bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11802: Clinical Implementation Of CYP2C19-genotype Guided Antiplatelet Therapy Reduces Cardiovascular Events After PCI
Authors: Cavallari Larisa H , Magvanjav Oyunbileg , Anderson R.David , Gong Yan , Owusu-Obeng Aniwaa , Kong Ben , Vo Teresa , Ashton Jennifer N , Staley Benjamin J , Elsey Amanda R , Allan Robert W , Starostik Petr , Cooper-DeHoff Rhonda M , Weitzel Kristin W , Clare-Salzler Michael J , Nelson David R , Johnson Julie A
Published: July 2021

Introduction:
Clopidogrel is bioactivated by CYP2C19, and the CYP2C19 loss-of-function (LOF) genotype leads to reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). We examined whether clinical implementation of CYP2C19 genotype-guided antiplatelet therapy (APT) reduces the risk for cardiovascular events after PCI.

Methods:
CYP2C19 genotyping post-PCI was implemented at UF Health Shands Hospital in July 2012, with alternative APT recommended for LOF allele carriers. Major adverse cardiovascular events (MACE, comprised of cardiovascular death, MI, stroke and stent thrombosis) over the 6 months after PCI were determined via medical record review. MACE was compared between LOF allele carriers switched to alternative APT (LOF-alternative) and both LOF allele carriers who remained on clopidogrel (LOF-clopidogrel) and non-LOF carriers (non-LOF) using Kaplan-Meier method with additional multivariable Cox regression analysis and propensity score adjustment in LOF groups.

Results:
Of 412 patients (80% with ACS) who underwent PCI and genotyping, 126 (31%) had a LOF allele and 68 (54%) of these received alternative APT (prasugrel n=57, ticagrelor n=8, triple dose clopidogrel n=3). On Kaplan-Meier analysis (Figure), there was a lower incidence of MACE in LOF-alternative vs. LOF-clopidogrel groups and no significant difference between the LOF-alternative and non-LOF groups. On multivariable Cox regression analysis with propensity score adjustment, there was reduced risk of MACE in LOF-alternative vs. LOF-clopidogrel patients (HR 0.09, 95% CI 0.01-0.84, p=0.035). In the LOF-clopidogrel group, the majority of events (83%) occurred within 30 days; all were in patients who presented with an ACS.

Conclusion:
Changing from clopidogrel to alternative APT after PCI in patients with the CYP2C19 LOF genotype reduces the risk for MACE. These data support CYP2C19 genotyping in patients undergoing PCI, especially in those with ACS.
Abstract 11809: Sodium Intake is Correlated to Total Calorie Intake and Potassium
Authors: Juneyoung Yoon , Seo Kyoung-Woo , Park Jin-Sun , Yang Hyoung-Mo , Lim Hong-Seok , Choi Byoung-Joo , Choi So-Yeon , Yoon Myeong-Ho , Lee Eun-Hyun , Lee Juyong , Hwang Gyo-Seung , Shin Joon-Han , Tahk Seoung-Jea
Published: July 2021

Background:
Selecting lower-sodium diets are not successful to reduce sodium intake in general population. If systemic approach is considered lowering sodium intake because of the culinary tendencies, we need to aware of the quantitative relationship between nutrients and sodium in daily usual food of the general population.

Hypothesis:
We assessed the hypotheses that are the positive correlation between total calorie intake, potassium and sodium intake; the cutoff values for sodium recommendation (≤2300 mg per day).

Method:
We studied 55,544 individuals who completed health examination and nutrition survey in 168,157 randomly selected participants that could represent the country from the 1998-2013 Korea National Health and Nutrition Examination Survey (KNHANES). The nutrition survey was 24 hours recall method to estimate the amount of standardized Korean food. We analyzed the quantitative relationship, and estimated the cutoff value of the total calories and potassium at the recommendation of the sodium intake.

Result:
The mean values were total calorie 1922±834 Kcal, sodium 4904±3218 mg, potassium 2935±1563 mg, protein 70±41 g (15% in total calorie), fat 37±31 (18%), and carbohydrate 312±123 (67%) in mean value. The standardized coefficients were potassium 0.309, protein 0.226, fat 0.070, carbohydrate 0.097 in model 1 (R2=0.402); total calorie 0.271 and potassium 0.368 in model 2 (R2=0.384) with cardiovascular risk factors in multiple linear regression analysis (table). The optical cutoff value of the total calorie for sodium 2300mg is 1520 Kcal (74% sensitivity, 74% specificity, 93% positive predictive value, 38% negative predictive value, area under the curve: 0.826, 95% CI: 0.82 to 0.83 ; p < 0.001) and the potassium is 1956 mg (82% sensitivity, 69% specificity, 92% PPV, 44% NPV, AUC: 0.825, 95% CI: 0.82 to 0.83 ; p <0.001).

Conclusion:
In conclusion, the cutoff values for the sodium 2300 mg are the total calorie 1520 Kcal and potassium 1956 mg.
Abstract 11958: Predicting Heart Failure With Preserved and Reduced Ejection Fraction: The International Collaboration on Heart Failure Subtypes
Authors: Ho Jennifer E , Brouwers Frank P , Enserro Danielle , Shah Sanjiv J , Psaty Bruce M , Bartz Traci M , Santhanakrishnan Rajalakshmi , Lee Douglas S , Liu Kiang , Blaha Michael J , Hillege Hans L , van der Harst Pim , van Gilst Wiek H , Kop Willem J , Gansevoort Ron T , Vasan Ramachandran S , Gardin Julius M , Kizer Jorge R , Levy Daniel , Gottdiener John S , de Boer Rudolf A , Larson Martin G
Published: July 2021

Introduction:
Heart failure (HF) is a major growing public health burden, and preventive strategies focused on at-risk individuals are needed. Recent initiatives have advocated for early prevention and aggressive treatment in ACC/AHA stage A/B HF, but prior HF risk prediction models remain poorly defined and validated. Moreover, risk factors for HF-specific subtypes have not yet been examined.

