J Cardiovasc Transl Res
· 2026 Feb · PMID 41649701
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Intraosseous access, the fastest access in emergencies, is exclusively used for delivering medications or fluids. The correlation between intraosseous and arterial pressures remains unclear. This study aimed to explore t...Intraosseous access, the fastest access in emergencies, is exclusively used for delivering medications or fluids. The correlation between intraosseous and arterial pressures remains unclear. This study aimed to explore this correlation at baseline and in various clinical scenarios (e.g., different heart rates, arrhythmias, asystolic arrest, and CPR). In 11 male Yorkshire pigs (73.4 ± 5.9 kg), femoral artery and tibial Intraosseous lines were placed under anesthesia. Pressures were recorded during hemodynamic interventions and cardiac arrest. Analyses included Pearson's r, Wilcoxon rank-sum test, and BVAR. Intraosseous pressure showed correlating pulsatility with arterial pressure, ranging from 9 to 71% of mean arterial pressure. Correlation was strong under normal conditions (r = 0.75-0.96, p < 0.001) and during CPR (r = 0.65-0.99, p < 0.001), weakened during asystole (r = 0.26 ± 0.46, p < 0.001), and was disrupted by epinephrine (r = 0.04, p < 0.001). Asystole was identifiable on intraosseous tracings. Intraosseous pressure effectively reflects circulatory activity and may aid in accurately identifying asystole with possible clinical implications for CPR.
J Cardiovasc Transl Res
· 2026 Feb · PMID 41644776
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Myocardial ischemia-reperfusion injury (MIRI) is an unresolved clinically fatal complication in the management of acute myocardial infarction (AMI). Growth arrest and DNA damage-inducible gene 45 Gamma (GADD45G) plays a...Myocardial ischemia-reperfusion injury (MIRI) is an unresolved clinically fatal complication in the management of acute myocardial infarction (AMI). Growth arrest and DNA damage-inducible gene 45 Gamma (GADD45G) plays a vital role in the regulation of MIRI. However, the underlying mechanisms remain unclear. GADD45G and SP1 expression were upregulated in hypoxia/reoxygenation (H/R)-treated H9C2 cells. H/R treatment repressed H9C2 cell viability, and induced apoptosis, oxidative stress, and inflammatory response. Moreover, GADD45G deficiency could relieve H/R-triggered H9C2 cell injury. In mechanism, SP1 was a transcription factor of GADD45G and activated the transcription of GADD45G via binding to its promoter region. Besides, SP1 knockdown alleviated MI/R-induced pathological damage in the myocardial tissue of rats by regulating GADD45G. In conclusion, SP1 could promote H/R-induced cardiomyocyte injury and MI/R-caused rat myocardial tissue pathological injury by increasing GADD45G, providing a promising therapeutic target for MIRI treatment.
Chen R, Ma Y, Chen S
… +4 more, Qin C, Li H, Sun N, Cao F
J Cardiovasc Transl Res
· 2026 Feb · PMID 41644764
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Exposure to cold environments is physiologically challenging, with extreme cold stress (ECS) impairing the function of the left ventricle (LV) of the heart. We aimed to determine the role and mechanism of action of the m...Exposure to cold environments is physiologically challenging, with extreme cold stress (ECS) impairing the function of the left ventricle (LV) of the heart. We aimed to determine the role and mechanism of action of the miR-499-5p/phosphofurin acidic cluster sorting protein 2 (PACS2)/transient receptor potential cation channel subfamily V member 1 (TRPV1) axis in ECS-induced cardiomyocyte injury and LV dysfunction. Mice were placed in a -20 °C chamber to simulate an extremely cold environment. MiR-499-5p overexpression in the mice decreased PACS2 levels, and mitochondrial function was inhibited in vivo following ECS. Inhibiting miR-499-5p enhanced PACS2 expression, thereby reversing the structural and functional LV deficits caused by ECS. Cardiac-specific Pacs2 knock-in restored the decreases in mitophagy and mitochondrial energy metabolism caused by ECS via enhancing endoplasmic reticulum-mitochondrial calcium flux through TRPV1, a nonselective calcium channel. The findings indicate targets for preventing cardiac disease during exposure to extremely cold environments.
