CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma.

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.

Relationship between TyG index and the degree of coronary artery lesions in patients with H-type hypertension.

BACKGROUND: The TyG index, a prominent metric for assessing insulin resistance, has gained traction as a prognostic tool for cardiovascular disease. Nevertheless, the understanding of the prognostic significance of the extent of coronary artery stenosis in individuals afflicted with H-type hypertension remains limited. METHODS: A retrospective study was conducted at Wuhan Third Hospital, including a cohort of 320 inpatients who were diagnosed with hypertension in combination with coronary artery disease. The study period spanned from January 1, 2021, to February 1, 2023. The study cohort was stratified based on the severity of stenosis into three distinct groups: low stenosis, medium stenosis, and high stenosis, as determined by the Gensini score derived from coronary angiography findings. The present study aimed to investigate the association between the severity of coronary stenosis and the number of lesion branches, utilizing the TyG index as a testing indicator. The predictive ability of TyG for coronary lesion severity was assessed using logistic regression analysis. RESULTS: The results of our study indicate a positive correlation between elevated levels of TyG and an increased susceptibility to severe stenosis in individuals diagnosed with H-type hypertension. Upon careful consideration of potential confounding variables, it has been observed that the TyG index exhibits a robust association with the likelihood of severe stenosis in individuals with H-type hypertension (odds ratio [OR] = 4000, 95% confidence interval CI 2.411-6.635, p = 0.0001), as well as the prevalence of multivessel disease (OR = 1.862, 95% CI 1.036-3.348, p < 0.0001). The TyG index demonstrated superior predictive ability for severe coronary stenosis in patients with H-type hypertension compared to those without H-type hypertension (area under the curve [AUC] = 0.888, 95% confidence interval CI 0.838-0.939, p < 0.0001, versus AUC = 0.615, 95% CI 0.494-0.737, p < 0.05). CONCLUSION: The TyG index is an independent risk factor for the degree of coronary stenosis and a better predictor in patients with H-type hypertension combined with coronary artery disease.

Relationship between microvascular status and diagnostic performance of stress dynamic CT perfusion imaging.

OBJECTIVES: This study aimed to investigate the relationship between microvascular status in the non-ischemic myocardium and the diagnostic performance of stress dynamic CT perfusion imaging (CTP) in detecting hemodynamically significant stenosis. MATERIALS AND METHODS: This study included 157 patients who underwent coronary computed tomography angiography (CTA), CTP, and invasive coronary angiography (ICA), including fractional flow reserve (FFR). Hemodynamically significant stenosis was defined by FFR and ICA. A relative myocardial blood flow (MBF) for each myocardial segment was normalized to the highest MBF (remote MBF) among 16 segments. RESULTS: The receiver operating characteristic curve analysis for detecting hemodynamically significant stenosis at the vessel level indicated that patients with lower, intermediate, and higher remote MBF had areas under the curve (AUC) of 0.66, 0.70, and 0.80, respectively, for absolute MBF and AUCs of 0.63, 0.70, and 0.83, respectively, for relative MBF. The optimal cut-off values for absolute MBF were proportional to the levels of remote MBFs, while the ones for relative MBF were more consistent across lower to higher remote MBFs. For the patients with high remote MBF, the relative MBF demonstrated a sensitivity of 69%, specificity of 88%, and accuracy of 85% in detecting hemodynamically significant stenosis. CONCLUSION: The microvascular status in the non-ischemic myocardium influenced the diagnostic performance of dynamic CTP and threshold values of absolute MBFs, suggesting the potential preference for relative MBF over absolute MBF in clinical settings. Dynamic CTP's quantification of MBF offers the benefit of indicating reliability in ischemia detection relative to microvascular status. KEY POINTS: Question The relationship between microvascular status and diagnostic performance of dynamic CTP imaging has not been fully investigated. Findings The diagnostic performance of dynamic CTP and threshold values of absolute MBF were impacted by microvascular status. Clinical relevance The differences in diagnostic accuracy of dynamic CTP related to varying remote MBF values necessitate a personalized evaluation of myocardial perfusion in dynamic CTP images.

