bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1926Artificial intelligence in echocardiography for standard clinical metrics
Authors: Hewitt W , Curtis L , Spyker A , Howitt L , Walsh H , Gladding P 
Published: October 2019

Abstract

Introduction
A full transthoracic echocardiogram (TTE) study usually takes 40 - 60 mins to perform and report. Our aim was to validate an artificial intelligence (AI) which automatically calculates measurements with manual standard clinical metrics.

Methods
41 patients with heart failure (HF) and 19 controls were enrolled retrospectively. A shortened 5-minute TTE exam was performed. Studies were exported from the hospital database in a DICOM format and fed to an AI pipeline to classify, segment and analyse each image. A convolutional neural network (CNN) was used to label each view into one of 23 classes. Views of interest (Apical 2-, 4-Chamber and Parasternal Short/Long Axis) were individually segmented using a segmentation CNN. View classification was trained on 4,000 labelled studies, segmentation models were trained for each view with 72 manually segmented images for PSAX, 128 for PLAX, 168 for A4C and 198 for A2C. The area-length formula was used to calculate left-ventricular volumes (LVEDV/LVESV), ejection fraction (AI-LVEF). Indexed LA volume (LAVOLI) LV mass (LVMI) were also compared. LVEDV, LVESV, LVEF and LVMI were averaged over multiple videos.

Results
Mean manual LVEF (M-LVEF) in HF patients was 39±10% vs 57±5% in controls. Compute time using was between 4 to 7 mins for classification, segmentation and analysis using a single Graphics Processing Unit (GPU). 11 (18%) non-physiological AI-ESV and associated AI-LVEF were excluded vs 2 (3%) M-LVEF (×2 7 95% CI 3 to 27%, p=0.008). AI generated measurements correlated well with manual measures LVEDV r=0.77, LVESV r=0.8, LVEF r=0.71, LAVOLI r=0.71, LVMI r=0.6, p<0.005. Mean absolute error of M-LVEF vs AI-LVEF was 7.4±6.6%. AI-LVEF, M-LVEF and other HF biomarkers had a similar discrimination for HF (AUC M-LVEF 0.93 vs AI-LVEF 0.88, 95% CI-0.03 to 0.15, p=0.19).
AI vs Manual, Correlation Matrix and ROC

Conclusion
AI with minimal human input is approaching the accuracy required for clinical utility. AI has the ability to distinguish LV systolic dysfunction, and chamber volumes which could be applied to handheld ultrasound in real-time.

Acknowledgement/Funding
Health Research Council of New Zealand, Auckland Bioengineering Institute
P1931Effect of de-escalated switching dual antiplatelet therapy after acute myocardial infarction in patients undergoing percutaneous coronary intervention: real-world data from a nationwide cohort study
Authors: Hsu C.-Y , Yeh J.-S , Huang C.-Y 
Published: October 2019

Abstract

Background
Recently, both unguided (platelet function testing independent) and guided (platelet function testing dependent) DAPT de-escalation strategies have been investigated in different clinical studies but the data is still limited and conflicting. The aim of this study was to examine the effect of switching dual antiplatelet therapy (DAPT) on the major vascular risk after acute myocardial infarction (AMI) in patients undergoing percutaneous coronary intervention (PCI) by using Taiwan National Health Insurance Research Database.

Methods
In total, 1,903 and 4,059 patients defined as switched to aspirin and clopidogrel (switched DAPT) and continuation of aspirin and ticagrelor (unswitched DAPT) cohort, respectively who had received PCI during AMI hospitalization, on aspirin and ticagrelor initially and without occurring adverse events at 3 months were evaluated between 2013 and 2015. An inverse probability treatment of weighted approach was adopted to balance the baseline differences between two groups and Cox proportional hazard regression and competing risk regression were used to evaluated the effect of switching DAPT on death, AMI readmission, major bleeding and non-major clinically relevant bleeding.

