bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9760: Population-Level Cardiovascular Health Behavior and Health Factor Trends (1988-2008) and Projections to 2020 in US Men and Women: Results from the National Health and Nutrition Examination Surveys (NHANES)
Authors: Huffman Mark D , Lloyd-Jones Donald M , Ning Hongyan , Ford Earl S , Capewell Simon
Published: April 2024

Introduction:
The AHA 2020 Impact Goals recently defined 4 health behaviors (smoking, body mass index [BMI], diet, and physical activity) and 3 health factors (cholesterol, blood pressure, and plasma glucose) that serve as population-level metrics for evaluating cardiovascular (CV) health. However, there have been no forward projections of population trends of these metrics to 2020.

Methods:
We used data from cardiovascular disease-free individuals from NHANES III (1988-1994) and recent 2-year cycles (1999-2000, 2001-2, 2003-4, 2005-6, 2007-8) to provide population-level, sex-specific trends in prevalence of poor, intermediate and ideal levels of CV health behavior/factors. We also performed age-adjusted forward projections to 2020 using weighted linear regression coefficients.

Results:
The Table describes prevalence of poor, intermediate and ideal CV health behavior/factor levels from 1988-2008, weighted linear regression coefficients β (SE), and 2020 projections for men. Favorable trends from 1988-2008 included declines in prevalence of current and former smoking, hypercholesterolemia, and hypertension. In contrast, there were adverse trends in BMI, and dysglycemia. Prevalence of physical activity levels and remarkably low diet quality scores showed minimal changes over time. Women had generally similar trends in CV health profiles. Projections to 2020 suggest that obesity and impaired fasting glucose/diabetes could increase to affect more than 45% and 75% of US men, respectively, and 42% and 55% of US women.

Conclusions:
Improvements in prevalence of smoking, hypercholesterolemia and hypertension since 1988 have been offset by increases in adiposity and dysglycemia in US men and women. If current trends in obesity and dysglycemia are not reversed rapidly (likely through improvements in diet and physical activity), achievement of the 2020 Strategic Impact Goals will be difficult.
Abstract 9875: Ho-1/co Mediated Human Cardiac Stem Cell Survival Through Activation of Survival Signal Pathways and Cytokine Effects
Authors: Cai Chuanxi , Teng Lei , He Jia-Qiang , Vu Duc , Tang Xian-Liang , Guo Yiru , Li Qianghong , Hong Kyung , Rokosh Gregg , Bolli Roberto
Published: April 2024

Background:
Delivery of c-kit positive cardiac stem cells (CSCs) is a promising approach to repairing the infarcted heart, but is severely limited by the poor survival of donor cells, >90% of which disappear within 7 days of transplantation. Carbon monoxide (CO), a byproduct of heme oxygenase 1 (HO-1), has potent anti-apoptotic, cytoprotective, and preconditioning actions. Cobalt protoporphyrin (CoPP) is a well-known HO-1 inducer and has been used to promote CO generation and protect against ischemia/reperfusion injury. Therefore, we determined whether preconditioning CSCs with CoPP promotes CSC survival.

Methods and Results:
C-kit positive, lineage negative CSCs were isolated from human hearts. Lactate dehydrogenase (LDH) release assays demonstrated that preconditioning CSCs with CoPP markedly enhanced cell survival after oxidative stress (1 mM H
2
O
2
), concomitant with upregulation of HO-1 and other antiapoptotic proteins (e.g., Bcl2, Bcl2-A1, and Xiap). Conversely, knocking down HO-1 by shRNA inhibited the cytoprotective and antiapoptotic effects of CoPP. Both the annexin V/PI assay and the caspase-3 activity assay showed that pretreatment of CSCs with CoPP enhanced the cells’ resistance to apoptosis induced by oxidative stress. Preconditioning CPCs with CoPP also induced phosphorylation of NF-kappaB, Nrf-2, Erk1/2, and STAT1/3, which are known to modulate multiple cardioprotective genes. Further, preconditioning CSCs with CoPP led to a significant decrease in ROS generation and a global increase in release of cytokines such as EGF, FGFs, CSFs, and CXCL. Conditioned medium from cells pretreated with CoPP conferred naïve CSCs remarkable resistance to apoptosis, demonstrating that cytokines released by preconditioned cells play a key role in the antiapoptotic effects of CoPP.

Conclusions:
Preconditioning human cardiac stem cells with CoPP promotes cell survival and resistance to oxidative stress. The mechanism appears to involve activation of survival signaling pathways such as the NF-kappaB and ERK pathways, as well as paracrine effects via release of cytokines. These results provide a simple and effective strategy to enhance survival of CSCs after transplantation and, therefore, their efficacy in repairing infarcted myocardium.
Abstract 9878: Pioglitazone Ameliorates Atherosclerotic Lesions with the Modification of the Balance of Effector and Regulatory T Cells in Apolipoprotein E Deficient Mice
Authors: Kishimoto Chiharu , Yuan Zuyi
Published: April 2024

BACKGROUND:
Pioglitazone (PIO) affects T cell-mediated immunity through actions of peroxisome proliferator activated receptor γ. Effector and regulatory T cells control the development of atherosclerosis, a chronic inflammatory disease affecting the arterial blood vessels. PURPOSE: The aim of this study was to examine whether PIO ameliorates atherosclerosis by altering the balance of effector and regulatory T cells.

