bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16660: Estradiol-Induced Phosphorylation of Myosin Regulatory Light Chain Leads to Increased Female Cardiomyocyte Contractility
Authors: Kararigas Georgios , Bito Virginie , Sipido Karin R , Regitz-Zagrosek Vera
Published: April 2024

Myosin regulatory light chain (Mrlc) controls actin/myosin interactions and modulation of contraction by Mrlc in the heart has been well documented. Notably, mutant mice for Mrlc phosphorylation show defects in cardiac contraction. The sex steroid hormone 17β-estradiol (E2) has been shown to exert several cardioprotective actions. However, little is known about the effects of E2 on the regulation of Mrlc and contractile function. Here, we tested the hypothesis that E2 increases the phosphorylation of Mrlc, which in turn leads to improved cardiomyocyte contractile function. One set of 14-month old female C57BL/6J mice were injected intraperitonealy with 0.2 mg/kg E2 (
n
= 8) or vehicle (Ctrl;
n
= 5). Five hours after injection, cardiomyocytes (CMs) were enzymatically isolated with the Langendorff-perfusion system, which were used for unloaded cell shortening measurements. Another set of female mice with the same age and strain (
n
= 6 per group) were treated in exactly the same manner and left ventricles were collected for protein extraction. Western blot analysis revealed that E2-treated CMs had higher levels of phosphorylated Mrlc than Ctrl CMs. Recordings of unloaded cell shortening at 1, 2 and 4 Hz demonstrated that the treatment with E2 improved CM contractile function compared to Ctrl CMs. In particular, at 1 Hz there was a 29.6% increase (adjusted
P
= 0.005), at 2 Hz a 31.5% increase (adjusted
P
= 0.009) and at 4 Hz a 29.3% increase (adjusted
P
= 0.01). For each frequency, 37 E2-treated and 45 Ctrl CMs were measured. Similarly, there was a significant increase in the rate of contraction of E2-treated CMs compared to controls. To our knowledge, our present work is the first to implicate E2 in the modulation of Mrlc phosphorylation leading to improved contractile function.
Abstract 16777: Identification of Cardioprotective Factors Produced by Fetal Mesenchymal Stem Cells Through a Combined Transcriptomic and Proteomic Approach
Authors: Danieli Patrizia , Dekker Lennard , Kleijn Lennaert , Cervio Elisabetta , de Boer Rudol A , Luider Theo , Gnecchi Massimiliano
Published: April 2024

Background:
mesenchymal stem cells of fetal origin (F-MSC) can be isolated from the amniotic membrane of human placenta. We have data showing that F-MSC exert remarkable cardioprotective and proangiogenic effects through paracrine mechanisms. However, the complete nature and scope of the soluble mediators of cardioprotection have not been investigated yet.

Methods:
F-MSC were isolated from human term placenta. Human dermal fibroblasts were used as control population. Total RNA and proteins were extracted from cultured F-MSC (N=10) and fibroblasts (n=10) after 48 hrs of serum deprivation. Genome-wide expression profiling was performed on RNA samples with Illumina platform. Proteins extracted from both cell populations were analyzed by liquid chromatography-Fourier transform mass spectrometry (LC-FTMS).

Results:
whole-transcriptome gene expression analysis revealed that 647 genes are significantly over-expressed in F-MSC vs fibroblasts. Among these genes, 131 are up-regulated more than 2 fold in F-MSC. Computational analysis led to the identification of 32 genes encoding for secreted factors. Among them, the known cardioprotective factors Midkine (MDK) and SPARC are highly up-regulated in F-MSC vs fibroblasts. qPCR confirmed that MDK (+8 fold, p<0.01) and SPARC (+5.8, p<0.01) are up-regulated in F-MSC. Intriguingly, the role of the majority of the identified secreted factors in heart repair is still unknown. LC-FTMS proteomic analysis identified 266 proteins significantly up-regulated in F-MSC vs fibroblasts, including 22 secreted proteins. Some of these candidates may have a potential beneficial role in heart repair. In particular, Pentraxin-3 (PTX3) and Galectin-1 (GAL1) emerged as putative mediators of the cardioprotective effects exerted by F-MSC.

Conclusion:
using a combined transcriptomic and proteomic approach we identified known and novel putative cardioprotective factors produced by F-MSC. In particular, MDK, SPARC, PTX3 and GAL1 seem strong candidates. Further studies will help to fully dissect their role in myocardial repair.
Abstract 16789: Plasminogen Activator Inhibitor-1 is Predictive of Endothelial Dysfunction Measured as Digital Reactive Hyperemia
Authors: Morris Alanna , Binongo Jose , Poole Joseph , Patel Riyaz , Ahmed Yusuf , Stoyanova Neli , Gibbons Gary , Vaccarino Viola , Din-Dzietham Rebecca , Quyyumi Arshed
Published: April 2024

Background:
Local hemostasis is regulated by the endothelium, and plasminogen activator inhibitor-1 (PAI-1) acts as the main inhibitor of the fibrinolytic system. Production of PAI-1 is upregulated in chronic inflammatory states such as cardiovascular disease (CVD), and may reflect endothelial dysfunction. Digital reactive hyperemia (RHI) is a convenient test of microvascular and endothelial function. Lower RHI is associated with worse long term outcome. Whether levels of PAI-1 reflect microvascular function measured by RHI has not been studied.

Methods:
We measured CVD risk factors in 682 participants (mean age 51±9 years, 57% female) enrolled in the Morehouse-Emory Partnership to Eliminate Cardiovascular Health Disparities (META-Health) study. Levels of PAI-1 were examined as continuous, log-transformed values. Digital pulse wave amplitude during reactive hyperemia was assessed using the Endo-PAT 2000 device (Itamar Medical, Israel). Briefly, a reactive hyperemia index (RHI) was calculated as the ratio of baseline to post-hyperemic pulse wave after 5 minutes of forearm cuff inflation. RHI was used as both a continuous and dichotomous variable.

