bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19530: Functional Assessment of Coronary Artery Disease Using Low-dose Dynamic Computed Tomography Perfusion
Authors: Hubbard Logan , Ziemer Benjamin , Lipinski Jerry , Sadeghi Bahman , Javan Hanna , Groves E M , Molloi Sabee
Published: July 2021

Introduction:
Computed tomographic angiography (CTA) is, despite its limitations, a powerful modality for noninvasive assessment of coronary artery disease (CAD). Current dynamic CT perfusion (CTP) techniques aim to improve CAD assessment, but deliver high radiation doses, limiting their clinical feasibility. Therefore, we propose a low-dose, dynamic CTP technique that allows for vessel-specific, functional assessment of CAD.

Methods:
A coronary angioplasty balloon was advanced into the proximal left anterior descending (LAD) coronary artery of seven swine (35-45 kg) to induce several levels of stenosis at maximal hyperemia (IC adenosine, 240 μg/min). Reference fluorescence microspheres and IV contrast (370 mg/mL iodine, 25 mL, 7 mL/s) were injected and prospective, ECG-gated dynamic CTP was performed using a 320-slice CT scanner at 100 kVp and 200 mA. Twenty volume scans were acquired per stenosis level for dose comparison to current techniques, but only two volume scans, denoted as V
1
and V
5
, were used for CTP measurement. V
1
was the first volume scan after the aortic input function exceeded a triggering threshold of 180 HU, and V
5
was the fifth volume scan post aortic triggering. All CTP measurements were compared to reference microsphere perfusion measurements using linear regression.

Results:
The result of dynamic CTP measurement was in good agreement with reference microsphere perfusion measurement (P
CTP
= 0.91 P
MICRO
+ 0.37, R
2
= 0.85), as shown in the figure. Additionally, the effective dose of the proposed technique using a two-volume scan acquisition protocol was 2.6 mSv; much lower than the ~10 mSv effective dose of current dynamic CTP techniques.

Conclusions:
The results indicate the potential for substantial dose reduction in dynamic CTP while maintaining measurement accuracy. By reducing the number of volume scans necessary for accurate perfusion measurement, vessel-specific functional assessment of CAD by dynamic CTP is clinically feasible.
Abstract 19565: The Safety and Efficacy of Platelet Glycoprotein Iib Iiia Antagonist by Intracoronary Administration versus Intravenous Administration in Patients With St Segment Elevation Myocardial Infarction: A Meta-analysis
Authors: Pang Jun , Zhang Zheng , Zheng Tongzhang , Bai Ming , PENG YU , Liu xingbin , Liu xingbin , Cheng Mao
Published: July 2021

Objective:
Evaluate the administration (IC) and intravenous(IV) administration of platelet glycoprotein IIb / IIIa antagonist in STEMI patients.

Methods:
We searched PubMed, EMBASE, Web of Science, the Chinese Biomedical Medical Literature database, and the Cochrane Library, the retrieval time is May 2015. The papers which compared the safety and efficacy of IC and IV STEMI patients with platelet glycoprotein IIb / IIIa antagonist were included.Two researchers evaluated the trails and collected data according to 5.0.2 Cochrane Handbook. The data were merged by RevMan 5.0 software.

Results:
Finally we included 17 RCTs(n=8279, including 4260 IC administration patients, and 4019 IV administration patients). The GP IIb / IIIa antagonist was injected in the coronary after stent releasing during PCI in the IC group. Meta analysis showed: In the STEMI trials, intracoronary group had better clinical outcomes than intravenous group in the following index: short time MACE (one month after PCI) [OR=0.47,95%CI:0.23-0.97], congestive heart failure [OR=0.59,95%CI:0.41-0.84], left ventricular ejection fraction [MD=1.11, 95%CI: 0.48-1.74], infarct size [MD=-1.00, 95%CI: -1.65~ -0.35], myocardial blush grade 3 [OR=1.60, 95%CI: 1.12-2.27], drug occupational rate [OR=4.16, 95%CI: 1.45-11.92], wall motion score index[MD=-0.27,95%CI: -0.51~ -0.03]. And the IC and IV group were similar in the death, long time MACE(1 year after PCI), stent thrombosis, sever bleeding, ST-segment resolution -1 month after PCI, target vessel revascularization, myocardial infarction recurrence, TIMI grade 3 after PCI, left ventricular end systolic volume, left ventricular end diastolic volume, intervention success rate, life threatening arrhythmia, stroke after PCI, CK-MB, operation time, E/ A, cardiac death, minor bleeding, with no significant difference (P> 0.05).

Conclusions:
This updated meta-analysis shows, compared to the IV, IC administration of platelet glycoprotein IIb / IIIa antagonist could reduce the risk of short time MACE (one month after PCI), congestive heart failure, and improve left ventricular ejection fraction, so IC administration of platelet glycoprotein IIb / IIIa antagonist could be a considerable way to be used in STEMI patients.
Abstract 19600: Patients With Cardiovascular Risk Factors Were More Likely to Have Lower Life Satisfaction
Authors: Baumann Michèle , Tchicaya Anastase
Published: July 2021

Introduction:
Five years after coronary angiography, life satisfaction (LS) among patients may be related to incidents of cardiovascular diseases, risk factors and unhealthy behaviours and socioeconomic conditions but their respective influence remains unclear. Our aim is to analyze LS and its relationships with those factors.

Methods:
Among the 4,391 patients initially contacted, 547 deaths were reported and 209 had an invalid address. 3,635 patients who underwent coronary angiography in 2008-2009 at the National Institute of Cardiac Surgery and Cardiological Intervention (INCCI) in Luxembourg completed a self-questionnaire assessing LS [1-10] and other covariates. Data were analysed via multiple regression models adjusted initially on age, sex and income, and for a second time with the addition of all CVRF.