METHODS AND RESULTS:
To explore the effect of PIO on early and advanced atherosclerosis, apolipoprotein E deficient (ApoE-/-)mice were fed western diet and received PIO (20mg/kg/day) by gastric gavage at 6 or 14 weeks of age, respectively for 8 weeks (each n=12). Data showed that PIO markedly inhibited early fatty streak formation. Although the advanced fibrofatty plaque sizes were not significantly reduced, the numbers of smooth muscle cells within lesions were increased and higher collagen concentrations were produced by PIO. In general, macrophage expression in lesions was decreased by PIO. Additionally, the expression of Foxp3+ cells (regulatory T) was increased in lesions and spleens in mice at all PIO treatment stages, whereas the CD4+interferon-γ+/CD4+interleukin-4+cell ratios were reduced.

CONCLUSION:
PIO inhibited early atherosclerotic lesion formation and increased the stability of advanced atherosclerotic plaques in ApoE-/- mice, which was associated with altering the balance of effector and regulatory T cells.
Abstract 9910: Chronic Inflammatory Responses to Polymer Can Evoke Both Late Restenosis and Very Late Stent Thrombosis After Sirolimus-Eluting Stent Implantation in Human Coronary Arteries
Authors: Inoue Katsumi , Imai Masao , Kimura Takeshi , Nobuyoshi Masakiyo
Published: April 2024

Background:
Sirolimus-eluting stents (SES) can reduce the rate of restenosis by marked inhibition of neointimal hyperplasia. However, late adverse events occurring more than 1 year (Y) after SES implantation, in-stent late luminal loss (LLL) and very late stent thrombosis (VLST), have been reported. The detailed mechanisms of these events are poorly understood at present.

Methods and Results:
Postmortem histopathological investigation of late vascular responses of coronary arteries was performed in 32 consecutive patients (pts) more than 1 Y after SES implantation. Although most simple lesions with a single SES showed gradual endothelial coverage (80 to 90%) after 1 Y, there was considerable inflammatory reaction involving T lymphocytes (T cells), macrophages (MΦ) and multinucleated giant cells adjacent to the struts. Furthermore, 14 cases showed necrotic core formation with numerous circumferential cholesterol clefts and pronounced infiltration by lipid-laden MΦ that were immunoreactive for collagen-degrading matrix metalloproteinases around the struts. In 3 of these arteries, the luminal surface was focally ruptured and massive thrombi composed of platelets and fibrin were observed. Furthermore, in 2 pts who died of VLST more than 2 Y after SES implantation, the arterial wall of SES segments was aneurysmally dilated with an extensive inflammatory infiltrate involving the intima, media and adventitia consisting predominantly of T cells and eosinophils, and occasional giant cells. Furthermore, 2 other pts developing coronary aneurysms in the stented segments demonstrated diffuse restenosis. Granulomatous inflammatory reaction with mild to moderate inflammatory cell infiltration but remarkable smooth muscle cell proliferation was clearly observed in the restenotic regions in these pts.

Conclusions:
These findings suggest that the polymer of SES can evoke significant chronic destructive and/or proliferative inflammatory responses followed by severe adverse clinical events such as LLL or VLST, depending on the intensity of inflammation. Although relatively milder inflammatory changes induce intimal hyperplasia, vessel wall destruction by severe inflammation can lead to aneurysm formation in extreme cases.
Abstract 18355: Predictors of Fatigue in Heart Failure
Authors: Perez-Moreno Ana C , Jhund Pardeep S , Cleland John G , van Veldhuisen Dirk J , Gullestad Lars , Wikstrand John , Kjekshus John K , Lewsey James D , McMurray John J
Published: April 2024

Introduction
Although fatigue is regarded as a prototypical symptom of heart failure (HF), little is known about its prevalence, severity and predictors. We examined which baseline characteristics predicted fatigue at baseline in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).

Methods CORONA enrolled 5011 patients aged ≥ 60 years with symptomatic (NYHA class II-IV), ischemic, systolic (LVEF ≤ 40%) heart failure. Fatigue
“during the past few days”
was measured using a five point scale: 0 none, 1 on heavy exertion, 2 moderate exertion, 3 slight exertion, 4 at rest. For the purposes of analysis, patients were grouped into 3 categories: fatigue score 0-1 (n= 588), 2 (n=1,898) and 3-4 (n= 2,525). The 3 category fatigue outcome was analyzed using ordered logistic regression, checking covariates for linearity and the proportional odds assumption. Only baseline variables that were significant (P< 0.05) predictors of fatigue in univariate analyses were included in the multivariable models.

Results Fatigue was reported by 96% of patients with half scoring 4 or 5 out of a possible score of 5. The baseline variables which were independent predictors of fatigue are shown in the table. NYHA class was the strongest predictor. Both atrial fibrillation/flutter and higher heart rate were predictors. Lower serum creatine kinase (CK) levels were associated with more fatigue. Adding drug therapy made little difference to the models although some treatments were additional predictors of fatigue (e.g. diuretics) whereas others (e.g. beta-blockers) were not. Notable by their absence as predictors were LVEF, blood pressure, body mass index, diabetes, renal dysfunction and NT proBNP. Discussion Fatigue was an almost universal symptom and was pronounced in many patients. Fatigue was associated with NYHA class but not measures of cardiac function (LVEF, NT proBNP). Interestingly, fatigue was associated with lower CK, probably indicative of lower muscle mass.
Abstract 18390: Testing a Dietary Intervention Called ‰Pro-Heart” to Reduce Adiposity and Enhance Cardiac Structure, Functional Status, Lipid Profiles, Glycemic Control, and Quality Of Life in Obese, Diabetic Patients with Advanced Heart Failure
Authors: Evangelista Lorraine S , Lombardo Dawn , Cooper Dan , Horwich Tamara , Fonarow Gregg C
Published: April 2024

BACKGROUND:
To date, no known clinical trials have been done to test the effects of high protein (HP) diets in obese, diabetic patients with heart failure (HF). The goal of this four-year study is to explicate the role of HP diets in delaying the progression of disease in 90 patients with HF, New York Heart Association class II and III, body mass index (BMI) ≥30 kg/m
2
, and diabetes mellitus. We hypothesize that participants randomized to the HP diet compared to a standard protein (SP) diet will show greater reductions in adiposity (e.g. weight, waist circumference, percent body fat) and greater improvements in cardiac structure, functional status, lipid profiles, glycemic control, and quality of life following the 12-week intervention and that these changes will be maintained over time.

