bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4999Cardiomyocyte ErbB4 receptors are essential for developmental cardiac hypertrophy and cardiac function in adult hearts
Authors: Reichelt M , Wang Z , Thorn C , Paravicini T , Thomas W G 
Published: October 2019

Abstract

Background/Introduction
Activation of ErbB4 by neuregulin 1 (NRG1) promotes cardiomyocyte hypertrophy and proliferation in both adult and neonatal mice, while treatment of patients with NRG1 following myocardial infarction reduces scar size and improves function. In mice, deletion of ErbB4 from cardiomyocytes mid-gestation results in development of dilated cardiomyopathy and reduced survival, pointing to a critical role for ErbB4 in the heart.

Purpose
We sought to evaluate the role of ErbB4 in the adult heart.

Methods and results
We deleted ErbB4 in αMHC-MerCreMer (cCre Tg+/)/ErbB4 homozygote floxed (ErbB4 fl/fl) mice at ∼2 months of age with 10 injections of Tamoxifen (20 mg/kg/day). Contractile function was reduced in vivo (echocardiography, 16%) and ex vivo (isolated-perfused, 33%) 3 months after gene deletion, while survival in mice up to 8 months after tamoxifen treatment was mot modified by cardiomyocyte ErbB4 deletion. We next evaluated the role of ErbB4 in response to physiological and pathological hypertrophic stressors. ErbB4 deletion did not modify cardiac enlargement in response to Angiotensin II (1000ng/kg/min, 14 days) or exercise (twice daily swimming, 20 min/session increasing 10 min/day to 90 min followed by 7 days at 90 min/session). Taken together, this indicated that ErbB4 is not essential for survival and adaptation in the adult heart, pointing instead towards a critical window for ErbB4 in neonatal heart development. To test this hypothesis, ErbB4ff and ErbB4ww neonates were injected at P1 with AAV9-cTNT-eGFP-iCre (2.16x1011viral particles, temporal vein) and culled at P6. We confirmed the presence of iCre mRNA, and suppression of ErbB4 in ErbB4 ff/ff mice, coincident with increased NRG1a, and reduced body and ventricular weights. By day 28, a number of hearts showed evidence of dilated cardiomyopathy.

Conclusion
Thus, ErbB4 is critical to cardiac hypertrophy and growth in neonatal mice, and maintains adult heart function.

Acknowledgement/Funding
National Health and Medical Research Council
P5000Wnt/b-catenin signalling drives angiotensin II induced cardiac fibrosis via WISP-1
Authors: Connolly G M , Li Z , Young M , Brown B A , Johnson J L , Williams H , George S J 
Published: October 2019

Abstract

Background
Myocardial infarction (MI) and hypertension lead to myocardial injury, which induces negative remodelling and cardiac fibrosis. Cardiac fibrosis, which involves inflammatory cell infiltration and myofibroblast activation, causes worldwide mortality and morbidity. In response to MI or hypertension induced by prolonged angiotensin II (AngII) exposure, activated myofibroblasts produce extracellular matrix proteins. However, if unchecked, excessive collagen deposition occurs leading to myocardial stiffening, heart failure and arrhythmias.

Purpose
The underlying mechanisms leading to pathological collagen deposition are not fully elucidated. There is debate regarding the involvement of the Wnt signalling pathway and its product Wnt Inducible Signalling pathway protein-1 (WISP-1) in cardiac fibrosis. Therefore, this project aimed to investigate the interaction of AngII and the Wnt/β-catenin signalling pathway in cardiac fibrosis.

Methods
The effect of AngII (100nM) on collagen levels in human cardiac fibroblasts was investigated in vitro (data expressed as fold change from control ± SEM). In vivo experiments (n=6–8) determined the involvement of the Wnt/b-catenin pathway, specifically WISP-1, in response to AngII infusion (500ng/kg/min) for 4 weeks (Apolipoprotein E−/−/WISP-1+/+ vs. ApolipoproteinE−/−/WISP-1−/− mice on a high-fat diet, data expressed as mean positive pixel % ± SEM).