Results:
LS of 1,289 volunteers (69.2 years) was 7.3/10. Most were men, Luxembourgish, employees and manual workers, had secondary education and an income of 36,000 euros or more per year. LS was lowest in female patients, those with a low to middle income. Patients who live in couple had the best LS. Patients with a history in the previous 5 years of physical inactivity (regression coefficient: - 0.903), angina pectoris (rc -0.843), obesity (rc -0.512), diabetes, or hypercholesterolemia, were more likely to have lower LS. The previous associations were mostly maintained on the second analysis, with the exceptions of diabetes and obesity. In addition, patients who stopped smoking because of peer pressure (rc -0.011) had a lower LS.

Conclusions:
Profiles of patients are linked with least LS: ‘inclined abstainers’ who intended to modify their behaviours, but could not do it, and ‘disinclined abstainers’ who had no intention of changing and were insufficiently concerned to do so. Patients who stopped smoking and perceived it as unpleasant also had the lowest LS. ‘Declined actors’ were those patients who had to adjust their lifestyles, but were ambivalent about their intentions and the behaviour, which they continued. Health promotion programs would benefit from targeting factors that moderate the unfavourable intention-behaviour relationship and can help enhance LS.
Abstract 19655: Elevated Oxidative Stress Induces Smooth Muscle Cell Death via Superoxide Anion in Bicuspid Aortic Valve-associated Aortopathy
Authors: Phillippi Julie A , Billaud Marie , Hill Jennifer C , Buchwald Julianna E , Kotlarczyk Mary P , Cantu-Medéllin Nadiezhda , Velayutham Murugesan , Cardounel Arturo J , Kelley Eric E , Gleason Thomas G
Published: July 2021

Introduction:
Bicuspid aortic valve (BAV) is associated with an aortopathy that manifests as a dilatation of the proximal ascending aorta. The mechanisms of aneurysm formation in BAV patients are not completely understood. Our group established that medial smooth muscle cells (SMC) from aneurysmal BAV patients exhibit a weakened oxidative stress defense.

Hypothesis:
The weakened oxidative stress defense of medial SMCs in BAV patients leads to elevated oxidative stress in the proximal ascending aorta and decreases SMC viability.

Methods:
Aortic specimens were harvested from patients undergoing aortic valve and/or ascending aortic replacement due to aneurysm, or heart transplant, with IRB approval and informed patient consent. Levels of the superoxide anion-specific oxidation product 2-OH-E
+
was detected via HPLC in hydroethidine-exposed fresh human aortic specimens. Lipid peroxidation was quantified by ELISA-based detection of 8-iso-prostaglandin F2α. Superoxide anion (O
2

•-

) production and cell viability in primary SMC were detected using the cytochrome c reduction assay, and the MTT assay respectively.

Results:
Levels of O
2

•-

and lipid peroxidation were elevated in BAV specimens when compared with tricuspid aortic valve (TAV) specimens (8.7 ± 0.90 vs 6.1 ± 0.90 pmol/mg, and 610±32 vs 458±45 pg/mg, Fig A and B respectively). Elevated O
2

•-

production was detected in primary SMC
in vitro
when compared with SMC from TAV patients (13.2 ± 2.9 vs 6.7 ± 1.7 pmol/min/mg, Fig C). Addition of peroxide to primary SMC resulted in intracellular O
2

•-

-mediated cell death (Fig D).

Conclusions:
Our results indicate that accumulation of O
2
•-
in SMC is associated with increased oxidative stress and with increased cell death in the setting of BAV. Ongoing studies are focused on defining mechanisms of O
2
•-
generation and the impact on aortic wall biomechanics. Importantly, this could help to develop novel interventions for BAV patients who are at risk for aortic catastrophe.
Abstract 19658: Physicians on Cardiac Arrest Teams are Most Often Non-specialists With Limited Clinical Experience
Authors: Lauridsen Kasper G , Schmidt Anders S , Caap Philip , Aagaard Rasmus S , Løfgren Bo
Published: July 2021

Introduction:
The quality of in-hospital resuscitation is poor and may be affected by clinical experience and cardiopulmonary resuscitation (CPR) training. This study aimed to investigate the clinical experience, self-perceived skills, CPR training, and knowledge of guidelines on when to abandon resuscitation among physicians on cardiac arrest teams.

Methods:
This is a nationwide cross-sectional study in Denmark. Telephone interviews were performed with physicians on cardiac arrest teams in public somatic hospitals. Telephone interviews were performed using a structured questionnaire.

Results:
In total, 93 physicians (53% male) from 45 hospitals participated. Median age was 34 interquartile range (30-39) years. Participants were medical students working as locum physicians (5%), residents and fellows (79%), chief physicians (16%), and median postgraduate clinical experience was 48 (19-87) months. Most physicians (92%) felt confident in treating a cardiac arrest, while less felt confident in performing intubation (41%) and focused cardiac ultrasound (39%) during cardiac arrest. Median time since last CPR training was 4 months (2-10) and 48% had attended a European Resuscitation Council (ERC) Advanced Life Support (ALS) course. The majority (84%) felt confident in terminating resuscitation however only 9% were able to state ERC guidelines on when to abandon resuscitation.

Conclusions:
Physicians on Danish cardiac arrest teams are most often non-specialists with four or less years of clinical experience. Several physicians are not able to perform important clinical skills during resuscitation. Less than half of physicians have attended an ERC ALS course. Only very few physicians know the ERC guidelines on when to abandon resuscitation.
Abstract 19660: Scoring System to Predict Major Bleeding Complications in Atrial Fibrillation Patients With Oral Anticoagulant After Drug-eluting Stent Implantation
Authors: Kobayashi Norihiro , Ito Yoshiaki , Hirano Keisuke , Yamawaki Masahiro , Araki Motoharu , Muramatsu Toshiya
Published: July 2021

Background:
We aimed to introduce scoring system to predict major bleeding complications after triple antithrombotic therapy (TAT) in patients with atrial fibrillation (AF) and drug-eluting stent (DES) implantation.