Myocardial ischemia caused by the synergistic effect of myocardial bridge and moderate stenosis: case report.

BACKGROUND: Clinical events such as angina pectoris, acute coronary syndrome, and sudden death caused by myocardial bridge (MB) have attracted increasing attention. It is still a challenge to diagnose whether MB can cause the symptoms of patients with MB. For most MB patients, medication remains the primary treatment. CASE PRESENTATION: This article reports a case of chest pain in a patient with MB in the middle segment of the left anterior descending artery (LADm) with moderate stenosis in the proximal segment (LADp). Through functional assessment, we found that neither MB nor fixed stenosis had sufficient effect on coronary blood flow to cause myocardial ischemia, but their synergistic effect resulted in myocardial ischemia. Finally, a stent was implanted in LADp and good clinical results were achieved. CONCLUSIONS: For symptomatic patients with MB combined with fixed stenosis, functional evaluation may be necessary, which has significant guiding significance for treatment strategy selection. For asymptomatic patients, early detection of myocardial ischemia may also improve the prognosis of patients.

Triglyceride glucose index and triglyceride HDL ratio as predictors of coronary artery stenosis in diabetic and non-diabetic patients.

BACKGROUND AND AIM: The current study investigated the association between triglyceride-glucose index (TyG) and triglyceride/HDL-C indices and coronary atherosclerosis extent in diabetic and non-diabetic patients. METHODS AND RESULTS: In this case-control study, 1538 individuals were classified into two groups: diabetic and non-diabetic subjects. Each group was further grouped as follows: (1) angiography+ (2) angiography-and (3) subjects without a history of cardiovascular diseases. The TyG and TG/HDL-C indices were compared between the subgroups of the diabetic (n = 407) and non-diabetic (n = 1131) groups. In both diabetic and non-diabetic patients, there was no significant association in TG/HDL-C; and diabetic subjects, angiography+ and angiography-groups had significantly higher TyG (p < 0.05). A high TyG index was associated with a higher risk of angiography+ (OR: 1.883 (1.410-2.514)). CONCLUSIONS: The TyG index, but not the TG/HDL-C, was an independent marker for predicting the severity of coronary stenosis in non-diabetic patients.

Association of the PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study.

BACKGROUND: Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. METHODS: This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. RESULTS: 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. CONCLUSION: Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

Serum Exosomal MicroRNA-186-5p Positively Correlates with Lipid Indexes, Coronary Stenosis Degree, and Major Adverse Cardiovascular Events in Coronary Heart Disease.

Our previous study finds that exosomal microRNA (miR)-186-5p promotes viability and invasion of vascular smooth muscle cells to accelerate atherosclerosis via inactivating phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin pathway. Subsequently, this study aimed to identify the linkage of serum exosomal miR-186-5p with clinical features and major adverse cardiovascular events (MACE) in coronary heart disease (CHD) patients. Serum exosomal miR-186-5p was quantified in 175 CHD patients and 50 healthy controls (HCs) via reverse transcription quantitative polymerase chain reaction. Our study revealed that serum exosomal miR-186-5p was enhanced in CHD patients vs. HCs (P < 0.001). In CHD patients, serum exosomal miR-186-5p was positively correlated with total cholesterol (P = 0.002) and low-density lipoprotein cholesterol (P = 0.003). Elevated serum exosomal miR-186-5p was linked with increased Gensini score (P = 0.028) and stenosis degree categorized by the Gensini score (P = 0.018). Regarding MACE, the 1-year and 2-year accumulating MACE rate was 6.6% and 15.6%, respectively. Serum exosomal miR-186-5p was elevated in CHD patients with MACE vs. those without (P = 0.042). By Kaplan-Meier curves and log-rank analyses, serum exosomal miR-186-5p > 1.000 (P = 0.404) and > 1.610 (P = 0.328) was not related to accumulating MACE. While serum exosomal miR-186-5p > 3.390 exhibited a correlative trend with increased accumulating MACE, but not achieving statistical significance (P = 0.071). The 1-year and 2-year accumulating MACE rate of patients with serum exosomal miR-186-5p > 3.390 was 11.5% and 21.5%, respectively; while the rate was 3.3% and 11.5% in patients with serum exosomal miR-186-5p ≤ 3.390, accordingly. Conclusively, serum exosomal miR-186-5p positively associates with lipid level, coronary stenosis degree, and the risk of MACE in CHD patients.