Methods:
We developed and validated separate HF risk prediction models for preserved and reduced ejection fraction (HFPEF, HFREF) in four community-based prospective cohorts (FHS, CHS, PREVEND, MESA). Fine-Gray proportional sub-distribution hazards models were used to account for competing risks (death, other HF subtype, and unclassified HF). FHS, CHS, and PREVEND samples were combined and a 2:1 random split was used for derivation and internal validation. MESA served for external validation.

Results:
There were 982 incident HFPEF and 909 HFREF events among 28,820 participants during follow-up (median 12 years). We created a HFPEF-specific model which included age, sex, systolic blood pressure, body mass index, hypertension treatment, and prior myocardial infarction; it had good discrimination in derivation (c-statistic 0.80, 95% CI 0.78-0.82) and validation samples (internal 0.79, 95% CI 0.77-0.82; external 0.76, 95% CI 0.71-0.80). The HFREF-specific model added smoking, left ventricular hypertrophy (LVH), left bundle branch block (LBBB), and diabetes; it had good discrimination in derivation (c-statistic 0.82, 95% CI 0.80-0.84) and validation samples (internal 0.80, 95% CI 0.78-0.83; external 0.76, 95% CI 0.71-0.80). Age had a greater effect on HFPEF risk, whereas male sex, LVH, LBBB, previous myocardial infarction, and smoking had greater effects on HFREF risk (P for comparison ≤ 0.02 for all).

Conclusions:
We describe and validate risk prediction models that are distinct for HF subtypes, and we demonstrate good discrimination in four community-based cohorts. Some risk factors differed in HFPEF vs HFREF, supporting distinct pathogenesis between HF subtypes. Studies are needed to examine the clinical utility of risk models, with the ultimate goal of targeted preventive strategies.
Abstract 12018: Cardiac Ultrasound Performed During Cardiac Arrest has Potential to Detect Pulmonary Embolism as a Reversible Cause of Cardiac Arrest when Compared to Hypoxia and Ventricular Fibrillation - A Randomized Porcine Study
Authors: Aagaard Rasmus , Caap Philip , Hansson Nicolaj C , Bøtker Morten T , Granfeldt Asger , Løfgren Bo
Published: July 2021

Introduction:
Survival from non-shockable cardiac arrest is unlikely unless a reversible cause is identified and treated. Guidelines state that ultrasound has the potential to identify reversible causes. Currently, ultrasonographic findings from patients with spontaneous circulation are extrapolated to patients in cardiac arrest. While right ventricular (RV) dilation is a finding normally associated with pulmonary embolism (PE), porcine studies have shown that RV dilation is also seen in ventricular fibrillation (VF) and severe hypoxia. No studies have investigated how causes of cardiac arrest affect RV size during resuscitation.

Hypothesis:
The RV diameter is larger during resuscitation of cardiac arrest caused by PE when compared to hypoxia and VF.

Methods:
Pigs were anesthetized and randomized to cardiac arrest induced by VF, hypoxia, or PE. Advanced life support (ALS) was preceded by 7 minutes of untreated cardiac arrest. Cardiac ultrasound images of the RV from a subcostal 5-chamber view were obtained during induction of cardiac arrest and ALS. The RV diameter was measured two centimeters from the aortic valve at end diastole. RV diameter at 3rd rhythm analysis was the primary endpoint. Based on pilot studies a sample size of 8 animals in each group was needed.

Results:
Eight animals were included in each group. RV diameter was not statistically different at baseline (mean (95%CI)) in VF: 19.8 (18.0-21.5) mm, hypoxia: 19.8 (16.6-22.9) mm, and PE: 21.8 (19.2-24.3) mm. During induction of cardiac arrest the RV diameter increased to 29.6 (27.3-31.9) mm in the hypoxia group and 38.0 (33.4-42.6) mm in the PE group (difference to baseline and between groups, both p<0.01). Induction of VF caused an immediate increase in the RV diameter to 25.0 (21.2-28.8) mm (difference to baseline p<0.01). At 3rd rhythm analysis, RV diameter was 32.4 (28.6-36.2) mm in the PE group, which was significantly larger than both the hypoxia group at 23.3 (19.5-27.0) mm and the VF group at 24.9 (22.2-27.5) mm (difference between groups p<0.01).

Conclusions:
Cardiac arrest due to VF, hypoxia, and PE all caused an increase in RV diameter. During resuscitation the RV was larger in PE compared to VF and hypoxia. Cardiac ultrasound thus has the potential to detect PE during resuscitation.
Abstract 12047: Quality of Life in Adults With Congenital Heart Disease Worldwide: A Multilevel Study in 15 Countries
Authors: Apers Silke , Kovacs Adrienne H , Luyckx Koen , Moons Philip ,   APPROACH-IS consortium and the International Society for Adult Congenital Heart Disease
Published: July 2021

Objectives:
Health care should be evaluated not only on the basis of saving lives, but also in terms of improving the quality of life (QOL). However, results regarding QOL in adults with congenital heart disease (CHD) are inconsistent and vary across the world. Methodological differences and limitations hamper the interpretation of these results. Therefore, we aimed (1) to describe QOL in an international sample of adults with CHD using a uniform method; (2) to investigate the association between patient characteristics and variation in QOL; and (3) to explore international variation in QOL and the relationship with country-specific characteristics.

Methods:
For this cross-sectional multilevel study, patients were recruited from adult CHD centers or national registries from 15 countries. QOL was assessed by a linear analog scale (0-100). Patient characteristics included sex, age, marital status, educational level, employment status, CHD complexity and patient-reported New York Heart Association (NYHA) class. Country-specific characteristics included national happiness score and six cultural dimensions. Multilevel generalized linear mixed models were conducted and Empirical Bayes estimates for QOL were calculated to account for the sample size in each country.

