bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13276: DHA but not Etanercept Expedites Resolution of Inflammation leading to Improved Survival Following Myocardial Infarction in Aging Mice
Authors: Ingle Kevin A , Kain Vasundhara , Halade Ganesh V
Published: July 2021

Dietary intake of n-3 polyunsaturated fatty acids (PUFA) has been touted for cardioprotective benefits. n-3 PUFA contains docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) but their individual effects on left ventricle (LV) remodeling remains unclear compared to anti-inflammatory molecule. We assessed the individual component of n-3 PUFA and their therapeutic potential on LV remodeling post-MI in aging mice (n=150). Male C57BL/6J mice were fed chow diet for first 12 months and then placed on safflower oil (SO; 10% w/w) enriched diet (n-6 PUFA) for 3 months to induce obesity. Then mice were randomized into 5 isocaloric groups: SO or DHA or EPA or DHA+EPA (D+E) or Etanercept (ETAN; 5mg/kg/day) (n=26-30 mice/group) for 2 months. At 17 months of age, mice were subjected to permanent coronary artery ligation resulting in MI and monitored for d1 and d5 survival; maintaining no-MI as d0 naïve controls. Post-MI survival was highest in DHA fed mice compared with ETAN and all other groups (p<0.05). Mice in all groups had lower fractional shortening and extensive ventricular remodeling post-MI compared to d0 control. DHA and D+E mice reduced neutrophil infiltration at d1 compared to SO (p<0.05). The DHA and EPA fed mice showed increased ccr2 and cxcl2 expression at d1 indicating the higher monocyte density, expediting the clearance of dead LV tissues. DHA and EPA groups (both p<0.05) showed early induction of resolving enzyme HO-1 (hemeoxygenase) at d1 which peaked at d5 facilitating resolution of inflammation post-MI. LV immunohistochemistry of DHA fed mice showed enhanced expression of COX-2 (cyclooxygenase-2) at d1 and 5-LOX (5-lipoxygenase) at d5 post-MI compared to d0, and other 4 groups (all p<0.05). Further, DHA fed mice showed the higher expression of timp-1, timp-2 and timp-3 with decrease in MMP-9 levels at d5 stabilizing the matrix maturation within the infarcted LV and thus promoting resolution. In summary, our results suggest that DHA but not ETAN improved post-MI survival in aging and obese mice by reducing neutrophil density, via coordination of COX, LOX and HO-1, leading to enhanced resolution of inflammation post-MI.
Abstract 13342: Patient Demographics, Clinical Characteristics, Medication Utilization, Medical Resource Use and Outcomes Associated with Patients with Symptomatic Peripheral Artery Disease
Authors: Reed Chase Monica , Navaratnam Prakash , Friedman Howard , Heithoff Kim , Simpson Ross J
Published: July 2021

Background:
Symptomatic peripheral artery disease (SPAD) [defined as intermittent claudication (IC) and/or critical limb ischemia requiring peripheral revascularization (PRV)] is associated with significant CV and PAD-related morbidity and mortality. However, the real world impact of SPAD has not been well characterized to date.

Methods:
An algorithm that selectively identifies SPAD patients using a combination of PAD related ICD-9 diagnostic and DRG codes, PRV CPT-4 procedure codes, and IC medication NDC codes was used to select study eligible patients from the MarketScan Commercial and Encounters database from 01/01/06 to 06/30/10. The earliest date of a record of SPAD was the index date and a period of 1 year pre- and 3 years post-index was the study time frame. Patients with stroke/TIA, with bleeding complications and contraindications to anti-platelet therapy were excluded. Descriptive statistics comparing patient demographics, clinical characteristics, medication utilization, medical resource utilization and outcomes (event risk estimates for MI, any stroke, revascularization (coronary and peripheral), limb amputation, acute ischemic event hospitalizations and costs) were generated.

Results:
A total of 16,663 patients (58.0% male; mean age (± SD) 67.2 ± 12.9 years) were identified with SPAD. SPAD patients had significant comorbidities with 31.5% CAD, 36.0% diabetes, 31.0% hyperlipidemia and 53.1% hypertension. Twenty percent (20%) of SPAD patients were on clopidogrel in the pre-index. Pre-index use of beta-blocker, ACE, ARB and statin use was 42.1%, 37.1%, 21.1% and 48.5% respectively. SPAD patients experienced CV events such as any stroke (8.9%), NSTEMI (4.1%), STEMI (4.8%) and UA (7.5%) in the post-index. SPAD patients also experienced a limb amputation (11.5%), endovascular PRV (17%), and open PRV (14.6%) in the post-index. Annualized SPAD-related hospitalization rates, inpatient costs and outpatients costs were significantly higher in the post-index (0.1 vs 0.01, $2,073 vs $175, $1,313 vs $936; all p<0.0001).

Conclusion:
In an insured population, SPAD patients have low utilization of preventive medications, high rates of major vascular events (both CV and PAD related) and high costs.
Abstract 13344: Higher Ambient Fine Particulate Matter Air Pollution and Temperature Levels Adversely Impact Cardiopulmonary Exercise Performance Among Patients Beginning Cardiac Rehabilitation
Authors: Giorgini Paolo , Rubenfire Melvyn , Das Ritabrata , Bard Robert L , Gracik Theresa , Wang Lu , Morishita Masako , Jackson Elizabeth , Ferri Claudio , Brook Robert D
Published: July 2021

Introduction:
Fine particulate matter (PM
2.5
) air pollution increases the risk for acute cardiovascular (CV) events. Extreme levels of ambient temperature (T) have also been linked to heightened CV risk. While several mechanisms have been proposed, no large-scale study has assessed the effect of PM
2.5
and T on directly-measured aerobic functional capacity among high-risk patients.

Methods:
We evaluated the effects of ambient PM
2.5
and T levels (during the prior 1 to 7 days at a local monitoring station) on cardiopulmonary exercise testing results performed among 2078 patients during enrollment into a cardiac rehabilitation program at the University of Michigan (from January 2003 to August 2011) using multiple linear regression analyses (controlling for age, sex, body mass index).

