bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computed tomography plaque analysis identifies residual inflammation in recent acute myocardial infarction patients
Authors: Wang X , Yew M S , Adamson P D , Chan M Y Y , Raffiee N A S , Yap H T , Loong Y T , Elankovan A , Leng S , Huang W , Lee H K , Teo L L S , Zhong L , Hausenloy D J , Baskaran L 
Published: November 2023

Abstract

Introduction
Residual inflammatory risk (RIR) following acute myocardial infarction (AMI) patients is associated with recurrent major adverse cardiovascular events. Atherosclerotic plaque quantification using computed tomographic coronary angiography (CTCA) can specifically identify inflamed plaque characteristics. We compared plaque burden and tissue composition in AMI patients with those of stable coronary artery disease (CAD) patients to identify imaging markers of RIR.

Purpose
We aimed to identify signs of residual inflammation in recent AMI patients via CTCA atheroma quantification. We hypothesised that recent AMI patients have plaque characteristics suggestive of inflammation.

Methods
108 patients recruited from multiple sites with AMI &lt;1 month were propensity-matched via CAD risk factors (age, gender, diabetes, hypertension, hyperlipidaemia, smoking and family history of CAD) with stable CAD patients in a 1:1 ratio. Propensity matched recent AMI and stable CAD patient cohorts had similar profiles: age (60±9.7 vs 57±10.0 years), gender (91.7% vs 92.6% male), diabetes (13.9% vs 15.7%), hypertension (44.4% vs 50.9%) and hyperlipidaemia (50.9% vs 63.9%, p&gt;0.05 for all). Total plaque burden (total lesion volume/total vessel volume) and plaque composition (fibrous fatty [fibrofatty, FF, 31 – 130 HU], necrotic core [NC, -30 – 30 HU], fibrous [131 – 350 HU] and calcium [&gt; 350 HU]) were extracted from CTCA scans and aggregated per patient. Culprit lesions of recent AMI patients were excluded from the analysis due to the fact that coronary stents would affect plaque characterisation. Multivariate linear regression, corrected for CAD risk factors, was used to compare these parameters between the two cohorts.

Results
Recent AMI patients and stable CAD patients had similar total plaque burden (β=0.001±0.013, p=0.950, Figure 1a). Patients with recent AMI had higher non-calcified plaque volume ratio (β=0.071±0.026, p&lt;0.05, Figure 1b) due to higher FF (β=0.094±0.019, Figure 1d) and NC (β=0.025 ± 0.005, Figure 1e) plaque volume (p&lt;0.05 for all), but less fibrous plaque volume (β = -0.048±0.019, p&lt;0.05, Figure 1c).

Conclusions
Recent AMI patients had a greater non-calcified plaque burden than stable CAD patients due to larger FF and NC plaque burden. Since FF and NC components indicate ongoing inflammation in the plaque, while fibrous content indicates resolved inflammation; increased NC and FF burden suggest increased coronary plaque inflammation in non-culprit lesions of recent AMI patients, supporting the presence of residual inflammation in recent AMI patients.Figure 1
Combination of nicorandil and beta-adrenergic receptor blockers in patients with coronary heart disease: a real-world observational study
Authors: Zhou N , Cheng J , Qiu L , Zhang Z X , Li N , Shu H Y , Xiao Z C 
Published: November 2023

Abstract

Background and objective
Nicorandil and beta-adrenergic receptor blockers (BBs) are commonly used anti-anginal drugs. However, the effect of combined nicorandil and BBs compared with that of BBs alone on long-term clinical outcomes in patients with coronary heart disease (CHD) remains undetermined. Accordingly, a real-world observational study was performed to assess the long-term potential of nicorandil combined with BBs in Chinese patients with CHD.

Methods
A multicenter retrospective cohort study involving two tertiary healthcare institutions in our city was performed. Adult patients who had been hospitalized for CHD and treated for angina with a combination of nicorandil and BBs or BBs alone between August 2002 and March 2020 were included. The effect of different treatments on the cumulative incidence of major adverse cardiovascular events (MACE) and their components (myocardial infarction [MI], stroke, and all-cause mortality) within a follow-up duration of 2.5 years were analyzed using Kaplan–Meier survival curves. An inverse probability of treatment weighting (IPTW) method was used to adjust for the possible effect of confounding factors. The hazard ratio (HR) and corresponding 95% confidence interval (CI) were calculated using a Cox regression analysis. Sensitivity analyses based on IPTW with trimming or limited to patients admitted after January 1, 2012, were performed to evaluate the robustness of the findings.