Methods:
Between April 2007 and December 2011, 119 patients with AF and DES implantation were enrolled in this study. All of these patients received oral anticoagulant therapy and dual antiplatelet therapy (DAPT). We investigated the incidence of major bleeding complications including intracranial and gastrointestinal bleeding. Each variables which seem to be associated with major bleeding complications were analyzed using the univariate logistic regression model. All variables tested in univariate analysis with p<0.10 were included in multivariate logistic regression model. The scores for each variables were transformed from regression coefficients and computed in a total score.

Results:
The mean follow-up period was 43.6 ± 25.5 month. The incidence of major bleeding was 17.6%. In multivariate analysis, age > 75 (OR 3.67, 95%CI 1.01-13.3, p = 0.048), continuation of DAPT (OR 7.85, 95%CI 1.50-41.2, p = 0.015), INR > 2.2 (OR 9.19, 95%CI 2.65-31.9, p < 0.001) were predictors of major bleeding complications. Each item’s score ranged from 0 to 2 and the total score ranged from 0 to 5. The area under the receiver operating characteristics curve revealed that there was 82.8% accuracy in the total scores predicting the likelihood of major bleeding complications. The rate of major bleeding complications was 2.3% in low-risk group (scores 0-1), 20.0% in moderate-risk group (scores 2-3), and 53.3% in high-risk group (scores 4-5) (p<0.001).

Conclusions:
This scoring system is useful for the risk stratification of major bleeding complications in AF patients with TAT after DES implantation.
Abstract 19690: Association of Pericardial Fat Density With Progression of Coronary Artery Calcification Differs by Diabetes Status in the CACTI Study
Authors: Alman Amy C , Smith Steven R , Sudini Preethi R , Eckel Robert H , Hokanson John E , Burkhardt Brant R , Snell-Bergeon Janet K
Published: July 2021

Density of adipose tissue can be measured by CT attenuation in Hounsfield Units (HU). Increased visceral fat density has been associated with coronary artery calcification (CAC). However, the relationship between pericardial fat density and CAC is unknown. We examined the association of pericardial fat density (PAT HU) with the presence (CAC > 0) and progression of CAC in the Coronary Artery Calcification in Type 1 Diabetes study (CACTI). CACTI is a prospective cohort study of adults with and without type 1 diabetes (T1D) with a mean age of 38 years (±9) at baseline. Participants were free of CVD at the time of enrollment in the study. PAT volume was measured from baseline EBCT scans within a range of HU from -190 to -30. CAC was measured at baseline and at the follow-up exam with a mean follow-up of 6 years (±0.5). Logistic regression was used to examine the association between PAT HU and CAC. Prevalence of CAC was defined as any CAC (>0) at baseline. Progression of CAC was defined as a change in volume of ≥2.5 square-root transformed units between the baseline and followup exams. PAT volume and triglycerides were log transformed. Interaction terms for diabetes and PAT HU were tested in the models. PAT data were available on 1319 subjects for the prevalence model, and 952 for the progression model. PAT HU was significantly higher (less-negative) in those with T1D compared to those without (-75.7 ±3.7 vs -77.8 ±4.2; p<0.001). Results from the regression models are shown in table 1. Increasing PAT HU was significantly associated with the prevalence of CAC in both those with T1D and without. However, increasing PAT HU was significantly associated with progression of CAC only in those with T1D. These results suggest that higher PAT fat density may be an important factor in subclinical atherosclerosis, particularly for those with T1D.
Abstract 19700: Bystander CPR Saves Lives and Generates the Gift of Life
Authors: Bowers Victor , Davila Marbelly , Buggs Jacentha
Published: July 2021

Introduction:
A fundamental gap in correlation appears to exist between bystander Cardiopulmonary Resuscitation (CPR) and preservation of the gift of life for people who die each day awaiting organ transplantation. As a result, the incidence of bystander CPR as a bridge to organ donation has not been articulated. Hypothesis: We assessed the hypothesis that kidneys recovered with bystander CPR demonstrate equivalent survival rates with first responder CPR and or no CPR.

Methods:
We retrospectively analyzed our transplant database from 2008-2013. We also evaluated the nationwide, population-based database from the United Network for Organ Sharing.

Results:
A total of 643 deceased donors were utilized to sustain life in a sample size of 882 kidney transplant recipients at our center. There were 77 bystander CPR - mean age 49.8 (SEM 1.75), 192 first responder CPR - mean age 52.45 (SEM 1.05), and 613 no CPR - mean age 52.58 (SEM 0.63). The mean length of stay days were 9.42 (SEM 0.64) bystander CPR, 9.03 (SEM 0.51) first responder CPR, and 10.73 (SEM 0.49) no CPR. The mean one year graft survival rate was 97.4% (SEM 0.01, CI 94.85-99.94) bystander CPR, 93.8% (SEM 0.02, CI 90.46-97.03) first responder CPR and 94.1% (SEM 0.01, CI 92.33-95.86). The mean death-censored graft survival days were 2230 (SEM 67.98) bystander CPR, 2351.22 (SEM 38.02) first responder CPR, and 2292.41 (SEM 26.32) no CPR; with a Log rank p-value=0.338. The United States’ data demonstrated 133,369 deceased donors with 44,469 receiving CPR (33.34%). The mean graft survival rate at one year was 92.62% (CI 92.18-93.06) with CPR and 91.54 % (CI 91.21-91.88) no CPR. No distinctions were made regarding the type of CPR in the national database. Conclusions: Bystander CPR saves lives both with the primary return to baseline function and the secondary gain of the gift of life. Intentional effort should be devoted to tracking the results of bystander CPR and the parallel consequence of organ donation.
Abstract 19702: Excessive Hydration Volume Tends to be Associated With a Higher Risk of Contrast-induced Nephropathy After Percutaneous Coronary Intervention in Patients With Chronic Kidney Disease
Authors: Liu Yong , Li Hualong , Chen Jiyan , Tan Ning , Zhou Yingling , Liu Yuanhui , Ye Piao , Ran Peng , Duan Chongyang , Chen Shiqun , Chen Pingyan
Published: July 2021

Introduction:
Adequate hydration with isotonic saline is generally recommended to prevent contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD). However, no well-defined protocols regarding the optimal rate and duration of normal saline administration currently exist.