Results:
Peak exercise oxygen consumption (VO
2peak
) was significantly decreased by approximately 14.9% per 10 μg/m
3
increase in ambient PM
2.5
levels (lag days 6-7) (Figure). Increases in PM
2.5
were also related to significant decreases in anaerobic threshold (AT) (lag days 5-7), peak heart rate (lag days 2-3) and increases in peak systolic blood pressure (lag days 4-5). A 10°C increase in T was associated with reductions in VO
2peak
(20.6% to 27.3%) (Figure) and AT (22.9% to 29.2%) during all 7 lag days. While PM
2.5
results were attenuated by adjusting for T due to co-linearity, the effects of ambient T remained significant after adjusting for same-day PM
2,5
and accounting for season.

Conclusions:
Short-term elevations in ambient PM
2.5
and/or T were associated with detrimental effects upon several aerobic exercise parameters among this cohort of cardiac rehabilitation patients. Both environmental factors may thus be important public health risk factors for an impaired exercise performance linked to an adverse quality of life and worse CV prognosis.
Abstract 13357: MDCO-216 (ApoA-I Milano/POPC) Induces Reverse Cholesterol Transport in Stable Coronary Artery Disease Patients with a Dose Proportional Pharmacokinetics after Single Ascending Doses
Authors: Bellibas S. Eralp , Kallend David , Bobillier Alain , Kempen Herman , Wijngaard Peter L
Published: July 2021

Introduction:
MDCO-216, a complex of dimeric recombinant apolipoprotein A-I Milano (apoA-I M) and a phospholipid (POPC), is currently under development to improve cardiovascular outcomes by reducing plaque burden in patients with atherosclerotic disease. An earlier version of MDCO-216 has been shown effective in animal models and in patients with ACS. The purpose of this study was to assess the pharmacokinetics (PK), pharmacodynamics (PD) and safety of MDCO-216, manufactured by an improved process, first time in stable coronary artery disease (CAD) patients.

Methods:
24 patients with known stable CAD received a single dose of MDCO-216 (10, 20, 30 or 40 mg/kg) or placebo (in 2:1 ratio) as a 2 hour IV infusion in a double-blind, randomised design. Blood samples were collected for PK and anti-drug Antibody (ADA) analysis. Ex-vivo cholesterol efflux assays were used as exploratory PD biomarkers for MDCO-216 activity.

Results:
Plasma mean T
1/2
of MDCO-216 ranged from 45 to 59 hours (53 hr. in average) and median T
max
ranged between 2 to 3 hours. No obvious difference in CL was observed with increases in dose and this ranged from 0.7 to 0.8 mL/hr/kg. Exposure parameters (C
max
and AUC) increased with dose in a dose-proportional manner. No ADA was detected with any dose at any time point. Dose-dependent increases in ABCA1-mediated efflux (up to 4-fold above baseline) and smaller increases of SRB1-mediated efflux occurred rapidly after infusion. The dose-response analysis for ABCA1-mediated efflux best fitted into a sigmoid E
max
(maximum effect) PD model and predicts an E
max
of 12.7% which saturates around a 16 mg/kg dose (see figure).

Conclusions:
This data is consistent with the findings of the previous IVUS study in ACS patients with MDCO-216 where maximum regression of atherosclerotic plaque burden was seen at a dose of 15 mg/kg; and support further development of this agent as a potential treatment for atherosclerotic disease.
Abstract 13438: Rivaroxaban, a Direct Factor Xa Inhibitor, Attenuates Neointima Formation after Mechanical Vascular Injury
Authors: Hara Tomoya , Fukuda Daiju , Tanaka Kimie , Higashikuni Yasutomi , Hirata Yoichiro , Yagi Shusuke , Yamada Hirotsugu , Soeki Takeshi , Wakatsuki Tetsuzo , Shimabukuro Michio , Sata Masataka
Published: July 2021

Bachground:
Activated factor X (FXa) is a key member in the coagulation cascade responsible for thrombin generation, although accumulating evidence suggests it also has various biological functions in many cell types, contributing to the pathogenesis of neointima formation after vascular injury. In this study, we assessed the hypothesis that rivaroxaban, a direct FXa inhibitor, attenuates neointima formation after mechanical vascular injury by inhibiting both pro-inflammatory activation of macrophages and proliferative activation of vascular smooth muscle cells (VSMCs).

Methods and Results:
Rivaroxaban (5 mg/kg/day) was administered for 4 weeks to C57BL/6 mice after wire-mediated vascular injury. Plasma lipid levels and blood pressure were similar between rivaroxaban group and the control group. Rivaroxaban significantly reduced neointima area (30452 ± 2531 μm2 vs. 19582 ± 2531 μm2; P < 0.05) and intima/media ratio (4.37 ± 0.50 vs. 2.60 ± 0.50; P < 0.05) in the injured arteries at four weeks after injury, as determined by elastica van Gieson staining, compared with the control group. In vitro experiments using mouse peritoneal macrophages or murine macrophage cell line RAW264.7 demonstrated that FXa increased mRNA expression of inflammatory molecules (e.g., IL-1β and TNF-α) and vasoproliferative molecules (e.g., PDGF and BMP-2), which was blocked in the presence of rivaroxaban. In vitro experiments using rat VSMCs demonstrated that FXa stimulation promoted both mitogenesis and migration of this cell type, as determined by MTS assay and scratch-wound assay, respectively. Rivaroxaban attenuated these FXa-induced mitogenesis and migration.

Conclusions:
Rivaroxaban attenuates neointima formation in a mouse model of vascular injury. Our analyses suggest that FXa contributes to both pro-inflammatory activation of macrophages and proliferative activation of VSMCs, participating in the progression of neointima formation after vascular injury. FXa may serve as a potential therapeutic target for neointima formation after vascular injury.
Abstract 13490: Patterns of In-Hospital Management and Disposition of Patients Over 90 Years of Age Admitted with an Acute Coronary Syndrome at a Tertiary Medical Center
Authors: Shammas Nicolas W , Shammas Gail A , Shanks Carolyn , Dvorak Amanda , Serrano Patricia , Harb Christine , Voelliger Cara M , Koepke Christopher , Jerin Michael
Published: July 2021

Introduction:
It is estimated that by 2020 there will be 2.6 million nonagenarians and 135,000 centenarians in the United States. The in-hospital management and disposition of these patients remain poorly defined.

