bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11270: Including the Patient’s Perspective in the Planning of Data Collection in the Recurrent Pericarditis Registry, RESONANCE
Authors: Luis Sushil A , Cremer Paul , Portman Michael A , raisinghani ajit , Malinowski Alexandra , Marden Lora , Reid Alison , Martin Dana
Published: March 2022

Introduction:
In conjunction with pericardial disease physician specialists, industry experts, and recurrent pericarditis (RP) patients the RESONANCE Registry was designed to collect retrospective and prospective, longitudinal, observational data in real-world clinical practice across the United States (US). We aimed to collect data that were complete and meaningful in terms of patient experience and health related quality of life (HRQoL). Herein, we describe a novel patient-centric research approach to obtain feedback on evaluation tools for incorporation in the RESONANCE Registry (NCT04687358).

Methods:
Ten adult patients with a self-reported duration of disease ranging from 8 months to 25 years participated in an advisory board during which they provided feedback through a virtual platform. Their feedback informed development of multiple registry aspects. These included selection of patient reported outcomes measures (PROMs), to be collected every three months at prospective data collection timepoints, and design of several questionnaires, including evaluation of specific RP episode characteristics.

Results:
Prior to finalization, registry case report forms were optimized based on feedback provided by patients. Areas of data-capture informed by patient input included selection of PROMs to be assessed and patient-centric tools used for self-assessment of disease experience and HRQoL. For example, sections of a patient questionnaire were modified to include documentation of the presenting symptom, breathlessness, fear of episodes, and patient management of each episode.

Conclusions:
This patient-centered research collaboration resulted in enhancements to the RESONANCE Registry that enabled capture of information meaningful to patients’ daily experiences, preferences, and expectations. Patient participation in tangible aspects of research, including registry tools and design, can increase engagement with the communities that have a vested interest in improving patient care. In addition, patient involvement can help to ensure research efforts reflect the needs of not only the healthcare community but of patients alike, with an ultimate goal of improving clinical outcomes.
Abstract 11277: Early Diastolic Strain Rate in Relation to Long Term Prognosis Following Isolated Coronary Artery Bypass Grafting
Authors: Lassen Mats C , Lindberg soeren , Olsen Flemming J , Fritz-Hansen Thomas , Pedersen Sune H , Iversen Allan Z , Galatius Søren , Mogelvang Rasmus , Biering-Sørensen Tor
Published: March 2022

Introduction:
The ratio of early mitral inflow velocity to early diastolic strain rate (E/e’sr) is a novel echocardiographic measure to estimate early left ventricular (LV) filling pressure.

Hypothesis:
We hypothesize that E/e’sr is a predictor of outcome following coronary artery bypass grafting (CABG) and that it is superior to the conventionally used E/e’.

Methods:
Consecutive patients undergoing isolated CABG at Gentofte Hospital (n=652) were included. Prior to surgery, all patients underwent an extensive echocardiographic examination. The outcome was all-cause mortality. Cox proportional hazard regression models were used to assess the prognostic value of E/e’sr in relation to the outcome.

Results:
The mean age of the study population was 67±9 years, 84% were male, mean LV ejection fraction was 50±11%. During follow-up (median 3.8 years [IQR: 2.7; 4.9 years]), a total of 73 (11%) died. Both E/e’ and E/e’sr were significant predictors in univariable models. In a multivariable model adjusted for demographic, clinical and echocardiographic covariates, E/e’sr remained an independent predictor of outcome (HR:1.05 [1.01-1.10], p=0.049, per 10cm increase) whereas E/e’ did not (HR:1.05 [0.99-1.11], p=0.053, per 1-unit increase). The relationship between E/e’sr, and the outcome was significantly modified by GLS (p for interaction = 0.043) (
Figure
). In the multivariable model, E/e’sr was still significantly associated with the outcome in patients with high GLS (≥13.6%) (HR:1.18 [1.02-1.36], p=0.029) but not in patients with low GLS (HR 1.04 CI95%: [0.99-1.10], p=0.14). E/e’ was not a significant predictor of all-cause mortality after multivariable adjustment in neither of the groups. E/e’sr improved net reclassification with 0.33 when added to the EuroSCOREII model.

Conclusions:
Following CABG, preoperative E/e’sr is an independent predictor of all-cause mortality, especially in patients with preserved systolic function and superior to E/e’.
Abstract 11282: Meta-Analysis of Residential Portable Air Cleaner Use and Circulating Inflammatory Biomarkers
Authors: Wittkopp Sharine , Walzer Dalia , Thorpe Lorna , Roberts Tim , Xia Yuhe , Gordon Terry , Brook Robert D , Thurston George , Newman Jonathan D
Published: March 2022

Introduction:
Fine particulate matter air pollution (PM
2.5
) exposure is associated with elevated circulating inflammatory biomarkers implicated in cardiovascular disease (CVD). Portable Air Cleaners (PAC)s reduce PM
2.5
exposure and may lower concentrations of inflammatory biomarkers.

Methods:
We performed a systematic review and meta-analysis of randomized crossover trials of in-home high efficiency particulate air (HEPA) PACs vs. sham control on changes in CRP, IL-6, and/or TNFα among adults with no smoking exposure using Medline, Embase, and Cochrane Central Register of Controlled Trials with the Ovid Platform, Inspec, Compendix, and Web of Science Core Collection. Two investigators (S.W, D.W.) independently screened and reviewed the studies. We used RevMan 5.3 to perform the meta-analysis.