Results
The incidence rates (per 100 person-year) of death and AMI readmission were 3.97 (95% confidence interval [CI] = 3.19–4.84) and 3.84 (95% CI = 3.09–4.73) in switched cohort and 1.83 (95% CI = 1.47–2.24) and 2.23 (95% CI = 1.82–2.68) in unswitched cohort, respectively. After adjustment for patients' clinical variables, switched cohort had higher risk of death (adjusted hazard ratio = 2.18, 95% CI = 1.62–2.93, P<0.001), and AMI readmission (adjusted sub-distribution ratio = 1.72, 95% CI = 1.27–2.34, P<0.001) compared to these in unswitched cohort; however, there was no difference in the risk of bleeding. Subgroup analysis showed a similar findings in many specific groups, except the patients who were younger age and had lower comorbidity score.

Conclusion
Switching DAPT might increase the risk of death and AMI readmission among patients with AMI undergoing PCI.
P1935Pharmacokinetic and pharmacodynamic assessment of a lipid-based aspirin formulation: results of a prospective, randomised, crossover study
Authors: Angiolillo D J , Bhatt D L , Lanza F , Cryer B , Dong J , Jeske W , Von Chong E , Prats J , Deliargyris E , Marathi U 
Published: October 2019

Abstract

Objectives
Aspirin, or acetylsalicylic acid (ASA), can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer, underscoring the need for ASA formulations with a more favorable safety profile while maintaining an effective pharmacologic profile. A liquid formulation using a novel pharmaceutical lipid aspirin complex (PL-ASA) has been designed to prevent the disruption of the protective mucosal bilayer. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with traditional, immediate release aspirin (IR-ASA).

Methods
In this active-control crossover study, 16 healthy volunteers were randomized to receive a single dose of either IR-ASA 325 mg or PL-ASA 325 mg in a sequential fashion with a 2-week washout period between treatment assignments. The primary objectives of the study were to assess PK (i.e., plasma salicylic acid levels) and PD (i.e., serum thromboxane B2 levels) bioequivalence over a 24–hour period after drug administration, of PL-ASA and IR-ASA using established criteria.

Results
The PK parameter values were similar for PL-ASA and IR-ASA, with median AUC 0-t and Cmax values nominally higher for PL-ASA. Log-transformed PK parameters meeting FDA-criteria for bioequivalence (80% to 125%) are provided in the Table. Serum thromboxane B2 levels were similar for PL-ASA and IR-ASA, with Cmin values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) for both drugs. Both drugs also showed >99% inhibition of serum thromboxane B2 levels (≥95% inhibition represents the cut-off to define aspirin responders). Several secondary PK/PD parameters showed similarities between the two drugs (data not shown). Overall, these findings support functional and clinical equivalence between PL-ASA and IR-ASA.
PK Results Parameter Ratio (PL-ASA/IR-ASA) 90% Confidence Interval AUC0-t 96.51 89.24, 104.37 Cmax 103.73 92.06, 116.89

Conclusions
PL-ASA's novel liquid formulation has similar PK and PD performance compared with IR-ASA. The improved endoscopic safety profile of PL-ASA coupled with its pharmacologic efficacy equivalent to IR-ASA may result in an improved benefit-risk performance, warranting evaluation in future trials.

Acknowledgement/Funding
PLx Pharma, Inc.
P1940Reciprocal regulation of Endothelial-Mesenchymal Transition by MAPK7 and EZH2 activity in Intimal Hyperplasia and Coronary Artery Disease
Authors: Vanchin B , Sol M , Gjaltema R A F , Van Der Pol B , Brinker M G L , Kiers B , Pereira A C , Harmsen M C , Moonen J A J , Krenning G 
Published: October 2019

