Routine carotid B-mode ultrasound is widely used for plaque assessment, but vulnerability evaluation remains subjective, and its prognostic value is uncertain. We developed and validated a cascaded multitask AI framework for plaque detection, characterization of five B-mode features, and vulnerability assessment. The multicenter cohort included 6618 participants at high cardiovascular risk and 38,090 images from four centers. Plaque presence and B-mode features were evaluated against expert B-mode consensus, whereas vulnerability was evaluated against multimodal expert consensus. Internal and external AUCs were 0.95 and 0.96 for plaque detection, 0.85–0.94 and 0.81–0.92 for feature characterization, and 0.90 and 0.88 for vulnerability classification. The model outperformed six independent B-mode readers and showed greater net benefit in decision-curve analysis. Prognostic validation included 2174 participants; 277 ischemic cerebrovascular events occurred over a median of 37 months. AI-defined high-risk status remained independently associated with events after adjustment for clinical risk factors (hazard ratio, 2.09; 95% confidence interval, 1.69–2.58), and adding the AI score improved the C-index from 0.769 to 0.795. These findings support standardized plaque vulnerability assessment and clinically meaningful cerebrovascular risk stratification from routine B-mode ultrasound.

BACKGROUND:Angiography-derived index of microcirculatory resistance (angio-IMR) is a reliable measure for assessing coronary microvascular function. However, the prognostic significance of changes in angio-IMR (Δangio-IMR) remains unclear. OBJECTIVES:The aim of this study was to assess the long-term prognostic utility of Δangio-IMR following percutaneous coronary intervention (PCI) in patients with intermediate coronary stenosis. METHODS:A total of 814 vessels with intermediate coronary stenosis that underwent PCI were enrolled from the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial. The primary endpoint was target vessel failure (TVF) during long-term follow-up, defined as a composite of cardiac death, target vessel-related myocardial reinfarction, and target vessel revascularization. RESULTS:The median Δangio-IMR was 2.02 (Q1-Q3: 0.50-5.00). Using the 75th percentile (Δangio-IMR >5) as the cutoff, 203 vessels were assigned to the high Δangio-IMR group. Vessels with high Δangio-IMR demonstrated a significantly elevated risk for TVF compared with those with low Δangio-IMR (15.62% vs 9.47%; HR: 1.82; 95% CI: 1.15-2.88; P = 0.011). High Δangio-IMR independently predicted TVF (HR: 1.72; 95% CI: 1.04-2.83; P = 0.034). There was a notable interaction effect between Δangio-IMR and post-PCI angio-IMR (P = 0.028). A stratified analysis by post-PCI angio-IMR revealed that vessels with high Δangio-IMR showed a markedly increased TVF risk compared with vessels with low Δangio-IMR in those with post-PCI angio-IMR >25 (26.2% vs 11.9%; HR: 5.18; 95% CI: 1.28-20.94; P = 0.021), whereas no such association was observed in those with post-PCI angio-IMR ≤25 (12.6% vs 9.3%; HR: 1.33; 95% CI: 0.77-2.29; P = 0.305). CONCLUSIONS:An elevated Δangio-IMR correlates with a heightened risk of TVF in vessels with intermediate coronary stenosis underwent PCI. ΔAngio-IMR could be used as a valuable risk stratification indicator, particularly in patients with high post-PCI angio-IMR.

Deubiquitinating enzymes (DUBs) are critically involved in diabetic cardiomyopathy (DCM), yet the function of OTU domain-containing protein 7B (OTUD7b), a recently identified DUB, in DCM remains unknown. Here, we identified that OTUD7b expression was significantly elevated in cardiomyocytes from both type 1 and type 2 diabetic mouse hearts. Cardiomyocyte-specific deletion of OTUD7b ameliorated cardiac dysfunction, hypertrophy, and fibrosis in diabetic mice, without affecting systemic hyperglycemia. Mechanistically, combining ubiquitinome and interactome analyses, we identified transforming growth factor β-activated kinase 1 (TAK1) as a direct substrate of OTUD7b in cardiomyocytes. Under diabetic conditions, OTUD7b binds to TAK1 via its zinc finger domain and catalyzes K48-linked deubiquitination at the K346 of TAK1, thereby enhancing TAK1 protein stability. This OTUD7b-mediated stabilization increased the levels of both TAK1 and p-TAK1, which led to hyperactivation of the TAK1-MAPK (JNK/p38) axis, subsequently promoting extrinsic apoptosis and inflammatory responses in cardiomyocytes. Crucially, cardiomyocyte-specific reconstitution of a deubiquitination-resistant TAK1-K346R mutant in diabetic mice completely abolished the cardioprotective effects of OTUD7b deficiency, confirming that OTUD7b drives DCM primarily through deubiquitinating TAK1 at K346. Taken together, our study unveils a novel OTUD7b-TAK1 axis in cardiomyocytes driving diabetic heart injury and positions OTUD7b as a promising therapeutic target for DCM.

