bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12465: Dabigatran in Real World of Atrial Fibrillation: Systematic Review and Meta-analysis of Comparison Studies With Vitamin K Antagonists
Authors: Carmo João , Costa Francisco M , Ferreira Jorge , Mendes Miguel
Published: July 2021

Background:
In the clinical trial RE-LY, dabigatran showed a better efficacy/safety profile in comparison with warfarin, but clinical trials are few representative of the real world. We aim to access if dabigatran in real-world patients with atrial fibrillation (AF) showed a better profile in comparison with warfarin, through a systematic review and meta-analysis of observational studies comparing with vitamin K antagonists.

Methods:
PubMed, Embase and Scopus databases were searched through December 2014. We include observational studies comparing dabigatran to warfarin for non-valvular AF that reported clinical events during a follow-up for dabigatran 75mg, 110 mg or 150 mg, and warfarin. We proceeded to the extraction and analysis of data for clinical thromboembolic events, bleeding and mortality. Data were pooled by meta-analysis using a random-effects model.

Results:
We selected 9 studies involving a total of 291,703 patients, 85,399 treated with dabigatran and the remaining 206,304 with warfarin. The incidence of stroke was 1.71 / 100 patient-years for dabigatran and 2.44 / 100 patient years for warfarin (relative risk [RR] 0.91, 95% CI 0.66 to 1.27, p=0.58). The major bleeding rate was 3.90 / 100 patient-years for dabigatran and 3.92 / 100 patient years for warfarin (RR 0.90; 0.78 to 1.03, p=0.11). The all-cause mortality (RR 0.81, 0.75-0.88, p<0.001) and intracranial hemorrhage (RR 0.45, from 0.27 to 0.76, p=0.002) were significantly lower in patients treated with dabigatran in comparison to those treated with warfarin. There were no significant differences in risk of myocardial infarction (RR 0.55; 0.29 to 1.07, p=0.08), total hemorrhage (RR 1.00; 0.57 to 1.77, p=0.99), and gastro-intestinal bleeding (RR 1.14; 0.78 to 1.69, p=0.50).

Conclusions:
In this combined analysis of observational studies of real world, dabigatran compared to warfarin was associated with a similar risk of stroke, myocardial infarction, major bleeding, total bleeding and gastrointestinal bleeding, and a lower risk of intracranial hemorrhage and mortality.
Abstract 12494: Optimal Timing for Echocardiographic Assessment of Left Ventricular Function During Reduced Left Ventricular Assist Device Support
Authors: Salahuddin Ayesha , Fujikura Kana , Birks Emma J , Cunningham Chris , Kallel Faouzi , Spevack Daniel M , Garcia Mario J
Published: July 2021

Introduction:
In some circumstances left ventricular assist devices (LVAD) can be used to bridge patients with advanced heart failure to myocardial recovery or “remission”. Evaluation of the underlying myocardial function in patients supported with an LVAD is often performed with the pump speed turned down to minimal support for 15 minutes, to simulate unassisted ventricular loading conditions. Longer duration of reduced support and performance of exercise may allow for a more realistic evaluation of myocardial function to assess for recovery.

Methods:
Nine turn-down exams from 4 patients were analyzed. Subjects were participants in a multi-center prospective non-randomized study of LV recovery with HeartMate II LVAD together with a standardized protocol of pharmacological therapy (REmission from STAGE D Heart Failure (RESTAGE-HF)). LVEF and speckle tracking parameters were measured during full support, at 15 minutes of reduced support (6000 rpm) and again after a 6-min walk test. Averaged radial and circumferential strain, and global circumferential strain were analyzed from papillary muscle level short-axis view using speckle-tracking.

Results:
LV systolic parameters for each of these patients are shown, (Table). Improvement in LV function was not evident at 15 minutes of reduced support, compared to full support but was evident after the 6-min walk test.

Conclusions:
After 15 minutes of LVAD turndown, LV systolic parameters did not differ from full support values. Improvement in LV function compared to full support became evident when the protocol was extended to include imaging after a longer period of turndown with the addition of a 6-min walk test.
Abstract 12514: Elevated Intracellular Adenosine Epigenetically Regulates Endothelial Inflammation
(Best of Basic Science Abstract)
Authors: Xu Yiming , Wang Yong , Yan Siyuan , Zhou Yaqi , Liu Zhiping , Zeng Xianqiu , Weintraub Neal L , Huo Yuqing
Published: July 2021

Background and Objectives:
Adenosine is a potent modulator of endothelial inflammation. However, the molecular mechanisms by which adenosine regulates endothelial inflammation has not been fully understood. This study aims to determine the effect of elevated intracellular adenosine on endothelial inflammation and investigate the involvement of epigenetic mechanism in this effect.

Methods and Results:
Adenosine but not adenosine receptor agonists alleviated the TNF-α-induced expression of endothelial adhesion molecules (E-selectin, ICAM-1 and VCAM-1). This effect was abrogated by nucleoside transporter inhibitor NBMPR but not by adenosine receptor antagonists. Knockdown of adenosine metabolic enzyme adenosine kinase (ADK) by shRNA or inhibition of ADK by inhibitors augmented intracellular adenosine and also attenuated TNF-α-induced expression of adhesion molecules. This effect was also not affected by adenosine receptor antagonists. Mechanistically, adenosine treatment or ADK knockdown deactivated the SAH hydrolase (SAHH) and histone H3K4 methyltransferase (HMT) and lowered H3K4 di- and tri- methylation levels. Erasing these histone marks by inhibition of SAHH and depletion of WDR5, a core subunit of HMT complex blocked the anti-inflammatory effects of adenosine and ADK knockdown. Co-IP assay showed that ADK can bind with SAHH and WDR5 to methylate H3K4 in a spatially effective manner. With the intravital microscopy we observed the compromised rolling and adhesion of leukocytes in postcapillary venues of endothelial specific ADK deficient mice. Furthermore, atheroprotection in Apoe-/- mice on a Western diet and neuroprotection in acute cerebral ischemic mice were conferred in endothelial specific ADK deficient mice.