METHODS/DESIGN:
Recruitment and enrollment in this prospective, two-group, randomized trial is on-going; participants are randomized to either a HP diet which consists of 30% protein (∼110 g/day), 40% carbohydrates (CHO, ∼150 g/day) and 30% fat (∼50 g/day) or standard protein (SP) diet which consists of 15% protein (∼55 g/day), 55% CHO (∼200 g/day) and 30% fat (∼50 g/day). Participants will complete an intensive 12-week supervised weight loss intervention consisting of personalized nutritional counseling and support at baseline and asked to return at 2, 4, 8, and 12 weeks. After the intensive weight loss intervention, participants will be seen in clinic every 3 months for one year (6, 9, and 12 months) to monitor weight maintenance. Data will be obtained at baseline, 12 weeks (immediately after the intensive weight loss phase), and 15 months.

DISCUSSION:
Data from the proposed study will provide researchers and clinicians with evidence for rational recommendations for weight loss modalities that can be integrated in HF management and treatment guidelines.
Abstract 18411: Dietary Intake of n-3 Long-Chain Polyunsaturated Fatty Acids, Diabetes Mellitus and Risk of Myocardial Infarction in Patients with Suspected Coronary Artery Disease
Authors: Nygård Ottar , Strand Elin , Pedersen Eva R , Ebbing Marta , Svingen Gard , Schartum-Hansen Hall , Bjørndal Bodil , Seifert Reinhard , Mayer Klaus , Nilsen Dennis W , Nordrehaug Jan E
Published: April 2024

Background:
A high intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) is usually recommended in secondary prevention of coronary heart disease, particularly in patients with high triglyceride levels. Furthermore, a beneficial effect has been observed in patients with heart failure, who are frequently insulin resistant. Objective: The aim was to study the influence of impaired glucose metabolism and diabetes mellitus on the relation between dietary intake of n-3 LCPUFAs and risk of acute myocardial infarction (AMI) in patients undergoing coronary angiography for suspected coronary artery disease in 2000-2004. Design: This study included 2378 participants of the Western Norway B-Vitamin Intervention Trial (WENBIT). Daily intakes of n-3 LCPUFAs were estimated based on average dietary intakes during the last year as reported in a food-frequency questionnaire at baseline. Hazard ratios (HRs (95% CI)) of AMI (fatal and non-fatal) according to n-3 LCPUFA intake were calculated using Cox-regression adjusted for cardiovascular risk factors by comparing upper vs. lowest tertile and as trend across tertiles. Patients were followed until 31 December 2006.

Results:
Mean age of the participants was 62 years and 80% were male. Patients were sub-grouped into non-diabetics (HbA1c <5.7%), pre-diabetics (HbA1c ≥5.7%), and diabetics (diagnosed), and were also stratified according to median triglyceride levels. Among patients with diabetes there was a significantly reduced risk of AMI in the upper vs. the lowest tertile of n-3 LCPUFA intake, multivariate HR (95% CIs) 0.34 (0.14, 0.82), P for trend=0.008. In non-diabetic patients with HbA1c <5.7% there was an increased risk of AMI in the upper tertile of n-3 LCPUFA intake, 1.97 (1.05, 3.67), P for trend=0.02. Risk estimates were strengthened in their respective directions in both diabetic and non-diabetic patients with triglyceride levels above median. No risk associations were seen in pre-diabetics.

Conclusions:
Among patients with established coronary artery disease, a high intake of n-3 LCPUFAs was associated with a reduced risk of AMI in diabetic patients and an increased risk of AMI in non-diabetic patients. The effects were particularly pronounced in those with elevated triglyceride levels.
Abstract 18482: cAMP-mediated Cardiac Myocyte-fibroblast Crosstalk
Authors: Sassi Yassine , Truong Jeffery , Ahles Andrea , Engelhardt Stefan
Published: April 2024

Cyclic adenosine monophosphate (cAMP) serves as an intracellular second messenger to transduce the effects of the stimulation of Gs-coupled receptors. Recent studies indicated that cAMP can be extruded by the multidrug resistance associated-protein 4 (MRP4) from many cell types including cardiac myocytes (CM). The present study investigated whether the cAMP extruded from CM acts as a signalling molecule. We employed a fluorescence resonance energy transfer (FRET)-based sensor (Epac2-cAMPs) to directly assay for the formation of cAMP in CM and fibroblasts (CF). We found cAMP to be extruded from neonatal and adult CM upon β-adrenergic receptor (βAR) stimulation (1µM isoproterenol, ISO), an effect that was largely sensitive to MRP inhibition. Extracellular cAMP blocked the βAR-mediated increase in intracellular cAMP in CM. This negative feedback was reversed by a non-specific adenosine receptor antagonist (DPSPX) and an A1 adenosine receptor specific antagonist (DPCPX) but not by an A2 adenosine receptor specific antagonist (ZM-241385) (FRET ratio: 12.6±0.6 after ISO treatment vs. 4.5±0.8 after ISO+ecto-cAMP, 12.6±1.3 after ISO+ecto-cAMP+DPSPX, p<0.001). In contrast, application of extracellular cAMP onto CF induced an increase in intracellular cAMP levels while A2 adenosine receptor specific antagonist blocked this effect (FRET ratio: 8.1±1.1 after ecto-cAMP treatment vs 0.07±0.3 after ecto-cAMP+ZM, p<0.001). To determine if extracellular cAMP released from CM is sufficient to stimulate cAMP formation in CF, we stimulated CF isolated from β1β2-AR-deficient mice with conditioned medium (coM) from ISO or control-treated CM. Exposure of βAR-deficient CF to coM from ISO-treated CMs yielded a significant increase in intracellular cAMP compared to control-coM. DPSPX again markedly attenuated the elevation of cAMP in response to ISO-coM (FRET ratio: control-coM: 3.1±0.6, ISO-coM: 7±1.2, ISO-coM+DPSPX: 2.2±1.3, p<0.05). In conclusion, this study provides evidence that βAR stimulation of CM induces an inside-out signaling through secreted cAMP. cAMP is exported from CM, metabolized to adenosine and in an autocrine and paracrine manner stimulates adenosine receptors on CM (A1 receptors) and CF (A2a,2b receptors).
Abstract 18583: A Method for Improving the Identification of Heart Failure Patients for Quantitative Clinical Performance Measures using Electronic Health Records
Authors: Seicean Sinziana , Seicean Andreea , Marwick Thomas H
Published: April 2024