Results:
In total, 4,028 adults with CHD were enrolled (median age=32 y; 53% women; 26% mild, 49% moderate, 26% complex CHD). Median QOL for the total sample was 80. Age, marital status, employment status and NYHA class were significantly associated with variation in QOL (p<.001). Australia had the highest QOL estimate (82) and Japan the lowest (72). Four countries had a QOL estimate of ≥80 (i.e., Australia, Switzerland, USA, Malta). After adjusting for patient characteristics, happiness and cultural dimensions were not significantly associated with variation in QOL.

Conclusions:
This is the first international study comprehensively assessing QOL in any subgroup of cardiac patients. We found that QOL in adults with CHD varies across countries and is related to patient characteristics but not to country-specific characteristics. The identification of significant patient characteristics can support the development of interventions targeting the QOL of adults with CHD around the world.
Abstract 12048: Minimally Invasive Access for Aortic Valve Surgery in Octogenarians: Is it Still Justified in the Days of TAVI ?
Authors: Boeken Udo , Rajah Sudharson , Minol Jan Philipp , Akhyari Payam , Lichtenberg Artur
Published: July 2021

Introduction:
Increasing life expectancy in the western world and improvements in surgical techniques and postoperative care have resulted in a significant number of patients aged over 80 undergoing cardiac operations. At times of transapical and transfemoral AVR we aimed to evaluate the feasibility of partial sternotomy for patients over 80 years of age and to compare these results with a historical group of octogenarians who underwent aortic valve surgery via full sternotomy in our department between 1998 and 2006.

Methods:
72 of the 275 patients (26.2 %) who underwent aortic valve replacement (AVR) after partial sternotomy between 8/2009 and 05/2013 were octogenarians. Mean age was 83.1 ± 3.9 years (group ps).

We compared this group with 165 patients (mean age 81.6 ± 3.1 years) who underwent AVR via full sternotomy between 1998 and 2006 (group fs).

Results:
ICU- and hospital stay were significantly reduced in patients with partial sternotomy (ps: 28 ± 9 hours, 12.8 ± 4.7 days vs. fs: 59 ± 15 h, 14.7 ± 3.5 d, p<0.05). We found a higher in-hospital mortality in group fs, but without significance (4.2 vs. 2.8 % in ps). Duration of operation, of extracorporeal circulation, and of aortic cross-clamping was tendentially prolonged in patients with partial sternotomy (p>0.05). Necessity for re-operation due to bleeding was comparable in both groups (ps: 2.8 % vs. fs: 3.0 %).

The incidence of postoperative complications did not differ significantly between both groups: neurological complications (ps: 2.8 vs. fs: 3.0 %), sternal wound infections (2.8 % vs. 2.4 %) and postoperative LCOS (4.2 % vs. 5.5 %).

Conclusions:
We could prove the feasibility of ministernotomy for aortic valve surgery for patients over 80 years of age. Despite a tendentially prolonged duration of surgery compared to procedures via full sternotomy, we found a comparable morbidity and a reduced mortality after partial sternotomy. From an economic perspective, the reduction of intensive care unit- and hospital stay after minimally invasive access was the most interesting finding. Moreover, our results after minimally invasive AVR have to be considered carefully when selecting patients for a conventional or for a TAVI procedure.
Abstract 12098: S-nitrosoglutathione Reductase Deficiency Prevents Neurological Injury After Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Hayashida Kei , Hirai Shuichi , Ikeda Kohei , Kai Shinihci , Marutani Eizo , Ichinose Fumito
Published: July 2021

Introduction:
Nitric oxide (NO) exerts many of its effects via protein S-nitrosylation (SNO). Protein SNO levels are critically controlled by the activity of denitrosylase S-nitrosoglutathione reductase (GSNOR). The objective of this study was to examine the impact of enhanced protein SNO induced by GSNOR deficiency on the outcomes of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in mice.

Methods and Results:
Wild-type (WT) mice and mice deficient for GSNOR (GSNOR-/-) were subjected to CA for 8 min whereupon CPR was performed with chest compression and mechanical ventilation. There were no differences in characteristics before CA and during CPR except for lower mean blood pressure in GSNOR-/- mice at baseline. WT mice that were subjected to CA/CPR exhibited a poor 6-day survival rate (16.7%), depressed neurological function, and increased hydrogen peroxide production in the brain. In contrast, GSNOR-/- mice exhibited better neurological recovery, attenuated hydrogen peroxide production, and markedly improved 6-day survival rate (66.7%, P<0.05 vs WT). The protective effects of GSNOR deficiency were associated with markedly reduced mitochondria complex I activity in the brain at 5 min after CPR compared with sham-operated GSNOR-/- mice as evidenced by the ATP turnover rate in isolated cerebral mitochondria. Administration of a mitochondria-targeted S-nitrosothiol MitoSNO to WT mice 1min before CPR similarly depressed cerebral mitochondrial complex I activity and improved neurological outcomes, and survival rate. These results suggest that SNO-based inhibition of mitochondrial activity prevents ischemic neurological injury after CA and CPR.

Conclusions:
GSNOR-deficiency improves outcomes after CA and CPR in mice at least in part by modulating mitochondrial complex I activity and reducing reactive oxygen species generation during early reperfusion phase. Pharmacological augmentation of protein SNO may limit long term neurological impairment and death after CA/CPR.
Abstract 12112: Clinical Outcomes of Percutaneous Epicardial Ablation
Authors: Killu Ammar M , Al-Hijji Mohammed , Sugrue Alan M , McLeod Christopher J , Hodge David O , Munger Thomas M , Mulpuru Siva K , Packer Douglas L , Asirvatham Samuel J , Friedman Paul A
Published: July 2021

Introduction:
Percutaneous epicardial access (EAc) is increasingly performed as part of VT/PVC ablation, especially in those that have failed prior ablation. We aimed to delineate the outcomes of EAc.

Methods:
We retrospectively analyzed individuals undergoing EAc for arrhythmia ablation between June 2004 and July 2014. Acute procedural success was defined as elimination/non-inducibility of the clinical arrhythmia after ablation; clinical success was defined as absence of symptoms/arrhythmia.