Results:
Search results included 459 articles screened, 26 selected for full review, and 14 that met inclusion criteria, representing N=724 participants included in the meta-analysis. Ten studies reported CRP, 9 reported IL-6, and 5 reported TNFα. Based on WHO guidelines, 5 studies were in regions of extreme PM
2.5
exposure (>35 μg/m
3
), 3 were high (10-35 μg/m
3
), 3 were low (<10 μg/m
3
), and 2 lacked baseline PM
2.5
. Median (± S.D.) duration of HEPA/sham use was 9 ± 6.6 days. Reductions in PM
2.5
ranged from 2.6 to 54.9 μg/m
3
(35-82%) and varied by baseline PM
2.5
, although reporting of baseline PM
2.5
was incomplete across trials. Compared to sham PAC use, active PACs were associated with a 7% lower CRP (95% CI -13%, 0%) and 12% lower IL-6 (-22%, -2%), P<0.05 for both (Figure). Subgroup analyses demonstrated consistency of effect of PACs across levels of baseline PM
2.5
.

Conclusions:
Our data demonstrate that PAC use is associated with significant reductions in circulating CRP and IL-6, with a magnitude of effect similar to clinical trials of statins and IL-1β inhibition. Given the role of inflammation in CVD, PACs may be useful to reduce systemic inflammation and cardiovascular risk.
Abstract 11284: Relationship of Inflammatory Cytokines and Six-Month Hospital Readmission in Heart Failure
Authors: Corvera-Tindel Teresita , Doering Lynn V
Published: March 2022

Hospital readmission rates (HRR) in heart failure (HF) remains high. Psychosocial and clinical factors are linked with HF hospital readmission. Brain natriuretic peptide (BNP) is strongly associated with acute decompensated HF. However, the relationships of inflammatory cytokines (i.e. tumor necrosis factor-alpha [TNFα], interleukin-6 [IL6], interleukin-10 [IL10]) and HRR in HF are rarely evaluated.

Objective:
Evaluate the relationship of BNP, TNF-α, IL6 and IL10 with all-cause HRR within 6 months post-HF hospital discharge.

Methods:
A cross-sectional study was conducted in 104 HF patients: age 68.4 ± 11.7 years, left ventricular ejection fraction 37.9% ± 17%, Specific Activity Scale (SAS) I/II- 40 (39%), and III/IV- 64 (61%) , Charlson Comorbidity Index (CCI) score: 0-1= 24%, 2-3= 26%, and =/>4= 50%. Hospital readmission rate is the number of hospital readmissions of all causes occurring 2 weeks to 6 months after HF hospital discharge. Initially, we analyzed bivariate correlations of HRR with sociodemographic, depression (via Hamilton depression rating scale [HDRS] score), functional status, comorbidities, BNP, and inflammatory cytokines (i.e. TNF-α, IL-6 and IL10). A multiple linear regression was performed, with important and significant psychosocial and clinical variables entered first as a block, followed by BNP and inflammatory cytokines.

Results:
Incidence of 6-month HRR: 0= 49 (47%); 1-2= 43 (41%); 3-6= 12 (12%). Bivariate correlation of HRR with: 1) sociodemographic: age- (
r
= .21, p= .02), non-white- 37% (
r
= .04, p= .36), living alone- 42% (
r
= .17, p= .04); 2) functional status: SAS (
r
= .28, p= .002); 3) CCI score (
r
= .21, p= .02); 3) HDRS score (
r
= .14, p= .07); 4) BNP: (
r
= .14, p= .08); and 5) inflammatory cytokines: IL6 (
r
= .41, p= <.001, and IL10 (
r
= .16, p= .06). Together, age, living alone, being non-white, HDRS score, SAS, CCI score, and IL6 accounted for 24% of the variance in HRR (p= .001). Specific variables contributing significant variance to HRR were: higher IL6- 34% (p= .001), and living alone= 14% (p= .10).

Conclusion:
Six-month HRR in HF remains high. Higher IL6 is associated with high HRR. After HF hospital discharge, patients with high inflammatory cytokines may require more frequent monitoring and intervention.
Abstract 11285: Non-Vitamin K Antagonist Oral Anticoagulant Drug-Drug Interactions in Patients with Atrial Fibrillation Using Dronedarone and Non-Dronedarone Antiarrhythmic Drugs
Authors: Wu Victor Chien-Chia , Wang Chun-Li , Huang Yu-Chang , Tu Hui-Tzu , Huang Yu-Tung , Kuo Chang-Fu , Chen Shao-Wei , Hung Kuo-Chun , Wen Ming-Shien , Chang Shang-hung
Published: March 2022

Introduction:
Non-vitamin K antagonist oral anticoagulant (NOAC) do not normally require INR-monitoring. We aimed to investigate drug-drug interactions of NOACs in patients with atrial fibrillation (AF) using antiarrhythmic drugs.

Hypothesis:
Dronedarone may have less drug-drug interaction compared to non-dronedarone antiarrhythmic drugs.

Methods:
National Health Insurance Research Database were retrieved between 2012 and 2017 for patients with AF. We excluded patients not taking antiarrhythmic drugs, bradycardia, heart block, history of heart failure, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Primary outcomes were major bleeding, intracranial hemorrhage, and gastrointestinal bleeding.

Results:
In total, 84,933 patients used NOAC in patients with AF were enrolled. After exclusion criteria, there were 26,773 patients with 204,937 person-quarters remained for analysis after the exclusion criteria were applied In terms of major bleeding, there was no increased major bleeding due to DDI between NOAC and dronedarone (adjusted rate ratio [aRR]: 0.77, 99% confidence interval [CI]: 0.54-1.12, p = 0.074). In terms of intracranial hemorrhage, there was no increased major bleeding due to DDI between NOAC and dronedarone (aRR: 0.64, 99% CI: 0.34-1.20, p = 0.0668). In terms of gastrointestinal bleeding, there was no increased major bleeding due to DDI between NOAC and dronedarone (aRR: 0.86, 99% CI: 0.55-1.35, p = 0.3819).