Results:
Median levels of PAI-1 were 13.3 (IQR 7.2, 26.3) ng/mL. Levels of PAI-1 correlated inversely with the RHI (r=-0.112, p=0.005). Participants with PAI-1 levels in the highest tertile had lower RHI compared to those in the lowest tertile (2.1±0.6 vs. 2.3±0.7, p=0.004). Furthermore, levels of PAI-1 in the highest tertile increased the odds of a RHI <1.35, a value indicative of coronary endothelial dysfunction, by 3.7 (95% CI 1.2, 11.3). After adjustment for age, gender, race, smoking, hypertension, diabetes, waist circumference, mean arterial pressure, glucose, and lipid profile, PAI-1 remained a significant predictor of lower RHI (p=0.02).

Conclusion:
PAI-1 predicts lower RHI, indicating reduced digital microvascular reactivity that may be due to endothelial dysfunction. Since impaired RHI has been associated with worse long-term outcomes, this may be a useful tool for monitoring risk and following response to therapeutic PAI-1 antagonists
Abstract 16805: Early Short-Term Unloading with Left Ventricular Assist Device Prevents Remodeling, Reduces Regional Hypertrophy After Myocardial Infarction via Multiple Pathways
Authors: wei Xufeng , Li Tieluo , Williams Katrina , Zhang Pei , Bianchi Giacomo , Son HoSung , Li Shuying , Wu Zhongjun , Griffith Bartley P
Published: April 2024

Introduction
Left ventricular assist device (LVAD) has garnered great interest recently for its remodeling reversal of end-stage heart failure (HF). However, recovery sufficient to permit device removal is low, with relatively high incidence of early HF recurrence. In the present study, we utilized early intervention and placement of a minimally-invasive axial LVAD post-MI to prevent cardiac remodeling after MI.

Methods
Eighteen sheep were used in the study. Six sheep underwent an apical MI and were unloaded with an axial LVAD in first 2 weeks and terminated at 12 weeks. Eight sheep with MI and Four sham sheep were used as control. Sixteen sonomicrometry transducers were implanted to record the deformation of the end-diastolic LV geometry (diastolic strain). Global hypertrophy was evaluated by mass index. Regional hypertrophy in non-ischemic adjacent zone (AZ) and remote zone (RZ) of MI were evaluated by thickness of free wall of the LV and cardiomyocyte size. Three pro-hypertrophic pathways, PI3K/Akt/GSK-3β, Calcineurin/NFAT, Raf/MEK/ERK1/2 pathway were investigated regionally.

Results
LV dilation and dysfunction post MI were mitigated in the MI+LVAD group (LVEDV: 85.9±7.3 ml vs 106.1±14.3 ml; EF: 44.9±1.7% vs 39.4±2.4%, P<0.05). Adjacent zone strain was exacerbated in the MI group, whereas MI+LVAD group strain was ameliorated in comparison. Regional hypertrophy was evident in adjacent zone compared with in remote zone in the MI group (thickness of the wall: 0.96±0.13cm vs 0.71±0.22cm; the increase of cardiomyocyte size: 76.2±6.1% vs 14.5±3.5%, P<0.05). There was no significant regional hypertrophy in the MI+LVAD group. All the three mechanical stress related hypertrophic pathways were activated in the adjacent zone in MI group but not in MI+LVAD group as shown in table 1.

Conclusions
Early short-term LVAD unloading could prevent cardiac remodeling; reduce regional hypertrophy after MI through inhibiting the activation of multiple hypertrophic pathways.
Abstract 16806: Assesment of Diastolic Ventricular Function in Fetuses of Gestational Diabetic Mothers
Authors: Pac Feyza A , Balli Sevket , Ece Ibrahim
Published: April 2024

Objectives:
To identify ventricular diastolic disfunction by tissue Doppler in fetuses of diabetic mothers and compare with control groups.

Material and methods:
Between November 2009, April 2011 36 mother with gestational diabetes mellitus and 55 control subjects were recruited prospectively. Fetal echocardiogram was performed at 24, 28, 32 and 36 weeks of gestation to assess cardiac diastolic function by using tissue Doppler and pulse wave Doppler echocardiography. Early(Ea) and late (Aa) diastolic peak tissue Doppler imaging at the base of right ventricular free wall, ventricular septum, left ventricular free wall and both atrioventricular valves early(E), late(A) inflow velocities were analyzed and compared between groups. Haemoglobin glycated(HbA1c) levels were obtained at 24 week of gestation. Values above 6,5 % were excluded. Blood glucose levels of gestational diabetic mothers were under control.

Results:
Fetal interventricular septal thickness increasing progressively with advanced gestation were significantly more than control group in the presence of gestational diabetes mellitus (p< 0.001). Mean levels of HbA1c were 5,79±0.73 % in gestational diabetic mothers, 5.02±0.36 % in control group(p<0.003). HbA1c was significantly higher in the gestational diabetic mothers. E, A, Ea, Aa, Ea/Aa and E/A ratios increased with gestational age at all sites in both group. Peak velocities of mitral E (p<0.001), mitral A(p<0,007), tricuspid E(p<0.001) and tricuspid A (p<0.002) were significantly higher in diabetic group. The ratio of E/A and Ea/Aa increase as a function of more rapid augmentation in early when compared with late diastolic velocities in both group. Increases of mitral E/A and tricuspid E/A ratios were lower in diabetic group with advancing gestation. Ea:Aa ratio of right ventricle was higher in fetuses of diabetic mothers with advancing gestation (p<0,03).

