bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3495: Obesity and Development of New Atrial Fibrillation in the Women’s Health Study
Authors: Tedrow Usha B , Conen David , Koplan Bruce A , Manson JoAnn E , Buring Julie E , Albert Christine M
Published: July 2021

Obesity and atrial fibrillation (AF) are increasing public health problems, especially among women. Overweight and obesity (as defined by WHO criteria) have been previously associated with incident AF in existing cohorts; however, relatively few women with AF were included. We sought to further characterize the risk of incident AF over the entire range of body mass index (BMI) in a large prospective cohort of women enrolled in the Women’s Health Study. Women included in this analysis provided information on BMI and were free of cardiovascular disease and AF at baseline. Among the 38,807 women, 1022 incident AF cases were reported (9.8 +/− 1.2 person-years of AF). Compared with women not reporting AF, those who developed AF were older (58.8 +/− 8.0 vs 54.4 +/− 6.9 years), had higher BMI (27.2 +/− 5.7 vs 26.0 +/−5.0 kg/m2), and were more often diabetic (4.3% vs 2.5%), hypertensive (41.5% vs 2.5%), and hyperlipidemic (35.4% vs 29.1%), p < 0.0001 for each comparison. Continuous BMI was associated with AF in age-adjusted (HR 1.05; 95%CI, 1.04 –1.06) and multivariable Cox proportional hazards models controlling for age, diabetes, hypertension, hyperlipidemia, smoking, and physical activity (HR = 1.04; 95%CI, 1.03–1.05, p < 0.0001). When BMI was divided into 7 pre-specified categories, risk of AF was significantly increased among those with a BMI > 30 (see graph). Compared with women with BMI < 21, women with BMI > 35 were at 1.90-fold (95%CI, 1.42–2.55) increased risk of AF even after controlling for the listed obesity-associated comorbidities.

Conclusion:
These prospective data suggest a nonlinear relationship between BMI and risk of AF, with significant risk above a BMI threshold of 30 kg/m2.
Abstract 3502: Serum Phosphorus Levels are Associated with Incident Fatal and Non-Fatal Coronary Disease in Men but not in Women in the Community
Authors: Cardarelli Francesca , Bellasi Antonio , Onufrak Stephen J , Shaw Leslee J , Herzog Charles A , Veledar Emir , Vaccarino Viola , Raggi Paolo
Published: July 2021

Mineral metabolism disorders are associated with coronary atherosclerosis and poor outcomes in chronic kidney disease (CKD) and cardiovascular disease (CVD) patients. A recent study suggested that elevated levels of serum phosphorus are associated with increased risk of CVD in subjects free from CKD and CVD. However, data suggest that the distribution of serum phosphorus differs by gender and it is not known whether phosphorus carries the same prognostic significance in men and in women. We tested the association of baseline serum phosphorus levels with incidence of CHD (myocardial infarction or fatal coronary disease) in 13,998 subjects 45 to 64 years old free of CHD, stroke, or CKD from the Atherosclerosis Risk in Communities (ARIC) study with public use data. The mean follow up was 12.5 years. Serum phosphorus was classified according to quintiles. Elevated phosphorus was significantly associated with age, female gender, smoking, hypercholesterolemia, and fibrinogen levels (p < 0.0001 for each), but was inversely associated with hypertension and not associated with estimated glomerular filtration rate (eGFR). We observed a j-shaped relationship of serum phosphorus with CHD among men but not among women. Compared to men in the 2nd quintile, men in the 1st quintile experienced a 30% increased rate of CHD (multivariable adj. HR: 1.30, 95% CI: 1.01, 1.68) while HRs increased incrementally from 1.17 (95% CI: 0.89, 1.54) to 1.51 (95% CI: 1.09, 2.09) from the 3rd through 5th quintiles. This relationship in men remained significant after adjustment for classic CVD risk factors and estimated GFR (table

). Among women, serum phosphorus was not significantly associated with CHD (table

). In conclusion, this study suggests a j-shaped association of serum phosphorus with CHD risk in men but not women free of CKD and CHD at baseline.

Table
Abstract 152: Urotensin-II Activates Rac-1 And ROS Production In Pulmonary Artery Smooth Muscle Cells Involving GPR14 And Gα
I3
Proteins
Authors: Djordjevic Talija , Schaefer Nicola , Weitnauer Michael , Hess John , Görlach Agnes
Published: July 2021

Human urotensin II (hU-II) has recently been described as a potent vasoactive peptide associated with remodelling processes within the vasculature, thus contributing to various cardiovascular diseases including pulmonary hypertension. hU-II acts via the G-protein coupled receptor GPR14. However, the mechanisms mediating GPR14 signalling remain unclear. ROS have been shown to act as signalling molecules in vascular cells, and NADPH oxidases which are activated by Rac-1, are important sources of ROS generation. Therefore, we investigated whether hU-II and GPR14 can activate Rac-1 and NADPH oxidase-mediated ROS production in pulmonary artery smooth muscle cells (PASMC). Urotensin-II activated Rac-1 within 15 seconds and this response was abolished by treatment of PASMC with the GPR14 antagonist urantide. In line, urotensin-II induced a rapid increase in ROS levels within 5 minutes of application, which was prevented by urantide or transfection of a dominant-negative mutant of Rac-1 (RacT17N). Furthermore, in cells overexpressing GPR14 or constitutively active Rac-1 (RacG12V), hU-II-stimulated ROS generation was further enhanced. Interestingly, in the presence of
Pertussis toxin,
hU-II-induced Rac-1 activation and ROS generation were abolished, indicating coupling of GPR14 to Gα
i
proteins. Indeed, transfection of dominant-negative G α
i3
completely diminished hU-II-stimulated ROS generation in PASMC. Similar effects were observed upon depletion of the NADPH oxidase subunit NOX4. Furthermore, hU-II, RacG12V and NOX4 stimulated proliferation of PASMC, whereas antioxidants, RacT17N or NOX4 depletion had opposite effects.These results show that hU-II is a potent activator of Rac-1 leading to rapid activation of NADPH oxidase and ROS generation involving GPR14 and Gα
i3
proteins, and subsequent stimulation of PASMC proliferation. Thus, activation of NADPH oxidase by GPR14 and Rac-1 provides a novel mechanism how hU-II can promote vascular remodelling processes and may provide a novel therapeutic target for pulmonary vasculopathies associated with pulmonary hypertension.
Abstract 471: Systemic Chymase Inhibition Directs Atherosclerotic Plaques Towards a Stable Phenotype in ApoE Deficient Mice
Authors: Bot Ilze , van Heiningen Sandra H , Fingerle Jurgen , Hilpert Hans , van Berkel Theo , Biessen Erik A
Published: July 2021