Critical left main coronary artery stenosis presenting as cardiac arrest in coarctation of the aorta patient.

Congenital coronary artery stenosis coexisting with aortic coarctation in nonsyndromic patients has not previously been reported. This report describes a nonsyndromic aortic coarctation patient who experienced intraoperative cardiac arrest due to a previously undiagnosed critical left main coronary artery stenosis. The patient was successfully resuscitated, underwent patch coronary ostioplasty, and was discharged home. He remains well for four months following repair.

Artificial intelligence-supervised vectorcardiography for the diagnosis of a young adult with abnormal origin of the right coronary artery from aorta.

Coronary anomalies occur in 0.2% to 1.2% of the population, with the anomalous aortic origin of the coronary arteries accounting for one third of these cases. Clinical presentations can vary from asymptomatic to experiencing cardiac symptoms and sudden death, making diagnosis challenging. In this report, we present a novel artificial intelligence-supervised vectorcardiographic analysis and the subsequent successful surgical treatment of a young patient.

Coronary Computed Tomography Angiography-Derived Modified Duke Index Is Associated with Peri-Coronary Fat Attenuation Index and Predicts Severity of Coronary Inflammation.

Background and Objectives: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary stenosis. However, it does not take into consideration the presence or severity of peri-coronary inflammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors, and peri-coronary inflammation in the coronary arteries of patients with coronary artery disease. Materials and Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1-patients with low index, ≤3 (n = 107), and group 2-patients with high index, >3 (n = 65). Demographic, clinical, and CCTA data were collected for all patients, and FAI analysis of coronary inflammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia, or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score, 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, 13.26 ± 10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84% ± 25.86% vs. 16.87% ± 15.80%; p < 0.0001). ROC analysis identified a cut-off value of 12.1% of the CaRi-Heart® risk score for predicting a high severity of coronary lesions, with an AUC of 0.69. Conclusions: The CT-derived modified Duke index correlates well with local perilesional inflammation as assessed using the FAI score at different levels of the coronary circulation.

Multiaxial pressure-strain analysis of regional myocardial work in the setting of graded coronary stenoses and dobutamine stress.

We present a detailed analysis of regional myocardial blood flow and work to better understand the effects of coronary stenoses and low-dose dobutamine stress. Our analysis is based on a unique open-chest model in anesthetized canines that features invasive hemodynamic monitoring, microsphere-based blood flow analysis, and an extensive three-dimensional (3-D) sonomicrometer array that provides multiaxial deformational assessments in the ischemic, border, and remote vascular territories. We use this model to construct regional pressure-strain loops for each territory and quantify the loop subcomponent areas that reflect myocardial work contributing to the ejection of blood and wasted work that does not. We demonstrate that reductions in coronary blood flow markedly alter the shapes and temporal relationships of pressure-strain loops, as well as the magnitudes of their total and subcomponent areas. Specifically, we show that moderate stenoses in the mid-left anterior descending coronary artery decrease regional midventricle myocardial work indices and substantially increase indices of wasted work. In the midventricle, these effects are most pronounced along the radial and longitudinal axes, with more modest effects along the circumferential axis. We further demonstrate that low-dose dobutamine can help to restore or even improve function, but often at the cost of increased wasted work. This detailed, multiaxial analysis provides unique insight into the physiology and mechanics of the heart in the presence of ischemia and low-dose dobutamine, with potential implications in many areas, including the detection and characterization of ischemic heart disease and the use of inotropic support for low cardiac output.NEW & NOTEWORTHY Our unique experimental model assesses cardiac pressure-strain relationships along multiple axes in multiple regions. We demonstrate that moderate coronary stenoses decrease regional myocardial work and increase wasted work and that low-dose dobutamine can help to restore myocardial function, but often with further increases in wasted work. Our findings highlight the significant directional variation of cardiac mechanics and demonstrate potential advantages of pressure-strain analyses over traditional, purely deformational measures, especially in characterizing physiological changes related to dobutamine.