Conclusions:
We conlude that maternal diabetes mellitus is associated with alterations ventricular diastolic function in the fetus. This is not closely related with interventricular septal hypertrophy. Impaired ventricular diastolic function develops as a result of decreased relaxation and compliance.
Abstract 16809: Robust Vessel Forming Capability Of Endothelial Cells Which Are Differentiated From Human Pluripotent Stem Cells via a Novel Two-Dimensional Serum Free Differentiation System
Authors: Lee Shin-Jeong , Kim Julie J , Park Chanjin R , Kim Sangsung , Byun Jaemin , Han Ji Woong , Yoon Young-sup
Published: April 2024

Background:
Human pluripotent stem cells (hPSCs) which include human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have emerged as an important source of endothelial cells (ECs) that can used for cardiovascular regenerative therapy. However, current EC differentiation systems have limitation in their efficiency and their clinical applicability due to the use of animal serum or feeders. To overcome this pitfall, we developed a novel two-dimensional differentiation system in which hPSCs can be efficiently differentiated into ECs without using embryoid body (EB) formation and animal derivatives.

Methods and Results:
We used three lines of hPSCs: two hESCs (H1 and H9) and one hiPSC line. First, these cells were induced to differentiate into the mesodermal lineage by being cultured onto collagen-coated plates with GSK3-β inhibitor for 3 days. These cells were then cultured under DMEM-F12 supplemented with KSR and defined angiogenic factors (VEGF, EGF, bFGF, heparin) followed by mechanical shear stress to the cultured cells. These cells expressed endothelial specific proteins such as CHD5 (VE-cadherin)(22±4%) and von Willebrand factor (vWF) (18±5%) by FACS, formed tubes when cultured in Matrigel, and expressed EC-specific genes (KDR, TIE2, CD34, eNOS, CDH5, vWF) measured by qRT-PCR analysis. We next sorted CDH5+ cells using MACS. To verify in vivo EC characteristics and vasculogenic potential of sorted CDH5+ cells in vivo, a Matrigel plug assay and a hindlimb ischemia model were employed. The sorted CDH5+ cells, pre-labeled with a DiI were injected into the ischemic limbs in the HLI model or injected into the backs of athymic mice after being mixed with Matrigel. Tissues were harvested 7 to 14 days after perfusion with an EC marker, isolectin B4. Confocal examination of the tissues showed robust incorporation of CDH5+ cells into vascular structures, suggesting functional vasculogenesis.

Conclusions:
We developed a novel stepwise, animal component-free, two-dimensional system to differentiate hPSCs into functional ECs. This system will serve as a useful platform for investigating endothelial development and the resultant ECs can be useful for treating ischemic cardiovascular diseases.
Abstract 16821: Reductions in Vascular Function Correlate with Age in a Novel Non-Human Primate Model for Assessment of Vascular Health
Authors: Schroeder Richard L , Smith Andrew H , Beebe David A , Sokolowski Sharon A , Huang Chunli , Knight Delvin R
Published: April 2024

Background:
Non human primates develop cardiovascular disease over decades. Whether the progression of vascular dysfunction with age is like that observed in humans is unclear. We hypothesize that, like humans, monkeys show age-related reductions in flow-mediated dilation (FMD, an index of endothelium-dependent vascular reactivity) and increases in pulse-wave velocity (PWV, an index of aortic stiffness). We also explored a potential relationship between the age-related vascular effects and circulating biomarkers of endothelial health, endothelial microparticles (EMP) and endothelial progenitor cells (EPC).

Methods and Results:
In
M. fascicularis
monkeys (N=21, 14 males and 7 females, 6 to 25 years of age), blood was sampled for EPC and EMP that were measured using flow cytometry. Monkeys were then sedated (midazolam + torbugesic) and baseline femoral artery diameter (4mm segment) was measured by ultrasonography. FMD was calculated as the peak %change from baseline diameter following a 5-minute cessation of blood flow below the knee. PWV was calculated using a modified SphygmoCor program and pulse waves from the radial and femoral arteries. FMD and PWV ranged from 6 to 33% and from 3 to 7 m/s, respectively, and multiple samplings showed high reproducibility up to 4 months (inter-assay variation <5%). FMD negatively (r=-0.94, p<0.0001), while PWV positively (r=0.60, p<0.002) correlated with age in these monkeys. Numbers of EPC (CD45- CD31+ CD34+ VEGFR2+) and EMP [CD45- CD42a- CD54(ICAM-1)+, CD45- CD42a- CD105(endoglin)+, and CD45- CD42a- CD144(VE-cadherin)+] were highly variable between individuals. Neither the EPC nor any of the EMPs significantly correlated with the age or age-related changes in FMD or PWV. Significance = p<0.05.

Conclusion:
For the first time in non-human primates, we established two non-invasive, clinically-relevant assessments of vascular function, FMD and PWV. Like humans, monkeys show age-related reductions in endothelium-dependent vascular reactivity and increases in aortic stiffness. The circulating numbers of EMP and EPC, independent of the chronic, age-related changes in FMD and PWV, may better serve as biomarkers of acute changes in vascular health associated with disease or therapeutic interventions.
Abstract 16823: Care Standardization in the Cardiac Surgical Intensive Care Unit: Clinical Outcome and Value
Authors: Pulido Juan N , Cook David J , Thompson Jeffrey E , Sundt Thor , Rohleder Thomas R , Roger Veronique L
Published: April 2024

Objective
: Practice analysis of cardiac surgical service lines suggested that, for patients having routine cardiac surgery, standardization of care processes in the ICU could reduce cost and improve outcomes. We tested this hypothesis in a large surgical practice.

Methods
: Patients eligible for a standardized care pathway were prospectively identified preoperatively. ICU protocol development and practice redesign occurred in 2009 with implementation in 2010. In the ICU, all major process steps to recovery were managed by tiered and integrated protocols whereby care advancement is the default if clinical criteria are met. We compared outcomes of patients managed by protocol to those managed by standard care. ICU metrics (time intubated, drip weaning, length of stay) were benchmarked against a sample of 65 CABG patients from 2008. Return to ICU and to OR for standardized care patients were compared to concurrent patients under routine care. We report on all patients having cardiac surgery for 12 months beginning March 2010.