Hypothesis:
We describe in-hospital management and disposition of patients over the age of 90 years presenting with an acute coronary syndrome (ACS) at a tertiary medical center.

Methods:
All patients admitted between January 1, 2008 to December 31, 2012 with the diagnosis of an ACS and are over the age of 90 were included in this study. Demographic, clinical variables, in-hospital treatment, and post-hospital disposition were reviewed from medical records. The use of aspirin (ASA), beta-blockers, statins, ACEI/ARB, clopidogrel and aggressive versus conservative management were recorded.

Results:
109 patients (13.9% males) were included. Demographics and clinical variables were as follows: Prior CAD 63.3%, prior MI 25.7%, renal insufficiency 33%, HT 80.7%, hyperlipidemia 45%, DM 23.9%, heart failure 30.3%, dementia 15.6%, smoking history 21.1%, and atrial fibrillation 22%. Patients were admitted from home 50.9%, nursing home/assisted living 35.2%, transfer from a local cath lab 12% and from primary care physician’s office 1.2%. ACS symptoms consisted of UA 23.9%, NSTEMI 65.4%, STEMI 11%. Coronary intervention was performed in 43.5%. Conservative management was driven by: dementia 4.6%, patient or family wishes 34.2%, physician 13%, non-treatable disease 4.6%. Pharmacologic management on discharge included ASA 82.1%, beta blockers 72%, statins 41.1%, ACEI 31.5%, ARB 8.3%, clopidogrel 52.4%. In-hospital mortality was 8.4% (cardiac related 7.5%) and length of hospital stay was 4.8 ± 4 days. Patients were discharged to home with visiting nurse (VN) support 30.1%, without VN 7.8%, to a family member’s home 4.9%, nursing home 29.1%, skilled nursing/rehabilitation 15.5%, and hospice 5.8%.

Conclusions:
In-hospital mortality rates of patients over the age of 90 is acceptable. Frequently these patients are treated with PCI. Conservative management is mostly guided by the patient and family wishes. Unfortunately, these patients remain markedly undertreated with standard post MI or UA drugs. Less than half of these patients returned home.
Abstract 13616: Aorta Atheroma Burden Predicts Acute Cerebrovascular Events after Transcatheter Aortic Valve Implantation: Insights from Volumetric Multislice Computed Tomography Analysis
Authors: Kataoka Yu , Puri Rishi , Pisaniello Anthony D , Worthley Mathew I , Montarello Joseph , Nicholls Stephen J , Worthley Stephen G
Published: July 2021

Backgrounds:
Cerebrovascular accidents (CVAs) are a major complication of transcatheter aortic valve implantation (TAVI). Proposed mechanisms include atheroembolization of debris during balloon aortic valvuloplasty, deployment of the device or catheter passage through the aorta. The relationship between aortic atheroma burden and acute CVAs after TAVI has not been established.

Methods:
Preoperative multislice computed tomographic (MSCT) images in 218 patients treated with TAVI were analyzed. Vessel and lumen areas in each 1-mm cross-sectional image from ascending to abdominal aorta were measured. Total atheroma volume (TAV) was calculated and compared in patients with (n=18) and without (n=200) acute CVAs.

Results:
Patients with acute CVAs were more likely to have a history of cerebrovascular disease (61 v. 14%, p<0.01). MSCT analysis demonstrated that patients having acute CVAs exhibited greater TAV in the ascending aorta (11.9 ± 2.4 v. 9.7 ± 2.0 cm3, p=0.02) and arch (3.1 ± 1.1 v. 2.5 ± 0.5 cm3, p=0.02) but not in the descending (p=0.93) and abdominal aorta (p=0.77). Aortic valve calcification volume did not predict CVAs. TAV in the ascending (p=0.03) and arch (p=0.02), as well as a history of cerebrovascular disease (p=0.03), were independent predictors for acute CVAs after TAVI on multivariate analysis. Receiver-operating characteristic curve analysis identified TAV in the ascending aorta >10.2 cm3 and in the arch >2.8 cm3 as the optimal cutoff for predicting acute CVAs. The incidence of acute CVA was highest (66%) if patients had a history of cerebrovascular disease and TAV in the ascending aorta and arch above these cutoff values (Figure).

Conclusions:
Patients with acute CVAs after TAVI harbored greater atheroma burden in the ascending aorta and aortic arch. Our finding might underscore preoperative MSCT analysis of aorta atheroma burden to identify high-risk patients for acute CVAs, who may benefit from embolic protection devices during TAVI procedure.
Abstract 13624: Perceived Health and Physical Activity among Patients treated with Ablation for Atrial Fibrillation or Atrial Flutter compared with a Healthy General Population - Results from a Nationwide Survey
Authors: Risom Signe S , Berg Selina K , Christensen Anne V , Zwisler Ann-Dorthe , Svendsen Jesper H , Thygesen Lau C
Published: July 2021

Introduction:
Patients with atrial fibrillation (AF) or atrial flutter (AFL) report poor perceived health and avoidance behavior when suffering the arrhythmia. It is important to investigate if this perception and behavior changes after treatment with ablation, so that normality is regained.

Objective:
To describe patients’ perceived health and physical activity 6-12 months after ablation for AF or AFL and compare with an age- and sex- matched healthy general population.

Methods:
The nationwide cross-sectional survey was mailed to participants >18 years old who had been hospitalized for ablation for AF or AFL from January to June 2011.

The patients were identified in the Danish National Patient Register (n=714). The mailed questionnaire included Short Form 36 (SF-36) and a question about physical activity and was sent in Dec 2011 to eligible patients (n=627). The nationally representative Danish Health Interview Survey 2005 was used to sample an age- and sex-matched reference population.

Differences in perceived health (SF-36) were tested with t-test and chi2-test was used to determine the differences in physical activity levels.

Results:
The questionnaire was answered by 462 patients (74%). We found in all domains on SF-36 significantly lower scores for patients treated for AF and AFL compared with the reference group (p=0.0001) (see Table 1). Physical activity levels were also significantly lower for the patients treated for AF and AFL (p<0.0001).

