BACKGROUND: Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship.
METHODS: Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation.
RESULTS: The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation.
CONCLUSIONS: Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

BACKGROUND: The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM.
METHODS: This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression.
RESULTS: A total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: β = 0.116; positive remodelling: β = 0.138; spotty calcification: β = 0.091; NOS: β = 0.427; OS: β = 0.659: SIS: β = 1.114; SSS: β = 2.987; PID: β = 2.716, all P value < 0.001).
CONCLUSIONS: Abnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.

UNASSIGNED: The diagnostic performance of fractional flow reserve with computed tomography (FFR-CT) is affected by the presence of calcified plaque. Subtraction can remove the influence of calcification in coronary computed tomography angiography (CCTA) to increase confidence in the diagnosis of coronary artery stenosis. Our purpose is to investigate the accuracy of post-subtraction FFR-CT in predicting early revascularization.
UNASSIGNED: Based on CCTA data of 237 vessels from 79 patients with coronary artery disease, subtraction CCTA images were obtained at a local post-processing workstation, and the conventional and post-subtraction FFR-CT measurements and the difference in proximal and distal FFR-CT values of the narrowest segment of the vessel (ΔFFR-CT) were analyzed for their accuracy in predicting early coronary artery hemodynamic reconstruction.
UNASSIGNED: With FFR-CT ≤ 0.8 as the criterion, the accuracy of conventional and post-subtraction FFR-CT measurements in predicting early revascularization was 73.4% and 77.2% at the patient level, and 64.6% and 72.2% at the vessel level, respectively. The specificity of post-subtraction FFR-CT measurements was significantly higher than that of conventional FFR-CT at both the patient and vessel levels (P of 0.013 and 0.015, respectively). At the vessel level, the area under the curve of receiver operating characteristic was 0.712 and 0.797 for conventional and post-subtraction ΔFFR-CT, respectively, showing a difference (P = 0.047), with optimal cutoff values of 0.07 and 0.11, respectively.
UNASSIGNED: The post-subtraction FFR-CT measurements enhance the specificity in predicting early revascularization. The post-subtraction ΔFFR-CT value of the stenosis segment > 0.11 may be an important indicator for early revascularization.

Patients with acute coronary syndrome (ACS), frequently caused by plaque rupture (PR), often have vulnerable plaques in residual lesions as well as in culprit lesions. However, whether this occurs in patients with plaque erosion (PE) as well is unknown. We retrospectively analyzed the data of 88 patients with ACS who underwent both optimal coherence tomography (OCT) and intravascular ultrasound (IVUS). Based on plaque morphology of the culprit lesions identified using OCT, patients were classified into PE (n=23) and PR (n=35) groups. The tissue characteristics of residual lesions evaluated using integrated backscatter IVUS were compared between both groups after percutaneous coronary intervention. The PE group had a significantly lower percent lipid volume and a higher percent fibrous volume than the PR group (35.0±17.8% vs 49.2±13.4%, p<0.001; 63.2±17.1% vs 50.3±13.1%, p=0.002, respectively). Receiver operating characteristic curve analysis revealed that percent lipid volume in the residual lesions was a significant discriminant factor in estimating the plaque morphology of the culprit lesion (optimal cut-off value, <43.5%; sensitivity and specificity values were 73.9% and 68.6%, respectively). In conclusion, patients with PE had a significantly lower percent lipid volume and a significantly higher percent fibrous volume in the residual lesions than those with PR, suggesting that the nature of coronary plaques in patients with PE is different from that of those with PR.

Decreased myocardial capillary density has been reported as an important histopathological feature associated with various heart disorders. Quantitative assessment of cardiac capillarization typically involves double immunostaining of cardiomyocytes (CMs) and capillaries in myocardial slices. In contrast, single immunostaining of basement membrane protein is a straightforward approach to simultaneously label CMs and capillaries, presenting fewer challenges in background staining. However, subsequent image analysis always requires expertise and laborious manual work to identify and segment CMs/capillaries. Here, we developed an image analysis tool, AutoQC, for automatic identification and segmentation of CMs and capillaries in immunofluorescence images of basement membrane. Commonly used capillarization-related measurements can be derived from segmentation results. By leveraging the power of a pre-trained segmentation model (Segment Anything Model, SAM) via prompt engineering, the training of AutoQC required only a small dataset with bounding box annotations instead of pixel-wise annotations. AutoQC outperformed SAM (without prompt engineering) and YOLOv8-Seg, a state-of-the-art instance segmentation model, in both instance segmentation and capillarization assessment. Thus, AutoQC, featuring a weakly supervised algorithm, enables automatic segmentation and high-throughput, high-accuracy capillarization assessment in basement-membrane-immunostained myocardial slices. This approach reduces the training workload and eliminates the need for manual image analysis once AutoQC is trained.

