT follow-up at 2 years. The primary endpoint was 2-year angiographic in-segment late lumen loss (LLL). Powered secondary endpoints included target vessel quantitative flow ratio (QFR) and OCT-derived cross-sectional mean flow area. Other secondary endpoints included target lesion failure (cardiac death, target vessel myocardial infarction [MI], or ischemia-driven target vessel revascularization), the patient-oriented composite endpoint (all-cause death, MI, or any revascularization), their individual components, and device thrombosis. RESULTS:Between March 10 and December 13, 2022, 518 patients were randomized to IBS (n = 259) or CoCr-EES (n = 259). At 2 years, lesion-level in-segment LLL was 0.28 (0.52) mm with IBS and 0.23 (0.43) mm with CoCr-EES (difference: 0.08 mm; 95% CI: -0.02 to 0.18; Pnoninferiority = 0.03). Mean QFR was 0.90 (0.13) with IBS and 0.92 (0.09) with CoCr-EES (difference: -0.02; 95% CI: -0.04 to 0; Pnoninferiority = 0.05). Mean OCT flow area was 6.92 (3.48) mm2 with IBS and 6.64 (2.44) mm2 with CoCr-EES (difference: 0.27; 95% CI: -0.09 to 0.63; Pnoninferiority < 0.0001). Two-year target lesion failure occurred in 7.4% of IBS patients and 5.4% of CoCr-EES patients (HR: 1.37; 95% CI: 0.69-2.73; P = 0.37). No significant between-group differences in the rates of patient-oriented composite endpoint, death, or MI were present between the 2 groups. No scaffold thromboses occurred in the IBS group, whereas 1 stent thrombosis occurred with CoCr-EES. Binary restenosis and revascularization rates were higher with IBS, however, most such events were non-ischemia-driven. CONCLUSIONS:In IRONMAN-II, the sirolimus-eluting IBS was noninferior to CoCr-EES for 2-year in-segment LLL, QFR, and OCT-derived flow area. Clinical event rates were also comparable between groups although non-ischemia-driven revascularization rates were higher after IBS. Longer-term follow-up is necessary to demonstrate whether late benefits are realized after complete IBS resorption. (A Clinical Investigation to Evaluate the Safety and Efficacy of IBS in Patients With Coronary Artery Disease; NCT05206084).

BACKGROUND:Timely detection of left atrial appendage thrombus (LAAT) is critical for stroke prevention in atrial fibrillation. Current diagnostic approaches such as traditional models and physician visual analysis face challenges in comprehensive capturing image information. The study aimed to develop and validate a multimodal model integrating coronary computed tomography angiography-based radiomics features with clinical parameters for noninvasive LAAT detection in patients with atrial fibrillation. METHODS:The diagnostic study retrospectively enrolled 670 patients with nonvalvular atrial fibrillation undergoing coronary computed tomography angiography and transesophageal echocardiography from May 2015 to May 2023 and stratified into training and internal validation sets. An independent prospective cohort (n=114) from May 2023 to May 2025 served for external validation. Semiautomated LAA segmentation extracted 1231 radiomics features, with 25 features selected by random forest. A multimodal LAAT detection model was developed and evaluated using receiver operating characteristic, calibration curve, and decision curve analysis and compared against traditional models and physician visual analysis. RESULTS:The Radiomics-LAAT model achieved significantly superior discrimination in both internal validation (area under the curve, 0.963 [95% CI, 0.945-0.980], accuracy: 0.929) and external validation (areas under the curve, 0.920 [95% CI, 0.886-0.953], accuracy: 0.807), outperforming traditional models and physician visual analysis, with optimal calibration (Brier score: 0.067) and clinical net benefit. The Radiomics-LAAT model achieved high sensitivity (0.953), specificity (0.905), negative predictive value (0.950), and positive predictive value (0.910). CONCLUSIONS:The Radiomics-LAAT model significantly enhances noninvasive LAAT detection performance compared with traditional models and physician visual analysis, demonstrating its potential for stroke risk stratification in patients with atrial fibrillation.