Conclusions:
We found that patients treated for AF or AFL’s perceived health and physical activity levels were significantly impaired compared with a healthy general population. This is vital information for the health professional seeing the patients for follow-up after the ablation and rehabilitation should be considered.
Abstract 13740: Significance of Chronic Low-Grade Inflammation and Diabetes Mellitus (DM) for Coronary Spasm Following Drug-Eluting Stent Implantation in Patients with Coronary Heart Disease (CHD)
Authors: Hokimoto Seiji , Akasaka Tomonori , Arima Yuichiro , Kaikita Koichi , Nakagawa Kazuko , Ogawa Hisao
Published: July 2021

Background:
Coronary spasm is a manifestation of coronary endothelial dysfunction characterized by transient total or subtotal occlusion or severe diffuse vasoconstriction of an epicardial artery and contributes importantly to the pathogenesis of coronary heart disease (CHD). Coronary spasm and diabetes mellitus (DM) are reported to be associated with low-grade inflammation. However, it is unknown about the relation between chronic inflammation and DM in atherosclerotic high-risk patients following drug-eluting stent (DES) implantation. The aim was to examine the relation between coronary spasm and chronic inflammation or DM.

Methods:
We performed intracoronary acetylcholine test for coronary spasm provocation in 60 consecutive patients (41 male, age 69.1±9.1yrs) who had underwent new generation DES (cobalt-chromium everolimus-eluting stent, Xience (n=33); or biolimus-eluting stent, Nobori (n=27)) in left ascending coronary artery at 9 months before and examined plasma levels of tumor necrosis factor (TNF) α, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP) in the chronic phase without acute inflammation findings. Patients were divided into 3 groups: presence of both coronary spasm and DM (n=18), presence of each spasm or DM (n=31), and non-spasm and non-DM (n=11).

Results:
Coronary spasm was induced in 31 (51.6%) of 60 patients. Levels of TNFα, IL-6, and hs-CRP in spasm and DM group were increased compared with those in non-spasm and non-DM group (TNFα; 2.123±0.441 vs. 1.267±0.079 pg/ml, P=0.073: IL-6; 2.668±0.429 vs. 1.346±0.241 pg/ml, P=0.039: hs-CRP; 0.183±0.208 vs. 0.058±0.042 mg/dl, P=0.037). Levels of TNFα, IL-6, and hs-CRP in the each spasm or DM group were in between spasm / DM group and non-spasm / non-DM group, respectively (TNFα, 1.901±0.841pg/ml; IL-6, 2.125±0.651pg/ml; hs-CRP; 0.091±0.073mg/dl). Coronary spasm was not induced in statin-users among the total patients, and non-use of statin was associated with positive for coronary spasm (P=0.041) and increased inflammation levels.

Conclusions:
Coexistence of coronary spasm and DM in the chronic phase after new generation DES implantation may be associated with low-grade inflammation. The prevention of coronary spasm is related to the use of statin.
Abstract 13793: Role of Cardiac Autoantibodies for the Prediction of Recurrence Following Cryoballoon-based Lone Atrial Fibrillation Ablation
Authors: Yalcin Muhammed U , Gurses Kadri M , Kocyigit Duygu , Kesikli Sacit A , Yorgun Hikmet , Sahiner Mehmet L , Kaya Ergun B , Guc Dicle , Oto Mehmet A , Ozer Necla , Aytemir Kudret
Published: July 2021

Introduction:
Recent evidence have suggested that autoantibodies may play an important role in the development of atrial fibrillation (AF). Predictive value of pre-procedural autoantibodies against beta-1 adrenergic receptor (anti-β1-R) and M2-muscarinic acetylcholine receptor (anti-M2-R) for AF recurrence following cryoballoon-based pulmonary vein isolation (PVI) is still unclear. We aimed to determine the predictive value of pre-procedural anti-β1-R and anti-M2-R levels for AF recurrence in lone AF patients following cryoballoon-based PVI.

METHODS:
80 patients (mean age 54.25±7.7 years; 40% males) with lone AF who underwent cryoballoon-based PVI were included in the study. Pre-procedural anti-M2-R and anti-β1-R levels were measured with ELISA.

RESULTS:
At one-year follow-up after ablation, late AF recurrence was observed in 17 (21.25%) patients. In the Cox regression model including number of antiarrhythmic drugs, early AF recurrence, anti-β1-R levels >159.88 ng/mL, anti-M2-R levels >277.65 ng/mL, AF duration and left atrial volume index; only anti-β1-R levels >159.88 ng/mL (HR: 4.281, p=0.039) and anti-M2-R levels >277.65 ng/mL (HR: 4.313, p=0.030) were found to be independent predictors of late AF recurrence. Anti-β1-R level >159.88 ng/mL was shown to predict late AF recurrence with a sensitivity of 70.59% and specificity of 90.48%. A cut-off value of 277.65 ng/mL for anti-M2-R level predicted AF recurrence with a sensitivity of 70.59% and specificity of 95.24%.

CONCLUSION:
Pre-procedural serum anti-β1-R and anti-M2-R levels are independent predictors of late AF recurrence following cryoballoon-based PVI in lone AF patients. Detection of pre-procedural anti-β1-R and anti-M2-R levels may serve as a novel method for determination of lone AF patients who may not benefit from cryoballoon-based PVI.
Abstract 13850: Outcomes and Resource Utilization in ST Elevation Myocardial Infarction in the United States: Evidence for socioeconomic disparities
Authors: Agarwal Shikhar , Garg Aatish , Parashar Akhil , Jaber Wael A , Menon Venu
Published: July 2021

Background:
Socioeconomic status (SES) as reflected by residential zip code status may detrimentally influence a number of pre-hospital clinical, access-related and transport variables that influence outcome for patients with ST-elevation myocardial infarction (STEMI) undergoing reperfusion. We sought to analyze the relationship between SES and in-hospital mortality following STEMI.

Methods:
We used the 2003-2011 US Nationwide Inpatient Sample for this study. All admissions with a principal diagnosis of STEMI were identified using standard ICD codes. SES was classified based on median household income of the residential zip code of every patient. In-hospital death and timely reperfusion within day 0 of presentation were the primary outcomes for the study.

