bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apixaban versus Warfarin in Patients with Left Ventricular (LV) Thrombus, a prospective randomized trial
Authors: Alcalai R , Rashad R , Butnaru A , Moravsky G , Leibowitz D 
Published: November 2020

Abstract

Background
Patients with acute myocardial infarction (MI) have an elevated risk of stroke, mostly due to left ventricular (LV) thrombus formation, which typically occur within the first 2 weeks following an anterior MI. Currently the recommended management of LV thrombus after acute MI is anticoagulation with vitamin K antagonist. To date, there are no prospective data on the use of direct oral anticoagulants (DOACS) for stroke prevention in the setting of LV thrombus.

Aim
To assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI.

Methods
The study is a prospective, randomized, multi-center open label trial comparing apixaban (at a dose of 5 mg twice daily) with s.c enoxaparin 1mg/kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months in patients with LV thrombus detected by echocardiography 3 to 14 days after acute MI. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation as assessed by 2D echocardiogram. Secondary outcomes were stroke or systemic embolism, major bleeding and death from any cause.

Results
25 patients have been enrolled to date in 3 medical centers, 13 were randomized to apixaban and 12 to warfarin. Mean age was 59.8±10.7 and 19 (76%) were males with no difference between the study groups. Mean LV thrombus size at enrollment was 24X15 mm in the apixaban group and 19X14 in the warfarin group (p=NS). After 3 months of treatment thrombus completely resolved in all patients in the warfarin group and in 12 of 13 in the apixaban group. In one patient in the apixaban group who had a very large thrombus of 40x20mm size upon enrollment the thrombus size was reduced significantly to 20x12 after 3 months. No death, stroke or systemic embolism was documented in either group. There were two patients with major bleeding in the warfarin group, one had sub-arachnoid hemorrhage after 2 months and anticoagulation was stopped, and another had GI bleeding after 1 month and was switched to enoxaparin. One patient in the warfarin group refused to continue the treatment after 3 weeks. No major bleeding events were recorded in the apixaban group and all patients completed 3 months of treatment.

Conclusions
Our preliminary results indicate that apixaban is a safe and effective treatment for patients with LV thrombus post anterior wall MI.

Funding Acknowledgement
Type of funding source: None
Epigenetic interaction of miRNA-26a and P2Y12 gene DNA methylation on platelet reactivity under clopidogrel and their impact to the coronary flow after primary PCI in STEMI
Authors: Syam H , Sukmawan R , Dharma S , Alaztha G , Giyantini A , Prakoso R , Rudiktyo E , Zamroni D , Rejeki V.G , Juzar D.A , Rahardjo S.B , Adriantoro H , Santoso A 
Published: November 2020

Abstract

Background
Epigenetic factors such as miRNA-26A and P2Y12 DNA methylation play role in pathophysiology of cardiovascular disease. Clopidogrel-resistance is associated with worse cardiovascular outcome. The interactions between the expression of platelet miRNA-26a and P2Y12 DNA methylation to clopidogrel resistance and post procedural TIMI flow in STEMI patients undergoing primary PCI is unclear.

Purpose
To define interaction of epigenetic factors micro-RNA (miRNA)-26a expression and P2Y12 gene DNA methylation to the platelet reactivity under clopidogrel therapy, and their impact on the coronary flow after Primary PCI in patients with STEMI.

Methods
We studied STEMI patients who underwent primary PCI, receiving 600 mg loading dose of clopidogrel. Platelet reactivity assessed by VerifyNow P2Y12. Realtime PCR was performed to measure the expression of platelet miR-26a and DNA methylation of P2Y12 gene. Postprocedural epicardial coronary flow was assessed semi quantitatively.

Results
There were 100 patients were recruited. Among them, 59% have high miRNA-26a platelet expression, 60% had no methylation in their P2Y12 gene, and 27% had high platelet reactivity index under clopidogrel therapy. There was association between high miR-26a expression and reduced platelet inhibition under clopidogrel (OR 4.2, p&lt;0.01), but not with DNA methylation of P2Y12 gene. High platelet reactivity index under clopidogrel therapy was associated with suboptimal coronary flow after primary PCI in STEMI patients (OR 3.3, p&lt;0.05).

