bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2245Sex differences in the in-vivo markers of platelet activation among patients with ischemic heart disease: insights from the EVA study
Authors: Raparelli V , Romiti G F , Sperduti N , Santangelo G F , Vano M , Recchia F , Proietti M , Lenzi A , Basili S 
Published: October 2019

Abstract

Background/Introduction
Ischemic heart diseases (IHD) are not synonymous with obstructive flow-limiting coronary artery disease (CAD), especially in women. Platelet dysfunction is suggested as a potential mechanism favouring ischemia in non-obstructive CAD. However, it is unknown whether sex differences in platelet function of patients with non-obstructive CAD exist.

Purpose
We assessed for sex differences in in-vivo markers of platelet activation among patients with the acute coronary syndrome and chronic stable angina, with or without obstructive CAD

Methods
From the “Endocrine Vascular disease Approach” (EVA) study, we selected IHD patients undergoing urgent or elective coronary angiography with complete baseline clinical characteristics and angiographic data. Non-obstructive CAD was defined as the presence of coronary stenosis <50%. Thromboxane B2 (TxB2) and soluble P-selectin (sP-s) were measured at baseline. A sex-stratified analysis of platelet biomarkers was performed.

Results
Among two-hundred-seventy-seven patients (mean age 67±11, 37% women), non-obstructive CAD was documented in 25% of patients. Acute coronary syndrome (ACS) was the reason for angiography in 61% of cases. Women had more frequently ACS, as compared with men (54.8% vs 41.3%, p=0.001), with predominantly non-obstructive CAD. Median serum TxB2 (121.5 [92.7–174.0] vs 103.5 [83.0–140.2] pg/ml, p=0.005) and plasma sP-s (27.0 [18.7–35.0] vs 22.0 [16.0–30.0] ng/ml, p=0.006) levels were higher in patients with ACS as compared with the ones with stable chronic angina. The median concentration of TxB2 was significantly increased in women as compared with men, regardless of the clinical presentation and the coronary stenosis degree (all comparison, p<0.001). However, women with non-obstructive CAD were the group with the highest serum levels of TxB2 (140.0 [111.0–152.0] pg/ml). Sex differences in the plasma sP-s level were also observed among patients with stable chronic angina (women, 26 [20.0–34.0] vs men, 21 [16.6–27.7] ng/ml, p=0.002) and with non-obstructive CAD (women, 26 [20.5–34.5] vs men, 18.5 [16.6–26.0] ng/ml, p=0.003).

Conclusion(s)
Women with IHD and non-obstructive CAD had increased level of TxB2 and sP-s as compared with men, independently by the clinical presentation. Further investigations are warranted to verify the role of platelet hyperactivation in the pathogenesis of myocardial ischemia with non-obstructive coronary artery disease among women.

Acknowledgement/Funding
Scientific Independence of Young Researchers Program (RBSI14HNVT) - Ministry of Education, University and Research (MIUR)
P2252Hyperglycemia drives myeloid CD34+ stem cells differentiation towards pro-inflammatory and senescent monocyte subpopulations
Authors: Vinci M C , Vigorelli V , Raucci A , Genovese S , Pompilio G 
Published: October 2019

Abstract

Background/Introduction
Diabetes is characterized by a chronic low-grade inflammatory status mediated by cellular senescence and alterations of the circulating cytokine profile and of innate immune system cell components. An abnormal expansion of intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocyte subpopulations with highly inflammatory and senescent-associated secretory phenotype (SASP) have been observed in T2DM patients with cardiovascular (CV) complications. It is unknown whether CD34+ hematopoietic stem cells (HSCs), players of CV prognosis, are involved in this process.

Purpose
To assess whether hyperglycemia might induce a pro-inflammatory priming of hematopoietic CD34+ HSCs that through senescence and acquisition of SASP skew their myeloid differentiation into more aggressive monocyte populations.