Results:
A total of 372984 admissions with STEMI were analyzed. There was a significantly higher mortality among the lowest SES quartile as compared to the highest quartile [OR (95% CI): 1.11(1.06-1.17)] (Fig). There was a highly significant trend indicating a progressively reduced timely reperfusion among patients from lower quartiles [OR (95% CI): 0.80 (0.74-0.88)] (Fig). In addition, there was a greater utilization of circulatory support devices and Swan Ganz catheterization among patients from higher as compared to lower quartiles (Fig). Furthermore, the mean adjusted cost of hospitalization among quartiles 2,3, and 4, as compared to quartile 1 was significantly higher by $913, $2140 and $4070 respectively.

Conclusions:
Patients residing in zip codes with lower SES had increased mortality and decreased timely reperfusion following STEMI as compared to patients residing in higher SES zip codes. Despite higher mortality, the utilization of circulatory support devices and Swan Ganz catheterization was paradoxically lower among patients from lower SES zip codes. In addition, cost of hospitalization of patients from higher SES quartiles was significantly higher than those from lower quartiles.
Abstract 13877: Comparison of Incidence of Radial Artery Occlusion in Patients Undergoing Trans-radial Intervention With or Without a Sheath: A Prospective Cohort Study
Authors: Palamaner Subash Shantha Ghanshyam , Pancholy Samir B
Published: July 2021

Introduction:
Sheathless transradial access, by decreasing the profile of hardware, is expected to lower the incidence of radial artery occlusion (RAO).

Hypothesis:
We sought to compare the risk of RAO in patients undergoing coronary intervention with introducer sheath (SG) or without introducer sheath (SLG).

Methods:
1251 consecutive patients undergoing 6 French percutaneous coronary intervention (PCI) between January 1, 2009 and December 31, 2013 in Scranton, PA, formed the study cohort. Radial artery patency was assessed using reverse Barbeau’s test and RAO was confirmed by ultrasonography. Unadjusted, adjusted and propensity matched association between type of radial access (SG vs SLG) and RAO were assessed using logistic regression analysis.

Results:
Mean age was 65 years, 63% were men 37% were diabetics. 78% attained patent hemostasis (PH). Patients in SG had lower pre-discharge RAO [unadjusted (OR: 0.31, 95% CI: 0.21 - 0.46, P < 0.001), adjusted (OR: 0.10, 95% CI: 0.05 - 0.20, P < 0.001) and propensity matched (OR: 0.20, 95% CI: 0.13 - 0.32, P < 0.001)], 24 hours RAO [unadjusted (OR: 0.20, 95% CI: 0.12 - 0.34, P < 0.001), adjusted (OR: 0.12, 95% CI: 0.06 - 0.24, P < 0.001) and propensity matched (OR: 0.13, 95% CI: 0.07 - 0.25, P < 0.001)] and 30 day RAO [unadjusted (OR: 0.28, 95% CI: 0.14 - 0.54, P < 0.001), adjusted (OR: 0.22, 95% CI: 0.10 - 0.50, P < 0.001) and propensity matched (OR: 0.18, 95% CI: 0.10 - 0.40, P < 0.001)], compared to those in SLG. Spontaneous recanalization rates were significantly higher in SG compared to SLG at 24 hours (62% Vs 38%, P = 0.007) but similar at 30 days (38% Vs 50%, P = 0.338) post PCI. Diabetes diagnosis was an effect modifier for RAO at pre-discharge, 24 hours and 30 days post PCI.

Conclusions:
Sheath use during radial access for PCI, despite diametrically increasing hardware profile, is associated with less RAO, likely by reducing friction induced intimal trauma. Diabetes is an effect modifier in this association.
Abstract 13917: Inhibition of GRK2 Prevents Cardiac Fibroblast-Mediated Maladaptive Ventricular Remodeling
Authors: Philip Jennifer L , Xu Xianyao , Han Mei , Li Jinju , Razzaque Abdur , Akhter Shahab A
Published: July 2021

Remote (non-infarct) territory fibrosis is a significant cause of post-myocardial infarction (MI) heart failure (HF). We have previously shown that increased activity of G protein-coupled receptor kinase-2 (GRK2) in adult human cardiac fibroblasts (CF) isolated from failing hearts is an important mechanism of cardiac fibrosis. This study investigates the potential therapeutic role of GRK2 inhibition on CF biology in vivo. Adult male rats underwent LAD ligation to induce post-MI HF. GRK2 was inhibited by intra-coronary adenoviral-mediated delivery of a GRK2 inhibitor (Ad-GRK2ct) immediately following LAD ligation (n=11). Control rats received a null adenovirus (n=10). Animals were studied prior to and up to 12 weeks (wks) post-MI and adenoviral delivery. There was a significant decline in LV function at 2 wks post-MI which was present through 12 wks [Fractional shortening: 0.35±0.01 vs. 0.52±0.01, p<0.01] in Ad-null rats vs. pre-MI. Remote territory (non-infarct area) fibrosis increased by 2 wks post-MI [6±1% vs. 2±1% fibrosis, p<0.01] progressing by 12 wks to 12% fibrosis [p<0.01], consistent with adverse remodeling. Collagen synthesis was upregulated 2.9-fold in CF isolated 12 wks post-MI [p<0.03] and GRK2 activity was increased 1.4-fold [p=0.002]. There was a 42% decrease in intracellular cAMP [p<0.05] and loss of β-agonist-stimulated inhibition of collagen synthesis characteristic of normal CF [3969±1058 vs. 708±95 cmp/mg protein, p<0.01]. Intra-coronary delivery of Ad-GRK2ct following LAD ligation significantly inhibited post-MI LV dysfunction vs. Ad-Null as measured by improved fractional shortening [0.42±0.01 vs. 0.30±0.02, p<0.01] and ejection fraction [72±1% vs. 57±2%, p<0.01]. Ad-GRK2ct also decreased peri-infarct and remote territory fibrosis by 60% [p<0.001]. Consistent with these findings, Ad-GRK2ct resulted in decreased a-SMA, collagen I, and collegen III expression in CF isolated 12 wks post-MI vs. Ad-Null providing evidence of decreased post-MI CF activation and myofibroblast transformation with Ad-GRK2ct. Targeted inhibition of GRK2 and restoration of β-adrenergic signaling/cAMP production in CF may represent a novel therapeutic approach to prevent pathological fibrosis and maladaptive remodeling post-MI.
Abstract 13969: Effect of Endothelial Shear Stress on the Serial Changes of Vein Grafts Assessed by Optical Coherence Tomography during the First Year After Coronary Artery Bypass Graft Surgery: Analysis from the CABG-PRO Study
Authors: Kotsia Anna , Papafaklis Michail , Michael Tesfaldet , Rangan Bavana , Pelz Matthias , Roesle Michele , Jessen Michael , Willis Bernice , Christopoulos Georgios , Nakas Georgios , Giannitsi Sofia , Sioros Spyros , Argyropoulos Konstantinos , Fotiadis Dimitris , Michalis Lampros , Banerjee Subhash , Brilakis Emmanouil
Published: July 2021

