bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11667: Red Cell Indices and Long-Term Prognosis of Heart Failure Patients
Authors: Mayer Otto , Bruthans Jan
Published: December 2023

Introduction:
It has been demonstrated that some properties of red blood cells also play a role in the etiology of cardiovascular diseases and their complications.

Hypothesis:
We determined to what extent red blood cell indices observed during hospitalization for heart failure (HF) affect the long-term prognosis of these patients.

Methods:
We followed 3697 patients [mean age 71.4 years (±SD10.1), 59.1% males] hospitalized for decompensated HF between 2010-20. In the multivariate model, we assessed the five-year all-cause mortality risk associated with red cell distribution width (RDW), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin concentration (dichotomized by tertiles).

Results:
Kaplan-Meier survival curves comparing the tertiles of red cell indices are in Figure. Patients with RDW in the top tertile showed roughly two-fold higher 5-year mortality risk than those in the bottom tertile; increased risk we also observed in the middle tertile of RDW. This association remained significant even after complex adjustments for individual characteristics (age, gender, ejection fraction, HF etiology, history of malignancy, revascularization, hypertension, diabetes, LDL, atrial fibrillation, and glomerular filtration) as well as treatments (furosemide, beta-blockers, RAS blockers, MRA′s, statins). [HRR 1.83 (95% CIs: 1.53-2.18), p<0.0001, 3
rd
versus
1
st
; 1.42 (95%CIs: 1.19-1.68), p<0.0001, 2
nd
versus
1
st
] Similarly, we observed increased mortality risk in the bottom tertile of MCHC [HRR 1.34 (95%CIs:1.14-1.59), p=0.001, 1
st

versus 3
rd
(

fully adjusted)] or hemoglobin [HRR 1.37 (95%CIs: 1.15-1.62), p<0.0001]. In contrast, MCV did not show any additive mortality risk.

Conclusions:
High degree of anisocytosis and low red cell status of hemoglobin represents independent indicators of poor prognosis in heart failure patients, even long-term after an acute manifestation.
Abstract 11709: High Rates of Hyperkalemia Recurrence After Medical Nutrition Therapy in Patients With Heart Failure: REVOLUTIONIZE I Real-World Evidence Study
Authors: Agiro Abiy , Rowan Christopher G , Desai Pooja , Chan K. Arnold , Colman Ellen , White Katie , Dwyer Jamie P
Published: December 2023

Introduction:
Medical nutrition therapy (MNT) slows chronic kidney disease (CKD) progression but its effect on serum potassium (K
+
) and hyperkalemia (HK) recurrence in patients with heart failure (HF) and comorbid CKD is unclear. REVOLUTIONIZE I is a real-world study of HK recurrence in patients who received MNT after experiencing HK.

Aims:
This analysis aims to describe HK recurrence in a subgroup of patients with HF and comorbid CKD in the REVOLUTIONIZE I study.

Methods:
Patients aged ≥18 years with HF and stage 3/4 CKD who received MNT within 30 days after a serum K
+
value of >5.0 mEq (1/1/2019 to 10/31/22) were identified from TriNetX Dataworks de-identified electronic health records data. Patients were excluded if they received outpatient K
+
binder therapy within 6 months before the index date (MNT date + 7 days). Patients were censored at the first of: 6 months post-index, outpatient K
+
binder therapy initiation, death, or 10/31/22. HK recurrence was calculated for 1-6-month intervals post-index and compared with the estimated
a priori
HK recurrence rate (50%) by Chi-square test.

Results:
The HF subgroup included 1179 patients. Of 861 patients with ≥6 months’ follow-up, 485 (56.3%) had ≥1 HK recurrence (
Figure
), with a mean ± SD of 2.6 ± 2.2 recurrences (range 1-14). Time between HK recurrences decreased with each recurrence, from a mean of 42 days for the first recurrence to 35 days for the second and <30 days for additional recurrences.

Conclusions:
This real-world study showed that HK is a chronic, recurrent condition for the majority of patients with HF and comorbid CKD, despite the use of medical nutrition therapy. There is unmet need to consider long-term anti-HK therapy with newer K
+
binders to reduce HK recurrence in this patient population.
Abstract 11710: The Integrative Experimental and Computational Approach to Assess Patient Lipid-Lowering Drug Adherence for Coronary Artery Disease Risk Diagnostics
Authors: Ivanova Anna A , Kusovschi Jennifer , Gardner Michael , Kraus William E , McGarrah Robert , Kuklenyik Zsuzsanna , Barr John R
Published: December 2023

Background:
Statins, lipid-lowering drugs, are the first-line pharmaceutical therapy against Atherosclerotic Cardiovascular Disease (ASCVD). The emphasis on providing statin treatment as a preventive measure before the first cardiac event burdens low-risk individuals with adverse side effects. Furthermore, inaccurate self-reporting of statin use by patients or their poor adherence to statins complicates the monitoring of long-term benefits and side effects of statins and ASCVD risk assessment. New sensitive, multiplexed and high throughput methods to confirm actual statin use by patients are urgently needed.

Methods:
We used 690 plasma samples from individuals with known number of diseased vessels, established lipid profiles, and medication records of statin use. The samples were obtained from the CATHeterization GENetics (CATHGEN) sample archive. The levels of 7 statins (atorvastatin, simvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and fluvastatin) in the plasma samples were determined by a 4-minute-long Liquid Chromatography-Mass Spectrometry Method (LC-MS/MS). Nominal logistic regression algorithms were employed to model coronary artery disease (CAD) outcomes with the incorporation of statin use, phenotypic, and lipid profile characteristics.