Findings
: Over 12 months, the ICU care of 1289 patients followed standardized tiered protocols, while 1309 patients were managed by standard care. After implementation of standardized protocols, ICU metrics improved in protocol patients relative to 2008 (2010 versus 2008): mean intubation time in hours (7.4 vs 11.6), mean time on hemodynamic drips in hours (16.2 vs 25.3), average ICU length of stay in hours (25.1 vs 35.9). The safety of protocol based care is demonstrated by lower rates of return to ICU and to OR among patients under protocol vs non-protocol: return to OR (1.8% vs 8.9%), return to ICU (1.6% vs 6.2%).

Conclusions:
With proper patient selection and rigorous protocols that make care advancement the default, cardiac surgical care in the ICU can be standardized and clinical metrics improved. The safety of this strategy is demonstrated by very low rates of return to OR or ICU. This practice model is translatable to other ICU practices.
Abstract 16824: Aortic Valve Calcium Score as a Predictor For Periprocedural Complications and 1-Year Mortality After Tavi Using the Corevalve and the Sapien XT Device
Authors: Leber Alexander , Kasel Markus , Antoni Diethmar , Ebersberger Ulrich , Hoffmann Ellen
Published: April 2024

Background:
Percutaneous aortic valve replacement is a novel treatment option for patients with severe aortic stenosis and high risk for conventional surgery due to significant co morbidity. Risk scores for surgical valve replacement failed to accurately predict periprocedural MACE and 1-year mortality and there is an obvious lack of alternative parameters or scores to risk stratify candidates for TAVI.Objective: We sought to determine and analyze the amount of aortic valve calcification derived from preprocedural contrast enhanced CT-scans as a risk factor for subsequent adverse events.

Methods:
The transfemoral TAVI procedure was performed in 68 patientsusing the CoreValve device and in 60 patients using the Edwards Sapien XT Device. All patients were refused for conventional surgery due to a high perioperative risk. In all patients the aortic valve calcium score was determined from preprocedural ECG-triggered 64-sclice CT scans.

Results:
The 30-day MACE rate including death, Stroke and MI was 10.7%, one-year mortality was 11.2%. Using linear regression analysis the aortic valve calcium score turned out as the only significant predictor for 30-day MACE and for 1-year Mortality. Patients with a valve calcium score > 750 had a significant lower one- year survival rate compared to patients with scores <750 (56% vs. 95%, p<0.05). In the patient cohort treated with the CoreValve Device the valve calcium-score was strongly associated with the incidence and severity of postprocedural aortic regurgitation (r=0.26, p<0.05), whereas there was no such relation after treatment with the Sapien XT Device.

Conclusion:
The aortic valve calcification score is significantly associated with severe procedural complications and one year mortality after TAVI. Large amounts of valve calcium pose a high risk for postprocedural aortic regurgitation in patients treated with the CoreValve system but not for patients treated with the balloon expandable Sapien XT device. Thus the aortic valve calcium score may be used for risk stratification before TAVI and may also help to guide the individual device selection in future.
Abstract 16843: Waist Measures are an Important Factor Further Specifying Adiposity-Related Cardiometabolic Risk for Children Classified by Body Mass Index
Authors: Khoury Michael , Manlhiot Cedric , McCrindle Brian W
Published: April 2024

Background:
Body mass index (BMI) is commonly used as an indirect indicator of adiposity in children reflective of its association with cardiometabolic risk. The interaction of waist circumference percentile (WC%) and waist-to-height ratio (WHtR) with BMI may provide further risk specification in children.

Methods:
Data were analyzed from 5 NHANES surveys from 1999-2008. Two sets of groups were created based on categories of BMI/WC% and BMI/WHtR to assess the interaction of waist measures and BMI percentile (WHO charts) in association with cardiometabolic risk factors, including fasting lipids, glucose and insulin, C-reactive protein (CRP) and blood pressure category.

Results:
Data were available for 14,802 subjects (age range 5-18.9 years, 50% male, 4,542 fasting blood work). Overweight (BMI≥85%) and obesity (BMI≥95%) were noted for 13% and 27%, respectively. WC% ≥ 90% and WHtR ≥ 0.6 were noted in 16% and 10%, respectively. Both between and within BMI categories, increasing waist measures were significantly associated with increased lipid abnormalities (Figure A), higher insulin and glucose values, increased likelihoods of higher hypertension categories, and higher CRP levels (Figure B). Adjusted multivariable regression models for cardiometabolic risk factors had similar R
2
and c statistic values when waist measure categories were studied independently of or interacting with BMI categories. Interactions remained significant with continuous variables.

Conclusions:
Waist measures further specify cardiometabolic risk within classifications based on BMI, and should be included in the routine screening and assessment of risk in the pediatric population.
Abstract 16846: Tricuspid Insufficiency After Laser Lead Extraction
Authors: Mesa Julian , Arguelles Eric , Carrillo Roger C
Published: April 2024

Background
The use of laser lead extraction (LLE) to remove pacemaker (PCM) and implantable cardiac defibrillator (ICD) leads has become more prevalent in the past decade. Though the procedure is associated with a low level of complications, LLE still poses some risks to patients. Some reports have suggested an increase in Tricuspid Insufficiency (TI) associated with LLE. We present a series of patients who underwent both LLE and complete evaluation for TI with echocardiographic techniques.

Methods
From August 2008 through January 2010, 173 prospective, consecutive patients underwent LLE in a single center. All patients had transesophageal echocardiograms (TEE) during the extraction. 53 patients had tricuspid valve function evaluated a day prior to the procedure with a transthoracic echocardiogram (TTE), during the procedure with a TEE and 2 days postoperatively with a TTE. Descriptive analysis of the data was performed. All echocardiography data was analyzed by a cardiologist specialized in cardiac echocardiograms.