Methods
CD34+ cells were purified from cord blood of healthy donors and expanded in normal-glucose (NG; with 30 mM mannitol for osmotic control) or high-glucose (HG; 30 mM) serum-free medium plus cytokines. The cell were counted after 10, 20 and 30 days. The expression of p27, p21 RELA/p65, IL6, TNFα genes and telomere length was assessed by qPCR and secreted cytokines by ELISA. Apoptosis, ROS and monocyte subpopulations were evaluated by flow cytometry after Annexin V, CellRox and CD14/CD16 staining respectively.

Results
CD34+ HSCs cultured in HG (HG-CD34+) displayed a significant proliferation impairment when compared to their osmotic control (NG-CD34+). This loss of glucose tolerance was associated with a significant increase in mitochondrial ROS production (n=6; p≤0.01) without induction of apoptosis as showed by flow cytometry analysis for Annexin V. Moreover, qPCR assay revealed a significant telomere shortening (n=4; p≤0.05) and up-regulation of cyclin-dependent kinase inhibitors p27 and p21 in HG-CD34+cells (n=13; p≤0.05) along with an enhanced expression and secretion of TNFα (n=9; p≤0.05) and IL6 (n=10; p≤0.05) in HG-CD34+ when compared with NG-CD34+. SASP phenotype in HG-CD34+ was associated to a significant up-regulation of RELA/p65 gene in HG-CD34+ when compared with NG-CD34+ (n=8; p≤0.05). Furthermore, we found that in vitro HG-CD34+ differentiation into myeloid lineage generated higher levels of pro-inflammatory intermediate (n=3; p≤0.05) and non-classical (n=3; p≤0.01) monocyte subsets when compared with the normoglycemic counterpart.

Conclusion(s)
These data suggest that HG exposure primes HSCs myeloid differentiation towards inflammatory and senescent monocyte subpopulations.

Acknowledgement/Funding
This work was supported by Ricerca Finalizzata, Ministero della Salute [PE-2011-02348537]
P2256Aging and inhibition of Nox4 and Nox1 exacerbate perivascular inflammation in spontaneous hypertension
Authors: Nosalski R , Mikolajczyk T , Siedlinski M , Maciag J , Guzik T J 
Published: October 2019

Abstract

Introduction
Hypertension is associated with enhanced NADPH oxidase activation and increased accumulation of immune cells leading to perivascular inflammation. However, while aging and oxidative stress are a major factor for the development of hypertension, their effect on perivascular inflammation remains unclear.

Purpose
We aimed to establish the interaction between aging, oxidative stress and perivascular inflammation.
We hypothesize that the modulation of oxidative stress, by NADPH oxidase inhibition, could affect perivascular inflammation during the aging.

Methods
Using flow cytometry, we studied leukocyte infiltration in the perivascular adipose tissue (PVAT) in 1-, 3-, 6- and 12-month-old SHR (Spontaneously Hypertensive Rats) and normotensive WKY (Wistar-Kyoto) rats (n=5–12). Additionally, 1-month-old rats were treated with GKT137831 or ML171 (60mg/kg; NOX1/4 and NOX1 inhibitor, respectively) for 4 weeks. Blood pressure (PB) was measured by tail cuff. Statistical analysis was performed using two-way ANOVA or t-test. Data are presented as means±SEM.