Abstract

Introduction
Endothelial cells play a pivotal role in the formation of neointimal lesions by the acquisition of a fibro-proliferative phenotype through endothelial-to-mesenchymal transition (EndMT). Uniform laminar shear stress activates the mitogen-activated protein kinase 7 (MAPK7) which suppresses EndMT. It is elusive how MAPK7 activity is regulated in fibroproliferative disease. We recently found in intimal hyperplasia the signaling activity of MAPK7 is rapidly lost through the activation microRNA-374b.
The histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2), which is the catalytic subunit of the Polycomb Repressive Complex 2, plays a pivotal role in endothelial dysfunction. EZH2 trimethylates lysine 27 on histone 3, which silences gene expression and is elevated in endothelial cells in atherosclerotic lesions. Here, we found the reciprocity that exists between MAPK7 and EZH2 in the regulation of EndMT and in human coronary artery stenosis.

Materials and results
In endothelial cells, activation of MAPK7 increases the expression of microRNA-101, which represses the expression of EZH2. Reciprocally, the loss of EZH2 coincides with a decreased expression of the Dual Specificity Phosphatase (DUSP)-1 and DUSP-6 – the phosphatases responsible for the dephosphorylation of MAPK7 - which facilitates the activation of MAPK7.
H3K27Me3, the repressive histone mark placed by EZH2, is abundantly present in the promoter regions of the miR-200b/a/429 and miR-200c/141 gene clusters, which are responsible for the loss of DUSP-1 and DUSP-6 expression. Endothelial cells deficient in EZH2 have reduced levels of H3K27Me3 at these gene promoters, which associates with the increased expression of miR-200b and miR-200c and concurrent increased MAPK7 activation. In endothelial cells with constitutively active MAPK7 signaling (MEK5D), the enrichment of H3K27Me3 at the promoter regions of miR-200b/a/429 (1.6-fold, p=0.034) and miR-200c/141 (1.9-fold, p=0.035) is decreased, suggesting that MAPK7 activation results in a decreased EZH2 activity. Disbalances in this reciprocal signaling circuit culminate in the induction of EndMT and associate to the severity of human coronary artery stenosis.

Conclusion
In summary, we show that in endothelial cells there is reciprocity between MAPK7 signaling and EZH2 expression and that disturbances in this reciprocal signaling circuit associate with the induction of EndMT and severity of human coronary artery stenosis. The reciprocity between MAPK7 and EZH2 is governed by a complex mechanism involving microRNAs and the phosphatases DUSP-1 and DUSP-6. Our study contributes to a better understanding of the molecular and epigenetic cascades that underlie EndMT during coronary artery stenosis and might identify novel targets for therapy.

Acknowledgement/Funding
Mongolian Government Scholarship #621
P1944Relationship between the duration of hypertension and cerebral and cardiovascular disease in the adult Korean population
Authors: Rha S W , Choi B G , Choi S Y , Byun J K , Cha J A 
Published: October 2019

Abstract

Background
Although advances in medical technology and health care have led to increased life expectancy, the prevalence of chronic diseases such as hypertension, diabetes, stroke and cardiovascular events has increased.

Purpose
This study evaluated the prevalence of hypertension, treatment, and the impact of hypertension on cardiovascular disease (CVD) and stroke risk in Koreans.

Methods
The Korean National Health and Nutritional Examination Survey (KNHANES) database, which is a stratified random sampling to assess the health and nutritional status of Koreans (https://knhanes.cdc.go.kr), was analyzed for this study. The subjects of the survey were sampled to represent the entire population of the Republic of Korea. The endpoints of the study are the risk of CVD and stroke due to the prevalence of hypertension. We also examined the relationship between the control of hypertension and the risk of CVD and stroke.

