bluuebunny/crossref_metadata_2025_split huggingface dataset:
P6010Deficiency in milk fat globule-epidermal growth factor 8 delays thrombus resolution
Authors: Hofbauer T M , Alimohammadi A , Altmann J , Sharma S , Ondracek A S , Sadushi-Kolici R , Seidl V , Mangold A , Lang I M 
Published: October 2019

Abstract

Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the obstruction of pulmonary vessels by organized thrombotic and fibrotic lesions. Efferocytosis refers to the engulfment of apoptotic cells (ACs) by phagocytes, a process that is facilitated by bridging proteins. Milk fat globule-epidermal growth factor 8 (MFG-E8) connects phosphatidylserine on ACs with integrin alpha-v beta-III on phagocytes. MFG-E8-deficient mice develop auto-immune disease closely resembling systemic lupus erythematosus. In humans, decreased MFG-E8 levels were observed in patients with coronary heart disease and chronic obstructive pulmonary disease. Whether defective efferocytosis is involved in failure to resolve thrombi in CTEPH remains unknown.

Purpose
We aimed to assess whether deficiency in MFG-E8 is responsible for of chronic non-resolving thrombosis in CTEPH.

Methods
We employed a murine model of chronic thrombosis by inferior vena cava ligation, in MFG-E8 knockout (KO) or wild-type (WT) mice to assess thrombus formation and resolution. Thrombus size at days 3, 7, 14 and 28 after ligation was assessed using either histologic trichrome stainings (n=4–13 per group and time point) or in vivo high-frequency ultrasound (n=10 per group and time point). We furthermore recruited CTEPH patients (n=60, 53% female, mean age 56±11 years) and sex- and age-matched healthy controls for measurement of MFG-E8 plasma levels using ELISA. In CTEPH patients, hemodynamic measurements were performed. Human lung specimens harvested during surgery for CTEPH or from healthy controls, and isolated monocytes from whole blood of CTEPH patients or controls were analyzed using RT-qPCR.

Results
We observed substantially increased thrombus volume in MFG-E8 KO mice compared to WT, which persisted until day 14 after ligation. In human CTEPH patients, MFG-E8 in plasma was increased compared to healthy controls. Similarly, CTEPH monocytes displayed higher concentrations of MFG-E8 mRNA. Conversely, MFG-E8 expression of CTEPH pulmonary artery specimens was downregulated. No correlations between MFG-E8 levels and hemodynamic parameters were observed.

Conclusion
MFG-E8 plays an important role in thrombus resolution. In CTEPH, dysregulation of efferocytosis via impaired MFG-E8 expression in the pulmonary arteries, might drive persistence of thrombus in pulmonary arteries. The absence of a correlation between MFG-E8 and hemodynamic measures argues against pressure as a confounder of the observation.
P6012Active selexipag metabolite MRE-269 increases endothelin receptors in pulmonary artery smooth muscle cells
Authors: Maruyama H , Sakai S , Ieda M 
Published: October 2019

Abstract

Background
The pathology of pulmonary arterial hypertension (PAH) indicates the abnormal outgrowth of pulmonary artery smooth muscle cells (PASMCs) of the media. Abundant expression of endothelin 1 (ET-1) is observed in vessels of PAH, and has been considered to play a pathogenic role. There are several endothelin receptors including ETA, ETB. Compared to ETA, ETB mRNA is less expressed in PASMCs from control individuals, and is reported to be increased in those from PAH patients. However, how ETB is involved in PAH remains unclear. Selexipag, a non-prostanoid IP receptor agonist, was recently authorized for treating PAH. Compared to selexipag, the active metabolite MRE-269 has a higher affinity for the IP receptor. Initial combination therapy come to be accepted as a standard strategy for this disease, although the interaction of each drug has not been discussed enough.

Purpose
To assess the effect of selexipag on ET-1 receptors in PASMCs.

