bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and outcomes of type 2 myocardial infarction: a cohort study of a national population-based registry
Authors: Ho J S Y , Zheng H , Ho A F W , Foo D , Foo L L , Lim P Z Y , Liew B W , Chua T , Hausenloy D J , Yeo T C , Tan H C , Yip J W L , Chai P , Chan M Y Y , Sia C H 
Published: November 2023

Abstract

Background/introduction
Type 2 myocardial infarction (T2MI), caused by myocardial oxygen supply/demand mismatch without acute thrombotic plaque disruption, makes up 2-25% of reported MI. T2MI may be triggered by conditions such as arrhythmias, anaemia, sepsis, heart failure, but the incidence, outcomes and predictors of poor outcomes post-T2MI requires further study.

Aims
In this study, we characterised the incidence, outcomes and predictors of poor outcomes in T2MI in Singapore.

Methods
We performed an ambidirectional cohort study of 10720 consecutive T2MI patients from January 2012 to December 2018 from the national Singapore MI Registry (SMIR). The primary outcome was major adverse cardiovascular events (MACE; composite of MI, stroke and mortality) within 30 days and 1 year. The secondary outcomes were all-cause mortality, cardiovascular death and stroke.

Results
Of 10,724 patients with T2MI, 3852 (35.9%) had MACE within 30 days and 5947 (51.4%) had MACE within 1 year (Table 1). The incidence of T2MI increased from 20 per 100,000 residents in 2012 to 80 per 100,000 residents in 2017 (Figure 1A). Significant independent predictors of MACE at 30 days on multivariable analysis include age (hazard ratio [HR] 1.01, 95% confidence interval (CI) 1.00-1.01), history of hypertension (HR 1.23, 95% CI 1.06-1.42) or diabetes mellitus (HR 1.32, 95% CI 1.17-1.48), Killip classes 2-4 and left ventricular ejection fraction &lt;50% during hospitalization. Low hemoglobin (Hb) 8-9 (HR 1.42, 95% CI 1.07-1.88) and 10-11 (HR 1.36, 95% CI 1.05-1.76) compared to Hb 14-15, were predictors of MACE at 30 days and Hb &lt;13 showed significant associated with MACE at 1 year. Hb &lt;12 was also significantly associated with all-cause mortality at 1 year, but not cardiovascular death or stroke. Significant predictors of stroke at 1 year included current smoking (HR 1.53, 95% CI 1.04-2.23) and atrial fibrillation (AF) (HR 1.54, 95% CI 1.21-1.97). Troponin levels were not significantly associated with MACE at 30 days or 1 year.

Conclusions
The incidence of T2MI has been increasing since 2012, with generally poor outcomes within 1 year. Predictors of poor outcomes include age, history of cardiovascular risk factors, AF, reduced LVEF during hospitalization, and low hemoglobin. A higher target Hb may be needed post-T2MI, and further research is needed to establish this.
Point-of-care biomarkers of thrombotic status predict spontaneous reperfusion in ST-segment elevation MI and clinical outcomes
Authors: Kanji R , Gue Y X , Memtsas V , Spencer N H , Gorog D A 
Published: November 2023

Abstract

Background
Spontaneous reperfusion, seen in ∼20% of patients with ST-segment elevation myocardial infarction (STEMI), manifests as normal epicardial flow in the infarct-related artery (IRA), with or without ST-segment resolution, before percutaneous coronary intervention (PCI). The drivers mediating this are unknown.

Purpose
We aimed to assess whether the thrombotic profile of patients with and without spontaneous reperfusion differed significantly, and whether such patients had better outcomes.

Methods
We performed a prospective, observational study in consecutive patients presenting with STEMI. Blood samples were taken from a 6 Fr arterial sheath immediately before emergency angiography, before PPCI, after dual antiplatelet therapy loading, but before the administration of heparin or other anticoagulant. Blood samples were tested using a point-of-care global test of thrombotic status, measuring occlusion (OT) and endogenous fibrinolysis (LT) times. Spontaneous reperfusion was defined as IRA TIMI III flow pre-PCI. Patients were followed for major cardiovascular events (MACE; death, myocardial infarction, stroke).