Results
All 173 patients experienced no change in tricuspid valve function during the procedure with TEE. 53 patients had complete TI evaluation, 38 males (72%), 15 females (38%), and a mean age of 69.45±14.08. Mean ejection fraction was 35.82±14.72. 3 (6%) patients experienced tricuspid insufficiency after the procedure (2 mild and 1 severe, all with device endocarditis); 16 (30%) patients were found to have TI before LLE that returned to normal valve function during or after the procedure. 34 (64%) patients did not experience any significant change of the tricuspid valve performance after LLE.

Conclusions
Laser lead extraction was not associated with increased TI.
Abstract 16865: Severe Physical and Sexual Abuse in Childhood and Adolescence Predicts Cardiovascular Events in Women
Authors: Rich-Edwards Janet , Mason Susan , Rexrode Kathryn , Spiegelman Donna , Hibert Eileen , Kawachi Ichiro , Jun Hee-Jin , Wright Rosalind
Published: April 2024

Context:
Although physical and sexual abuse of girls is widespread and has been associated with increased risks of obesity, hypertension, and diabetes, no study has investigated the extent to which early abuse increases risk of confirmed cardiovascular disease (CVD) events in women.

Hypothesis:
Child and adolescent abuse has a dose-response association with risk of CVD events.

Design, Setting, and Participants:
We examined associations of child and adolescent abuse reported in 2001 with confirmed CVD events from 1989-2007 among 67,102 women in the Nurses' Health Study II.

Main Outcome Measures:
Proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for myocardial infarction (MI, n=263), stroke (n=251), and total CVD events (n=514).

Results:
Nine percent of participants reported severe physical abuse and 11% reported forced sex during childhood or adolescence. With adjustment for age, race, body type at age five, parental education and family history, the hazards ratio (HR) for cardiovascular events was 0.91 (95% confidence interval: 0.70-1.17) for mild physical abuse, 1.03 (0.83-1.27) for moderate physical abuse, and 1.45 (1.10-1.90) for severe physical abuse compared to no physical abuse in childhood or adolescence. Compared with women reporting no sexual abuse in childhood or adolescence, the HR was 1.10 (0.89-1.36) for unwanted sexual touching, 1.56 (1.14-2.15) for one episode of forced sexual activity, and 1.62 (1.17-2.22) for repeated forced sex in childhood or adolescence. Associations of severe abuse with stroke were somewhat stronger for stroke than for MI. Adult body mass index, smoking, alcohol use, hypertension, and diabetes accounted for 41% (21% - 66%) of the association of severe physical abuse and 37% (22% - 55%) of the association of forced sex with CVD events.

Conclusions:
Severe physical and sexual abuse in childhood and adolescence are prevalent risk factors for heightened CVD risk in adult women. Mild and moderate abuse were not associated with increased CVD risk. The excess risk associated with severe abuse is mediated by elevated adult CVD risk factors in women with a history of early abuse.
Abstract 16878: Troponin Release Overestimates Infarct Size in the Presence of Left Ventricular Hypertrophy
Authors: Fernández-Jiménez Rodrigo , López-Romero Pedro , Suárez-Barrientos Aida , Montes Lorena , Olmos Carmen , Silva Jacobo , Garcia-Ruiz Jose Manuel , Fernández-Ortiz Antonio , Macaya Carlos , Fuster Valentin , Ibanez Borja
Published: April 2024

INTRODUCTION
Infarct size has been shown to be a better predictor of mortality than classical predictors following a ST-segment elevation myocardial infarction (STEMI). Therefore it is increasingly used for risk stratification. Biomarker release (CK and troponins) have been shown to overall good correlate with gold standards for MI size quantification (MRI, SPECT). In clinical practice, some patients display a discordant CK and troponin release in STEMI (CK in the higher quartiles with troponin in the lower or the other way around). The cause of this discordance has not been systematically analyzed. It has been shown that myocyte hypertrophy results in an increase of contractile proteins (like troponins) with no increase in cytosolic ones (like CK).

HYPOTHESIS
In the current work we have tested the hypothesis that patients with left ventricular hypertrophy (LVH) who suffer a STEMI have a disproportional total CK/troponin blood concentrations compared to STEMI patients with no LV hypertrophy.

METHODS
Consecutive STEMI patients (n=657) admitted to our Coronary Care Unit were retrospectively studied. CK and troponin I levels were measured on admission and then every 4 hours until a fall in both enzymes occurred. Patients were classified into four categories according to standard echocardiography recommendations. All the statistical analyses were performed using the open-source statistical scripting language R Version 2.11.0 (R Development Core Team).

RESULTS
Distribution of patients was as follows. Normal LV wall thickness: 426 patients (64.84%); mild LVH: 140 patients (21.31%); moderate LVH: 81 patients (12.33%); and severe LVH: 10 patients (1.52%). While CK peak values were similar in all categories, troponin I peak values were significantly higher in patients with LVH: mild LVH ([1.8 to 21] % higher than no-LVH patients, p<0.02) and moderate/severe LVH ([7.8 to 35] % higher than no-LVH patients, p<0.001).

CONCLUSIONS
We found that STEMI patients with LV hypertrophy (35% of our cohort) have significantly higher troponin release at the same level of CK release in comparison to patients without LV hypertrophy. In the presence of LV hypertrophy, troponin-I peak value significantly overestimates infarct size.
Abstract 16879: Predictors of “Metabolically Healthy” Obesity in a High Risk Population
Authors: Brown Rochelle V , Kral Brian G , Yanek Lisa R , Vaidya Dhananjay , Moy Taryn , Levine David M , Becker Lewis C , Becker Diane M
Published: April 2024

Introduction:
Some obese individuals are thought to be “metabolically healthy” (MHO) with lower risk for cardiovascular disease. This study was designed to identify healthy obesity and its associated risk factors in asymptomatic obese African Americans (AA) and European Americans (EA) from high risk families.