Background:
Electronic Health Records (EHR) are recommended for providing relevant data measures for quantifying and improving health care quality in pts with Heart Failure (HF). However, little is known on the feasibility and reliability of corroborating data fields automatically extracted from EHR to detect the HF population. We sought to improve the definition of pts diagnosed with HF using clinical and revenue functions of EHR.

Methods:
A standardized approach was developed using Epic's Clarity application to extract and integrate expanded administrative raw data from two sources: “Problem List Diagnosis Files” (PLDF) and “Encounter Diagnosis Administrative Files” (EDAF). HF diagnosis was extracted from the combined data, with each source considered equally valid, by using the ICD-9-CM Diagnosis Code set and methodology recommended by the 2010 Heart Failure Working Group.

Results
were compared against the “gold standard”, comprised through manual extraction of HF diagnosis by three clinicians, which was further validated by an experienced EHR research data extractor in a sample of 1000 in- and outpatients.

Results:
68 HF pts were identified by "gold standard manual extraction", while the administrative files (EDAF) detected only 50 pts; use of both sources detected HF 64 pts. Automated data extraction showed high specificity (0.99) for both methods, sensitivity increased from 0.72 with traditional administrative claims to 0.93 by corroborating EDAF with the PLDF.

Conclusions:
Corroborating two automated extracted data fields: PLDF and EDAF as equally valid sources was a superior strategy to ensure that patients were not incorrectly excluded from quality measures. The detection of HF using ICD9 codes appeared feasible. Correct definition of the patient population with HF is a critical prerequisite for accurate assessment of all quantitative clinical performance measures.
Abstract 18584: The Hypoxic Microenvironment Alters Macrophage Lipid Metabolism and Reprograms Inflammatory Responses Through STAT3 and HIF1α Signaling
Authors: Goonewardena Sascha N , Anyanwu Anuli C , Emery Sarah , Liao Hui , Pinsky David J
Published: April 2024

Background:
Atherosclerosis is a chronic inflammatory disease mediated by numerous heterotypic interactions between cells and the microenvironment. Hypoxia in the arterial wall has been implicated in atherogenesis and is known to modulate immune responses. Macrophages, heterogeneous sentinels of the innate immune system, are involved in all phases of atherogenesis. In addition to their role in immune responses, macrophages are important orchestrators of systemic cholesterol metabolism. However, the molecular mechanisms underlying the relationship between macrophage inflammatory responses, lipid metabolism, and the hypoxic microenvironment remain poorly understood.

Objective:
To examine the molecular effects of hypoxia on macrophage immune responses and cholesterol metabolism.

Methods and Results:
Bone marrow-derived macrophages and RAW264.7 cells were stimulated with the Toll-like receptor ligand LPS (100 ng/ml for 2h) in the presence or absence of hypoxia (1% O
2
). Activation of inflammatory and metabolic signaling pathways and transcriptional profiles were examined. Macrophages stimulated with LPS demonstrated phosphorylation of MAPK (ERK, JNK, and p38) and STAT3 and stabilization of HIF1α. In contrast, LPS stimulation of hypoxic macrophages had increased HIF1α stabilization and blunting of STAT3 phosphorylation with essentially no changes in MAPK activation, suggesting that hypoxia differentially modulates LPS signaling pathways. Additionally, LPS stimulation led to distinct transcriptional changes in macrophage inflammatory (NOS2, TNFα, CD36, mannose receptor; p<0.005) and metabolic (PTGS2, ABCA1, ACAT1; p<0.005) profiles. These transcriptional profiles were greatly altered by hypoxia, mirroring the changes in activation of macrophage signaling pathways.

Conclusions:
Hypoxia modulates macrophage inflammatory responses and their metabolic activity through differential activation of STAT3 and HIF1α and their transcriptional targets. These studies advance preliminary identification of close links between oxygen sensing and cholesterol biosynthesis, and highlight the potentially critical relationship between macrophages, metabolism, and the hypoxic microenvironment in atherogenesis.
Abstract 18678: Symptoms Fail to Predict Ischemia and Cardiac Outcomes in Outpatient Diabetic Patients Referred for SPECT Myocardial Perfusion Imaging
Authors: Bourque Jamieson M , Patel Chetan A , Perez Margarita , Watson Denny D , Beller George A
Published: April 2024

Introduction:
Studies have shown a substantial prevalence of ischemic heart disease in asymptomatic diabetic patients. However, the relationship of symptoms to ischemia and events is unclear in the modern era of intensive medical management. We sought to identify the effect of symptoms on the prevalence of ischemia by SPECT myocardial perfusion imaging (MPI) and subsequent cardiac events in a cohort of outpatient, stable patients with diabetes referred for SPECT MPI.