Results:
Of 175 patients, 126 (72%) were male with a mean age of 52.8±15.7 years. Eighty-three (47.4%) patients had NICM, 25 (14.3%) had ICM and 34 (19.4%) had normal hearts. Baseline EF was 44±16%. Patients had failed an average of 1.7±1.2 antiarrhythmic drugs; 139 patients (79%) had failed prior endocardial (endo) ablation (average 1.3±1.1). Six (3.4%) had prior EAc and 18 (10.3%) prior cardiac surgery. The indication for ablation was VT or PVC in 113 (64.6%) and 60 (34.3%) patients, respectively. Successful access was obtained in 168 (98%) patients. Anterior access, inferior access, or both, was utilized in 89 (52.7%), 77 (45.6%) and 2 (1.2%) patients, respectively. There were an average of 2.7±2.2 VT/PVCs identified, and 1.6±1.1 ablated. Endo, epicardial (epi) or combined ablation was performed in 58 (33.1%), 14 (8%), and 100 (57.1%) patients, respectively; 3 did not undergo ablation. Procedural success was obtained in 158 of 173 (91.3%) patients for whom data was available. At 12 months, clinical success was maintained in 62% with no difference between endo, epi or combined ablation (figure). Cardiac tamponade requiring repeat EAc occurred in 12 (6.9%) patients. There were no procedural related deaths.

Conclusion:
Epicardial access is feasible in almost all patients with no prior cardiac surgery, and permits acute procedural success in 91.3% of patients, most of whom had failed previous ablation. Furthermore, complications are relatively infrequent in this complex cohort.
Abstract 12151: Contrast-Enhanced Carotid Plaque for Detection of Myocardial Damage Risks After PCI in ST-segment Elevation Myocardial Infarction
Authors: Deyama Juntaro , Nakamura Takamitsu , Nakamura Jun , Horikoshi Takehusa , Futamata Mika , Matsuoka Satoshi , Shimizu Takuya , Uematsu Manabu , Kobayashi Tsuyoshi , Fujioka Daisuke , Saito Yukio , Nakamura Kazuto , Kawabata Ken-ichi , Obata Jun-ei , Kugiyama Kiyotaka
Published: July 2021

Background:
The presence of coronary vulnerable plaque has been shown to increase the risk of myocardial damage after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients. It is possible that coronary plaque vulnerability may be assessed by evaluating plaque characteristics in other vessels such as the carotid arteries. Contrast-enhanced ultrasound (CEUS) of carotid plaque has been shown to detect the plaque neovascularization of carotid plaques, which is a feature of vulnerable plaque. Thus, in this study we examined whether CEUS of the carotid artery may provide information for myocardial damage risks after PCI in STEMI patients.

Methods and Results:
CEUS of the carotid plaques using perfluorobutane microbubbles as an ultrasound contrast agent were performed in consecutive 95 STEMI patients treated with emergent PCI. Intraplaque neovascularization was identified on the basis of microbubbles within the carotid plaque and graded as: G0, not visible; G1, moderate; or G2, extensive microbubbles. Obtained coronary flow and myocardial damage after PCI were estimated by corrected TIMI frame count (cTFC), Myocardial Blush Grade (MBG), peak CK-MB and Troponin T. The presence of G2 in the carotid arteries was associated with higher levels of cTFC (G0, 34±19 frames; G1, 41±21 frames; 43±24 frames,ρ=0.005) , lower levels of MBG (G0, 2.3±0.7; G1, 1.7±0.9; G2, 1.5±0.9,ρ=0.013), and higher levels of carotid IMT, fast blood glucose, hemoglobin A1c, hsCRP, and troponin T (ρ=0.049, 0.042, 0.046, 0.048, 0.01, and 0.02).

Conclusion:
The presence of carotid plaque neovascularization was related with myocardial damage after PCI in STEMI patients. Measurement of CEUS of Carotid Plaque is useful for risk stratification of STEMI patients underwent emergent PCI.
Abstract 12156: Greater Regression of Coronary Atherosclerosis With the Pre-Beta High-Density Lipoprotein Mimetic CER-001 in Patients With More Extensive Plaque Burden
Authors: Kataoka Yu , Andrews Jordan , Duong MyNgan , Nguyen Tracy , Schwarz Nisha , Fendler Jessica , Puri Rishi , Butters Julie , Keyserling Constance , Paolini Jofn F , Dasseux Jean-Louis , Nicholls Stephen J
Published: July 2021

Introduction:
Infusing high-density lipoprotein (HDL) has been shown to promote plaque regression in patients with acute coronary syndrome (ACS). The factors associated with a greater propensity to regression have not been elucidated.

We hypothesized greater plaque regression with HDL infusion would be observed in patients with greater baseline plaque burden.

Methods:
The CHI-SQUARE study compared the effect of infusing the pre-beta HDL mimetic CER-001 (3 to 12 mg/kg) versus placebo weekly for 5 weeks in patients with a recent ACS on plaque burden using serial intravascular ultrasound. Receiver operating characteristics curve analysis determined that a baseline percent atheroma volume (PAV) ≥30% optimally associated with greater regression. Clinical and imaging characteristics were compared in patients with baseline PAV <30% (n=74) or ≥30% (n=271).

Results:
There were no differences between the groups apart from greater use of statin in patients with baseline PAV ≥30% (100 v. 90%, p=0.01). Patients with a greater baseline PAV were more likely to demonstrate echolucency (20 v. 9%, p=0.02) and ultrasound attenuation (21 v. 7%, p=0.01), consistent with lipidic and inflammatory material. On serial evaluation, PAV decreased with CER-001 infusion in patients with baseline PAV ≥30% by -0.27% (p=0.01 v. baseline), but not in those with baseline PAV <30% (+0.43%, p=0.15 v. baseline, p=0.01 between plaque burden groups). The greatest PAV regression was observed with infusing CER-001 3 mg/kg in patients with baseline PAV ≥30% by 0.96% (p=0.04 v. baseline, p=0.02 v. placebo) (Table), but not in those patients with baseline PAV <30% (+0.08%, p=0.55 v. baseline, p=0.004 for comparison between plaque burden groups).