Conclusions:
In this study, NOACs and dronedarone coprescription is not associated with an increased risk of major bleeding, intracranial hemorrhage, nor gastrointestinal bleeding. The results suggest that such NOAC with dronedarone coprescription should be practiced in place of NOAC with amiodarone when the clinical criteria are appropriate.
Abstract 11286: Human-Induced Pluripotent Stem Cell Derived Exosomal Protein Induces Cardiac Regeneration
Authors: Magadum Ajit , Mallaredy Vandana , Roy Rajika , Joladarashi Darukeshwara , Gurrala Charan Thej , Cheng Zhongjian , Cimini Maria , Huang Grace , Wang Chunlin , Lucchese Anna Maria , Truongcao May , Benedict Cindy , Kishore Raj
Published: March 2022

Introduction:
Cardiovascular diseases are the leading causes of death worldwide. After myocardial infarction (MI), there is a permanent loss of cardiomyocytes (CMs), and as the mammalian heart has limited regenerative capacity, it leads to Heart Failure. Recent studies from zebrafish and 1-day old mice showed that they could regenerate their heart through inducing existing CM proliferation. Attempts have been made to transiently reconstitute embryonic signaling in adult hearts, including overexpression of cell cycle activating genes with limited success. iPSC-derived extracellular vesicles (EV)/exosomes have been shown to improve cardiac function and some degree of CM renewal. However, the iPSC-EVs-mediated cardiac regeneration mechanism remains unclear and largely pertains to microRNAs and other RNAs, with a little elucidation of the role of iPSC-exosome proteins.

Hypothesis:
The myocardial delivery of iPSC-EV-specific protein improves cardiac function and remodeling post-MI by activating pro-proliferative and anti-oxidative stress molecular pathways.

Methods and Results:
Our preliminary studies showed that hiPSC-EVs induced the CM cell cycle in mice post-MI, and by employing a proteomic approach, we found a novel protein exclusively expressed in iPSC-EVs. The overexpression of hiPSC-EV enriched protein in the form of modRNA (modified mRNA) induced a robust CM cell cycle in rat neonatal CMs and in adult hearts post-MI. This increase in the CMs cell cycle by the modRNA was associated with reduced scar size, improved cardiac function (%EF 49.76 ± 5.8 vs. 27.47 ± 6.9 (control, Luc modRNA), respectively), and mice survival 28 days post-MI. Furthermore, using the siRNA and modRNA (inhibition and over-expression) approach, we found that the protein-induced Yap1-β-catenin molecular pathway stimulates CM proliferation. Furthermore, the overexpression protein post-MI inhibited the CM apoptosis (TUNEL
+
CMs, 1.3% ± 0.1 vs. 2.1% ± 0.11 (control)) by reducing oxidative stress and DNA damage response.

Conclusion:
The myocardial injection of iPSC-EV specific protein through a highly therapeutic modRNA tool improve cardiac function by inducing CMs proliferation, inhibiting oxidative stress, and reactivating cardiac regeneration post-injury.
Abstract 11289: Sedentary Time in Uganda: Influence of Sex and HIV Status and Associations with Atherosclerotic Cardiovascular Disease Risk
Authors: Horvat Davey Christine , Webel Allison R , Brinza Ellen , Kityo Cissy , Nazzinda Rashidah , Longenecker Chris T
Published: March 2022

Introduction:
Sub-Saharan Africa (SSA) is disproportionately impacted by HIV and HIV-related atherosclerotic cardiovascular disease (ASCVD). Since physical activity may prevent ASCVD events, it is important to understand how physical activity and inactivity relate to ASCVD risk among men and women with and without HIV in SSA.

Methods:
One hundred people with HIV (PWH) and 100 people without HIV (PWOH) matched by age and sex were enrolled into this observational study in Kampala, Uganda. Physical activity was objectively measured by actigraphy for 7 days, including steps per day, light activity time, moderate-to-vigorous activity time and sedentary time. ASCVD risk was assessed using the pooled-cohort equations. Coronary artery disease was quantified by cardiac computed tomography angiography. Multivariable linear and logistic regression models were used to determine the relationship between physical activity, ASCVD risk, and subclinical coronary disease.

Results:
Median age was 57 years; 63% were female and median ASCVD risk score was 7.9%. All PWH were on antiretroviral therapy and 86% had undetectable HIV viral load. Physical activity patterns were similar by HIV status (all p>0.2). Compared to males, females took more steps per day (
p
=0.001) and engaged in more light activity time (
p
<0.001), but less moderate-to-vigorous activity time (
p
<0.001). Sedentary time was similar by HIV status and sex (both p>0.8). After adjusting for moderate-to-vigorous activity time, sedentary time remained positively associated with ASCVD risk (standardized β=0.334,
p
<0.001). In stratified models, sedentary time was associated with ASCVD risk in females (β=0.258,
p
=0.028) but not males (p=0.194) and in PWOH (β=0.430, p=0.001) but not PWH (p=0.380). Sedentary time was associated with the presence of coronary artery disease plaque, even after adjustment for ASCVD risk score (adjusted OR= 1.039 per hour of sedentary time,
p
=0.018).

Conclusions:
Sedentary time is strongly associated with atherosclerotic cardiovascular disease risk in Uganda, particularly among females, but less so among PWH. Future studies should consider the influence of sex and HIV status while developing targeted strategies to improve physical activity and reduce sedentary time.
Abstract 11293: Trends in Pulmonary Embolism Mortality Rates Among Racial Minorities in the United States, 1999-2019
Authors: Cash Ayla , Minhas Abdul Mannan Khan , NAZIR SALIK , Ariss Robert W , Gupta Rajesh
Published: March 2022

Introduction:
Acute pulmonary embolism (PE) is a major cause of mortality in the United States (US). Recent reports indicate that PE-related mortality rates have increased among all Americans, non-Hispanic White Americans, and non-Hispanic Black Americans in the last decade. Here, we report PE-related mortality trends in the US among non-Hispanic American Indian or Alaska Natives (NHAIAN), non-Hispanic Asian or Pacific Islanders (NHAPI), and Hispanic and/or Latino Americans (HL) between 1999 and 2019.

