bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10986: Use of the “Pill in the Pocket” Approach for Atrial Fibrillation Termination as Determined from the Antiarrhythmic Medication for Atrial Fibrillation (AIM-AF) Study: A Physician Survey on the Prescription of Antiarrhythmic Drugs in the USA and Europe
Authors: Reiffel James A , Blomstrom-Lundqvist Carina , Boriani Giuseppe , Goette Andreas , Kowey Peter R , Merino Jose L , Piccini Jonathan P , Saksena Sanjeev , Camm Alan
Published: March 2022

Introduction:
USA and European guidelines recognize that an oral antiarrhythmic drug (AAD) for acute conversion of symptomatic atrial fibrillation (AF) can be effective in AF termination, provided a drug with rapid effect is used and safety precautions are followed. How the ‘pill in the pocket’ (PIP) approach is used in physicians’ practices has not been examined. We performed a survey to understand clinicians’ AAD PIP prescription practices in the USA and Europe.

Methods:
An online physician survey of 629 cardiologists and interventional electrophysiologists (EPs) was conducted in the USA, Germany, Italy, Sweden, and the UK. Respondents were treating ≥10 AF patients who received AAD therapy and/or had received or were referred for ablation. This exploratory survey contained 96 questions on physician demographics, AF types, and drug treatment practices.

Results:
Respondents in the USA and Europe, reported PIP use in 24% and 19% of their patients, respectively. Frequency of PIP use was greatest in paroxysmal AF without structural heart disease (SHD; 41%) vs paroxysmal AF with SHD (16%). In contrast to guideline recommendations, PIP was used in persistent AF (pers-AF) in 18% without SHD and in 12% with SHD. Use for pers-AF was highest in the USA and by EPs. For AF without SHD, class IC AADs were used most often (flecainide, 77%; propafenone, 32%), but there was notable use of amiodarone (Amio) (13%) and sotalol (Sot) (13%), the latter more in the USA and by EPs. For AF with SHD, class IC use diminished considerably. PIP was given with a rate control agent (new or chronically, beta blocker > calcium channel blocker) in 71%, while 29% gave PIP AADs without concomitant rate control agents. Optimal arrhythmia frequencies for PIP were felt to be: monthly (13%), q2-3 months (46%), q4-6 months (26%), q7-12 months (11%), and yearly or less (4%), with no notable differences between the USA and Europe, or cardiologists and EPs.

Conclusions:
Our survey revealed that clinicians in both the USA and Europe use PIP in almost a quarter of their patients, mostly for AF with minimal or no heart disease (guideline appropriate). However, Amio and Sot use for PIP and use of PIP for pers-AF was evident, highlighting the need for further interventions on the appropriate and optimal use of the PIP strategy.
Abstract 10987: Effect of False Lumen Status on Systemic Inflammatory Response Induced by Acute Aortic Dissection
Authors: Kimuira Naoyuki , Machii Yojiro , Matsuda Akio , Hori Daijiro , Shiraishi Manabu , Matsumoro Kenji , Yamagishi Atsushi , TANAKA MASASHI
Published: March 2022

Introduction:
Acute aortic dissection (AAD) frequently induces a systemic inflammatory reaction. However, the influence of dissection morphology on immune response remains to be elucidated.

Hypothesis:
False lumen (FL) status influences peripheral blood cytokine expression in patients with AAD.

Methods:
Serum concentrations of 29 cytokines were measured on admission (within 48 hours of symptom onset) in 44 patients with AAD. None were suffering shock or aortic rupture and none had an autoimmune or hematologic disease. The 44 patients were divided into 2 groups based on FL patency: those with a thrombosed FL (Group T [n=21]: median age, 76 years) and those with a partially thrombosed or fully patent FL (Group P [n=23]: median age, 61 years). Stanford classes did not differ between these groups (Group T: type A, n=7; type B, n=14 vs. Group P: type A, n=14; type B, n=9) (p=0.068). Laboratory values, including cytokine concentrations, were compared between these groups and a control group (Group C—patients with a non-ruptured atherosclerotic thoracic aortic aneurysm—n=20]: median age, 75 years) by Mann-Whitney test, with multiple comparisons subjected to Bonferroni correction.

Results:
Leukocyte counts (x10e3/μL) were increased in both groups (Group T: 9.5 [7.7, 11.7]; Group P: 14.0 [10.4, 18.0] vs. Group C: 5.8 [5.0. 7.1]) (both p<0.001), but CRP concentrations (mg/dL) were not (0.51 [0.15, 3.3], p=0.077 and 0.38 [0.10, 2.7], p=0.165 vs. 0.2 [0.1, 0.21]). D-dimer concentrations (μg/mL) were increased in Group P (28.8 [8.6, 108], p<0.001) but not in Group T (2.9 [1.5, 5.3], p=0.87) (vs. Group C: 2.5 [1.4, 4.9]). Seventeen cytokines [IFNγ, IL-2, IL-4, IL-17α, TNFα, etc.] did not differ significantly between the 2 AAD groups; 12 did differ significantly. The differentially expressed cytokines fell into 3 hierarchical clusters: cluster A (increased expression in both groups [G-CSF, IL-6, IL-10, IL-15]), cluster B (increased expression only in Group P [GM-CSF, IL-1Ra, IL-1b, IL-8, IL-12p70, IP-10], and cluster C (increased expression only in Group T [IL-5, VEGF]).

Conclusions:
A robust inflammatory response occurs regardless of FL status, but the response is somewhat attenuated in patients with a thrombosed FL vs. those with a patent FL.
Abstract 10988: Prevalence and Outcomes of Cardiac Amyloidosis in All-Comer Referrals for Bone Scintigraphy
Authors: Nitsche Christian , Mascherbauer Katharina , Wollenweber Tim , Koschutnik Matthias , Dona Carolina , Dannenberg Varius , Hofer Felix , Kammerlander Andreas , Traub-Weidinger Tatjana , Goliasch Georg , Hengstenberg Christian , Hacker Marcus , MASCHERBAUER Julia
Published: March 2022

Introduction:
The prevalence of cardiac amyloidosis (CA) in the general population as well as prognostic implications remain poorly understood.