Hypothesis:
Higher intravascular hydration volume of normal saline adjusted by weight (hydration volume/weight [HV/W], mL/kg) can reduce the risk of CIN in patients with CKD undergoing percutaneous coronary intervention (PCI).

Methods:
Patients with CKD (creatinine clearance [CrCl] <90 mL/min/1.73 m2) undergoing PCI with hydration at the speed recommended by the current guidelines (1 mL/kg/h [0.5 mL/kg/h for left ventricular ejection fraction <40% or severe congestive heart failure]) were included in the study (n=1406).

Results:
Individuals with higher HV/W ratios were more likely to develop CIN (Q1, Q2, Q3, and Q4: 4.3%, 6.6%, 10.9%, and 15.0%, respectively; P<0.001) and acute heart failure (0.29%, 2.28%, 2.73%, and 5.01%, respectively; P=0.001), and were associated with higher in-hospital costs (8,314, 8,634, 9,274, 10,073 dollars, respectively; P25 mL/kg), the adjusted OR was 1.93 (95% CI: 1.09~3.42; P=0.025). Additionally, higher hydration was significantly associated with an increased risk of death (Q2 vs. Q1: adjusted hazard ratio [HR]: 3.59, 95% CI: 1.19~10.84; Q3 vs. Q1: adjusted HR: 3.51, Q4 vs. Q1: adjusted HR: 4.29, P<0.05).

Conclusions:
Excessive intravascular hydration volume at routine speed was associated with higher risks of CIN, acute heart failure, and death, as well as increased health care costs.
Abstract 19722: Cardiac Output Estimation by Inert Gas Rebreathing is Accurate in Mechanically Ventilated Children With Heart Disease
Authors: Marma Amanda , Opotowsky Alexander R , Walsh Brian K , Esch Jesse J , Dinardo James A , Kussman Barry D , Rhodes Jonathan
Published: July 2021

Introduction:
Real time estimates of pulmonary (Qp) and systemic blood flow (Qs) could improve pediatric cardiac care. Current generation inert gas rebreathing (IGR) devices are safe, portable, and easy to use; can estimate Qp and Qs rapidly at the bedside; and can now be adapted for use in intubated patients. We compared IGR and two types of Fick Qp estimates, those using measured (FickM) and assumed (FickA) oxygen consumption (VO2) values, in mechanically ventilated pediatric cardiac patients with no shunt lesion or exclusive right-to-left shunt. Secondarily, we compared measured VO2 with assumed values and values back-calculated from the Fick equation (using measured saturations, hemoglobin and IGR Qp).

Methods:
In 18 intubated patients in the pediatric catheterization laboratory, the modified ventilator-compatible InnocorTM device was used to measure IGR Qp and breath-by-breath VO2; assumed VO2 was taken from LaFarge tables. Sampled pulmonary arterial and venous saturations were used to calculate FickM and FickA. Bland-Altman agreement and Spearman correlation were assessed for IGR Qp with FickA Qp and FickM Qp. Secondarily, agreement was analyzed between measured VO2, assumed VO2, and VO2 calculated from the Fick equation.

Results:
Subjects were aged 4-23 years, with a range of cardiac diagnoses. The figure shows Bland-Altman plots for Qp. Compared with FickA, IGR Qp had mean bias -0.9 L/min, 95% limits of agreement (=±1.96 SD) -2.8 to +1.0 L/min, and r=0.75. Compared with FickM, IGR Qp had mean bias -0.2 L/min, 95% limits of agreement -1.3 to +1.0 L/min, and r=0.90. Agreement of assumed and measured VO2 was poor (bias +23%, ±55%); measured VO2 agreed better with Fick calculated VO2 than assumed VO2.

Conclusions:
IGR Qp estimates agree well with Fick Qp estimates. This agreement improves when VO2 is measured, as assumed VO2 agrees poorly with measured VO2. IGR is an attractive option for bedside monitoring of Qp in intubated children.
Abstract 19724: Renoprotective Effect of Remote Ischemic Peri-conditioning During Air Medical Transport of Patients With ST-segment Elevation Myocardial Infarction
Authors: Olafiranye Oladipupo , Ladejobi Adetola , Martin-Gill Christian , Toma Catalin
Published: July 2021

Background:
Acute kidney injury (AKI) manifesting as acute increase in serum creatinine is a recognized complication to cardiac catheterization. Patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) have a markedly increased risk of developing AKI. At present, there is no universally accepted strategy for prevention of AKI in the setting of primary PCI. We assessed whether remote ischemic peri-conditioning (RIPC) stimulus during ambulance transport of STEMI patient would reduce the rate of creatinine rise post primary PCI.

Method:
We evaluated STEMI patients transferred to two hospitals participating in the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry-GWTG) between March, 2013 and March, 2015. Patients were transferred by an air medical critical care service utilizing RIPC as part of a standard protocol and compared to controls matched by referring location/facility. Patient demographics, clinical characteristics, treatments, cardiac biomarkers, left ventricular function, serum creatinine and rate of any increase in creatinine post PCI were compared by the presence or absence of RIPC during transport.