Methods:
Obese (BMI > 30) family members of index patients with early-onset coronary disease < 60 years of age underwent standard risk factor and fitness evaluation on a standard maximal treadmill test. MHO was defined as having <3 of the following: fasting plasma glucose ≥ 100 mg/dL, waist circumference > 102 cm (men) or > 88 cm (women), blood pressure ≥ 130 mm Hg systolic and 85 mmHg diastolic, HDL < 40 mg/dL (men) or < 50 mg/dL (women), or triglycerides ≥ 150 mg/dL.

Results:
The sample (N=631) was 58% AA and 67% female, with 49.8% meeting criteria for MHO. Metabolically healthy individuals were more fit compared to unhealthy (76.3 ± 41.99 versus 70.48 ± 35.64 MET-minutes, p=0.06). In multivariable regression analysis predicting MHO versus unhealthy obesity, female sex (OR 2.05, 95% CI 1.37-3.09), AA race (OR 2.00, 95% CI 1.41-2.85), lower LDL (beta= -0.008, p<.0001), and higher total levels of fitness (beta=0.01, p= 0.0006) were independently associated with greater likelihood of being classified as MHO. Neither BMI nor age was associated with MHO status (p= 0.19 and p=0.15 respectively).

Conclusions:
Among obese individuals from high risk families, age and BMI were not significantly associated with metabolically healthy status, as has been found in other studies. Among mutable risk factors, importantly, the association between better fitness levels and metabolic health suggest that improving fitness may hold promise in moving obese persons to a more metabolically healthy status independent of body weight.
Abstract 16892: Trends in the Presentation, Diagnosis and Outcomes of Acute Aortic Dissection Over 15 Years, From the International Registry of Acute Aortic Dissection (IRAD).
Authors: Pape Linda , Awais Mazen , Suzuki Toru , Trimarchi Santi , Evangelista Arturo , Myrmel Truls , Larsen Magnus , Harris Kevin M , Greason Kevin , Di Eusanio Marco , Montgomery Daniel , Eagle Kim A , Nienaber Christoph A , Isselbacher Eric M , O'Gara Patrick
Published: April 2024

Introduction/Purpose:
To examine trends in patient presentation, diagnosis and outcomes of acute aortic dissection over 15 years since the original report from the International Registry of Acute Aortic Dissection (IRAD).

Methods:
Patient data were collected at 28 international referral centers from 1996 up to the present. Trends were analyzed among 3275 patients divided according to date of enrollment into 6 equal groups and by Type: A (n=2110) or B (n=1165).

Results:
There was no change over time in the presenting complaints of severe or worst ever pain for Type A and Type B (90% and 96%, respectively), or in the incidence of chest pain ( 80% in Type A and 70% in Type B, respectively), with considerable overlap in chest vs. back pain between types. The report of pulse deficits did not change over time, present in 30% of Type A patients. Normal chest X-ray on presentation increased in Type A acute aortic dissection (AoD) from 13.7% to 31.3% over time (p-value for trend <0.001). In Type B the report of normal chest X-ray increased from 19.9% to 40.9% (p-value for trend <0.001). There were significant trends in initial imaging modalities for Type A: increased use of CT (from 49.4% to 71.6%, p-value for trend <0.001) and decreased use of TEE (from 45.3% to 25.4%, p-value for trend <0.001). For Type B, use of CT increased from 77.2% to 88.4% (p-value for trend .013). A decrease in overall mortality over time was significant for both Type A and Type B patients (see graph). Surgical mortality in Type A patients fell from 25.3% to 16.5% (p-value for trend 0 .003).

Conclusions:
No significant difference was seen over time in pain severity, chest pain, and presence of pulse deficits. The incidences of a normal chest X-ray, originally thought to be uncommon in dissection cases, increased over time to 30% in Type A and 40% in Type B AoD. Use of CT as the initial imaging modality increased for both Type A and Type B. Lastly, a significant decrease in overall mortality was seen for both Type A and Type B patients.
Abstract 16931: The Changing Course of Aortic Valve Disease in Scotland: Hospitalizations, Outcomes and Temporal Trends
Authors: Berry Colin , Lloyd Suzanne M , Wang Yangzong , MacDonald Alyson , Ford Ian
Published: April 2024

Introduction
Aortic valve disease (AVD) is a chronic health problem with a poor prognosis. We hypothesized that the incidence and burden of AVD is increasing. We studied the contemporary course of aortic stenosis (AS), aortic regurgitation (AR) and mixed AVD in Scotland, UK.

Methods
Using record linkage with ICD10 codes, we identified all first emergency admissions with a diagnosis of non-congenital AVD in Scotland (pop
n
5.1 million) from 1 Jan 1997 to 31 Dec 2005 with follow-up to 31 Dec 2006.

Results
20,218 subjects aged ≥18 yrs had an index hospitalization with a final diagnosis of AVD in a primary (n=5341 (26.4%)) or secondary diagnostic position (2
nd
-6
th
positions, n=14,877 (73.6% cases)). AS, AR, mixed or unspecified AVD occurred in 13,429 (66.5%), 2,956 (14.6%), 714 (3.5%) and 3,119 (15.4%), individuals, respectively (Fig 1). 10,298 (50.9%) patients had died (all causes) by 31 Dec 2006. Compared to AS, the likelihood of death from any cause was less with AR (Fig 2). In multivariable analyses, female gender, admission year and hypertension reduced the likelihood of death in AS patients. AS increased the risk of death or myocardial infarction, heart failure or stroke/transient ischemic attack. 3,749 (18.5%) patients had a first aortic valve replacement (AVR) of whom 72.7% had AS, 11.9% had an unspecified type of AVD and 10.5% had AR and 4.9% had mixed AVD. The likelihood of AVR increased by admission year in patients with AS and by endocarditis in patients with AR. Age, female gender, and co-morbidity reduced the likelihood of AVR.