Introduction:
Saphenous vein grafts (SVGs) have high rates of both early (≤ 1 year) and late failure following coronary arterial bypass graft surgery (CABG).

Hypothesis:
Endothelial shear stress (ESS) is a critical determinant of the natural history of coronary atherosclerosis, but the influence on the structural changes of SVGs has not been studied. We evaluated the effect of ESS on the serial anatomic outcomes of SVGs assessed by optical coherence tomography (OCT) during the first postoperative year.

Methods:
We performed 3-dimensional SVG reconstruction in 8 SVGs using fusion of angiographic and OCT data 5-7 days after surgery (baseline) and at 12-month follow-up. Baseline ESS was assessed using computational fluid dynamics. The reconstructed SVGs were divided in consecutive 3-mm segments (n=181), and we assessed the association of baseline ESS with the anatomic outcomes in the corresponding segments at follow-up: change in lumen area and plaque burden, and neointimal area at follow-up. Baseline ESS was categorized according to the tertiles of the ESS frequency distribution.

Results:
Median baseline ESS in SVGs was 0.48 Pa [IQR: 0.37-0.61 Pa]). Baseline low ESS was associated with: (i) the largest decrease in lumen area (low ESS category: -8.72±0.95 mm2 vs. moderate ESS category: -5.67±0.95 mm2 vs. high ESS category: -3.64±0.95 mm2; p<0.001 low vs moderate and high ESS category), (ii) the largest increase in plaque burden (low ESS category: 24.3±3.4% vs. moderate ESS category: 22.6±3.4% vs. high ESS category: 20.9±3.4%; p=0.011 low vs high ESS category), and (iii) the largest neointimal area at 12 months (low ESS category: 4.02±0.45 mm2 vs. moderate ESS category: 3.65±0.45 mm2 vs. high ESS category: -3.57±0.45 mm2; p=0.020 low vs moderate ESS category, and p=0.009 low vs high ESS category).

Conclusions:
SVG areas with the lowest local ESS develop the largest lumen constriction, plaque burden increase and neointima formation. These findings provide important insights into the pathogenesis of early SVG failure.
Abstract 13973: Impaired Right Ventricular Hemodynamics Suggest Preclinical Pulmonary Hypertension in Patients With Metabolic Syndrome
Authors: Gopal Deepa M , Wang Yi-Chih , Ayalon Nir , Donohue Courtney , Santhanakrishnan Rajalakshmi , Rahban Youssef , Gokce Noyan , Perez Alejandro J , Downing Jill , Liang Chang-seng , Colucci Wilson S , Ho Jennifer E
Published: July 2021

Introduction:
Metabolic syndrome (MetS) is associated with preclinical metabolic heart disease (MHD) as reflected by left ventricular (LV) diastolic dysfunction. Very little is known about right ventricular (RV) function and/or pulmonary hypertension in MetS or early MHD.

Hypothesis:
We tested the hypothesis that that MetS is associated with subclinical RV dysfunction and pulmonary hypertension.

Methods:
A total of 164 subjects with MetS but without cardiovascular disease (mean age 45 years, 71% women, mean BMI 41 kg/m
2
), 40 similarly obese controls without MetS, and 36 non-obese healthy controls underwent echocardiography, including pulsed-wave Doppler measurement of pulmonary artery acceleration time (PAAT) and ejection time (ET). PA systolic pressure was estimated from PAAT using validated equations.

Results:
MetS was associated with lower tricuspid valve e', shorter PAAT, shorter ET, and larger PA diameter compared with controls (Table). A total of 24% of individuals with MetS had an abnormal PAAT (<100 msec). Estimated PA systolic pressure based on PAAT was 42±10 mmHg in MetS compared with 32±10 and 32±9 mmHg in healthy and obese controls (P for ANOVA <0.0001). In contrast, RV structure and systolic function were similar in MetS compared with controls (
Table
). After adjustment for age, sex, hypertension, diabetes, and body-mass index, MetS remained associated with shorter PAAT (P=0.03 vs healthy; P=0.0005 vs obese). Among MetS, PAAT was correlated with mitral mean e’ (r=0.20, P=0.004), E/A ratio (r=0.21, P=0.008), and tricuspid e’ (r=0.20, P=0.04). A total of 40% of participants with abnormal PAAT also had low mean e’ (<8 cm/s).

Conclusions:
MetS is associated with abnormal RV hemodynamics as evidenced by shorter PAAT, which correlates with measures of LV diastolic function. Estimated PA systolic pressures are significantly higher in preclinical MetS and MHD, and raise the possibility that pulmonary hypertension contributes to the pathophysiology of MHD.
Abstract 13979: Left Atrial Symmetry Changes in Atrial Fibrillation: Relation With Diastolic Dysfunction and Symptom Severity
Authors: Nedios Sotirios , Breithardt Ole-A. , Koutalas Emmanuel , Kosiuk Jedrzej , Sommer Philipp , Arya Arash , Rolf Sascha , Husser Daniela , Hindricks Gerhard , Bollmann Andreas
Published: July 2021

Introduction:
Atrial fibrillation (AF) progression has been associated with asymmetric left atrial (LA) dilatation and left ventricular diastolic dysfunction (LVDD). LVDD has been also correlated with symptom severity.

