bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3437Impact of epicardial adipose tissue on global longitudinal strain: a study in patients with normal left ventricular ejection fraction
Authors: Maimaituxun G , Kusunose K.E.N.Y.A , Fukuda D.A.I.J.U , Yagi S , Torii Y , Hirata Y.U.K.I.N.A , Nishio S , Yamada N A O , Yamada H , Soeki T , Wakatsuki T , Sata M , Shimabukuro M 
Published: October 2019

Abstract

Background
Epicardial adipose tissue (EAT) locates anatomically and functionally contiguous to the myocardium and coronary arteries. It has been suggested that EAT accumulation is associated with cardiac remodeling and impaired cardiac performance. However, its role in left ventricular (LV) wall strain remains unclear.

Purpose
In this study, we aimed to clarify: whether EAT accumulation is related to global longitudinal (GLS), circumferential (CS) and radial strain (RS); and if so, in which extent or by which amount of EAT are required to deteriorate these strain.

Methods
Total 180 patients who had no obstructive coronary artery disease (CAD) on multi-detector computed tomography (MDCT) coronary angiography and normal left ventricular ejection fraction (LVEF) on conventional echocardiography were recruited. Cardiac CT was used to quantify EAT volume (EATV) and echocardiographic speckle tracking was used to measure the GLS, CS and RS. EATV index (EATV/Body surface area) was determined as: EAT volume, the sum of the EAT area from the base to the apex of the heart (cm3)/body surface area (m2). Adipose tissue was determined as the density range between −190 and −30 Hounsfield unit. According to the median value (68 cm3/m2), patients were divided into lower and higher EATV index two groups.

Results
In higher EATV index group (95±19 cm3/m2), mean age, body mass index (BMI), prevalence of hyperlipidemia and prevalence of CAD were larger than in lower EATV index group (48±14 cm3/m2). Male gender, hypertension, diabetes, smoking and LV mass index were comparable between two groups. Patients in higher EATV index had lower GLS than those in lower EATV index (−19.4±1.2% vs. −18.8±1.3%, p=0.002). However, there were no significant difference between two groups regarding to the CS and RS. Linear regression analysis showed that there was strong correlation between EATV index and GLS (R=0.216, p=0.004); whereas, both RS and CS were strongly associated with the interventricular septum thickness (RS: R=0.248, p=0.003; CS: R= −0.192, p=0.023) and relative wall thickness (RS: R=0.178, p=0.036; CS: R= −0.184, p=0.030) but not with EATV; on multiple regression analysis, EATV was a predictor of GLS independent of age, male gender, BMI, diabetes, hyperlipidemia, hypertension and CAD (Adjusted R2=0.238, p<0.001).

Conclusion
EATV is independently associated with GLS despite the preserved LVEF and lacking of obstructive CAD, and may play a significant role in estimating impaired longitudinal LV performance.
P3444Overweight and obesity in a Mediterranean pediatric population: impact in cardiac chambers morphology and systolic function
Authors: Fernandez Cabeza J , Aristizabal Duque C U , Blancas Sanchez I M , Ruiz Ortiz M , Delgado Ortega M , Rodriguez Almodovar A , Romero Saldana M , Fonseca Del Pozo F J , Pan Alvarez Ossorio M , Mesa Rubio D 
Published: October 2019

Abstract

Background
Obesity is a major medical and public health problem. A high body mass index has been associated with increased mortality and cardiovascular disease morbidity. Obesity in adults is related to hypertrophy and left ventricular dilatation. Previous studies have shown that, in Spain, the prevalence of overweight and obesity in childhood is 26% and 12.6% respectively. The association between obesity and left ventricular morphology has been poorly studied in the pediatric population.

Aim
To investigate the relationship between childhood obesity and the dimensions of cardiac structures and systolic function in a Mediterranean pediatric population.

Methods
A random sample of children and adolescents in primary and secondary education was selected, stratified by age, gender and educational centers in a rural town of 2864 inhabitants in southern Spain. Children between 6 and 17 years old were included. A transthoracic echocardiogram was performed for the evaluation of cardiac chambers morphology and systolic function.