Results
Overall, 4,669 patients receiving the combined treatment and 12,243 receiving BBs alone were included. After IPTW, the results demonstrated that the combined treatment was associated with a significantly reduced incidence of MACE (HR 0.80, 95% CI: 0.73–0.87, P &lt; 0.0001)(Figure 1) and stroke (HR 0.48, 95% CI 0.42–0.54) but not of MI (HR 1.03, 95% CI 0.92–1.15) or all-cause mortality (HR 0.93, 95% CI 0.64–1.37). Interaction analyses were performed for the following subgroups: age (younger than 65 or is and older than 65 years), gender, acute coronary syndrome (ACS), smoking, drinking, revascularization, diabetes and hypertension, and showed a favorable consistency with the primary outcome (Figure 2).

Conclusion
A combined anti-angina treatment of nicorandil and BBs may be more effective than a treatment of BBs alone in reducing the long-term incidence of MACE in patients with CHD.The Kaplan-Meier curves of the outcomesThe forest plot of the subgroup analysis
Non-clinical evaluation of YN001-a promising drug for atherosclerotic therapy by targeted delivery system
Authors: Ma Q , Zhang W E I , Li Y I N G , Sun J F , Chen Y A N , Wu S J , Zhou W X , Wang Z J , Yang S W , Su H F , Ren X M , He C Q , Jiang M J , Chen X M , Zhou Y J 
Published: November 2023

Abstract

Background
Atherosclerosis (AS) is a systemic disease and the common cause of heart attacks, strokes and peripheral vascular disease collectively referred to as cardiovascular diseases (CVD). In AS plaques, CD44 is upregulated and functionally activated on vascular endothelial cells, smooth muscle cells, and macrophages.
YN001 is a liposome encapsulated Rosuvastatin calcium which was initially approved for the reduction of cholesterol levels and slowing the progression of atherosclerosis. YN001 is being developed for the treatment of AS by targeted enrichment of Rosuvastatin in the local atherosclerotic plaques by CD44 active targeting ability of HPD, one of the components of liposome.

Purpose
Investigating pharmacology, PK and toxicity of YN001 to evaluate its clinical use potential for AS patients.

Results
As expected, YN001 could bind to CD44 with KD as 485.5pm while there’s no binding affinity of non-targeted liposome (encapsulate Rosuvastatin without HPD). In stimulated human macrophages in which CD44 was overexpressed, YN001 showed enhanced uptake and higher cholesterol effluxion ability than Rosuvastatin, meanwhile more MCP-1 reduction was also observed. In ApoE AS mice model, single YN001 administration showed much higher drug concentrations in the plaque of aortas compared to Rosuvastatin (oral or iv) or non-targeted liposome which demonstrated targeted enrichment ability by HPD. With repeat treatment of YN001 at 5mg/kg in AS mice model, atherosclerotic plaque weight decreasing and plaque area reduction were observed, following MCP-1 reduction. YN001 may down-regulate the expression of inflammatory signaling pathways, such as chemokine-related signaling pathway to reduce the inflammatory response of atherosclerotic plaques to decrease plaque levels. In pharmacokinetic studies in rats and dogs, YN001 had much higher exposure in plasma and prolonged existence compared to Rosuvastatin i.v administration. A comprehensive safety evaluation package was performed in rats and dogs including safety pharmacology, general toxicity, genotoxicity, immunotoxicity and local tolerance. Results showed YN001 has promising safety with NOAEL as 40mg/kg in both or rats and dogs.

Conclusion
YN001 demonstrated excellent efficacy in AS model, a favorable pharmacokinetic and safety profiles in rats and dogs. These support its FDA IND approval and phase I study is ongoing to investigate further character in clinical.Efficacy and pharmacokinetics resultsSafety evaluation
Current use of antiplatelet therapy in the management of acute myocardial infarction: overview of the FRENCHIE national registry
Authors: Gautier A , Ducrocq G , Danchin N , Simon T , Nekrouf C , Rousseau A , Cottin Y , Coste P , Prunier F , Cayla G , Lemesle G , Angoulvant D , Steg P G 
Published: November 2023

Abstract

Background
There are many options for antiplatelet therapy (APT) at various stages in the management of acute myocardial infarction (MI) but few contemporary data regarding use in routine clinical practice in unselected patients.

Purpose
to describe the contemporary use of APT treatments in unselected MI patients.