Brooke N, Roberts KC, Heinz SAS
… +5 more, Metzler E, Peskoe S, Whitson HE, Ginsberg JP, Acker LC
J Cardiovasc Transl Res
· 2026 Feb · PMID 41644756
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Low preoperative heart rate variability (HRV) is associated with adverse cardiovascular outcomes and delirium after geriatric surgery, but in-person testing is burdensome and impractical. To evaluate wrist-based wearable...Low preoperative heart rate variability (HRV) is associated with adverse cardiovascular outcomes and delirium after geriatric surgery, but in-person testing is burdensome and impractical. To evaluate wrist-based wearables for remotely capturing preoperative outpatient and postoperative inpatient data for HRV analysis. RR-intervals were extracted, and data missingness was assessed for systematic differences. Delirium incidence was evaluated. Preoperatively, 76.9% of participants provided high-quality outpatient data, with no systematic demographic or clinical differences. Postoperatively, 80.2% had high-quality inpatient data; however, missing data were associated with older age, lower BMI, ICU admission, and longer surgeries and hospitalizations. Postoperative HRV did not significantly differ between participants with and without delirium. Outpatient HRV capture via wrist-based wearables is broadly feasible in older surgical patients, while postoperative inpatient data are disproportionately missing in higher-risk patients. These differences highlight both the translational potential and limitations of wearable HRV measurements for perioperative outcome prediction.
J Cardiovasc Transl Res
· 2026 Feb · PMID 41642559
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For decades, the pathogenesis of Acute Rheumatic Fever and Rheumatic Heart Disease has been primarily attributed to autoimmune activation in genetically predisposed children, triggered by molecular mimicry between Group...For decades, the pathogenesis of Acute Rheumatic Fever and Rheumatic Heart Disease has been primarily attributed to autoimmune activation in genetically predisposed children, triggered by molecular mimicry between Group A Streptococcus antigens and cardiac tissue components. Recent evidence reveals that immune priming generates complement-fixing and non-complement-fixing cross-reactive antibodies, initiating inflammatory cascades. Tissue-infiltrating neutrophils, T lymphocytes, macrophages, and neutrophil extracellular traps (NETs) critically contribute to rheumatic carditis immunopathology. These effectors damage endothelium, release acute-phase reactants, facilitate infiltration, exposing autoantigens, and promoting epitope spreading. All the three complement pathways emerge as key inflammatory amplifiers enhancing NET formation (NETosis) via PAD4-mediated histone citrullination, depositing on NET scaffolds, stabilizing them and perpetuating tissue injury. Dysregulated complement-NET interactions drive progression from acute inflammation to chronic valvular fibrosis. Circulating biomarkers such as cell-free DNA, MPO-DNA complexes, and complement fragments may indicate disease activity. Emerging therapeutic strategies include PAD4 inhibition, DNase-based NET clearance, and complement modulation.
Hu J, Alameddine D, Wang H
… +6 more, Mani A, Scharfe C, Jiang YH, Murray MF, Chaar CIO, DeWan AT
J Cardiovasc Transl Res
· 2026 Feb · PMID 41642540
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This study explored the association between 19 peripheral artery disease (PAD)-associated variants and PAD severity. We classified PAD cases into 4 groups with increasing levels of severity based on age of PAD diagnosis...This study explored the association between 19 peripheral artery disease (PAD)-associated variants and PAD severity. We classified PAD cases into 4 groups with increasing levels of severity based on age of PAD diagnosis and surgical status. Genetic association analysis for PAD severity and markers was conducted using REGENIE, and a 19-variant polygenic risk score (PRS) was developed to further evaluate the associations with severity subtypes. Two SNPs (rs4722172 and rs505922) showed stronger odds ratios (ORs) with more severe subtypes. The 19-variant PRS was significantly higher in surgical compared to non-surgical groups (OR = 1.14, 95% CI: 1.08, 1.20; p-value = 5.85 × 10) while no significant difference for non-premature and premature PAD (OR = 0.98, 95% CI: 0.9, 1.07, p-value = 0.64). This same pattern was observed in the subjects from Generations dataset. Our findings demonstrate that PAD-associated SNPs may also be associated with PAD severity as assessed by surgical intervention and age of onset (or diagnosis).