Results:
Out of the 221 STEMI patients (Age, 63±12.7 yrs; 32.6% female) in this analysis, 107 received RIPC and 114 did not. Baseline characteristics were similar between the two groups. RIPC group had significantly lower rate of creatinine rise post PCI (38.6% vs 55.2%; OR, 1.40; CI, 1.03-1.90; p=0.03) despite having similar baseline serum creatinine (median (IQR), 1.0(0.36) mg/dl vs. median (IQR), 1.0(0.4) mg/dl; p=0.46). In multivariable logistic regression analysis adjusting for demographic factors and clinical characteristics, RIPC (OR, 1.62; CI, 1.12-2.35; p=0.01) was independently associated with lower rate of creatinine rise post PCI.

Conclusion:
Among patients with STEMI undergoing primary PCI, RIPC before hospital arrival compared with no RIPC was associated with significantly lower rate of creatinine rise post PCI. The use of RIPC as a potential renoprotective strategy for STEMI patients warrants further investigation.
Abstract 19911: Markers of Survival in Septuagenarians and Octogenarians With Heterozygous or Homozygous Familial Hypercholesterolemia
Authors: Khoury Étienne , Brisson Diane , Tremblay Gérald , Tremblay Karine , Gaudet Daniel
Published: July 2021

Objective:
Familial hypercholesterolemia (FH) is an autosomal dominant trait characterized by elevated low-density lipoprotein-cholesterol (LDL-C) concentrations appearing at birth and is associated with an increased risk of premature atherosclerotic cardiovascular disease (CAD). Some homozygous (Ho) FH subjects survive over 80 years of age and a proportion of heterozygous (He) FH subjects aged over 70 years have never experienced CAD symptoms. The objective of this study consists in identifying genetic, clinical and/or environmental factors associated with survival over 70 years in FH.

Methods and Results:
The familial analysis of 1,860 French-Canadian FH individuals carrying either the French-canadian Type 1 (15KB deletion) or the French-canadian Type 2, (W66G), which are both FH-causing mutations in the LDLR gene, was performed to identify HoFH and HeFH subjects over 70 years of age. Out of this number, we were able to list a total of 112 subjects (among which 2 HoFH aged 72 and 84 years with baseline cholesterol 18 and 21 mmol/L respectively). Multivariate regression analyses revealed that the gender, high-density lipoprotein-cholesterol (HDL-C) level, the proportion of LDL-C decrease under therapy and the type of mutation in the LDLR gene were significant contributory factors of survival over 80 years or of CAD-free survival over 70 years (p-value under 0.001). In these models, the contribution of HDL-C was independent from that of LDL-C reduction. Notably, HDL-C and gender were shown to be significant covariates of survival among HoFH relatives. Fine phenotyping and exome sequencing analyses are ongoing.

Conclusion:
Based on a monogenic model of high LDL-C and premature CAD, these results demonstrated that despite the reduction of LDL-C, several other covariates would probably constitute major targets for cardiovascular disease (CVD) risk management.
Abstract 19967: Differential Roles of the NADPH-Oxidase 1 and 2 in Platelet Activation and Thrombosis
Authors: Delaney Michael K , Kim Kyungho , Estevez Brian , Stojanovic-Terpo Aleksandra , Shen Bo , Ushio-Fukai Masuko , Cho Jaehyung , Du Xiaoping
Published: July 2021

Objective:
Reactive oxygen species (ROS) generated from activated platelets is known to regulate platelet activation. However, it remains unclear whether and how different isoforms of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases (NOXs) play roles in different platelet activation pathways. Here we investigated the role of NOX1 and NOX2 in different platelet activation pathways using NOX1 and NOX2 knockout mice.

Approach and Results:
NOX1-/- platelets showed selective defects in G protein coupled receptor (GPCR)-mediated platelet activation induced by thrombin, protease-activated receptor 4 agonist peptide (PAR4AP) and thromboxane A2 analog U46619, but was not affected in platelet activation induced by collagen-related peptide (CRP), a glycoprotein VI (GPVI) agonist. In contrast, NOX2-/- platelets showed potent inhibition of CRP-induced platelet activation, and also showed partial inhibition of thrombin-induced platelet aggregation and secretion. Consistently, production of reactive oxygen species (ROS) was inhibited in NOX1-/- platelets stimulated with thrombin, but not CRP, whereas NOX2-/- platelets showed reduced ROS generation induced by CRP or thrombin. Interestingly, laser-induced arterial thrombosis was impaired in NOX2-/- mice, and in thrombocytopenic mice transfused with NOX2-/- platelets, suggesting an important role for NOX2-dependent platelet ROS production in the laser-induced injury model of thrombosis.

Conclusions:
NOX1 and NOX2 play differential roles in different platelet activation pathways: NOX1 mediates GPCR-mediated ROS production and platelet activation, whereas NOX2 plays a general role in GPVI- and GPCR-induced ROS production and platelet activation
in vitro
, and in laser-induced thrombosis
in vivo
.
Abstract 19974: Medicalized Prehospital Care in the Elderly: Facing Age Discrimination
Authors: Wiel Eric , Segal Nicolas , Di Pompéo Christophe , Marc Jean-Baptiste , Vanderstraeten Carine , Doukhan Mathieu , Escutnaire Joséphine , Gueugniaud Pierre-Yves , Hubert Hervé ,   GR-RéAC
Published: July 2021

Introduction:
Few studies report results on cardiac arrests (CA) care in the elderly. Even if age is not considered as an essential prognostic factor some studies questioned if cardiopulmonary resuscitation (CPR) in the elderly could be futile. Nevertheless in daily clinical practice, age seems to be an important factor conditioning CA care.