Methods:
The study cohort included 575 consecutive outpatients with diabetes who underwent quantitative, gated-SPECT MPI. Data was prospectively collected and compared using Chi-Square, Kaplan-Meier, and Cox proportional hazards analyses.

Results:
The study population was at intermediate risk of coronary artery disease (CAD) or had known CAD (40.3%). There were no significant differences between the symptomatic patients and asymptomatic subgroup in the prevalence of ischemia (21.8% versus 22.3%, respectively, p=0.890) or significant (≥10%) left ventricular (LV) ischemia (5.1% versus 4.8%, respectively, p=0.876). Over a median 4.4 years of follow-up, the yearly rate of cardiac death/nonfatal myocardial infarction was moderate and similar between those with and without symptoms (2.3% versus 2.2%, p=0.854). Symptoms did not provide incremental prognostic benefit over clinical risk factors (p=0.230) in Cox modeling.

Conclusions:
The presence of symptoms failed to predict any or significant ischemia or cardiac events in a consecutive cohort of stable, outpatient diabetic patients referred for SPECT MPI. These findings highlight the need for alternative and improved risk stratification strategies in diabetic patients.
Abstract 18697: C-Reactive Protein Performance as a First-Line Biomarker for Cardiovascular Risk Assessment Among Healthy Women
Authors: Laurinavicius Antonio G , Nary Fernando C , ConceiÇão Raquel , Carvalho Jose A , Santos Raul
Published: April 2024

Background:
Over 20% of coronary events in women occur in the absence of traditional cardiovascular risk factors. Framingham Risk Score (FRS) limitations in assessing cardiovascular risk in this group are well known. C-Reactive Protein (hs-CRP) has been shown to correctly reclassify cardiovascular risk among women, more specifically among those ones initially categorized as at intermediate risk by FRS. However, evidence supporting hs-CRP use as a first-line test in clinical practice is lacking. We assessed hs-CRP performance in cardiovascular risk re-classification among healthy women routinely attended at a preventive medicine unit.

Methods:
We evaluated 1.455 consecutive asymptomatic non-diabetic women (mean age: 42 ± 7.9 years) submitted to a routine health evaluation. As part of the evaluation, FRS, hs-CRP levels and Reynolds Score were assessed.Two different models were set to re-classify cardiovascular risk initially estimated by FRS: the first one (Model A) established hs-CRP levels >3<10mg/dL as a
cut-off
to switch women from FRS “intermediate risk” to the “high risk” category; the second one (Model B) re-stratified cardiovascular risk using Reynolds Score. We studied the performance of both models in cardiovascular risk re-classification.

Results:
Cardiovascular risk estimated by FRS was low in 98.6% (N=1,435) of the study population; intermediate in 1.1% (N=16); and high in 0.3% (N=4). Hs-CRP >3<10 mg/dL was found in 197 women (13.5%). Among those with high hs-CRP levels, 196 (99,5%) presented low FRS and 1 (0,5%) intermediate FRS.
Model A
led to risk re-classification of one woman in 1,455 (0.07%). Reynolds score was highly concordant with FRS (p<0.001), so that
Model B
did not significantly improve hs-CRP performance.

Conclusion:
Routine measurement of hs-CRP levels has minimal impact on cardiovascular risk re-classification of healthy women in clinical practice, due to the very low average cardiovascular risk of such population. Check-up protocols should not measure hs-CRP routinely in women and leave this determination as a second-line test for cardiovascular risk assessment in specific groups of individuals.
Abstract 18723: Genetic Variants Associated with QT Prolongation in Patients Exposed to Sotalol: A Genome Wide Association Study
Authors: Weeke Peter E , Delaney Jessica T , Mosley Jonathan D , Kannankeril Prince J , Wells Quinn , Van Driest Sara , Norris Kris , Kucera Gayle , Stubblefield Tanya , Tanaka Toshio , Nakamura Yusuke , Roden Dan M
Published: April 2024

Introduction
Sotalol is a frequently used antiarrhythmic drug known to cause QT-prolongation and increase the risk of the malignant arrhythmia Torsades de Pointes. We performed a genome wide association study (GWAS) to identify genetic markers associated with QT prolongation in sotalol exposed patients who were followed in an electronic medical record (EMR) system.

Methods
We identified 404 consented European American patients who initiated sotalol treatment via an EMR system through 2001-2011. Genotpying was performed on the Illumina 610-Quad BeadChip or the Illumina Human OMNI-express BeadChip, and the set of single nucleotide polymorphisms (SNPs) common to the two were analyzed initially. Maximum QT intervals were evaluated before and ≥48 hours after the start of therapy. Tests of association using linear regression were performed for change in the QTc interval assuming an additive genetic model adjusted for age and sex.

Results
After quality control, we analyzed a total of 314,618 SNP’s with a minor allele frequency of >1% and a call rate of ≥98%. The strongest associations were found for SNPs harbored in genes FAM107B (p= 2.09E-07), NRG-3 (p=1.94E-06), and SVEP (p=6.44E-06). NRG-3 is involved in cardiac development and has previously been associated with QT prolongation. The estimated effect size of the top SNP in NRG-3 (rs7073972) is 12.3ms with a MAF=27%. FAM107B encode proteins of unknown function and SVEP encodes membrane proteins involved in cell adhesion processes. Both are expressed in cardiac tissue although neither has previously been associated with cardiac electrophysiology.