Methods:
Death certificate data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database were examined to determine all-cause PE mortality trends from 1999 to 2019 among adults older than twenty-five years old. The annual mortality rates were calculated per 100,000 population and age-adjusted based on the US population in the year 2000. The annual percentage change (APC) with corresponding 95% confidence intervals (CIs) were calculated to determine trends.

Results:
While overall AAMR decreased from 14.7 to 13.5 (APC -0.4 [95% CI -0.6 to -0.2) between 1999 and 2013, overall AAMR increased from 13.5 to 14.5 (APC 1.3 [95% CI 0.7 to 1.9]) between 2013 and 2019. NHAIAN AAMR increased from 9.68 to 12.09 (APC 1.2 [95% CI 0.5 to 1.9]) between 1999 and 2019. Among NHAPI, AAMR fluctuations prior to 2016 were not statistically significant. NHAPI AAMR increased from 3.81 to 4.58 (APC 6.2 [95% CI 0.5-12.3]) between 2016 and 2019. Among HL, AAMR decreased from 8.91 to 8.19 (APC -0.5 [95% CI -0.8 to -0.1]) between 1999 and 2019.

Conclusions:
Despite significant improvements in PE risk stratification and clinical management, PE related mortality increased significantly among NHAIAN between 1999 and 2019 and NHAPI between 2016 and 2019. The only racial cohort with a statistically significant reduction in AAMR during the entire study period was HL.
Abstract 11296: Short-Term Low-Saturated Fat Diet Compared to High-Saturated Fat Diet in Patients with Hypertriglyceridemia: Lipids and Lipoproteins Associated with Monocyte Phenotypic Changes
Authors: lian zeqin , Perrard Xiaoyuan , Antony Antu , Perrard Xiaoyuan , Saeed Anum , Jia Xiaoming , Hussain Aliza , Hoogeveen Ron C , Ballantyne Christie M , Wu Huaizhu , OBrien Veronica , Xu Lu , Zhang Bingqian
Published: March 2022

Background:
Monocyte phenotypic changes play a pivotal role in atherogenesis and can be induced by plasma lipids. We analyzed associations of monocyte phenotypes with lipid profiles and the potential of predicting monocyte phenotypes by lipid variables in subjects with hypertriglyceridemia (HTG) after short-term intake of low-saturated fat diet (LSFD) and high-saturated fat diet (HSFD).

Method:
Subjects with HTG (n=19, 10 men and 9 women, aged 53.9±13.7 years) received isocaloric LSFD (~25% of calories from fat, 5% from saturated fat) and HSFD (~52% of calories from fat, 25% from saturated fat) in randomized order for 4 days (days 1-4) and a test meal on day 5, separated by a 4- to 6-week washout period. Blood was taken on day 1 fasting before the diets and on day 5 fasting and 4 and 6 hours after the test meal to examine lipoprotein profile by enzymatic assay, fatty acids by nuclear magnetic resonance spectroscopy, and monocyte phenotypes by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression models were built to identify influential lipid variables for key monocyte markers that responded differently to the two diets.

Results:
LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride (TG), VLDL-TG, and LDL-TG and fasting and postprandial total cholesterol and LDL-cholesterol and altered fatty acid composition, with reduced saturated fatty acids (SFAs) but increased polyunsaturated fatty acids (PUFAs). Compared to HSFD, LSFD reduced monocyte lipid accumulation and levels of several surface markers involved in monocyte adhesion and migration including CD11c, a β2 integrin, on intermediate monocytes. Using the LASSO regression models, we identified that total cholesterol, LDL-TG, and apoB were positively correlated and n-3 PUFAs negatively correlated with lipid accumulation in intermediate monocytes and that total TG, LDL-TG, and apoCIII were positively correlated with CD11c levels on intermediate monocytes.

Conclusions:
In subjects with HTG, short-term LSFD compared to HSFD improves lipid profiles and monocyte phenotypes. We also identified specific plasma lipid parameters that may be reliable predictors for and contribute to specific monocyte phenotypic changes in HTG.
Abstract 11303: Reduced Level of ErbB Receptors in Non-Myocyte Left Ventricular Cells in Patients with Diabetes Mellitus Undergoing Coronary Artery Bypass Grafting Surgery Contributes to Vascular Dysfunction
Authors: Robich Michael P , Kosta Angela , Carver Joshua , Jackson Teaka , Shevenell Bailey , deKay Joanne T , Sawyer Douglas , Ryzhov Sergey V
Published: March 2022

Introduction:
ErbB signaling contributes to the regulation of vascular function through endothelial cell differentiation, proliferation, survival, and regulation of barrier integrity. Patients with diabetes (DM) are at an increased risk for endothelial dysfunction and worse outcomes after CABG. We investigated the level of ErbB expression on CD31 endothelial cells and CD105+ cells in DM and non-DM patients undergoing CABG.

Methods:
With IRB approval, left ventricular (LV) epicardial biopsies and blood samples from 25 patients (non-DM=9, DM=16), were obtained during surgery. Flow cytometry was used to determine the cell surface expression of ErbB receptors on cardiac endothelial and CD105+ cells isolated from the LV. Subpopulations of white blood cells were determined in blood samples. Plasma levels of IL-6, IL-8, and TNFα were measured.

Results:
Lower levels of ErbB1 and ErbB2 receptors expression on endothelial cells isolated from LV biopsies were found in patients with DM compared to non-DM control, and the expression of ErbB receptors negatively correlated with HgbA1c level. There were fewer CD105+ cells in DM patients (122 vs 153 cell/mg tissue, P=.021). Trends toward a negative association were found between the expression of ErbB2 in CD105+ cells and the number of neutrophils, as well as, HgbA1c level. No differences were found between DM and non-DM patients in the number of white blood cell subsets or plasma levels of IL-6, IL-8 and TNFα.