Results
A total of 212 children were studied (10.9±3.0 years old and 51.9% males): 106 (50%) were normal weight, 57 (26.9%) were overweight and 49 (23.1%) were obese. Results are shown in the table. Age and sex were similar in the three groups. Overweight and obesity were related to larger values of left ventricle end-diastolic diameter and volume, left atrial volume and right ventricle basal diameter, and lower values of left ventricle ejection fraction.
Normal weight Overweight Obese p Age 10.9±3.2 10.7±2.7 11.0±2.8 0.79 Male (%) 50.9% 49.1% 57.1% 0.69 End-diastolic left ventricle diameter (mm) 41.1±5.5 42.8±5.4 44.2±5.5 0.003 End-diastolic left ventricle volume (mm) 57.9±18.6 64.3±18.3 78.1±22.4 <0.0005 Interventricular septum (mm) 6.3±1.4 6.7±1.3 7.0±1.7 0.01 Left ventricle mass (g) 69.3±30.1 80.9±30.2 94.8±36.5 <0.0005 Left atrium volume (mm) 19.7±6.8 22.6±6.5 27.9±7.4 0.004 Basal right ventricle diameter (mm) 27.6±4.5 28.0±3.9 30.2±4.2 0.001 Left ventricle ejection fraction (%) 65.7±3.6 63.6±4.7 61.5±4.6 <0.0005

Conclusions
Overweight and obese children have larger cardiac chambers, higher left ventricular mass, and worse systolic function compared with normal weight children of similar age and sex.
P3453Gender difference in impact of ischemic heart disease on long-term outcome in patients with heart failure reduced ejection fraction
Authors: Kim H J , Kim M A , Lee D I , Kim H L , Choi D J , Han S , Cho M C , Jeon E S , Kim J J , Yoo B S , Shin M S , Chae S C , Ryu K H , Kang S M 
Published: October 2019

Abstract

Background
Ischemic heart disease (IHD) is a major underlying etiology in patients with heart failure (HF). Although the impact of IHD on HF is evolving, there is a lack of understanding of how IHD affects long-term clinical outcomes and uncertainty about the role of IHD in determining the risk of clinical outcomes by gender.

Purpose
This study aims to evaluate the gender difference in impact of IHD on long-term clinical outcomes in patients with heart failure reduced ejection fraction (HFrEF).

Methods
Study data were obtained from the nationwide registry which is a prospective multicenter cohort and included patients who were hospitalized for HF composed of 3,200 patients. A total of 1,638 patients with HFrEF were classified into gender (women 704 and men 934). The primary outcome was all-cause death during follow-up and the composite clinical events of all-cause death and HF readmission during follow-up were also obtained. HF readmission was defined as re-hospitalization because of HF exacerbation.

Results
133 women (18.9%) were died and 168 men (18.0%) were died during follow-up (median 489 days; inter-quartile range, 162–947 days). As underlying cause of HF, IHD did not show significant difference between genders. Women with HFrEF combined with IHD had significantly lower cumulative survival rate than women without IHD at long-term follow-up (74.8% vs. 84.9%, Log Rank p=0.001, Figure 1). However, men with HFrEF combined with IHD had no significant difference in survival rate compared with men without IHD (79.3% vs. 83.8%, Log Rank p=0.067). After adjustment for confounding factors, Cox regression analysis showed that IHD had a 1.43-fold increased risk for all-cause mortality independently only in women. (odds ratio 1.43, 95% confidence interval 1.058–1.929, p=0.020). On the contrary to the death-free survival rates, there were significant differences in composite clinical events-free survival rates between patients with HFrEF combined with IHD and HFrEF without IHD in both genders.
Figure 1

Conclusions
IHD as predisposing cause of HF was an important risk factor for long-term mortality in women with HFrEF. Clinician need to aware of gender-based characteristics in patients with HF and should manage and monitor them appropriately and gender-specifically. Women with HF caused by IHD also should be treated more meticulously to avoid a poor prognosis.

Acknowledgement/Funding
None
P3462IDO activity forecasts obesity in premenopausal females in 10-year follow-up study: the Cardiovascular Risk in Young Finns Study
Authors: Niinisalo P , Raitakari O T , Kahonen M , Viikari J , Juonala M , Kaaja R 
Published: October 2019

Abstract

Background
Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that has an important immunomodulator function. Human inflammatory response promotes upregulation of IDO level in blood. This may lead to suppression of inflammation in atherosclerotic vessel wall and consequently may slow the progression of the disease. Previous studies have shown that IDO activity correlates with early signs of atherosclerosis especially in females but is not an atherosclerosis-specific marker.

Materials and methods
IDO levels were measured from females (n=544; age 24–39; weight 40.5–134.4 kg) in 2001 along with several risk factors for atherosclerosis. Follow-up risk factor measurements were performed in 2007 and 2011. Here we aimed to elucidate the relationship between IDO measurements from 2001 and several atherosclerotic risk factors from 2007 and 2011 by analyzing correlations and risk ratios from the Cardiovascular Risk in Young Finns Study patient cohort.

