bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11826: Device Detected Atrial Fibrillation Poses Significant Risk of Heart Failure Related Hospitalization
Authors: Crossley George H , Boyle Andrew , Mead R Hardwin , Bergeman Tracy
Published: July 2021

Background:
Implantable cardioverter-defibrillators (ICDs) collect advanced diagnostics on the progression of the patient’s heart disease. Arrhythmia detection algorithms continuously identify atrial arrhythmias.

Methods:
The CONNECT (Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision) study was a multicenter, prospective, randomized evaluation involving 1980 randomized patients from 136 clinical sites who underwent an ICD implant and followed for 15 months. Health care utilization data included all CV-related hospitalizations, emergency department visits, and clinic office visits. The analysis here focuses on heart failure (HF) related hospitalizations. Device-detected atrial arrhythmias were collected throughout follow-up. A non-parametric estimate of the nonlinear relationship between average atrial tachycardia / atrial fibrillation (AT/AF) burden per day and hazard of HF-related hospitalization or death was modeled via a third-order P-spline. The number of AT/AF episodes greater than 12 hours long was tested as a time-dependent covariate in a Cox model.

Results:
Information was available on arrhythmia detection in 1939 of 1980 randomized patients. There were 1540 patients with at least one device-detected AT/AF episode. Estimation of average AT/AF burden per day and risk of HF-related hospitalization or death indicated that the risk of an event increased with increasing AT/AF burden and that the risk was consistently higher with AT/AF episodes ≥ 12 hours per day. The incremental hazard ratio of HF-related hospitalization or death associated with a 12 hour AT/AF episode was 2.58 (CI: 1.57--4.24; p = 0.0002). The risk remains after adjustment for other clinical variables of interest.

Conclusions:
Device-detected AT/AF episodes of at least 12 hours in duration pose significant and increased risk for HF-related hospitalizations.
Abstract 11835: Title: Quality and Efficacy of Patient Self-Management of Warfarin
Authors: Bonaventura Kathleen R , Milner Kerry
Published: July 2021

Objective:
Patient self-management (PSM) is self-testing and altering the dose of their warfarin which allows for more frequent self-testing of warfarin levels, rapid results, timely dosage change, less dependency on the healthcare provider, and can be done anywhere. The objective of this study was to determine if PSM of warfarin is as safe and effective as healthcare provider dosing.

Method:
The setting for this study was a large cardiology practice that manages over 1000 patients on warfarin. Of these patients, 500 (50%) were using warfarin due to a valve replacement and 155 (16%) were engaged in self-testing. The final sample included 50 (32%) patients using self-testing who completed a 2-hour structured educational program on PSM of warfarin and practiced PSM for a 13-week period. Percentage of time the INR was maintained in therapeutic range, variance from the prescribed INR, and the adverse events of bleeding or thromboembolism were measured for 13 weeks pre-PSM and 13 weeks during PSM. Data were analyzed using t-test, correlation and Wilcoxson rank sum test.

Results:
There was no significant difference in pre-PSM time in therapeutic range compared with during PSM time in therapeutic range (p = .74). The mean INR variance from the prescribed INR range decreased significantly during PSM compared with pre-PSM, (p = .03), and when the INR did vary from the patient-specific prescribed range it tended to be in the high range but this did not reach significance (p = .67). These were desirable effects because this patient population is at high risk for embolic events. There was no significant increase in adverse events during PSM (p = .32).

Conclusion:
PSM of Warfarin was found to be as safe and effective as provider management. Moreover, PSM resulted in tighter control of INR variance compared with provider dosing. These results support the use of PSM of warfarin for eligible patients. Furthermore the model of PSM used in this study elicited patient engagement in behaviors that reduced the impact of their disease and decreased the burden of care on the healthcare provider.
Abstract 11885: Differential Contributions of Abdominal Visceral Fat and Epicardial Fat to Coronary Atherosclerosis in Non-Obese Japanese Patients
Authors: Harada Ken , Kataoka Takashi , Takeshita Masahiro , Harada Kazuhiro , Kunimura Ayako , Okumura Satoshi , Shinoda Norihiro , Kato Bunichi , Uetani Tadayuki , Kato Masataka , Marui Nobuyuki , Ishii Hideki , Matsubara Tatsuaki , Amano Tetsuya , Murohara Toyoaki
Published: July 2021

Introduction:
Epicardial fat is a source of adipocytokines that have both paracrine and systemic effects and is implicated in coronary atherosclerosis. The relation between epicardial fat volume (EFV) and circulating adipocytokine levels has remained unknown, however.

Objectives:
We assessed the relation between EFV and both plasma adipocytokine concentrations and coronary atherosclerotic plaque.

Methods:
Consecutive Japanese patients suspected of having coronary artery disease (n = 216) were examined. Individuals with acute coronary syndrome or with inadequate CT imaging were excluded. A total of 164 patients (65 ± 10 years; 70% men; BMI, 23.8 ± 3.6 kg/m2) was enrolled. Plasma levels of adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), and vascular endothelial growth factor (VEGF) were measured. The characteristics of coronary plaque, abdominal visceral fat area, and EFV were determined by 64-slice CT.

Results:
EFV was greater in subjects with noncalcified plaque than in those with no plaque or with calcified plaque (126 ± 39 vs. 98 ± 34 and 97 ± 45 mL, respectively; P = 0.010). EFV was significantly correlated with BMI, plasma triglyceride concentration, and the triglyceride/HDL-cholesterol ratio (r = 0.51, 0.19, and 0.20, respectively) but not with plasma adipocytokine levels, whereas plasma adiponectin and IL-6 levels were significantly correlated (r = -0.49 and 0.20, respectively) with visceral fat area, in patients with coronary plaque.