Ischemic skin flaps are highly susceptible to distal necrosis because of insufficient perfusion, oxidative stress, and dysregulated cell death. Here, we investigated the role of Hippo/YAP signaling in ischemic flap survival and identified its upstream regulatory mechanism. Hippo pathway inactivation, characterized by reduced MST1/2 and LATS1/2 phosphorylation and enhanced YAP nuclear localization, was preferentially associated with viable flap regions. Mechanistically, ischemia-induced HIF-1α upregulated miR-210-3p, which suppressed ephrin-A3 (EFNA3), weakened the EFNA3–YAP interaction, and promoted YAP nuclear translocation. Re-expression of EFNA3 partially reversed miR-210-3p-induced YAP activation and cytoprotection, confirming its functional involvement. Mechanistically, ischemia-induced HIF-1α increased miR-210-3p expression, which suppressed EFNA3 and facilitated YAP nuclear localization. EFNA3 re-expression partially reversed miR-210-3p-induced YAP activation, supporting its functional involvement. MiR-210-3p treatment was further associated with reduced oxidative injury, lipid peroxidation, mitochondrial dysfunction, and ferroptosis-related molecular alterations, together with improved perfusion and flap survival. In vivo, miR-210-3p improved local perfusion and flap survival. We further developed a virus-inspired biomimetic nanoparticle for miR-210-3p delivery, which achieved protective effects comparable to AAV-mediated delivery in vitro and in vivo. These findings identify the miR-210-3p–EFNA3–YAP axis as an important regulator of ischemic tissue adaptation and provide a non-viral miRNA delivery strategy for ischemic flap repair.

BACKGROUND:The association between coronary microcirculation and clinical outcomes in patients with intermediate stenosis remains unclear. OBJECTIVES:The aim of this study was to assess the prognostic significance of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with intermediate coronary stenosis. METHODS:This post hoc analysis included 1,658 patients from the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial, with angio-IMR measured in each vessel exhibiting intermediate stenosis. The primary endpoint was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction, or revascularization over a 2-year period. RESULTS:The median follow-up period was 24.8 months (Q1-Q3: 24.4-26.4 months). Over the 2-year follow-up period, patients with angio-IMR >25 exhibited a significantly higher POCO rate in both the percutaneous coronary intervention (PCI) group (35.06% [27 of 77] vs 7.2% [51 of 708]; P < 0.001) and the non-PCI group (17.95% [21 of 117] vs 4.23% [32 of 756]; P < 0.001). After adjusting for potentially related risk factors, angio-IMR >25 remained an independent predictor of the POCO in the PCI group (HR: 6.235; 95% CI: 3.811-10.203; P < 0.001) and the non-PCI group (HR: 5.282; 95% CI: 2.948-9.462; P < 0.001). The addition of angio-IMR demonstrated incremental prognostic value in both an angiographic risk factor model (C-index 0.710 [95% CI: 0.663-0.756] vs 0.615 [95% CI: 0.563-0.664] [P < 0.001]; net reclassification index 0.268 [95% CI: 0.191-0.362; P < 0.001]; integrated discrimination improvement 0.055 [95% CI: 0.030-0.108; P < 0.001]) and a clinical risk factor model (C-index 0.705 [95% CI: 0.658-0.751] vs 0.594 [95% CI: 0.544-0.644] [P < 0.001]; net reclassification index 0.268 [95% CI: 0.171-0.350; P < 0.001]; integrated discrimination improvement 0.057 [95% CI: 0.027-0.102; P < 0.001]). CONCLUSIONS:In individuals with intermediate coronary stenosis, elevated angio-IMR is linked to an adverse prognosis. Using angio-IMR significantly enhanced the capability to reclassify patients and accurately estimate the risk for the POCO.