Conclusions
The hospital burden of AS has substantially increased in Scotland in recent years. AS predicts morbidity and mortality compared to other types of AVD.
Abstract 16972: Abnormalities of the Aorta Are Common Following Pulmonary Vein Isolation: A Cardiac Magnetic Resonance Imaging Study
Authors: Tung Patricia , Hong Susie N , Chan Raymond H , Peters Dana C , Hauser Thomas H , Manning Warren J , Josephson Mark E
Published: April 2024

BACKGROUND:
Esophageal injury has been reported following pulmonary vein isolation (PVI), but few data are known regarding involvement of other mediastinal structures such as the aorta. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMR) has been used to identify myocardial fibrosis and inflammation, and may provide a way of identifying extramyocardial involvement. We sought to determine the frequency of aortic wall LGE post-PVI to examine potential aortic involvement.

METHODS:
Consecutive patients who underwent their first PVI with pre and post-LGE CMR at our institution between 2009-2011 were retrospectively identified. Left atrial (LA) and aortic wall hyperenhancement were analyzed using a commercial workstation (QMass MR). LA and aortic hyperenhancement were defined as any evidence of LGE at 10 standard deviations (SD) greater than the mean signal intensity of the aortic blood pool. Studies were visually assessed for geometric contact between the LA and aorta.

RESULTS:
Of 46 patient datasets meeting entry criteria, 9 were excluded due to poor quality CMR, leaving 37 patients (age 60.5 + 8.6 years, 68% male) and 74 studies for analysis. No patient had evidence of a clinical aortic complication. Aortic wall LGE was seen in 35% (13/37) pre-PVI and in 57% (21/37) post-PVI (p= 0.068). All (100%) patients with post-PVI aortic wall enhancement also had post-PVI LA hyperenhancement (Figure 1). The vast majority (85%) of patients with aortic wall LGE post-PVI had direct contact of the LA and aortic wall on the pre-PVI CMR study.

CONCLUSION:
Aortic wall LGE is common post-PVI, with a universal finding of concomitant LA LGE in all patients with aortic enhancement. The vast majority of those with aortic LGE had direct contact of the left atrium and aorta. These data suggest that LGE CMR evidence of aortic involvement post-PVI is common. The clinical implications of this imaging abnormality remain to be defined.
Abstract 16997: The Magnitude and Nature of Unfunded Published Cardiovascular Research
Authors: Mai Tuan V , Agan Donna L , Collins Glenn , DeMaria Anthony N
Published: April 2024

Objectives:
To determine the extent, type (staff, equipment, etc), and sources of funding for published cardiovascular research. Background: Important cardiovascular research is often performed without direct financial support. The degree to which medical research is performed on an unfunded basis remains uncertain.

Methods:
We sent an electronic survey (Survey Monkey) to 938 authors who published papers in the Journal of the American College of Cardiology in 2007-2009. The data sought included the authors’ characteristics (age, institution, type of research, etc), funding, sources of funding, and types of support for their research.

Results:
The response rate was 41% (388/938). The percentage of authors who were fully funded was 26%, partially funded 44.1%, and those without any direct funding amounted to 29.9%. Most funding came from government (41.8%) and industry (35.1%), whereas institutional, foundation, association, philanthropy, and other grants contributed the remaining. More authors received supplies (43.6%), staff (41.5%), and salary (39.7%) than equipment (27.3%) or administrative (24.7%) support. Significantly fewer authors age 40 years or younger (24.3%) were partially funded (p<.05). Significantly fewer authors from a community hospital (0%), from Europe (16.7%), or performing interventional (7.3%) or heart rhythm (11.5%) studies were fully funded (p<.05). Although only a trend, clinical investigators were more likely to be unfunded (35.7%). Those significantly more likely to be fully funded were authors from the United States (35.3%) and working in a government or VA hospital (45.9%) (p<.05). The authors who were 50 years of age or older, from the United States, had PhD degrees, doing basic as well as clinical research, or studying genetics/genomics had significantly more sources of funding and types of support (p<0.05).

Conclusion:
Considerable published cardiovascular research is currently being performed without direct financial support. This is particularly true for young clinical investigators. The inability to accommodate this investigation in the medical enterprise would substantially diminish the amount of new knowledge coming forth.
Abstract 17006: Genistein Rescues Pulmonary Hypertension Induced Right Ventricular Failure by Inhibiting the Proliferation of Pulmonary Artery Smooth Muscle Cells and Reversing Cardiac Hypertrophy
Authors: Nadadur Rangarajan D , Matori Humann , Umar Soban , Iorga Andrea , Partow-Navid Rod , Eghbali Mansoureh
Published: April 2024

INTRODUCTION
Pulmonary Hypertension (PH) induced Right Ventricular Failure (RVF) is a major cause of morbidity and mortality. PH is characterized by thickening of pulmonary vasculature and gradually increasing pulmonary arterial pressure, resulting in RV hypertrophy and failure. We have previously shown that genistein (Gen), a soy isoflavone, is able to rescue PH induced RVF. Here we explore whether inhibition of pulmonary smooth muscle cell proliferation as well as reversal of hypertrophy are the mechanisms involved in the rescue.

METHODS
To induce PH, male rats received a single injection of Monocrotaline (60mg/kg, s.c.) or saline as control (CTRL n=7). At day 21, when rats had developed severe PH, Gen therapy was begun (1 mg/kg/day, s.c.) to one group (n=8) until day 30. Some were left untreated to develop severe RVF (n=7). In vitro, proliferation of human pulmonary artery smooth muscle cells (HPASMCs) was measured with or without Gen by MTT assay. Hypertrophy of cardiomyocytes was measured by incubating neonatal rat ventricular myocytes (NRVMs) with pro-hypertrophic phenylephrine (PE, 10uM) with and without Gen. P<0.05 were considered significant. Values are given mean±SE.