Conclusions:
Patients with noncalcified plaque had increased EFV but their plasma adipocytokine levels had not increased. Adipocytokines in plasma may be derived mainly from abdominal visceral fat, whereas epicardial fat may promote coronary atherosclerosis directly through a paracrine mechanism rather than by systemic effects. In conclusion, abdominal visceral fat and epicardial fat may thus contribute to coronary atherosclerosis by distinct mechanisms in nonobese individuals.
Abstract 11888: MyD88 Expressed by Myeloid Cells is Essential for Angiotensin II-Induced Vascular Dysfunction, Inflammation and Arterial Hypertension
Authors: Kossmann Sabine , Schönfelder Tanja , Finger Stefanie , Brähler Melanie , Minwegen Daniel , Knorr Maike , Daiber Andreas , Radsak Markus , Münzel Thomas , Wenzel Philip
Published: July 2021

Background:
Angiotensin II (ATII) causes hypertension and promotes infiltration of inflammatory cells into the vessel wall. Vascular superoxide formation and shear stress mediated inflammatory remodeling of conduit arteries was shown to be myeloid differentiation factor 88 (MyD88) dependent, but the exact mechanism are unknown.

Objective:
The goal of this study was to determine the mechanism, how MyD88 contributes to the development of ATII-induced vascular dysfunction and arterial hypertension.

Methods and Results:
MyD88 deficiency profoundly attenuated ATII-induced (1 mg/kg/d for 7 days) blood pressure increase (measured by radio telemetry) and vascular dysfunction (assessed by aortic ring relaxation studies). Additionally vascular superoxide levels as well as mRNA expression levels of VCAM-1, iNOS, Nox2 were decreased in ATII-infused MyD88
-/-
mice compared to WT controls. Aortic flow cytometric analysis revealed that ATII-induced infiltration with CD11b
+
Ly6C
high
inflammatory monocytes was significantly dampened in MyD88
-/-
mice. ATII led to an increased expression of inflammatory monocyte markers in blood and aorta, which was blocked in MyD88
-/-
mice, indicating a role of MyD88 for myeloid cell differentiation. Additionally less IFN-gamma
+
NK cells were detected in the vessel wall of ATII-treated MyD88
-/-
mice and aortic lysates showed reduced mRNA levels of several proinflammatory cytokines like IL-12 and IL-1beta. Bone marrow transfer experiments further revealed a protective effect of MyD88 deficiency in inflammatory cells represented by a reduction of vascular dysfunction and inflammation.

Conclusion:
We provide first evidence that MyD88 expressed by bone marrow-derived cells plays an essential role in ATII-induced vascular dysfunction and arterial hypertension. Our data indicate that MyD88 is important for cytokine production and might be required for ATII-induced differentiation of monocytes into an inflammatory phenotype.
Abstract 11914: Coronary Sinus Lead Extraction_Laser Required
Authors: Fender Erin A , Henrikson Charles A
Published: July 2021

Introduction:
Studies of coronary sinus (CS) lead extraction have reported high success rates with manual traction, but largely included leads with dwell times less than 3 years. Our aim was to evaluate CS lead extractions of more chronic leads and establish if dwell time was correlated to complexity of extraction.

Methods:
This is a single center, retrospective review of 96 consecutive lead extraction procedures. A total of 14 CS leads were identified.

Results:
Of the 14 CS lead extractions, 13 were successful from an endovascular approach. Indications included 8 cases of endocarditis, 4 pocket infections, 1 dislodged lead and 1 malfunctioning lead. Six extractions were performed with manual traction, dwell time of these leads ranged from 5 months to 28 months, with an average implant time of 10.8 months. Eight extractions required use of a laser sheath (LS) to free the lead from adhesions. In no case was the LS used within the CS. The dwell time of these leads ranged from 45 months to 114 months, with an average lead age of 83.4 months. One LS case also required use of a rotating mechanical sheath. In one LS assisted extraction, the lead fragmented within the CS and could not be recovered endovascularly despite the use of multiple snares. This lead fragment was removed via an open surgical approach.

Conclusion:
CS leads require the use of advanced extraction tools in the majority of patients. All leads placed in the preceding 28 months were removed with simple manual traction, however all leads that were in place for more than 3 years required use of a LS. In contrast to prior reports, we found that coronary sinus leads posed the same procedural challenges as other cardiac leads and typically require advanced extraction tools.
Abstract 11916: Changes in Symptoms Predicted Changes in Health-Related Quality of Life in Patients With Heart Failure
Authors: Heo Seongkum , Moser Debra K , Lennie Terry A , Fischer Mary , Smith Eugene , Walsh Mary N
Published: July 2021

Background:
Patients with heart failure (HF) have notably poor health-related quality of life (HRQOL), which is associated with high hospitalization rates. Physical symptoms have been associated with poor HRQOL. However, whether improvement in physical symptoms actually leads to improvement in HRQOL has not fully examined in patients with HF.

Purpose:
To examine the effects of changes in physical symptoms on changes in HRQOL at 12 months, after controlling for age, comorbidities, New York Heart Association (NYHA) functional class, and modifiable psychosocial and behavioral factors.

Methods:
Data on physical symptoms (Symptom Status Questionnaire-HF) and HRQOL (Minnesota Living with Heart Failure) were collected from 94 patients with HF (mean age 58 ± 14 years, 44% male, 58% NYHA functional class II/III) at baseline and 12 month follow-up. Age, comorbidities, and NYHA functional class were collected using standard questionnaires at baseline. Psychosocial variables (depressive symptoms [Patient Health Questionnaire], perceived control [Control Attitudes Scale-Revised], and social support [Multidimensional Scale of Perceived Social Support]) and behavioral variables (medication adherence [Micro-Electro-Mechanical Systems], sodium intake [24-hour urine], and self-care management [Self-care management subscale of the Self-Care of Heart Failure Index]) were collected at baseline. Hierarchical multiple regression analyses were used to analyze the data.