Conclusions:
Greater plaque regression with CER-001 3 mg/kg was observed in ACS patients with greater atheroma burden and more vulnerable features. The findings identify ACS patients with high-risk plaque features most likely to benefit from HDL mimetic therapy.
Abstract 12185: Complete Disruption of All Nitric Oxide Synthases Markedly Reduces Cerebral Infarct Size After Middle Cerebral Artery Occlusion in Mice
Authors: Tsutsui Masato , Haruaki Kubota , Noguchi Katsuhiko , Matsuzaki Toshihiro , Hattori Fumiya , Sakanashi Mayuko , Kina-Tanada Mika , Ishida Masayoshi , Nakasone Junko , Shimokawa Hiroaki , Ohya Yusuke , Sugahara Kazuhiro , Kakinohana Manabu
Published: July 2021

Background:
The role of each nitric oxide synthase (NOS) isoform in cerebral infarction has been studied in individual NOS isoform-deficient mice. It has been reported that, in a model of middle cerebral artery occlusion (MCAO), neuronal and inducible NOSs exacerbate cerebral infarction, whereas endothelial NOS conversely alleviates it. Although the role of the whole NOSs system in cerebral infarction has been examined in pharmacological studies with non-selective NOS inhibitors, the results are quit inconsistent, possibly because of non-specificity of the agents. In this study, we addressed this point in mice in which all three NOS genes are completely disrupted.

Method and Results:
We newly generated triple NOSs
-/-
mice and wild-type littermates by crossbreeding single NOS
-/-
mice. Transient (1 hour) or permanent MCAO was performed in male triple NOSs
-/-
and wild-type mice at 8-12 weeks of age (n=8-11). There was no anatomical difference in the structure of cerebral arteries between the triple NOSs
-/-
and the wild-type mice. Reductions in cerebral blood flow during MCAO were also comparable between the two genotypes. However, cerebral infarct size at 24 hours after transient MCAO was markedly reduced in the triple NOSs
-/-
genotype as compared with the wild-type genotype (
P
<0.05). Cerebral infarct size at 24 hours after permanent MCAO was also markedly smaller in the triple NOSs
-/-
than in the wild-type genotype (
P
<0.05). In addition, neurological deficit was significantly less and the survival rate was significantly better in the triple NOSs
-/-
genotype compared with the wild-type genotype (each
P
<0.05). Importantly, 3-nitrotyrosine protein levels (a marker of peroxynitrite production) in the cerebral infarct region were significantly decreased in the triple NOSs
-/-
genotype as compared with the wild-type genotype (
P
<0.05), suggesting an involvement of decreased oxidative stress.

Conclusions:
These results provide the first evidence that complete disruption of all NOS genes markedly reduces cerebral infarct size after MCAO in mice, demonstrating a novel injurious role of the entire NOSs system in the pathogenesis of cerebral infarction. Inhibition of the NOSs system may be a new therapeutic option in the treatment of cerebral infarction.
Abstract 12261: Improving Discharge Timeliness on a Pediatric Inpatient Cardiology Unit Through the Implementation of Medical Discharge Criteria Decreases Length of Stay and Reduces Hospital Charges
Authors: Porter Andrew , Cable Rhonda , Kolb Amanda , Statile Angela , White Christine , Lorts Angela , Hanke Samuel , Madsen Nicolas L
Published: July 2021

Background:
Prior improvement work integrating standardized medical discharge criteria in general pediatric inpatients led to improved discharge timeliness and reduced length of stay (LOS). Our aim was to develop standardized medical discharge criteria on a quaternary pediatric cardiology unit in an effort to improve the timeliness of discharge. We hypothesized that timely discharge would lead to cost savings and a reduced LOS.

Methods and Results:
Over 18 months (Jan. 2014 - June 2015), a multi-disciplinary team worked toward the quality improvement aim of increasing the percentage of pediatric cardiology inpatients discharged within 2 hours of achieving medical discharge criteria. We established preset ‘medically ready’ discharge criteria in our hospital EMR, initiated upon admission for all inpatients and modified daily as needed. We organized criteria into 7 categories (congenital heart disease (CHD) medical, CHD post-operative, heart failure/transplant medical, transplant post-operative, electrophysiology (EP) medical, EP post-procedure, and catheterization post-procedure). The median percentage of patients discharged within 2 hours of meeting criteria increased steadily from 35% to 78% over the project period. Concurrently, the median number of patients discharged before noon increased from 18% to 31%. Physician and nursing compliance with necessary process measures was 87% and 89%, respectively. LOS decreased by 8% (3.6 to 3.3 days) from the first 6 months of work to the last 6 months. All-cause readmission remained stable at 15% over the improvement time frame. Review of inpatient charges between Oct. 2014 and June 2015 demonstrated 169 patients (190 discharges) who experienced a delayed discharge based on the set criteria. The sum of charges from care provided after meeting criteria was $231,201 (average of $1,217 per delayed discharge).

Conclusions:
Discharge timeliness in pediatric cardiology patients can be improved by standardizing medical discharge criteria. We demonstrate that this can be achieved across all subcategories of pediatric cardiology without increasing the rate of readmission. Improved discharge timeliness not only reduces LOS; it provides an opportunity to substantially decrease medical charges.
Abstract 12266: Treatment and Outcomes of Dual Medicare/Medicaid Eligible Older Adults With Myocardial Infarction
Authors: Doll Jacob A , Hellkamp Anne , Goyal Abhinav , Sutton Nadia , Peterson Eric D , Wang Tracy Y
Published: July 2021

Introduction:
Patients with dual Medicare-Medicaid eligibility typically have higher burden of chronic disease conditions and increased healthcare utilization than patients with Medicare coverage alone. For patients with acute MI, in-hospital treatment patterns and longitudinal outcomes of dual eligible patients are unknown.