Hypothesis:
We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals.

Methods:
Between 2010 and 2020, consecutive all-comers undergoing 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy were included retrospectively. CA was defined as positive cardiac tracer uptake (Perugini grade-1: subclinical CA; grade-2/3: clinical CA). All-cause mortality, cardiovascular (CV) death and hospitalization for heart failure (HHF) served as endpoints.

Results:
17387 scans from 11527 subjects (61±16 y/o, 63.0% female, 73.6% cancer) were analyzed. Prevalence of CA was 3.3% (n=376/11527; grade-1: 1.8%, grade-2/3: 1.5%), and was higher among cardiac vs. non-cardiac referrals (18.2% vs. 1.7%). In 4 individuals with >1 scan, progression from subclinical to clinical CA was observed. Cardiac biopsy revealed underlying transthyretin CA in 3 grade-1 patients. After a median of 6 years, clinical event rates were: 29.4% mortality, 2.6% CV death, and 1.5% HHF, all independently predicted by CA. Overall, adverse outcomes were driven by clinical CA (clinical vs. no CA, mortality: adjusted hazard ratio [AHR] 1.46 [95% confidence interval 1.12-1.90]; CV death: AHR 2.34 [1.49-3.68]; HHF: AHR 2.25 [1.51-3.37]). In non-cancer patients, subclinical CA had equally increased mortality to clinical CA (log-rank, p >0.05), presumably due to longer observation/life expectancy.

Conclusions:
CA was identified in a substantial number of consecutive DPD referrals and associated with adverse outcomes. Subclinical (grade-1) progressed to clinical (grade-2/3) CA at follow-up and both had similarly increased mortality among non-cancer patients. Thus, in grade-1, clarification of the underlying pathology using myocardial biopsy is indicated to enable timely targeted therapy.
Abstract 10994: The Interaction of the Transcriptional Coactivator P300 with the Chromatin Remodeling Factor Brg1 Increases the Acetylation of the Histone H3 Globular Domain in Heart Failure
Authors: uehara sho , Morimoto Tatsuya
Published: March 2022

Background:
Epigenetic regulatory mechanisms such as histone post-translational modifications are involved in the development of heart failure. Although the acetylation of tail domains, such as H3K9, has been extensively studied, that of H3K122, the globular domain, has received much less attention. Acetylation of the globular domain directly activates transcription by destabilizing histone-DNA binding. However, the mechanism of the acetylation of these domains during the transition from left ventricular hypertrophy (LVH) to heart failure (HF) remains unknown.

Methods and Results:
Primary cultured cardiomyocytes prepared from neonatal rats were treated with phenylephrine (PE). PE increased the acetylation of H3K9 and H3K122. The acetylation of H3K9 and H3K122 on the promoters of ANF and BNP , which are hypertrophic reaction genes, was increased in cardiomyocyte hypertrophy. To investigate whether the transcriptional coactivator p300 is involved in the acetylation of H3K9 and H3K122, p300 knockdown was used. p300 knockdown suppressed PE-induced cardiomyocyte hypertrophy and the acetylation of H3K9 and H3K122. In Dahl-salt sensitive rats,
in vivo
chromatin-immunoprecipitation assays revealed that the acetylation of H3K9 on the promoter of the hypertrophic response genes was significantly increased in LVH, but the acetylation of H3K122 was not increased in LVH. However, H3K122 acetylation was significantly increased in HF. On the other hand, there was no difference in the amount of p300 recruitment in LVH and HF. Interestingly, immunoprecipitation -WB showed that binding of p300 with BRG1, a key component of the SWI/SNF complex, was enhanced in HF. The recruitment of BRG1 was increased significantly in HF compared to LVH. Moreover, PFI-3, a BRG1 inhibitor, significantly suppressed PE-induced increases in cardiomyocyte surface area, the mRNA levels of ANF and BNP, and the acetylation of H3K9 and H3K122 in cultured cardiomyocytes.

Conclusion:
This study demonstrates that the acetylation of H3K122 is enhanced via the interaction of p300 and BRG1 in heart failure, providing novel insights into the epigenetic regulatory mechanism governing transcriptional activity in these processes.
Abstract 11001: Wnt/Planar Cell Polarity Pathway Mutations Are Over-Represented in Children with Concomitant Congenital Cardiac and Cleft Malformations
Authors: Toubat Omar , Munabi Naikhoba C , Craig David W , Magee William , Subramanyan Ram Kumar
Published: March 2022

Introduction:
We have demonstrated a high association between cleft lip and/or palate (CL/P) and outflow tract congenital heart disease (CHD) in the pediatric population. Despite this strong phenotypic association, the molecular genetics underlying these concomitant disease processes remains unclear.

Hypothesis:
Genomic profiling of concomitant outflow tract CHD+CL/P patients will unravel mutations in signaling pathways with overlapping importance in heart and palatal development.

Methods:
Patients with outflow tract CHD+CL/P and no previously known genetic syndromes or positive chromosomal microarrays at our institution between January 2004 and December 2018 were identified. Whole exome sequencing was performed on blood specimens collected from patients and phenotypically normal parents. Gene ontology and pathway analysis of de novo variants identified in probands was performed using PANTHER and DAVID databases and reinforced with a primary literature search. Functional assessment of non-canonical Wnt signaling variants was performed through siRNA-knockdown and wound-healing assays in murine myoblasts.