Conclusions
High miRNA-26a platelet expression, but not DNA methylation of P2Y12 gene, in patients with acute STEMI have significant association with high platelet reactivity under clopidogrel therapy. Furthermore, high platelet reactivity under clopidogrel is associated with suboptimal coronary flow in STEMI patients undergoing primary PCI.

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): Harapan Kita Honor Research Grant
Long-term differences in clot formation and endothelial function between STEMI patients with occlusion of infarct-related artery and those with spontaneous reperfusion
Authors: Kalinskaya A , Dukhin O , Uzhakhova K.H , Shpektor A , Vasilieva E 
Published: November 2020

Abstract

Introduction
Enhanced activation of endogenous fibrinolysis in ST-elevation myocardial infarction (STEMI) patients is the main cause of spontaneous reperfusion of the infarct-related artery (IRA) in the acute period. Whether this enhanced activation remains in the deferred period of myocardial infarction remains unclear.

Purpose
The main purpose of our work was to analyze the process of clot formation and endogenous fibrinolysis in patients with a history of myocardial infarction.

Methods
We included 51 patients with a history of myocardial infarction (median, 35 months). Of these patients, 19 had a spontaneous reperfusion of the IRA (SR group) during the index event, and 32 had a total occlusion of the IRA (occlusion group). We assessed parameters of clot formation and endogenous fibrinolysis using thromboelastometry and a thrombodynamics assay. We analyzed endothelial function using the flow-mediated dilation test (FMD).

Results
The process of clot formation was more active in the occlusion group than in the SR group. Thus, the initial, mean, and total clot velocity times were significantly higher in the occlusion group than in the SR group: 57.2 mcm/min vs. 60.25 mcm/min; 28,1 mcm/min vs. 31.9 mcm/min; and 28.7 mcm/min vs. 31.9 mcm/min, respectively; p&lt;0.01. The clot size was much bigger in the occlusion group than in the SR group (1,190.5 mcm vs. 1,315 mcm; p&lt;0.01). No differences in endogenous fibrinolysis parameters were observed between the two groups. Endothelium function was better in the SR-group than in the occlusion group (FMD 17.4% vs 11.3%, p&lt;0.01).

Conclusion
STEMI patients with occlusion of the IRA and those with spontaneous reperfusion remain different in clot formation and endothelial function even after many years.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Russian Science Foundation grant
Coronary plaque instability is associated with inflammatory activity of visceral adipose tissue and carotid artery: a prospective pilot F-18 FDG PET/CT study
Authors: Pahk K , Kwon H.W , Eo J.S , Seo H.S , Kim S 
Published: November 2020

Abstract

Background
Dysfunctional Visceral adipose tissue (VAT) secretes pro-inflammatory cytokines and promotes inflammatory cell infiltration into VAT thereby boosting insulin resistance and systemic inflammation which eventually lead to increased risk of cardiovascular disease (CVD). F-18 FDG PET/CT is well known to reflect the inflammatory activity of classically activated (M1) macrophage.

Purpose
We hypothesized that F-18 FDG PET/CT could reflect the inflammatory activity of dysfunctional VAT and carotid artery which were associated with coronary plaque instability.

Methods
A total of 90 participants were enrolled in this prospective study. F-18 FDG PET/CT was performed in 32 participants with acute myocardial infarction (AMI) within a week of disease onset, 33 participants with stable coronary artery disease (CAD), and 25 control subjects. Maximum standardized uptake value (SUVmax) was calculated in VAT, subcutaneous adipose tissue (SAT), spleen, and bone marrow (BM). Target-to-background ratio (TBR) was calculated in right carotid artery and right jugular vein.