Conclusion:
Our study provides evidence that intracellular adenosine attenuates endothelial inflammation through epigenetic pathways and ADK is a promising therapeutic target to treat inflammatory vascular diseases.
Abstract 12579: Efficacy and Safety of Transcatheter Aortic Valve Replacement in Low-Moderate Surgical Risk Patients: A Systematic Review and Meta-analysis
Authors: Khan Abdur R , Khan Sobia , Simo Herman , Luni Faraz K , Bin Abdulhak Aref A , Bavishi Chirag , Riaz Haris , Flaherty Michael P
Published: July 2021

Background:
The efficacy of transcatheter aortic valve replacement (TAVR) in patients at high surgical risk has been established. The data in patients with low-moderate risk for surgery is still not conclusive. We sought to perform a meta-analysis of studies comparing the safety and efficacy of TAVR with surgical aortic valve replacement (SAVR).

Methods:
Several databases were searched from inception to February 2015, which yielded 10 eligible studies. Studies were selected if they compared TAVR to SAVR in patients at low-moderate risk for surgery. The measured outcomes of efficacy were all-cause and cardiovascular mortality. Data on safety included cerebrovascular events (CVA), permanent pacemaker implantation (PPI), aortic regurgitation (AR), vascular access complications and major bleeding reported during the procedure. Outcomes were pooled and relative risk was calculated using the Mantel-Haenszel method using a random effects or a fixed effect model based on heterogeneity. If studies had zero events in any of the arms, Peto odds ratio was used to pool data.

Results:
There were 10 studies with 3107 participants in our analysis. There was no difference in either short-term (RR, 0.85; CI: 0.57–1.28; p=0.44; I2=0%) or medium to long-term all-cause mortality (RR, 0.97; CI: 0.80–1.18; p=0.78; I2=0%). Our analysis suggested a decreased risk of cardiovascular mortality in the short-term (RR, 0.42; CI: 0.19–0.91; p=0.03; I2=0%) and a statistically non-significant trend towards decrease in long-term mortality (RR, 0.53; CI: 0.26–1.08; p=0.08; I2=0%) with TAVR. There was increased incidence of AR (RR, 4.01; CI: 2.24–7.19; p< 0.00001; I2=0%), PPI (RR, 5.00; CI: 3.47–7.19; p< 0.00001; I2=21%) and vascular access complications (RR, 6.36; CI: 3.75–10.76; p< 0.00001; I2=27%) in patients with TAVR. There was no difference in the risk of stroke between TAVR and SAVR (RR, 1.17; CI: 0.62–2.21; p=0.64; I2=15%) and an increased risk of major bleeding with SAVR was found (RR, 1.81; CI: 1.08–3.03; p< 0.0001; I2=86%).

Conclusions:
In this meta-analysis we found that TAVR may be an acceptable alternative to SAVR in patients with low-moderate risk for surgery. However, more evidence is needed from the current randomized trials before more widespread adoption of the procedure.
Abstract 12616: Interactive Protein Network of Factor XIII In Platelet Lipid Rafts
Authors: Rabani Vahideh , Montange Damien , Meneveau Nicolas F , Davani Siamak
Published: July 2021

Background:
Factor XIII plays a pivotal role in platelet aggregation. Factor XIII depends on lipid rafts to assemble the proteins required for clot retraction. Several proteins in this assembly remain unidentified. The aim of this study was to investigate which proteins localized in platelet lipid rafts are related to Factor XIII.

Methods:
Lipid rafts of platelets were isolated by using Lubrol WX 0.05% (w/v) and sucrose gradient. After ultracentrifugation, sucrose fractions were sampled. Lipidomic analysis was performed to identify the platelet lipid raft fractions enriched in cholesterol (Ch) and sphingomyelin (SM) and less so in phosphatidylcholine (PC). These fractions were selected for further proteomic analyses. The network of associated proteins was drawn by STRING database.

Results:
Sucrose fractions containing platelet lipid rafts were identified (Figure 1A). After proteomics analysis, an interactive network of proteins around FXIIIA was observed (Figure 1B). For these 19 proteins, their STRING score (range 0.576 to 0.900) and the type of their interaction with FXIIIA (activation, binding, catalysis and reaction) are summarized in Table 1.

Conclusion:
We identified 19 associated proteins with Factor XIII in human platelet lipid rafts. This could provide further insights into clinical targets of pathways through this molecule.
Abstract 12621: Gender Differences Among Implantable Cardioverter Defibrillators Recipients in the Setting of Primary Prevention
Authors: Marijon Eloi , Providencia Rui , Defaye Pascal , Klug Didier , Gras Daniel , Algalarrondo Vincent , Deharo Jean-Claude , Leclercq Christophe , Fauchier Laurent , Babuty Dominique , Bordachar Pierre , Sadoul Nicolas , Piot Olivier , Boveda Serge ,   on Behalf of the DAI-PP Investigators
Published: July 2021

Background:
Data regarding sex specificities in the use, benefits and complications of implantable cardioverter-defibrillators (ICDs) in primary prevention in the real-world European setting are sparse.

Methods:
Using a large multicentric cohort of consecutive patients referred for ICD implantation for primary prevention (2002-2012), in the setting of coronary artery disease or dilated cardiomyopathy, we examined potential sex differences in subjects’ characteristics and outcomes.

Results:
Of 5,539 patients, only 837 (15.1%) were women and 53.8% received cardiac resynchronization therapy (CRT-D). Compared to men, women presented a significantly higher proportion of dilated cardiomyopathy (60.2% vs. 36.2%, P120ms: 74.6% vs. 68.5%, P=0.003), higher New York Heart Association functional class (2.5±0.7 vs. 2.4±0.7, P=0.003) and lower prevalence of atrial fibrillation (18.7% vs. 24.9%, P<0.001). During a 16,786 patient-years follow-up, overall, fewer appropriate therapies were observed in women (HR = 0.59, CI95% 0.45-0.76; P<0.001). By contrast, no sex-specific interaction was observed for inappropriate shocks (OR for women = 1.00, 95%CI 0.74-1.35, P=0.997) and mortality (HR = 0.87; 95%CI 0.66-1.15, P=0.324), with similar patterns of cause of deaths.