Results:
De novo loss-of-function mutations were observed in all 17 probands, in a total of 28 genes. Five genes (18%) have previously been implicated in both heart and palate development (CHD7, MED12, NDST1, GRHL2, SMARCA4). Three genes (11%) were mutated in more than one proband (CHD7, CELSR3, SAPCD2). Gene ontology and pathway analysis of deleterious de novo variants predicted involvement in binding (n=11, 39%), gene-specific transcription (n=9, 32%), and molecular and transcriptional function (n=8, 29%). The Wnt pathway (n=14, 50%) was the most strongly enriched signaling pathway, mutated in 10 (59%) probands, followed by Semaphorin and Endothelin signaling (n=2 variants, 7.1%, each). Knockdown of Wnt/PCP genes SAPCD2, CELSR3, and CCDC88C disrupted myoblast cellular migration
in vitro,
validating the functionality of these gene candidates.

Conclusion:
Our study is the first to characterize the genomic profile of patients with concomitant outflow tract CHD+CL/P. Excess de novo mutations in genes involved in Wnt pathway signaling suggests that this pathway plays a crucial role in CHD+CL/P disease pathogenesis.
Abstract 11011: Comparison of Prognostic Value of Liver Dysfunction Scores and Serum Cholinesterase Level in Acute Decompensated Heart Failure Patients with Preserved Left Ventricular Ejection Fraction: Insights from Pursuit-hfpef Registry
Authors: Kogame Takehiro , Seo Masahiro , Yamada Takahisa , Yano Masamichi , Hayashi Takaharu , Nakagawa Akito , Nakagawa Yusuke , Tamaki Shunsuke , YASUMURA YOSHIO , Hikoso Shungo , Sotomi Yohei , Sakata Yasushi ,   the OCVC-Heart Failure Investigator.
Published: March 2022

Background:
Cardiohepatic interactions have been a focus of attention in heart failure. Liver dysfunction scores such as Fibrosis-4 (FIB-4) index, albumin-bilirubin (ALBI) and nonalcoholic fatty liver disease (NAFLD) scores have been shown to be useful for predicting poor outcome in patients (pts) with heart failure. On the other hand, malnutrition is one of the most important comorbidities in patients with heart failure with preserved ejection fraction (HFpEF), and serum cholinesterase level (CHE) was reported to be associated with adverse prognosis. We sought to compare the prognostic value of liver dysfunction scores and CHE in HFpEF pts admitted for acute decompensated heart failure (ADHF).

Methods and Results:
Data were extracted from a prospective multicenter observational study (PURSUIT-HFpEF) in which collaborating hospitals in Osaka recorded clinical, echocardiographic, and outcome data of HFpEF pts with ADHF. We analyzed 737 pts who survived to discharge. CHE, FIB-4 index, ALBI and NAFLD scores were obtained just before the discharge. During a follow-up period of 1.8±1.0 years, 157 pts had all-cause death. At multivariate Cox analysis, CHE (p<0.0001) was independently and significantly associated with all-cause death after adjustment with important baseline clinical and study characteristics, although FIB-4 index, ALBI and NAFLD scores showed the association with all-cause death at univariate analysis. Receiver-operating characteristic curve analysis showed that CHE had the largest area under the curve for the prediction of all-cause death. Kaplan-Meier analysis revealed that the pts with lower CHE (<208 IU/L=median value) had a significantly higher risk of all-cause death than those with higher CHE (31% vs 11%, p<0.0001, adjusted hazard ratio 3.29 [95% CI 2.31 to 4.69]).

Conclusion:
CHE would be a more useful and simple prognostic marker for the prediction of total mortality than liver dysfunction scores in HFpEF pts with ADHF.
Abstract 11024: Interferon-Gamma Impairs Human Coronary Artery Endothelial Glucose Metabolism via Tryptophan Catabolism and Activates Fatty Acid Oxidization
Authors: Lee Laurel Y , Oldham William M , He Huamei , Wang Ruisheng , Mulhern Ryan , Handy Diane E , Loscalzo Joseph
Published: March 2022

Introduction:
Endothelial cells depend on glycolysis for much of energy production. Deranged endothelial glycolysis has been associated with various vascular pathobiologies. Interferon-gamma (IFN-γ) producing T-cells have been identified as the predominant pathologic cell subset in human atherosclerotic plaque. While the immunological consequences of these cells have been evaluated, their metabolic effects on endothelial cells remain unknown. The objective of this study was to determine the metabolic consequences of IFN-γ on human coronary artery endothelial cells (HCAEC).

Hypothesis:
We hypothesized that IFN-γ inhibits endothelial glucose metabolism and results in pathologic phenotypic changes in HCAEC.

Methods:
The metabolic effects of IFN-γ on primary HCAEC were assessed by unbiased transcriptomic and metabolomic analyses combined with real-time extracellular flux and molecular mechanistic studies. Relevant cellular phenotype was assessed by measuring endothelial intracellular cGMP content and wound healing capacity.

Results:
IFN-γ inhibited glycolysis of HCAEC by 20 % (
p =
0.006) via global transcriptional suppression of glycolytic enzymes resulting from decreased basal nuclear hypoxia inducible factor 1α (HIF1α) availability. HIF1α destabilization (FC 0.72;
p =
0.0039) was mediated by the sequestration of its binding partner HIF1β by aryl hydrocarbon receptor via a kynurenine surge (FC 6.24;
p
< 0.0001) resulting from IFN-γ-induced tryptophan degradation. Endothelial fatty acid oxidation (FAO) increased by 19% (
p =
0.014) with its inhibition leading to a 23% ATP deficit (
p
< 0.0001). These metabolic derangements were associated with pathologic endothelial phenotypic changes, including decreased intracellular cGMP by 29 % (
p
= 0.025) and impaired wound healing capacity by 38 % (
p
= 0.0098).