Results
The prevalence of hypertension has increased rapidly as with longer life expectancy of the population. As the duration of hypertension increases, CVD and stroke risks are increased. Achieving a target goal blood pressure below 140/90 mmHg can reduce the risk of all CVD and stroke by nearly half.
Korea-HTN

Conclusion
The risk of CVD and stroke in hypertensive patients can be significantly reduced by achieving optimal blood pressure control.
P1957Impact of fraility on the super elderly patients with peripheral artery disease
Authors: Nishigawa K , Nagae A , Miura T , Katoh T , Hirabayashi M , Miyashita Y , Kashiwagi D , Mochidome T , Sakai T , Senda K , Saigusa T , Ebisawa S , Okada A , Motoki H , Kuwahara K 
Published: October 2019

Abstract

Background
The current consensus is that frail patients have high risks of mortality. However, it remains unclear whether frailty is associated with mortality risks in super-elderly patients with peripheral artery disease (PAD).

Methods
The I-PAD registry was a prospective multicenter observational study involving 12 institutions in Nagano prefecture in Japan. From July 2015 to July 2016, the I-PAD registry enrolled 371 consecutive PAD patients who had undergone endovascular therapy (EVT). Among them, we selected and analysed 109 PAD patients who were >80 years old when they had undergone EVT and divided them into two groups: those with frailty (Clinical Frailty Scale≥5, n=47) and those without frailty (Clinical Frailty Scale≤4, n=62). The primary endpoints were overall survival and major adverse limb events (MALE), defined as a composite of all-cause death, major amputation and revascularization.

Results
The median follow-up period was 1.58±0.3 years. Overall, 109 patients with a mean age of 84.8±4.0 years, of whom 63.3% were men, were included. Overall survival and freedom from MALE were significantly lower among patients with frailty than among those without frailty (60.5% vs. 91.6%, P<0.001; 51.4% vs. 87.5%, P<0.001; respectively).

Conclusion
The prognosis of super-elderly patients with frailty is worse than that of patients without frailty.
P1958Baseline glycated hemoglobin level was differently associated with long-term prognosis in peripheral artery disease patients with and without hemodialysis
Authors: Shirotani S , Jujo K , Mizobuchi K , Ishida I , Minami Y , Haruki S , Akashi M , Nakao M , Hagiwara N 
Published: October 2019

Abstract

Introduction
Diabetes (DM) is the leading cause of induction of hemodialysis (HD), and both are major prognostic factors in patients with peripheral artery disease (PAD). However, the prognostic importance of baseline glycated hemoglobin (HbA1c) levels in PAD patients with and without HD is yet to be elucidated.

Purpose
We hypothesized that baseline HbA1c levels had different prognostic impacts after endovascular therapy (EVT) in between PAD patients with and those without regular HD.

Methods
This observational study included 643 consecutive patients who received EVT between 2013 and 2017. Each of 313 HD patients and 330 Non-HD patients was respectively divided into 2 groups by the comorbidity of diabetes, and DM patients were further divided into 3 subgroups depending on HbA1c level at the time of EVT; DM-Low (HbA1c: <6.0%), DM-Mid (6.1–7.0%), and DM-High (>7.1%) groups. The primary endpoint of this study was major amputation-free survival (AFS).

Results
HD group included significantly more patients presenting critical limb ischemia than Non-HD group (46.6% vs. 30.0%, p<0.001). During the observation period after EVT, there were 81 events (25.9%), including 55 death and 26 major amputations in HD group, and 45 events (13.6%), including 30 death and 15 major amputations in Non-HD group. Kaplan-Meier analysis revealed that DM patients had a significantly higher AFS rate in HD group (Log-rank: p=0.003, Figure A). In contrast, in Non-HD group, there was no statistical difference in AFS between DM and Non-DM patients (p=0.36). In Cox regression analysis in HD group, the higher HbA1c-DM group showed the higher hazard ratio (HR) for AFS (p=0.039, Figure B), and DM patients with HbA1c >6.0% had significantly higher HR than Non-DM patients. Whereas, in Non-HD group, HbA1c-DM class adversely associated with HR for AFS (p=0.003), even any classes did not reach statistical differences from Non-DM patients.
Figure 1