Conclusion:
In our real life registry, women account for the minority of ICD recipients. While female ICD recipients present with features of more severe heart failure in the setting of primary prevention of sudden cardiac death, we observed they have a 40% lower incidence of appropriate therapies.
Abstract 12622: The Modeling of Werner Syndrome by Induced Pluripotent Stem Cells
Authors: Yozu Gakuto , Yuasa Shinsuke , Motoda Chikaaki , Kusumoto Dai , Kunitomi Akira , Kashimura Shin , Takei Makoto , Shimojima Masaya , Hayashiji Nozomi , Seki Tomohisa , Tohyama Shugo , Yokote Koutaro , Daita Hiroyuki , Fukuda Keiichi
Published: July 2021

Backgrounds:
Werner syndrome (WS) is a rare autosomal recessive disorder characterized by premature onset of several aging-associated diseases, such as atherosclerosis, diabetes, cancer, and early death. The aging phenotypes of WS is resembling to those of normal aging. To uncover the mechanism of aging, we tried to model WS by patient-specific induced pluripotent stem cells (iPSCs). WS is caused by mutations in WRN gene belonging to the RecQ DNA helicase family which plays a role in genomic stability. But some of WS phenotypes are hardly explained by genomic instability. Thus, we aimed to model WS by patient-specific iPSCs to elucidate the mechanisms.

Methods and Results:
We sampled T lymphocytes from a patient with WS. Then we transduced with Yamanaka factors (OCT4, SOX2, KLF4, and MYC) by sendai virus, and iPSC colonies were derived. We confirmed that WS-iPSCs expressed pluripotent markers, could differentiate into all three germ-layer derived tissues, and retained a normal karyotype. We could culture WS-iPSCs over 2 years with pluripotent status. Then, we differentiated WS-iPSCs into fibroblasts-like cells. The proliferation rate of WS-iPSC-derived fibroblast-like cells (WS-iPSC-fibroblasts) was significantly decreased. WS-iPSC-fibroblasts showed a vulnerability to cellular stress and resulted in increased cell population which is positive for senescence associated β-galactosidase activity and γ-H2AX foci. Singled WS-iPSC-fibroblasts showed excessive blebbing of plasma membrane and increased apoptosis compared with control-iPSC-fibroblasts. To compare global gene expression profiles, we performed microarray analysis in WS-iPSC-fibroblasts and control-iPSC-fibroblasts. Interestingly, WS-iPSC-fibroblasts reproduced the global gene expression pattern of physiological aging. To confirm whether the phenotypes of WS-iPSCs are induced by WRN mutation, we generated isogenic control of WS-iPSC (corrected-WS-iPSC) by homologous recombination using helper-dependent adenovirus vector. Corrected-WS-iPSCs lost the aging-associated phenotypes but showed the phenotypes resembling to control-iPSCs.

Conclusion:
We modeled aging phenotypes by WS-specific iPSCs. This model would be utilize for uncovering the aging mechanisms.
Abstract 12660: Impact of Aortic Valve Replacement versus Medical Management on Survival of Low Flow Low Gradient Severe Aortic Stenosis With Normal Ejection Fraction
Authors: Fanari Zaher , Barmpouletos Dimitrios , Reddy Vivek K , Hammami Sumaya , Zhang Zugui , Weintraub William S , Marshall Erik S
Published: July 2021

Background:
The impact of aortic valve replacement (AVR) versus medical management (MM) in patients with paradoxical low flow is unclear. The objective of this study was to compare outcomes of AVR versus MM in patients with severe aortic stenosis and normal ejection fraction and different transaortic flow and gradient.

Methods:
We identified consecutive patients presenting to our echo lab with an aortic valve area (AVA) < 1.0cm
2
and EF≥ 50%. We stratify patients depending on gradient (≥ 40 vs. < 40 mmHg) and stroke volume index (SVI < 35 vs. ≥35 ml/m
2
). 4 groups were identified (, normal flow, high gradient [NF/HG]; normal flow, low gradient [NF/LG]; low flow, high gradient [LF/HG] and low flow, low gradient [LF/LG]. These 4 groups were also stratified depending on management (AVR vs. MM). All patients were retrospectively followed for the occurrence of death.

Results:
A total of 954 patients were included in analysis. Mean follow up was 2.45 ± 1.9 years. The mean age was 75.4 ± 5.6 years. Comparing all 4 AS subgroups, the mortality was higher in LF/HG followed by LF/LG, NF/HG and NF/LG (LF/HG 37.1% vs. LF/LG 33.9% vs. NF/HG 30.3%vs. NF/LG 20.2%; Log Rank Test, P=0.003). Patients who underwent medical therapy have a higher mortality than the overall cohort in all subgroups (LF/HG 44.3% vs. NF/HG 36.6% vs. LF/LG 33.7% vs. NF/LG 21.2%; Log Rank Test, P=0.001). Patients with HG had a higher chance of getting aortic valve replacement (AVR) than those with LF/LG and NF/LG (20.7% NF/HG vs. 10.6% LF/HG vs. 4.7% LF/LG and 3.6% NF/LG; P=0.01). Patients who underwent AVR had lower mortality rates when compared with the overall cohort in all subgroups (LF/HG 21.4% vs. 18.9% NF/HG vs. 6.6% LF/LG and 7.1% NF/LG; Log Rank Test, P= 0.253).