Methods
FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is a multicenter observational study (38 centers in France) consecutively enrolling patients with spontaneous MI whose symptoms were &lt; 48 hours. Exclusion criteria were age &lt; 18 years, no health coverage, unstable angina and procedure-related MI.

Results
Between September 2019 and December 2020, 10190 patients with MI were enrolled. Complete data on APT use were available for 9842 patients. Of these, 54.5% had ST elevation myocardial infarction (STEMI) and 45.5% non-STEMI (NSTEMI). During the first 24 hours, APT use for STEMI and NSTEMI patients, was as follows, respectively: acetylsalicylic acid (ASA) 95.1% and 88.8%, clopidogrel 12.4% and 17.7%, ticagrelor 79.5% and 55.0%, prasugrel 4.8% and 3.6%, GPIIb-IIIa inhibitors 23.8% and 6.5%, Cangrelor 1.1% and 0.8%. Among STEMI patients, 3.2% had undergone thrombolysis, 92.2% primary percutaneous coronary intervention (pPCI) and 4.5% did not have reperfusion during acute phase management. The use of ASA was similar regardless of the initial reperfusion strategy, but that of P2Y12 inhibitors (P2Y12i) was different. Clopidogrel was mainly used in case of thrombolysis, 69.6% of cases, while ticagrelor was mainly used in case of pPCI or medical treatment alone, respectively in 83.9% and 59.7% of cases. GPIIb-IIIa inhibitors were used in 9.3%, 26.2% and 11.4% in patients who had undergone thrombolysis, pCI and medical treatment respectively. At hospital discharge, APT use was as follows, respectively for STEMI and NSTEMI patients: ASA 94.6% and 91.2%, clopidogrel 14.7% and 21.8%, ticagrelor 72.6% and 54.9%, prasugrel 6.9% and 5.7%. The first P2Y12i administered was different from that retained at discharge in 15.4% of STEMI and 12.5% of NSTEMI patients. The most common scenario was switching from ticagrelor to clopidogrel in 64.2% of STEMI patients and 57.2% of NSTEMI patients. No P2Y12i was prescribed at discharge in 3.6% of STEMI patients and 11.3% of NSTEMI patients.

Conclusion
In contemporary practice in France, P2Y12i use was different according to MI type and to initial reperfusion strategy. GPIIb-IIIa inhibitors were used in more than a quarter of STEMI patients with pPCI. Switching between P2Y12i occurred in 1/8 of patients before discharge and deserves further investigation.
Meta-analysis of 3-month vs 12-month dual anti-platelet therapy after percutaneous coronary intervention
Authors: Gerardo F , Fialho I , Passos M , Mateus C , Miranda I , Lima Lopes J , Faria D 
Published: November 2023

Abstract

Background
The optimal duration of dual antiplatelet therapy (DAPT) in the era of second generation drug-eluting stents is a matter of debate as increasing evidence suggests that shorter periods of DAPT are feasible and reduce bleeding events. However, the non-inferiority design of the published trials regarding ischemic events still raises doubt on its effectiveness.

Methods
We performed a meta-analysis to evaluate short-term (≤ 3 months) vs long-term (≥ 12 months) DAPT after percutaneous coronary intervention (PCI). PubMed, Embase and Cochrane Central were searched from inception to February 2023 to identify randomized controlled trials that compared outcomes of patients between these two regimens. Primary outcome of interest included a composite of ischemic events (cardiovascular death, myocardial infarction, re-revascularization and stroke) and secondary outcome was major bleeding as assessed by Bleeding Academic Research Consortium (BARC) classification ≥ 3 after 1 year of follow up. Event rates were extracted and Mantel-Haenszel fixed-effects
model was used to perform the meta-analysis.

Results
We identified a total of 5 trials with 18.682 randomized patients. The use of short-term DAPT was not associated with increased risk of ischemic events (0.90 [0.75-1.08], p=0.250; Figure 1) and was associated with reduced risk of major bleeding (0.74 [0.65-0.84], p&lt;0.001; Figure 2).