Results:
The mean score changes in physical symptoms and HRQOL were -3.8 (± 14.1) and -9.2 (± 24.1), respectively (negative scores indicate improvement.). Among the sociodemographic and clinical characteristics, psychosocial variables, behavioral variables, baseline physical symptoms, and changes in physical symptoms, only changes in physical symptoms predicted changes in HRQOL at 12 months (F = 6.384, R2 = .46, p < .001). Improvement in physical symptoms led to improvement in HRQOL.

Conclusion:
It is critical to improve physical symptoms to improve HRQOL. Thus, development and delivery of effective interventions targeting improvement in physical symptoms are warranted in this population.
Abstract 11936: Development of Monthly to Quarterly Subcutaneous Administration of RNAi Therapeutics Targeting the Metabolic Diseases Genes PCSK9, ApoC3 and ANGPTL3
Authors: Borodovsky Anna , Querbes William , Sutherland Jessica , Hutabarat Renta , Milstein Stuart , Kuchimanchi Satya , Kuchimanchi Rajeev , Charisse Klaus , Yucius Kristina , Liebow Abigail , Sprague Andrew , Maier Martin , Kallend David , Simon Amy , Horton Jay , Fitzgerald Kevin
Published: July 2021

Introduction:
Cardiovascular disease remains the top cause of mortality in the United States. We have developed, and validated in human trials, a platform for reducing the synthesis of genes expressed in the liver. The platform utilizes a GalNAc sugar ligand attached to the 3’end of the sense strand of an RNAi molecule to enable delivery specifically to the liver. Here we present data from this platform on multiple targets of interest in cardiovascular disease, including PCSK9, ANGPLT3 and ApoC3.

Hypothesis:
RNAi therapeutics targeting liver genes of interest (such as PCSK9, ApoC3 and Angptl3) will allow for control of lipid levels and reduce the risk of cardiovascular disease.

Methods:
Chemically modified siRNAs were designed using bioinformatic algorithms and were screened for potency
in vitro
. pM active siRNA molecules were developed targeting PCSK9, ANGPLT3 and ApoC3.

Results:
ALN-PCSsc: In NHPs a single dose of ALN-PCSsc at ≥ 6 mg/kg reduced circulating PCSK9 levels up to 97% and LDL-C up to 67%. Moreover the nadir effect ( where LDL-C is clamped) lasted ~90 days suggesting that once monthly to quarterly dosing could be supported. Multidose studies in NHP at 2 mg/kg reduced circulating PCSK9 levels up to 94% with a subsequent lowering of LDL-C up to 67%. Safety studies in rat and NHP at doses up to 300 mg/kg (multi-dose) showed that ALN-PCSsc was safe demonstrating potential for a very wide therapeutic index. ALN-PCSsc was selected as a development candidate and is being advanced towards an IND for the treatment of hypercholesterolemia.

ALN-ANGsc: Was tested in two models of hyperlipidemia, the OB/OB mouse and the hCETP-ApoB mouse. In the Ob/Ob model, treatment with ALN-ANGsc at 3mg/kg resulted in a significant lowering ANGPLT3 protein (>95%), cholesterol (>60%) and triglycerides (>85%).

ALN-ApoC3: Was tested in the db/db mouse model of hyperlipidemia. A robust lowering of plasma ApoC3 (>90%) lead to a >50% lowering of triglycerides. Screening for both programs is underway for a development candidates.

Conclusions:
We have developed a modular, robust and reliable platform for the delivery of RNAi therapeutics to the liver with a large therapeutic index. This small volume, subcutaneous, platform has a remarkable duration of effect.
Abstract 11963: Randomized Ivus Comparison Between a Durable and a Biodegradable-Polymer Second Generation Drug-Eluting Stents: The Bioactive Trial
Authors: Costa Jose de Ribamar , Almeida Breno , Costa Ricardo , Chamie Daniel , Perin Marco , Abizaid Andrea , Sousa Amanda , Abizaid Alexandre
Published: July 2021

Background:
New generation drug-eluting stents (DES), biolimus-eluting stents (BES) and everolimus-eluting stents (EES) were conceived to minimize local coronary inflammation allowing better endothelial healing. The aim of this study is to compare the IVUS patterns observed with both stents at midterm follow-up.

Methods:
The Bioactive trial is a multicentre, randomized trial (1:1) comparing BES and EES based on surrogate safety and efficacy endpoints. Inclusion criteria was single, de novo lesions in native coronary arteries of 3.0 to 3.5mm and maximum lesion length of 20 mm. Patients with in-stent restenosis, lesion in grafts and treated in the setting of STEMI were excluded. The present analysis aims to compare the main IVUS findings for both DES at 9-month invasive follow-up. IVUS analyses were performed in an independent corelab blinded to the type of DES used.

Results:
A total of 40 patients were enrolled in the trial and 35 had IVUS performed. Procedure success was achieved in all cases. Baseline clinical characteristics as well as reference vessel diameter and lesion length did not significantly differ between the 2 cohorts. At 9 month, QCA measured in stent late loss was also comparable (0.15±0.18mm for BES vs. 0.20±0.47mm for EES, p=0.7). By IVUS, vessel volume (349±158mm3 for BES vs. 326±127mm3 for EES, p=0.6) and stent volume (178±78 for BESmm3 vs. 154±54mm3 for EES, p=0.4) did not significantly differ between the groups as well as neointimal tissue volume (3.6±2.8mm3 for BES vs 4.3±6.1mm3 for EES, p=0.4) and the % of stent obstruction (2.3±2.1% for BES vs. 2.5±2.8% for EES. OF note, the pattern of neointimal distribution was very similar between the two DES (figure).