Results
AngII significantly increased collagen type 1 protein levels produced by human cardiac fibroblasts (2.94±0.75 vs 1±0, p<0.05). Inhibition of Wnt/b-catenin signalling with 25nM iCRT14 significantly suppressed AngII-induced collagen levels (0.46±0.07 vs. 1±0, p<0.05). As expected, AngII infusion significantly induced hypertension in all mice. Immunohistochemistry demonstrated type 1 collagen was markedly higher in AngII mice than control mice (1.07±0.27 vs. 0.29±0.06, p<0.05). However, in the absence of WISP-1, AngII did not enhance collagen type 1 levels. Further immunohistochemical analysis of murine hearts demonstrated that AngII infusion caused significant alterations in the Wnt/β-catenin signalling markers AXIN-2 (35±3.9 vs. 10.7±2.6 p<0.05) and PPAR-d (92±1.4 vs. 17.3±4.3 p<0.05). This effect was reduced by WISP-1 deletion. Furthermore, AngII-infusion disrupted N-cadherin junctions (0.55±0.08 vs. 0.29±0.02 p<0.05) suggesting modulation of cell-to-cell contacts and enhanced β-catenin signalling.

Conclusion
This study indicates that AngII enhances cardiac fibrosis via modulation of the Wnt signalling pathway, in part via WISP-1. Further delineation of this interaction may lead to the use of Wnt/β-catenin or WISP-1 inhibitors to suppress myocardial injury induced cardiac fibrosis in post-MI or hypertensive patients.

Acknowledgement/Funding
Elizabeth Blackwell Institute, British Heart Foundation
P5241Balancing limited resources, infra-structure deficits & cultural differences in sustaining the growth of LATIN telemedicine program
Authors: Mehta S , Botelho R , Fernandez F , Feres F , Abizaid A , Cade J , Perin M , Prudente M , Cavalcanti R , Dusilek C , Nola F , Pisana L , Safie R , Aboushi H , Lopez C 
Published: October 2019

Abstract

Background
In resource-constrained nations, population-based AMI coverage is daunting. Telemedicine can transform with efficient, cost-effective and scalable programs. We present our data with screening >780,000 patients with innovative hub and spoke strategies.

Purpose
Scientifically pristine protocols, rigorous training, unflinching quality assurance, technology upgrades and education of broad stakeholders are essential attributes for creating population-based AMI programs.

Methods
Latin America Telemedicine Infarct Network (LATIN) required methodical groundwork during a 12-month pilot prior to its formal launch and sustenance for 5 years. It involved scrupulous site selection, technology, and telemedicine optimization and system-wide process metrics. Spokes are the LATIN nucleus and require constant (3-T) training: Triage, Telemedicine, and Transportation. Plus, a mandatory deconstruct of their role in LATIN, of urgent transfer and desist non-critical care. Telemedicine requires constant upgrading of platform, tele-equipment and cloud computing. Ambulance availability is a constant challenge as is the battle with payers. Data entry has required meticulous training and oversight. Strict QA processes have monitored critical metrics: Spokes (Door In Door Out, DIDO and Transport Times); Hubs (Door to Balloon Times, D2B); Telemedicine Platform (Time to Telemedicine Diagnosis, TTD).

Results
Linear growth is observed in the number of sites and telemedicine screenings with simultaneous and sustained improvements in D2B and TTD. 784,395 patients were screened at 350 LATIN centers (Brazil 143, Colombia 118, Mexico 82, Argentina 7). With expanded reach, 8,440 (1.08%) patients were diagnosed and 3,924 (46.5%) urgently reperfused, including 3,048 (77.7%) with PCI. Time to Telemedicine Diagnosis (TTD) was 3 min, tele-accuracy 98.9%, D2B 51 min and in-hospital morality 5.2%. Major reasons for non-treatment were insurance, lack of ICU beds and delayed presentation.