Methods:
We linked MI patients 65 years or older in the ACTION Registry-GWTG from 2007 to 2009 to Medicare claims data. We used multivariable Cox regression to compare risks of all-cause readmission by 30 days and major adverse cardiovascular events (MACE: death, MI, stroke) by 1 year between dual eligible vs. Medicare-only patients.

Results:
Of 17,419 Medicare patients discharged after MI, 4,674 (27%) were dual eligible. Dual eligible patients were more likely to be female (64% vs. 49%) and non-white (29% vs. 6%), to have a greater prevalence of comorbid conditions (mean Charlson comorbidity index 3.7 vs. 3.0) and to present with non-STEMI (75% vs. 69%). Rates of reperfusion for STEMI (91 vs 93%, p=0.006) and revascularization for NSTEMI (58% vs. 65%, p<0.001) were significantly lower for dual eligible compared with Medicare only patients in the absence of contraindications. Unadjusted rates of 30-day all-cause readmission and 1-year MACE were higher among dual eligible patients (Figure). After adjustment for differences in patient characteristics and in-hospital treatment, dual eligible status remained associated with higher risk of 30-day readmission (HR 1.16, 95% C.I. 1.06-1.26) and 1-year MACE (HR 1.21; 95% C.I. 1.12-1.31).

Conclusions:
Patients with dual Medicare/Medicaid eligibility were less likely receive reperfusion or revascularization during the index MI hospitalization and had worse short- and long-term outcomes than patients with Medicare coverage alone. Despite the additional support provided by Medicaid coverage, this is a vulnerable population that will benefit from interventions to optimize post-MI outcomes.
Abstract 12276: The Changing Landscape of Ventricular Assist Device Utilization in Children Bridged to Transplant: The “Revolution” Begins
Authors: Villa Chet R , Khan Muhammad S , Zafar Farhan , Byrnes Jonathan W , Morales David L , Lorts Angela
Published: July 2021

Introduction:
Growing clinical experience and innovative implantation techniques have allowed individual pediatric centers to push the boundaries of VAD use. However, data describing the global trends in VAD utilization are lacking. We sought to assess temporal trends in the use of VADS as a bridge to transplant in children across the US.

Methods:
Children <18 years listed for heart transplant 1/2006-6/2014 who were bridged with a VAD were identified in the UNOS database. Patients were stratified by era (Early: 2006-2010, Current: 2011-2014). Descriptive statistics were used to assess trends.

Results:
Of 3986 patients listed, 589 (15%) received a VAD as bridge to transplant during the study period. The percentage of patients bridged with a VAD increased in the current era (12% vs. 18%, p<0.001), while both durable cfVAD use and waitlist times increased (Table). Children < 25 kg continue to be bridged to transplant almost exclusively with pulsatile devices while 95% of patients ≥ 25 kg were bridged with a cfVAD in 2014 (Figure).

Conclusions:
The current era has seen a 1.5-fold increase in the percentage of children bridged to transplant with a VAD as well as a 3-fold increase in the percentage of patients bridged with a durable cfVAD in patients > 25 kg. The emergence of cfVAD technology in an era of increasing waitlist times, raises the prospect of a dramatic increase in the number of children discharged from the hospital while supported with a cfVAD. This underscores the need to rapidly define pediatric specific best care practices in outpatient VAD management.
Abstract 12289: The Nuclear Receptor NR4A1 Regulates Transcriptional Programs Involved in Cardiac Fuel Metabolism and Hypertrophic Growth
Authors: Hayashi Yasuhiro , Lai Ling , Kim Michelle H , Leone Teresa C , Vega Rick B , Kelly Daniel P
Published: July 2021

The transcriptional coregulators, peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) alpha and beta, are inducible master regulators of mitochondrial biogenesis and metabolism. Studies in rodents and in humans have shown that expression and activity of PGC-1 coactivators is downregulated in the failing heart. Surprisingly, we found that adult mice with cardiac-specific deletion of the PGC-1alpha/beta genes exhibit relatively normal cardiac function despite a significant reduction in mitochondrial state 3 respiration, suggesting the existence of a compensatory energy metabolic pathway. Unbiased transcriptional profiling demonstrated upregulation of the orphan nuclear receptor NR4A1 (Nur77) and the related nuclear receptor NR4A3 (Nor1) in PGC-1 null hearts, consistent with an adaptive response to energetic stress. We found that expression of NR4A1 family members is induced in heart by a variety of physiological stress stimuli. In addition, activation of beta-adrenergic signaling with isoproterenol led to rapid and dramatic induction in the expression of all NR4A members in the mouse heart. To identify cardiac NR4A1 targets, total RNA-seq was performed in neonatal rat ventricular myocytes (NRVMs) overexpressing NR4A1. NR4A1 expression of genes involved in glucose uptake/utilization pathways and high energy phosphate transfer including Slc2a4 (Glut4), Eno3 (enolase 3), and Ckmt2 (mitochondrial creatinine kinase). Consistent with the transcriptomic changes, NR4A1 increased myocyte 2-deoxylglucose uptake and oxygen consumption rates (OCR) in these cells. Interestingly, the RNA-seq data also revealed that NR4A1 overexpression downregulated many cardiac pathologic hypertrophic markers such as ANF and BNP. NR4A1 overexpression also significantly inhibited phenylephrine-induced NRVM hypertrophy. Finally, NR4A1 knockout mice exhibit exuberant cardiac hypertrophy following chronic isoproterenol administration. Taken together, these data suggest NR4A1 serves as a stress-induced transcription factor that regulates fuel metabolism and cardiac remodeling. The long-term goal of this project is to determine if activation of this pathway holds therapeutic benefit in acute heart failure.
Abstract 12338: Production of Plasminogen Activator Inhibitor-1 in Infarcted Lesion was Associated With Coronary Endothelial Vasomotor Dysfunction and Progressive Dysfunction of Left Ventricle in Patients With Acute Myocardial Infarction
Authors: Shimizu Takuya , Uematsu Manabu , Yoshizaki Toru , Obata Jun-ei , Nakamura Takamitsu , Saito Yukio , Kugiyama Kiyotaka
Published: July 2021

Experimental studies showed that plasminogen activator inhibitor-1 (PAI-1) is abundantly expressed in the infarcted myocardium and that the increased PAI-1 expression causes an impairment of fibrinolysis in the coronary vascular beds and left ventricular (LV) adverse remodeling after acute myocardial infarction (AMI). However, little is known in humans. Thus, this study examined whether PAI-1 produced in the infarcted lesion may contribute to coronary endothelial dysfunction and LV dysfunction in patients with AMI.