Methods
We stimulated purchased human PASMCs and endothelial cells by MRE-269 (300 nM), ET-1 (100 nM) or combination of them in vitro. Quantitative PCR was performed to quantify mRNA expressions. Cell proliferation was assessed by CCK8 cell proliferation assay kit. BQ123, A192621, bosentan was used as blocker against ETA, ETB, or both, respectively.

Results
In PASMCs, MRE-269 increased ETA and ETB expressions 2- and 7-fold, respectively. On the other hand, it increased ETB 1.2-fold in pulmonary artery endothelial cells; ETA was not detected in those cells. After pretreatment by MRE-269, ET-1 accelerated the proliferation of PASMCs. A192621 and bosentan abrogated this proliferation. In contrast, BQ123 did not abrogate it.

Conclusions
In PASMCs, active selexipag metabolite MRE-269 increases ETB more strongly than ETA, resulting in accelerated cell proliferation by ET-1 predominantly via ETB. These data call for further study focused on the choice of ET-1 receptor antagonists in the case of combination therapy with selexipag.
P6015Histological pattern of penetrating His bundle division: implications for atrioventricular conduction damage during and following transcatheter aortic valve implantation
Authors: Cabrera J A , Porta-Sanchez A , Nunez Pernas D , Rubio J M , Navarro F , Salvador-Montanes O , Macias Y , Nevado-Medina J , Sanchez-Quintana D 
Published: October 2019

Abstract

Background
Severe damage to the atrioventricular conduction system is one of the most common complications of transcatheter aortic valve implantation (TAVI) and can be linked to important comorbidity, increased healthcare expense, need for long-term monitoring and pacemaker implantation.

Purpose
To provide a detailed description of the His bundle (HB) arrangement within the left ventricular outflow tract.

Methods
We examined by dissection techniques and histological sections the course of the AV conduction axis (penetrating, non-branching and branching HB) in relation with the membranous and muscular interventricular septum in 57 structurally normal human heart specimens (48 males, 77±7 years)

Results
The AV conduction axis is located along the inferior edge of the membranous septum (MS). The MS is divided into AV and interventricular components and is located at the base of the interleaflet triangle between the right and non-coronary leaflets of the aortic valve. The conduction axis enters the AV component of the MS and is encircled by the fibrous tissue of the central fibrous body to reach the left ventricular outflow tract. The MS showed in cadaveric hearts variable dimensions in length (4.6±1.5 mm) with a range bewteen 1 to 9mm. In 17.5% of specimens the MS length was ≤2 mm. After penetrating the AV membranous septum it has a non-branching component that in 85.5% of cases runs only for a short distance (1–3 mm) along the septal crest before giving rise to the fascicles of the left bundle (LB) on the septal surface (Type A). The most anterior fibers of the LB originate at the end of the branching portion located underneath the inferior edge of the MS. In 5 hearts (9%) the HB division was found before it reached the interventricular MS (Type B) and in 3 cases (5.5%)2–3.5 mm distal to the crest (Type C). 22 hearts (49%) were shown to have a relatively left-sided deviation of the AV bundle with the anterior part of the bundle closely related to the nadir of attachment of the right coronary leaflet of the aortic valve. In the remaining 51% of hearts, the bundle coursed centrally or with a right-sided deviation. The HB measures were (mm, mean±SD (range)): length: 3±0.6 (2–4.5), width: 3.7±1.4 (2.5–5.6), thickness: 1.4±0.5 (0.5–2.2), HB to endocardium: 0.7±0.3 (0.2–1.5).
His bundle position types

Conclusions
A shorter membranous septum length, the variable HB dimensions and the left-sided deviation of the AV conduction axis are extremely relevant anatomic features that are linked to the frequent injury to the HB branch or complete AV block following TAVI.
P6135Improving detection of AF: insights from real world screening programme
Authors: Khan S , Butt H , Khokhar A , Orlowski A , Porter B , Unger-Graeber B , Khan S 
Published: October 2019

Abstract

Background
AF related stroke places a significant burden on individuals, carers and health and social care systems. The observed prevalence of AF in populations is often lower than expected and this results in high rates of AF diagnosis at the time of the stroke event. Opportunistic screening for AF in at risk populations is recommended by ESC, however, is often missed due to time constraints and lack of expertise. Technological advancements such as m-health ECG monitors can aid in the diagnosis of AF with improvements in timely risk assessment and initiation of protective anticoagulation.