Conclusion:
Patients with LF/LG represent an under-recognized high-risk group with similar prognosis to NF/HG. Although these patients may benefit tremendously from AVR, they are less likely to undergo AVR when compared to HG patients.
Abstract 12689: Cardiovascular Responses to Energy Drinks in a Healthy Population: The C-energy Study
Authors: Kozik Teri M , Bhattacharyya Mouchumi , Nguyen Teresa T , Connolly Therese F , Chien Walther , Charos George , Shah Sachin , Pelter Michele M
Published: July 2021

Introduction:
Energy drinks are presumed to enhance energy, physical endurance, mood, and boost metabolism. Serious health risks have been reported with energy drink consumption such as myocardial infarction, cardiac arrest, stroke, seizures, and arrhythmias. More than 20,000 emergency department visits related to energy drink consumption were reported in 2011. Little is known about the possible pathophysiological mechanisms and adverse events associated with energy drinks. Unlike the tobacco and alcohol industry, there are limited restrictions regulating the purchasing and marketing of these drinks.

Purpose:
To determine if consumption of energy drinks alter; vital signs (blood pressure, temperature), electrolytes (magnesium, potassium, calcium), activated bleeding time (ACT), or cardiac responses measured with a 12-lead electrocardiographic (ECG) Holter.

Method:
Subjects consumed two-16 ounce cans of an energy drink within one hour and remained in the lab where data was collected at base line (BL) and then during four hours post consumption (PC). Vital signs were taken every 30 minutes; blood samples were collected at BL, one, two and four hours PC and ECG data was collected throughout the entire study period. Paired students t-test and a corresponding non-parametric test (Wilcoxon signed rank) were used for analysis of the data.

Results:
Fourteen healthy young subjects were recruited (mean age 28.6 years). Systolic blood pressure (BL=132, ±7.83; PC= 151, ±11.21; p=.001); QTc interval (BL=423, ±22.74; PC=503, ±24.56; p<.001); magnesium level (BL 2.04, ± 0.09; PC=2.13, ±0.15; p=.05); and calcium level (BL=9.31, ±.28; PC=9.52, ±.22; p=.018) significantly increased from BL. While potassium and ACT fluctuated (increase and decrease) no significant changes were observed. Eight of the fourteen subjects (57%) developed a QTc >500 milliseconds PC.

Conclusions:
In our sample, consumption of energy drinks increased systolic blood pressure, serum magnesium and calcium, and resulted in repolarization abnormalities. Because these physiological responses can lead to arrhythmias and other abnormal cardiac responses, further study in a larger sample is needed to determine the effects and possible consequences of energy drink consumption.
Abstract 12727: The Clinical Impact of Eicosapentaenoic Acid/Arachidonic Acid Ratio in Adult Patients With Congenital Heart Disease
Authors: Kanoh Miki , Inai Kei , Shimada Eriko , Shinohara Tokuko , Shimizu Mikiko , Ishii Tetsuko , Sugiyama Hisashi , Park In-Sam
Published: July 2021

Background:
Recent studies showed that intake of long-chain n-3 polyunsaturated fatty acids reduces the incidence of cardiovascular events. Furthermore, low levels of eicosapentaenoic acid (EPA) are associated with heart failure (HF), arrhythmia, and cardiac sudden death. However, there have been few studies regarding the clinical implication of the EPA/arachidonic acid (AA) ratio in adult patients with congenital heart disease (CHD).

Objectives and methods:
The present study was a prospective study of 64 adult patients with CHD. We measured serum EPA and AA and divided the patients into two groups according to their EPA/AA ratio: <0.25, low group; ≥0.25, high group. Patients were observed for a mean duration of 13 months. We investigated the association between the EPA/AA ratio and clinical data and analyzed the prognostic predictive value of the EPA/AA ratio in these patients.

Results:
There were no significant differences between the low (n = 36) and high (n = 28) groups in age, sex, blood pressure, systemic ventricular ejection fraction, medications, or serum levels of hemoglobin A1c, creatinine, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglyceride, or B-type natriuretic peptide. A low EPA/AA ratio had significant prognostic value for arrhythmia (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.1-14.8, p = 0.03) and composite events of arrhythmia and HF hospitalization (HR 5.6, 95% CI 1.53-27.8, p < 0.01). Subgroup analysis revealed that the patients with two-ventricle circulation in the low group (n = 23) were at significantly higher risk of arrhythmia (HR 6.7, p = 0.02), HF hospitalization (HR 16.2, p < 0.01), and composite events of arrhythmia and HF hospitalization (HR 6.7, p = 0.03) than those in the high group (n = 23). In patients with single-ventricle circulation, serum EPA levels were significantly lower compared with patients with two-ventricle circulation.

Conclusions:
The EPA/AA ratio had a significant predictive value for cardiac events in adult patients with CHD, especially in patients with two-ventricle circulation. The effect of EPA treatment for patients with CHD should be elucidated in the future.
Abstract 12732: Risk of Heart Failure After Contemporary Radiotherapy for Breast Cancer in the Community
Authors: Saiki Hirofumi , Finley Randi R , Scott Christopher G , Yan Elizabeth S , Petersen Ivy A , Redfield Margaret M
Published: July 2021

Background:
Contemporary breast cancer radiotherapy (RT) results in variable cardiac radiation exposure. While cardiomyocytes are radio-resistant, radiation induces coronary microvascular endothelial damage and inflammation which may ultimately lead to myocardial inflammation, ischemia and fibrosis and put patients at risk for heart failure (HF) and particularly, HF with preserved ejection fraction (HFpEF).

Methods:
Community based (Olmsted County, MN), HF case-control study of contemporary (1999-2014) breast cancer RT patients with CT-based RT planning for precise mean cardiac radiation dose (MCRD) calculation. HF cases (n=66) and controls (n=129) were matched (1:2) for age at RT, HF risk factors, tumor side and chemotherapy use. Matched controls and cases had identical follow-up (index interval). Proportion of HF and clinical characteristics in categories of MCRD were reported (table) and conditional logistic regression was used to estimate the HF odds ratio (OR) associated with MCRD as a continuous variable.