Conclusions
As other regions of the world develop large, population-based AMI management initiatives, LATIN can provide important lessons in the sustainability of these processes.
P5268Prognostic implications of cardiac magnetic resonance in patient with mid range ejection fraction: can we predict worse outcomes?
Authors: Lorente Ros A , Pascual Izco M , Flores M , Hinojar Baydes R , Alonso Salinas G L , Fernandez Mendez M A , Plaza Martin M , Garcia De Vicente A , Del Prado Diaz S , Abellas Sequeiros M , Garcia Martin A , Gonzalez Gomez A , Zamorano Gomez J L , Fernandez-Golfin Loban C 
Published: October 2019

Abstract

Purpose
According to current ESC guidelines, mid-range ejection fraction (mrEF) might represent a separate subgroup of patients with distinct underlying characteristics, prognosis and treatment response. Cardiac magnetic resonance (CMR) is the gold standard for measuring volumes, mass and ejection fraction of the heart. We aimed to find long-term prognostic value of various CMR parameters in patients mrEF.

Methods
137 patients with mrEF underwent CMR (1.5T) between 2012 and 2018 and were consecutively included. Volumes, mass and ejection fraction were assessed using short axis SSFP images and the Simpson method (using commercially available software). Myocardial fibrosis was determined by late gadolinium enhancement (LGE). Clinical parameters after a median of 762 (230–1315 days) were recorded. Patients with other significant cardiac affection rather than mrEF were excluded (pre-capillary pulmonary hypertension and significant valve disease). The primary endpoint was defined as a combined outcome of all-cause death or heart failure decompensation requiring in-hospital admission.

Results
Mean age was 63.0±12.4 years. 76.6% were males. Mean left ventricle ejection fraction (LVEF) was 45±2.69%. Main aetiologies were ischemic (46%), idiopathic (32.12%), myocarditis (9.5%), tachycardiomyopathy (6.57%) enolic (2.2%) stress cardiomyopathy (0.7%) and others (2.9%).
A combined model for predicting outcomes in patients with mrEF using CMR parameters was obtained. This model was able to predict 32.7% (coefficient of determination, R-squared) of the adverse events (p<0.01). Significant CMR parameters and results are shown on table 1.
Combined model for predicting outcomes in patients with mrEF using CMR parameters Variable p value iRVEDV (indexed right ventricular end-diastolic volume) <0.01 RVEF (right ventricle ejection fraction 0.03 iRVESV (indexed right ventricular end-systolic volume) <0.01 Presence of late enhancement (yes/no) 0.09 iLA (indexed left atrial) Volume <0.01 iLV (indexed left ventricle) mass <0.01 Variables and their significance are shown individually.

Conclusions
In patients with mid-range ejection fraction, RV volumes and ejection fraction, as well as LV mass and LA volume, were significant predictors of worse outcomes in a combined model. If supported by further studies, these findings may help the clinician select the patients with higher risk of complications and in need of a closer follow-up.
P5272Right versus Left Ventricular Remodelling after Surgical myectomy for HOCM
Authors: Abdelkhalek M , El Sawy A , Doss R , Samaan A , Donia M , Morais P , Aguib Y , Bogaert J , Elguindy A , Romeih S , Aguib H , Yacoub M 
Published: October 2019

Abstract

Background
Surgical myectomy for (HOCM) results in complex structural and functional changes. “Remodelling” in different cardiac chambers. To date, changes in the Right versus the left Ventricle have not been studied.

Methods
Fourty five patients (mean age = 32±16, 68% males) who underwent extended septal myectomy for LVOTO and Fourty “normal” controls (mean age = 32±12 years, 52% males) were studied by cardiac magnetic resonance imaging (CMR). The patients were studied pre-operatively and 6–18 months post-operatively (median = 9 months). The images were analysed by both commercial and in-house software.