Results
Spontaneous reperfusion was associated with longer OT (435s vs. 366s, p&lt;0.001) and shorter LT (1257s vs. 1616s, p&lt;0.001), lower troponin and better LV function. LT was superior to OT for predicting spontaneous reperfusion (AUC for LT: 0.707, 95% CI 0.661-0.753; AUC for OT: 0.629, 95% CI 0.581-0.677). Amongst patients with spontaneous reperfusion, those with complete, versus partial ST-segment resolution, had longer OT (p=0.002) and shorter LT (p&lt;0.001). Spontaneous reperfusion was unrelated to clinical characteristics or pain-to-angiography times.
Over 4-years, patients with spontaneous reperfusion experienced fewer MACE than those without (4.1% vs. 10.6%, p=0.013), especially in those with both spontaneous reperfusion and complete ST-segment resolution (1.5% vs. 10.1%, p=0.029).

Conclusions
We demonstrate a novel haematological signature in STEMI patients with spontaneous reperfusion, namely reduced platelet reactivity and faster endogenous fibrinolysis, relating to smaller infarcts and improved survival. This indicates a role for modulating thrombotic status early following STEMI-onset, to facilitate spontaneous reperfusion and improve outcomes.Visual abstractThrombotic profile predicts outcome
Association of inflammatory activation with acute stent thrombosis
Authors: Krychtiuk K A , Braeu K , Schauer S , Sator A , Galli L , Gangl C , Roth C , Hengstenberg C , Lang I M , Berger R , Speidl W S 
Published: November 2023

Abstract

Background
Acute stent thrombosis (ST) is a rare but deleterious event. Acute infection and inflammation may lead to activation of the coagulation system and of platelets. Coronary angiography with stent implantation is often deferred because of increased inflammatory markers.

Purpose
The aim of this study was to investigate whether an acute inflammatory state is associated with increased risk of early stent thrombosis.

Methods
Within a prospective single-center registry, the association between pre-procedural acute inflammatory activation, defined as C-reactive protein (CRP) plasma levels &gt;5mg/dL or leukocytes &gt;12 G/L, and occurrence of early stent thrombosis within 30 days after PCI was evaluated.

Results
We included 11327 patients that underwent coronary stenting. 3964 (35%) were treated for acute coronary syndrome (ACS) and 7363 (65%) had chronic coronary artery disease. The number of definite early ST within 30 days was 91 (0.8 %). Leukocyte count and plasma levels of C-reactive protein (CRP) were available in 6880 patients (87 patients with ST). 1715 patients showed signs of an acute inflammatory state as defined by a leukocyte count &gt; 12 G/L or plasma levels of CRP &gt; 5mg/dL. Stent implantation in patients with acute inflammation was associated with significant increased risk for ST (HR 3.01; p&lt;0.0000001) independent of age, gender, kidney function, number and type of stents, presence of multivessel disease, choice of P2Y12 inhibitor and clinical presentation. This was the case in patients with (HR 2.48; p&lt;0.001) and without acute coronary syndromes (HR 3.59; p&lt;0.001). The incidence of ST in patients with ACS with and without signs of inflammation was 2.7% vs. 1.1% (p&lt;0.001) and in patients with chronic coronary artery disease with and without inflammation was 2.3% vs 0.7% (p&lt;0.001)

Conclusions
An acute inflammatory state as defined by a leukocyte count &gt; 12 G/L or plasma levels of CRP &gt; 5mg/dL at time of stent implantation was associated with a significant increased risk of acute ST. In particular in patients with chronic coronary artery disease acute inflammatory activation should lead to a deferral of elective interventions. In patients with ACS and increased inflammatory parameters, in which acute PCI is mandatory, future studies are needed, whether more intensive therapy could reduce risk of early ST in this particular high-risk cohort.
Analysis of immune infiltration and cuproptosis-related genes in acute myocardial infarction
Authors: Xiao Y , Pan R J , An Z H , Liu Q M , Zhou S H 
Published: November 2023

Abstract

Background
Acute myocardial infarction (AMI) is a major global health concern. The identification of key genes associated with AMI and cuproptosis is crucial for developing effective diagnostic and prognostic tools.

Purpose
To identify differentially expressed genes (DEGs) associated with AMI, and investigate their correlation with cuproptosis and immune infiltration to improve diagnosis and prognosis.

Methods
Six datasets (GSE48060, GSE83500, GSE97320, GSE974, GSE19339, and GSE66360) containing normal control and AMI samples were integrated from the Gene Expression Omnibus (GEO) database. DEGs between AMI and control samples were identified and cross-referenced with ferroptosis-associated genes. GO and KEGG analyses were performed to explore the functions and pathways associated with the identified genes. Immune infiltration analysis was also conducted to investigate the correlation between the genes and immune infiltration. An AMI prediction model was constructed using statistical analysis.