Conclusions:
IFN-γ impairs endothelial glucose metabolism via tryptophan catabolism destabilizing HIF1α and results in a metabolic shift toward increased FAO. These findings suggest a novel mechanistic basis for pathologic T-lymphocyte-endothelial interaction in coronary artery disease mediated by IFN-γ, linking endothelial glucose, amino acid, and fatty acid metabolism and their adverse endothelial functional consequences.
Abstract 11028: Gender Inequality in Enrollment in Late-Breaking Cardiovascular Clinical Trials
Authors: Kaur Gurleen , Holtzman Jessica , Power Juliette , Ambinder Daniel , Goyal Amit , Gulati Martha
Published: March 2022

Introduction:
Cardiovascular disease is the leading cause of mortality in both men and women. Prior studies have demonstrated the underrepresentation of women in published clinical trials, but to date no study has assessed inclusion of women in late-breaking clinical trials (LBCT) presented at national meetings.

Methods:
Using the American College of Cardiology’s 2021 Scientific Sessions’ LBCT, the inclusion of women was assessed. The inclusion to prevalence ratio (IPR) was calculated by dividing the percentage women participants in the trial by the percentage women in each disease population. IPRs less than 1 indicate under-enrollment of women. Of the 26 LBCT, 1 trial was excluded, as it exclusively enrolled women.

Results:
Inclusion of women ranged from 16.8% to 53.1%. The average IPR was 0.71 for all trials and did not vary based on single vs. multi-center, size, or funding source. The average IPR varied based on sub-specialty, with statistical differences noted between electrophysiology (EP) and heart failure (0.53 vs 0.86, p=0.02), as well as between EP and general/preventive (0.53 vs 0.72, p=0.04). The average IPR was significantly lower for procedural studies compared with medication trials (0.51 vs 0.73, p=0.02). There was no difference in IPR based on female authorship (Figure 1).

Conclusions:
LBCT can impact novel drug/device approval, indications, and patient management. Nonetheless, most LBCT under-enroll women. In particular, EP, interventional cardiology, and procedural LBCT have the lowest inclusion of women. These findings warrant further investigation into ways to increase enrollment of women, including potential requirements for consideration as LBCT by meeting organizers.
Abstract 11037: Procedural Success, Valve Hemodynamics and Outcomes in Patients with Moderate Aortic Stenosis Undergoing Supra-Annular Transcatheter Aortic Valve Replacement
Authors: Sharma Ravi , Laham Roger J , Sorajja Paul , Shah Binita , Garcia Santiago , Jain Renuka , Fender Eric , Philip Femi , Eisenberg Ruth , Chetcuti Stanley
Published: March 2022

Introduction:
Limited evidence supports the hypothesis that early treatment of symptomatic moderate aortic stenosis (AS) may be beneficial. We seek to study procedural success, valve hemodynamics and clinical outcomes in moderate AS patients who underwent transcatheter aortic valve replacement (TAVR) using a supra-annular self-expanding bioprosthesis.

Methods:
All patients in the STS/ACC/TVT Registry™ with Evolut R, PRO and PRO+ attempted procedures for indication of primary symptomatic (NYHA class II-IV) moderate AS were included. Moderate AS was defined as mean gradient ≥20 and <40 mm Hg, valve area >1.0 and <1.5 cm
2
, and Vmax >3 and <4 m/s. 2.9% of patients had concurrent severe aortic regurgitation at baseline. Valve-in-valve procedures were excluded. Site reported 30-day event rates are reported using Kaplan-Meier analysis. As a quality-of-life metric, KCCQ scores at 30 days and 1 year are compared to baseline scores using paired t-tests.

Results:
A total of 811 patients (62.1% men, 77.7 ± 8.7 years of age, STS-PROM score 5.3 ± 3.6, baseline LVEF 56.7 ± 13.3 %) were analyzed. The majority of patients underwent elective procedure (n=762, 94.0%) under conscious sedation (n=439, 54.3%) via iliofemoral approach (n=775, 95.6%). Successful device implantation, defined as correct valve positioning, was achieved in 99.3% of patients with low rates of intraprocedural complications (0.4%). Clinical events at 30 days were: all-cause mortality 1.4%, neurological events 2.5%, major bleeding 4.7% and conduction disturbance requiring pacer/ICD 16.1%. Valve hemodynamics improved post procedure compared to baseline (mean gradient 29.8 ± 4.9 to 8.4 ± 4.9 mm Hg, Vmax 3.5 ± 0.2 to 1.9 ± 0.5 m/s), with mean gradient sustained at 1 year (8.6 ± 4.4 mm Hg). Moderate/severe paravalvular regurgitation was present at similar levels at post procedure and 1 year (1.6% and 3.0%). A significant improvement in quality of life was noted from baseline KCCQ score to 30 days (Δ27.5 ± 25.5, 95% CI 25.4 - 29.5, p<0.001) and 1 year (Δ29.1 ± 26.1, 95% CI 26.2 - 32.1, p<0.001).

Conclusions:
Patients undergoing TAVR with a self-expanding bioprosthesis for symptomatic moderate AS have high procedural success with sustained improvements in valve hemodynamics and quality of life at 30 days and 1 year.
Abstract 11039: Platelets Contribute to Disease Severity in Covid-19
Authors: Barrett Tessa , Bilaloglu Seda , Cornwell Macintosh , Burgess Hannah , De Moura Virginio Vitor W , Drenkova Kamelia , Ibrahim Homam , Yuriditsky Eugene , Aphinyanaphongs Yindalon , Lifshitz Mark , Liang Feng Xia , Alejo Julie , Smith Grace , Pittaluga Stefania , Rapkiewicz Amy , Wang Jun , Iancu-Rubin Camelia , Mohr Ian , Ruggles Kelly , Stapleford Kenneth , Hochman Judith S , Berger Jeffrey S
Published: March 2022

Objective:
Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Platelets are key regulators of thrombosis, inflammation, immunity and are prime candidates for a role in the pathogenesis of COVID-19. The objective of this study was to analyze the platelet phenotype in COVID-19.