Results
The SUVmax of VAT and the TBR of right carotid artery were highest in patients with AMI, intermediate in patient with stable CAD, and lowest in control subjects. Systemic inflammation surrogate markers such as high-sensitivity C-reactive protein, spleen SUVmax were also showed similar pattern like the SUVmax of VAT and the TBR of right carotid artery. Furthermore, multiple linear regression analysis showed that the SUVmax of VAT and spleen SUVmax were independently associated with the TBR of right carotid artery.

Conclusions
F-18 FDG PET/CT could reflect the synchronized systemic inflammation in VAT and carotid artery which could affect the coronary artery instability. Furthermore, our findings offer clinical insights into risk stratification, monitoring of therapy, and physiological changes in the development of CAD.

Funding Acknowledgement
Type of funding source: None
Low-dose colchicine in patients treated with percutaneous coronary interventions for myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)
Authors: L'Allier P.L , Tardif J.C , Kouz S , Waters D.D , Diaz R , Maggioni A.P , Pinto F.J , Gamra H , Kiwan G.S , Berry C , Lopez-Sendon J.C , Koenig W , Blondeau L , Guertin M.C , Roubille F 
Published: November 2020

Abstract

Background/Introduction
Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent anti-inflammatory medication that was shown to significantly lower the risk of ischemic cardiovascular events compared to placebo among subjects with a recent myocardial infarction (MI) in the main COLCOT trial. Patients treated with percutaneous coronary intervention (PCI) after MI represent an important subpopulation that may derive particularly important benefits from colchicine.

Purpose
To assess the impact of low-dose colchicine on cardiovascular events in subjects treated with PCI for an index MI.

Methods
We performed an international, randomized, double-blind trial involving patients recruited within 30 days after a MI (main COLCOT trial; n=4745). In this trial, patients were eligible if they had a confirmed myocardial infarction within 30 days before enrollment, had completed any planned percutaneous revascularization procedures and were treated medically according to national guidelines that included the intensive use of statins. Subjects were randomly assigned to receive oral colchicine 0.5 mg once daily or matching placebo. Among the entire COLCOT study population, 4408 subjects were treated with PCI for the index MI and form the COLCOT-PCI study population. We analyzed the time to the first positively adjudicated event of the composite of CV death, resuscitated cardiac arrest, acute MI, stroke or urgent hospitalization for angina requiring coronary revascularization (primary endpoint).

Results
In the main COLCOT trial, low-dose colchicine led to a significantly lower risk of the primary endpoint (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; p=0.02). In the COLCOT-PCI subpopulation, low-dose colchicine was associated with a large reduction in the risk of a primary endpoint event (hazard ratio, 0.72; 95% confidence interval [CI], 0.57 to 0.92; p=0.008). The hazard ratios for individual components of the composite primary endpoint were 0.71 (95% CI, 0.37 to 1.33) for death from cardiovascular causes, 0.84 (95% CI, 0.26 to 2.75) for resuscitated cardiac arrest, 0.90 (95% CI, 0.66 to 1.21) for myocardial infarction, 0.25 (95% CI, 0.08 to 0.76) for stroke, and 0.42 (95% CI, 0.25 to 0.71) for urgent hospitalization for angina requiring coronary revascularization.

Conclusion
Low-dose colchicine markedly reduces the risk of ischemic cardiovascular events in patients treated with PCI for their index MI.

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): Government of Quebec and Canadian Institutes of Health Research
Gut microbiota profile of patients with acute coronary syndrome, effect of the most frequent comorbidities
Authors: Martin De Miguel I , Fernandez A.I , Lozano N , Gutierrez-Ibanes E , Sanz Ruiz R , Diez-Delhoyo F , Vazquez S , Reigadas E , Garcia De Viedma D , Elizaga Corrales J , Fernandez-Aviles F.J , Bermejo J 
Published: November 2020

Abstract

Introduction
Gut microbiota dysbiosis may modify the inflammatory state, which could trigger the development of acute coronary syndrome (ACS). Moreover, cardiovascular risk factors may alter the microbiota profile involved in ACS development.

Purpose
To address the potential role of alterations in microbiota as triggers of ACS and their cardiovascular comorbidities in patients with ACS.