Activated mast cells have been identified at the site of rupture in human coronary artery plaques and appear to contribute considerably to plaque progression and stability. We and others have previously demonstrated that the mast cell constituents chymase and tryptase promote apoptosis of plaque cells. In this study, we aimed to investigate whether inhibition of mast cell chymase by a specific chymase inhibitor indeed has a beneficial effect on plaque stability. Preincubation of 48/80 activated MC/9 murine mast cells or freshly isolated peritoneal mast cells with chymase inhibitor RO5010226 – 000 – 004 (RO501; 1 μM) inhibited mast cell activation, as illustrated by a decreased β-hexosaminidase activity in the releasate (−41% compared to control MC/9 cells, *P=0.04, and −80% compared to control peritoneal mast cells, *P=0.02) as well as chymase release and activity (−71% and −65%, *P=0.04, respectively). Next, we addressed whether chymase inhibition also was effective in vivo. Atherosclerotic carotid artery lesions were induced in ApoE
−/−
mice by perivascular collar placement; during lesion development mast cells were activated by a DNP challenge once weekly for 4 weeks. Concomitantly, a subset of mice received the chymase inhibitor (50 mg/kg/day, n=14) as diet supplement, leading to continuous serum concentrations of ~2 μM or control diet (n=12). After 6 weeks, the advanced plaques were analyzed for size and stability. While plaque size did not differ, collagen content of the lesions was 2-fold enhanced in mice treated with the chymase inhibitor compared to controls (RO501: 1.4 ± 0.5% versus controls: 0.7 ± 0.2%). This was accompanied by a significant decrease in necrotic core size of the plaques (RO501: 52 ± 3% versus controls: 41 ± 4%, *P=0.04) as well as by an increased plaque cellularity (RO501: 2.6 ± 0.1*10
3
versus controls: 2.3 ± 0.1*10
3
cells/mm
2
tissue). In agreement with these data we did observe increased peritoneal leukocyte numbers in the RO501 treated mice (RO501: 4.2 ± 1.1*10
6
cells versus 2.2 ± 0.3*10
6
cells in controls, *P=0.04). In conclusion, our data suggest that chymase inhibition indeed results in enhanced plaque stability, identifying chymase inhibition as a new therapeutic approach in the prevention of acute coronary syndromes.
Abstract 3541: Resistance Exercise Training Improves Heart Rate Recovery In Young Men
Authors: Heffernan Kevin S , Jae Sae Young , Fahs Christopher A , Fernhall Bo
Published: July 2021

Introduction.
Heart rate recovery (HRR) after exercise, an index of cardiac parasympathetic function, is associated with increased risk for arrhythmia and other cardiovascular morbidities and mortality. Although aerobic/endurance exercise training has been shown effective in improving HRR, little is known regarding the effects of resistance training (RT) on HRR. The purpose of this study was to test the hypothesis that RT would improve HRR.

Methods.
Twenty-nine healthy young men (age 23.5 ± 0.7 yrs, body mass index 25.6 ± 0.9) completed a cross-over design consisting of a 4-week time control period followed by a 6-week RT intervention (3 days per week, total body regimen). HRR was calculated from a graded maximal exercise test as maximal heart rate attained during the test minus heart rate at 1-minute post exercise. Body fat was measured using air displacement plethysmograpy. Strength was assessed using a 1 repetition maximum (1RM) bench press. All measurements were made at baseline (Pre1), following the time control (Pre2) and following RT (Post).

Results.
A time effect was detected for HRR as there was no change in HRR over the time control portion of the study but a significant increase in HRR from pre training to post training (Table 1

, p<0.05). A time effect was also detected for 1RM as there was no change over the time control portion of the study but a significant increase following RT (77.4 ± 4.0 kg to 78.2 ± 3.9 kg to 84.5 ± 3.9 kg, p <0.05). There was no change in VO
2max
, blood lipids, glucose, body fat, or white blood cell (WBC) count over the course of the study (Table 1

, p>0.05).

Conclusions.
These findings suggest that RT has a favorable effect on parasympathetic modulation without changing cardiorespiratory fitness, body composition, WBC count or metabolic profile in young healthy men.

Table 1.