Conclusions
Comorbidity of diabetes at the time of EVT worsened long-term prognosis in PAD patients receiving regular HD, but not in those without HD. Additionally, baseline HbA1c levels oppositely affected prognosis in PAD patients with and without HD.
P2247Pregnancies and childbirth in women with arrhythmogenic right ventricular cardiomyopathy are associated with low risk of ventricular arrhythmias
Authors: Platonov P G , Carlson J , Castrini I , Svensson A , Christiansen M K , Gilljam T , Madsen T , Hansen J , Astrom M A , Haagua K , Jensen H K , Edvardsen T , Svendsen J H 
Published: October 2019

Abstract

Background
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a risk of ventricular arrhythmias (VA) and sudden cardiac death (SCD). Even though female patients with ARVC are considered to be at lower risk of VA, the impact of pregnancy and child birth on the arrhythmic risk and development of arrhythmic substrate in the context of ARVC remains insufficiently studied.

Objective
To assess the risk of VA in relation to childbirth in women with ARVC and the impact of multiple pregnancies on progression of arrhythmic manifestations of the disease.

Methods
The study included 186 females with definite ARVC (n=107, 70 probands) or unaffected mutation-carriers (n=79) with median age at the end of follow up of 48 (IQR 34–60) years. Seventeen women had 1, 59 had 2 and 29 had ≥3 child births by the age of 40 years. VA was defined as ventricular tachycardia, appropriate ICD therapy, aborted cardiac arrest or SCD. Proportions of patients who experienced VA by the age of 40 years were compared between nulliparous women (n=81) and those with reported child births (n=105). VA-free survival after accomplished pregnancies was assessed for women ≥40 years of age (n=119). Cumulative probability of VA for each pregnancy (n=230) was assessed from conception through 2 years after child birth and compared between those that occurred before ARVC diagnosis (Pre-Ds, n=164), after it (Post-Ds, n=11) and in unaffected mutation carriers (No-Ds, n=55).

Results
The nulliparous women had lower age at ARVC diagnosis (37 vs 44, p=0.023) and more often had VA before the age of 40 (31% vs 13%, p=0.003) while the number of child births was not related to the prevalence of VA (18% among women with 1 childbirth, 12% in those with 2 and 14% in those with 3 or more, ns). Three women suffered SCD before the age of 40. VA-free survival after 40 years did not differ between nulliparous and those who gave birth (Figure A). Only four pregnancy-related events were documented (Figure B): 1 in the Post-Ds group and three in the Pre-Ds group. No pregnancy-related events were reported in the unaffected mutation carriers.

Conclusion
In this Scandinavian cohort of women with ARVC we observed no indication of an increased VA risk either associated with pregnancies or during long-term follow up after the last child birth.
P2257Self-care abilities and depression symptoms linked to brain injury in heart failure
Authors: Woo M A , Roy B , Kumar R 
Published: October 2019

Abstract

Heart failure (HF) patients show brain damage in regions controlling mood, autonomic, and cognitive functions. HF patient's exhibit symptoms related to depression, anxiety, poor sleep quality, daytime sleepiness, impaired cognition, and poor self-care, however, the relationship between brain damage and disease related symptoms is unclear. Therefore, our aim was to correlate gray matter density in prefrontal cortices, hippocampus, and insular lobe with disease symptoms using T1-weight voxel based morphometry procedure and evaluate the measure that predicts the brain damage.

Methods
Two high-resolution T1-weighted data were collected from each 42 HF subjects (age, 55.65±7.61; 30 male; LVEF 27.74±9.40%; NYHA class II/III) using a 3.0-Tesla MRI scanner. Depression, anxiety, sleep quality, daytime sleepiness, cognition, and self-care issues were examined with Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Montreal Cognitive Assessment (MoCA), and Self-Care of Heart Failure Inventory (SCHFI) respectively. Both T1-weighted scans were realigned, averaged, and segmented into gray matter (GM), white matter, and cerebrospinal fluid tissue type. GM maps were normalized (unmodulated) to a common space and smoothed to obtain GM density maps. The smoothed GM density maps were used to examine the association of brain damage with disease symptoms (SPM 12; partial correlation; covariates, age and gender; p<0.005). Region of interest analyses were performed in prefrontal cortices, insular lobe and hippocampus to evaluate the correlation using partial correlation (SPSS, covariates, age and gender, p<0.05).