Results
After age standardization, IDO correlated significantly with BMI (p=0.0008), waist (p=0.0009) and logarithmically modified triglycerides (p=0.0488) and CRP (p=0.0014) in female samples (n=434) from 2007. When female samples (n=384) from 2011 were examined, statistically significant correlations were discovered in BMI and Waist in both unadjusted (p<0.0001 and 0.0003, respectively) and age-adjusted analysis (p=0.0007 and 0.006, respectively). In contrast, only weak correlations were found in male samples. In risk ratio analysis IDO promoted obesity (RR=1.027, p=0.01) in females (n=431) in 10-year follow-up study even after the data was adjusted for age, CRP and BMI.

Conclusions
It is concluded that IDO activity forecasts obesity – a well-characterized risk factor for diabetes and atherosclerosis – in premenopausal females.
P3503Transcriptome changes in atrial myocytes during the transition from a proliferative into a contractile phenotype and vice versa
Authors: Liu J , Tsonaka R , Mei H , Akerboom B , Schalij M , Pijnappels D , De Vries A 
Published: October 2019

Abstract

Background
iAM-1 cells are conditionally immortalized neonatal rat atrial myocytes allowing toggling between proliferative and contractile phenotypes by a single-component change in culture medium composition. In the absence of proliferation stimuli, the cells synchronously differentiate into functional cardiomyocytes. Following re-expression of the immortalization factor, the fully differentiated iAM-1 cells dedifferentiate and start to proliferate again.

Purpose
The aim of our study was to investigate the changes in gene expression profile in iAM-1 cells during one round of cardiac differentiation and dedifferentiation in order to identify potential (new) regulators of atrial myocyte differentiation and proliferation.

Methods
RNA sequencing was performed on iAM-1 cells at 9 time points during one cycle of cardiomyogenic differentiation and dedifferentiation (20 million 150-bp paired-end reads per sample, 4 samples per time point). The resulting sequence data were analysed by EdgeR. Hierarchical clustering and principle component analysis were performed in R. GO category enrichment was determined using DAVID.

Results
Approximately 13,000 genes were extracted from the RNA sequencing analysis. In general, dynamic changes in mRNA levels during the transition from a proliferative into a contractile phenotype opposed those that occurred when differentiated iAM-1 were re-exposed to proliferation stimuli. These inverse trends were most evident for genes involved in cell cycle progression, DNA replication, sarcomere formation and cardiac contraction. Moreover, the RNA-SEQ data allowed us to make a distinction between genes contributing to the early and late phases of cardiomyogenic differentiation and dedifferentiation and to identify similarities and differences in the transcriptional programs underlying the cardiomyogenic differentiation of iAM-1 cells versus those of embryonic stem cells and induced pluripotent stem cells. The transcriptome analysis also unveiled several genes with potentially important and previously unrecognized roles in cardiomyocyte differentiation and proliferation.
iAM-1 differentiation and dedifferention

Conclusions
Due to their ability to homogenously and synchronously differentiate and dedifferentiate, iAM-1 cells offer unique new insights into the transcriptional regulation of cardiomyocyte differentiation and proliferation.
P3506A novel urinary biomarker predicts 1 year mortality after discharge from Intensive Care
Authors: Zhang Z Y , Nkuipou-Kenfack E , Yang W Y , Mujaj B , Thijs L , Latosinska A , Acloque E , Mischak H , Mebazaa A 
Published: October 2019

Abstract

Rationale
Tools reflecting molecular processes predicting death after discharge from intensive care unit (ICU) are currently unavailable.

Objectives
To construct a urinary proteomic biomarker predicting 1-year post-ICU mortality.

Methods
In 1081 patients, enrolled in the French and European Outcome Registry in Intensive Care Unit (NCT01367093), the urinary proteome was measured at ICU discharge using capillary electrophoresis couple with mass spectrometry along with clinical variables; circulating biomarkers (NT-proBNP, hsTnT, biologically active adrenomedullin, soluble ST2, and NGAL) and urinary albumin were available in 886 patients.