Results
After myectomy. Follow up CMR showed changes in RV mass (21±5 to 23±7) g/m2, volume (60±15 to 66±12) ml/m2 and shape using 3 different methods. RV deformation parameters showed significant changes with circumferential strain (−8±2 to −14±4), filling (38±16 to 62±19) ml/s/m2 and ejection rate (−44±17 to −75±22). Changes in RV were substantially higher than those observed in the LV (Figure. 1, Table. 1). All patients reported significant symptomatic improvement with 31 (78%) patients in NYHA class I and 9 (22%) in class II at follow up. Significant reduction in peak gradient across the LVOT by 75%.
Table 1. Summary of reported parameters related to RV Shape for pre and post operation HOCM patients and Normal Healthy Volunteers LV RV Pre Post Normal P-value Pre Post Normal P-value EDV ml/m2 75±18 81±14 73±10 0.005 60±15 66±12 71±12 0.002 ESV ml/m2 20±9 24±8 26±6 0.008 16±7 19±9 26±7 0.02 SV ml/m2 56±13 57±10 51±13 0.38 44±11 48±10 49±14 0.009 EF 74±7 70±7 65±5 0.001 74±8 72±7 64±6 0.228 Mass g/m2 74±33 62±29 27±8 0.0456 21±5 23±7 18±5 0.2100 PFR ml/m2 173±48 141±48 141±40 <0.0001 38±16 62±19 55±24 <0.0001 PER ml/m2 −179±35 −172±42 −144±42 0.29 −44±17 −75±22 −57±22 <0.0001 Peak Strain −20±3 −20±3 −20±3 0.49 −8±2 −14±4 −12±3 <0.0001

Conclusion
LV septal myectomy is followed by structural and functional remodelling which is more extensive in the right than the left ventricle. The clinical significance of these findings needs further study.
P5281Synthetic extracellular volume quantification by cardiac magnetic resonance imaging - a reliable tool in clinical practice?
Authors: Unbehaun C , Nunn S , Vietheer J , Wolter J S , Zipse L , Kriechbaum S , Weferling M , Fischer-Rasokat U , Keller T , Liebetrau C , Hamm C W , Rolf A 
Published: October 2019

Abstract

Background
Extracellular volume (ECV) quantification by CMR imaging allows the measurement of changes in the extracellular space indicating diffuse edema and fibrosis, especially in early stages of myocardial disease. Usually venous hematocrit (Hct) is needed in order to calculate standard ECV. Recent findings suggest the alternative use of the blood pool T1-relaxation time (T1blood) instead of the venous Hct to generate “synthetic Hct ” and furthermore “synthetic ECV”, allowing a more routine and user-friendly application without the need of a current blood sample.

Purpose
Purpose of this study is to re-evaluate whether the connection between venous Hct and T1blood can be used to generate a synthetic ECV in a large number of volunteers and patients with various myocardial diseases from a tertiary care centre.

Methods
945 volunteers and patients were divided into a derivation (n=490) and a validation group (n=455). Standard ECV was calculated using T1-relaxtion times acquisitioned in the septal myocardium and blood pool, each on pre- and post-contrast Images using a modified look-locker sequence at a 3 Tesla MR-scanner. In addition venous Hct was measured in a blood sample drawn prior to the scan. Synthetic Hct was derived through linear regression analysis between venous Hct and 1/T1blood and was then compared to venous Hct. Also we derived standard ECV and synthetic ECV and examined these using Lin's rho and Bland-Altman comparison.