Results
Aging in SHRs was associated with an increase of BP (139±4 vs. 180±4 vs. 203±3 vs. 209±3, mmHg) and an elevation of PVAT leukocytes (2090±164 vs. 2255±359 vs. 2502±496 vs. 3255±408, cell/mg) in 1-, 3-, 6- and 12-month-old rats, respectively. These effects were not seen in WKY.
These were associate with similar changes of NK cells (p int <0.001) and macrophages (p int <0.001) in the SHR PVAT. Within T cell compartment, TH17 cells in PVAT were only elevated with age in SHR (1.04±0.08% vs. 1.89±0.2%, 1.08±0.1% vs. 2.03±0.2%, 1.71% vs. 4.37±0.5%, WKY vs. SHR, 3-,6- and 12-months, respectively, p int<0.001).
While an age-related increase of Nox4 mRNA in the vessels was observed in both groups, this increase was more dynamic in SHRs, (p int <0.05). Furthermore, 5-, 6- and 9-fold induction of Nox1 mRNA was observed in the vessels of 3-, 6- and 12-months-old SHRs, respectively (p<0.01).
Interestingly, GKT137831 increased BP in both WKY and SHR rats (p<0.01, 2-way ANOVA). This was accompanied by the elevation of leukocytes (988±180 vs 147±188 cell/mg, 1487±945 vs 1878±164 cell/mg) and macrophages (107±14 vs. 153±14 cell/mg, 228±26 vs. 298±42 cell/mg) in PVAT of both WKYs and SHRs treated with GKT137831. Moreover, GKT137831 treatment significantly increased (p int<0.01) percentage of TH17 in PVAT of both normotensive (1.4±0.2% vs. 2.5±0.2%) and hypertensive (2.3±0.1% vs. 2.9±0.1%) animals. On the contrary, ML171 treatment, inhibiting only Nox1, in turn protected against an increase of PVAT leukocytes especially among macrophages, TH17 cells (p<0.01).

Conclusion
Aging and spontaneous hypertension is associated with a trajectory of BP elevation and perivascular inflammation. This state is hastened after NOX1/4 inhibition, while ML171 treatment protects against perivascular inflammation.

Acknowledgement/Funding
National Science Centre 2013/11/N/NZ4/00310
P2259Cognitive function and adherence to treatment in patients with chronic heart failure and reduced left ventricular ejection fraction: relation and prognostic meaning
Authors: Solonovych A S , Voronkov L G 
Published: October 2019

Abstract

Background
Poor adherence to treatment increases risk of hospitalization and has negative impact on quality of life and clinical prognosis in chronic heart failure (CHF). Cognitive impairment (CI) is observed in more than half of patients (pts) with CHF and may affect their adherence to treatment. Nevertheless, association between cognitive function (CF) and adherence to treatment in CHF pts is studied insufficiently.

Purpose
To establish relationship between the state of CF and adherence to treatment in pts with CHF and reduced left ventricular ejection fraction (rLVEF).

Methods
124 pts with stable CHF and rLVEF (<40%) NYHA II-III non older than 75 years old were examined. Besides routine clinical examination, standard neuropsychological tests (MMSE, Schulte test, the HADS scale) were used. To assess adherence to treatment, Morisky-Green questionnaire (MGQ) was used. CI was defined as MMSE ≤26 points. Statistic methods included descriptive statistics, Mann-Whitney U-test, Spearman's rank correlation, Kaplan-Meier method. The difference was considered statistically significant at p<0.05.

Results
CI was observed in 85 (68.5%) of pts. The presence of CI was associated with significantly lower survival rate (fig. 1). According MGQ poor adherence to treatment was observed in 37 (43.5%), moderate – in 30 (35.3%), good adherence – in 18 (21.2%) of pts. After distribution of pts to three groups depending on their adherence to treatment (0–2 poor, 3-moderate, 4-good adherence), it was found that they significantly differed in MMSE and Shulte test results (p=0.006 and p=0.038 respectively). At the same time, groups were comparable by HADS anxiety and depression scores. The number of MGQ points directly correlated with MMSE (r=0.186, p=0.038).
Survival curves of CI vs non-CI pts

Conclusion
Insufficient adherence to treatment accessed by MGQ is observed in majority of CI pts with CHF and rLVEF. Adherence to treatment is reliably associated with cognitive status of pts, which, in turn, related to poor clinical outcome.
P2428Comparison of Newtonian and non-Newtonian rheology in calculation of endothelial shear stress
Authors: Thondapu V , Poon E K W , Revalor E , Zhu S , Dijkstra J , Serruys P , Ooi A , Barlis P 
Published: October 2019

Abstract

Background
Although blood is a non-Newtonian fluid, most clinical computational fluid dynamic (CFD) studies assume blood to be a Newtonian fluid with constant viscosity. At higher blood flow rates in larger arteries, the two models should present similar results, and the Newtonian assumption can be considered acceptable. However, whether the Newtonian assumption is valid in patient-specific coronary arteries under pulsatile flow has not been evaluated.