Approach and Results:
Severe acute respiratory syndrome
coronavirus
2 (SARS-CoV-2) is detected in human megakaryocytes and platelets in COVID-19 patients and following incubation with the virus
in vitro
. We show a direct interaction between SARS-CoV-2 and megakaryocytes that alters the platelet transcriptome and platelet activity. COVID-19 platelets are hyperreactive and have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. We find transcriptomic changes mediated by SARS-CoV-2 do not occur following exposure of megakaryocytes with a coronavirus responsible for the common cold, CoV-OC43. In a cohort of 3,915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication use, and biomarkers of inflammation and thrombosis, platelet count, size, and immaturity are each associated with increased critical illness and all-cause mortality.

Conclusions:
Our findings demonstrate that SARS-CoV-2 virions invade megakaryocytes and platelets, inducing alterations to the platelet transcriptome and activation profile, which correlate with critical illness and mortality in hospitalized COVID-19 patients.
Abstract 11049: Rare Genetic Variants in Individuals with Low ASCVD Risk and Hard Chd or High Coronary Artery Disease: Multi-Ethnic Study of Atherosclerosis
Authors: Shabani Mahsima , Dutta Diptavo , Post Wendy , Lowenstein Charles J , Ambale Venkatesh Bharath , Chatterjee Nilanjan , Budoff Matthew , Rich Stephen S , Rotter Jerome I , Arking Dan E , Lima Joao
Published: March 2022

Introduction:
Even though various risk estimators are widely used to predict atherosclerosis from subclinical levels to hard CHD, there is a remarkable proportion of low-risk individuals with inordinately high coronary artery calcification (CAC) or with hard CHD events. Rare pathogenic variants (<0.1%) in the atherosclerosis gene panel with larger effect sizes may predispose low-risk individuals to develop atherosclerosis.

Hypothesis:
There are rare pathogenic variants in the atherosclerosis gene panel in low-ASCVD-risk individuals with high CAC scores or hard CHD events than low-risk individuals with a CAC score of zero or no events.

Methods:
The MESA whole-genome sequencing data (2000-02) was evaluated to capture variants in 224 atherosclerosis-related genes. Coding variants with a frequency of <0.1% in each racial/ethnic group and damaging effects were assessed by the ClinVar and ACMG-AMP guidelines for pathogenicity. Participants with an ASCVD score of <7.5% were defined as low risk. Two different case groups were defined based on (1) hard CHD events and (2) CAC scores higher than the 90
th
percentile of age, sex, and race-adjusted reference scores. Associated control groups were age-, sex-, and race-matched participants with no CHD events or zero CAC score.

Results:
A total of 159 cases with high CAC and 1256 matched controls were evaluated within the low-risk group. In the case group, there were three rare, likely pathogenic variants (

LDLR
c.681C>G, p.D227E and c.2026G>A, p.G676S; and
AHI1
c.2168G>A, p.R723Q

)
. None of these variants were observed in the control group. A total of 86 cases had a hard CHD event, among whom two had rare, likely pathogenic variants (
KCNQ1
c.517G>A, p.A173T and
LDLR
c.1201C>G, p.L401V). None of the 1546 controls had these variants. The
LDLR
c.1201C>G variant is currently a variant of uncertain significance that would be likely pathogenic with the assumption of genotype-phenotype specificity [pathogenicity supporting criterion 4].

Conclusions:
We observed five likely pathogenic variants in atherosclerosis-related genes in low-risk individuals for ASCVD who had high CAC scores or hard CHD events. Rare variants with large effect sizes may unravel the missed risk prediction of a common trait like atherosclerosis.
Abstract 11054: A Novel Method of Conjunctival Vascular Screening to Detect Hemodynamic Alterations in Patients with Coronary Microvascular Disease
Authors: Mailey Jonathan A , Moore Julie S , Brennan Paul F , Jing Min , Awuah Agnes , McLaughlin James A , Nesbit Andrew A , Nesbit Andrew T , Spence Mark S
Published: March 2022

Introduction:
A large proportion of patients with cardiovascular disease (CVD) remain asymptomatic until presentation with myocardial infarction. Conventional CV risk assessment can be augmented by investigations such as CT coronary artery calcium scoring; but are limited by cost, availability and exposure to ionizing radiation.

This study utilizes the conjunctiva as a network of blood vessels that can be assessed non-invasively in order to compare hemodynamic parameters in patients with and without established coronary microvascular disease (MVD).

Methods:
We assessed the conjunctival microcirculation of patients diagnosed with angina undergoing invasive coronary angiography and physiological evaluation of epicardial stenoses and MVD. All patients had haemodynamically insignificant epicardial disease (FFR ≥0.80). Conjunctival imaging was performed using an adapted iPhone 11pro and slit-lamp biomicroscope. We compared a cohort of patients with MVD (IMR ≥25); to a group of controls without MVD (IMR <25).

Results:
A total of 54 patients were included (19 MVD and 35 controls).
Table 1
demonstrates a comparison of baseline demographics and hemodynamics between the groups. A total of 866 conjunctival vessels were analysed (366 MVD and 500 controls) and the differences in microvascular parameters between groups determined (
Table 2)
. Statistically significant differences were observed in axial velocity, cross sectional velocity and blood flow rate.

Conclusion:
This study demonstrates the ability to non-invasively detect abnormal microvascular function. The conjunctival microcirculation therefore has potential merit to complement conventional CV risk screening.
Abstract 11057: Measures of Heart Rate Variability as Predictors of Clinical Outcome in Patients with Chronic Heart Failure - Results from the Myovasc Study
Authors: Schuch Alexander , Zeid Silav , Buch Gregor , Velmeden David , Heidorn Marc , Mueller Felix , Troebs Sven-Oliver , Lackner Karl J , Gori Tomaso , Muenzel Thomas , Prochaska Juergen , Wild Philipp
Published: March 2022

Introduction:
Evidence supports a potential prognostic value of heart rate variability (HRV) in patients with chronic heart failure (HF). Comprehensive data comparing different domains of HRV in relation to clinical outcome in HF are scarce.