Prognostic value of CT-derived coronary artery disease characteristics varies by ASCVD risk: insights from the PROMISE trial.

OBJECTIVES: To compare the prognostic value of individual CT-derived coronary artery disease (CAD) characteristics across categories of clinical cardiovascular risk. METHODS: The central core laboratory assessed coronary artery calcium (CAC), obstructive CAD (stenosis ≥ 50%), and high-risk plaque (HRP) in stable outpatients with suspected CAD enrolled in the PROMISE trial. Multivariable Cox regression models (endpoint: unstable angina, nonfatal myocardial infarction, or all-cause mortality; median follow-up: 2 years) were used to compare hazard ratios (HR) of the CT measures between low-borderline (< 7.5%) and moderate-high (≥ 7.5%) atherosclerotic cardiovascular disease (ASCVD) risk based on the pooled cohort equation. RESULTS: Among 4356 included patients (aged 61 ± 8 years, 52% women), 67% had ASCVD risk ≥ 7.5%. Stratified by ASCVD risk, CAD ≥ 50% had nearly threefold greater HR in individuals with ASCVD < 7.5% (aHR, 6.85; 95% CI, 2.33-20.15; p < 0.001) vs. ASCVD ≥ 7.5% (aHR: 2.66, 95% CI: 1.67-4.25, p < 0.001; interaction p = 0.041). CAC predicted events solely in ASCVD ≥ 7.5% patients (aHR: 1.92, 95% CI: 1.01-3.63, p = 0.045; interaction p = 0.571), while HRP predicted events only in ASCVD < 7.5% (aHR: 3.11, 95% CI: 1.09-8.85, p = 0.034; interaction p = 0.034). CONCLUSIONS: Prognostic values of CT-derived CAD characteristics differ by ASCVD risk categories. While CAD ≥ 50% has the highest prognostic value regardless of ASCVD risk, CAC is prognostic in high and HRP in low ASCVD risk. These findings suggest that CAD ≥ 50% and HRP detection rather than CAC scoring may better risk-stratify symptomatic low-risk patients and thus potentially improve downstream care. KEY POINTS: • Prognostic value of individual CT-derived CAD characteristics differs by categories of cardiovascular risk. • Presence of obstructive coronary artery stenosis ≥ 50% has the highest prognostic value regardless of cardiovascular risk. • Coronary artery calcium is independently prognostic in high and high-risk plaque features in low cardiovascular risk.

Radiomics features of pericoronary adipose tissue improve CT-FFR performance in predicting hemodynamically significant coronary artery stenosis.

OBJECTIVES: To evaluate the value of radiomics-based model of pericoronary adipose tissue (PCAT) combined with CT fractional flow reserve (CT-FFR) in predicting hemodynamically significant coronary stenosis. METHODS: Patients with suspected or known coronary artery disease, who had coronary computed tomography angiography (CCTA), invasive coronary angiography (ICA), and FFR within 1 month, were retrospectively included. Radiomics features of lesion-based PCAT were extracted. The lesion-specific CT-FFR values, CCTA-derived diameter stenosis, lesion length, and PCAT attenuation were also measured. FFR values were used as the reference standard to assess the diagnostic performance of radiomics model, CT-FFR, and combined model for detection of flow-limiting stenosis. RESULTS: A total of 146 patients with 180 lesions were included in the study. All lesions were divided into training and validation cohorts at a ratio of 2:1. CT-FFR model exhibited the highest area under the curve (AUC) (0.803 for training, 0.791 for validation) in predicting hemodynamically significant stenosis, followed by radiomics model (0.776 for training, 0.744 for validation). However, no statistically significant difference was found between the AUCs of the above two models (p > 0.05). When CT-FFR was combined with radiomics model, the AUC reached 0.900 for training cohort and 0.875 for validation cohort, which were significantly higher than that of CT-FFR and radiomics model alone (both p < 0.05). CONCLUSION: The diagnostic performance of PCAT radiomics model was comparable to that of CT-FFR for identification of ischemic coronary stenosis. Adding PCAT radiomics model to CT-FFR showed incremental value in discriminating flow-limiting from non-flow-limiting lesions. KEY POINTS: • Radiomics analysis of lesion-based PCAT is potentially an alternative method to identify hemodynamic significance of coronary artery stenosis. • Adding radiomics model of PCAT to CT-FFR improved diagnostic performance for the detection of flow-limiting coronary stenosis. • Radiomics features + CT-FFR is a promising noninvasive method for comprehensive evaluation of hemodynamic significance of coronary artery stenosis.