Results:
Of the 66 HF cases, 46 (70%) had HFpEF and 20 (30%) had HF with reduced ejection fraction (HFrEF). The proportion of patients with HF (any) or HFpEF increased and proportion with HFrEF tended to increase with increasing MCRD. The prevalence of HF risk factors (hypertension, diabetes, coronary disease) at time of RT did not vary by MCRD while left sided tumor, cancer stage and adriamycin use increased with increasing MCRD. The OR per 1 unit increase in log MCRD was 3.71 (1.98, 6.94) for total HF (p<0.001), 4.91 (1.93, 9.09) for HFpEF (p<0.001) and 2.78 (0.91, 8.47) for HFrEF (p=0.07). The mean index interval was 5.0±3.2 years.

Conclusion:
Cardiac radiation incident to contemporary breast RT increases the risk of HF, and particularly HFpEF over a short post-RT interval. These data may guide use of proton beam therapy in breast cancer. These data also provide support for the role of coronary microvascular compromise in the pathophysiology of HFpEF.
Abstract 12773: Dose-dependence of Beta-blocker Therapy on Subsequent Mortality in One Year Survivors After Myocardial Infarction
Authors: Goldberger Jeffrey
Published: July 2021

Background:
Beta-blocker (BB) therapy after acute myocardial infarction (MI) improves survival. The benefits of long term treatment remain debated.

Methods:
Of 7058 patients enrolled in the OBTAIN prospective multi-center registry of patients with acute MI, follow-up BB dosing information was available in 2822 patients who survived ≥1 year. BB dose was indexed to the target BB dose used in RCTs (when available), reported as %; only BBs studied in RCTs were included in this analysis. Dosage groups were No BB (n=302), ≤12.5% (n=557), 12.6-25% (n=848), 26-50% (n=687), and >50% (n=428) of target dose respectively. Vital status was obtained by chart review, Social Security Death Index, or direct contact. Adjustment for baseline differences among groups was achieved by propensity score analysis (predicted 1-year BB dose as control variable).

Results:
In the 5 groups, mean age was 62-64 years, with significant differences in gender, clinical, and MI characteristics. Mean ejection fractions were 47-50%. The figure shows Kaplan-Meier survival curves (unadjusted, p=0.06). Propensity score analysis showed an independent effect of BB dose on mortality (p=0.047). Compared to No BB, only the 12.6-25% dose group had a significant mortality reduction (HR 0.46, 95% CI 0.25-0.86, p=0.014).

Conclusions:
At one year after MI, continued BB therapy may be associated with lower mortality, but there appears to be a dose-dependence to this effect. Further studies are needed to optimize BB dosing strategies for long-term treatment after MI.
Abstract 12776: Long Term Mortality With Right Ventricular Apical Versus Septal Pacing
Authors: Witt Chance M , Lenz Charles J , Shih Henry H , Ebrille Elisa , Rosenbaum Andrew N , Aung Htin , van Zyl Martin , Manocha Kevin K , Deshmukh Abhishek J , Hodge David O , Asirvatham Samuel J , McLeod Christopher J
Published: July 2021

Introduction:
Right ventricular apical (RVA) pacing appears to have detrimental effects on cardiac function and long term outcomes. Right ventricular non-apical (RVNA) pacing, especially in the septal position, has been postulated as an alternative that may lead to less morbidity and mortality. Prior studies have shown conflicting results and been limited by small numbers and short follow-up. We aimed to determine if right ventricular septal lead position was associated with a reduction in long-term mortality compared to RVA lead position.

Methods:
Patients who underwent dual-chamber pacemaker implantation from 2004 through 2013 were evaluated for right ventricular lead position based on chest radiographs. Lead positions were divided in to apical or non-apical. Non-apical lead positions were subdivided to isolate a septal lead position group. Mortality was compared between these groups.

Results:
During the study period, 3456 patients underwent dual-chamber pacemaker placement and had images appropriate for lead position evaluation. The group was 53.5% male with a mean age of 74 ± 13 years. RVNA lead position was found in 976 (28.2%) patients, including 243 (7.0%) with a septal position. There was no significant difference in age or prior heart failure diagnosis between groups. Kaplan-Meier survival analysis did not reveal a significant difference in mortality between patients with RVA versus RVNA lead position during 5 year follow-up (p = 0.82). However, septal lead position was associated with a significantly lower mortality compared with RVA position (p = 0.03) (figure).

Conclusions:
Right ventricular septal lead position is associated with a lower long-term mortality than RVA lead position. This has substantial implications regarding the preferred site for ventricular pacing lead placement.
Abstract 12788: Adiponectin Modulates the Cardiovascular Risk Associated With Obesity: Results From the Framingham Offspring Study
Authors: Anthanont Pimjai , Zhou Yanhua , Asztalos Bela F , Ai Masumi , Otokozawa Seiko , Nakajima Katsuyuki , Liu Ching-Ti , Cupples L. Adrienne , Schaefer Ernst J
Published: July 2021

Objectives:
Our objective was to examine the interrelationships of cardiovascular disease (CVD) risk factors with obesity, lipoproteins and their subfractions, markers of glucose homeostasis, and the inflammation markers adiponectin, and C reactive protein (hs-CRP).

Methods:
We measured fasting plasma lipids, low-density lipoprotein (LDL)-C, small dense LDL-C (sdLDL-C), high-density lipoprotein (HDL)-C, HDL subfractions, triglycerides, glucose, insulin, adiponectin, and hs-CRP in 2,691 male and female participants (median age 58 years) in cycle 6 of the Framingham Offspring Study. We carried out univariate and multivariate statistical analyses.