Conclusions:
In this head-to-head to comparison, both second-generation DES were shown to be effective and safety in the treatment of coronary artery disease with no significant differences in terms of IVUS findings.
Abstract 11964: Circulating Levels of 2-Aminobutyric Acid Reflect Myocardial Redox State in Patients With Atrial Septal Defects
Authors: Irino Yasuhiro , Toh Ryuji , Mori Takeshige , Nagao Manabu , Honjo Tomoyuki , Satomi-Kobayashi Seimi , Shinke Toshiro , Ishida Tatsuro , Miyata Okiko , Hirata Ken-ichi
Published: July 2021

Heart failure (HF) is a major cause of morbidity and mortality worldwide. However, conventional biomarkers are insufficient to detect early stage of HF and identification of more sensitive markers is an urgent task. We conducted the comprehensive quantification of water-soluble metabolites in blood of atrial septal defect (ASD) patients using a gas chromatograph-mass spectrometry. We found the mean level of 2-Aminobutyric acid (2-AB) in ASD patients was significantly higher than that in healthy volunteers, and 1 month after transcatherter closure of ASD using the Amplatzer septal occluder, serum 2-AB levels in patients decreased to almost the same levels as healthy volunteers (healthy-volunteers: 15.74±1.75 μM, ASD (pre-closure): 22.38±1.99 μM, ASD (post-closure):15.50±1.50 μM, P=0.017). In contrast, serum levels of brain natriuretic peptide (BNP), frequently used as the biomarker in heart disease, did not show such relationships. In addition, 2-AB concentration had a significant correlation with tricuspid regurgitation peak gradient (TRPG) (R2=0.517, P=0.029). Because TRPG reflects right ventricular loading conditions, we examined whether mechanical stress to cardiomyocyte induces 2-AB. Mechanical stretch induced an accumulation of 2-AB, suggesting that circulating 2-AB increased in ASD patients were derived from their hearts.

Next, we tried to identify the 2-AB synthesis pathway. 2-AB is known as a key molecule in the biosynthesis of ophthalmic acid that is an analogue of glutathione (GSH) and indicates GSH depletion under oxidative stress. We revealed that 2-AB was produced as the byproduct of GSH synthesis reactions. We also demonstrated that oxidative stress lead to 2-AB production by H2O2 stimulation in cardiomyocyte. Mechanical stress-induced 2-AB accumulation might be mediated by oxidative stress.

In summary, circulating 2-AB levels changed before and after closure of ASD and indicated heart condition more efficiently than BNP. We also demonstrated that 2-AB reflects myocardial redox state. Thus, 2-AB monitoring may facilitate the early diagnosis strategy for HF.
Abstract 11968: Nocturnal Blood Pressure in Young Adults and Cognitive Function in Midlife: The CARDIA Study
Authors: Yano Yuichiro , Ning Hongyan , Muntner Paul , Reis Jared , Calhoun David , Viera Anthony , Levine Deborah , David Jacobs , Shimbo Daichi , Liu Kiang , Greenland Philip , Lloyd-Jones Donald
Published: July 2021

Nocturnal blood pressure (BP) is associated with risk for cardiovascular events. However, the effect of nocturnal BP in young adults on cognitive function in midlife remains unclear.

We used data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, including 224 participants (mean age 30 years, 45% men, 63% African Americans) followed for 20 years (6 visits). At the 20-year follow-up, the Stroop test (higher score indicates worse executive function), Digit Symbol Substitution Test (DSST, lower score indicates worse psychomotor speed), and Rey Auditory Verbal Learning Test (RAVLT, lower score indicates worse verbal memory) were assessed.

Baseline mean office, daytime, and nocturnal BP were 109/73mmHg, 120/74mmHg, and 107/59mmHg, respectively. Nocturnal BP dipping, calculated as (nocturnal systolic BP [SBP]-daytime SBP)х100/daytime SBP, was divided into quartiles (Q1;-39.3% to -16.9%, Q2;-16.8% to -13.2%, Q3 [reference];-13.1% to -7.8%, and Q4;-7.7% to +56.4%).

Cognitive function score according to the quartile of nocturnal SBP dipping is shown in Figure. In linear regression models, the least nocturnal SBP dipping (Q4 vs. reference) and higher nocturnal diastolic BP (DBP) level were associated with worse Stroop scores, with adjustments for demographic and clinical characteristics, and cumulative exposure of BP during follow-up (β [standard error]: 0.37[0.18] and 0.19[0.07] respectively; all P<0.05). Neither DSST nor RALVT was associated with either nocturnal BP dipping or nocturnal SBP/DBP levels.

Among healthy young adults, less nocturnal SBP dipping and higher nocturnal DBP levels were associated with lower executive function in midlife, independent of long-term office BP levels. Nocturnal BP measures in young adults could be potentially useful to identify those who may be at risk for developing lower cognitive function in midlife.
Abstract 11981: ECG-Derived Vectorcardiography Identifies Disease and Genotype Status in Hypertrophic Cardiomyopathy
Authors: Cortez Daniel , Bos Johan Martijn , Schlegel Todd T , Ackerman Michael
Published: July 2021

Introduction:
Vectorcardiography (VCG) has clinical prognostic and diagnostic value in various disease states. Hypertrophic cardiomyopathy is a disease state which can lead to sudden cardiac death, where genotype status has been shown to predict worse outcomes..

Hypothesis:
We set out to determine the utility of vectorcardiographic parameters in one of the largest genotyped cohorts of patients with hypertrophic cardiomyopathy (HCM) and to determine whether they can identify genotype status.

Methods:
Between 1997 and 2007, research based genetic testing was performed on 1053 patients with HCM (60% males; mean age at diagnosis 44.4 years); yield of genetic testing was 34%. Of these, 967 had ECG’s appropriate for computerized derivation of VCG parameters including the spatial mean and peaks QRS-T angles, spatial ventricular gradient and the spatial QRS, QT, and Tpeak-Tend (TpTe) intervals. Results were compared against those from a group of healthy control subjects (N=418).Subsequent genotype positive versus negative comparisons were performed using paired student T-tests or Mann-Whitney U-tests as appropriate.