Ye J, Zong K, Liu Y
… +6 more, Wang W, Sheng Y, Liu J, An D, Xu B, Zong G
J Cardiovasc Transl Res
· 2026 Feb · PMID 41642484
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Ischemic mitral regurgitation (IMR) commonly complicates pPCI in STEMI patients. GDF11, a protective cardiovascular factor, may influence IMR progression and prognosis. Among 310 STEMI patients, 126 with recent normal ec...Ischemic mitral regurgitation (IMR) commonly complicates pPCI in STEMI patients. GDF11, a protective cardiovascular factor, may influence IMR progression and prognosis. Among 310 STEMI patients, 126 with recent normal echocardiography underwent pPCI with pre-procedural GDF11 testing. Cox regression, ROC analysis, and Spearman's correlation assessed GDF11's predictive value for IMR exacerbation and cardiac function. Lower GDF11 predicted IMR worsening (HR = 0.982, P = 0.004; AUC = 0.744, P < 0.001). High GDF11 patients had reduced IMR progression (P = 0.0013) and heart failure risk (P = 0.0003). GDF11 correlated with LVEF and left atrial changes (P < 0.05). Serum GDF11 independently predicts IMR exacerbation and post-pPCI heart failure, serving as a prognostic biomarker in STEMI.
J Cardiovasc Transl Res
· 2026 Feb · PMID 41642391
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Heart failure is the leading cause of hospitalization globally, burdening healthcare systems and the economy. Heart failure is a multifactorial cardiac syndrome, where the heart fails to maintain sufficient cardiac outpu...Heart failure is the leading cause of hospitalization globally, burdening healthcare systems and the economy. Heart failure is a multifactorial cardiac syndrome, where the heart fails to maintain sufficient cardiac output to support body function. As the population ages, heart failure rates will increase. Current treatments, such as medications and surgery, are not suitable for all patients, creating a need for alternative therapies. Gene therapy offers promising new approaches, with therapeutic angiogenesis, regenerative strategies, and calcium ion regulation as key targets. SERCA2a plays a critical role in calcium regulation, and clinical trials have focused on its potential as a therapeutic agent. VEGF-B, which specifically targets the myocardium, also regulates myocardial metabolism and SERCA2a activity. Although clinical trials have been conducted, results have not consistently replicated pre-clinical success. This review summarizes the current state of gene therapy for heart failure, including therapeutic agents, vectors, delivery methods, and preclinical models.
Natov PS, Reyelt L, Bhave S
… +9 more, Mahmoudi E, John KJ, Dellaripa BC, Stolyarov A, Qiao X, Curran J, Unudurthi S, Swain L, Kapur NK
J Cardiovasc Transl Res
· 2026 Feb · PMID 41642388
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Device-based therapies may augment decongestion in acute decompensated heart failure. We investigated the efficacy and safety of prolonged mechanical superior vena cava occlusion using the preCARDIA system in a swine mod...Device-based therapies may augment decongestion in acute decompensated heart failure. We investigated the efficacy and safety of prolonged mechanical superior vena cava occlusion using the preCARDIA system in a swine model of heart failure. Over 6 h of preCARDIA activation, right- and left-sided filling pressures were significantly reduced. Plasma levels of the brain injury marker ubiquitin C-terminal hydrolase L1 and intracerebral arterial pressure were not significantly changed. Post-mortem evaluation did not identify gross cerebral or histologic injury. Future studies are needed to compare continuous versus cyclic preCARDIA activation and to further confirm the neurologic safety of sustained superior vena cava occlusion.
Jin J, Shi Z, Gao Q
… +4 more, Yu J, Jin I, Liang J, Fan X
J Cardiovasc Transl Res
· 2026 Feb · PMID 41639534
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To develop a predictive model for optimal anastomosis sizing in TAPVC surgery, focusing on the role of pulmonary venous confluence (PVC) size. A patient-specific fluid-structure interaction (FSI) model simulated blood fl...To develop a predictive model for optimal anastomosis sizing in TAPVC surgery, focusing on the role of pulmonary venous confluence (PVC) size. A patient-specific fluid-structure interaction (FSI) model simulated blood flow through various anastomosis sizes. Key variables included body weight, anastomosis length, and PVC size. The model's predictions were validated against postoperative echocardiographic measurements from nine TAPVC cases. A strong positive correlation was found between flow velocity and the ratio of body weight to anastomosis length and PVC circumference. Including PVC size significantly improved predictive accuracy. No significant difference was observed between predicted and measured velocities. PVC size is a critical factor for planning TAPVC surgery. Incorporating it into computational models enhances the prediction of flow dynamics and supports personalized surgical decision-making.