Conclusion
This GWAS identified genetic markers associated with change in the QTc interval during sotalol treatment. Notably, NRG-3 has previously been linked to drug induced QT interval prolongation. The results of this pharmacogenomics study provide novel insight into the clinical response to sotalol with the ultimate goal of directing therapy of future patients.
Abstract 18754: Prognostic Evaluation of Catalytic Iron in Patients with Acute Coronary Syndromes: Observations from OPUS-TIMI 16
Authors: Steen Dylan L , Cannon Christopher P , Lele Suhas , Rajapurkar Mohan , Mukhopadhyay Banibrata , Scirica Benjamin M , Morrow David A
Published: April 2024

BACKGROUND: The potential of iron to generate reactive oxygen species (ROS) has motivated a long-standing interest in whether excess iron is causally linked to atherosclerotic heart disease. Catalytic iron, or “free” iron, is the circulating store of iron that is not bound to transferrin or ferritin and is available to generate ROS that may have deleterious vascular effects.

METHODS: We investigated the association of catalytic iron with clinical outcomes in 1701 patients with UA, NSTEMI, or STEMI who were followed for a median of 10 months. All endpoints were adjudicated by a blinded Clinical Endpoints Committee. RESULTS: The median catalytic iron level was significantly higher in those who died, 0.45μmol/L (0.37, 0.57), compared with survivors 0.37μmol/L (0.31, 0.46), p= 0.016. Catalytic iron was associated with a step-wise increased risk of death, with the highest quartile at an almost 4-fold risk compared to baseline (HR 3.94, p=0.035), which persisted after adjustment for age, diabetes, prior MI, prior CHF, ST deviation, CrCl, BNP, and Killip class (adjHR 3.89, p=0.038, FIGURE). There was no association between catalytic iron and risk of myocardial infarction, recurrent ischemia, heart failure, or bleeding. CONCLUSION: Increasing catalytic iron levels were associated with all-cause mortality. Our findings suggest that catalytic iron is not likely to add to currently available tools as a routine clinical biomarker for risk stratification of ischemic events, but its association with mortality is intriguing and leaves open the question of whether cardiovascular therapeutics aimed at catalytic iron may have utility.
Abstract 18794: Temporal Relationship Between Mitochondrial Membrane Potential (ΔΨm) Depolarization and Loss of Excitability in Globally Ischemic Rabbit Heart
Authors: Venable Paul W , Taylor Tyson G , Shibayama Junko , Warren Mark , Spitzer Kenneth W , Zaitsev Alexey V
Published: April 2024

Mitochondrial membrane potential (ΔΨm) depolarization has been implicated in the loss of excitability during ischemia, which could be relevant for resuscitation after cardiac arrest. The timing and degree of ΔΨm loss during no-flow ischemia in whole hearts is still poorly documented, in part due to the difficulty of estimating ΔΨm dynamics under this condition. We use a new approach based on the spatially periodic pattern present in the fluorescence emitted by potentiometric fluorophore TMRM when the dye accumulates in well-polarized mitochondria. This periodicity creates a distinct “mitochondrial” peak (MP) in the spatial Fourier spectrum corresponding to the sarcomere length (∼2 μm). Redistribution of TMRM upon ΔΨm depolarization diminishes the area under MP (MPA). We used Langendorff-perfused rabbit hearts mechanically uncoupled with blebbistatin (5.7μM) and stained with TMRM (450 nM). Confocal images were obtained from posterior left ventricular epicardium. Mitochondrial uncoupler FCCP (5 μM) and glycolytic inhibitior iodoacetate (IA, 15 mM) were used to validate MPA method. Eight hearts underwent minimum 1 hour global-ischemia; 4 hearts remained in sinus rhythm, 4 hearts were paced at 6.67 Hz to simulate ventricular fibrillation. FCCP reduced MPA to 32+/-6% of baseline; subsequent application of IA made MPA undetectable. During global ischemia ΔΨm loss started after a variable delay, was gradual and was not different between paced and non-paced hearts. MPA decreased to 50% of baseline at 44±17 (from 10 to 64) minutes and to 32% of baseline at 49±16 (from 27 to 70) minutes of ischemia. The minimum MPA value was 7±9% (range, 0-26%) of baseline and was observed at 65±9 minutes of ischemia (range, 51-72 minutes). Complete loss of excitability occurred earlier in paced than in non-paced hearts (33.2±3.1 vs. 45.0±7.2 min, p<0.05) but no clear relationship between ΔΨm dynamics and loss of excitability could be found.

Conclusions:
In this model a significant ΔΨm loss, comparable with severe metabolic inhibition, occurs only after prolonged time of global ischemia, is not accelerated by rapid pacing and is not correlated with the loss of excitability. This suggests a limited the role of ΔΨm dynamics in the outcomes of resuscitation after sudden cardiac arrest.
Abstract 18802: Differential Chamber and Cell-specific Expression of MicroRNAs in Experimental Heart Failure
Authors: Chen Yu , Dawson Kristin , Wu Chia-Tung , Wakili Reza , Luo Xiaobin , Kääb Stefan , Dobrev Dobromir , Nattel Stanley
Published: April 2024

Background:
Heart failure (HF) causes differential remodeling of left atrium (LA) vs left ventricle (LV), with much more prominent fibrosis in LA. Fibroblasts (FB) are central in fibrotic responses, with microRNAs (miRs) important regulators. This study determined the profile of miR expression changes underlying LA/LV remodeling, as well as FB/cardiomyocyte (CM) selectivity during the development of experimental HF.

Methods:
HF was induced in dogs by ventricular tachypacing (240 bpm) for 0 (CTL), 12, 24 hrs, 1 and 2 wks (n=5-12/group). FB and CMs were freshly isolated from LA and LV of each dog. Gene expression was assessed by qPCR. MiRs were selected based on preliminary microarray data.