HRR and select variables before and after RT
Abstract 3578: Local Atherosclerotic Plaques Hide Information That Is Predictive For The Occurrence Of Adverse Cardiovascular Events And Will Help To Identify The Vulnerable Patient: A Prospective Cohort Study In 667 Patients.
Authors: Pasterkamp Gerard , Hellings Willem E , De kleijn Domique , de Vries Jean-Paul , Seldenrijk Cees A , De Bruin Peter , Velema Evelyn , Moll Frans L
Published: July 2021

Introduction
Atherosclerosis is a systemic disease and the risk for ischemic events in any vascular bed increases when one arterial bed has been affected. It could be speculated that atherosclerotic lesions within the vascular bed share common denominators that destabilize multiple atherosclerotic lesions and increase risk for a subsequent cardiovascular event. We hypothesized that atherosclerotic plaques hide a cellular and molecular fingerprint that is shared by many plaques within the same individual, and that some of these characteristics would be predictive for the occurrence of clinical events due to progression of atherosclerotic disease.

Methods
Atherosclerotic specimens were collected after carotid endarterectomy and patients underwent clinical follow-up for the duration of 3 years. This first report summarizes the results of a study which investigated the predictive value of histological examination atherosclerotic plaques (macrophage and smooth muscle cell infiltration, collagen, calcifications, thrombus and lipid core) for the occurrence of future adverse cardiovascular events.

Results
A total of 164 (24.7%) of 667 patients reached the composite primary endpoint of myocardial infarction [n=11], PCI [n=14], CABG [n=6] cardiovascular death [n=12], stroke [n=24], cerebral bleeding [n=14], aneurysm surgery [n=8], peripheral artery surgery [n=64], non cardiovascular death [n=11]. The extent of macrophage or smooth muscle cell infiltration, collagen, calcification and lipid core size within the plaque did not predict systemic adverse cardiovascular events during follow up [p>0.20]. However, the presence of thrombus in the dissected plaque was strongly positively associated with reaching the primary endpoint [Cox Regression: Hazard ratio = 1.6; 95% Confidence interval = 1.1 – 2.5].

Conclusion
This atherosclerotic biobank with a longitudinal study design allows identifying local plaque markers related with progression of atherosclerotic disease in the entire vascular system. For the first time we show proof of concept that local plaques hide information that may help to identify the vulnerable patient who is likely to suffer a cardiovascular event.
Abstract 3581: Predicting Mortality in Acute Coronary Syndromes; A Comparison of the TIMI and GRACE Risk Scores
Authors: Aragam Krishna , Tamhane Umesh , Kline-Rogers Eva , Li Jin , Fox Keith A , Goodman Shaun , Eagle Kim A , Gurm Hitinder S
Published: July 2021

Background:
The Thrombolysis In Myocardial Infarction (TIMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores are widely recognized tools for assessing risk in patients with acute coronary syndromes (ACS). However, their relative predictive abilities remain poorly defined in broad-spectrum ACS populations.

Objective:
We sought to compare the effectiveness of the GRACE and TIMI risk scores in predicting in-hospital and 6-month post-discharge mortality in unselected patients presenting with ACS.

Methods:
Data were collected for 3451 patients admitted to the University of Michigan between 1999 and 2005 with an admission diagnosis of ACS. Six month follow-up data were available for 3170 of these patients. GRACE and TIMI scores were calculated for each patient based on previously established criteria. The predictive ability of each score was assessed for two primary outcomes - in-hospital mortality and 6-month mortality - by analyzing the area under each receiver operating characteristic (ROC) curve.

Results:
The observed mortality was 3.97% (137 deaths) in-hospital and 7.38% (234 deaths) at 6 months among those surviving to hospital discharge. The GRACE score was significantly better than the TIMI score in predicting in hospital and 6-month mortality (p<0.0001 in both cases, Figure

).

Conclusion:
The GRACE score was significantly better than the TIMI score in predicting in-hospital and 6-month mortality in unselected patients presenting with ACS.
Abstract 3628: Differences in Implantation-Related Complications between Men and Women Receiving ICD Therapy for Primary Prevention
Authors: Peterson Pam N , Luther Stacie A , Wang Yongfei , Vidaillet Humberto J , Krumholz Harlan M , Heidenreich Paul A , Curtis Jeptha P , Masoudi Frederick A
Published: July 2021

Background:
Studies suggest that women are at higher risk for complications with some invasive cardiac procedures. Little is known about ICD implantation-related complications in community practice. We compared rates of in-hospital complications in men and women receiving an ICD for primary prevention.

Methods:
Using the NCDR ICD registry, we identified a cohort of patients receiving an ICD for primary prevention of sudden cardiac death between January 2005 and April 2007. Outcomes included all complications and major complications (cardiac arrest, perforation, valve injury, coronary venous dissection, hemothorax, pneumothorax, deep phlebitis, TIA/stroke, tamponade, MI, and AV fistula). Multivariable analysis assessed the association between gender and complications, adjusting for demographic, clinical, procedural, physician, and hospital characteristics. Secondary analyses stratified by device type (ICD vs. biventricular (BiV) ICD).

Results:
Of the 59,833 patients, 73% were male and 27% were female. Women were more likely to have a history of heart failure (88% vs. 83%; p<0.01), worse NYHA functional status (57% vs. 50% NYHA Class III; p<0.01), and non-ischemic cardiomyopathy (47% vs. 28%; p<0.01). Women were also more likely to receive BiV ICDs (46% vs. 39%; p<0.01). In unadjusted analyses, women were more likely to experience any complication and major complications (Table

). In multivariable models, women had a significantly higher risk of any complications and major complications. Results were similar when stratified by device type.