Results
In the derivation group venous Hct and 1/T1blood showed a linear relationship (R2=0,22; p=ehz746.02521). This was used to calculate synthetic Hct and synthetic ECV. Synthetic ECV correlated well with standard ECV (Lin's rho= 0,903; p<0,0001). Mean difference 0,004, limits of agreement −0,038 and 0,047. See table 1 for patient characteristics and figure 1 for Bland-Altman plot on standard and synthetic ECV.
Table 1. Patient characteristics Sex female (%) 312 (33%) Age, yrs 60±15 EDVi, ml/m2 86±31 ESVi, ml/m2 43±30 LVEF, % 54±16 Hematocrit, % 43±5
Figure 1

Conclusion
Despite only weak correlation of synthetic and venous Hct we found excellent correlation in synthetic and standard ECV. Therefore we could confirm the value of synthetic ECV in a large cohort of volunteers and patients, providing a feasible and non-invasive marker for extracellular myocardial alterations in everyday clinical practice.
P5300Study of b2-adrenergic receptor (ADRB2) gene polymorphism in patients with coronary artery disease and obesity
Authors: Zaletova T , Bogdanov A , Derbeneva S , Nesterova V , Shevtchenko I 
Published: October 2019

Abstract

Introduction
B2-adrenoreceptors participate in mobilizing fat from fat cells to enable energy production in response to hormones (adrenaline, noradrenaline); they stimulate glycogenolysis in the liver and glucose release into the circulation to replenish energy needs; and enhance glycogen breakdown in skeletal muscles. Glu27 allele is associated with an increased risk of obesity when the diet is rich in carbohydrates. In the 27Glu variant the production of adrenoreceptors is increased, thus increasing sensitivity to beta-agonists; hyperinsulinemia and hypertriglyceridemia can be also observed. In 27Gln variant, on the contrary, beta-agonists production and sensitivity to them are reduced, and increased production and insulin resistance are likely to affect patients with normal body weight.

Objective
To search for molecular and genetic predictors of metabolic disorders (a combination of protein hypercatabolism (high protein oxidation rate (POR) and decreased oxidation of carbohydrates (low carbohydrate oxidation rate (COR), identified with respiratory indirect calorimetry in the previous studies.

Methods
The study involved 182 patients with multivessel coronary artery disease and clinical features of coronary artery disease (CAD), requiring surgical myocardial revascularization, and a body mass index of 35.0–50.0 kg/m2. The average age was 59.6±3.5 years old. Frequencies of allele and genotype polymorphism in ADRB2 (27Glu) were analyzed.
Multiplicative mode of inheritance “MD−” “MD+” χ2 P OR value 95% Cl ADRB2(27Glu)   Allele C 0.60 0.885 3.56 0.03 0.21 0.05–1.10   AlleleG 0.40 0.115 4.11 0.91–18.76   Genotype C/C 0.40 0.77 3.44 0.03 0.22 0.03–1.22   Genotype C/G 0.50 0.23 3.13 0.56–19.95   GenotypeG/G 0.10 0.00 4.27 0.16–116.34 MD: metabolic disorders (↑POR+↓COR).

Results
Our results showed that metabolic changes in obesity may be associated with ADRB2 gene mutation, namely when 27Glu variant is present. Thus, the odds ratio for developing metabolic disorders with G allele was 3.44 times higher (p=0.02, CI (95%) = 1.24 - 19.46), and in patients with genotype G/G - 4.27 times higher (p=0.03, CI (95%) = 15.6 - 199.5).

Acknowledgement/Funding
Research No. 0529-2019-0061 Diagnostics, prevention and dietaterapy of patients with alimentary-dependent diseases
P5312Sleep duration and carotid atheromatic burden. Insights from the Corinthia study
Authors: Oikonomou E , Tsalamandris S , Vogiatzi G , Lazaros G , Christoforatou E , Chasikidis C , Mistakidi C V , Galiatsatos N , Asimakopoulou M , Papamikroulis G A , Zacharia E , Anastasiou M , Mavrantzas T , Papakonstantinou M , Tousoulis D 
Published: October 2019

Abstract

Background
Sleep is an essential physiological process and disturbance of sleeping pattern may be associated with cardiovascular risk profile and atheromatosis. Short but also long sleep duration (LSD) may be adversely affect cardiovascular parameters.

Purpose
To study how sleep duration is associated with cardiovascular risk profile and carotid atherosclerotic burden.