Prognostic value of myocardial flow reserve derived by quantitative SPECT for patients with intermediate coronary stenoses.

BACKGROUND: Functional assessment of myocardial ischemia is critical for patients with intermediate coronary stenosis. As the diagnosis performance of absolute quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) by single-photon emission tomography (SPECT) has been proven, its prognostic value in patients with intermediate coronary stenosis remains to be evaluated. METHODS: Patients with one or more target lesions of ≥ 50% to ≤ 80% diameter stenoses on invasive coronary angiography were prospectively included in this study. All patients were scheduled for clinically indicated SPECT myocardial perfusion imaging (MPI) within 3 months and agreed to provide informed consent to participate in quantitative SPECT acquisitions to obtain MBF and MFR values. The primary endpoint was defined as a composite of the major adverse cardiac events (MACE): Cardiac death, myocardial infarction, late revascularization and heart failure or unstable angina-related rehospitalization. RESULTS: One hundred and nineteen patients (mean age 57 ± 8 years, 62.2% men) were included in the analysis. The average lumen stenosis of patients was 67.0 ± 10.4%. Over a median follow-up duration of 1408 days (interquartile range 1297-1666 days), 18 patients (15.1%) had MACE. Patients with impaired MFR (MFR < 2) had a significantly higher incidence of events than those with preserved MFR (MFR ≥ 2) in Kaplan-Meier survival analysis (Log-rank = 8.105, P = 0.004), while no significant difference was found between patients with normal relative perfusion and those with relative perfusion abnormalities (log-rank = 0.098, P > 0.05). In a multivariate Cox hazards analysis, the SPECT-derived MFR remained an independent predictor of MACE (HR 0.352, 95% CI 0.145-0.854, P = 0.021). CONCLUSIONS: In a cohort of patients with angiographic intermediate coronary lesions, SPECT-derived MFR was an independent predictor of prognosis.

Sex-specific associations of cardiovascular risk factors and coronary plaque composition for hemodynamically significant coronary artery stenosis: a coronary computed tomography angiography study.

BACKGROUND: It has been reported that there are sex differences in plaque composition and hemodynamically significant stenosis. This study aimed to explore the impact of sex on cardiovascular risk factors for specific plaque compositions and hemodynamically significant stenosis. METHODS: Data regarding demographics and cardiovascular risk factors were collected. Hemodynamically significant stenosis was identified by a computed tomography-derived fractional flow reserve of ≤ 0.8. Associations among cardiovascular risk factors, plaque composition, and hemodynamically significant stenosis were assessed using a multivariate binary logistic regression analysis across sexes. The discriminating capacity of diverse plaque components for hemodynamically significant stenosis was assessed by area under the receiver-operating characteristics curve with 95% confidence intervals. RESULTS: A total of 1164 patients (489 men and 675 women) were included. For men, hyperlipidemia and cigarette smoking were risk factors for each plaque component (all P < 0.05), and diabetes mellitus also predicted fibrotic components (P < 0.05). For women, risk factors for each plaque component were hypertension and diabetes mellitus (all P < 0.01). Nonetheless, hyperlipidemia (P < 0.05) was a specific risk factor for non-calcified components. Calcified components combined with fibrotic components showed superior discrimination of hemodynamically significant stenosis in men and calcified components alone in women (all P < 0.01). Hypertension (P < 0.01) was a risk factor for hemodynamically significant stenosis in women. In contrast, diabetes, hyperlipidemia, and cigarette smoking were risk factors for hemodynamically significant stenosis in men (all P < 0.05). CONCLUSIONS: In men, hemodynamically significant stenosis was predicted by a combination of calcified and fibrotic components with multiple risk factors. In women, hemodynamically significant stenosis was predicted by calcified components caused by a single risk factor. It might be a key point to improve prognosis by more precise risk management between men and women, which needs to be proved by further prospective trials.