Conclusions:
Women are more likely than men to have in-hospital complications related to ICD implantation. As complications attenuate the benefits that might accrue from ICD therapy, the higher risk of complications may influence the decision to implant a device in women. Additionally, strategies specifically directed at preventing complications will be important to improving outcomes after ICD implantation.
Abstract 3674: Association of waist-to-thigh ratio with history of cardiovascular diseases among US adults: Findings from the National Health and Nutrition Examination Survey 1999–2004
Authors: Li Chaoyang , Ford Earl S , Mokdad Ali H , Giles Wayne H
Published: July 2021

Background and Objective:

Limited studies have shown that elevated waist-to-thigh ratio (WTR) may be associated with increased risk of type 2 diabetes and ischemic heart disease. We sought to examine the association of WTR with history of cardiovascular diseases (CVD) among US adults.

Methods:

A total of 11,137 men and nonpregnant women aged 20 years or older in the National Health and Nutrition Examination Survey 1999–2004 were analyzed. WTR was calculated using measured waist and thigh circumferences. A positive history of CVD was defined as having any of the following conditions diagnosed by a doctor: congestive heart failure, coronary heart disease, angina pectoris, heart attack, or stroke. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were obtained in logistic regression analyses.

Results:

The mean WTR was 1.87 for men and 1.75 for women. The age-adjusted prevalence of CVD increased with increasing WTR (p <0.05 for men and p<0.01 for women for linear trends) (Figure

). After adjusted for multiple potential confounders, there was a significant linear trend for the association of WTR with CVD among men (p <0.01), but not among women (p =0.18) (Figure

). There was a two-fold increased likelihood of having CVD comparing the forth to the first quartile of WTR among men (AOR, 2.1; 95% CI, 1.1 to 4.2). This association persisted after further adjustment for body mass index or waist circumference.

Conclusions:

In this most recent nationally representative sample, WTR was significantly associated with history of CVD independent of body mass index or waist circumference, particularly among men..
Abstract 3698: Decreased Circulating Endothelial Progenitor Cells and Endothelial Dysfunction: a Novel Mechanism of Atherogenesis in Obesity.
Authors: Leite Paulo F , Andrade Claudia R , Poppe Santa , Cesar Luiz A , Coimbra Silmara , Luz Protasio L Da , Debbas Victor , Goes Marisa F , Laurindo Francisco R
Published: July 2021

Underlying mechanisms of endothelial dysfunction in obesity are not fully understood. Circulating Endothelial Progenitor Cells (EPCs) are known to promote endothelial repair. Our aim was to assess the number/function of EPCs in morbid obese individuals and its correlation with endothelial function and inflammatory markers. EPCs were isolated from 33 morbid obese patients (age 47±1.8 y; men=34%; BMI=49±2.1 kg/m
2
, metabolic syndrome=84%) and 20 lean controls. Peripheral blood EPC number was significantly reduced in obese patients both with flow cytometry (KDR
+
/CD34
+
; 0.041±0.04 vs 0.074±0.05 %events, p<0.001) and fluorescence analysis after short-term culture (49±4 vs 28±2 cells/field, p<0.001). The plasma number of primitive CD 133
+
cells, and concentrations of VEGF (Elisa) and nitrogen oxides (which potentially recruit EPCs), were similar to control, suggesting that reduction of EPCs occurs distally to early cell differentiation. Importantly, C-Reactive Protein (CRP), robustly increased in obese patients (0.15±0.04 vs 1.3±0.3; p=0.003), was a strong predictor of reduced EPC number at multivariate analysis (r=0.623; p < 0.001). Likewise, the migratory response of EPCs to VEGF in vitro was significantly impaired in obese vs controls, despite similar VEGF receptor numbers. Multivariate analysis suggested potential roles of metabolic syndrome and leptin in such effect. Endothelial function at flow-mediated brachial artery reactivity was markedly reduced (by 60%) in obese patients, and had a significant inverse correlation with EPC number (r= 0.678; p< 0.001). Carotid intimal thickness was also increased in obese patients (0.68±0.02 vs 0.58±0.08; p=0.001). On the other hand, the number of circulating endothelial cells (CD31
+
/CD106
+
) was similar in both groups, suggesting that apoptosis was not enhanced in the obese. These results suggest for the first time that reduced number and migratory capacity of EPCs correlate with endothelial dysfunction or increased CRP and may be a key underlying mechanism of vascular complications and atherosclerosis in obesity.
Abstract 3742: Elevated Brain Natriuretic Peptide and C-reactive Protein Interactively Increased Cardiovascular and All-cause Mortality Risk in Hemodialysis Patients
Authors: Furuhashi Kyuichi , Ishii Hideki , Takahashi Hiroshi , Aoyama Toru , Toriyama Takanobu , Kumada Yoshitaka , Tanaka Miho , Morishita Tetsuji , Amano Tetsuya , Murakami Ryuichiro , Izawa Hideo , Matsubara Tatsuaki , Murohara Toyoaki
Published: July 2021

Background:
It has been established that elevated brain natriuretic peptide (BNP) and C-reactive protein (CRP) levels are increasingly associated with cardiovascular (CV) morbidity. We examined the prognostic usefulness of combining BNP and CRP for predicting CV mortality in hemodialysis (HD) patients.

Methods:
Plasma BNP and serum CRP were measured consecutively in 500 HD patients. These patients were divided into 4 groups according to plasma BNP levels; Quartile 1 (Q1): < 45 ng/L, Q2: 145–266 ng/L, Q3: 267– 628 ng/L, and Q4: >628 ng/L, and serum CRP levels; Q1: <0.09 mg/dl, Q2: 0.09 – 0.27 mg/dl, Q3: 0.27–1.17mg/dl and Q4: >1.17mg/dl, respectively. All patients were followed up for 8 years.