Results:
In both men and women the presence of obesity compared to those of normal weight was significantly (P<0.05) associated with: 1) a 60% increase in the prevalence of CVD, 2) a two to three fold higher prevalence of major CVD risk factors (hypertension, diabetes, and low HDL-C < 40 mg/dL), 3) a doubling of plasma levels of hsCRP, insulin, and triglycerides, 4) increased sdLDL-C, and 5) significant decreases in adiponectin and the levels of apoA-I in very large protective α-1 HDL. Surprisingly there was no relationship of obesity with levels of LDL-C in men. By multivariate analysis, in both men and women, adiponectin level emerged as the statistically most important parameter determining the variability of HDL-C and apoA-I levels in very large α-1 HDL, and sdLDL-C, while for systolic blood pressure age was the most important determinant, and for hsCRP levels it was plasma insulin levels. Interestingly over half of obese subjects were not hypertensive or prediabetic, and less than 20% had premature CVD or diabetes. By tertile analysis in obese subjects, low adiponectin was associated with a doubling of the prevalence of diabetes, and significant increases in triglycerides, and sdLDL-C (men only), and significant decreases in HDL-C and apoA-I in large α-1 HDL.

Conclusions:
Our data indicate that the prevalence of CVD and its risk factors increases with body mass index, and that the level of circulating adiponectin is a significant determinant of cardiovascular risk, especially diabetes prevalence, and levels of LDL and HDL subfractions in obese subjects.
Abstract 12827: Alterations in Flow Patterns and Wall Shear Stress in Pulmonary Artery Visualized With Phase-resolved 3D Cine Phase Contrast MRI (4D-Flow) in Patients With Systemic Sclerosis
Authors: Suwa Kenichiro , Sakakibara Tomoaki , Saitoh Takeji , Kaneko Yutaro , Sano Makoto , Saotome Masao , Urushida Tsuyoshi , Katoh Hideki , Satoh Hiroshi , Takehara Yasuo , Sakahara Harumi , Hayashi Hideharu
Published: July 2021

Background:
The pulmonary circulation is impaired in patients with systemic sclerosis (SSc), and the analysis of pulmonary arterial (PA) blood flow has a great clinical significance. Using 4D-Flow, we studied the changes in PA blood flow velocity vectors and wall shear stress (WSS) in SSc patients.

Methods:
Twenty one SSc patients (M/F: 1/20, 56±15 years) including 2 PA hypertension, and 7 control subjects underwent 4D-Flow. We set planes traversing the main and first branches of PA, and the velocity vectors were post-processed to delineate streamline images. WSS images were obtained at the surface of PA. The plane-averaged flow velocity at the main PA, surface-averaged WSS, and oscillatory shear index (OSI), the %WSS acting in other directions from the mean WSS vector during a cardiac cycle, were compared.

Results:
(1) The PA flow showed laminar flow pattern at the early systolic phase in all patients and subjects, but diffuse helical flow in 11 SSc patients (right upper), focal helical flow in 6 SSc patients and 2 control subjects at the late systolic to early diastolic phase. The other 4 SSc patients and 5 control subjects had continuous laminal flow (left upper). (2) The peak systolic PA flow velocity did not differ between them, whereas the diastolic flow velocity was significantly greater in SSc patients (minimum velocity; 26±24 mm/sec vs. -26±52 mm/sec, p<0.01). (3) WSS at the peak systolic flow velocity was significantly lower and spatially heterogeneous in SSc patients (lower figs; 1.1±0.2 Pa vs. 1.4±0.4 Pa, p<0.01). Both WSS at the diastolic phase and OSI were significantly greater in SSc patients (minimum WSS; 0.28±0.07 Pa vs. 0.19±0.04 Pa, p<0.01, OSI; 0.14±0.03% vs. 0.09±0.02%, p<0.05).

Conclusions:
The 4D-Flow disclosed the different PA flow patterns between SSc patients and control subjects. In SSc patients, WSS at the PA was generally decreased and varied spatially and temporally. 4D-Flow has a potential to detect the subclinical changes of PA flow dynamics in SSc.
Abstract 12846: Resuscitation of Out-of-Hospital Cardiac Arrest Without CPR: The 13-Year Experience of Progetto Vita
Authors: Capucci Alessandro , Aschieri Daniela , Guerra Federico , Pelizzoni Valentina , Nani Stefano , Villani Giovanni Q , Bardy Gust H
Published: July 2021

Introduction:
Cardiopulmonary resuscitation (CPR) currently represents standard of care in out-of-hospital cardiac arrest (OOHCA) despite the demonstration of its many side effects. To date, CPR has never been tested in a randomized, prospective clinical trial against an automated external defibrillator (AED) quick deployment, as such a trial is considered impossible for ethical reasons. Nevertheless, insights on the effective role of CPR when an AED is quickly available can be provided from the Progetto Vita of Piacenza, Italy: the first early defibrillation project established in Europe.

Hypothesis:
To compare differences in 13-year survival between OOHCA victims rescued by standard care and patients rescued by AED-only trained responders.

Methods:
Prospective, non-randomized parallel study comparing mortality when rescuers only used automated external defibrillators (AEDs) and did not perform CPR with mortality from the standard Emergency Medical Services (EMS) response, including CPR. Survival was followed over 13 years, from June 2001 to July 2014.

Results:
In 3366 OOHCAs, survival to hospital discharge occurred in 39 of the 95 patients treated with an AED only and in 193 of the 3271 patients treated by standard EMS (41.4% vs. 5.9%; p<0.001) The Kaplan Meier estimates of survival after 13-years follow-up are 31.8% when AEDs only were used versus 2.4% for standard EMS response. Estimates of survival also are significantly better for Progetto Vita when survival was stratified by gender and location of cardiac arrest. Presence of a shockable rhythm at rescuers arrival was associated with a 16.8-fold increased chance of survival to discharge. Progetto Vita intervention was independently associated with a 2.8-fold increased chance of survival to discharge, regardless of minutes from dispatch to arrival, cardiac arrest location, rhythm presentation, and age.