Methods:
Plasma levels of PAI-1 activity and tissue-plasminogen activator (tPA) protein were measured by ELISA in plasma obtained from aortic root (AO), anterior interventricular vein (AIV), and peripheral vein (PV) in 41 patients with a first AMI due to occlusion of a proximal segment of the LAD at 6 months (M) after MI. Coronary blood flow responses in the LAD to intracoronary infusion of acetylcholine (ACh, 50 μg/min) were measured by an intracoronary flow wire technique 6M after MI. Left ventriculography was repeated twice, 2 weeks (2W) and 6M after MI.

Results:
The trans-myocardial gradient of PAI-1 from AO to AIV (0.14 ± 0.15 ng/mL), reflecting a production/release of PAI-1 from the infarcted lesion, had an inverse correlation with coronary blood flow response to ACh (r = -0.43 , p = 0.02). The trans-myocardial gradient of PAI-1 had an inverse correlation with the % changes in LV regional motion in the LAD territory from 2W to 6M after MI (r = -0.37, p = 0.02). PAI-1 level in the PV and the trans-myocardial gradient of tPA had no significant correlation with the coronary blood flow response to ACh and the LV regional motion. The trans-myocardial gradient in PAI-1 level was lower in patients taking than not taking angiotensin II receptor blocker (ARB) (n = 22, -0.15 ± 0.19 ng/mL vs. n = 19, 0.48 ± 0.21 ng/mL, respectively, p = 0.03).

Conclusions:
PAI-1 produced in the infarcted myocardium and released into the coronary circulation was associated with endothelial dysfunction in resistance vessels of the infarct-related coronary arteries and progressive dysfunction of the infarcted region of LV in AMI survivors. ARB might inhibit PAI-1 production in the infarcted myocardium in the chronic phase of MI, which may represent an additional benefit of ARB therapy.
Abstract 12350: Pressure-flow Relationship of Pulmonary Circulation Determines Six-minute Walk Distance in Connective Tissue Disease
Authors: Kusunose Kenya , Yamada Hirotsugu , Bando Mika , Nishio Susumu , Hirata Yukina , Ise Takayuki , Yamaguchi Koji , Yagi Shusuke , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka
Published: July 2021

Introduction:
The 6-minute walk distance (6MWD) as a surrogate of exercise capacity is often shown to be the best predictor of mortality in pulmonary hypertension (PH). Recent studies have described that mean pulmonary artery pressure (mPAP) - cardiac output (CO) relationships have a potential to assess the detail of pulmonary circulation.

Hypothesis:
We hypothesized that pressure-flow relationships of the pulmonary circulation (mPAP/CO) would be associated with 6MWD in connective tissue disease (CTD).

Methods:
We prospectively performed 6-minute walk test and echocardiographic studies in 202 CTD patients (56±14 years; 11% male) with measurements of cardiac output using electric cardiometry. We have calculated the pulmonary artery pressure-cardiac output relationships as mPAP divided by CO (mPAP/CO).

Results:
Firstly, we have checked the accuracy of CO by electric cardiometry. In our cohort with invasive data, there is a good correlation between right heart catheter and electric cardiometry values of cardiac output (r=0.85; p <0.001) with electric cardiometry measurements slightly underestimating cardiac output (bias -14% of the mean). Correlates of 6MWD were age (partial R= -0.19, p=0.009), early-diastolic mitral annular motion velocity (e’, partial R= 0.20, p=0.005), E/e’ (partial r= -0.16, p=0.028) and CO (partial r= 0.21, p=0.019) in the univariate analysis. In multivariate analysis, the mPAP/CO was strongly associated with 6MWD (t= -2.06, p= 0.042). Male gender and early-diastolic tricuspid annular motion velocity were also associated with 6MWD (t= 2.09, p=0.038 and t =2.92, p =0.004, respectively).

Conclusions:
Elevated mPAP/CO was associated with reduced 6MWD independent from LV and RV diastolic function. These results may recommend that we would assess not only the pressure but also the pressure-flow relationships of the pulmonary circulation in high risk group of PH.
Abstract 12381: Ast-120, an Adsorbent of Uremic Toxins Normalized the Cardiac Hypertrophic/pro- Apoptotic And Cardioprotective/anti-apoptotic Signaling in Pacing-induced Heart Failure in Dogs
Authors: Chung Hyemoon , Asanuma Hiroshi , Ito Shin , Min Kyung-Duk , Shindo Kazuhiro , Imazu Miki , Fukuda Hiroki , Takahama Hiroko , Asakura Masanori , Kitakaze Masafumi
Published: July 2021

Background:
Renal dysfunction increases the plasma levels of indoxyl sulfate (IS), a uremic toxin excreted from the kidney. Interestingly, IS is reported to directly stimulate both collagen synthesis and cardiomyocyte hypertrophy in vitro via the modulation of ERK and p38-MAPK. However, it is unclear whether the pathophysiology of heart failure (HF) changes such intracellular signaling via the IS-dependent pathways. AST-120 is known to inhibit the uptake of indole and decrease the plasma IS levels.

Hypothesis:
We tested the hypothesis that the removal of plasma IS by using AST-120 modulates the intracellular signaling for hypertrophy, collagen synthesis and apoptosis of the myocardium in the canine HF model in vivo.