Results
The average scores for BAI 9.55±9.90, BDI 8.69±7.05, ESS 7.00±3.72, MoCA 24.64±3.48, PSQI 6.62±3.90, maintenance 73.12±13.78, management 70.28±13.98, and confidence 73.77±15.96 were calculated. Significant negative correlations was observed between GM density values and BAI (prefrontal cortices, r=−0.532, p<0.001), BDI (prefrontal cortices, r=−0.60, p<0.001; insula, r=−0.528, p<0.001, hippocampus, r=−0.432, p<0.005), ESS (prefrontal cortices, r=−0.419, p=0.007; insula, r=−0.443, p=0.004), and PSQI (prefrontal cortices, r=−0.517, p=0.001) scores, and positive correlation between GM density values, MoCA (prefrontal cortices, r=0.462, p=0.003) and SCHFI scores (maintenance: prefrontal cortices, r=0.422, p=0.007; insula, r=0.412, p=0.009, hippocampus, r=0.455, p=0.004; management: prefrontal cortices, r=0.728, p=0.001; insula, r=0.707, p=0.001, hippocampus, r=0.775, p<0.001) (Figure 1).
Figure 1

Conclusions
HF subjects show more wide-spread and significant correlations between regional GM density values and BDI as well as SCHFI management scores compared to the other disease symptom measures. The findings suggest that damage in mood, autonomic, and cognitive functions sites better correlate with BDI and SCHFI over other measures.

Acknowledgement/Funding
NIH/NINR 1R01 NR014669
P2263Prognostic impact of perceived social isolation in patients with heart failure
Authors: Ikeda T , Iwatsu K , Matsumura K , Ashikawa H , Takabayashi K , Fujita R , Kitaguchi S , Nohara R 
Published: October 2019

Abstract

Background
Perceived social isolation (SI), the subjective sense of feelings of loneliness or isolation, has a negative impact on health outcomes, particularly in older adults. Although SI may also contribute to poor prognosis in patients with HF, evidence on the relationship between SI and outcomes in patients with HF is limited.

Purpose
The aim of this study was to investigate the relationship between SI and hospital readmission in patients with HF.

Methods
This study was a single center prospective cohort study. We consecutively enrolled 203 patients (mean age 72.9±11.7) who admitted for acute HF or exacerbation of chronic HF. At hospital discharge, we assessed perceived SI by using Lubben Social Network Scale - 6 (LSNS-6). Lower scores in LSNS-6 represents greater SI. Study outcome was rehospitalization for worsening HF within 180 days after discharge. We selected the optimal cutoff point of LSNS-6 that predict a worse outcome by the receiver operating characteristic (ROC) curve analysis. We investigate the association between SI and 180-days HF rehospitalization by using Cox proportional-hazard models, controlling for potential confounding factors.

Results
During follow up, A total of 40events (19.7%) were observed. The optimal cut-off point of LSNS-6 score was 17 points (the area under the ROC curve: 0.62, p<0.05, sensitivity: 82.5%, specificity 42.4%). Kaplan-Meier survival curves showed that those patients with greater SI (LSNS-6≤17) presented significantly higher HF rehospitalization rate (Figure). After adjusting for several pre-existing prognostic factors, LSNS-6≤17 was independently associated with HF rehospitalization (hazard ratio2.15,95% confidence interval 1.00–4.89).

Conclusion
The present study shows that SI is a independent predictor of HF rehospitalization in patients with HF. Assessing SI in the clinical practice with a brief screening tool may help identify patients with heart failure at greater risk of rehospitalization.