Results:
On Cox proportional hazards analysis, hazard ratio (HR) of elevated BNP levels was 3.93 (95%CI 2.06 –7.52 for Q4 vs Q1) for CV mortality and 3.51 (95%CI 2.18 –5.64 for Q4 vs Q1) for all-cause mortality, respectively (both p<0.0001). Similarly, HR of elevated CRP levels was 6.00 (95%CI 2.89 –12.45) for CV mortality and 8.19 (95%CI 4.53–14.77) for all-cause mortality, respectively (both p<0.0001). In the setting of combination of BNP and CRP, the risk of CV mortality was 23.6-fold in the highest quartile on both BNP and CRP compared with the lowest quartile on both BNP and CRP. Similarly, the risk of mortality was 45.3-fold (Figure

). These variables were significant after adjustment for other CV risk factors.

Conclusions:
Elevated BNP and CRP interactively increased CV and all-cause mortality risk in HD patients. The combination of BNP and CRP is useful for risk stratification in HD patients because the combination of these variables is more closely related to outcome than either variable alone.
Abstract 3782: Persistent Prehypertension is a Risk Factor for Left Ventricular Hypertrophy
Authors: Markus Marcello R , Stritzke Jan , Mayer Björn , Lieb Wolfgang , Luchner Andreas , Döring Angela , Keil Ulrich , Hense Hans W , Schunkert Heribert
Published: July 2021

BACKGROUND:
We aimed to study whether persistent prehypertension has detrimental effects on left ventricular (LV) geometry and function and increases cardiovascular risk.

METHODS:
Subjects (n=1005, aged 25 to 74 years) from a gender and age stratified random sample of residents of the Augsburg (D) area, were examined by standardized echocardiography at baseline and a second time, at a ten year follow-up. We defined two groups of individuals who persistently had either normal systolic and diastolic blood pressures (nBP, i.e., <120 mm Hg and <80 mm Hg; n=142) or prehypertensive blood pressures (preBP, 120 – 139 mm Hg or 80 – 89 mm Hg; n=119) at both examinations. We prospectively evaluated temporal changes in geometry, mass and function occurring with either persistent normotension or prehypertension using linear regression models adjusting for relevant confounders. Subjects taking antihypertensive medications or having hypertensive blood pressures (≥ 140 mm Hg or ≥ 90 mm Hg) were excluded from this analysis.

RESULTS:
After ten years of follow-up, individuals with preBP , as compared to nBP, showed larger relative increases in LV wall thickness (WT, 11.9% [95% CI: 9.3 to 14.5] versus 4.7% [2.4 to 7.1]; p<0.001), relative wall thickness (RWT, 12.9% [9.3 to 16.5] versus 4.3% [1 to 7.5]; p=0.001) and LVM indexed to height
2.7
(LVM/height
2.7
, 15.8% [12.4 to 19.3] versus 8.5% [5.4 to 11.6]; p=0.004) and decrease in E/A (early/late diastolic peak transmitral flow velocity, 15.7% [12 to 19.3] versus 7.7% [4.4 to 11]; p=0.003), respectively. Persistent prehypertension was also associated with a markedly elevated incidence of concentric remodeling of the left ventricle (RWT >0.43) with an odds ratio OR =9.38 [2.94 to 29.9] (p<0.001), of LV hypertrophy (LVM/height
2.7
>44 g/m
2.7
in women and >48 g/m
2.7
in men) with OR =5.59 [1.69 to 18.4] (p=0.009) and of diastolic dysfunction (E/A <1 or E/A ≥ 1 and left atrial end-systolic diameter larger than 40 mm for males or 38 mm for females) with OR=2.52 [1.01 to 6.31] (p=0.048).

CONCLUSIONS:
Persistent prehypertension is associated with an increased risk of concentric remodelling and hypertrophy of the left ventricle and a worse diastolic function suggesting that prehypertension is related to detrimental alterations of the left ventricle.
Abstract 3791: Improved Ventricular-Arterial Coupling After 4 Weeks of Exercise Training in Patients with Chronic Heart Failure
Authors: Sandri Marcus , Gielen Stephan , Mangner Norman , Adams Volker , Erbs Sandra , Linke Axel , Hambrecht Rainer , Schuler Gerhard C
Published: July 2021

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF.

METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO
2
max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound.

RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET.

CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.
Abstract 507: The Glycome Is Functionally Remodeled Throughout The Developing Myocardium
Authors: Montpetit Marty L , Stocker Patrick J , Haslam Stuart M , Head Steven R , Gilmartin Timothy , Schaffer Lana , North Simon J , Jang-Lee Jihye , Marth Jamey D , Bennett Eric S
Published: July 2021

Cell surfaces are replete with complex, biologically important glycan structures responsible for multiple cellular functions including cell adhesion and cellular communication. Proper protein glycosylation is essential for normal development and physiology with the effects of improper glycosylation being severe and even lethal. Gene products involved in glycan formation (glycosylation-associated genes) comprise 1–2% of the genome, resulting in a glycome of thousands of structures; possibly more extensive than the proteome. Using GeneChip microarray analyses, we provide evidence that glycosylation-associated gene expression is highly regulated throughout the developing myocardium. Nearly one-third of the glycosylation-associated genes were significantly differentially expressed in neonatal atria versus neonatal ventricles while 46.8% of these same genes were differentially expressed in neonate versus adult ventricles. Quantitative-PCR of individual genes confirmed the microarray analyses. Such gross glycosylation-associated gene expression remodeling likely modifies the complexity and size of glycosylation structures attached to cell surface proteins. To confirm this, glycan structures were determined and compared among myocyte types using mass spectrometry. The data indicated that the observed regulation in gene expression translated into a change in glycan structure. Further, we report that remodeled glycans are likely responsible for alterations in voltage-gated sodium channel activity and action potential waveforms, suggesting a physiological role for regulation of glycosylation-associated genes in the heart. Specifically, differences in sodium channel gating in neonatal atria versus neonatal ventricles were abolished by knocking out a single polysialyltransferase expressed only in neonatal atria. Atrial action potential duration and the rate of depolarization were altered in the absence of this polysialyltransferase, while ventricle action potential waveforms were unaffected. Together, these data indicate that the glycome is tightly controlled in the heart, and proper glycosylation is apparently essential for normal myocyte functions.
Abstract 515: Expression of Leptin, Adiponectin, and Activation of AMP Kinase in Failing and Mechanically Unloaded Human Hearts
Authors: McGaffin Kenneth , Burkhead Benjamin , Gibson Gregory , Moravec Christine , McTiernan Charles
Published: July 2021