Methods
Corinthia study is a cross sectional epidemiological study based on 2043 inhabitants (age 40–99 years) of Corinthia region in Greece. Ultrasonography was used to measure intima media thickness (IMT) in the left and right common carotid artery, carotid bulb and internal carotid artery. The mean IMT (meanIMT) were determined as representative values of carotid atherosclerosis burden. Thickness of IMT>1.5 mm or protrusion >50% compared to adjacent segments was considered as atherosclerotic plaque. Based on questionnaires of Corinthia study, total sleeping time per day was recorded. A sleep duration of 7 to 8 h was consider normal (NSD), sleep duration <6 h was consider very short (VSSD), 6–7 h sleep duration was considered short (SSD) and participants with >8 h sleep duration was categorized as LSD.

Results
Concerning gender more men than women were categorized in the NSD (26% vs. 21%, p<0.001). Subjects in the NSD were also younger compared to subjects categorized in other sleeping patterns (VSSD: 66±12 y vs. SSD: 63±12 y vs. NSD: 62±12 y vs. LSD: 66±12 y, p<0.001), have less prevalence of diabetes mellitus (p<0.05). There was no difference according to sleeping pattern in body mass index, prevalence of hypertension, cardiovascular disease, hyperlipidemia and on current smoking habits according to sleeping patterns. Interestingly, meanIMT (VSSD: 1.08±0.51 mm vs. SSD: 0.97±0.42 mm vs. NSD: 0.97±0.41 mm vs. LSD: 1.14±1.64 mm, p=0.04) and carotid atherosclerotic plaque (VSSD: 35% vs. SSD: 25% vs. NSD: 20% vs. LSD: 30%, p=0.006) was decreased in NSD subjects. Importantly, even after adjustment for the confounders logistic regression analysis revealed that subjects in the NSD group have 50% less odds of carotid atheromatic plaque than subjects in the VSSD (Odds ratio: 0.5, 95% CI 0.28–0.90, p=0.02) (Figure).

Conclusion
A balanced sleeping pattern with 8h of sleep daily can act as an additive cardioprotective factor in the modern western type societies. Short especially less than 6 hours and long (>8 hours) sleeping duration may act as a cardiovascular risk factor.
P5321The association of Lp(a) levels and cardiovascular disease in adult patients with familial hypercholesterolemia: analysis from the HELLAS-FH registry
Authors: Liberopoulos E , Rizos C , Skoumas I , Tziomalos K , Rallidis L , Kotsis V , Athyros V , Skalides E , Kolovou G , Garoufi A , Koutagiar I , Papagianni M , Kiouri E , Antza C , Elisaf M 
Published: October 2019

Abstract

Introduction
Familial hypercholesterolemia (FH) as well as elevated Lp(a) levels are both associated with increased cardiovascular disease (CVD) risk. There are limited data on the association of Lp(a) levels with CVD in FH Patients.

Purpose
To evaluate the association between Lp(a) levels and CVD in adult FH patients included in the HELLAS-FH registry in Greece.

Methods
Adult patients with FH and measured Lp(a) levels were included in this analysis. Demographics, CVD prevalence and lipid profile were evaluated.

Results
A total of 337 patients were evaluated (46% male, 48.3±15.4 years old). The median [IQR] of Lp(a) at baseline was 22.6 (9.7–56.2) mg/dL. Patients were categorized into 4 different groups according to the Lp(a) levels quartiles. There was no gender or age difference between the 4 groups. Moreover, all groups had similar smoking status, hypertension, body mass index and type 2 diabetes prevalence. There was no significant difference between groups regarding baseline and on treatment lipid profile. We observed a significant positive association between Lp(a) quartile and coronary artery disease (CAD) prevalence (p=0.004). Patients in the highest vs lowest quartile had greater CAD prevalence (21.7% vs 7%, p=0.006). No association was observed between Lp(a) quartile and the prevalence of cerebrovascular disease or peripheral artery disease.

Conclusions
Elevated Lp(a) levels have a positive correlation with CAD in patients with FH.