Conclusion
The present meta-analysis provides an updated data on the use of DAPT duration. Short-term DAPT appears to be equivalent to long-term DAPT regarding ischemic risk and a superior strategy in optimizing bleeding risk reduction.Forest plot of ischemic outcomesForest plot of bleeding outcomes
Cardioprotective potential of exosomes derived from blood outgrowth endothelial cells in ischemic cardiomyopathy
Authors: Wu M , Wibowo A , Delrue L , Veltman D , Vanhaverbeke M , Trenson S , Gillijns H , Caluwe E , Pokreisz P , Luttun A , Bartunek J , Janssens S 
Published: November 2023

Abstract

Introduction
Blood outgrowth endothelial cell (BOEC)-derived exosomes can effectively induce vascular network formation in vitro and mediate therapeutic neovascularization in a skin wound healing model. We hypothesized that BOEC-derived exosomes can enhance myocardial repair in mice after ischemia-reperfusion (I/R) injury.

Methods
BOECs were isolated and culture-expanded from peripheral blood of patients with severe ischemic cardiomyopathy (ICMP) in normoxic and hypoxic (1% O2) conditions. Exosomes were isolated from the medium by differential ultracentrifugation, and their size, number, and surface markers were determined by nano tracking analysis (NTA) and immunoblot analysis. Myocardial infarction (MI) was induced via transient LAD ligation for 60 min followed by reperfusion. BOEC-derived exosomes and were resuspended in small fractions (120x10^8 particles per 10 µl) 2.5 µl 4 aliquots were injected under direct vision into the epicardial wall of the peri-infarct region. One month later, left ventricular (LV) structure and function were analyzed using a 7T Bruckner MRI with commercial software Segment in mice that received exosome injections or placebo injections (n=10 and n=8, respectively).

Results
Quantification of exosomes by NTA showed higher concentrations in the medium of BOECs cultured in hypoxia. Immunoblot analysis confirmed robust expression of exosome markers TSG101 and Flotilin-1. One month after intramyocardial exosome injections, heart rate, LV volumes or LV ejection fraction were similar between mice receiving myocardial exosomes injections (n=10) in the border zone as compared to those receiving placebo (n=8). However, in vivo exosome transfer mediated favorable structural remodeling after MI with lower LV mass indices (p=0.01) and better preserved regional wall thickness in all 4 segments receiving exosomes aliquots (p&lt;0.05) (Figure).

Conclusions
Our results suggest that BOEC-derived exosomes have favorable post-infarction myocardial structural remodeling. Exosomes may constitute an attractive cell-free therapeutic modality.Figure
Drug-interacting gene expression levels differ between atherosclerotic plaque subtypes
Authors: Palm K , Marsman J , Boltjes A , De Borst G J , De Kleijn D P V , Den Ruijter H M , Van Steenbeek F G , Mokry M , Pasterkamp G , Engels S 
Published: November 2023

Abstract

Background
Recent transcriptomic-based clustering of human atherosclerotic plaques revealed that plaques have a diversity and complexity that cannot be accurately described by classical concepts. Previous plaque RNA sequencing that we performed identified five major plaque types that reflect the severity of the atherosclerotic disease. These include the following plaque subtypes: 0. Fibro-collagenous, 1. Intermediate, 2. Lipo-necrotic, 3. Fibro-inflammatory, and 4. Fibro-cellular. We hypothesised that identifying these different plaque types could explain differential responses following drug treatment.

Objective
To assess differential expression levels of drug-responsive genes between the earlier described five plaque subtypes. For this pilot experiment, we selected genes that are differentially expressed after colchicine treatment in smooth muscle cells and endothelial cells.

Methods
A web-based search identified 46 published colchicine interacting genes. Colchicine was also applied to smooth muscle and endothelial cells to identify direct-effect genes via differential gene expression analysis. Differences in gene expression between plaque types were assessed for those genes that were considered drug-responsive. Finally, to model the effect of colchicine on an atherosclerotic plaque, we projected the in vitro derived expression changes onto the gene expression data from carotid plaques of 654 patients that participated in the ATHERO-EXPRESS study.

Results
34 out of the 46 publicly known colchicine interacting genes were differently expressed between plaque types (Figure 1). These genes included established determinants of cell motility and atherosclerosis development (SCD, ITGB1, Tubulins). Furthermore, in-silico colchicine treatment revealed colchicine's strong effect on the atherosclerotic plaques' transcriptome. We are currently assessing if these perturbations may lead to changes in plaque subtypes.

Conclusion
The pilot data demonstrated major differences in drug-interacting gene expression levels in advanced atherosclerotic lesions. Therefore, novel and standard drugs used to treat atherosclerosis may have varying effects depending on the atherosclerotic plaque subtype.Figure 1
Baseline characteristics of patients enrolled in the EMPACT-MI trial
Authors: Butler J 
Published: November 2023

Abstract

Background
Empagliflozin has been shown to reduce the risk of adverse cardiovascular (CV) outcomes in patients with type 2 diabetes (T2DM) and in those with heart failure (HF). The impact of empagliflozin in post-acute myocardial infarction (AMI) patients is unknown.