Methods:
Subjects with chronic HF (i.e. AHA stage C or D) from the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study, were analyzed. Individuals with pacemaker or atrial fibrillation were excluded. All participants received a highly standardized medical-technical examination during a five-hour visit in a dedicated study center. Data from 24-hour Holter ECG recordings were analyzed resulting in HRV markers from the time and frequency domain, and non-linear HRV measures. Information on clinical outcome, i.e. worsening of HF (WoHF), was derived from structured follow-up with subsequent validation and independent adjudication of endpoints. Random forest models were used to identify the most predictive marker of each HRV domain, which were further analyzed with multivariable Cox regression.

Results:
The analysis sample comprised 554 HF subjects (mean age: 66.4±9.9 years, 34.3% female sex) with HRV data. During a median observational period of 4.08 years (interquartile range 2.22; 5.22), 153 participants experienced WoHF. In random forest analyses, the rMSSD (time domain), high frequency power in normalized units (HF
nu
; frequency domain), and SD1/SD2 (non-linear measure) were ranked as most predictive HRV markers for WoHF in each HRV domain. Subsequent Cox regression analysis demonstrated that log(SD1/SD2) (hazard ratio (HR) per standard deviation 1.50, 95%CI 1.29;1.75; P<0.0001), HF
nu
(HR
SD
1.47, 95%CI 1.23;1.77; P<0.0001) and log(rMSSD) (HR
SD
1.36, 95%CI 1.17;1.57; P<0.0001) were strong predictors of HF outcome independent of age, sex, clinical profile, and medication. In Cox regression analysis with adjustment for NT-proBNP and the established HF risk score MAGGIC, HF
nu
(HR
SD
1.25, 95%CI 1.05;1.48; P=0.012) and log(SD1/SD2) (HR
SD
1.24, 95%CI 1.07;1.43; P=0.005) remained independent predictors of WoHF.

Conclusions:
Markers of HRV were identified as strong predictors for HF outcome independent of established risk markers, suggesting a potential to advance risk stratification.
Abstract 11060: Clinical Impact of the Barthel Index/Blood Urea Nitrogen Ratio to Predict the Post-Discharge Prognosis in Patients with Acute Decompensated Heart Failure
Authors: Ohashi Koichi , Abe Daisuke , Nagatomo Riki , Kato Taichi , Okouchi Mikiko , Aoyama Takunori , Hirano Hitoshi , Takayama Akira , Kimata Akira , Hattori Ai , Kuroki Norihiro , Suzuki Kou
Published: March 2022

Purpose:
Several clinical models and scales have been reported to predict prognosis of patients who have hospitalized due to acute decompensated heart failure (ADHF). It is known that high blood urea nitrogen (BUN) levels and low activities of daily living are associated with a worse prognosis in patients with HF. Barthel Index (BI) is an ordinal scale used to measure performance in activities of daily living and functional independence in the domains of personal care and mobility. The aim of this study was to investigate the association between BI/BUN ratio and the incidence of clinical outcomes in patients with ADHF.

Methods:
A cohort of 76 patients admitted to our institution from August 2019 to December 2019 due to ADHF was enrolled. We investigated the characteristics of these patients and BI at their discharge. Clinical outcome was major adverse cardiovascular event (MACE) which include cardiovascular death and re-hospitalization for worsening HF. We performed ROC analysis for MACE.

Results:
The patients had a mean age of 78.0 years and 61.8% were male. Incidence of MACE was 51.3% in entire patients. We explored the association between BI/BUN ratio and post-discharge MACE. Area under the curve of BI/BUN ratio for MACE was 0.66(95% CI: 0.54-0.78) and the cut off value was 2.01 (specificity 0.784, sensitivity 0.538). We divided patients into 2 groups according to cut off value; high BI/BUN (>2: n=48) and low BI/BUN (<2: n=28). During the follow up periods (193±118 days), incidence of MACE was significantly higher in low BI/BUN group than in high BI/BUN group (71.4% vs. 39.6%, p=0.007). Kaplan-Meier curve of MACE showed high BI/BUN was better outcome compared with low BI/BUN (p=0.002, between log-rank test). After adjustment of multiple cofounders, BI/BUN ratio was a negative independent predictor for MACE (OR: 0.26 per increase, 95% confidence interval: 0.13-0.54, p=0.0003).

Conclusion:
We suggest that low BI/BUN ratio predicts poor prognosis in patients admitted due to ADHF.
Abstract 11065: Continuation versus Discontinuation of Beta Blockers in Patients Admitted with Acute Decompensated Heart Failure Requiring Inotropes
Authors: Raby Kirsten , German Charles A , Seals Austin , Xu Jiaqian , Crespo Eric , Green Stan , Banoian Dion , Hilton Thomas , Goslen Kevin , Pisani Barbara A
Published: March 2022

Introduction:
Heart failure is one of the leading causes of morbidity and mortality globally. The use of beta blockers (BB) in patients with chronic heart failure is the cornerstone of guideline directed medical therapy and is recommended by national guidelines. However, BB are often discontinued when a patient is admitted to the hospital with ADHF, especially when inotropic support is needed. Little is known about the effects of continuing BB therapy in patients with ADHF requiring inotropes. This study sought to compare the effect of BB continuation vs discontinuation on in-hospital mortality among patients admitted to the hospital in ADHF requiring inotropic therapy.