Methods
Patients admitted for ACS were prospectively included. Stool samples were collected in the first 24 hours after admission. For microbiota analysis, Operational Taxonomic Unit (OTUs) method from V4 amplicon of 16S rRNA was employed. Identification, quantification, clusterization and taxonomic classification of OTUs was performed in Mothur through RDP database. ACS patient microbiota was compared with the microbiota of 10 healthy controls. The microbiota changes analyses were evaluated with ANOVA analysis.

Results
41 ACS patients with a mean age of 62±11 years old were included. 34 (83%) were males, 17 (42%) suffered arterial hypertension, 18 (44%) dyslipidaemia, 37 (90%) diabetes mellitus and 16 (39%) were current smokers. A multidimensional scaling model allowed us to clearly delineate different clusters between patients with ACS and healthy controls. This was due to important differences in the main phylum of the human microbiota (Table) Bacteroidetes, Firmicutes / Bacteroidetes ratio and Actinobacteria. In addition, there was a significant decrease in protective Cyanobacteria (p=0.03) and Proteobacteria (p=0.04) in men. Hypertensive and dyslipidaemic patients had a significantly higher amount of Firmicutes, Clostridia (p=0.05) and Erysipelotrichia (p=0.03) classes, respectively. Patients with diabetes had significantly less protective Proteobacteria (p=0.002) and Spirochaetes (p=0.04). Finally, smoking was associated with a significant increase in pathogenic Lentisphaerae (p=0.04).

Conclusions
Patients with ACS have clear pathogenic alterations of their gut microbiota. Classical cardiovascular risk factors induce different patterns of gut dysbiosis.
Gut microbiota profile.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Carlos III Health Institute
Pericoronary adipose tissue attenuation (PCAT) is associated with high-risk atherosclerotic plaque and subsequent acute coronary syndrome in patients with stable coronary artery disease
Authors: Yuvaraj J , Lin A , Nerlekar N , Munnur R.K , Cameron J , Nicholls S.J , Wong D.T.L 
Published: November 2020

Abstract

Background
High-risk plaque (HRP) features detected on computed tomography coronary angiography (CTCA) are associated with subsequent development of acute coronary syndrome (ACS). Pericoronary adipose tissue attenuation (PCAT) is a novel CT-derived non-invasive marker of coronary inflammation. The association between PCAT, HRP and outcomes is unknown.

Purpose
To evaluate the association between high-risk plaque HRP characteristics, ACS and PCAT attenuation as a surrogate marker of coronary inflammation.

Methods
Patients with stable chest pain referred for CTCA between 2011 and 2013 with outcome data were included. Patients with HRP were propensity matched to patients without HRP. PCAT-RCA and PCAT-lesion were assessed using semi-automated software (AutoPlaque version 2.0). PCAT-RCA was measured around the proximal 10–50 mm of the right coronary artery (RCA). PCAT-lesion was measured around the HRP or lesion with highest-grade stenosis in patients without HRP.

Results
78 patients (67±10 years, 67% males) included 41 (52.6%) patients with HRP. Median PCAT-RCA was higher in HRP patients than non-HRP patients (−80.4 HU [IQR −86.1, −76.5] vs. −86.3 HU [IQR −92.2, −77.0], p=0.02). PCAT-Lesion was not significantly different between HRP and non-HRP patients (−78.7 HU [IQR −84.4, −73.4] vs. −82.8 HU [IQR −91.1, −75.4], p=0.16). More patients with HRP developed a subsequent ACS (24.4% vs. 5.4%, p=0.008). HRP patients who experienced an ACS demonstrated a higher PCAT-RCA (−76.6 HU [IQR −81.3, −72.4] vs. −82.6 HU [IQR −87.4, −78.0], p=0.018) and PCAT-lesion (−74.3 HU [IQR −77.1, −68.4] vs. −80.7 HU [IQR −84.8, −74.9], p=0.04) compared to those who did not experience an ACS.