Hypothesis:
Aim of this study was to test the hypothesis that the pattern of LA asymmetry is associated to LVDD and symptom severity.

Methods:
In 104 patients (58±10 years old, 69% male) referred for AF ablation, CT data were used to determine the LA volume (LAV) after exclusion of the appendage and the pulmonary veins (PVs). A cutting plane, between the PV ostia and the appendage and parallel to the posterior wall, divided LAV into anterior- (LA-A) and posterior-LA (LA-P) parts. The ratio LA-A/LAV was defined as asymmetry index (ASI). LVDD was evaluated according to current guidelines and symptom severity was quantified using the European Heart Rhythm Association score.

Results:
Univariate linear regression revealed that ASI is associated with LVDD, LAV and mitral regurgitation. ASI was higher in patients with LVDD (n=35, 62±5% vs. 59±6%, p=0.013) and in patients with mitral regurgitation (n=67, 61±6% vs. 58±5%, p=0.025) than those without. LAV increase was associated with an ASI increase (r=0.26, p=0.008). Multiple linear regression analysis revealed that LAV (β=0.211, 95% CI: 0.003-0.071, p=0.033) and LVDD (β=0.207, 95% CI: 0.167-5.011, p=0.036) were the only independent predictors of ASI increase (adjusted r2=0.92, F=6.2, p=0.003). Patients with moderate-severe AF symptoms (n=61) had higher ASI (61±6% vs. 58±5%, p=0.012) and higher prevalence of LVDD (43% vs. 21%, p=0.034) than those with mild symptoms.

Conclusions:
LA symmetry changes are associated with dilatation and left ventricular diastolic dysfunction and correlate with symptom severity in AF.
Abstract 13983: Tricuspid Regurgitation is Independently Associated With Increased Risk of Mortality in Patients with Low-Flow Low-Gradient Aortic Stenosis and Reduced Ejection Fraction-Results From the TOPAS Study
Authors: Dahou Abdellaziz , Magne Julien , Clavel Marie-Annick , Capoulade Romain , Bartko Philipp E , Bergler-klein Jutta , Senechal Mario , Mundigler Gerald , Burwash Ian G , Ribeiro Henrique B , O’Connor Kim , Mathieu Patrick , Baumgartner Helmut , Dumesnil Jean G , Rosenhek Raphael , Larose Eric , Rodés-Cabau Josep , Pibarot Philippe
Published: July 2021

Background:
Tricuspid regurgitation (TR) is often observed in patients (pts.) with low-flow, low-gradient aortic stenosis (LF-LG AS) and low ejection fraction (EF). Its impact on prognosis remains unknown. The objective of this study was to examine the impact of TR on mortality in these pts.

Methods:
211 pts. (age=73±10 yrs; 77% men) with LF-LG AS (mean gradient<40 mmHg, AVA ≤0.6 cm2/m2) and low EF (≤40%) were prospectively enrolled and 125 (59%) underwent aortic valve replacement (AVR) within 3 months following inclusion. AS severity was assessed by the projected AVA. The severity of TR was graded according to ASE guidelines. Right ventricular (RV) function was assessed using an integrative approach and classified as normal or reduced.

Results:
Among the 211 pts., 76 (36%) had TR (24% mild TR and 12% moderate/severe TR). During a mean follow up of 2.4±2.2 yrs, 104 (49%) died. In univariable analysis, TR was associated with an increased risk of all-cause mortality (overall TR: HR=1.82; 95% CI=1.22-2.71; p=0.004; mild TR: HR=1.62; 95% CI=1.02-2.54; p=0.04; moderate/severe TR: HR=2.30; 95% CI=1.27-3.93; p=0.007). After adjustment for risk factors and echocardiographic parameters including RV function, TR was an independent predictor of mortality (overall TR: HR=1.88; 95% CI=1.08-3.23; p=0.02; mild TR: HR=2.19; 95% CI=1.00-4.77; p=0.05; moderate/severe TR: HR=2.68; 95% CI=1.08-6.32; p=0.03). Furthermore, moderate/severe TR was an independent predictor of 30-day mortality following AVR compared to none/trace TR (OR=7.24; p=0.01) and mild TR (OR=4.70; p=0.05).

Conclusion:
In patients with LF-LG AS and low EF, TR is independently associated with an increased risk of mortality. Moderate/severe TR is associated with increased 30-day mortality following AVR. Further studies are needed to determine whether TR is a risk marker or risk factor of mortality, and whether concomitant surgical correction at the time of AVR can improve outcome in these high risk patients.
Abstract 14019: Electrophysiological Effects of the Late Sodium Current Inhibitor GS967 in
Scn5a
-1798insD Mouse and Human
SCN5A
-1795insD iPSC-derived Cardiomyocytes
Authors: Portero Vincent , Hoekstra Maaike , Verkerk Arie O , Mengarelli Isabella , Davis Richard P , Freund Christian , Bezzina Connie R , Belardinelli Luiz , Rajamani Sridharan , Veldkamp Marieke W , Remme Carol Ann
Published: July 2021

Background and Aim:
Selective inhibition of cardiac late sodium current (I
Na,L
)

is an emerging target in the treatment of ventricular arrhythmias. The electrophysiological effects of GS967, a potent I
Na,L
inhibitor, were investigated in an overlap syndrome model of both gain and loss of sodium channel function, comprising cardiomyocytes derived from human
SCN5A
-1795insD induced pluripotent stem cells (iPSC-CMs) and mice carrying the homologous mutation
Scn5a
-1798insD.