Conclusions:
We demonstrated that DM and high glucose blood levels are associated with reduced expression of ErbB1 and ErbB2 on endothelial cells and decreased number of CD105+ cells in the LV. Cardiac CD105+ are endothelial progenitor cells that differentiate in response to ErbB ligands. A decreased pool of CD105 endothelial progenitors in combination with down-regulation of ErbB1 and ErbB2 receptors in endothelial cells represent a novel mechanism for vascular dysfunction and adverse remodeling seen in diabetic patients.
Abstract 11305: Protective Effects of Homoarginine on Cardiovascular Function in a Mouse Model of Chronic Kidney Disease
Authors: Ding Billy , Raidah Anisa , Schram Eric , Kaungumpillil Neil , Singh Mohnish , Savinova Olga V
Published: March 2022

Introduction:
The level of homoarginine (hArg) in plasma correlates inversely with cardiovascular and renal disease. However, the cardioprotective mechanism of hArg in renal disease is currently unknown. In this study, we assessed hArg’s effects on cardiovascular function in mice with chronic kidney disease (CKD).

Hypothesis:
We have previously reported that hArg reduces fibrosis and helps preserve ejection fraction in a model of coronary artery disease. We now hypothesize that hArg supplementation will 1) decrease cardiac and renal fibrosis and inflammation in a model of CKD, 2) preserve cardiac geometry and function, 3) increase renal artery blood flow, and 4) increase survival.

Methods:
The mice used in this study had a mutation in the low density lipoprotein receptor on the C57BL/6 genetic background. Mice of both sexes (n=28) were fed a standard rodent diet supplemented with 0.1% (F) and 0.2% (M) adenine to induce CKD. Mice were randomly assigned to 14 μg/ml hArg (in drinking water) or placebo (PBO). Cardiac structure and function as well as renal blood flow were measured via high frequency ultrasound (Vevo 3100, VisualSonics).

Results:
LV geometry data of hArg treated male mice showed increased left ventricular (LV) mass (p<0.05) with normal LV internal diameter and increased LV wall thickness (p<0.01). In terms of cardiac function, ejection fraction (EF, p<0.05), fractional shortening (p<0.01), and cardiac output (p<0.01) were also increased in hArg treated male mice compared to placebo. No differences in renal blood flow were observed. Survival was not affected by hArg. Additionally, we observed decreased food consumption (p<0.01) and fecal output (p<0.001) in hArg treated mice with no difference in urine output compared with placebo.

Conclusion:
hArg treated male mice developed physiologic cardiac hypertrophy with preserved EF in the absence of LV dilation. Additionally, hArg affected the metabolic state of treated mice reflected in food consumption.
Abstract 11309: Significance of Blood Pressure Drops in Patients Hospitalized for Acute Heart Failure: A Patient-Level Analysis of 4 Randomized Placebo-Controlled Serelaxin Trials
Authors: Grand Johannes , Miger Kristina , Sajadieh Ahmad , Kober Lars , Torp-Pedersen Christian , Ertl Georg , Lopez-sendon Jose L , Maggioni Aldo P , Nielsen Olav W
Published: March 2022

Introduction:
Hypotensive events and drops in systolic blood pressure (SBP-drop) are frequent in patients with acute heart failure (AHF). We investigated SBP-drop and associations with outcomes and whether treatment with the vasodilator serelaxin affected the association between SBP-drops and outcomes.

Methods:
Analyses of data from four randomized, controlled trials investigating serelaxin as an intervention in patients hospitalized with AHF. Main inclusion criteria were SBP 125-180 mmHg, pulmonary congestion, elevated NT-proBNP. SBP-drops (predefined as an SBP-value below 100 mmHg and/or a drop of 40 mmHg from baseline) were prospectively registered during the first 48 hours of hospitalization. Outcomes were a composite outcome (worsening heart failure, hospital readmission for heart failure or all-cause mortality through 14 days) and 180-day mortality.

Results:
Overall, 2558/11226 (23%) patients had an SBP-drop, with a median time from randomization to event of 15 (6-25) hours. In multivariable analyses, SBP-drop was associated with 180-day mortality (hazard ratio 1.21, 95% CI 1.05-1.39; p=0.009) and the composite outcome (1.29 (1.13-1.49); p<0.001). Treatment-allocation interacted significantly on the relationship between SBP-drops and outcomes (p-interaction=0.003 for composite outcome, p-interaction=0.11 for 180-day mortality). In patients treated with placebo (n=5141), there was a strong association between SBP-drops and the composite outcome (HR: 1.46, 95% CI 1.19-1.79), p=0.0003), but no significant association in patients treated with serelaxin (HR 1.18, 95% CI 0.97-1.42, p=0.10) (Figure).

Conclusions:
SBP-drops in hospitalized patients treated for AHF is an independent risk factor for adverse short- and long-term outcomes, and its occurrence highlights the need for careful monitoring and urgent treatment. However, in patients treated with serelaxin under careful observation, SBP-drops were not associated with worse outcome.
Abstract 11311: Geographic Variation and Temporal Trends in Management and Outcomes of Cardiac Arrest Complicating Acute Myocardial Infarction in the United States
Authors: Patlolla Sri , Atreya Auras R , Vallabhajosyula Saraschandra
Published: March 2022

Introduction:
Regional variation in the uptake of newer techniques, procedures, and management strategies have been previously reported with acute cardiac care. Limited contemporary information exists on regional differences in the care of acute myocardial infarction (AMI) patients with cardiac arrest (CA).

Methods:
Using the National Inpatient Sample (2000-2017), we identified adults with AMI and concomitant CA admitted to the United States census regions of Northeast, Midwest, South, and West. Clinical outcomes of interest including in-hospital mortality, use of coronary angiography, percutaneous coronary intervention (PCI), mechanical circulatory support (MCS), hospitalization costs, and length of stay were compared across these four regions.