Hypothesis:
The aim of this case-control study was to compare out of hospital cardiac arrest care and outcome between young (<65 years old) and elderly patients.

Methods:
We performed a prospective case-control study based on data extracted from the French National CA registry. All adult patients (>18 years old) with CA recorded between July 2011 and May 2014 were included. Each elderly (>=65 years old) patient (case) was matched on 3 criteria: sex, initial cardiac rhythm, and the no-flow duration.

Results:
We studied 4,347 pairs. We significantly found less BLS starting, ACLS duration, mobile medical team (MMT) automated chest compression, MMT ventilation and MMT epinephrine injection in the elderly. Statistical differences were also observed for return of spontaneous circulation (ROSC) (OR=0.84[0.77-0.92]), transport to hospital (OR=0.58[0.51-0.61]), vital status at hospital admission (OR=0.55[0.50-0.60]), vital status at Day 30 (OR=0.42[0.35-0.50]), and Cerebral Performance Category (CPC) at Day 30 (OR=0.44[0.37-0.53]).

Conclusions:
All CA guidelines, ethical statement, clinical procedures do not propose age as a discrimination criterion in OHCA care. However, our study shows that with similar CA conditions, elderly patients are victims of medical discrimination by a shorter duration and less intensive care leading to a lower survival rate compared to young people.
Abstract 20016: Genetic Anticipation in Familial Hypertrophic Cardiomyopathy
Authors: Liu Liwen , Zuo Lei , Sun Chao , Wang Bo , Guo Ruiqi , Yang Fan , Yu Bowen , Dong Menglong , Zhang Yanmin , Xu Yongyong , Wang Lifeng
Published: July 2021

Introduction:
To identify HCM at the earliest time possible, estimating the onset of disease based on diagnostic criteria is vital in timing the initiation of screening and interventions.

Hypothesis:
Clinic observations indicate an early diagnose of HCM in second generation of most affected families. From the pedigrees with or without mutations in beta-myosin heavy chain gene (MYH7) affected in two or more generations with hypertrophic cardiomyopathy (HCM), ages and maximal wall thickness (MWT) of left ventricles at diagnosis were evaluated to investigate the potential genetic anticipation in patients with familiar HCM (FHCM).

Methods:
56 individuals from 25 families were analyzed. Linear mixed effects models were adopted to prevent misinterpretation resulting from the cohort effect. Published data containing 9 sarcomere mutations (181 individuals in 52 families) also were extracted.

Results:
MYH7 mutations were detected in 9 of the 25 probands, The median age of HCM diagnosis was 24 in the younger generation and 55 in the older (p < 0.001). In the parametric model, the estimated change in the expected age at diagnosis for the entire cohort was 25.8 years (p <0.001). Statistically significant earlier ages at diagnoses were also observed within subgroups of MYH7+ and MYH7- mutations, and probands older and younger than 30 years old. Although the estimated change in MWT at diagnosis for the entire cohort was only 2.161 mm (p =0.212), the subgroup of probands in the younger generation aged less than 30 years had 10.393 mm (p=0.018) thicker MWT and showed a significant reverse correlation with age. Analysis of published data also supports these findings.

Conclusions:
Genetic anticipation was observed in patients with FHCM. FHCM is prone to be diagnosed at an earlier age in younger generations. Patients who are younger with relatives affected by HCM, especially those who are diagnosed before 30 years of age, should continue to be tracked to offer appropriate screening modalities as earlier as possible.
Abstract 20023: Impact of Targeted Temperature During Therapeutic Hypothermia: A Pooling Analysis of Published Literature
Authors: Schenone Aldo L , Cohen Aaron , Patarroyo Gabriel , Shishehbor Mehdi H , Menon Venugopal , Duggal Abhijit
Published: July 2021

Introduction:
Two small RCTs demonstrated benefit of therapeutic hypothermia (TH) after out-hospital cardiac arrest (OHCA). We explored the benefit of targeted temperature during TH and also performed an updated meta-analysis to determine the intervention effect in the community.

Methods:
We identified studies by searching electronic databases (MEDLINE, EMBASE and Cochrane Library). We selected RCTs and cohort studies restricted to those reporting achieved temperature during TH after OHCA, and describing mortality and neurological outcomes at discharge. Studies were assessed for risk of bias. Data from all individual hypothermia arms were pooled by achieved temperature. Pooled outcomes were compared across achieved temperatures. Meanwhile, we meta-analyzed controlled studies comparing hypothermia against normothermia.

Results:
The search identified 32,275 studies of which 24 studies (34 hypothermia arms) were used in the pooling analysis and 14 controlled studies were meta-analyzed. Pooling analysis reported an overall in-hospital mortality of 47.2% with a rate of good neurological outcome at discharge of 38%. There was no difference in hospital mortality (p=0.86) or neurological outcomes at discharge (p=0.32) across temperatures (Figure 1). Sub-group analysis by rhythm showed a non-significant trend towards benefit when the lower temperature were applied to non-shockable rhythms. Meta-analysis demonstrated a MTH mortality (OR 0.51, 95%CI:0.41-0.64, I2=4.1%) and neuro-protective benefit (OR 2.48, 95%CI:1.91-3.22, I2=0%).

Conclusions:
No discernible clinical benefit was noted based on target temperature achieved. The signal toward potential benefit when applying lower temperature to non-shockable rhythms warrants exploration. Consistent with prior meta-analysis, TH provides mortality and neuro-protective benefit after OHCA even when including cohort studies thought to be more representative of performance in the community.
Abstract 20032: Outpatient Exposure to Potentially Harmful Drugs in Patients With Heart Failure
Authors: Alvarez Paulino , Ganduglia Cecilia , Putney David , Estep Jerry D
Published: July 2021

Background:
Several drugs have the potential to cause or decompensate heart failure (HF).