Methods and Results:
On patch-clamp analysis, isolated mouse
Scn5a
-1798insD cardiomyocytes and human
SCN5A
-1795insD iPSC-CMs showed decreased peak I
Na
and action potential (AP) upstroke velocity (Vmax) and increased I
Na,L
and AP duration at 90% repolarization (APD
90
) as compared to wild-type. GS967 (50-300 nM) significantly decreased APD
90
in mouse
Scn5a
-1798insD cardiomyocytes by 8±2% (mean±SEM) at 50 nM (n=7), 13±3% at 100 nM (n=11) and 20±5% at 300 nM (n=6) (all
p
<0.01 vs. control), without affecting Vmax. GS967 (300 nM) selectively inhibited I
NaL
in mouse
Scn5a
-1798insD cardiomyocytes (GS967-sensitive current of 0.7±0.1 pA/pF, n=6), but had no effect on peak I
Na
.
Furthermore, GS967 (100 nM) suppressed fast (5 Hz) pacing-induced afterpotentials and triggered activity. In human
SCN5A
-1795insD iPSC-CMs (n=6), GS967 (300 nM) significantly reduced APD
90
without affecting the resting membrane potential or Vmax. In Langendorff-perfused, isolated mouse
Scn5a
-1798insD hearts (n=5), GS967 (300 nM) had no effect on ventricular activation time or conduction velocity (as assessed by epicardial mapping).

Conclusion:
Selective inhibition of I
NaL
by GS967 attenuated AP prolongation and prevented pro-arrhythmic activity in mouse
Scn5a
-1798insD cardiomyocytes and human SCN5A-1795insD iPSC-CMs, thus suppressing the gain-of-function features of this overlap syndrome mutation. Importantly, these beneficial actions of GS967 occurred in the absence of deleterious effects on sodium channel availability or cardiac conduction, despite a pre-existing decrease in peak I
Na
. Thus, selective inhibition of I
Na,L
constitutes a promising pharmacological treatment of cardiac channelopathies associated with enhanced I
NaL
, even in overlap syndromes whereby peak I
Na
is decreased.
Abstract 146: Neurological Prognostication by Gender in Patients with Out-of-Hospital Cardiac Arrest Receiving Hypothermia Treatment
Authors: Kim Min Jung , Shin Sang Do , McClellan William , McNally Bryan
Published: July 2021

Objectives:
This study aimed to to examine whether neurologic recovery of out-of-hospital cardiac arrest patients receiving hypothermia treatment is enhanced for women of childbearing age.

Methods:
A cross-sectional analysis was conducted using a nationwide surveillance database in Korea of out-of-hospital cardiac arrest (OHCA) that occurred between 2008 and 2012. The exposure and outcomes studied were hypothermia treatment and neurologic outcome at discharge. Patient characteristics between hypothermia-treated and non-treated groups were compared. Multivariate logistic regression was used to account for the patient characteristics. The association was examined for each stratum of gender, age (<45, 45-65, and >65 years old), and initial cardiac rhythm. Cardiac rhythms were considered in two different categorizations: 1) shockable/non-shockable rhythm, and 2) VF.VT/PEA/asystole.

Results:
Crude analysis showed that women of childbearing ages treated with hypothermia had enhanced neurologic recovery than older aged women and all men. After adjusted, men had stronger association between hypothermia and good neurologic recovery than women. The highest association was found in men who are under 45 years of age and have shockable cardiac rhythm (OR=2.00 (1.26, 3.19)). The association between hypothermia and neurologic recovery was not statistically significant in all women. The magnitude of association decreased with age. Shockable rhythm was associated with better neurologic recovery than non-shockable rhythms in all gender and age groups. Using VF.VT/PEA/asystole categorization of cardiac rhythms, men consistently showed higher ORs than women. In all gender and age groups, having PEA rhythm was associated with better neurologic outcome than shockable rhythms (VF/VT) or asystole.

Conclusion:
The unadjusted association between hypothermia and neurologic recovery was the strongest in women of childbearing ages. After adjustment, men had a better neurologic outcome than women across all ages. Shockable rhythms were associated with enhanced neurologic recovery. Our results suggest that among OHCA patients, the effect of hypothermia treatment on neurologic recovery is greater for men, young ages, and having shockable cardiac rhythm.
Abstract 14664: SIRT3 Protects Cardiomyocytes From Doxorubicin-induced Mitochondrial Damage and Cell-death by Activating Opa1
Authors: Samant Sadhana , Pillai Vinodkumar , Wolfgeher Don , Gupta Mahesh
Published: July 2021

Introduction:
The anti-cancer drug therapy with doxorubicin (Dox) is known to produce cardiomyopathy associated with fragmentation of mitochondria and excess production of reactive oxygen species (ROS). Sirtuin3 (SIRT3), a mitochondrial deacetylase regulates many mitochondrial functions including energy production, ROS synthesis and cell-death. A role of SIRT3 in regulating the aging process and aging-associated diseases like heart failure, cancer and diabetes has been also documented. This study was undertaken to investigate whether SIRT3 can protect cardiomyocytes from Dox-induced mitochondrial damage and cell-death.

Methods and Results:
Neonatal rat cardiomyocytes were over expressed with a vector synthesizing SIRT3 or a mock vector. Cells were treated with Dox (100nM) for 72 hours and cell-death was analyzed by measuring TUNEL-positive nuclei, ROS synthesis and expression of apoptotic markers by the western blotting. There was marked reduction of TUNEL-positive nuclei, ROS levels and expression of apoptotic markers such as Bax, Bim and FasL in SIRT3 over expressing cells, compared to control cells received the mock vector. Confocal imaging of myocytes revealed that Dox-treatment caused swelling and fragmentation of mitochondria in control cells, but not in cells over expressed with SIRT3. To understand the mechanism involved in SIRT3-mediated protection of mitochondria we analyzed acetylation of proteins involved in regulating mitochondrial fusion-fission dynamics. We found that OPA1 (optic atrophy-1), an essential inner membrane fusion protein, was hyper-acetylated in Dox-treated cells, leading to its reduced GTPase activity. SIRT3 was capable of deacetylating and augmenting GTPase activity of OPA1 both
in vitro
and
in vivo
assay conditions. Furthermore, by studying OPA1 null cells we found that it is necessary for SIRT3-mediated protection of cardiomyocytes from mitochondrial damage and cell-death.

Conclusions:
These results indicated that SIRT3-dependent activation of OPA1 contributes to preservation of mitochondrial population and protection of cardiomyocytes from Dox-mediated cell-death. We believe that SIRT3 could be utilized as a therapeutic target for treatment of Dox-induced cardiomyopathy of the heart.