Introduction:
The failing heart displays contractile dysfunction, increased workload and energy demands, and a switch in substrate utilization for ATP production from free fatty acid to glucose oxidation. ATP production is regulated by AMP Kinase (AMPK). In skeletal muscle, the cytokines leptin (OB) and adiponectin (AD) stimulate AMPK activity and result in preferential glucose metabolism. Both OB and AD are elevated in human heart failure (HF), but it is unknown whether these cytokines may alter AMPK activation in the failing and/or mechanically unloaded heart.

Hypothesis
: In human HF, elevated OB and AD levels: 1) are in part due to increased production by the cardiomyocyte; 2) are associated with cardiac AMPK activation; and 3) are downregulated under conditions of reduced workload and ATP requirement such as occurs with mechanical unloading.

Methods/Results:
Left ventricular tissue was obtained from 5 non-failing (NF), 10 end stage failing (F), and 8 paired pre/post ventricular assist device (VAD) patients. Results reported are fold change ±
SEM
relative to NF or pre VAD, compared by
t-test
. Relative to NF, F hearts showed (Real-time PCR) increased mRNA for BNP (4.4±0.4,
P
=0.04), OB (5.4±0.3,
P
=0.03), OBR (7.3±0.2,
P
=0.01) and AD (9.1±0.9,
P
=0.01), while levels of an unrelated gene, the grehlin receptor, were decreased (0.10±0.01,
P
=0.01). Immunoblotting confirmed similar changes in OB, OBR and AD protein levels, and immunoflurescence localized these proteins to the cardiomyocyte. Increased activation of AMPKα was observed in F hearts (1.9±0.2 fold increase vs NF,
P
=0.02) as assessed by the ratio of phosphorylated to total AMPKα. In paired pre and post VAD supported hearts, these changes were reversed after mechanical unloading as decreased BNP (0.020±0.001,
P
=0.01), OB (0.030±0.001,
P
=0.03), OBR (0.25±0.01,
P
=0.02) and AD (0.22±0.01,
P
=0.04) mRNAs were seen relative to the pre VAD state, whereas increased grehlin receptor mRNA was observed (7.6±0.5,
P
<0.01 ) Further, relative to the pre VAD heart, post VAD showed a 1.7±0.2 fold (
P
=0.04) decrease in the activation of AMPK.

Conclusions:
OB and AD are produced by failing cardiomyocytes and may contribute to preferential use of glucose for energy production in HF through activation of AMPK.
Abstract 516: Pathologic Remodeling of Myocardial Cardiolipin in a Porcine Model of Diet-Induced Obesity and Insulin Resistance
Authors: Sparagna Genevieve , Xu Ya , Lu Li , Chicco Adam , Bergman Bryan , Schwartz Gregory G
Published: July 2021

Background:

Cardiolipin is a dimeric phospholipid required for normal mitochondrial function. The majority of cardiolipin molecules contain four linoleic acid (18:2) residues. Pathologic decrease in (18:2)
4
cardiolipin content has been associated with cardiomyopathy. Patients with obesity and insulin resistance have poorer outcomes after myocardial infarction compared with lean subjects. In the present study, we determined if cardiolipin content and composition are altered in a new porcine model of diet-induced obesity and insulin resistance.

Methods:

Yucatan micropigs (n=16) were assigned to a control diet (4% w/w fat, 2% simple sugars, quantity fed 30 g/kg/day) or an intervention diet (25% fat from coconut oil, 17% simple sugars, 50 g/kg/day) for 7 months. Pigs were then anesthetized and subjected to 45 min low-flow myocardial ischemia and 120 min reperfusion (I/R, n=11). Regional myocardial external work and O
2
consumption were measured. After euthanasia, neutral lipid content in myocardial samples was assayed by solid phase extraction and gas chromatographic mass spectrometry, and cardiolipin species were quantified by electrospray ionization mass spectrometry.

Results:

Compared with controls, the intervention diet group recapitulated characteristics of the clinical “metabolic syndrome” with obesity (73 ± 4 vs 40±4 kg), insulin resistance by glucose tolerance testing, hypertension, and hyperlipidemia. There was abnormal substitution of saturated fatty acyl moieties in all myocardial lipid pools. Myocardial content of normal cardiolipin (18:2)
4
was reduced by an average of 13% (p=0.02), while several smaller pools of abnormal cardiolipin species were increased. For example, cardiolipin with one myristic acid residue substituted for a linoleic acid residue was increased by an average of 400% (p=0.001). After I/R, external work was approximately 20% lower (p=0.2) and MVO
2
was 50% lower (p=0.07) in the intervention diet group.