Results:
Spatial peaks and spatial mean QRS-T angles were significantly higher in HCM patients (129.3±26.4 and 121.8±38.6 degrees, respectively) than in controls (25.0±15.0 and 43.0±-21.0 degrees, respectively, p<0.001). Sensitivities for HCM, based on cutoff values of 2 standard deviations above the mean values reported for control patients, were 84.5% and 81.5% for spatial peaks and spatial mean QRS-T angles, respectively. VCG predicted genotype status as genotype positive patients had significantly higher spatial peaks (132.4±-29.2 vs. 127.9±24.8 degrees; p = 0.02) and spatial mean (129.7±33.8 vs. 117.6±40.3 degrees; p<0.001) QRS-T angles, spatial TpTe (118.0±40.8 vs. 107.9±48.7 ms; p<0.001) as well as significantly lower spatial ventricular gradients (0.059±0.044 vs. 0.067±0.04; p<0.001).

Conclusions:
Patients with HCM can be distinguished from normal subjects through the study of the spatial QRS-T angle. Whether incorporation of spatial peaks QRS-T angle to pre-existing genetic test prediction tools will further improve prediction of genotype status remains to be determined.
Abstract 12019: Differential Effect of Ticagrelor versus Clopidogrel on Coronary Microvascular Function in Patients With Coronary Aertery Disease
Authors: Choi Woong Gil
Published: July 2021

Introduction:
Differential Effect of Ticagrelor Versus Clopidogrel on Coronary Microvascular Function in Patients with Coronary Aertery Disease

Background and Objectives:
Ticagrelor is a new antiplatelet drug directly blocking P2Y12-adenosine diphosphate (ADP) receptors, which show a better clinical profile compared to clopidogrel in patients with acute coronary syndrome. Ticagrelor inhibits adenosine reuptake and increases coronary blood flow by a direct dilation of the microcirculation. We aimed to evaluate the effect of ticagrelor on coronary mircrovascular function in patient with coronary artery disease (CAD) in comparison with clopidogrel.

Subjects and Methods:
Twenty four patient with CAD were randomized to receive a single dose of ticagrelor (180 mg) or clopidogrel (300mg or on treatment state). Coronary microvascular function was invasively measured by using the index of microvascular resistance (IMR) and coronary flow reserve (CFR). The IMR was calculated from the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit time (hTmn). The CFR was calculated dividing the hTmn by baseline mean transit time.

Results:
There were no significant differences in baseline clinical and angiographic characteristics.CFR was not significantly different in both groups. (median: 4.00 [interquartile range(IQR) 2.30 to 4.92] vs 5.10 [IQR: 3.72 to 7.90],
p
= 0.24) However, IMR was significantly lower in ticagrelor than clopidogrel treated patients at 140 μg/kg per minute adenosine infusion rate. (median: 10.74 [interquartile range (IQR) 8.02 to 12.31] vs 15.56 [IQR: 10.77 to 29.74],
p
=0.05).

Conclusions:
In patients with CAD, ticagrelor might improves coronary microvascular functionel. These results suggest that ticagrelor could contribute to better clinical outcomes in CAD patients.
Abstract 12022: Long-Term Clinical Outcomes of Everolimus-Eluting Stents versus Sirolimus-Eluting Stents: Systematic Review and a Meta-Analysis of 14 Randomized Control Trials, Focused on Stent Thrombosis
Authors: TOYOTA TOSHIAKI , Shiomi Hiroki , Morimoto Takeshi , Kimura Takeshi
Published: July 2021

Background:
We sought to compare the long-term clinical outcomes between everolimus-eluting stent (EES) and sirolimus-eluting stents (SES) with a meta-analysis method. The long-term clinical outcomes, especially stent thrombosis (ST), after EES versus SES implantation has not been clearly defined among trials directly comparing the 2 types of stents.

Methods:
We searched PubMed, Cochrane database, and ClinicalTrials.gov. for trials comparing outcomes between EES (Xience V/Promus) and SES (Cypher select/Cypher select plus) in patients with native coronary artery disease using randomized controlled trial (RCT) design. We selected the article reporting the longest follow-up outcomes from each RCT. The outcome measure was all-cause death, myocardial infarction (MI), definite ST, and target-lesion revascularization (TLR). ST was further classified as those occurring early (<=30 days), late (30-365 days), or very late (<365 days).

Results:
We identified 14 RCT comparing EES and SES including 2 trials reporting the longest follow-up outcomes as a pooled analysis. We analyzed 13,434 randomly assigned patients with the weighted follow-up period of 2.1 years (Follow-up <=1-year: 7 trials, and 3191 patients; >1-year: 7 trials, and 10243 patients). EES as compared to SES was associated with significantly lower risks for overall ST, and early ST (pooled odds ratio (OR) 0.49, 95% confidence interval (CI) 0.30-0.81, P=0.01, and OR 0.42, 95% CI 0.18-0.99, P=0.046, respectively), while there was no significant difference in the risk for late ST and very late ST (OR 0.49, 95% CI 0.17-1.43, P=0.19, and OR 0.66, 95% CI 0.23-1.85, P=0.43, respectively). EES as compared to SES was also associated with significantly lower risks for TLR (OR 0.84, 95% CI 0.71-0.99, P=0.04). There was no significant difference in the risk for all-cause death, and MI between EES and SES. (OR 0.91, 95% CI 0.78-1.07, P=0.11, and OR 0.92, 95% CI 0.75-1.13, P=0.44, respectively).

Conclusions:
In the current meta-analysis of 14 RCT directly comparing EES with SES, implantation of EES as compared to SES implantation was associated with significantly lower risk for definite ST and TLR.
Abstract 12030: Trends in Blood Pressure Among Adults With Hypertension: United States, 2003-2012
Authors: Yoon Sung Sug (Sarah) , Gu Qiuping , Nwankwo Tatiana , Wright Jacqueline , Hong Yuling , Burt Vicki
Published: July 2021

Objectives:
To describe trends in the awareness, treatment and control of hypertension; mean blood pressure; and the classification of blood pressure among U.S. adults 2003-2012.