Objective:
To evaluate the frequency of potentially harmful drug exposure after hospital discharge in patients with heart failure.

Methods:
This was a retrospective analysis of Blue Cross Blue Shield of Texas (BCBSTX) claims data (2008-2013) which contains information for medical and pharmacy services. We included patients with at least one admission with a primary or secondary diagnosis for heart failure as defined by ICD-9 codes. We then analyzed all pharmaceutical claims for those patients as of day of discharge. Exposure to potentially harmful drugs (PHD) was defined as the use of non-steroidal anti-inflammatory agents (NSAIDS), Thiazolidinediones (TZD), Alpha-blockers (AB), Antiarrhythmic (AA) and non-dihydropyridine calcium channel blockers (non DPCCB) as recorded in pharmaceutical claims using AHFS Pharmacologic-Therapeutic Classification.

Results:
A total of 35317 discharges with a primary or secondary diagnosis of heart failure were identified, of which we analyzed a subset of 13,926 discharges from a total of 9,784 patients who had pharmacy coverage through BCBSTX.

We found that of 5,730 (69%) had a prescription for at least one PHD after discharged. NSAIDS were the most common category 77% (4430) followed by AA 781(13.6%), non DPCCB 322 (5.6%), TZD 103 (1.8%) and AB 94 (1.6%). Most cases were recorded as new prescription claims with a relatively short interval between discharge and prescription. (Table 1)

Conclusion:
In patients discharged from the hospital with a primary or secondary diagnosis of heart failure, exposure to potentially harmful drugs is not uncommon, especially NSAIDS. Further research to define the consequences of this exposure is needed.
Abstract 20051: Divergent Actions of Circulating Angiopoietin-2 on Vascular Inflammation and Leak in a Mouse Model of Acute Lung Injury
Authors: Schlosser Kenny , Taha Mohamad , Deng Yupu , Mei Shirley H , Stewart Duncan J
Published: July 2021

Introduction:
Angiopoietin-2 (Angpt2) is a partial agonist/antagonist of the vascular-stabilizing endothelial Tie2 receptor. In both animal models and patients with acute lung injury (ALI), Angpt2 circulating levels are elevated; however, it remains unclear whether these elevated levels contribute to, or protect against, the lung inflammation and vascular leak associated with ALI.

Objective:
To evaluate the biological consequences of elevated circulating Angpt2 levels in a mouse model of endotoxin-induced ALI.

Methods and Results:
Transgenic mice (Angpt2OVR) with elevated circulating levels of human (h)Angpt2, via conditional hepatocyte-specific overexpression, were examined at several timepoints (from 3 h to 72 h) following lipopolysaccharide (LPS)-induced ALI (n=7-14 mice/genotype group/timepoint). Bronchoalveolar lavage (BAL) neutrophil and inflammatory cytokine levels were significantly higher (P<0.05) in Angpt2OVR versus littermate controls at 48 h and 6 h post LPS, respectively. In contrast, vascular leak, evidenced by decreased BAL IgM and albumin levels at 24 and 48 h, was attenuated in Angpt2OVR mice. Systemic Angpt2 overexpression showed no net detriment or benefit for survival following LPS-induced injury (n=37-38 mice/group). Tail vein injection of an anti-hAngpt2-neutralizing aptamer (versus non-functional scrambled-sequence control; n=12-13 mice/group), reversed the pro-inflammatory and anti-leak effects observed at 48 h in LPS-injured Angpt2OVR mice. Transcript profiling, via PCR array, was also conducted to probe the effects of Angpt2 neutralization on the lung tissue expression of 84 genes involved in vascular biology. Angpt2 neutralization via aptamer caused alterations in multiple genes linked to angiogenesis, vascular tone, inflammation, apoptosis, cell adhesion, coagulation, and platelet activation (P<0.05 versus scrambled control, n=4/group).

Conclusions:
Angpt2 exerts differential effects on lung inflammation and permeability under pathological conditions in vivo. These data establish novel context-dependent actions of Angpt2, and suggest elevated circulating levels may help regulate multiple pathways necessary to fine-tune the vascular response to lung injury.
Abstract 20100: Parental Presence at Cardiac Intensive Care Unit Bedside Transfer Rounds Reduces Parental Anxiety: Results of a Randomized Controlled Trial
Authors: Anand Vijay , Williams Elina , Elgendi Mohamed , Meakins Leanne , Cunningham Chentel , McCrady Heather , Tawfiq Gerda , Devlin Nicola , Shine Kumar , Larsen Bodil , Rebeyka Ivan , Adatia Ian
Published: July 2021

Introduction:
The transfer of children from the pediatric cardiac intensive care unit (PCICU) to the ward is a time of great anxiety for the parents of children and medical vulnerability for children who are receiving complex therapies.

Hypothesis:
We assessed the hypothesis that parental presence at bedside transfer rounds would reduce parental anxiety and improve patient safety following transfer of children from PCICU to the ward.

Methods:
We undertook a randomized controlled trial of children discharged from the PCICU to the ward. Consenting parents were randomized to be absent (control group) or present (intervention group) at multidisciplinary face to face bedside transfer rounds. The primary outcome measure was parental stress measured by the validated Spielberger’s State -Trait Anxiety Inventory (STAI) pre and post transfer. Secondary outcome measures included unplanned readmission to the PCICU, medication errors and emergency calls to the ward. We excluded patients being transferred between intensive care units.