Purpose
The purpose of this study was to determine whether introduction of a suite of m-health tools including electronic patient record based tools and smart phone based ECG recording could improve the rates of AF detection and subsequently reduce the rate of AF related strokes.

Methods
The study was conducted in a city region with a population of around 300 000, served by 48 primary care practices. The project involved a three staged approach; education and support for primary care staff, creating an “at-risk” register on primary care electronic patient record for those over 60 or with relevant co-morbidities associated with electronic prompts for screening and a standardized assessment template and the roll-out of smart phone based single-lead ECG monitors to facilitate rhythm checks. The population was followed over a 4 year period to monitor rates of AF diagnosis, anticoagulation and stroke rates.

Results
The study population were male (53%), aged between 30–39 (22.4%) and were of white ethnicity (40%). At baseline, in 2014, the prevalence of AF was 0.89% (2492 individuals). By 2018, this had increased to 1.1% (3328 individuals) with on average 40 new diagnoses of AF compared to 26 in the baseline period (see figure).Anticoagulation prescription within 30 days of diagnosis increased from 29.80% to 50.00% whilst prescription of antiplatelet monotherapy within same time period decreased from 12.73% to 6.4%. This was also associated with a reduction in the proportion of strokes seen in the population secondary to AF with 35% (n=143) of strokes secondary to AF in 2014 and 25% (n=127) secondary to AF in 2017.

Conclusion
The study found that implementation of a screening programme across a wide range of primary care practices led to an improvement in AF diagnosis, management and timeliness of care. This highlights the benefit of using simple methods such as GP educations in conjunction with new technology device to detect AF more effectively and subsequently treat in an appropriate and time-effective fashion. In our population this appears to be associated with real reductions in AF related strokes

Acknowledgement/Funding
CLAHRC NWL, NHS Hounslow CCG, Pfizer
P6140Health education program at the “happy life, healthy heart” school: a randomized clinical trial
Authors: Alievi Mari M , Santin Dal Ri C , Portal Teixeira P , Campos Pellanda L 
Published: October 2019

Abstract

Background
School interventions based on playful activities are good strategies to provide health knowledge to children, impacting on healthy habits and potentiating the prevention of cardiovascular diseases.

Purpose
To verify whether classroom intervention for cardiovascular health prevention increases the health knowledge of schoolchildren and makes behavioral changes in the lifestyle of teachers and students.

Methods
The study was placed in ten public schools of Frederico Westphalen, a city in the south of Brazil, where students from the 1st to 5th grade of elementary school aged 6 to 12 years and 32 teachers were recruited. Randomized clinical trial which examined the effects of an intervention with teachers and students on their health knowledge. Subjects such as cardiovascular health, nutrition and physical activity (PA) were broached with the teachers undergoing training and with students in classroom by the teachers themselves. Nutritional status of schoolchildren was evaluated by weight, height and z-score, level of PA and food consumption by DAFA questionnaire and health knowledge by CARDIOKIDS. Socio-demographic, nutrition and physical activity data of the teachers were evaluated by semi-structured questionnaire.