Purpose
To compare CFD results using Newtonian and non-Newtonian models of blood in order to determine whether the Newtonian assumption can be considered valid in patient-specific coronary arteries.

Methods
Coronary arteries of 16 patients were reconstructed from fusion of angiography and intracoronary optical coherence tomography imaging. Pulsatile CFD simulations using Newtonian and non-Newtonian models were performed to calculate endothelial shear stress (ESS). The absolute and percent difference in time-averaged and instantaneous ESS values (calculated as non-Newtonian minus Newtonian) were compared on a point-to-point basis. The percent area of the vessel exposed to proatherogenic ESS values (considered <1 Pa) in each model was also calculated.

Results
The Newtonian and non-Newtonian models produce similar qualitative distributions of ESS. However, quantitative comparison shows that compared to the Newtonian results, the non-Newtonian model estimates significantly higher time-averaged ESS (2.04±0.63Pa versus 1.59±0.54Pa, 95% CI 0.39–0.49, p<0.001) throughout the cardiac cycle. This results in significantly greater estimate of area exposed to ESS <1Pa in the Newtonian model (50.43±14.16% versus 37.20±13.57%, 95% CI 11.28–15.18, p<0.001). Instantaneous ESS plotted through the cardiac cycle indicates the greatest divergence in ESS values occurs at the transition between end-systole and early diastole, at approximately 0.35 seconds (FIGURE).

Conclusions
Despite similar qualitative ESS distributions, Newtonian and non-Newtonian simulations provide significantly different quantitative ESS values. This suggests that in patient-specific simulations of coronary blood flow, the non-Newtonian model may increase accuracy of ESS measurements. We hypothesize that using a non-Newtonian model may improve the diagnostic accuracy of abnormal ESS to predict clinically significant progression of atherosclerosis, however further study is necessary.
P2437Screening for cardiac relaxation abnormalities using surface ECG wavelets for identifying high-risk cardiac phenotypic abnormalities
Authors: Piccirilli M , Shrestha S , Kagiyama N , Hu L , Kulkarni H , Sengupta P P 
Published: October 2019

Abstract

Background
The impairment of myocardial relaxation is a strong predictor of all-cause mortality and has been proposed to be a potential tool for cardiovascular (CV) risk stratification. We investigated a novel signal-processed electrocardiography (spECG) technique to extract the features of abnormal myocardial relaxation as a screening tool to identify high-risk CV patients.

Methods
Time–frequency-energy features extracted from continuous wavelet-transformed spECG (Fig. A) were obtained in 1,006 cases. A machine learning model was trained for predicting abnormal myocardial relaxation as a screening tool for detecting high-risk CV patients. High-risk CV phenotype was defined as presence of LV hypertrophy, advanced LV diastolic dysfunction (grade 2 or 3), LV ejection fraction <50%, and/or significant valvular heart disease.