The protective function of the tetrandrine (TET)-mediated transient receptor potential vanilloid 2 (TRPV2) channel in myocardial ischemia/reperfusion injury (MI/RI) has been established in numerous investigations. The objective of the current study was to explain how TRPV2 further modulates downstream factors to influence the progression of MI/RI. To this end, an MI/RI model in rats and a hypoxia–reoxygenation (H/R) cell model in H9c2 cells were constructed. Based on western blotting analyses, the effects of TRPV2 on the levels of apoptosis-related proteins as well as calcineurin and nuclear factor of activated T cells (NFAT) were ascertained. Evans blue/triphenyltetrazolium chloride (TTC) double staining and H E staining were, respectively, used to examine the pathological changes and infarction size of myocardial tissues in rats. Cardiomyocyte apoptosis was assessed with TUNEL assays and flow cytometry. Ca2+ concentration and reactive oxygen species (ROS) production were determined using a calcium assay kit and dichlorodihydrofluorescein diacetate (DCFH-DA) staining, respectively. Downregulated TRPV2 showed a significant ameliorative effect on cardiomyocyte histopathology and infarction area. Cardiomyocyte apoptosis, Ca2+ concentration, and ROS amounts were also inhibited when TRPV2 was silenced. Furthermore, results indicated that TET could significantly decrease TRPV2, while knocking down TRPV2 markedly suppressed the expression of calcineurin and NFAT. These findings shed light on the possible mechanisms behind the TET-mediated TRPV2 channel in MI/RI, indicating that TET has protective functions through downregulation of TRPV2 expression and suppression of the Ca2+/calcineurin/NFAT pathway.

BACKGROUND AND OBJECTIVES:The Fractional Flow Reserve and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. METHODS:A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography). The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. RESULTS:From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. CONCLUSIONS:Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02673424.

BACKGROUND:A recent randomised trial demonstrated fractional flow reserve (FFR) guidance for percutaneous coronary intervention (PCI) was non-inferior to intravascular ultrasound (IVUS) guidance regarding clinical outcomes, with a lower frequency of PCI. AIMS:We sought to evaluate the prognosis of FFR versus IVUS guidance for PCI of intermediate coronary artery stenosis and low lesion complexity in diabetic and non-diabetic patients. METHODS:This study is a prespecified post hoc analysis from the FLAVOUR trial. The primary outcome was major adverse cardiac events (MACE) at 24 months, defined as a composite of death, myocardial infarction or any revascularisation. The secondary outcomes were target vessel failure (TVF) and each component of MACE and TVF at 24 months. RESULTS:Among 1,682 randomly assigned patients, 554 (32.9%) had diabetes, and the mean SYNTAX score was 8.64±6.03 at baseline. The FFR group had a lower PCI rate than the IVUS group in both diabetic (48.2% vs 69.1%; p<0.001) and non-diabetic (42.6% vs 63.3%; p<0.001) patients. At 24 months, there was no difference in the cumulative incidence of MACE between the FFR and the IVUS groups in either diabetic (9.3% vs 8.3%; p=0.90) or non-diabetic (7.5% vs 8.6%; p=0.50) patients. The cumulative incidence of TVF was also comparable between the FFR and the IVUS groups regardless of diabetic status. CONCLUSIONS:In patients with intermediate coronary stenosis and low lesion complexity, regardless of diabetic status, FFR guidance had no significant differences in MACE or TVF with a lower frequency of PCI compared with IVUS guidance.