Measurements and main results
In the discovery sample (60/256 deaths/survivors), support vector machine modelling identified ACM150, mainly consisting of collagen fragments, yielding an AUC of 0.676 (95% CI, 0.615–0.737). In the replication sample (151/608 deaths/survivors), AUC was 0.704 (0.659–0.750). While accounting for center and clinical risk factors, the hazard ratios in all available patients were 1.27 (1.18–1.37) for ACM150 (+1 SD), 1.20 (1.16–1.33) for the Charlson score (+1 point), and ≥1.30 (P≤0.0071) for the other biomarkers (+ 1 SD). Model performance assessed by adding ACM150 to a basic model including the aforementioned covariables, the Charlson score or any other biomarker confirmed the prognostic accuracy of ACM15 with significant increases (P≤0.0038) in integrated discrimination (≥ +0.50) and net reclassification improvement (≥ +53.7) and AUC (≥ +0.037). Interactome mapping (STRING) based on 72 sequenced peptides and 25 parental proteins gravitated around collagen nodes.

Conclusions
ACM150 is a urinary proteomic classifier predicting 1-year post-ICU mortality over and beyond other biomarkers and reflects dysregulation of collagen turnover as underlying pathophysiological process.
P3509Leukocyte derived tumour necrosis factor modulates cardiac function in health and disease
Authors: Walker S , Gutierrez Del Arroyo A , Sanchez J , Ackland G L 
Published: October 2019

Abstract

Purpose
Tumour necrosis factor alpha (TNFα) regulates both normal and pathophysiological cardiac function. The regulatory role of TNFα derived from different sources (leukocyte versus cardiac cells) in cardiac physiology is unclear. Deficiency of iRhom2 protein prevents circulating immune cells from shedding TNFα (and CD62L, an adhesion molecule essential for effective immune function). Here we investigated the role of leukocyte derived TNFα in constitutive cardiac function and after cardiac injury.

Methods
Adult iRhom2-deficient mice (KO) and wildtype (Wt) littermates, of both genders, underwent echocardiography to assess cardiac physiologic function at least 1 week before receiving a single dose of isoproterenol (300mg/kg IP) to induce cellular death in 10% of the cardiomyoctes [1]. Cardiac echocardiography was repeated 36 hours after isoproterenol. Peripheral and cardiac-resident leukocytes were phenotyped by flow cytometry and molecular markers of cardiac stress (atrial and brain natriuretic protein, ANP, BNP) and inflammation (NFkB) were quantified using RT-PCR.

Results
Peripheral leukocytes from iRhom2 KO mice failed to shed CD62L in response to isoproterenol induced cardiac injury (e.g. neutrophils CD62L Mean Fluorescence Intensity KO: 9149±4616, Wt: 972±558, p<0.0001, n=9). iRhom2-deficient mice had higher cardiac output at baseline (KO 23±2 mL/min, n=11) compared to their wildtype littermates (Wt 18±3 mL/min, n=9). Wild type mice increased contractility after isoproterenol (Wt ejection fraction: baseline 60±6%, isoproterenol 68±6%, n=8) whilst iRhom2-deficient mice were unable to (KO ejection fraction: baseline 66±9%, isoproterenol 61±5%, n=8). ANP and BNP mRNA were elevated in ventricular tissue of iRhom2-knockout mice after isoproterenol, when compared to naïve tissue (ANP 2ΔCT: 3x increase, BNP 2ΔCT: 1.6x increase) whereas only ANP was elevated in wildtypes (ANP 2ΔCT: 2.7x increase, BNP 2ΔCT: 0.9x increase). No difference in immune cell infiltration of ventricular cardiac tissue was observed (number of CD45+ cells KO: 3014±3482, Wt: 2555±1411, p=0.7, n=9) NFkB mRNA was upregulated at baseline (2ΔCT KO: 0.2±0.08, Wt: 0.1±0.09) suggesting constitutive cardiac inflammation in iRhom2-deficient mice.

Conclusions
Inability to shed CD62L and TNFα is associated with constitutive and acquired cardiac dysfunction in iRhom2-deficient mice. These data support the hypothesis that leukocyte-derived TNFα is required for maintaining cardiac function in health and disease.

Acknowledgement/Funding
National Institute of Academic Anaesthesia/Royal College of Anaesthetists/British Journal of Anaesthesia; National Institute for Health Research
P3519Sex-based disparities in end of life care among patients with heart failure
Authors: Van Spall H G C , Hill A , Fu L , Ross H , Wunsch H , You J , Fowler R 
Published: October 2019

Abstract

Background
There are sex-based disparities in care and outcomes among patients with heart failure (HF), but the association between sex and health care services received at the end-of-life health is unknown.

Purpose
To assess for sex-based differences in location of death and the type and intensity of health care services received at the end of life among patients with HF.