Methods:
A single center, retrospective, non-blinded study was conducted in patients hospitalized with ADHF requiring inotropes over a three-year period. Inclusion criteria were patients ≥ 18 years of age admitted with ADHF and treated with inotropes (milrinone, dobutamine) from 1/1/2017-1/1/2020 at Wake Forest Baptist Medical Center. We assessed BB continuation and discontinuation on admission. Continuation of BB was defined as BB given at least 50% of patient’s hospitalization time. A time to event analysis framework was implemented using Cox proportional hazards models to analyze the effect of BB use on in-hospital mortality.

Results:
A total of 449 patients were admitted with ADHF requiring inotropes who met study criteria. Of those patients, 206 (45.9%) were admitted and continued on BB therapy. Continuation of BB therapy was associated with significant improvements in survival compared with patients whose BB was discontinued. Compared with the BB discontinuation group, a 70% reduction in the likelihood of in-hospital mortality was observed among individuals that continued BB therapy [HR 0.30, 95% Cl: 0.18-0.61, p<0.002].

Conclusion:
In our study, among patients admitted with ADHF requiring inotropes, those continued on BB therapy were 70% less likely to die during their hospitalization.
Abstract 11076: Cardiac AKAP12 Overexpression Reduces Cyclic Amp Accumulation in the Vicinity of β
2
Ar
Authors: Qasim Hanan , Reyes Alcaraz Arfaxad , McConnell Bradley K
Published: March 2022

Introduction:
In Heart Failure (HF), signaling downstream the β
2-
Adrenergic Receptor (β
2
AR) is critical. Sympathetic stimulation of β
2
AR triggers Protein Kinase A (PKA) dependent phosphorylation of proteins that regulate cardiac function. Cyclic adenosine monophosphate (cAMP) accumulation in the vicinity of β
2
AR is crucial for PKA stimulation. cAMP levels are regulated in part by phosphodiesterases (PDEs). A Kinase Anchoring Protein 12 (AKAP12) has been reported to directly bind β
2
AR, PKA, and PDE4. Previously, we reported that cardiac overexpression of AKAP12 (oxAKAP12) in both male and female mice reduced left ventricular ejection fraction (EF) and fractional shortening (FS) significantly after 14-days of chronic Isoproterenol treatment when compared to control groups.

Hypothesis:
AKAP12 overexpression progresses HF development by reducing local cAMP levels in the vicinity of β
2
AR.

Methods:
AC16 cells (Human ventricular cell lines) were grouped into [1] control group or [2] cells stably transfected to overexpress human AKAP12 (oxAKAP12). cAMP accumulation in real-time downstream the β
2
AR was detected for 60 minutes in live cells using the luciferase-based biosensor (GloSensor) post-treatment with 10μM Epinephrine (EPI). Additionally, cells were pre-treated for 2 hours with either 10μM Rolipram (selective PDE4 inhibitor) or 0.1mM IBMX (non-selective PDE inhibitor) followed by 10μM EPI treatment.

Results:
oxAKAP12 cells (expressing AKAP12 protein 3 folds higher than controls) had significantly lower maximum cAMP accumulation post-EPI treatment downstream the β
2
AR (2.06 ± 0.32) compared to controls (9.04 ± 0.73), [p=0.0001]. Rolipram pretreatment increased cAMP levels in the oxAKAP12 group to (3.75± 0.72), however, the control group was still significantly higher (9.63 ± 0.95), [p=0.0032]. IBMX pretreatment increased cAMP levels in the oxAKAP12 group to (6.94 ± 1.55) which wasn’t significantly different from the control group (9.75 ± 2.52), [p=0.4152].

Conclusions:
Cardiac overexpression of AKAP12 significantly reduces cAMP levels downstream of the β
2
AR. Potentially through scaffolding other PDEs aside from PDE4.
Abstract 11088: Trend, Predictors and Outcomes of Transcatheter Aortic Valve Implantation in Patients with Bicuspid Aortic Valve; A National Inpatient Sample Database Analysis
Authors: Ullah Waqas , Khalil Fouad , sarwar usman , Zahid Ullah Muhammadzai Hamza , Zahid Salman , Yasmin Farah , Minhas Abdul , Alam Mahboob , Virani Salim S , Fischman David L
Published: March 2022

Background:
Transcatheter aortic valve implantation (TAVI) has increasingly been utilized in patients with bicuspid aortic valve (BAV) related to aortic stenosis (AS) with insufficient data on its safety and efficacy.

Hypothesis:
TAVI in BAV has worst outcomes.

Methods:
The National Inpatient Sample (NIS) database was queried to identify patients undergoing TAVI for BAV-AS. The major adverse cardiovascular events (MACE), its components [in-hospital mortality, stroke, subsequent myocardial infarction (MI)] and procedure related complications were assessed using a propensity-matched analysis (PSM) to calculate adjusted odds ratios (aOR).

Results:
A total of 435,841 TAVI crude and 10,743 matched population [trileaflet aortic valve (TAV) 5347, BAV 5396] was included in the final analysis. On PSM, the adjusted odds of cardiac tamponade (aOR 0.61, 95% CI 0.41-0.90), vascular complications (aOR 0.37, 95% CI 0.24-0.56) and stroke (aOR 0.81, 95% 0.65-1.02) were significantly lower in the BAV group, while there was no difference in the risk of in-hospital mortality, post-procedural myocardial infarction, major bleeding, acute kidney injury (AKI) and need for hemodialysis between the two groups. The yearly trend of in-hospital endpoints showed a steady decline in the overall annual rate of complications among those with BAV undergoing TAVI. Compared to early years, the odds of mortality, MI, need for PPM and IABP were identical between the two groups in 2016-2018. A stratified analysis based on age (<65 vs. >66 years), sex (male vs. female), history of coronary artery disease (CAD) and end-stage renal disease (ESRD) followed the net results.