Method:
A canine HF model was produced by continuous rapid ventricular pacing at 230 bpm for 6 weeks. We treated the canine with oral AST-120 (1g/kg/day) administration between 4th and 6th week following the onset of rapid pacing (HF with AST-120 group, HF without AST-120 group, n=7 in each). We also set a control (Control group, n=7) without pacing for 6 weeks. We extracted the protein from the hearts and analyzed it by Western blotting.

Result:
AST-120 treatment reduced both plasma IS elevated in the canine HF model. HF without AST-120 group showed the activation of ERK signaling and the deactivation of both Akt and p38-MAPK signaling compared with Control group. The treatment with AST-120 increased the phosphorylation levels of Akt and p38-MAPK, and suppressed the ERK phosphorylation. HF without AST-120 group also showed an increased expression of pro-apoptotic Bax protein, and a decreased expression of anti-apoptotic Bcl-2 protein. The increased Bcl-2/Bax ratio was significantly ameliorated by AST-120 treatment.

Conclusion:
The decreases in plasma levels of indoxyl sulfate by the treatment with AST-120 1) deactivates the cardiac hypertrophic signaling, 2) activates the cardiac survival and anti-apoptotic signals and 3) suppresses the pro-apoptotic signals in failing heart in vivo. Indoxyl sulfate may become a sensitive and novel biomarker/mediator of heart failure explaining the cardio-renal syndrome that links renal dysfunction to heart failure.
Abstract 12607: Renin Angiotensin Aldosterone System Inhibition Prevents the Arterial Stiffness Elevation Resulting in the Amelioration of Inappropriate Cardiovascular Response During Exercise in Patients With Hypertension
Authors: Yabu Kanae , Masuda Takashi , Ogura Misao , Shimizu Ryosuke , Kamekawa Daisuke , Akiyama Ayako , Kamada Yumi , Tanaka Shinya , Hamazaki Nobuaki , Aoyama Akihiro , Nakamura Takeshi , Maekawa Emi , Tojo Minako , Ako Junya
Published: July 2021

Introduction:
Patients with hypertension (HT) are known to show an increased activity of renin-angiotensin-aldosterone system (RAAS) secondary to sympathetic hyperactivity. The RAAS hyperactivity was reported to induce vascular endothelial dysfunction and elevated functional arterial stiffness resulting in an inappropriate cardiovascular response during exercise such as an excessive blood pressure (BP) elevation. This study investigated whether a long-term RAAS inhibition ameliorated the inappropriate cardiovascular response during exercise in HT patients.

Methods:
Eighty HT patients (64±14 years, 48 males) were divided into two groups based on antihypertensives: angiotensin II receptor blocker (ARB) group and L-type calcium channel blocker (CCB) group. Patients were followed up for one year, after their BP was controlled below 140/90 mmHg. Patients received a cycle ergometer test, and blood examination before and after the follow-up period. We determined systolic blood pressure (SBP) elevation during the exercise test as the change from baseline SBP to peak SBP (ΔSBP). We assessed the changes in plasma renin, aldosterone, noradrenaline (NORA) and adrenaline (ADRN), and brachial-ankle pulse wave velocity (PWV) before and after the exercise test (ΔNORA and ΔADRN as sympathetic activity parameters and ΔPWV as a functional arterial stiffness).

Results:
ΔSBP after the follow-up period was significantly lower in the ARB group than in the CCB group (P<0.001). ΔADRN and ΔPWV increased significantly after the follow-up period in the CCB group as compared with baseline assessment (P<0.05, respectively) despite no significant changes in the ARB group. Those after the follow-up period were significantly lower in the ARB group than in CCB group (P<0.05, P<0.001).

Conclusions:
RAAS inhibition prevented the arterial stiffness elevation resulting in the amelioration of inappropriate cardiovascular response during exercise in HT patients.
Abstract 12642: Left Atrial Diameter as a Predictor of World Health Organization Group Two Pulmonary Hypertension Severity
Authors: Purga Scott L , Penner Elizabeth A , Mauer Elizabeth , Sobol Irina , Horn Evelyn M , Karas Maria G
Published: July 2021

Objective:
Left atrial (LA) enlargement and dysfunction have poor prognostic significance in heart failure and coronary artery disease. However, the correlation between LA diameter and World Health Organization (WHO) Group 2 pulmonary hypertension (PH) severity has not been well studied.

Hypothesis:
We hypothesized that LA enlargement as a marker of LA remodeling in response to pressure and volume overload may contribute to higher pulmonary arterial pressures (PAP) in this population, independent of comorbidities and left ventricular ejection fraction (LVEF).

Methods:
After exclusion for severe left-sided valvular disease, 100 patients with isolated or mixed WHO Group 2 PH defined by right heart catheterization were studied in a cross-sectional retrospective analysis at a single institution. Linear LA anteroposterior diameter was obtained from the parasternal long-axis view on two dimensional TTE. LVEF, LV E/A Ratio, and LV Mass Index were measured according to ASE guidelines. LV E/A and LV Mass Index was recorded in 80 subjects and 79 subjects, respectively. Mean PAP was assessed on RHC. TTE and RHC were performed within one year of each other.

Results:
LA diameter was significantly associated with mean PAP after adjustment for age, sex, body-mass index, presence of coronary artery disease, hypertension, atrial fibrillation, and LVEF in multivariable linear regression analysis. In this multivariable model, a one centimeter increase in LA diameter predicted an average increase in mean PAP of 2.78 mmHg (95% CI 0.10, 5.46, p = 0.0423). In a subset of this population, LVEF, LV E/A Ratio, and LV Mass Index were not significant predictors of mean PAP. Reduction in cardiac index was noted with increasing LA diameter but this trend did not reach statistical significance.

Conclusion:
LA enlargement is significantly associated with increased mean PAP in patients with WHO Group 2 PH. LA enlargement may be a proxy for LA dysfunction and our data suggests that increased LA diameter may be a predictor of WHO Group 2 PH severity. Further studies of LA dimension, volume, and function are warranted to further our understanding of the left atrium’s relationship to PH.