Results
After training with 5-fold cross validation using data from 810 patients, the machine learning model when tested in an independent hold-out validation set of 180 cases, showed an area under receiver-operating characteristic curve (AUC) of 0.83 (p<0.001) for prediction of myocardial relaxation impairment (Fig. B). A prediction of abnormal relaxation was associated with older patients (64±11 vs. 45±16 years old, p<0.001) with a higher prevalence of coronary artery disease (23% vs. 7%, p=0.004), hypertension (70% vs. 40%, p<0.001), and diabetes (30% vs. 9%, p=0.001). Furthermore, a prediction of abnormal myocardial relaxation was associated with increased likelihood of high-risk CV phenotypes (Odds ratio: 3.93, p<0.001) including LV hypertrophy (Odds ratio: 2.62, p=0.028), advanced LV diastolic dysfunction (Odds ratio: 11.4, p=0.020), and LV ejection fraction <50% (Odds ratio 10.5, p=0.025). Age and gender modified the prediction of abnormal relaxation with higher diagnostic value seen for patients under 60 years (Fig C, AUC: 0.88, p<0.001) and in male patients (Fig D, AUC: 0.87, p<0.001). The algorithm for abnormal relaxation also showed robust prediction of LV ejection fraction <50% (Fig E, AUC: 0.91, p<0.001) in male patients. spECG showed significant net reclassification improvement (0.47, p<0.001) and integrated discrimination improvement (0.16, p<0.001) over traditional surface ECG interpretation using Glasgow score for predicting abnormal relaxation and other high-risk phenotypic presentations.
ROC curves

Conclusion
The spECG provided a robust prediction of abnormal myocardial relaxation and may be a valuable screening strategy for early detection of high-risk cardiac structural and functional abnormalities.
P2438Deep learning model for atrial fibrillation detection based on single beat morphology
Authors: Baalman S W E , Schroevers F E , Oakley A , Ramos L A , Lopes R R , Van Der Stuijt W , Brouwer T F , Knops R E , De Groot J R 
Published: October 2019

Abstract

Background
The electrocardiogram (ECG) is commonly used, but most recent rhythm discrimination algorithms still lack both specificity and sensitivity. Deep learning techniques have shown promising results in the classification of physiological signals like ECGs.

Purpose
To develop and test a deep learning (DL) model to discriminate between atrial fibrillation (AF) and sinus rhythm (SR).

Methods
For the development of the DL model we used 1499 ECGs sampled at 500 Hz of patients diagnosed with AF. All ECGs were labeled by two experienced investigators. Only ECGs labeled as SR or AF were included in the dataset. To simplify the learning process, solely the first ECG channel was used. The ECG waveforms were preprocessed using the Fourier cosine series to correct for baseline wander. Input data was generated by normalizing and scaling all different heartbeats by centralizing the R peak, leading to 15744 single heart beat samples of 80 data points (figure A). Multiple feedforward architectures were tested with different numbers of layers, filters and activation functions. The models were trained by equally splitting the data (50%SR, 50%AF) in a training (65%), validation (25%) and test set (15%). The best performing model was chosen based on the accuracy.

Results
A total of 1469 ECGs (1061 (72%)SR, 408 (28%)AF) were included. The model with the best performance was a feedforward model consisting three dense layers with ReLU activation and four dense layers with Linear activation. Training of the model was performed in 32 epochs. Validation of the model resulted in an accuracy of 96% (figure B), precision of 95% and recall of 96%.

Conclusions
The morphology based deep learning model developed in this study was able to discriminate atrial fibrillation from sinus rhythm with a fairly high accuracy using a limited size dataset and only one lead.
P2440Increased mortality with high versus normal ejection fraction in elderly women
Authors: Haghi A , Playford D , Stewart S , Bulsara M , Strange G 
Published: October 2019

Abstract

Mortality with impaired left ventricular ejection fraction (LVEF) has been clearly demonstrated. However, the prevalence and significance of increased LVEF (beyond the guideline-recommended normal range) in the community is unclear. We used the National Echo Database Australia (NEDA) to compare mortality in patients with normal and high LVEF.

Methods
NEDA contains echo data (>530,000, years 1997–2017) from laboratories (N=14) across Australia, linked to the National Death Index (NDI). 331,344 individuals aged >18 years (n=172,251 [52%] men, age=60.8±18.0 years and 152,095 [48%] women, 60.9±19.2 years) had a mean follow up of 5.4 person-years and 63,142 fatal events. LVEF using Method Of Discs (MOD) could be calculated in 116,544 individuals. We compared mortality in those with normal LVEF (52–72% for males and 54–74% for females) compared with high LVEF (>72% and >74% for males and females, respectively).