Results
A total of 473 students were evaluated, 211 (44.6%) in the Control Group (8.8±1.5 years, 57.3% girls) and 262 (55.4%) in the Intervention Group (8.5±1.6 years, 51.1% boys). 32 teachers were also divided into CG (CGt), 43.8% (n=14, Age 39.2±7.7) and IG (GIt), 56.3% (n=18, Age 43.4±9.6). CARDIOKIDS demonstrated that there was no interaction effect of time and group on the level of children's knowledge (effect size = 2.293, p=0.131), indicating an improvement in both groups. In relation to food consumption, IG increased 15.2% and 19.8% the number of students who followed the recommendations of pizza/hamburger (p<0.001) and soft drinks (p<0.001) respectively. In IGt there was an increase of 27.9% in the number of teachers who started practicing PA after the intervention.

Conclusions
Both groups of students increased the level of knowledge, but only the IG changed food behavior. This change was observed by greater adherence to the Brazilian Food Guide recommendations of not consuming pizza/hamburger and soft drinks. Teachers of the IGt started to practice more physical activity.

Acknowledgement/Funding
This work will be funded by Capes and Fappic
P6151Fully automated epicardial adipose tissue volume and density measured from non-contrast CT predict major adverse cardiovascular events in asymptomatic subjects
Authors: McElhinney P , Eisenberg E , Commandeur F , Chen X , Cadet S , Goeller M , Cantu S , Miller R , Slomka P , Wong N , Rozanski A , Achenbach S , Tamarappoo B K , Berman D , Dey D 
Published: October 2019

Abstract

Background
Epicardial adipose tissue (EAT) volume and density has shown to correlate with standard markers of coronary artery disease (CAD) and may predict major adverse cardiovascular events (MACE).

Purpose
We aimed to evaluate the prognostic value of EAT volume and density measured by fully automated deep-learning software from non-contrast cardiac computed tomography (CT).

Methods
We assessed 2071 consecutive asymptomatic subjects (age 56±9 years, 59% male) from the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) trial with long-term follow-up after coronary artery calcium (CAC) measurement. EAT volume and mean density were quantified using automated deep-learning software from non-contrast cardiac CT. MACE was defined as myocardial infarction (MI), cardiac death, late (>90 days) revascularization and acute coronary syndrome (ACS). EAT volume and density were systematically compared to CAC score and atherosclerotic cardiovascular disease (ASCVD) risk score using Cox proportional hazards regression for MACE prediction.

Results
At 14±3 years, 217 subjects suffered MACE. In age-and-gender-adjusted multivariate analysis, ASCVD risk score, CAC (two-fold increase) and EAT volume (two-fold increase) were associated with increased risk of suffering MACE [Hazard Ratio (HR) (95% CI): 1.03 (1.01–1.04); 1.25 (1.19–1.30); and 1.36 (1.08–1.70) respectively, p<0.01 for all] (Figure); the corresponding Harrell's C-statistic was 0.76. The area-under-the curve from receiver-operator characteristic analysis for MACE prediction increased significantly from 0.69 to 0.77 (p<0.0001) when EAT volume and CAC were added to the current clinical standard (ASCVD, family history and obesity measures BMI and BSA). Both in men and women, increase in EAT volume was associated with increased risk of MACE, with HR 1.14 (1.06–1.22), p<0.001 in men vs. 1.15 (1.01–1.31), p=0.03 in women, for each 20 cubic centimeter increase in volume. EAT density (HU) was independently inversely associated with MACE [HR: 0.96 (0.93–0.99), p=0.01].
MACE Prediction

Conclusions
EAT volume and density measurements improve prediction of MACE in asymptomatic populations over the current clinical standard. Fully automated EAT volume and density quantification by deep-learning from non-contrast cardiac CT can provide additional prognostic value for the asymptomatic patient.