Conclusions:
Progetto Vita demonstrates excellent long-term survival from out-of-hospital cardiac arrest without CPR use compared with standard resuscitation. The findings from the present study could provide solid "real-world" evidence for the broadscale dissemination of AEDs quickly available to layperson rescuers.
Abstract 12859: Prognostic Value of Neutrophil to Lymphocyte Ratio in Acute Decompensated Heart Failure With Reduced or Preserved Left Ventricular Ejection Fraction
Authors: Yamada Takahisa , Morita Takashi , Furukawa Yoshio , Tamaki Shunsuke , Iwasaki Yusuke , Kawasaki Masato , Kikuchi Atsushi , Kondo Takumi , Ishimi Masashi , Hakui Hideyuki , Ozaki Tatsuhisa , Satoh Yoshihiro , Satoh Yoshihiro , Seo Masahiro , Ikeda Iyo , Ikeda Iyo , Fukuhara Eiji , Fukunami Masatake
Published: July 2021

Backgrounds:
Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a measure of inflammation and as a prognosticating biomarker in various medical conditions ranging from infectious disease to cardiovascular disease. The prognostic significance of NLR in patients admitted with acute decompensated heart failure (ADHF) is not established. The aim of this study was to investigate the prognostic impact of NLR in ADHF patients, relating to reduced or preserved left ventricular ejection fraction (HFrEF or HFpEF).

Methods and Results:
We studied 264 patients admitted with ADHF and discharged with survival (HFrEF(LVEF<50%); n=144, HFpEF(LVEF≥50%;n=120). There was no significant difference in NLR at the discharge between patients with HFrEF (2.1±1.1) and HFpEF (2.1±1.0). During a follow up period of 4.2±3.2 yrs, 87 pts died. NLR was significantly associated with mortality in patients with HFrEF (p<0.0001) and HFpEF (p=0.006) at univariate Cox analysis. All cause-death was significantly frequently observed in patients with the highest tertile of NLR (>2.2) than those with the middle or lowest tertile of NLR(<1.5) in patients with HFrEF (60% vs 36% vs 20%, p<0.0001, respectively) and HFpEF (43% vs 20% vs 14%, p=0.004, respectively). After adjustment for baseline characteristics, echocardiographical findings, and blood tests such as hemoglobin, sodium level and estimated glomerular filtration rate, NLR remained a significant independent predictor for mortality in patients with HFrEF (hazard ratio: 1.23 [95%CI 1.04-1.54], p=0.017), while NLR tended to be a independent predictor in those with HFpEF (hazard ratio:1.29 [95%CI 0.98-1.71], p=0.07).

Conclusion:
NLR at the discharge provides a prognostic value for the prediction of total mortality in ADHF patients with HFrEF and HFpEF, although the prognostic significance of NLR in patients with HFpEF was weakened by adjustment for relevant covariates.
Abstract 12868: Morphine Decreases Ticagrelor Concentrations but Not Its Effects: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Hobl Eva-Luise , Reiter Birgit , Stimpfl Thomas , Schoergenhofer Christian , Schwameis Michael , Derhaschnig Ulla , Jilma Bernd
Published: July 2021

Introduction:
Our recent drug interaction trial with clopidogrel showed that morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in susceptible individuals. This study examined possible drug-drug interactions between ticagrelor and morphine.

Hypothesis:
We hypothesized that the pharmacodynamic consequences of drug-drug interactions would be less between morphine and ticagrelor.

Methods:
Twenty-four healthy subjects received a loading dose of 180mg ticagrelor together with placebo or 5mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and ticagrelor effects were measured by platelet function tests.

Results:
Concomitant i.v. injection of morphine slows drug resorption of ticagrelor and its active metabolite (p<0.05) by one hour and decreases plasma levels of ticagrelor and its active metabolite (by 25-31%; p
<
0.03) and the drug exposure (area under the curve by 22-23%; p
<
0.01). Importantly, however, the effects of ticagrelor on platelet aggregation in whole blood, platelet plug formation, and vasodilator-stimulated phosphoprotein (VASP) phosphorylation are not affected by morphine.

Conclusions:
Morphine co-administration moderately decreases ticagrelor plasma concentrations but does not inhibit ist effects. Therefore, a 180 mg loading dose of ticagrelor appears to provide consistent and reliable platelet inhibition when morphine has to be given for pain relief.
Abstract 12892: Intracoronary Brachytherapy For Treatment of In-stent Restenosis in Drug Eluting Stents is Safe and Effective
Authors: Singh Jaspreet , Doshi Rajkumar P , Shah Niraj , Srinivas Guru , Jauhar Rajiv , Kavanaugh-Hogans Marisa , Kaplan Barry , Meraj Perwaiz
Published: July 2021

Background:
Intracoronary brachytherapy (ICBT) is an effective treatment for restenosis (ISR) of bare metal stents (BMS) but its utilization has waned due to the advent of drug eluting stents (DES). ISR following DES occurs at a frequency of 10% or greater. The purpose of this study is to report on the results following ICBT for clinical ISR in patients with DES and to determine if there are predictors for its success.

Materials/Methods:
A retrospective analysis was performed to identify 135 patients treated on an IRB approved protocol using ICBT for DES ISR. All patients received ICBT after balloon angioplasty using Sr-90 with a centering balloon and an automated delivery device (Best Vascular Novoste System, Norcross, GA). A dose of 18.4Gy or 23Gy at 2mm depth was delivered based upon the diameter of the injured vessel. Coronary lesion location, length and diameter were evaluated at enrollment. Major adverse coronary events (MACE) defined by death, myocardial infarction, CVA, and target vessel revascularization (TVR) were the primary outcomes, while angina relief and repeat hospitalization were the secondary outcomes.

Results:
At 1 year, ICBT restenosis occurred in 27% of treated patients and MACE free survival was 13.6%. When comparing patients in whom restenosis after ICBT occurred, there was a higher association of post ICBT MI which remained significant after multivariate analysis. All other primary and secondary outcomes remained insignificant (Table 1 and 2).