Results
Fifteen DEGs were identified, including nine upregulated and six downregulated genes. Among these genes, 11 were found to be associated with cuproptosis, including SLC31A1, PDHB, PDHA1, LIPT1, LIAS, FDX1, DLS1, DLD, DLAT, DBT, and ATP7B. These genes were mainly enriched in the TCA cycle, pyruvate metabolism, glycolysis/gluconeogenesis, and carbon metabolism pathways. Immune infiltration analysis revealed significant differences in macrophages, Th1 cells, Th2 cells, tumor-infiltrating lymphocytes, cytolytic activity, and MHC class 1 between normal and AMI samples. A correlation between these genes and immune infiltration was also observed. The AMI prognostic model constructed had an AUC of 0.61047.

Conclusion
Cuproptosis-related genes (SLC31A1, PDHB, PDHA1, LIPT1, LIAS, FDX1, DLS1, DLD, DLAT, DBT, and ATP7B) may play significant roles in AMI and its immune infiltration. The identified genes and pathways could potentially serve as biomarkers for improving the diagnosis and prognosis of AMI.Flow chart of research designCuproptosis-related AMI genes
In patients with acute myocardial infarction interleukin-8 levels are related to impaired renal function and predict recurrent infarction or death at 1-year follow-up - a case-control study
Authors: Wang Y , Matter M A , Rossi V A , Heg D , Costantino S , Staehli B E , Raeber L , Windecker S , Mach F , Gencer B , Rodondi N , Nanchen D , Levesque M , Ruschitzka F , Matter C M 
Published: November 2023

Abstract

Introduction
Acute myocardial infarction (AMI) induces a surge of inflammatory cytokines. IL-8, secreted by endothelial cells and monocyte-macrophages, rapidly recruits immune cells to the infarcted tissue. Previous studies in chronic kidney disease reported IL-8 to be associated with an increased inflammatory burden. Little is known about the diagnostic and prognostic value of IL-8 plasma levels in patients with AMI.

Purpose
We aimed to explore the diagnostic and prognostic value of IL-8 plasma levels in AMI patients.

Methods
Patients with AMI (STEMI and NSTEMI) were included from the SPUM-ACS cohort selecting a time window &lt;24 h from symptom onset to blood sampling before PCI. Patients with malignancies or on immunosuppressive therapies were excluded. 160 patients with recurrent AMI or death within 1-year follow-up (cases) were compared to 160 counterparts with favorable outcome matched for age, sex, AMI subtype, and pain onset time (controls). 45 healthy blood donors (HD) without cardiovascular disease were added as an age- and sex-matched reference group. Heparin-plasma was used for Mesoscale U Plex cytokine analyses. The median and interquartile ranges (IQR) were compared using the non-parametric Kruskal-Wallis test. Relation of baseline characteristics to IL-8 levels within cases and controls was assessed with linear regression analyses. Kaplan-Meier curves were computed, selecting the cut-off value in consideration of the overall median IL-8 level.

Results
Cases (median=59.5, IQR=112.0 pg/mL) showed higher IL-8 plasma levels than HD (median=38.6, IQR=25.1 pg/mL, p=0.0006, Figure 1). Cases also had higher plasma IL-8 levels compared to controls (median=41.2, IQR=51.7 pg/mL, p=0.0006, Figure 1). Considering the median IL-8 level (50.1 pg/ml) as cut-off, cases with higher IL-8 had higher rates of recurrent MI or all-cause death than those with lower IL-8 levels within one year (log-rank p=0.002, Figure 2) with divergence between the subgroups seen early within the first two months. After correction for possible confounding factors (BMI, hypertension history, dyslipidaemia, diabetes, smoking, use of statins, LDL, Troponin, LVEF, and NT-proBNP), eGFR (estimated glomerular filtration rate) remained the only predictor for increased IL-8 (SRC: -0.178, p=0.016) in AMI patients.

Conclusions
In patients with AMI increased IL-8 levels predict subsequent MI or death at one-year follow-up. Lower eGFR is related to elevated IL-8 levels. Patients with AMI may thus profit from early IL-8 blocking therapies, particularly in the setting of impaired renal function.
Heterogeneity of plaque burden natural history within individual human coronary atherosclerotic plaques is based on local endothelial shear stress: insights for culprit areas and clinical events
Authors: Wentzel J J , Papafaklis M , Antoniadis A , Takahashi S , Cefalo N , Cormier M , Saito S , Coskun A , Stone P H 
Published: November 2023

Abstract

Background
Patterns of local endothelial shear stress (ESS) are heterogeneous along the course of individual coronary artery plaques. It is unknown how this heterogeneity affects the local natural history of plaque burden (PB) over time.