RESULTS
Gen was able to reverse depressed RV Ejection Fraction (RVEF=65.67±1.08% vs 28.76±0.79% in RVF, p<0.05). The RVF group was characterized by increased pulmonary arteriolar medial thickness (2.55±0.09 vs 1.00±0.05 in CTRL, p<0.05) as well as significant hypertrophy of the RV (RV/(LV+IVS)=0.69±0.08 vs 0.25±0.03 in CTRL, p<0.05). Gen was able to reverse arteriolar thickening and RV hypertrophy (thickening=1.09±0.04; RV/(LV+IVS)=0.35±0.03. all p<0.05 vs RVF). Gen was able to inhibit the proliferation of HPASMCs (0.47±0.07 vs 1.00±0.12 in CTRL, p<0.05). Gen treatment of NRVMs was also able to reverse cardiomyocyte hypertrophy (0.71±0.06 vs 2.45±0.16 in PE alone, normalized to untreated cell size, p<0.05).

CONCLUSION
Genistein therapy rescues depressed RV Ejection Fraction and reverses pulmonary arteriolar medial thickness as well as RV hypertrophy in PH-induced RVF rats. Genistein inhibits the proliferation of HPASMCs and reverses the hypertrophy of NRVMs in vitro. These provide a possible physiological mechanism for the rescue of PH induced RVF by Genistein therapy.
Abstract 17010: The Coronary Arteries Chronic Total Occlusion Recanalization Reduces Symptoms in Patients with Stabile Angina in Short- and Long-Term Observation
Authors: Jaguszewski Milosz J , Fijalkowski Marcin , Targonski Radoslaw , Lewicki Lukasz , Chmielecki Michal , Dubaniewicz Witold , Ciecwierz Dariusz , Rynkiewicz Andrzej
Published: April 2024

Objectives:
Despite the ongoing technological progress and the introduction of more advanced equipment, chronic total occlusions (CTO) remains a challenge. Technical difficulties imply higher exposure to contrast media and radiation but clinical benefits of this procedure are not well defined. The goal of the study was to assess the influence of a successful recanalization of the coronary arteries chronic total occlusion on the reduction of angina symptoms and risk of major cardiovascular events (death, myocardial infarction, further revascularizations) in stable ischemic heart disease.

Methods:
The study group consists of 401 patients (72.8% men), age 65.5±10.0 years, who underwent the PCI of the CTO in I Department of Cardiology, Medical University of Gdansk, Poland. We analyzed frequency of major adverse cardiac events (MACE) and CCS angina class in patients with successful procedure (group 1) and failure (group 2). The data from the 6-months and 18-months follow up was collected over the phone calls and clinical visits.

Results:
There was significant difference in the prevalence of the angina symptoms between both groups in 6-month follow up (group 1 vs. group 2: 178 vs. 33, p<0.01) and 18-month observation (group 1 vs. group 2: 145 vs. 11, p<0.05). Moreover, the patients with ineffective recanalization of the CTO had to undergo the CABG much more often than the patients with effective recanalization in 6- and 18-months follow up (4.2% vs. 0,4%, p<0,01 and 9.1% vs. 1.2%, p<0,01, respectively). However there were no differences between the group 1 and group 2 in death, myocardial infarction and TVR or TLR frequency in 6-month follow up (respectively: 0 vs. 0; 2.3% vs. 1.4%; 13.6% vs.11.2%, all p=NS) and 18-month follow up (respectively: 1.9% vs. 2.1%; 3.9% vs. 2.8% and 23.6% vs. 14.7%, all p=NS).

Conclusions:
Successful recanalization of the coronary arteries CTO considerably decrease angina intensity. The patients with the successful recanalization of the CTO had less frequent CABG. There is no influence of CTO recanalization results on the mortality, risk of myocardial infarction and new revascularizations during 6- and 18-month observation.
Abstract 17046: The Hibernator Metabolic Phenotype is Cardioprotective in the Setting of Deep Hypothermic Circulatory Arrest
Authors: Podgoreanu Mihai V , Ma Qing , Mackensen G. B , Zhang Zhiquan , Smith Michael P , Bain James , Newgard Christopher B , Kohl Franziska , Drew Kelly L , Barnes Brian M
Published: April 2024

Hibernating mammals offer an intriguing example of natural adaptation to physiologic extremes, illustrating mechanisms of metabolic rate depression and cell preservation strategies. Using a model of surgical deep hypothermic circulatory arrest (DHCA), we hypothesized that hibernating arctic ground squirrels (AGS) display reduced myocardial injury following I/R compared to a non-hibernator (rat) by preservation of PPARα nuclear receptor induced myocardial fatty acid utilization.

Methods:
Euthermic AGS aroused from hibernation and BN rats underwent either DHCA (45min, followed by 3, 6, or 24h of reperfusion) or sham. The following parameters were compared between species/time points by two-way ANOVA: 1) biochemical severity of myocardial injury (plasma HFABP, TnI, ELISA); 2) myocardial PPARα activity (ELISA) and levels of 167 metabolites (MS); 3) myocardial inflammation and leukocyte extravasation (ELISA).

Results:
Compared to rats, AGS displayed robust myocardial ischemic tolerance following DHCA. This was accompanied by preservation of myocardial PPARα activity in AGS, which was significantly downregulated in the rat. Organic and amino acid acid profiles suggested compromised citric acid cycle flux, enhanced urea cycle, and myocardial accumulation of dicarboxylacylcarnitines in rats vs AGS. Furthermore, myocardial inflammation was robustly attenuated in AGS vs rat (Table).

Conclusion:
In the first study assessing myocardial ischemic tolerance in AGS following in vivo global I/R injury, we found an association between the hibernator cardioprotective phenotype and specific differences in myocardial fuel utilization. These findings challenge the current paradigm for metabolic optimization in human myocardial I/R and heart failure, which involves promotion of glucose oxidation at the expense of fatty acid oxidation during early reperfusion by inducing an “adaptive” substrate switch opposite to that demonstrated by natural hibernators.