The clinical role of serum cell division control 42 in coronary heart disease.

Cell division control 42 (CDC42) regulates blood lipids, atherosclerosis, T cell differentiation and inflammation, which is involved in the process of coronary heart disease (CHD). This study aimed to evaluate the CDC42 level and its correlation with clinical features, the T-helper 17 (Th17)/regulatory-T (Treg) cell ratio and prognosis in CHD patients. In total, 210 CHD patients, 20 healthy controls and 20 disease controls were enrolled. Serum CDC42 levels of all participants were measured by enzyme-linked immunosorbent assay. In CHD patients, Th17 and Treg cells were discovered by flow cytometry; CHD patients were followed-up for a median of 16.9 months (range of 2.5-38.2 months). CDC42 level was lowest in CHD patients (median (interquartile range (IQR)): 402.5 (287.3-599.0) pg/mL), moderate in disease controls (median (IQR): 543.5 (413.0-676.3) pg/mL) and highest in healthy controls (median (IQR): 668.0 (506.5-841.3) pg/mL) (p < .001). Moreover, in CHD patients, lower CDC42 level was related to more prevalent diabetes mellitus (p = .021), and higher levels of C-reactive protein (p = .001), Gensini score (p = .006), Th17 cells (p = .001) and Th17/Treg ratio (p < .001) but was associated with lower Treg cells (p = .018). Furthermore, CDC42 low level [below the median level (402.5 pg/mL) of CDC42 in CHD patients] was correlated with higher accumulating major adverse cardiovascular event (MACE) risk (p = .029), while no correlation was found between the quartile of CDC42 level and accumulating MACE risk in CHD patients (p = .102). The serum CDC42 level is decreased and its low level is related to higher Th17/Treg ratio and increased accumulating MACE risk in CHD patients.

Non-contrast CT-based radiomics nomogram of pericoronary adipose tissue for predicting haemodynamically significant coronary stenosis in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients have a higher incidence of coronary artery disease than the general population. The aim of this study was to develop a radiomics nomogram of pericoronary adipose tissue (PCAT) based on non-contrast CT to predict haemodynamically significant coronary stenosis in T2DM patients. METHODS: The study enrolled 215 T2DM patients who underwent non-contrast CT and coronary computed tomography angiography (CCTA). CCTA derived fractional flow reserve (FFRCT) ≤ 0.80 was defined as hemodynamically significant stenosis.1691 radiomics features were extracted from PCAT on non-contrast CT. Minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to select useful radiomics features to construct Radscore. Logistic regression was applied to select significant factors among Radscore, fat attenuation index (FAI) and coronary artery calcium score (CACS) to construct radiomics nomogram. RESULTS: Radscore [odds ratio (OR) = 2.84; P < 0.001] and CACS (OR = 1.00; P = 0.023) were identified as independent predictors to construct the radiomics nomogram. The radiomics nomogram showed excellent performance [training cohort: area under the curve (AUC) = 0.81; 95% CI: 0.76-0.86; validation cohort: AUC = 0.83; 95%CI: 0.76-0.90] to predict haemodynamically significant coronary stenosis in patients with T2DM. Decision curve analysis demonstrated high clinical value of the radiomics nomogram. CONCLUSION: The non-contrast CT-based radiomics nomogram of PCAT could effectively predict haemodynamically significant coronary stenosis in patients with T2DM, which might be a potential noninvasive tool for screening of high-risk patients.

Drug-coated balloon combined with drug-eluting stent for the treatment of coronary bifurcation lesions: insights from the HYPER study.