Conclusions:

Pigs fed a diet high in saturated fat and energy content for 7 months develop a phenotype resembling the clinical metabolic syndrome. This is accompanied by pathologic remodeling of myocardial cardiolipin, which in turn may contribute to decreased contractile and metabolic performance after I/R.
Abstract 520: Changes in Plasma Von Willebrand Factor-cleaving Protease(ADAMTS13) Levels in Patients with Unstable Angina
Authors: Fuchigami Shunichiro , Kaikita Koichi , Soejima Kenji , Miura Mitsutoshi , Matsukawa Masakazu , Honda Tsuyoshi , Tsujita Kenichi , Sugiyama Seigo , Ogawa Hisao
Published: July 2021

Background
: Increased plasma levels of von Willebrand factor (VWF) has been reported in acute myocardial infarction (AMI), which indicates the injured endothelial damage in occluded coronary arteries. The larger VWF multimers are known to be more active biologically, and are more potent mediators of platelet thromubus formations. Recently, a metalloprotease that cleaves VWF multimers has been identified, namely, VWF-cleaving protease (ADAMTS13). We recently reported reduced ADAMTS13 activity in AMI patients and the importance of this protease in the prognosis after AMI. However, whether ADAMTS13 may affect the pathogenesis of unstable angina (UA) has not been fully elucidated. The purpose of this study is to examine changes in plasma VWF and ADAMTS13 levels in patients with UA.

Methods and Results
: Plasma VWF and ADAMTS13 levels (mU/ml) were measured in 39 patients with UA, 55 patients with stable exertional angina (SEA) and 47 patients with chest pain syndrome (CPS) at the time of coronary angiography by enzyme-linked immunosorbent assay. We measured these antigen levels after 6 months follow-up period in patients with UA. Plasma VWF antigen levels (mU/ml) increased significantly in patients with UA compared with SEA and CPS (2118.5 ± 810.5, 1571.8 ± 494.2 and 1536.0 ± 526.4, respectively; P < 0.0001 in UA vs. SEA or CPS). Plasma ADAMTS13 antigen levels (mU/ml) decreased significantly in patients with UA than SEA or CPS (741.2 ± 150.9, 875.3 ± 229.0 and 877.3 ± 199.7mU/ml, respectively; P < 0.01 in UA vs. SEA or CPS). Furthermore, there were significant inverse correlations between VWF and ADAMTS13 antigen levels (r = −0.320, P < 0.0001). Plasma VWF and ADAMTS13 antigen levels did not change compared to each level in acute phase in 15 UA patients that the blood samples could be obtained at 6 months follow-up periods.

Conclusions
: These findings suggested the prolonged endothelial damage in UA and tendency toward platelet thrombus formation at the injury sites after the attacks in patients with UA. The long-term antithrombotic therapy might be needed in those patients.
Abstract 526: Oral And Intravenous Anti-thrombotic Activities Of F 16618, A New Selective Par1 Antagonist With Minor Risk Of Bleeding
Authors: Letienne Robert , Perez Michel , Nadal-Wollbold Florence , Le Grand Bruno
Published: July 2021

F 16618 is a new phenyl-pentadienoyl derivative which competitively antagonizes PAR1 giving a prevention
in vitro
against human platelet aggregation. The main goal of the present study was to investigate the anti-thrombotic effects of F 16618 in two models of platelet aggregation-induced arterial thrombosis: an arteriovenous shunt in anesthetized rats and a photochemical-induced carotid artery thrombosis in anesthetized guinea-pigs. Firstly, a shunt was placed between the right jugular vein and the left carotid artery using polyethylene catheters. The kinetics of thrombus formation were assessed by a thermic probe fixed in the middle of the shunt. F 16618 was administered by gavage 15 min before anesthesia. F 16618 dose-dependently increased the occlusion time from 10 to 80 mg/kg, p.o. The first effective dose was 20 mg/kg and the maximal response was found at 40 mg/kg (54 ± 14 %, P < 0.001 vs. vehicle). In addition, 29 % of the shunts remained open 20 min after unclamping in presence of F 16618 (40 mg/kg, n = 7). Similarly, a high dose of F 16618 administered i.v. significantly delayed the occlusion time (29 ± 8 %, P < 0.05) without any significant effect on the tail bleeding time (358 ± 26 sec in the presence of F 16618 vs 397 ± 38 sec in the presence of vehicle). Secondly, the intravenous activity of F 16618 (from 40 μg/kg to 630 μg/kg) was investigated in a model based on the photochemical reaction between Rose Bengal and trans-illuminated green light to induce a transluminal thrombus in a guinea-pig carotid artery. F 16618 was administered as bolus over 2 min before Rose Bengal administration, followed by a constant infusion over 15 min immediately after the source of light was turned on. F 16618 at 80 μg/kg only tended to increase the occlusion time (29 ± 36 % vs. vehicle). From the dose of 160 μg/kg, F 16618 significantly prolonged this occlusion time and the maximal effect was obtained with 320 μg/kg (bolus and infusion, 112 ± 36 %, P < 0.001 vs. vehicle). Collectively, the results demonstrate that F 16618, a new PAR1 antagonist, dose-dependently prevents platelet-induced arterial thrombosis with minor risk of bleeding by both single intravenous or oral administration.
Abstract 5: CPR Fraction Prior to Defibrillation Determines Survival in Prehospital Cardiac Arrest in the Resuscitation Outcomes Consortium (ROC) Epistry
Authors: Christenson James , Andrusiek Douglas , Everson-Stewart Siobhan P , Kudenchuk Peter J , Hostler David , Powell Judy , Callaway Clifton W , Bishop Dan , Vaillancourt Christian , Davis Daniel P , Aufderheide Tom P , Adris Ahamed , Stouffer John A , Stiell Ian
Published: July 2021

Introduction
: In 2005, the American Heart Association recommended increased “hands-on time” during cardiopulmonary resuscitation (CPR) based on animal research and small case series. This study estimated the effect of increasing CPR fraction (proportion of resuscitation time with active CPR) on survival in a cohort of patients with out-of hospital ventricular fibrillation or ventricular tachycardia (VF/VT).