J Cardiovasc Transl Res
· 2026 Feb · PMID 41639531
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Ischemic heart disease is a leading cause of global morbidity and mortality, yet early diagnosis and targeted therapies remain limited. Exosomes, small extracellular vesicles carrying nucleic acids, proteins, and lipids,...Ischemic heart disease is a leading cause of global morbidity and mortality, yet early diagnosis and targeted therapies remain limited. Exosomes, small extracellular vesicles carrying nucleic acids, proteins, and lipids, mediate intercellular communication and show promise for diagnostic and therapeutic use due to their stability, biocompatibility, and targeted delivery. Circulating exosomal profiles reflect myocardial pathology, enabling early detection, risk stratification, and monitoring. Exosomes from mesenchymal stem cells, immune cells, endothelial cells, and other stem cells exert cardioprotective effects. This review summarizes advances in exosome-based diagnostics and therapies and highlights their potential as biomarkers and innovative treatments.
Yao D, Meng P, Huang B
… +10 more, Wu R, Lin Z, Li K, Wu L, Xia P, Liu Q, Wu W, Wang S, Wang Q, Ye F
J Cardiovasc Transl Res
· 2026 Feb · PMID 41639521
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Acute coronary syndrome, driven by vulnerable plaque (VP) instability, is a major cause of cardiovascular mortality. Current diagnostic methods for VPs are limited by invasiveness or low specificity, highlighting the nee...Acute coronary syndrome, driven by vulnerable plaque (VP) instability, is a major cause of cardiovascular mortality. Current diagnostic methods for VPs are limited by invasiveness or low specificity, highlighting the need for non-invasive biomarkers. Using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from coronary artery disease (CAD) patients with VPs and controls, we identified circulating T cell-platelet aggregates (TPAs) significantly enriched in VP patients and linked to plaque instability via pro-inflammatory pathways. Through high dimensional weighted gene co-expression network analysis, we discovered TPAs' hub genes and demonstrated their role in plaque destabilization. Furthermore, employing machine learning, including Boruta, least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), we screened for five blood biomarkers that can serve as diagnostic indicators for VPs. Our study demonstrates that TPAs are critically involved in VPs formation. Furthermore, we identified EPHB6, STAT1, RPL23, IKZF3 and AHCY as potential circulating biomarkers for non-invasive detection of VPs.
Ascione G, Stella S, Addis A
… +5 more, Ajmone Marsan N, Van Hauwermeiren H, Granada JF, Gelpi G, Denti P
J Cardiovasc Transl Res
· 2026 Feb · PMID 41639520
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Tricuspid regurgitation (TR) is a highly morbid and often untreated valvular heart disease. New devices are under development to address this unmet need, necessitating valid models to test their efficacy. Aim of this stu...Tricuspid regurgitation (TR) is a highly morbid and often untreated valvular heart disease. New devices are under development to address this unmet need, necessitating valid models to test their efficacy. Aim of this study was to assess feasibility and reliability of pulmonary artery banding (PAB) as a pathological acute model of functional TR. Eight pigs underwent right thoracotomy, with an umbilical tape placed around the main pulmonary trunk, followed by controlled reduction of the pulmonary artery lumen via a tourniquet system. No animals died during the procedure. After PAB, right ventricular (RV) mean pressure, RV basal and mid-diameter and tricuspid septo-lateral diameter significantly increased (+ 97%, + 23%, + 32%, + 20%, p < 0.01 for all). Consequently, TR was at least moderate-to-severe in all the animals and these modifications remained stable for up to one hour. PAB therefore represents a reliable, one-step model of functional TR ideal to test the efficacy of new tricuspid devices.