Conclusion:
ICBT is safe and effective for the treatment of DES ISR. Very few alternatives other than coronary bypass surgery exist to treat DES ISR. Given the success of ICBT in DES ISR, we propose that it should be utilized as the primary therapy. Restenosis after ICBT appears to be associated with post-ICBT MI. Additional data is needed to determine if there are other predictors for ICBT success.
Abstract 12898: Cigarette Smoking is Associated With Rapid Renal Function Decline in African Americans in The Jackson Heart Study
Authors: Hall Michael E , Wang Wei , Penman Alan , Okhomina Victoria , Dreisbach Albert W , Juncos Luis A , Hall John E , Winniford Michael D , Young Bessie A
Published: July 2021

Background:
Controversy exists regarding the association of cigarette smoking and renal dysfunction, particularly among African Americans who are disproportionately affected by chronic kidney disease (CKD). Therefore, we evaluated the relationship between cigarette smoking and rapid renal function (RRF) decline in the Jackson Heart Study (JHS).

Methods:
We evaluated the rates of RRF decline among a cohort of 5,301 African Americans enrolled as part of the JHS. Of those, 3648 with baseline creatinine were included for study. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. RRF decline was defined as an absolute decline of 30% over 10 years. Smoking status was defined as current, past (smoked at least 400 cigarettes/life) or never smoker. Poisson regression models were performed to estimate the association of smoking status with RRF decline.

Results:
There were 422 current, 659 past and 2567 never smokers identified at Visit 1. After adjustment for age, gender, BMI, diabetes, hypertension and total cholesterol, current smokers demonstrated a significantly higher incidence of RRF decline compared with never smokers (IRR 1.86, 95% CI 1.35-2.56). Current smokers using 1-19 cigarettes daily and ≥20 cigarettes daily also had an increased incidence of RRF decline (IRR 1.73, 95% CI 1.18-2.54 and IRR 2.03, 95% CI 1.23-3.35, respectively). There was a significant, stepwise reduction in eGFR from Visit 1 to Visit 3 in current and past smokers compared to never smokers (Figure).

Conclusions:
In a large cohort of African Americans, current cigarette smoking was independently associated with RRF decline in a dose-dependent manner.
Abstract 13032: Resolution of Congestion Before Coronary Angiography in Acute Heart Failure is Associated With Reduced Risk of Contrast-induced Acute Kidney Injury
Authors: Park Jonghanne , Park Jin Joo , Cho Young-Jin , Yoon Yeon-Yee , Oh Il-Young , Yoon Chang-Hwan , Suh Jung-Won , Cho Young-Seok , Youn Tae-Jin , Cho Goo-Yeong , Chae In-Ho , Choi Dong-Ju
Published: July 2021

Objectives:
We investigated the risk factors for contrast-induced acute kidney injury (CIAKI) after coronary angiography (CAG) in patients with acute heart failure (AHF), especially with regard to the volume status.

Background:
Heart failure is a well-known risk factor for CIAKI after CAG. In HF patients, renal perfusion decreases with systemic congestion. Thus, the standard prevention strategy with isotonic solution infusion may be inappropriate while decongestion may be beneficiary in AHF patients undergoing CAG. Deviation from dry body weight suggests imbalanced volume status.

Methods:
A total of 199 AHF patients who underwent CAG were eligible for the analysis. Absolute deviation of body weight (
Abstract 13053: Characteristics, Outcomes, and Predictors in Cardiovascular Shock Patients in Japan: Results From the Japanese Circulation Society Cardiovascular Shock Registry
Authors: Ueki Yasushi , Mohri Masahiro , Matoba Tetsuya , Kadokami Toshiaki , Suwa Satoru , Yagi Tsukasa , Takahashi Hiroshi , Tanaka Nobuhiro , Hokama Yohei , Fukuhara Rei , Tachibana Eizo , Yonemoto Naohiro , Nagao Ken
Published: July 2021

Introduction:
Despite the advances in the treatment of cardiogenic shock, mortality in these patients remains high. Data on the actual state of cardiovascular shock treatment and outcomes in Japan are scarce. In this study, we aimed to investigate the baseline characteristics and outcomes of patients with cardiovascular shock and identify the predictors of 30-day mortality.

Methods:
The Japanese Circulation Society Cardiovascular Shock registry was a prospective, observational, multi-center, cohort study. Between May 2012 and June 2014, a total of 980 patients with cardiovascular shock were enrolled from 82 centers in Japan. The median (interquartile range) age of the enrolled patients was 72 (63, 81) years, and 66% of the patients were male. The primary endpoint was all-cause death at 30 days.

Results:
The causes of shock included acute coronary syndrome (50.6%), non-ischemic arrhythmia (15.9%), aortic disease (14.9%), myocarditis (2.2%), cardiomyopathy (3.4%), pulmonary embolism (4.4%), valvular heart disease (1.3%), infective endocarditis (0.5%) and cardiac tamponade (1.4%). The all-cause mortality was 34.3%. On multivariate analysis, systolic blood pressure (odds ratio [OR], 0.986; 95% confidence interval [CI], 0.98-0.99, p<0.001), neurological status (OR, 1.694; 95% CI, 1.47-1.96, p<0.001), estimated glomerular filtration rate (OR, 0.982; 95% CI, 0.97-0.99, p<0.001), non-ischemic arrhythmia (OR, 0.516; 95% CI, 0.32-0.82, p=0.005), aortic disease (OR, 2.155; 95% CI, 1.41-3.30, p<0.001), and myocarditis (OR, 3.803; 95% CI, 1.41-10.23, p=0.008) were independent predictors of all-cause death at 30 days.

Conclusion:
Patients with non-ischemic arrhythmia had better prognosis, whereas those with aortic disease and myocarditis had poor prognosis. Blood pressure, neurological status, and renal function were also independent predictors of 30-day mortality.