Methods:
Patients were selected from the ROC Epistry who had a confirmed VF/VT cardiac arrest that was not witnessed by Emergency Medical Services (EMS), received no public access defibrillation shock prior to EMS arrival, and had impedance recordings of CPR before the first shock. The proportion of each minute with active CPR, from defibrillator pad application until the first shock, was measured from the electronic resuscitation record by skilled readers who were blinded to hospital discharge outcome. The effect of increasing CPR fraction on survival to hospital discharge was adjusted for age, sex, bystander CPR, public location, interval from 911 call to defibrillator activation, chest compression rate, and ROC community.

Results:
Of 7963 EMS-treated cases of cardiac arrest without public access defibrillation, 1893 had an initial rhythm of VF/VT and 283 of those had electronic tracings and confirmed outcome. Mean age was 63 years and 81% were male. Bystanders performed CPR on 51% and 41% arrested in a public location. Outcomes and odds ratios (OR) with 95% confidence intervals (CI) of survival are shown from lowest to highest category of CPR fraction.

Conclusions:
This study provides preliminary evidence that increasing CPR fraction is associated with increased survival from VF/VT cardiac arrest. Though the study was observational, relatively small, and able only to measure CPR fraction after pad application, these findings suggest that provision of minimally interrupted CPR has direct clinical impact on survival after VF cardiac arrest.
Abstract 8: What is the Frequency of Inappropriate of Emergency Department Catheterization Laboratory Activation For Patients with Potential ST Elevation MI?
Authors: Kontos Michael C , Kurz Michael , Roberts Charlotte S , Joyner Sarah , Kreisa Laura , Ornato Joseph P , Vetrovec George W
Published: July 2021

Background:
To decrease door to balloon time (D2B) for STEMI patients (pts), it is recommended that the Emergency Department (ED) activate the cardiac catheterization laboratory (Cath Lab) directly through a simultaneous group STEMI page that includes the Cath Lab staff and interventionalist. Anecdotal evidence suggests that inappropriate activation is infrequent; however quantitative data is lacking.

Methods
: We assessed the frequency and outcomes of ED STEMI pages to determine the number who had a true STEMI, those who had ECG findings worrisome for but not meeting STEMI criteria, and the frequency of MI. A pt was considered a “false alarm” if emergent cath was not done and MI was excluded. Angiographic findings and outcomes were also evaluated.

Results:
Over a 1 year period, ED activation of the Cath Lab via the STEMI page occurred 98 times. There were 61 (62%) pts with a true STEMI, of whom only two did not have an emergent cath (2 not done because of sepsis and acute stroke)(Table

). A total of 32 (33%) pts had ECG findings concerning for but not meeting STEMI criteria, of whom 31 (97%) underwent emergent cath, with PCI performed in 10 (32%). In 5 pts (5%), the Cath Lab was de-activated after further assessment, and would have been considered “false alarms”.

Conclusions:
A significant number of ED STEMI Cath Lab activations are for pts who do not meet standard STEMI criteria. However, most have suggestive ECG findings benefiting from emergent angiography, and have either significant disease, undergo PCI, and/or are diagnosed with non-STEMI. Only a small percentage (5%) are clear “false alarms. This data further support current recommendations for ED Cath Lab activation for potential STEMI pts.
Abstract 11: Medical Emergency Teams Reduce Unexpected Cardiac Arrests, But Not Overall Hospital Costs Per Case
Authors: Manyam Harish , Cratty Michael S
Published: July 2021

Introduction
: Medical emergency teams (MET) have been developed to meet the growing needs of hospitalized patients. Medical emergency teams have been shown to reduce unexpected cardiac arrests, unexpected ICU transfers, length of stay (LOS), and inpatient mortality. However, there is no data on overall hospital cost per case with the addition of a MET team.

Hypothesis
: We hypothesized that the addition of a MET to our hospital would reduce our hospital cost per case by reducing unexpected cardiac arrest.

Methods
: A MET was developed at our 714-bed teaching hospital in March 2006. Our goal was to perform a retrospective analysis of hospital costs per case related to cardiac arrest and MET responses before and after establishment of a MET team. The first comparison group included unexpected cardiac arrests for a 6-month period from March 2005-September 2005 before establishment of the MET team. The second group included unexpected cardiac arrest patients and patients seen by the MET team that required unexpected transfer to the ICU for a similar 6-month period from March 2006-September 2006 after development of the MET team.

Results
: Group 1 from 2005 included 76 unexpected cardiac arrest patients and Group 2 from 2006 included 48 unexpected cardiac arrests and 95 unexpected transfers to the ICU. Both groups had similar overall severity scores of 1.7. Overall we had a 37% reduction in unexpected cardiac arrests in the first 6 months after initiation of the MET team. The overall mean LOS was lower in group 2 at 15 days compared to 17 days in group 1, however there was no statistical significance (p=0.59). There was no difference in the mean total cost per case in group 2, $34,653± $32,500 compared to group 1, $37,657± $38,517 (p=0.58).

Conclusion
: The implementation of the medical emergency team at our hospital decreased unexpected cardiac arrests, but did not decrease mean total cost per case for patients suffering unexpected cardiac arrests and unexpected ICU transfer during activation of the medical emergency team.