Results:
Of 9,680,257 admissions for AMI, 494,083 (5.1%) had concomitant CA. The prevalence of CA in AMI was highest in the West (6.0%) compared to the Northeast (4.4%), Midwest (5.0%), and South (5.1%), p<0.001. Admissions in the West had higher rates of STEMI presentation, cardiogenic shock, multiorgan failure, mechanical ventilation, and hemodialysis. Northeast AMI-CA admissions had lower use of coronary angiography (52.0% vs. 67.9% vs. 60.9% vs. 61.5%), PCI (38.7% vs. 51.9% vs. 44.8% vs. 46.7%), and MCS (18.4% vs. 21.8% vs. 18.1%, vs. 20.0%) compared to the Midwest, West and South (all p<0.001). Compared with the Northeast, adjusted in-hospital mortality for AMI-CA was higher in the Midwest (odds ratio [OR] 1.06 [95% confidence interval {CI} 1.03-1.08]; p<0.001), South (OR 1.11 [95% CI 1.09-1.13]; p<0.001), and highest in the West (OR 1.16 [95% CI 1.13-1.18]; p<0.001). Temporal trends showed a decline in in-hospital mortality except in the West, which showed a slight increase. Compared to other regions, AMI-CA admissions from the Northeast had longer in-hospital stays and less frequent palliative care consultations (all p<0.001). Admissions in the West had higher rates of palliative care consultations, DNR status, and highest hospitalization costs.

Conclusions:
We identified significant regional disparities in the management and outcomes of AMI-CA. Efforts to improve and provide uniform care for AMI-CA across regions may be essential.
Abstract 11313: Pericarditis Recurrence After Initial Uncomplicated Clinical Course
Authors: Abbate Antonio , Vecchie Alessandra , Damonte Juan Ignacio , chiabrando juan guido , DELL MEGAN S , Bonaventura Aldo , VAN TASSELL Benjamin W , Berrocal Daniel , Gal Tamas S , Abbate Antonio
Published: March 2022

Introduction:
Acute pericarditis is an inflammatory disease associated with a non-negligible risk of acute complications and future recurrence. The exact incidence of pericarditis recurrence in patients with a first uncomplicated clinical course is, however, unknown.

Objectives:
We sought to evaluate the incidence and clinical predictors of recurrence after a first episode of acute uncomplicated pericarditis in a large urban hospital in the USA.

Methods:
We conducted a retrospective review, through electronic health records, to complete a database that includes patients admitted with a first episode of acute pericarditis (according to ESC criteria) and then selected only those with uncomplicated course (without in-hospital death, large pericardial effusion [>20 mm] or tamponade, constriction, or failure of treatment) at the VCU Medical Center (Richmond, VA) between 2009 and 2018.

Results:
A total of 240 patients met acute pericarditis criteria: 174 (72%) patients had an uncomplicated course (median age was 50 [interquartile range 34 to 62] years, 45% females, 51% Black). Pericarditis was considered idiopathic in 89 patients (51%). During a median follow-up time of 184 [17- 434] days, 23 (13%) patients experienced at least one episode of recurrent pericarditis. When compared with those without recurrence, patients with recurrent pericarditis were more frequently females (15 [65%] vs 63 [42%], p=0.035) and had a higher prevalence of subacute/delayed presentation (defined as symptoms over several days without a clear-cut acute onset) (3 [13%] vs 1 [0.7%], p=0.008). There were no other clinical (including the use of anti-inflammatory therapies and pericarditis etiology) or laboratory differences between those with and without pericarditis recurrence at follow-up. At multivariate logistic regression analysis only subacute presentation remained predictor of recurrence at follow-up (odds ratio 20, 95% confidence interval [1.81-198.11], p=0.014).

Conclusions:
Approximately one every six patients with an acute pericarditis experience a recurrence over a 6-month median follow-up despite an initial uncomplicated course. Subjects with subacute presentation were at significantly higher risk of recurrence.
Abstract 11319: Success and Complication Rates in Cardiac Implantable Electronic Device (CIED) Laser Lead Extractions: A Systematic Review
Authors: Herman Josh E , Somanader Deborah , Ishaq Laith , Abdelaal Ahmed , Ramendra Rayoun , Mehra Vrati , Morris Andrew
Published: March 2022

Introduction:
Laser extraction sheaths are a valuable tool for complex CIED lead extractions. While there is evidence to suggest they have a higher complication rate than simple traction, there has been no systematic review of the literature regarding the success and complication rate associated with laser lead extractions.

Objective:
To conduct a systematic review investigating success and complication rates of CIED lead extractions using laser sheaths.

Methods:
A search was performed of studies published between January 1, 2000-August 29, 2019 indexed on Medline, EMBASE and Cochrane. Inclusion criteria were: (a) transvenous removal of ICD, pacemaker or CRT device leads, (b) Age≥18, (c) n>100 patients. Exclusion criteria were: (a) generator only procedures, (b) planned surgical extractions, (c) data prior to 2000. From these studies, we further selected papers containing laser lead extractions only, or laser-only cohorts, that reported on our outcomes.

Outcomes:
Complete procedural success, major and minor complications and procedure-related mortality.

Results:
2307 abstracts were screened after de-duplication resulting in 164 papers. Of these papers, 11 were selected based on our inclusion criteria. All included studies follow the Heart Rhythm Society 2009 and 2017 or North American Society of Pacing and Electrophysiology 2000 guidelines criteria for extraction, major complications, minor complications and procedural success. Complete procedural success was reported by 9 studies which ranged from 89.26-100%; median 93.5% (IQR 89.26-97.56%). All 11 studies reported major complications which ranged between 1.08-6.25%; median 1.98% (IQR 1.50-3.57%). 8 reported minor complications which ranged from 1.09-5.69%; median 4.52% (IQR 3.80-4.94%). Procedure-related mortality was reported by 10 studies which ranged from 0-2.68%; median 0.10% (IQR 0.00-0.48%), while all-cause mortality during hospitalization was reported by 7 studies ranging from 0-2.17%; median 0.23% (IQR 0.00-1.18%).