Conclusion
PCAT attenuation is elevated in stable CAD patients with HRP features. Measures of periarterial inflammation were also more evident in HRP patients who develop ACS, indicating a potential contribution to vulnerability. The implications for integration of these measures in clinical practice require further investigation.

Funding Acknowledgement
Type of funding source: None
Sex-related differences in geometry, plaques and shear stress related plaque-progression in human coronary arteries
Authors: Wentzel J.J , Papafaklis M , Antoniadis A , Takahashi S , Cefalo N.V , Cormier M , Saito S , Coskun A , Stone P.H 
Published: November 2020

Abstract

Background
Atherosclerosis manifests itself differently in women compared to men. Since the pathophysiology of atherosclerotic plaques is known to be related to endothelial shear stress (ESS), it was hypothesized that female compared to male coronary arteries demonstrate a different i) ESS and ii) ESS related plaque progression.

Methods
1183 coronary arteries (male/female:944/239) from the PREDICTION trial were studied for differences in vessel geometry (plaque area (PA) and lumen area (LA)), hemodynamic parameters (flow, minimal ESS over 90 degree arc (minESS) and maximal ESS over 90 degree arc (maxESS)) and ESS related plaque progression (1 year follow up) measured as change in maximal plaque thickness and plaque burden comparing female to male arteries. Arterial geometry and ESS measures were derived from IVUS-based vascular profiling and reported per 3 mm segments. For plaque progression studies minESS was subdivided into low, mid and high (&lt;1,1–1.7,&gt;1.7 Pa). To test statistical differences univariate anova or linear mixed models were used.

Results
13030 3mm-segments (m/f: 10.465/2565) were analyzed. Female compared to male coronary arteries were smaller and presented with less plaque area (Table I). No differences in average ESS, minESS and maxESS were found for male versus female coronary arteries, partly explained by the lower flows in female arteries (Table I). The ESS-related plaque growth showed for both sexes an significant inverse relationship between maximal wall thickness (Figure, left) and plaque burden (Figure, right) and the three minESS categories. However, ESS-related plaque growth was not different for male vs females.

Conclusion
Our data demonstrated that vessel and plaque size are smaller in female compared to male coronary arteries. However, ESS and ESS related plaque progression were not different.
Shear stress related plaque progression

Funding Acknowledgement
Type of funding source: None
East Asian variant aldehyde dehydrogenase Type 2 genotype exacerbates myocardial ischemia/reperfusion injury in men among patients with ST-segment elevation myocardial infarction -sex differences-
Authors: Ishida T , Arima Y , Mizuno Y , Harada E , Yasue H , Tsujita K 
Published: November 2020

Abstract

Background
Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes including those generated during ischemia/reperfusion (I/R) injury in acute myocardial infarction. The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined whether ALDH2*2 exacerbates I/R injury in Japanese patients with acute ST-segment elevation myocardial infarction (STEMI) utilizing Mendelian randomization.

Methods and results
The study subjects comprised 248 Japanese patients with STEMI (187 men and 61 women, mean age 67.1±11.5) who underwent successful primary percutaneous coronary intervention. Of these patients, 129 (52.0%) were the carriers of ALDH2*2 and 119 (48.0%) those of wild ALDH2*1/*1 on genotyping by direct application of the TaqMan polymerase chain system. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit in the ALDH2*2 group. However, the peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, were significantly higher (a median 234.0 vs 150.0 U/L, P&lt;0.001 in the ALDH2*2 group. Furthermore, the peak CKMB levels were higher in ALDH2*2 group in men (a median 2 75.0 vs 144.9 U/L, P&lt;0.001) but not in women (P=0.855) and there was a significant interaction between sex and ALDH2*2 on I/R injury (χ2=8.362, P=0.004).

Conclusions
The peak plasma levels of CKMB were higher in STEMI patients with ALDH2*2 than in those with ALDH2*1/*1 among men but not women. These findings identified deficient ALDH2 activity to be targeted for treatment of STEMI specifically in men with ALDH2*2.
Visual overview

Funding Acknowledgement
Type of funding source: None