Methods and Results:
Using data from the National Health and Nutrition Examination Survey 2003-2012, a total of 9,255 adult participants aged 18 and older were identified as having hypertension, defined as measured blood pressure ≥ 140/90 mm Hg or taking prescription medication for hypertension. Awareness and treatment among hypertensive adults were ascertained via an interviewer administered questionnaire. Controlled hypertension among hypertensive adults was defined as systolic blood pressure <140 mm Hg and diastolic blood pressure < 90 mm Hg. Blood pressure was categorized as optimal blood pressure, prehypertension, stage I hypertension and stage II hypertension. Between 2003 and 2012, the percent of adults with controlled hypertension increased (
p
-trend <0.01). Hypertensive adults with optimal blood pressure and with prehypertension increased from 13% to 19% and 27% to 33%, respectively (
p
- trend < 0.01). Among hypertensive adults who were taking anti-hypertensive medication, uncontrolled hypertension decreased from 38% to 30% (
p
-trend <0.01). Similarly, a decrease in mean systolic blood pressure was observed (
p
-trend <0.01); however, mean diastolic blood pressure remained unchanged.

Conclusion:
The trend in the control of blood pressure has improved among hypertensive adults resulting in a higher percent with blood pressure at the optimal or prehypertension level and a lower percent in stage I and stage II hypertension. Overall, mean systolic blood pressure decreased as did the prevalence of uncontrolled hypertension among the treated hypertensive population.
Abstract 12075: Whole-Genome Sequencing at 10-Days of Life in Perinatal Long-QT Syndrome Yields New Insights Into Disease Pathogenesis
Authors: Priest James R , Gawad Charles , Kahlig Kris , Ceresnak Scott , Malloy-Walton Lindsey , Dunn Kyla , Grove Megan P , Perez Marco , Maeda Katsuhide , Dubin Anne , Belardinelli Luiz , Chen Rich , Quertermous Tom , Quake Stephen , Ashley Euan A
Published: July 2021

Introduction:
Perinatal LQTS represents a severe form of long-QT syndrome with poor outcomes and early genotype-specific treatment is limited by the 2 month turnaround time of standard panel genetic testing.

Hypothesis:
We aimed to provide a molecular diagnosis within a clinically actionable timeframe.

Methods:
We performed rapid CLIA-certified whole genome sequencing on two infants with perinatal long-QT syndrome delivering a molecular diagnosis at 10-days of life. Whole cell patch clamping and single cell genotyping were also performed.

Results:
In Case #1 we discovered a previously characterized variant in KCNH2 which was paternally inherited, however whole genome sequencing provided an unbiased assessment of the entire catalog of human genes revealing a second maternally inherited modifier variant in RNF207.

In Case #2 we discovered a novel mutation leucine replacing valine (V1762L) at residue 1762 in the SNC5A sodium channel. Whole-cell patch clamping experiments show the V1762L mutation causes a profound defect in late sodium current ~4.5 fold greater than the wild-type channel. A single cell analysis demonstrated that the mutation was present in the genome of only 3 of 36 individually isolated and genotyped patient cells, suggesting mosaicism. Conspicuously, standard panel genetic testing was negative.

Conclusions:
We report here the earliest molecular diagnoses of LQTS, and demonstrate that rapid whole genome sequencing may be fruitfully applied to perinatal LQTS. In case #1 we hypothesize that a polygenic inheritance may explain the early and severe perinatal presentation, and have identified a putative modifier gene for LQTS in RNF207. The observation of mosaicism in case #2 suggests that in studies of inherited disease, mosaicism represents a common mechanism by which causal variation may be missed.
Abstract 12105: Targeted Delivery of Therapeutic Agents After Myocardial Infarction
Authors: Dasa Siva Sai Krishna , Seamen Marc E , French Brent A , Kelly Kimberly A
Published: July 2021

Introduction:
Current therapies for heart failure (HF) after myocardial infarction (MI) only slow the progression of LV remodeling and have little capacity to regenerate cardiac muscle lost to MI. To expedite targeted delivery of regenerative therapies post-MI, we hypothesized that suitable targets could be identified by biopanning the heart with a phage display library in a mouse model of MI.

Methods:
A phage display library was biopanned in vivo to identify peptides specific for the infarct/border zone 4 days post-MI. Fluorescence molecular tomography (FMT) followed by tissue immunofluorescence was performed to interrogate the specificity of phage groups and individual clones with targeted phage at VT680 and neg control phage at VT750. The VT680 fluorophore on the targeted phage clones was then used to identify the cellular targets of those clones by counter-staining with antibodies against cell types of interest.

Results:
We identified phage clones specific for endothelium, cardiomyocytes, inflammatory fibroblasts and c-Kit+ cells present in the border zone post-MI. Liposomes conjugated with different cell type specific peptides had different accumulation rates in the post-infarct heart as visualized by FMT imaging (Fig. 1a). Immunofluorescence analysis demonstrated cell-type specific association of the targeted liposomes with cells expressing c-Kit, CD31 and Hrnr (Figs. 1b&c). We have also been successful in remote loading of anti-apoptotic and immune suppresive drugs into these liposomes and are currently studying their effect in mice after MI.

Conclusions:
Peptides identified by this screen enable the targeting of different cell types present in the border zone with different drugs. Identifying the molecular binding partners for these peptides may yield insight into the various events/pathways that evolve after a myocardial infarction.
Abstract 12145: Cardiac Magnetic Resonance Late Gadolinium Enhancement is Associated With Ventricular Elastance That May Predict Latent Ventricular Dysfunction After Fontan Procedure
Authors: Okuyama Michihiro , Ishigami Shuta , Ousaka Daiki , Kobayashi Junko , Arai Sadahiko , Kasahara Shingo , Sano Shunji , Oh Hidemasa
Published: July 2021

Backgrounds:
Systemic right ventricular circulation after Fontan procedures is known to have late hemodynamic complications. Although a number of studies have investigated the factors that may impact on survival, postoperative outcomes after palliations remain to be elucidated.

Objective:
The purpose of this study is to investigate the prognostic value of myocardial fibrosis identified by cardiac magnetic resonance imaging (cMRI) in patients with single ventricular physiology.