Conclusion:
Laser lead extraction is associated with a high success rate of complete removal. Mortality rates due to procedure related factors are very low, however major and minor complications are not uncommon.
Abstract 11320: Ablation of Sam68 in Cardiomyocytes Attenuates Cardiac Hypertrophy but Exacerbates Heart Failure
Authors: Jiang Ying , Xu Shiyue , Zhou Junlan , Boriboun Chan , Han Chaoshan , Ma Wenxia , Qiao Aijun , Qin Gangjian
Published: March 2022

Background & Hypothesis:
Src-associated-in-mitosis-of-68-kDa (Sam68) is a pleotropic adaptor protein shown to regulate signal transduction, RNA splicing, cell cycle, differentiation, and energy metabolism. Its function in the heart has never been studied. We hypothesize that Sam68 regulates cardiac hypertrophy and heart failure.

Methods & Results:
Pressure overload was induced by Ang II infusion (via osmotic pump) in 12-week-old male Sam68
-/-
, Sam68
+/-
, and WT littermates, followed by weekly assessments with echocardiography; Sam68
-/-
mice displayed attenuated left ventricular (LV) wall thickness compared to Sam68
+/-
or WT littermates. We then generated Sam68
floxed
mice and, by crossing with α-MHC-Cre transgenic (Cre
Tg
) mice, obtained cardiomyocyte-specific Sam68 knockout (Sam68
CM-KO
) mice. Consistently, Ang II-induced LV wall thickening was attenuated in Sam68
CM-KO
mice compared to Cre
Tg
littermates, confirming an autonomous role of Sam68 in promoting cardiac hypertrophy. Interestingly, in the surgically-induced transverse-aortic-constriction (TAC) model, Sam68
CM-KO
mice, while had an overall lesser LV wall hypertrophy over the course of 6 weeks, displayed higher rates of immediate post-surgery mortality and later-stage LV dilation and ejection-fraction drop, than Cre
Tg
littermates. The Sam68
CM-KO
mouse hearts showed smaller cross section area, fibrosis area, and cardiomyocyte size than Cre
Tg
mouse hearts. To gain mechanistic insights, we engineered a lentiviral vector coding for a Sam68 shRNA, which knocked down Sam68 protein expression in H9C2 cells (H9C2
Sam68KD
) by more than 90% (after selection). Sam68 knockdown led to a marked reduction in the expression of Raptor (by >50%), Rictor (by >50%), and ATG13 (by >80%) proteins, but no change in the level of mTOR protein or the mRNA expression of Raptor, Rictor, and ATG13. Furthermore, in H9C2
Sam68KD
, starvation-induced autophagy flux was increased as shown by elevated LC3II/LC3I ratio with Bafilomycin A treatment.

Conclusions:
Sam68 promotes cardiac hypertrophy and protects against heart failure likely through the activity of mTOR complexes.
Abstract 11327: Relationship of Neighborhood Socioeconomic Deprivation with Outcomes of a Comprehensive STEMI Protocol
Authors: Huded Chetan , Dalton Jarrod , Kumar Anirudh , Krieger Nikolas , Kassis Nicholas , Phelan Michael , Kravitz Kathleen , Reed Grant W , Krishnaswamy Amar , Kapadia Samir R , Khot Umesh N
Published: March 2022

Introduction:
Social determinants of health have an established impact on cardiovascular outcomes. STEMI quality improvement programs have resulted in reductions in door to balloon time (D2BT) and improved STEMI outcomes nationally. We evaluated whether a comprehensive STEMI protocol (CSP) improves care and outcomes in patients with moderate and high socioeconomic deprivation.

Methods:
Patients with STEMI treated with PCI at a single tertiary care hospital before (1/1/11-7/14/14, n=674) and after (7/15/14-7/15/19, n=1087) implementation of a CSP were included. Patients were stratified into low (
<
50
th
percentile), medium (51-90
th
percentile), and high (>90
th
percentile) deprivation groups based on census block group level area deprivation index. Outcomes were D2BT and mortality.

Results:
Neighborhood deprivation was 29.0% low (174 pre-CSP, 338 post-CSP), 40.8% moderate (268 pre, 450 post), and 30.2% high (232 pre, 299 post). Female sex (low 28.3%, moderate 31.9%, high 38.6%, p=0.001) and black race (2.5%, 20.7%, 61.8%, p<0.001) were associated with higher levels of deprivation. Improvements in median D2BT were observed in all deprivation groups after CSP implementation (Figure). Risk-adjusted median D2BT among ER/hospital patients from higher neighborhood deprivation levels was significantly non-inferior (non-inferiority limit = 5m) to those from lower deprivation levels after CSP implementation. In-hospital mortality was similar before and after CSP implementation in the low deprivation group (4.6% vs. 3.6%, p=0.56), and decreased significantly in moderate/high deprivation groups (7.0% vs. 3.1%, p=0.001).

Conclusions:
A CSP was associated with improvements in D2BT across all deprivation groups and a substantial mortality reduction in moderate/high deprivation groups. Standardized quality improvement initiatives may mitigate social determinants of health in time-sensitive high acuity conditions such as STEMI.
Abstract 11332: Integration of Protein Interactome Networks with Congenital Heart Disease Variants Reveals Candidate Disease Genes
Authors: Gonzalez Teran Barbara , Pittman Maureen , Thomas Reuben , Felix Franco , Richmond-Buccola Desmond , Choudhary Krishna , Moroni Elisabetta , Giorgio Colombo , Padmanabhan Arun , Costa Mauro , Huang Yu , Alexanian Michael , Lee Clara , Cole Bonie , Samse-Knapp Kaitlen , McGregor Michael , Gifford Casey , Huttenhain Ruth , Gelb Bruce , Conklin Bruce , Black Brian L , Bruneau Benoit , Krogan Nevan , Pollard Katherine , Srivastava Deepak
Published: March 2022