Methods and Results
The Study to Test the Effect of Empagliflozin on Hospitalization For Heart Failure And Mortality In Patients With Acute Myocardial Infarction (EMPACT-MI) trial screened 6610 participants with AMI and 6522 were randomized to empagliflozin or placebo in addition to standard of care. Patients were eligible for enrollment if they had no history of HF, had been hospitalized with a AMI and had either acute signs or symptoms of congestion that required treatment, and/or a newly depressed LVEF&lt;45%. Patients were also required to have at least one additional risk factor (enrichment criterion). The median (interquartile range) age of trial population was 64 (56-71) years and 75.1% were male. Major comorbidities included hypertension (69.1%), atrial fibrillation (10.9%), prior myocardial infarction (13.0%), and type 2 diabetes (31.7%). The majority (74.3%) of patients presented with an ST elevation myocardial infarction. Overall, 56.9% of patients randomized had acute signs or symptoms of congestion that required treatment, and 78.3% had newly developed left ventricular systolic dysfunction with ejection fraction &lt;45%. Key characteristics of EMPACT-MI patient population are presented on the figure 1.

Conclusion
EMPACT-MI has randomized 6522 patients with acute MI. EMPACT-MI will establish the benefit and risks of empagliflozin in these patients.
3-dimensional ct versus angiography guided pci for ostial rca lesions
Authors: Van Den Buijs D M F , Poels E M , Willems E , Cottens D , Ferdinande B , Vrolix M , Dens J , Ameloot K 
Published: November 2023

Abstract

Background
Geographical stent-ostium mismatch is an important predictor of target lesion failure (TLF) after PCI of an aorto-ostial right coronary artery (RCA) lesion.

Purpose
We hypothesize that a pre-procedural 3-dimensional coronary CT angiography (3DCT) to determine the optimal C-arm angle of the X-ray system with the most accurate visualization of the aorto-ostial angle could allow optimal stent implantation at the level of the ostium and avoid excessive use of radiation and contrast.

Methods
This is a single centre trial randomizing 30 patients with an indication for non-emergent PCI of an ostial RCA lesion between 3DCT (intervention group) versus angiography guided strategy (control group). While in the control group the C-arm angle was at the operators’ discretion, in the intervention group the angle was determined based on a pre-PCI CT scan with 3D reconstruction using Materialise Mimics Innovation Suite software.
A pre- and post-PCI IVUS is performed in all patients and analyzed by a blinded core lab. The primary endpoint is absence of geographical mismatch on IVUS defined as full stent coverage of the ostium and maximal aortic protrusion equal or less than 3mm. Secondary, we also aim to investigate whether a pre-procedural 3DCT may reduce procedural radiation, contrast use, may predict IVUS parameters (minimal luminal area (MLA), calcification), stent sizing and may promote stent expansion. Finally, MACE rate is evaluated at 1 month.

Results
The full patient dataset (n=30) including primary and all secondary endpoints will be available for presentation at the ESC congress. Currently, 27 patients were randomized. An interim analysis shows the following findings.
There is significant patient heterogeneity considering the optimal angle for stent implantation, underscoring the potential benefit for individualized pre-procedural CT planning. In general, more extreme LAO angles were used in patients randomized to the intervention group (picture 1).
While the stent was implanted in optimal position in 13/13 (100%) patients randomized to the intervention group, geographical stent mismatch was present in 5/14 (36%) patients randomized to the control group (interim p-value 0.07) (picture 2).
The number of cine acquisitions performed before stent implantation (1±1.87 vs. 3.5±0.60; p=0.0007), the amount of contrast used (60±24.5 vs. 114±37.8 mL; p=0.0002), radiation dose (209 [186,315] vs. 497 [411,678] mGy; p=0.01) and procedure time (30 [20,38] vs. 50 [39,66] min; p=0.005) were significantly lower in patients randomized to the intervention group.
There was a highly significant correlation between the calcium arc determined by CT and IVUS (R² = 0.84). No MACE occurred at 1 month.

Conclusion
We showed that pre-procedural CT planning for PCI of aorto-ostial RCA lesions allowed for optimal stent positioning while reducing procedure time, contrast and radiation use.Picture 1Picture 2