Methods:
Consecutive 23 patients undergoing Fontan procedures were prospectively scheduled to have cMRI study with late gadolinium enhancement (LGE) imaging and ventricle circumferential strain measurement before and 4 months after Fontan operation.

Results:
Of 23 patients (mean age 3.3±0.9 years), 7 were positive for LGE (LGE+) and median percent LGE was 3.0% (interquartile range 3.0% to 7.5%). Pre-Fontan examinations revealed that patients with LGE+ showed an increase in end-diastolic volume index (139.7±26.8 ml/BSA vs. 113.3±20.9 ml/BSA; P=0.02) and end-systolic volume index (ESVI: 99.9±32.2 ml/BSA vs. 70.8±20.0 ml/BSA; P=0.01) compared with those without LGE (LGE-). In contrast to LGE- group, LGE+ patients showed lower global circumferential strain (4.1±2.3% vs. 7.9±2.7%, P=0.006), decreased ejection fraction (EF: 29±9.1% vs. 38±8.7%; P=0.04), and reduced end-systolic elastance (1.1±0.3 mm Hg/ml/m2 vs. 1.7±0.5 mm Hg/ml/m2). In addition, LGE+ group had higher levels of BNP (91.0±72.4 pg/ml vs. 30.9±44.0 pg/ml, P=0.02) and New York University Pediatric Heart Failure Index (10.9±3.3 vs. 7.8±1.1, P=0.02) than LGE- group. This was validated by positive correlations between the area of LGE versus ESVI (r=0.85, P=0.01) and BNP levels (r=0.82, P=0.02), respectively. At 4 months after Fontan procedure, LGE- group showed higher EF (37.5±8.6% vs. 24.0±8.9%, P=0.02) compared with those in LGE+ patients, and increased global circumferential strain (6.5±2.0% to 7.4±2.7%, P=0.04).

Conclusion:
LGE identified by cMRI before operation may be associated with lower ventricular elastance that resulted in poorer functional recovery after staged palliation. This novel strategy may provide a prognostic value of latent myocardial dysfunction after Fontan procedure.
Abstract 12161: Dipeptidyl Peptidase IV Inhibitor Therapy Modifies Systolic Blood Pressure in High Blood Pressure Diabetic Patients: Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) 2 Trial
Authors: Soejima Hirofumi , Morimoto Takeshi , Okada Sadanori , Sakuma Mio , Nakayama Masafumi , Uemura Shiro , Kanauchi Masao , Doi Naofumi , Jinnouchi Hideaki , Sugiyama Seigo , Waki Masako , Saito Yoshihiko , Ogawa Hisao
Published: July 2021

Introduction:
It has been reported that dipeptidyl peptidase (DPP) IV inhibitor treatment increased glucagon like peptide (GLP)-1 and GLP-1 receptor expression levels, and subsequently endothelial nitric oxide synthase levels in experimental studies. It is possible that DPP IV inhibitors modify blood pressure (BP) through the improvement of endothelial function.

Hypothesis:
The aim of this study was to investigate whether DPP IV inhibitors ameliorated BP in diabetic patients.

Methods:
The JPAD trial, 2002 to 2008, a multicenter, prospective, randomized, open label, blinded, end-point study, was undertaken to examine the efficacy of aspirin therapy. After completion of the trial in 2008, we followed the same subjects until 2013 as JPAD2 trial cohort. BP was measured in 1244 patients in both 2009 and 2013. Among the 1244 patients, 4 patients received DPPIV inhibitors in 2009, 280 patients in 2011, 573 patients in 2013. We examined the change of BP in the 573 patients. Among them, 344 patients had systolic BP≥140 mmHg or diastolic BP≥90 mmHg or both (high BP group).

Results:
The systolic BP from 2009 to 2013 did not significantly change in the 1244 patients (Figure). The diastolic BP significantly decreased in the 1244 patients (Figure). The systolic BP from 2009 to 2013 did not significantly change in the 573 patients receiving DPPIV inhibitors (Figure). The diastolic BP significantly decreased in the 573 patients receiving DPPIV inhibitors (Figure). In the high BP group, the systolic BP from 2009 to 2013 significantly decreased in the 148 patients receiving DPPIV inhibitors (Figure). In the high BP group, the diastolic BP significantly decreased in the 148 patients receiving DPPIV inhibitors (Figure).

Conclusions:
In 4 year-observation of the JPAD2 trial cohort, diastolic BP decreased and systolic BP did not change in diabetic patients. User of DPPIV inhibitors has been dramatically increased, and it significantly modifies systolic BP in high BP diabetic patients.
Abstract 12178: Association of Inter-Arm Blood Pressure Differences (iad) With Future Cardiovascular Events (cv) in the Patients With Coronary Artery Disease (cad)
Authors: Tokitsu Takanori , Yamamoto Eiichiro , Hirata Yoshihiro , Fujisue Koichiro , Sugamura Koichi , Hokimoto, Seiji , Sugiyama Seigo , Ogawa Hisao
Published: July 2021

Background:
Recent studies have shown that IAD could be one of the risks of CV events. However, there is no report regarding IAD in patients with CAD. Hence, we investigated whether presence of IAD relates with the severity of CAD and predicts future CV events in CAD patients.

Methods:
We analyzed 657 stable patients with suspected CAD, we measured blood pressure(BP) of both hands simultaneously by using ankle brachial index (ABI) on admission, We examined the presence of CAD by coronary angiography (>75% stenosis) and calculated gensini score for evaluating the severity of coronary atherosclerosis. We defined higher IAD value is 10mmHg < differences and abnormal value of ABI is <0.9 in either leg.