True coronary bifurcation lesions (CBL) represent a challenging scenario for percutaneous coronary interventions (PCI), and are associated with a higher risk of target lesion failure (TLF), particularly when two stents are implanted. A hybrid strategy combining a drug-eluting stent (DES) in the main branch, and a drug-coated balloon in the side branch may improve outcomes by reducing the total stent length while maintaining an effective anti-prolipherative action. In this sub-study of the HYPER trial, 50 patients with true CBL were treated with a hybrid strategy: procedural success was 96%, one case of peri-procedural myocardial infarction and one case of TLF (in a DES-treated segment) at 1 year were reported. This study suggests that such a hybrid strategy may be a safe and effective option for true CBL PCI, and warrants additional investigations to compare outcomes with standard of care strategies.

Association of ambient PM10 and PM2.5 with coronary stenosis measured using selective coronary angiography.

BACKGROUND: Long-term ambient particulate matter (PM) exposure exerts detrimental effects on cardiovascular health. Evidence on the relation of chronically exposed ambient PM10 and PM2.5 with coronary stenosis remains lacking. Our aim was to investigate the association of PM10 and PM2.5 with coronary stenosis in patients undergoing coronary angiography. METHODS: We performed a retrospective cohort study consisting of 7513 individuals who underwent coronary angiography in Fujian Province, China, from January 2019 to December 2021. We calculated a modified Gensini score (GS) to represent the degree of stenosis in coronary arteries by selective coronary angiography. We fitted linear regressions and logistic models to assess the association of PM10 and PM2.5 with coronary stenosis. We employed restricted cubic splines to describe the exposure-response curves. We performed mediation analyses to assess the potential mediators. RESULTS: Long-term ambient PM10 and PM2.5 (prior three years average) exposure was significantly associated with the GS, with a breakpoint concentration of 47.5 µg/m3 and 25.8 µg/m3 for PM10 and PM2.5, respectively, above which we found a linear positive exposure-response relationship of ambient PM with GS. Each 10 µg /m3 increase in PM10 exposure (ß: 4.81, 95 % CI: 0.44-9.19) and PM2.5 exposure [ß: 10.50, 95 % CI: 3.14-17.86] were positively related to the GS. The adjusted odds ratio (OR) for each 10 µg/m3 increment in PM10 exposure on severe coronary stenosis was 1.33 (95 % CI: 1.04-1.76). Correspondingly, the adjusted OR for PM2.5 was 1.87 (95 % CI: 1.24-2.99). The mediation analysis indicated that the effect of PM10 on coronary stenosis may be partially mediated through total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, serum creatinine and blood urea nitrogen, and the effect of PM2.5 may be mediated in part by hemoglobin A1c. CONCLUSION: Our study provides the first evidence that chronic ambient PM10 and PM2.5 exposure was associated with coronary stenosis assessed by GS in patients with suspected coronary artery disease and reveals its potential mediators.

Pathophysiology and Treatment of Intraseptal-Course Left Coronary Anomaly: Surgery for All?

Intraseptal-course, ectopic coronary anomalies are not well characterized as to anatomy, function, prognosis, and treatment. Recently, a revolutionary but unsupported new theory is claiming that most patients with a Left Anomalous Coronary Artery originating from the Opposite Sinus with anomalous Intra-Septal course (L-ACAOS-IS)-even small children-have significant stenoses and require open-heart surgery to prevent acute myocardial infarction and death. This surprising view has spurred ongoing discussions among adult and pediatric cardiologists and cardiac surgeons, compelling us (the conservative party in the discussion) to offer an in-depth and comprehensive review of this anomaly, based on objective but opposite data. We and other adult cardiologists have followed numerous L-ACAOS-IS patients for many years and have observed none of the claimed catastrophes. Rather, we have consistently found that L-ACAOS-IS generally has a benign clinical prognosis. We present the general principle of coronary artery dysfunction in anatomical congenital anomalies (that only significant luminal coronary stenosis can have clinical repercussions). We then review anatomical and functional details of L-ACAOS-IS related to prognosis and treatment indications, which could explain many of the clinical presentations recently mentioned. Finally, we encourage our more liberal colleagues to recognize that, compared with normal coronary arteries, those with anomalies of origin and course are associated with frequent coronary spasm. In particular, we underscore that some of the ischemic manifestations and other results might actually be caused by pressure wire-induced artifacts (rigid wires tend to cause coronary spasm when advanced into tortuous coronary arteries).