Background:Scoring balloon angioplasty catheters are designed to induce high focal stress at low inflation pressure for better lesion modification. We aimed to assess the effectiveness and safety of a newly developed Wedge NC scoring balloon catheter compared to the ScoreFlex coronary dilatation catheter for treating coronary artery lesions. Methods:The Wedge NC trial was a prospective, multicenter, open-label, randomized controlled non-inferiority trial conducted during August 2021 and February 2022. There were 198 patients with indication for percutaneous coronary intervention (PCI) enrolled at nine centers in China. Patients undergoing angioplasty were randomly assigned to treatment with the Wedge NC scoring balloon or the ScoreFlex scoring balloon. The primary endpoint was procedure success, defined as the residual stenosis of the target lesion ≤30% immediately after PCI procedure, without complications (limited to death, Q-wave or non-Q-wave myocardial infarction, or emergent coronary artery bypass grafting during postoperative hospitalization). The secondary endpoints included rate of clinical success, device procedural success, balloon slippage, and angiographic traits measured by quantitative coronary analysis. Results:Baseline parameters showed no differences between the two groups. Procedure success was achieved in 98 of 99 patients in both groups. The mean difference between the Wedge group and the ScoreFlex group was 0 (95% confidence interval: -2.79% to 2.79%, 1-sided P<0.001 with both Wald method and minimum risk weights method). Noninferiority at a predefined margin of 7% was established. Immediately after the balloon inflation, minimal lumen diameter in the Wedge group was significantly larger than that of the ScoreFlex group (1.71±0.39 vs. 1.56±0.36 mm, P=0.02), resulting in a lower percent diameter stenosis and a higher acute lumen gain (36.04±11.43 vs. 41.14±10.63, P=0.004; 0.82±0.39 vs. 0.69±0.37 mm, P=0.02, respectively). There was comparable and low rate of procedural complications for both treatment groups. Conclusions:In patients undergoing PCI, the Wedge NC scoring balloon dilatation catheter was noninferior to the ScoreFlex coronary dilatation catheter regarding procedure success and had comparably low procedural complication rate. (Sponsored by BrosMed Medical.). Trial Registration:The trial was registered at clinicaltrials.gov with the identifier NCT06214247.

Background The optimal treatment strategy for patients with intermediate coronary stenosis remains uncertain. Objectives The aim of this study was to investigate the long-term outcomes of a randomized, open-label, multinational trial comparing fractional flow reserve (FFR)-guided vs intravascular ultrasound (IVUS)-guided treatment strategies. Methods Patients aged >= 19 years with de novo intermediate coronary stenosis (40%-70%) and target vessel diameters >= 2.5 mm were randomized 1:1 to FFR- or IVUS-guided treatment across 18 sites in Korea and China. The primary endpoint was a composite of all-cause death, myocardial infarction, and any revascularization occurring after the index procedure. Secondary endpoints included individual components of the primary outcome and per vessel outcomes according to treatment type. Extended follow-up continued through September 2024. Results Between July 2016 and August 2019, 1,682 patients were assigned to the FFR-guided (n = 838) and IVUS-guided (n = 844) groups. Over a median follow-up period of 6.3 years (Q1-Q3: 5.6-6.9 years), the primary outcome occurred in 339 patients (22.0%), with no statistically significant difference between groups (179 [23.1%] for FFR vs 160 [20.9%] for IVUS; HR: 1.15; 95% CI: 0.93-1.42; P = 0.208). The revascularization rate after the index procedure was higher in the FFR group (113 [14.9%] vs 87 [11.8%]; HR: 1.32; 95% CI: 1.00-1.75; P = 0.049), particularly for target vessel revascularization (72 [9.6%] vs 44 [6.2%]; HR: 1.67; 95% CI: 1.15-2.43; P = 0.007). Landmark analysis at 2 years and per vessel analyses indicated that the higher revascularization rate after the index procedure was driven primarily by late (2-7 years) revascularizations in vessels in which percutaneous coronary intervention (PCI) was initially deferred. Nevertheless, the overall rate of target vessel PCI, including procedures at index and during follow-up, was significantly lower in the FFR group (38.8% vs 60.5%; P < 0.001), with no statistically significant differences in the annual cumulative incidence of death or myocardial infarction between groups. Conclusions FFR-guided and IVUS-guided treatment strategies resulted in comparable long-term outcomes, with no significant difference in patient-oriented composite outcomes. Although FFR-guided treatment was associated with a higher incidence of late target vessel revascularization, the overall target vessel PCI rate, accounting for both the index procedure and revascularization during follow-up, remained significantly lower in the FFR-guided treatment group, with comparable rates of hard outcomes between the 2 groups. (c) 2025 by the American College of Cardiology Foundation.

The differences among immune subtypes in coronary artery disease (CAD), their interrelationships, and the associated immune biomarkers remain incompletely understood. The samples were collected from the GSE20686 and GSE42148 datasets for analysis. Principal component analysis (PCA) and Gene Set Variation Analysis (GSVA) were performed on the subtypes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine functional and pathways in CAD. Machine learning models were constructed for CAD prediction. Model validation was performed using GSE56885 and GSE71226 datasets. The expression and function of the identified genes were evaluated using immunohistochemistry, CCK-8 assays, wound healing assays, and Transwell invasion assays. Multiple immune cells showed correlations with CAD samples. Two immune cell subtypes were identified, with significant differences in programmed cell death-ligand (PD-L1) expression, immune scores, and stromal scores between subtypes (P < 0.05). Three CAD hub genes were identified by WGCNA. GO analysis revealed enrichment in Biological Process (BP) and Molecular Function (MF). Among the several machine learning models, the RF model was selected based on combining parameters. The model mainly included two CAD immune marker genes, AKT1 and PTK2B. Differential expression of AKT1 and PTK2B was observed in cardiac myocytes. Inhibition of PTK2B suppressed cell proliferation and invasion, and induced apoptosis in HUVEC cells. Immunophenotyping revealed an association between CAD and PD-L1. AKT1 and PTK2B were identified as key disease signature genes, which may hold clinical significance for the diagnosis, prognostic assessment and treatment of CAD.