Conclusion:
TAVI utilization in patients with BAV has increased remarkably over the recent years. The resultant risk of procedural complications such as in-hospital mortality, major bleeding and the overall rate of complications are comparable to those having TAV-AS.
Abstract 11093: Patients with Post-Acute Sequelae of Sars-cov-2 Syndrome Exhibit No Significant Abnormalities in Cardiac Energetics, Structure, Function, Blood Flow or Tissue Characteristics
Authors: Gorecka Mira , Thirunavukarasu Sharmaine , Jex Nicholas , Chowdhary Amrit , Sharrack Noor , Xue Hui , Kellman Peter , Plein Sven , Simms Alexander D , GREENWOOD John P , Levelt Eylem
Published: March 2022

Introduction:
Despite the initial recovery from the acute COVID-19 infection, an increasing number of patients are experiencing a wide spectrum of symptoms more than 12 weeks after the index diagnosis. The underlying pathophysiology of post-acute sequelae of SARS-CoV-2 (PASC) syndrome remains unknown. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease. The relative concentration of phosphocreatine to ATP (PCr/ATP) measured non-invasively by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) is a sensitive index of the myocardial energetic state. It is currently unknown whether PASC is associated with abnormalities of myocardial structure, function, perfusion and tissue characteristics or energetic derangement.

Methods:
A total of 13 patients with a clinical diagnosis of PASC syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and ten matching controls underwent 31P-MRS and CMR at 3T at a single time point.

Results:
Clinical characteristics and imaging results are provided in Table-1.

Between the PASC syndrome patients and controls there were no differences in myocardial energetics (PCr/ATP), in cardiac structure (left ventricular volumes, mass), function (ejection fraction, global longitudinal strain), tissue characterization (T1 and extracellular volume fraction mapping, late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve).

Conclusion:
Patients with a clinical PASC syndrome with no prior CVD exhibit no significant abnormalities in cardiac energetics, structure, function, myocardial blood flow or tissue characteristics.
Abstract 11101: The Creation and Early Outcomes of a Nurse Led, IV Diuretic Clinic in a Rural Setting
Authors: D'Anna Susan , Emmons Margaret , Cantlin Deborah , DeMark Carolyn , Ambrose Kim , Racine Amanda , Gilstrap Lauren
Published: March 2022

Introduction:
IV diuretic clinics are becoming an increasingly common way to manage HF in the outpatient setting. Limited data exists for the effectiveness and safety of these nurse led clinics when operating in rural areas. This is important because rural HF patients have poorer outcomes and limited access to HF-focused providers. This study aims to describe the development, implementation and outcomes of a nurse led, rural IV diuretic clinic.

Methods:
We began by conducting stakeholder interviews, including patients and caregivers, to establish goals for the clinic. We created a clinic eligibility criteria and diuretic dosing algorithms based on CARRESS-HF trial and other published studies. We worked with clinic staff to develop a workflow and schedule. We partnered with multidisciplinary providers to enable access to ancillary services while patients received care in clinic. Finally, we met with providers and groups within our hospital and referral institutions to advertise the clinic (
Figure 1
).

Results:
Since opening in January 2021, the clinic has had 39 appointments and treated 25 individual patients (min. 1 visit/pt, max. 6 visits/pt). The average patient was 68 years old, with an ejection fraction of 47%. In 85% of visits, the patient was NYHA III-IV. Sixty-eight percent reported that HF had limited their life “quite a lot” or “extremely.” The average patient was 17 lbs.
±
13 lbs. above their dry weight. Ninety-five percent received an IV furosemide bolus and 18% received a subsequent infusion as well. During the visit, 18% saw care management, and 10% saw wound care. The average urine output in clinic was 288cc and the average weight loss within 24-72 hours was 3.6lbs.

Conclusions:
By engaging local stakeholders and partnering with other providers, administering safe and effective outpatient IV diuresis and multidisciplinary care in a rural setting is possible. More work is needed to determine the impact of nurse led, rural IV diuretic clinics on long-term outcomes.
Abstract 11103: Associations of Smokeless Tobacco Use with Cardiovascular Disease Risk: Insights from the Population Assessment of Tobacco and Health Study
Authors: Rezk-hanna Mary , Warda Umme , Brecht Mary-Lynn , Benowitz Neal L
Published: March 2022

Introduction:
Combustible tobacco smoking is strongly associated with the development of cardiovascular disease (CVD). However, evidence is limited as to whether smokeless tobacco (ST) use is associated with CVD.

Methods:
Using data from 4347 adults in the Population Assessment of Tobacco and Health Study (2013-2014), we compared geometric mean concentrations of CVD-related harm biomarkers and biomarkers of exposure among current exclusive ST product users and exclusive cigarette smokers—in relation to nicotine exposure—and never tobacco users, adjusting for age, sex, race/ethnicity, income, BMI and CVD. Biomarker levels among exclusive ST users who were former established cigarette smokers were examined and compared to levels among exclusive cigarette smokers.

Results:
Compared to cigarette smokers, ST users had significantly higher concentrations of total nicotine equivalents (TNE) but lower concentrations of inflammatory (high-sensitivity C-Reactive-Protein, interleukin-6, intercellular adhesion molecule, fibrinogen) and oxidative stress (8-isoprostane) biomarkers (all P<0.05). Biomarker levels among ST users were similar to never smokers. Exclusive ST users who were former cigarette smokers had lower levels of inflammatory and oxidative stress biomarkers and biomarkers of exposure (including cadmium, lead, 1-hydroxypyrene, acrylonitrile and acrolein), compared to cigarettes smokers (p<0.05), despite having higher TNE levels (P<0.05). In cigarette smokers, but not among ST users, inflammatory biomarkers and TNE were highly correlated.

Conclusions:
ST use is not associated with increases in biomarkers of CVD-related harm and exposure, compared to never smokers, despite exposure to nicotine at levels higher than those observed among cigarette smokers. These findings support the concept that increases in CVD risk among cigarette smokers is caused primarily by constituents of tobacco smoke other than nicotine.