Huai B, Yao D, Wang Y
… +5 more, Zang J, Huang Z, Yang H, Li W, Wang D
J Cardiovasc Transl Res
· 2026 Feb · PMID 41639503
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This study aims to integrate lesion-specific pericoronary adipose tissue (PCAT) radiomics analysis with existing clinical and imaging methods under the guidance of CT-derived fractional flow reserve (CT-FFR), to develop...This study aims to integrate lesion-specific pericoronary adipose tissue (PCAT) radiomics analysis with existing clinical and imaging methods under the guidance of CT-derived fractional flow reserve (CT-FFR), to develop and validate an interpretable machine learning (ML) prediction model for patients with type 2 diabetes complicated by coronary artery disease (CAD). The performance of ML algorithms across different predictive models was compared using the area under the receiver operating characteristic curve (AUC). In the validation cohort, the XGBoost algorithm within the combined model achieved an AUC value of 0.908, outperforming the best algorithm in the traditional model (AUC = 0.834) and radiomics model (AUC = 0.840). Meanwhile, the Shapley algorithm highlights the additional incremental value of radiomic features. Our model enhances the predictive ability and provides clinicians with a comprehensive tool, facilitating early intervention for high-risk individuals and proactive secondary prevention strategies, which may potentially improve clinical outcomes.
J Cardiovasc Transl Res
· 2026 Feb · PMID 41639493
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Three-dimensional (3D) printing has rapidly evolved as a transformative technology in cardiovascular medicine, offering capabilities for anatomical modelling, surgical planning, and the development of biocompatible impla...Three-dimensional (3D) printing has rapidly evolved as a transformative technology in cardiovascular medicine, offering capabilities for anatomical modelling, surgical planning, and the development of biocompatible implants. This review synthesizes evidence from peer-reviewed studies to provide a comprehensive overview of 3D printing technologies, materials, and their clinical applications in cardiovascular fields, including myocardial tissue engineering, valve replacement, and vascular modelling. Emphasis is placed on patient-specific modelling, integration of bio-printing technologies, and recent clinical demonstrations of improved surgical precision and reduced implant rejection. Drawing on 28 primary sources, this review identifies current benefits and challenges of 3D printing in cardiovascular care, highlights emerging trends, and proposes future directions for research and clinical translation.
Perico F, Romagnoni C, Pappalardo F
… +3 more, Gelpi G, Fiore GB, Vismara R
J Cardiovasc Transl Res
· 2026 Feb · PMID 41639362
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Coronary obstruction following transcatheter aortic valve-in-valve implantation (VIV-TAVI) carries a high mortality risk. This in-vitro study assessed coronary perfusion in a high-risk VIV-TAVI scenario. A patient deemed...Coronary obstruction following transcatheter aortic valve-in-valve implantation (VIV-TAVI) carries a high mortality risk. This in-vitro study assessed coronary perfusion in a high-risk VIV-TAVI scenario. A patient deemed at high-risk and treated with preventive Chimney stenting was selected as case study. A 3D-printed aortic root model was fabricated from pre-operative imaging and used to replicate the patient's VIV-TAVI setting. A CoreValve-Evolut-23 was implanted within a Trifecta-19 at five depths, with commissural alignment and 60° misalignment, to explore procedural variability and associated risk margins. The model was tested in a pulsatile mock loop with a coronary perfusion simulator. Flow and pressure were recorded pre- and post-VIV-TAVI under physiological conditions. Across all tested configurations, VIV-TAVI didn't significantly impair left or right coronary flows. The recommended depth optimized hemodynamic valve performance. Findings suggest refining coronary obstruction risk stratification in VIV-TAVI to improve decision-making regarding preventive interventions.
Dabravolski SA, Ekta MB, Utkina AS
… +3 more, Asoyan AZ, Maltseva ON, Orekhov AN
J Cardiovasc Transl Res
· 2026 Feb · PMID 41636984
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Testosterone (TES) has complex roles in cardiovascular disease, influencing not only atherosclerosis development in general, but also atherosclerosis-related processes associated with hypertension, cholesterol metabolism...Testosterone (TES) has complex roles in cardiovascular disease, influencing not only atherosclerosis development in general, but also atherosclerosis-related processes associated with hypertension, cholesterol metabolism, vascular calcification, and arterial stiffness. This review examines TES's effects, particularly its atheroprotective role in various mice and minipig model systems and cell cultures. TES modulates the renin-angiotensin system (RAS), contributing to hypertension and vascular dysfunction, but its deprivation can mitigate these effects. TES also impacts cholesterol metabolism by regulating liver X receptor (LXRα) pathways, promoting both cholesterol clearance and synthesis. Moreover, TES is involved in vascular calcification via androgen receptor (AR) signalling, a process that contributes to arterial stiffness, especially in females. The review highlights gaps in understanding TES's specific molecular mechanisms in cardiovascular disease, emphasising the need for further research to explore sex-specific responses and potential therapeutic interventions.