Objectives
To determine the effect of local ESS patterns along the course of coronary plaques at baseline on the heterogeneity of subsequent PB progression, regression, and quiescence in human coronary arteries and its link to clinical events.

Methods
302 patients from the PREDICTION study were included in the study. The PREDICTION study was an anatomic natural history followup study of patients treated for an acute coronary syndrome (ACS) performed in 15 Japanese clinical sites, as previously published [1]. Invasive imaging was performed at baseline and, per protocol, at 6-10 months follow-up. Arterial geometry and ESS were derived from angiography/intravascular ultrasound-based vascular profiling. Plaques were identified as regions with plaque thickness &gt; 0.5 mm in at least 3 consecutive 3-mm segments. Plaque progression was defined as change in PB (plaque area/total vessel area*100%) PB &gt;+5% increase, regression as &lt;-5% decrease, and quiescence as no change. The location of each sequential 3-mm segment along the plaque was related to the minimum lumen area (MLA). Performance of PCI in followup was assessed relative to the magnitude of PB change over time.

Results
661 plaques (5,658 3-mm segments) from 591 coronary arteries were identified. 56% of 3-mm segments per plaque manifested PB progression, 60% PB regression, and 96% quiescence, and the presence and number of these PB changes were significantly related to plaque length (p&lt;0.002). PB change &gt;20% was associated with low ESS (0.75±0.31 Pa) and marked regression (PB change &lt;-20%) with high ESS (3.94±0.04 Pa) (p&lt;0.001, Figure 1 right panel). 3-mm segments exhibiting substantial PB progression were located along the full length of the plaque, and seldom at the MLA (p=0.874, (Figure 1 left panel), while substantial PB regression was significantly located at the MLA (p&lt;0.001). With increasing ∆PB progression in individual 3-mm segments, a significant increase in performance of PCI was observed (p=0.012, Figure 2).

Conclusions
PB natural history of 3-mm segments within an individual plaque is heterogeneous, driven by local ESS, with substantial plaque progression/luminal encroachment developing along the entire course of the plaque, and typically not near the MLA. PCI was associated with the magnitude of PB progression/luminal encroachment, regardless of where the progression occurred.Figure 1Figure 2
Triglyceride levels predict high-risk coronary artery plaque progression in asymptomatic patients with type 2 diabetes and normal LDL cholesterol
Authors: Heinsen L J , Pararajasingam G , Andersen T , Auscher S , Sheta H , Lambrechtsen J , Egstrup K 
Published: November 2023

Abstract

Background
Type 2 diabetes mellitus (T2D) is associated with an increased risk of coronary artery disease (CAD) and a significant residual risk remains despite management of conventional risk factors.

Purpose
The purpose of the present study was to assess the association of triglycerides and high-risk plaque progression in patients with asymptomatic T2D without known CAD.

Methods
Asymptomatic patients with T2D and no history of CAD were studied with serial computed tomography angiography with an inter-scan interval of 13 ± 0.8 months. The total atheroma volume (TAV), and plaque composition (dense calcium, fibrous, fibrous-fatty, and necrotic core plaque) were assessed at baseline and at follow-up. Lipid status was assessed at baseline and after a one-year follow-up. Patients were divided into two groups depending on progression in triglyceride (TG) levels (TG+) and regression of TG levels (TG-).

Results
Of the 261 patients who were enrolled, 209 patients (157 men and 52 women) were included in the final analysis. Based on changes in TG levels, 107 patients were categorized as (TG+) and 102 patients were categorized as (TG-). The mean age was 62 ± 10 years, and the mean diabetes duration was 11 ± 8 years. At baseline, 76 % of the patients received lipid-lowering treatment, and low-density lipoprotein (LDL) cholesterol was 2.0 ± 0.8 mmol/L. A significantly higher progression of TAV was observed in patients with TG+ compared to TG- (50.2 ± 144.3 vs. -28.5 ± 176.9 mm3, P&lt;0.001). This observation was primarily driven by an increase of fibrous fatty plaque (8.6 ± 41.2 vs. -12.8 ± 39.2 mm3, P&lt;0.001) and necrotic core plaque (-3.9 ± 51.4 vs. -23.7 ± 71.8 mm3, P=0.002). Furthermore, an increase in TG levels predicted rapid plaque progression independent of LDL and other risk factors (OR 1.36, 95% CI; 1.02 – 1.81, P=0.04).