Congenital heart disease (CHD) is present in 1% of live births, yet despite large-scale genomic sequencing efforts, identification of causal mutations remains a challenge. We hypothesized that genetic determinants for CHDs may lie in the protein interactomes of GATA4 and TBX5, two transcription factors whose mutation cause CHDs. Defining the GATA4 or TBX5 interactomes in human cardiac progenitors via affinity purification-mass spectrometry and integrating the results with genetic data from the
Pediatric Cardiac Genomic Consortium
revealed an enrichment of
de novo
variants associated with CHD. A consolidative score that prioritized interactome members based on variant, gene, and proband features identified likely CHD-causing genes, including the epigenetic reader GLYR1. GLYR1 and GATA4 widely co-occupied and co-activated cardiac developmental genes, and the GLYR1 missense variant identified disrupted interaction with GATA4 and impaired transcriptional co-regulation in cardiomyocyte differentiation in vitro and cardiogenesis in vivo. This integrative proteomic and genetic approach provides a framework for prioritizing and interrogating the contribution of genetic variants in disease.
Abstract 11335: Does Reduced Parasympathetic Heart Rate Variability Promote Obesity in Children?
Authors: Kaefer Lisa Maria M , Henderson Mélanie , McGrath Jennifer J , Poirier Paul , Van Hulst Andraea , Kakinami Lisa , Mathieu Marie-Eve , SAADE Marie-Beatrice , Paradis Gilles , Barnett Tracie A
Published: March 2022

Introduction:
Considering the contribution of the autonomic nervous system (ANS) in regulating both energy expenditure and energy intake, assessment of heart rate variability (HRV) may elucidate the etiology and adaptive processes in the development of obesity. Variations in the cardiac ANS are associated with changes in energy balance and eating behaviours, highlighting the potential key function of the ANS in the etiology of obesity. While it is broadly accepted that obesity impacts HRV, potential impacts of HRV patterns on obesity remain unexplored. We hypothesize that certain HRV patterns increase risk of excess weight in children.

Methods:
Participants included 406 White youth from the QUALITY cohort (56% boys). Children were considered at risk of CVD due to confirmed parental obesity status. Time- and frequency-domain HRV indices derived from short-term ECG recordings (SDNN, RMSSD, pNN50, LF, HF, and LF/HF ratio) were analyzed at baseline (mean = 9.6 years, SD = 0.9). Adiposity at 2-year follow-up was evaluated through dual-energy X-ray absorptiometry. Total body fat (BF) and BF distribution were captured; central adiposity was estimated using the android-to-gynoid ratio. Prospective associations between HRV at baseline and adiposity at 2-year follow-up were estimated using regression models including weights for well-established confounders (difference in adiposity measures over time, sex, age, sexual maturity, and physical activity).

Results:
8-10 year olds with a sympathovagal imbalance described by a sympathetic predominance (LF/HF) presented with higher BF (β = 3.32, p < 0.001) and higher android-to-gynoid ratio (β =0.03, p<0.001) at age 10-12 years. Furthermore, lower levels of parasympathetic indices at age 8-10 years predicted higher BF (RMSSD: β = -0.09, p < 0.01; pNN50: β = -0.13, p < 0.01) and higher android-to-gynoid ratio (RMSSD: β -0.001, p < 0.05; pNN50: β = -0.001, p < 0.01) two years later.

Conclusions:
Impaired cardiac ANS modulation appears associated with the occurrence of childhood obesity two years later. A sympathetic predominance paired with reduced parasympathetic indices in otherwise healthy children may foreshadow pathophysiological processes that lead to obesity and may help to identify intervention targets.
Abstract 11337: Sensitivity Analysis of an Electronic Health Record-Based Algorithm to Facilitate Detection of Familial Hypercholesterolemia: Results in Genetically Confirmed Familial Hypercholesterolemia
Authors: Mohammadnia Nieky , Bax Willem A , cornel Jan
Published: March 2022

Introduction:
Familial hypercholesterolemia (FH) is a genetic disorder resulting in elevated LDL-C levels and increased risk of cardiovascular disease. Algorithms have been developed to facilitate FH detection. We previously developed a continuous, electronic health record (EHR)-based algorithm using the Dutch Lipid Clinical Network (DLCN) criteria, with automated correction of LDL-C levels for use of lipid-lowering-therapy (LLT). In this study, we performed a sensitivity analysis of the algorithm in patients with previously genetically confirmed FH.

Methods:
We selected all patients with genetically confirmed FH, seen during 2018 and 2019. DLCN scores were calculated before and after correction for LLT at the most recent visit. The primary outcome was the number of FH patients with DLCN criteria ≥6 points for LDL-C (which would have been an indication for genetic testing) before and after correction for LLT. Secondary endpoint was the additional number of patients with ≥6 points after also adding data on patient- and family history.

Results:
We included 222 patients with genetically confirmed FH; mean (SD) age: 50 (17) years; female: n=134 (60,4%). In total, 210 patients (94,6%) used some type of LLT. Mean (SD) LDL-C was 3,0 (1,4) mmol/L before correction for LLT and 7,5 (3,7) mmol/L after correction for LLT. Before correction for LLT, the algorithm identified 3 patients (1,4%) with ≥6 DLCN points, increasing to 59 patients (26,6%) after correction for LLT and to 76 patients (34,2%) after adding data on patient-, and family history.

Conclusion:
We conclude that, even after correction for LLT and addition of data on patient-, and family history, the sensitivity of a DLCN-based algorithm appeared relatively low in a population with genetically confirmed FH. Correction for LLT is important to increase sensitivity of the algorithm. Interestingly, FH detection algorithms inevitably rely on phenotypical characteristics of patients, whereas the present data show that genotypical FH does not necessarily express as phenotypical FH recognized by the DLCN-based algorithm. These data highlight the need for improvement of the DLCN-based algorithm and the importance of cascade testing for FH.