J Cardiovasc Transl Res
· 2026 Jan · PMID 41507690
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Chronic myocardial ischemia (CMI) is a key pathological condition in coronary artery disease (CAD), yet small animal models for CMI are limited. This study developed and characterized a CMI mouse model using ApoE-/- mice...Chronic myocardial ischemia (CMI) is a key pathological condition in coronary artery disease (CAD), yet small animal models for CMI are limited. This study developed and characterized a CMI mouse model using ApoE-/- mice fed a high-fat diet for 3 months. Cardiac function was assessed through electrocardiography (ECG), myocardial action potential, and perfusion echocardiography. The model group exhibited elevated cholesterol, aortic lipid plaques, and T-wave flattening, correlated with atherosclerosis severity. Impaired myocardial perfusion, reduced ATP content, and accelerated inner cardiomyocyte repolarization were also observed. PET/CT scans revealed filling defects, while myocardial contractile function showed reactive suppression under CMI conditions. This model replicates CMI's pathological features, providing a valuable tool for studying CAD progression and treatment.
J Cardiovasc Transl Res
· 2026 Jan · PMID 41483453
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Hyperoside (Hyp) exhibits notable protective effects by targeting oxidative stress, ferroptosis, and apoptosis. In vivo experiments used a murine model of DOX-induced cardiotoxicity with Hyp co-treatment. Hyp co-administ...Hyperoside (Hyp) exhibits notable protective effects by targeting oxidative stress, ferroptosis, and apoptosis. In vivo experiments used a murine model of DOX-induced cardiotoxicity with Hyp co-treatment. Hyp co-administration mitigated doxorubicin-induced cardiac impairment in mice, demonstrated by enhanced ejection fraction (EF) and fractional shortening (FS), diminished inflammatory cell infiltration and fibrotic changes, reduced circulating levels of cardiac biomarkers including cTnT, CK, CK-MB, LDH, and LDH-1. Hyp reduced oxidative stress (lower MDA, higher SOD and GSH-Px activity), inhibited ferroptosis (decreased intracellular Fe2 + , MDA, 4-HNE, PTGS2, and ASCL4; increased GSH and Ferritin), and suppressed apoptosis (fewer TUNEL-positive cells, balanced Bax/Bcl-2). Mechanistically, Hyp activated the Nrf2/GPX4 axis: it promoted Nrf2 nuclear translocation, upregulated GPX4 expression as shown by molecular docking. These effects were abrogated by ML385, confirming Nrf2 dependence. Hyp alleviates DOX-induced cardiotoxicity via Nrf2/GPX4 activation, suppressing oxidative stress, ferroptosis, with potential as a therapeutic agent.
Lv S, Yang L, Jiang J
… +9 more, Liu X, Huang W, Mao J, Zhang J, Chen T, Tang L, Leng X, Mao W, Du C
J Cardiovasc Transl Res
· 2026 Jan · PMID 41483452
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This study evaluated coronary computed tomography angiography (CCTA)-based computational fluid dynamics (CFD) for predicting plaque dynamics in coronary artery disease. We retrospectively analyzed 22 patients (34 lesions...This study evaluated coronary computed tomography angiography (CCTA)-based computational fluid dynamics (CFD) for predicting plaque dynamics in coronary artery disease. We retrospectively analyzed 22 patients (34 lesions) with paired CCTAs (mean interval 2 years). Lesions were categorized as progression (increase in diameter stenosis ≥ 5%), stable (change within - 5% to 5%), or regression (decrease in diameter stenosis ≥ 5%). Hemodynamic indices were normalized to adjacent non-diseased segments. Logistic regression identified predictors: normalized minimum wall shear stress (odds ratio (OR) = 0.38, p < 0.001) and maximum helicity (OR = 1.44, p = 0.016) predicted progression; average vorticity (OR = 0.13, p = 0.019) and gradient oscillatory number (OR = 0.10, p = 0.001) predicted regression. Receiver operating characteristic (ROC) analysis showed good discrimination (area under the curve (AUC) = 0.78 for progression, 0.83 for regression). These noninvasive imaging- and hemodynamic-derived markers, which were independently associated with lesion progression, may enhance coronary artery disease risk stratification by identifying high-risk plaques beyond stenosis severity, thereby informing individualized follow-up and treatment.