Results:
HF changed the expression of 7/10 miRs in FB, while they were unchanged in CMs (miR-29b, miR-26a/b, miR-1, miR-208b and miR-133a/b, Table 1). Of these, FB selective miRs decreased only in LA (miR-29b decreased by ∼65%* and miR-26a/b by ∼57%*-79%*** beginning at 12 hrs), while the CM selective miRs decreased in both LA and LV (miR-1 by ∼37%-93%**, miR-208b by ∼67%-91%*), or only in LV (miR-133a/b by ∼77%***-89%***). MiRs downregulated in LA target multiple ECM genes, which showed LA-predominant increases in FB: miR-29b targets COL1A1 (increased by ∼11-fold*** from 1 wk) and COL3A1 (increased by ∼4.7-fold*** from 1 wk). MiR-29b and miR-208b both target fibrillin1 (increased by ∼1.9-fold** at 2 wks). MiR-1 may also participate in ECM remolding as it targets fibronectin1 (increased by ∼4.8*-14***-fold from 1 wk). The expression of miR-208a, miR-30a and miR-21 changed in both atrial FB and CMs, with smaller or nonsignificant changes in ventricular cells (Table 1), suggesting that these miRs play roles both in FB and CMs.

Conclusions:
Experimental HF causes greater FB-selective miR and ECM changes in LA compared to LV. The FB expression-profiles of ECM-targeting miRs in LA, accompanied by related ECM expression changes, implicate miRs in HF related LA-selective structural remodeling.
Abstract 18808: Two-dimensional Speckle-tracking Echocardiography to Assess the Viability of Acute Myocardial Infarction
Authors: Orii Makoto , Hirata Kumiko , Tanimoto Takashi , Shiono Yasutsugu , Shimamura Kunihiro , Ishibashi Kouhei , Yamano Takashi , Ino Yasushi , Kitabata Hironori , Yamaguchi Tomoyuki , Kubo Takashi , Imanishi Toshio , Akasaka Takashi
Published: April 2024

BACKGROUND
[[Unable to Display Character: ―]]Increasing infarct extent is associated with impaired prognosis after acute myocardial infarction (AMI). Two-dimensional speckle-tracking echocardiography (2DSTE) enables the assessment of myocardium deformation and identifies the amount and transmural distribution of viable myocardium. The objective of the study was to evaluate the predictive value of 2DSTE for improvement in cardiac function after AMI in comparison with contrast-enhanced cardiac magnetic resonance imaging (ceMRI).

METHODS and RESULTS
[[Unable to Display Character: ―]]In 25 patients with first-time acute ST elevation myocardial infarction, myocardial viability was assessed using 2DSTE and ceMRI to predict recovery of function at 6 months follow-up. For each left ventricular segment in a 16-segment model, peak radial, circumferential and longitudinal strain was determined using 2DSTE, and the relative extent of hyperenhancement using ceMRI. Of 128 segments with impaired function early after AMI, 65 showed regional recovery. Compared with segments showing functional improvement, those that failed to recover had lower peak radial (18 ± 16 % vs. 34 ± 23 %; p < 0.001), circumferential (-8 ± 5 % vs. -18 ± 7 %; p < 0.001) and longitudinal (-9 ± 5 % vs. -13 ± 5 %; p < 0.001) strain and a greater extent of hyperenhancement (71 ± 21% vs. 25 ± 20%; p < 0.001). Among strain parameters, circumferential strain yielded greater area under the curve (0.914) than radial and longitudinal strain (0.717 and 0.743, respectively). The predictive value of circumferential strain (sensitivity 83.1%, specificity 81.2%, at a cutoff value of -12.5%) could be comparable to that of hyperenhancement by ceMRI (sensitivity 87.8%, specificity 88.1%, area under the curve 0.939, at a cutoff of 46% hyperenhancement) (p=0.44).

CONCLUSIONS
[[Unable to Display Character: ―]]Circumferential strain by 2DSTE is a powerful novel parameter to identify reversible myocardial dysfunction after AMI.
Abstract 18846: Impact of Bleeding on Length of Stay and Total Cost in Atrial Fibrillation Patients
Authors: Amin Alpesh N , Bowdy Bruce D , Johnson Bernadette H , Jing Yonghua , Robinson Scott B , Wiederkehr Danny
Published: April 2024

Objectives:
To determine the impact of hospital acquired bleeding assessed in patients admitted for atrial fibrillation (AF) on length of stay (LOS) and total hospitalization cost.

Methods:
The Premier research database was queried to identify adult inpatients discharged between 2008 and 2011 who had a primary diagnosis code of AF and in whom bleeding was not present on admission. Bleeding was identified using ICD-9 diagnosis codes, charge codes for fresh frozen plasma or blood, or charge codes for transfusion of blood or blood components. Patients considered extreme outliers for LOS (greater than 1 standard deviation [SD] above the mean) were excluded from the study. Descriptive statistics including the outcomes of LOS and total hospitalization cost were calculated. In the univariate comparison of patients with and without bleeding, t-tests for continuous variables and chi-squared tests for categorical variables were used (alpha = 0.05). Gamma regression adjusting for demographics, comorbidities and antiplatelet/anticoagulant use were used to produce adjusted estimates for mean LOS and total hospitalization cost among patients with and without bleeding.