Acknowledgement/Funding
1R01HL133616, Forschungsstiftung Medizin Universitätsklinikum Erlangen, grant from Dr Miriam and Sheldon G. Adelson Medical Research Foundation
P6196Lipoprotein (a) and cardiovascular risk: are women at increased risk?
Authors: Santos M R , Pereira A , Mendonca F , Sousa J , Neto M , Monteiro J , Sousa A C , Freitas S , Henriques E , Ornelas I , Drumond A , Palma Dos Reis R , Mendonca M 
Published: October 2019

Abstract

Introduction
Coronary artery disease (CAD) is the leading cause of death worldwide, placing a major economic and resource burden on health and public health systems, so efforts are being made to accurately predict risk for major adverse cardiac events (MACE). The field of risk prediction and CAD prevention continues to evolve with the identification of novel risk factors and biomarkers, such as lipoprotein a [Lp)a]. Almost 20% of the population has elevated circulating levels of Lp(a), which is recognized as an independent risk factor for CAD, stroke, peripheral arterial disease, and aortic stenosis. Importantly, studies showed that this was particularly true for women.

Objective
To evaluate if the elevation of Lp(a) is associated with MACE in female, male or both.

Materials and methods
Case control study of 3050 subjects from the GENEMACOR study population. In female population (n=676): cases were 341 patients with at least one >75% coronary stenosis (median age 55.7±7.2) and 335 normal controls (median age 55.8±6) adjusted by age with cases. In male population (n=2374): 1278 patients with at least one >75% coronary stenosis (median age 52.7±8) and 1096 controls (median age 51.9±8) also adjusted by age. χ2 and T student tests were used to analyze the demographic, laboratorial, angiographic and anthropometric characteristics of the population. Lipoprotein (a) was determined by immunoturbidimetry. High Lp(a) level was considered if superior to 30 mg/dl. Logistic regression was used to evaluate Lp(a) as a risk factor for CAD in total, female and male populations.

Results
In female population 44.0% patients vs 21.2% controls (p<0.000) had Lp(a)>30mg/dl. In male population 39.4% patients vs 23.8% controls (p<0.000) had Lp(a)>30mg/dl. In total population Lp(a)>30mg/dl was a predictor for CAD (OR 2.24, 95% CI: 1.91–2.62, p<0.0001). Analyzing by gender, Lp(a)>30mg/dl was also a predictor for CAD either in male (OR 2.08, 95% CI: 1.74–2.5, p<0.0001) or female population (OR 2.92, 95% CI: 2.08–4.09, p<0.0001).

Conclusions
As opposed to other studies, in our population elevated Lp(a) levels (>30mg/dl) were associated with elevated CAD risk, in both men and women. We conclude that Lp(a) can be considered an independent risk factor for CAD disease in our population, and further strategies for Lp(a) reduction may indeed translate in improved outcomes in CAD disease.
P6198Lipoprotein(a) as a potential residual risk associated with coronary lipid-rich atheroma in type2 diabetic subjects with coronary artery disease who achieved lowdense lipoprotein cholesterol<1.7mmol/l
Authors: Nakamura H , Kataoka Y K , Hosoda H H , Nakashima T N , Honda S H , Fujino M F , Nakao K N , Yoneda S Y , Otsuka F O , Nishihira K N , Kanaya T K , Asaumi Y A , Noguchi T N , Yasuda S Y 
Published: October 2019

Abstract

Background
Type 2 diabetic patients with coronary artery disease (CAD) is a high-risk subjects who require intensive secondary preventive management. The current guideline recommends lowering LDL-C with a statin as a first-line therapy in diabetic patients with CAD. However, its anti-atherosclerotic efficacy is diminished compared to non-diabetic subjects. These suggest the need to further identify additional therapeutic target associated with diabetic atherosclerosis. Lipoprotein (a) [Lp (a)] is a plasma lipoprotein which consists of an LDL-like particle with apolipoprotein (a). While Lp (a) has been shown to associate with ASCVD, whether this lipoprotein promotes diabetic coronary atherosclerosis under LDL-C control with a statin remains to be fully elucidated.

Purpose
To investigate the relationship between Lp (a) and coronary lipidic atheroma by near-infrared spectroscopy (NIRS), which quantitatively measures lipidic burden in vivo.