INTRODUCTION:Senescent mesenchymal stem cells (MSCs) exhibit impaired self-renewal, limiting their therapeutic potential. While multi-omics have revealed downregulation of pan-tissue Fbn1 with aging, particularly in MSCs, the role of its derivative asprosin in MSC senescence is unknown. OBJECTIVES:To elucidate the regulation of senescence/reparative function in aged MSCs by asprosin and evaluate its therapeutic potential for aged MSC-mediated cardiac repair after myocardial infarction (MI). METHODS:Serum asprosin levels were measured by enzyme-linked immunosorbent assay, and asprosin expression in MSCs was determined by western blotting. Fbn1 expressiondynamics with aging were assessed using public transcriptomic/single-cell datasets. Gain/loss-of-function (lentiviral overexpression/CRISPR-Cas9 knockout) studies were employed to validate the role of asprosin. The effects of recombinant asprosin on senescent MSC proliferation, migration, and pro-angiogenic secretion were tested. Glycolytic flux (Seahorse), metabolites (glucose uptake, G-6-P, lactate), and lactylation (pan-lysine, H3K18la) were measured. Integrated H3K18la CUT&Tag/RNA-seq was performed to identify downstreamtargets, and therapeutic efficacy was assessed in an MI mouse model using intramyocardial injection of asprosin-overexpressing aged MSCs. RESULTS:Circulating asprosin was correlated with adipose mass in young obese mice but was attenuated in aged obese mice. Consistently, human cohorts (normal body mass index) showed an inverse age-asprosin correlation. Systemic and MSC-specific asprosin expression significantly declined with aging. Asprosin knockout intensified H2O2-induced MSC acute premature senescence, whereas its overexpression restored MSC self-renewal. Human recombinant asprosin protein (requiring post-translational modifications for bioactivity) enhanced proliferation, migration, and paracrine angiogenesis in senescent MSCs. Mechanistically, asprosin activated the PI3K/Akt-HIF-1 pathway to upregulate VEGF/TIMP1 (angiogenesis) and drive the glycolysis-lactate-H3K18la axis (proliferation/migration). H3K18la CUT&Tag/RNA-seq identified targets regulating DNA repair, proliferation, and migration. Asprosin deficiency impaired DNA repair. In MI mice, asprosin-overexpressing aged MSCs significantly improved retention and left ventricular ejection fraction, attenuated cardiac remodeling, and promoted peri-infarct angiogenesis. CONCLUSION:Asprosin is a novel MSC-specific rejuvenation factor that antagonizes senescence through metabolic-epigenetic interplay. Targeting the asprosin-driven "Glycolysis-Lactylation-Epigenetics" axis offers a transformative strategy to enhance MSC-based therapies for ischemic heart disease.

BACKGROUND:Females with stable coronary artery disease (CAD) often present with less obstructive disease on invasive coronary angiography (ICA) yet experience worse outcomes than males. Coronary computed tomography-derived fractional flow reserve (CT-FFR) guidance improves the physiological assessment of coronary lesions beyond coronary computed tomography angiography (CCTA), but its sex-specific clinical impact remains uncertain. AIMS:This study aimed to investigate sex-based differences in treatment and clinical outcomes between CT-FFR-guided and standard care strategies in patients with stable CAD. METHODS:In this post hoc subanalysis of the randomised TARGET trial, 1,216 patients with 30-90% coronary stenosis on CCTA were randomised to onsite CT-FFR-guided care or standard care. The primary endpoint was the proportion of patients who underwent ICA without obstructive CAD or had no intervention despite obstructive CAD on ICA within 90 days of CCTA. The secondary endpoint was major adverse cardiovascular events (MACE) at 2 years. RESULTS:Females were older than males (62.3±8.1 years vs 58.2±10.7 years; p<0.001) but had comparable anatomical CAD severity. CT-FFR-guided care significantly reduced ICA without obstructive CAD and increased early revascularisation in males but not in females. Over 2 years, CT-FFR-guided management was associated with a significantly lower MACE rate in females compared with standard care (adjusted hazard ratio [HR] 0.48, 95% confidence interval [CI]: 0.27-0.87; p=0.015), whereas no significant difference was observed in males (adjusted HR 0.89, 95% CI: 0.59-1.33; p=0.574). CONCLUSIONS:CT-FFR-guided management was associated with different clinical patterns between females and males. Particularly in males, CT-FFR guidance reduced unnecessary angiography. A lower 2-year adverse event rate was observed among females in the CT-FFR group. However, given the absence of a statistically significant interaction between sex and treatment strategy, these findings should be considered exploratory and hypothesis-generating. (ClinicalTrials.gov: NCT03901326).

Climate change has amplified the variability and intensity of cold weather, contributing to a growing health burden. Cold exposure serves as a significant, yet preventable, environmental trigger for acute chest pain–related life-threatening cardiovascular diseases (CVDs), such as acute coronary syndrome, acute aortic dissection, and pulmonary embolism. This scientific statement synthesizes multidisciplinary evidence from meteorology, environmental epidemiology, basic science, and clinical research to offer an updated evaluation of the impact of cold exposure on these acute chest pain-related life-threatening CVDs. The evidence consistently demonstrates that cold weather significantly increases the incidence of such events, often with delayed effects lasting several days to weeks. Vulnerable groups, including the elderly, individuals with chronic conditions, and those of lower socioeconomic status, are particularly at risk. Data also suggest that interventions, including central heating, integrated health warning systems, and appropriate personal protective measures, can effectively mitigate the associated risks. Based on this evidence, the statement provides expert consensus recommendations across clinical, policy, and behavioral domains. Strengthening prevention and response to cold-related cardiovascular risks is essential for building climate-resilient health systems and mitigating the health impacts of climate change.