Results:
There were 143,415 patients, average age of 69.4 (SD 14.5) that met the study criteria. Across the entire population, mean LOS was 3.5 (SD 3.1) days, and mean total cost was $7,498 (SD 8,557). Overall, 3,058 (2.1%) patients had a bleed during their hospitalization. After adjustment, the mean estimated LOS was 6.68 (95% CI 6.52-6.84) days in the bleed group and 3.28 (95% CI 3.27-2.29) days in the no bleed group. The adjusted mean estimated total hospitalization cost was greater in the bleed group $16,621 (95% CI 16,178-17,074) vs. $6,996 (95% CI 6,969-7,023) in the no bleed group.

Conclusions:
Occurrence of hospital acquired bleeding in patients with AF is associated with a significant increase in the LOS and total hospitalization cost. In this study, adjustment for demographic and comorbidity differences as well as the use of antiplatelets and anticoagulants did not change the magnitude or direction of these associations, though there may be residual confounding. In this cohort, the effect of bleeding accounted for approximately $30 million dollars in cost and 10,397 hospitalization days.
Abstract 18848: Frequent Missed Opportunities to Avert Heart Failure Hospitalization
Authors: Howard Brian G , Stevenson Lynne W , Desai Akshay
Published: April 2024

Background:
Although emphasis has been placed on events after discharge for patients with heart failure (HF), reducing hospitalization may also require focus on the route prior to hospitalization. We mapped the timing of worsening symptoms and provider contacts in the weeks leading up to HF hospitalization.

Methods:
Scripted interviews were conducted in 100 patients admitted with HF to assess when they recognized worsening symptoms, contacted their provider, and made any medication changes.

Results:
Patients recognized worsening
s
ymptoms including increased fatigue, lower extremity swelling, and worsening dyspnea on exertion a median of 17.5 days before hospitalization; this prompted contact with a medical provider prior to ED presentation in 74 patients. Initial provider contact occurred a median of 14 days prior to hospitalization and led to medication changes in 48 patients. 52 patients had multiple contacts with ambulatory providers prior to being hospitalized.

Conclusions:
Patients hospitalized for HF often contact a physician prior to hospital admission. Many receive pre-hospital interventions, though in our sample, these were insufficient to avert eventual admission. These data demonstrate the potential opportunity to decrease HF admissions by providing more effective intervention and rapid re-evaluation after patients call with worsening symptoms.
Abstract 19188: Effects of Continuous-Flow Left Ventricular Assist Device Unloading on the Diastolic Function of the Failing Human Heart
Authors: Wever-Pinzon Omar , Stehlik Josef , Kfoury Abdallah G , Passi Samuel , Gilbert Edward M , Alharethi Rami , Reid Bruce B , Budge Deborah , Diakos Nikolaos , Farnan Rory , Bader Feras M , Li Dean Y , Selzman Craig H , Drakos Stavros G
Published: April 2024

Background:
The serial effects of continuous-flow left ventricular assist devices (LVADs) on the diastolic function of the failing human heart are not known. We sought to evaluate the effects of continuous-flow mechanical unloading on the diastolic function of the failing heart.

Methods:
Consecutive patients with baseline characteristics consistent with end-stage chronic heart failure referred for LVAD implantation as a bridge to transplantation or destination therapy between 2008 and 2011 were prospectively enrolled. Serial echocardiograms were performed at the time of LVAD implant and at pre-defined time points during the first year of LVAD support.

Results:
Eighty patients (age 56±16 years, 80% males) formed the study group and the main echocardiographic findings are summarized in the Table. Effective and sustained unloading (Figure-panel A) was achieved by CF-LVADs as evaluated by the E/E’ ratio. Similarly, diastolic function improved as early as 1 month after LVAD implant and changes were sustained over a year period (Figure-panel B). Further, these changes were sustained under increased loading conditions (turn down echocardiograms).

Conclusions:
Continuous-flow LVADs effectively unload the left ventricle and improve its diastolic function. These findings might be important in the new and rapidly growing field of LVAD induced myocardial recovery.
Abstract 192: Does Neighborhood Matter? How Location Influences Cardiac Arrest Outcomes and Predictability of the Utstein Factors
Authors: Buick Jason E , Ray Joel G , Kiss Alex , Morrison Laurie J
Published: April 2024

Introduction: The Utstein factors only predict 72% of out-of-hospital cardiac arrest (OHCA) survival variability (AUC: 0.86). Previous studies demonstrated geographical variations in both OHCA incidence and outcomes, while others have related these differences to ethnic and socioeconomic measures. The objective of this study was to determine the role of neighborhoods in OHCA survival and predictability in a Canadian setting.

Hypothesis: We hypothesized that there are neighbourhood factors associated with survival and variability in cardiac arrest outcomes.

Methods: All treated OHCA between April 2006 and March 2010 were mapped into census tracts (CT) using Geographic Information System analysis. Based on their home address, patients were assigned neighborhood factors extracted from the 2005 Canadian Census and include: instability, dependency, deprivation, ethnic diversity, crime rate and density of family physicians. Hierarchical logistic modeling was performed to assess which factors were associated with survival.

Results: A total of 4,626 OHCA were eligible for enrollment and contained the required information for geographic mapping. Survival to hospital discharge was 4.3%. The CT survival varied between 0 - 50% (IQR: 0.0 - 7.7), where 68.4% had 0% survival. The Utstein factors predicted 85.4% (95% CI: 81.0 - 89.6%) of survival variability. After adjusting for the Utstein factors, only the ethnic concentration of the CT was associated with survival. Inclusion of CT variables increased the predictability of the Utstein factors to 87.2% (95% CI: 83.4 - 91.2%, p = 0.12).

Conclusions: In conclusion, although neighborhood differences in OHCA outcomes exist, this difference contributes minimally to the Utstein factors prediction of survival. Since bystander resuscitation efforts are the most powerful predictors of survival perhaps neighborhood differences in bystander resuscitation efforts may address the gap in the Utstein predictability.