Methods
Culprit lesions in 127 type 2 diabetic patients with CAD who already received a statin were evaluated by NIRS imaging. Maximum 4-mm lipid core burden index at culprit lesion (MaxLCBI4mm) was measured.

Results
High-intensity statin and ezetimibe were used in 13 and 14% of study subjects, respectively. Their on-treatment LDL-C level and Lp (a) were 2.0±0.7 mmol/l and 22.1±26.7 mg/dl. Despite these lipid lowering therapy, average MaxLCBI4mm was 419.6±248.2 and MaxLCBI4mm≥400 was observed in 49% of study subjects. Multivariate linear regression analysis demonstrated LDL-C and Lp (a) as independent determinants associated with MaxLCBI4mm (Table). Of note, in subjects who achieved LDL-C<1.8 mmol/l, an elevated Lp (a) level but not LDL-C predicts MaxLCBI4mmat culprit lesions (Table).
Multivariate linear regression analysis t p-value Entire subjects (n=127)   LDL-C 2.04 0.04   Lp (a) 2.88 <0.01 LDL-C <1.8 mmol/l (n=47)   LDL-C 0.45 0.66   Lp (a) 2.74 0.01

Conclusions
The association of Lp (a) with coronary lipid-rich atheroma even under guideline-recommended LDL-C control indictaes Lp (a) as an additional therapeutic target to further stabilize diabetic atherosclerosis.
P6211Efficacy of comprehensive Managed Care after Acute Myocardial Infarction (MC-AMI) in a long-term follow-up - preliminary experience of a single high-volume center
Authors: Wita K , Wilkosz K , Wita M , Kulach A , Wybraniec M , Polak M , Matla M , Maciejewski L , Skowerski T , Fluder J , Kalanska-Lukasik B , Gomulka S , Turski M , Szydlo K 
Published: October 2019

Abstract

Introduction
Despite substantial progress in the medical and interventional treatment of acute myocardial infarction (AMI), a long-term prognosis in MI survivors remains unsatisfactory. The Managed Care in Acute Myocardial Infarction (MC-AMI, KOS-zawal) is the first program of a comprehensive, supervised care for patients with AMI to improve long-term prognosis. It includes acute intervention, complex revascularization, cardiac rehabilitation (CR), outpatient follow-up, and prevention of SCD.

Purpose
To assess the effect of MC-AMI on major adverse cardiovascular and cerebrovascular events (MACCE) in 12 months follow-up.

Methods
In this single-center, retrospective observational study we enrolled 1211 patients, out of which 719 consented for participation in MC-AMI and compared them to 1130 subjects in the control group. After propensity score matching two groups of 529 subjects each were compared. Cox regression was performed to assess the effect of MC-AMI on clinical endpoints.

Results
Primarily, MC-AMI has been proved to reduce MACCE rate by 40% in a 12-month observation. Participants of MC-AMI had a higher adherence to cardiac rehabilitation (98 vs. 14%) higher rate of scheduled revascularisation (coronary artery bypass grafting: 9.8% vs. 4.9%, p<0.001; elective percutaneous coronary intervention: 3.0% vs 2.1%, p<0.05) and ICD implantation (2.8% vs. 0.6%, p<0.05) compared to control.
Multivariable Cox regression analysis revealed MC-AMI participation to be inversely associated with the occurrence MACCE at 12 months (HR=0.500, 95%Cl 0.349–0.718, p<0.001). Besides, older age, diabetes mellitus, hyperlipidemia, prior PAD, previous UA, and lower LVEF were significantly associated with the primary endpoint.
12-month FU - freedom from MACCE

Conclusions
MC-AMI is the first program of a comprehensive in-hospital and post-discharge care for AMI patients. MC-AMI improves prognosis by increasing the rate of patients undergoing CR, complete revascularization and ICD implantation, thus reducing MACCE rate by 40% in 12 months. Participation in MC-AMI is inversely related to mortality rate, recurrent MI and heart failure related hospitalization during 12 months.