Results:
We enrolled 230 subjects (control group n=93, intervention group n=91, failed to complete study n= 46). The 2 groups were matched with respect to gender (male 46% control vs 54% intervention), age (median age control 1.9 yrs (range 0.02 to 16.3) vs intervention 0.9 (0.02 to 17), parental age 32 yrs (18-64) vs 33 (20-60), parental years of schooling 15.5 years ( 7-26) vs 15 (9-24), presence of medical co-morbidities (33% each group). There was significantly greater reduction in trait (p=0.004, state (p=0.01) and total anxiety (p=0.0012) pre and post transfer in the intervention group vs the control group. There were no differences in minor medication errors (36 vs 33), unplanned PCICU re-admissions (11 vs 12) and emergency ward calls(7 vs 8)

Conclusions:
Parental presence at face to face multidisciplinary transfer rounds from the PCICU is associated with reduced parental anxiety without change in medication errors, readmission rates or emergency calls to the ward. Reduced parental anxiety may improve parental satisfaction with their child’s care.
Abstract 20130: Hypertrophic Cardiomyopathy in RAF1 Mutant-associated Noonan Syndrome Requires Complex Cellular Interplay
Authors: Yin Jiani C , Platt Mathew , Wu Xue , Simpson Jeremy A , Araki Toshiyuki , Neel Benjamin G
Published: July 2021

Hypertrophic cardiomyopathy (HCM) has multiple etiologies, including hypertension, cardiac valve disease or genetic defects. Most inherited HCM results from defects in sarcomere proteins, but ~25% are caused by aberrant cardiac signal transduction genes. RASopathies are developmental disorders with multiple variably penetrant features, including HCM, which are caused by mutations in genes encoding RAS/extracellular signal-regulated kinase (ERK) pathway components. The most common RASopathy, Noonan Syndrome (NS), results from gain-of-function alleles in PTPN11, KRAS, SHOC2, SOS1/2, RAF1 and RIT1. Activating mutations in RAF1 are strongly (~95%) associated with HCM. Global knock-in mice harboring the NS allele Raf1L613V recapitulate the features of NS-associated HCM, including ventricular chamber dilatation, enhanced cardiac contractility, and exacerbation of pressure-overload induced fibrosis. Here, using inducible Raf1L613V knock-in mice and lineage-specific Cre lines, we show that RAF1 mutant-associated HCM is caused by a complex interplay of multiple cardiac cell types. Surprisingly, cardiomyocyte-specific Raf1L613V expression caused minimal hypertrophy, yet markedly increased cardiac contractility. By contrast, endocardial/cardiac endothelial (EC)-specific Raf1L613V expression promoted cardiomyocyte hypertrophy without affecting contractility. In direct or Transwell co-cultures, Raf1L613V-expressing ECs increased the size of normal cardiomyocytes. Cytokine arrays revealed increased IL6 secretion from isolated Raf1L613V-expressing ECs, and JAK-STAT, PI3K, and MEK/ERK activation were enhanced in EC-Raf1L613V hearts. Blocking IL6 action with neutralizing anti-IL6 antibodies reversed cardiomyocyte hypertrophy in EC/cardiomyocyte co-cultures. Finally, Raf1L613V expression in cardiomyocytes or cardiac fibroblasts, but not in ECs, exacerbated fibrosis upon pressure-overload. Taken together, our data indicate that NS HCM requires complex, cell-autonomous and -non-autonomous interactions between cardiomyocytes, ECs, and fibroblasts. Furthermore, we identify the IL6 pathway as a potential therapeutic target for RASopathy-associated HCM.
Abstract 9740: Factors Associated With Performing Urgent Coronary Angiography in Out-of-Hospital Cardiac Arrest
Authors: Lam David H , Glassmoyer Lauren M , Davis Roger B , Cutlip Donald E , Donnino Michael W , Cocchi Michael N , Pinto Duane S
Published: July 2021

Introduction:
Out-of-hospital cardiac arrest (OHCA) is associated with high mortality and is most commonly caused by cardiovascular disease. Current guidelines recommend urgent coronary angiography (UCA) if ST-elevation myocardial infarction (STEMI) or high suspicion of acute myocardial infarction exist. Some have advocated for UCA in all OHCA without an obvious non-cardiac cause of arrest. The reasons for large clinical variation in performance of UCA in OHCA are not well understood.

Objective:
We sought to identify factors associated with performing UCA in OHCA.

Methods:
A retrospective chart review was conducted on 535 consecutive cardiac arrest patients who achieved return of spontaneous circulation (ROSC) and were admitted at a tertiary academic medical center from January 2008 to August 2014. Exclusion criteria included in-hospital cardiac arrests (201), outside hospital UCA (8), and lack of medical records (1). Univariable analysis followed by multivariable forward selection forcing age and gender were used to determine correlates of performing UCA, defined as within 6 hours of presentation.

Results:
Out of 325 resuscitated OHCA patients (mean age, 64; women, 35%), 69 were taken to UCA. Factors associated with performing UCA were history of coronary artery disease (CAD) (OR 2.76, 95% CI 1.22-6.28), initial shockable rhythm (OR 3.04, 95% CI 1.31-7.06), following commands post-ROSC (OR 2.77, 95% CI 1.06-7.25), and STEMI (OR 15.17, 95% CI 6.57-35.04). Increasing age (OR 0.97, 95% CI 0.95-0.999) and obvious non-cardiac cause of arrest (OR 0.10, 95% CI 0.03-0.37) were negatively associated. Gender, prior stroke, dementia, bystander cardiopulmonary resuscitation, hypotension, contraindication to anticoagulant, presenting from nursing home or rehabilitation, do not resuscitate order prior to admission, non-English primary language, and presenting during off-hours were not associated with the decision for UCA.

Conclusions:
In resuscitated out-of-hospital cardiac arrest patients, history of CAD, shockable rhythm, ability to follow commands, and STEMI were associated with performing urgent coronary angiography. Older patients and those with an obvious non-cardiac cause of arrest were less likely to receive coronary angiography.