BACKGROUND Recent randomized clinical trials have demonstrated the benefits of intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) over angiography-guided PCI. However, the role of angiography-based physiological assessment during IVI-guided PCI remains unclear. OBJECTIVES This study aimed to explore the discrepancies and significance of angiography-based physiological assessments in IVI-guided PCI. METHODS In the international multicenter randomized FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients With Intermediate Stenosis) trial, angiography-based physiological assessment was retrospectively performed using the Murray law-based quantitative flow ratio (mu QFR). In this post hoc analysis, patients were categorized based on intravascular ultrasound (IVUS)-guided treatment decisions (PCI or deferral) and mu QFR as follows: negative mu QFR with deferral of PCI (DEFER), negative mu QFR with PCI (PERFORM), and positive mu QFR with PCI (REFERENCE). The primary outcome was major adverse cardiovascular events, defined as a composite of death, myocardial infarction, and target vessel revascularization at the 24-month follow-up. RESULTS Of the 784 patients, 34.4% (270/784), 29.3% (230/784), and 31.5% (247/784) were categorized into the DEFER, PERFORM, and REFERENCE groups, respectively. Physiological assessment led to substantial reclassification, encompassing 48.2% (230/477) of patients who underwent IVUS-guided PCI. The REFERENCE group showed a higher risk for major adverse cardiovascular events at 2 years compared with the PERFORM group (adjusted HR: 2.46; 95% CI: 1.13-5.35; P = 0.023). However, the primary outcomes in the DEFER and PERFORM groups were similar (adjusted HR: 0.88; 95% CI: 0.37-2.11; P = 0.779). The quality of life at 2 years was comparable among the 3 groups (P = 0.198). CONCLUSIONS Angiography-based physiological assessments can offer additional prognostic insights for patients undergoing IVI-guided PCI. IVUS-guided PCI may not be advantageous in patients with functionally insignificant lesions. (JACC Cardiovasc Interv. 2025;18:145-153) (c) 2025 by the American College of Cardiology Foundation.

Background Coronary physiology measured by fractional flow reserve (FFR) is superior to angiography for assessing the efficacy of percutaneous coronary intervention (PCI). Yet, the clinical adoption of post-PCI FFR is limited. Murray law-based quantitative flow ratio (μQFR) may represent a promising alternative, as it can quickly compute FFR from a single angiographic view. Objectives The authors aimed to investigate the potential role of post-PCI μQFR in predicting clinical outcomes. Methods This was a post hoc blinded analysis of the FLAVOUR trial. Patients with angiographically intermediate lesions randomized 1:1 to receive FFR or intravascular ultrasound-guided PCI were included. Post-PCI μQFR was assessed in successfully stented vessels, blinded to clinical outcomes. Suboptimal physiological outcome post-PCI was defined a priori as post-PCI μQFR <0.90. The primary endpoint was 2-year target vessel failure, including cardiac death, target vessel myocardial infarction, and target vessel revascularization. Secondary endpoints included the diagnostic concordance of pre-PCI μQFR with FFR in the FFR-guidance arm. Results Post-PCI μQFR was successfully analyzed in 806 vessels from 777 participants (feasibility 97.0% [806 of 831]). Suboptimal physiological outcome post-PCI was identified in 24.7% (199 of 806) of vessels and post-PCI μQFR <0.90 was associated with higher risk of 2-year target vessel failure (6.1% [12 of 199] vs 2.7% [16 of 607]; HR: 2.45 [95% CI: 1.14-5.26]; P = 0.022). Pre-PCI μQFR was obtained in 877 of 919 vessels (feasibility 95.4%), showing 90% accuracy, 82% sensitivity, and 94% specificity for identifying physiologically significant stenosis defined by pre-PCI FFR ≤0.80. Conclusions In patients with intermediate lesions who underwent PCI with contemporary imaging or physiology guidance, lower post-PCI μQFR values predict subsequent adverse events. (Fractional FLow Reserve And IVUS for Clinical OUtcomes in Patients With InteRmediate Stenosis [FLAVOUR]; NCT02673424)