Results
Mortality was 11% higher in females with high LVEF vs females with normal LVEF. On multivariable logistic regression, high ejection fraction remained an independent predictor of mortality after correction for age, gender and body mass index. High LVEF was positively associated with female gender, age and diastolic dysfunction. Of 96,033 individuals in the study population, there were 46,876 males (48.8%), mean age 61.19±17.09 years, not significantly different from their female counterparts. 44,282 males had normal LVEF (52–72%) as opposed to 2,594 with high LVEF (>72%). In females, 46,186 had normal LVEF (54–74%) and 2,971 had high LVEF.InCox proportional hazard models, the hazard ratio (HR) for mortality in males with normal EF was 1.105 for age (95% CI 1.102 to 1.07) and 1.074 (95% CI 0.988 to 1.167) for high LVEF (p<0.001 for all outputs). In females, the corresponding adjusted HR was 1.107 for age (95% CI 1.105 to 1.110) and 1.140 for high LVEF (95% CI 1.057 to 1.230).

Conclusion
High LVEF, particularly in older women, is associated with increased mortality compared with an LVEF within the reference range. Further study is required to evaluate possible mechanisms for worse outcomes in patients with high LVEF.
P2443Diagnostic performance of 2d-echocardiography versus cardiac catheterization in assessing left ventricular end-diastolic pressure: a meta-analysis
Authors: Acosta K , Cano J , Esposo E , Shiu L , Masbang A 
Published: October 2019

Abstract

Introduction
Heart failure (HF) is a major public health problem that affects 23 million people worldwide. The global incidence and prevalence rates of HF are approaching epidemiologic proportions, as evidenced by the relentless increase in the number of HF hospitalizations, the growing number of HF deaths, and the spiraling costs associated with the care of HF patients. Its diagnosis may be challenging because symptoms are nonspecific. Determination of left ventricular filling pressure (LVFP) is important to interpret equivocal symptoms so as to optimize therapy. Catheterization remains to be the gold standard; however, it is not practical to submit many patients with clinical suspicion of HF to invasive studies. Although echocardiographic indices are recommended by recent guidelines (Level IIIB), studies have shown conflicting results on its diagnostic performance.

Purpose
This study aims to identify the diagnostic performance of 2D-echocardiography compared with cardiac catheterization in assessing LV end-diastolic pressure (LVEDP) among adult patients with suspected HF using a meta-analysis of observational studies.

Methods
Eight studies with a total of 1,153 patients with suspected HF who underwent simultaneous evaluation of echocardiographic estimates of LVFP and invasive measurement of LVEDP by cardiac catheterization were included in the final analysis after extensive searching. Review Manager 5.3 was used to the assess the sensitivity and specificity of E/e' lateral, septal and average, and left atrial volume index (LAVI). Meta-Disc was applied to obtain pooled estimates, receiver operating characteristic curve (ROC) and area under curve (AUC) using a 95% confidence interval.

Results
Overall, pooled estimates for E/e' septal >15, E/e' lateral >12, E/e' average >13 and LAVI >34 have significant diagnostic values with pooled sensitivity of 62% (95% CI 0.54 to 0.69), 39% (95% CI 0.33 to 0.45), 81% (95% CI 0.73 to 0.87) and 53% (95% CI 0.46 to 0.61) respectively; pooled specificity of 59% (95% CI 0.53 to 0.65), 87% (95% CI 0.81 to 0.91), 72% (95% CI 0.65 to 0.78) and 69% (95% CI 0.57 to 0.79) respectively; and pooled AUC of 0.624, 0.8486, 0.8190 and 0.69 respectively.

Conclusion
2D echocardiography have significant diagnostic performance compared with cardiac catheterization in assessing LVEDP among adults with suspected HF. Guidelines may be updated using this meta-analysis.