Methods
We conducted a retrospective cohort study of adults (≥18 years) who died between April 1, 2004 and March 31, 2017 in Ontario, Canada. We included decedents who had a diagnosis of HF and a hospitalization for HF in the year preceding their death. We obtained demographic, clinical, health care utilization, and healthcare system cost data from population-based administrative databases, using unique encrypted identifiers to link records. We used descriptive statistics and a 2-level multivariable logistic regression model with patients (1st level) nested in regions (2nd level) to assess whether sex was independently associated with death in hospital.

Results
We identified 396,024 adults (51.5% women) who died of HF between April 1, 2004 and March 31, 2017. Mean (SD) age at death was 81.8 (10.7) years and a majority of deaths (53.4%) occurred in the hospital. During the last 6 months of life, a significantly lower proportion of women than men experienced emergency department visits (81.7% vs 86.5%; p<0.001); hospitalizations (75.6% vs 80.8%; p<0.001); intensive care unit (ICU) admissions (22.8% vs 30.1%; p<0.001); mechanical ventilation (15.5% vs 20.8%; p<0.001); cardiac catheterization (2.8% vs 4.6%; p<0.001); coronary revascularization (1.5% vs 2.6%; p<0.001); hemodialysis (4.8% vs 7.7%; p<0.001); or care from 10 or more different physicians (57.6% vs 67.1%; p<0.001). In the last 6 months of life, women spent fewer days than men in the hospital (mean 16.4 vs 18.3; mean difference [MD] 1.9 [95% confidence interval 1.7–2.0]; p<0.001), in an ICU (mean 2.1 vs 3.0; MD 0.9 [95% CI 0.8–0.9]; p<0.001), and on a ventilator (mean 1.4 vs 1.9; MD 0.5 [95% CI 0.5–0.5]; p<0.001). These differences persisted and remained significant in the last month of life. There was no difference in the proportion of women vs men receiving palliative care services (45.1% vs 45.0%; p=0.53) in the last 6 months of life. After adjusting for age, socioeconomic status, comorbidities, place of residence, and year of death, women had lower odds of dying in a hospital than men (adjusted odds ratio 0.88 [95% CI 0.87–0.89]).

Conclusion
In this large cohort study in Ontario, Canada, women with HF received disproportionately lower in-hospital and invasive care services than men in their last 6 months of life and were more likely than men to die at home.

Acknowledgement/Funding
Canadian Institutes of Health Research
P3525Buspirone effect on chemoreflex and central apneas in heart failure
Authors: Borrelli C , Giannoni A , Mirizzi G , Emdin M , Passino C 
Published: October 2019

Abstract

Background
Increased chemosensitivity to carbon dioxide (CO2) is an important trigger of central apneas in heart failure (HF), contributing to HF progression and mortality. We hypothesized that buspirone, a 5HT1A receptor agonist that inhibits serotonergic chemoreceptor neuron firing in animals, can decrease CO2 chemosensitivity, thus preventing CA in patients with HF.

Methods
Sixteen patients with systolic HF (age 71.3±5.8 years, left ventricular ejection fraction 29.8±7.8%) and moderate-severe central apneas (nighttime apnea/hypopnea index AHI≥15 events/hour) underwent a double-blind, placebo-controlled, cross over, randomized study of oral buspirone administration (45 mg/day for 1 week).

Results
Buspirone reduced CO2 chemosensitivity compared to placebo (1.2 IR [1.1–1.5] vs. 2.0 [1.6–2.2] L/min/mmHg, p=0.008). Furthermore, buspirone improved: the AHI at nighttime (16.5 [8.5–24.7] vs. 27.5 [23.0–37.3] events/hour, p=0.002), and daytime (8.0 [2.3–11.5] vs. 11.5 [6.3–18.8] events/hour, p=0.006); the central apnea index at nighttime (4.0 [1.0–19.0] vs. 12.5 [8.3–27.3] events/hour, p=0.01) and daytime (1.0 [0.0–3.0] vs. 4.0 [1.3–6.0] events/hour, p=0.009); and the oxygen desaturation index at nighttime (4.7 [1.0–11.0] vs. 20.0 [8.7–26.5] events/hour, p=0.004) and daytime (0.2 [0.1–0.7] vs. 1.2 [0.3–4.8] events/hour, p=0.005). Buspirone showed a good safety profile and had no effect on neurohormones, arrhythmias, exercise capacity and mood/daytime sleepiness.

Conclusion
Buspirone reduces CO2 chemosensitivity and inhibits central apneas both during the day and the night in patients with systolic HF.