Conclusion
Changes in TG levels are associated with the progression of total and high-risk plaque volumes in asymptomatic patients with T2D and well-controlled LDL cholesterol.Low attenuation plaque vs. triglycerides
Influence of wall shear and structural stress on plaque progression of different phenotype in human coronary arteries
Authors: Wentzel J J , Tziotziou A , Hartman E , Korteland S , Van Der Steen A F W , Daemen J , Akyildiz A 
Published: November 2023

Abstract

Introduction
Atherosclerotic plaque progression is affected by local wall shear stress (WSS), .i.e. the frictional force of the blood at the vessel wall [1,2]. However, the blood pressure also induces stress inside the vessel wall (wall stress, WMS) and is mainly studied for plaque rupture [3]. Little is known on the impact of WMS on plaque progression.

Purpose
In order to have a comprehensive understanding of the involvement of the biomechanical factors (WSS and WMS) in atherosclerotic artery disease, we studied the individual and combined effects of WMS and WSS in plaque free as well as in atherosclerotic coronary segments.

Methods
Forty non-stented, non-culprit human coronary arteries (IMPACT study) were imaged with near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) at the baseline and after 12 months [3]. The 2D and 3D lumen, vessel wall and lipid-rich necrotic core (LRNC) geometries were reconstructed based on the co-registration of NIRS-IVUS and OCT. WSS was computed with Computational Fluid Dynamics [3]. The WMS on the peri-luminal region was calculated via ABAQUS with hyperelastic material models [4] using intraluminal pressure of 120mmHg. The vessels were divided into 1.5mm/45° sectors. In each sector wall growth was quantified as plaque burden (plaque area/total vessel area*100%) change over time. Plaque was defined as wall thickness &gt; 0.5 mm. The sectors were categorized as "plaque with lipid rich necrotic core (LRNC)", "plaque w/o lipid rich necrotic core (LRNC)", or "plaque free wall". The individual and combined effect of WSS and WMS on plaque progression was evaluated using Linear Mixed Model in SPSS and all stress metrics were divided into artery-based tertiles.

Results
Vessel sectors exposed to low WSS at baseline demonstrated a higher plaque burden increase over the follow up period compared to the vessel sectors exposed to mid or high WSS (Fig.1), which was significantly different for all the 3 categories (Plaque free wall, Plaque without LRNC, Plaque with LRNC). Vessel sectors exposed to increasing WMS demonstrated increasing plaque progression (Fig.1) Sectors that were simultaneously exposed to low WSS and high WMS revealed the highest change in plaque size and in particular in plaque sectors that were lipid rich (Fig.2).

Conclusion
Our findings suggest that the local atherosclerotic disease progression in coronary arteries is not only associated with the well-known WSS, but also with WMS. Moreover, our results show that there is an complex interplay between WSS, WMS and plaque composition, such that lipid rich plaques exposed to low WSS and high WMS demonstrated the highest plaque progression.Figure 1Figure 2
A long-term prognostic factor for cardiovascular risk in patients with chest pain without diabetes mellitus and significant coronary stenosis
Authors: Rha S W , Choi B G , Choi S Y , Byun J K , Cha J , Hyun S , Park S , Kim J B , Choi C U 
Published: November 2023

Abstract

Background
Chest pain is the most common symptom of coronary artery disease (CAD); diabetes mellitus (DM) is a well-known single largest risk factor for cardiovascular diseases and survival worldwide. So, the impact of CAD and DM on long-term clinical effects is reported widely. This study aimed to evaluate the long-term prognostic factor for major adverse cardiac and clinical events (MACCE) in patients with chest pain without DM and CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation test.

Methods
A total of 1,046 patients with chest pain without DM and significant CAD who underwent CAG and ACH tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. All subjects were followed clinically for up to 5 years.

Results
Coronary spasm (CAS) seems the most common cause of chest pain. However, long-term MACCE of CAS is not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a repeated chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year follows, MACCE has occurred 7.3%, including recurrent angina of 6.9%. Dyslipidemia, mild to moderate CAD, and the use of aspirin/nitrates are associated with long-term MACCE.

Conclusions
Among the patients with chest pain without DM and significant CAD, the occurring major adverse cardiac events, including death, MI, and de novo CAD, are rare, but recurrent angina is still a challenging problem who had the treatment by anti-anginal medications.