OBJECTIVE: The clinical benefits of complete revascularization (CR) in acute myocardial infarction (AMI) patients are unclear. Moreover, the benefit of CR is unknown in AMI with diabetes mellitus (DM) patients. We sought to compare the prognosis of CR and incomplete revascularization (IR) in patients with AMI and multivessel disease, according to the presence of DM.
METHODS: A total of 2,150 AMI patients with multivessel coronary artery disease were analyzed. CR was defined based on the angiographic image. The primary endpoint of this study was the patient-oriented composite outcome (POCO) defined as a composite of all-cause death, any myocardial infarction, and any revascularization within 3 years.
RESULTS: Overall, 3-year POCO was significantly lower in patients receiving angiographic CR (985 patients, 45.8%) compared with IR (1,165 patients, 54.2%). When divided into subgroups according to the presence of DM, CR reduced 3-year clinical outcomes in the non-DM group but not in the DM group (POCO: 11.7% vs. 23.2%, p<0.001, any revascularization: 7.2% vs. 10.8%, p=0.024 in the non-DM group, POCO: 24.3% vs. 27.8%, p=0.295, any revascularization: 13.3% vs. 11.3%, p=0.448 in the DM group, for CR vs. IR). Multivariate analysis showed that CR significantly reduced 3-year POCO (hazard ratio, 0.52; 95% confidence interval, 0.36-0.75) only in the non-DM group.
CONCLUSIONS: In AMI patients with multivessel disease, CR may have less clinical benefit in DM patients than in non-DM patients.

BACKGROUND: There are limited data about determinant factors of target lesion failure (TLF) in lesions after percutaneous coronary intervention (PCI) using a drug-coated balloon (DCB) for de novo coronary artery lesions, including optical coherence tomography (OCT) findings.
OBJECTIVE: The present study aims to investigate the associated factors of TLF in de novo coronary artery lesions with DCB treatment.
METHODS: We retrospectively enrolled 328 de novo coronary artery lesions in 328 patients who had undergone PCI with a DCB. All lesions had been treated without a stent, and both pre- and post-PCI OCT had been carried out. Patients were divided into two groups, with or without TLF, which was defined as a composite of culprit lesion-related cardiac death, myocardial infarction, and target lesion revascularisation, and the associated factors of TLF were assessed.
RESULTS: At the median follow-up period of 460 days, TLF events occurred in 31 patients (9.5%) and were associated with patients requiring haemodialysis (HD; 29.0% vs 10.8%), with a severely calcified lesion (median maximum calcium arc 215° vs 104°), and with the absence of OCT medial dissection (16.1% vs 60.9%) as opposed to those without TLF events. In Cox multivariable logistic regression analysis, HD (hazard ratio [HR]: 2.26, 95% confidence interval [CI]: 1.00-5.11; p=0.049), maximum calcium arc (per 90°, HR: 1.34, 95% CI: 1.05-1.72; p=0.02), and the absence of post-PCI medial dissection on OCT (HR: 8.24, 95% CI: 3.15-21.6; p<0.001) were independently associated with TLF.
CONCLUSIONS: In de novo coronary artery lesions that received DCB treatment, factors associated with TLF were being on HD, the presence of a severely calcified lesion, and the absence of post-PCI medial dissection.

Ischemic heart disease (IHD) affects more than 20 million adults in the United States. Although classically attributed to atherosclerosis of the epicardial coronary arteries, nearly half of patients with stable angina and IHD who undergo invasive coronary angiography do not have obstructive epicardial coronary artery disease. Ischemia with nonobstructive coronary arteries is frequently caused by microvascular angina with underlying coronary microvascular dysfunction (CMD). Greater understanding the pathophysiology, diagnosis, and treatment of CMD holds promise to improve clinical outcomes of patients with ischemic heart disease.

The cytokine profile of primary coronary artery endothelial cells cultivated in the presence of doxorubicin (2 μg/ml and 6 μg/ml) was evaluated using enzyme-linked immunosorbent assay and qPCR. Cultivation of cells in the presence of these concentrations of doxorubicin for 24 h, upregulated expression of the following genes: IL6 (by 2.30 and 2.66 times, respectively), IL1B (by 1.25 and 3.44 times), and CXCL8 (by 6.47 times and 6.42 times), MIF (2.34 and 2.28 times), CCL2 (4.22 and 3.98 times). Under these conditions the following genes were downregulated: IL10, IL1R2, TNF. Cultivation of cells in the presence of doxorubicin (2 μg/ml and 6 μg/ml) for 24 h also increased the secretion of IL-6.

UNASSIGNED: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular tachycardia and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear, and its use after myocardial infarction is limited by concerns for potential right ventricular dysfunction.
UNASSIGNED: Myocardial infarction was created in Yorkshire pigs (N=22) by left anterior descending coronary artery occlusion. Six weeks after myocardial infarction, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. Right and left ventricular hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity and intrinsic cardiac neural activity, and ventricular effective refractory periods and slope of restitution (Smax) were assessed before and after TEA. Ventricular tachyarrhythmia inducibility was assessed by programmed electrical stimulation.
UNASSIGNED: TEA reduced inducibility of ventricular tachyarrhythmias by 70%. TEA did not affect right ventricular-systolic pressure or contractility although left ventricular-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular effective refractory periods prolonged significantly at critical sites of arrhythmogenesis, and Smax was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both baroreflex sensitivity and intrinsic cardiac neural activity.
UNASSIGNED: TEA does not compromise right ventricular function in infarcted hearts. Its antiarrhythmic mechanisms are mediated by increases in ventricular effective refractory period and ARIs, decreases in Smax, and reductions in border zone electrophysiological heterogeneities. TEA improves parasympathetic function, which may independently underlie some of its observed antiarrhythmic mechanisms. This study provides novel insights into the antiarrhythmic mechanisms of TEA while highlighting its applicability to the clinical setting.