Atrial fibrillation (AF) is a significant precursor to cerebral embolism. Our study sought to unearth new diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE) by meticulously examining multiple GEO datasets and meta-analysis. The gene expression omnibus (GEO) database provided RNA sequencing data associated with AF and stroke. We began by pinpointing genes with varied expressions in AF-CE patient blood samples. A meta-analysis was subsequently undertaken using several RNA sequencing datasets to verify these genes. LASSO regression discerned key genes for AF-CE, with their diagnostic prowess verified through ROC curve examination. Active signaling pathways within stroke patients were discerned via GO and KEGG enrichment, with PPI interactions detailing gene interplay. Differential gene analysis revealed an upregulation of sixteen genes and a downregulation of four in stroke patient blood samples. Eight genes showcased varied expression in the meta-analysis. LASSO regression zeroed in on five of these, culminating in HIST1H2BH’s identification as a characteristic gene. HIST1H2BH’s prowess in predicting AF-CE was confirmed through ROC. Integrin signaling, platelet activation, ECM interactions, and the PI3K-Akt pathway were found active in stroke victims. HIST1H2BH’s interaction with the notably upregulated ITGA2B was spotlighted by PPI. Additionally, HIST1H2BH exhibited links with NK cells and eosinophils. HIST1H2BH emerges as an insightful diagnostic beacon for AF-CE. Its presence, post AF, potentially modulates pathways, accentuating platelet activation and consequent thrombus generation, leading to cerebral embolism.

Importance: Treatment strategies for intermediate coronary lesions guided by fractional flow reserve (FFR) and intravascular ultrasonography (IVUS) have shown comparable outcomes. Identifying low-risk deferred vessels to ensure the safe deferral of percutaneous coronary intervention (PCI) and high-risk revascularized vessels that necessitate thorough follow-up can help determine optimal treatment strategies.Objectives: To investigate outcomes according to treatment types and FFR and IVUS parameters after FFR- or IVUS-guided treatment.Design, setting, and participants: This cohort study included patients with intermediate coronary stenosis from the Fractional Flow Reserve and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients With Intermediate Stenosis (FLAVOUR) trial, an investigator-initiated, prospective, open-label, multicenter randomized clinical trial that assigned patients into an IVUS-guided strategy (which recommended PCI for minimum lumen area [MLA] <= 3 mm2 or 3 mm2 to 4 mm2 with plaque burden [PB] >= 70%) or an FFR-guided strategy (which recommended PCI for FFR <= 0.80). Data were analyzed from November to December 2022.Exposures: FFR or IVUS parameters within the deferred and revascularized vessels.Main outcomes and measures: The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, and revascularization at 2 years.Results: A total of 1619 patients (mean [SD] age, 65.1 [9.6] years; 1137 [70.2%] male) with 1753 vessels were included in analysis. In 950 vessels for which revascularization was deferred, incidence of TVF was comparable between IVUS and FFR groups (3.8% vs 4.1%; P = .72). Vessels with FFR greater than 0.92 in the FFR group and MLA greater than 4.5 mm2 or PB of 58% or less in the IVUS group were identified as low-risk deferred vessels, with a decreased risk of TVF (hazard ratio [HR], 0.25 [95% CI, 0.09-0.71]; P = .009). In 803 revascularized vessels, the incidence of TVF was comparable between IVUS and FFR groups (3.6% vs 3.7%; P = .95), which was similar in the revascularized vessels undergoing PCI optimization (4.2% vs 2.5%; P = .31). Vessels with post-PCI FFR of 0.80 or less in the FFR group or minimum stent area of 6.0 mm2 or less or with PB at stent edge greater than 58% in the IVUS group had an increased risk for TVF (HR, 7.20 [95% CI, 3.20-16.21]; P < .001).Conclusions and relevance: In this cohort study of patients with intermediate coronary stenosis, FFR- and IVUS-guided strategies showed comparable outcomes in both deferred and revascularized vessels. Binary FFR and IVUS parameters could further define low-risk deferred vessels and high-risk revascularized vessels.