Result:
Mean IAD values were significantly higher in CAD patients (n=407) compared to non-CAD patients (n=250) (4.3±5.2 mmHg vs. 2.8±2.5 mmHg, P<0.01). In CAD patients, 29 patients (7.1% of CAD patients) had higher IAD, and 63(15.5%) had lower ABI. IAD values of lower ABI group were significantly higher than normal group (6.9±7.8 mmHg vs. 3.8±4.5 mmHg, P<0.01). By multivariate logistic regression analysis, BMI, female, ABI, LDL, Gensini score, were independently associated with the presence of IAD. Gensini score was significantly elevated in higher IAD group than lower IAD group(60.9±32.4 mmHg vs.41.2±28.5 mmHg, P<0.01), and after patients were divided into 4 groups according to a combination of ABI value and IAD value, gensini score was highest (80.5±33.9)in lower ABI and higher IAD group among 4 groups (p<0.01) Kaplan-Meier analysis demonstrated that higher IAD group had a significantly higher probability of CV events than lower IAD group (log rank test, P<0.01), furthermore, lower ABI and higher IAD group had a highest probability of CV events among 4 groups (log-rank test, p<0.001). Cox hazard analysis revealed that higher IAD was independent predictor of CV events [hazard ratio: 2.86, 95% confidence interval (1.51-5.40), P=0.001] in the patients with CAD.

Conclusion:
IAD value was significantly higher in CAD patients and was correlated with severity of CAD. More than 10mmHg IAD independently associated with the occurrence of CV events. The measurement of BP of both hands simultaneously is useful for risk stratification of CAD patients.
Abstract 12182: Brain-Derived Neurotrophic Factor Maintains Exercise Capacity and Mitochondrial Function in the Skeletal Muscle Through Ampk-Pgc1α Signaling
Authors: Takada Shingo , Kinugawa Shintaro , Matsushima Shouji , Mizushima Wataru , Fukushima Arata , Furihata Takaaki , Kadoguchi Tomoyasu , Yokota Takashi , Suga Tadashi , Okita Koichi , Tsutsui Hiroyuki
Published: July 2021

Background:
Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, exists not only in the brain but also in the skeletal muscle. We have demonstrated that its serum levels are decreased in heart failure (HF) and are correlated with exercise capacity, indicating that it may regulate skeletal muscle function. We thus determined its physiological role in exercise capacity and mitochondrial function of skeletal muscle by using the gene deletion both in vivo and in vitro.

Methods and Results:
Experiments were performed using male wild type (WT, n=8) and BDNF knockout (KO+/-) mice (n=8, 15 to 17 weeks). Body and organ weights, cardiac function assessed by echocardiography, and metabolic parameters including blood sugar, insulin, and lipid profiles did not differ between groups. Plasma BDNF level (15±1 vs. 22±1 pg/mL) as well as BDNF protein levels and phosphorylation of TrkB (tyrosine kinase receptor), BDNF binding receptor were significantly decreased in the skeletal muscle from BDNF KO+/- compared to WT mice (all p<0.05). Citrate synthase (CS) (17±2 vs. 44±2 mM/min/μg protein, p<0.05) and mitochondrial complex I and III activities were significantly decreased in BDNF KO+/-. Phosphorylation of AMPK and peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α) levels were significantly lower in BDNF KO+/- by 20% and 25%, respectively (p<0.05). The work (distance x body weight; 26±1 vs. 16±1 J, p<0.05) and peak oxygen uptake (VO2; 162±4 vs. 136±3 mL/kg/min, p<0.05) evaluated by treadmill test were significantly decreased in BDNF KO+/-. Treatment of BDNF KO+/- mice with a specific activator of AMPK (AICAR, 500 mg/kg/day, i.p. for 5 weeks) significantly improved the reduced work (22±1 J), peak VO2 (159±2 mL/kg/min), and CS activity (34±2 mM/min/μg protein) in the skeletal muscle. To further determine the direct role of BDNF in the regulation of mitochondrial function in vitro, knockdown of BDNF in C2C12 myotube by using siRNA decreased the phosphorylation of AMPK and PGC1α protein level of by 70% and 42%, respectively.

Conclusions:
BDNF plays an essential role in the maintenance of exercise capacity and the regulation of mitochondrial function in the skeletal muscle thought the AMPK- PGC1α signaling.
Abstract 12188: Intensive Glycemic Control in Patients With Acute Coronary Syndrome: Evidence From a Meta-Analysis
Authors: Sardar Partha , Nairooz Ramez , Chatterjee Saurav , Udell Jacob A , Kumbhani Dharam J , Kosiborod Mikhail N , Ryan John , Mukherjee Debabrata , McGuire Darren K
Published: July 2021

Introduction:
Hyperglycemia is associated with unfavorable prognosis in patients with acute coronary syndrome (ACS). Studies with intensive glycemic control in ACS patients have provided inconsistent results. A meta-analysis was performed to evaluate the effectiveness and safety of intensive glycemic control in patients with ACS.

Methods:
Search of PubMed, Cochrane CENTRAL, EMBASE, EBSCO, Web of Science and CINAHL databases from their inception through April 2014, identifying randomized controlled trials (RCTs) comparing the effects of intensive versus standard glucose management in patients with ACS. We calculated summary random-effect odds ratios (OR) and 95% confidence intervals (CI).

Results:
Results from 10 RCTs comprising 2,621 patients were analyzed. All-cause mortality between intensive versus standard glucose management groups did not differ significantly (OR 1.00, 95% CI 0.75-1.34). Similarly, no significant differences were observed between the comparator groups for the odds of cardiac mortality (OR 0.87, 95% CI, 0.67 to 1.12), recurrent myocardial infarction (OR 1.07, 95% CI, 0.76 to 1.52), or stroke (OR 1.20, 95% CI, 0.60 to 2.40). The risk of hypoglycemia (OR 5.95, 95% CI, 2.73 to 12.97; p<0.001) was significantly higher with intensive compared with standard glucose management.

Conclusions:
Intensive glucose control compared with standard care in ACS patients did not reduce mortality or morbidity, but significantly increased the risk of hypoglycemia. These data from prior clinical trials should be interpreted in the context of their significant methodological limitations.