Results:
Our LC-MS/MS analysis has revealed discrepancies between the reported statin medication use and the detected statin levels in plasma. The reported statin use history was confirmed for 212 out of 261 patients. Among 429 specimens without a recorded history of statin use, statin was detected in 198 specimens. Comparison of logistic regression models built with statin use data as a covariate and with stratification by statin users and non-users revealed significant differences in covariate corrected mean lipid profile measures and their association with predicted atherosclerosis outcomes.

Conclusion:
In summary, high-throughput multiplexed LC-MS/MS analysis is highly applicable to uncover discrepancies between the self-reported and actual use of statins. By combining LC-MS/MS with statistical modeling, we showed that these discrepancies may significantly affect the modeled association between lipid profile measures and ASCVD outcome.
Abstract 11735: The Effect of Different NLRP3 Inflammasome Inhibitors on High-Sensitivity C-reactive Protein in Patients After Percutaneous Coronary Intervention
Authors: Yu Miao , Zhu Zheng-Feng , Yang Fen , Yuan Yuan-Fan , Liao Shu-De , Liu Mei-Lin , cheng xiang
Published: December 2023

Background:
Colchicine treatment inhibits the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome assembly and reduces atherothrombotic cardiovascular events in coronary artery disease (CAD). However, the effects of other inhibitors targeting NLRP3 inflammasome needs further verification in CAD.

Aims:
This study aimed to investigate whether inhibitors targeting NLRP3 inflammasome besides colchicine are effective in patients after percutaneous coronary interventions (PCI).

Methods:
The study included 132 patients aged 18-80 years who completed the planned PCI and were treated with aggressive secondary prevention strategies for four weeks. The subjects were randomly assigned to one of the following treatment groups for four weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in hsCRP levels at the end of four weeks.

Results:
In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male and 28 (25.69%) were female. The percentage changes in hsCRP after four weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups respectively. Compared with the control group, the colchicine group showed significantly greater reduction in hsCRP levels (P=0.022). The tranilast and oridonin groups did not show obvious changes. In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin,myeloperoxidase, myeloblastin), platelet aggregation (glycoprotein VI) and endothelial damage (galectin-3) were reduced with colchicine therapy.

Conclusions:
Colchicine could reduce hsCRP in patients after PCI, which is likely to act on neutrophils. Colchicine may still be the important choice for anti-inflammatory treatment of CAD.
Abstract 11752: Correlation of Myocardial Work Parameters With Left Ventricular Ejection Fraction in Patients With Chagas Disease From a Quaternary Hospital in Brazil
Authors: dos Santos Felix Alex , Lustosa Rodolfo De Paula , Kasal Daniel A , Rey Helena C , SPINETI PEDRO P , Bittencourt Marcelo I , Neves de Albuquerque Felipe N , Sales Ana Luiza F , Castier Marcia B , MOURILHE ROCHA RICARDO M
Published: December 2023

Introduction:
Although left ventricular ejection fraction (LVEF) is one important parameter for management of pts with heart diseases and a major prognostic factor in Chagas cardiomyopathy (CC), it has great variability. Myocardial Work (MW) is a new promising technique which integrates afterload to longitudinal strain analysis using noninvasive blood pressure (NIBP) values, calculating pressure x strain loops (PSL). Correlation of MW with LVEF in pts with CC is unknown.

Hypothesis:
LV MW may have good correlation with LVEF in pts with Chagas Disease (CD).

Methods:
We included 39 consecutive pts(74,4% women, median age 68,8±9,7) followed in a quaternary Brazilian hospital with diagnosis of CD, dividing them into groups based on the stages of heart disease: Group 1: normal Echocardiography (Echo) and ECG, Group 2: pts with alterations in ECG and/or Echo with preserved LVEF, Group 3: pts with reduced LVEF with or without heart failure. A comprehensive Echo was performed in all pts, and LVEF was measured by 2D biplane Simpson. LV MW was measured using speckle-tracking echo, using NIBP as an afterload index for generation of PSL by a specific software. Global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were measured.

Results:
11 pts (28,2%) were classified in group 1, 14 (35,9%) in group 2, and 14 (35,9%) in group 3. There was a very strong correlation of LVEF with GWI (p<0,001; r=0,781), GCW (p<0,001; r=0,813), a strong correlation pf LVEF with GWE (p<0,001; r=0,661) and a weak correlation of LVEF with GWW (p=0,046; r=-0,332). All MW parameters, except from GWW had good sensitivity and specificity to detect pts with reduced LVEF, with best cutoff for GWI = 1501mmHg% (AUC=0,980) and GCW=1719,5mmHg% (AUC=0,986).

Conclusions:
MW parameters, except from GWW, had strong correlation with LVEF in this subset of pts with CD, with good performance for the detection of LVEF≤52%, with high sensitivity and specificity.
Abstract 11754: Trends in Cardiovascular Mortality Before and During the COVID-19 Pandemic
Authors: Clarke Jacob , Greathouse Frances , Elkaryoni Ahmed , Desai Parth V , Mujer Mark , Darki Amir
Published: December 2023

Introduction:
The COVID-19 pandemic has placed increased strain on the US healthcare system, limiting the prevention and treatment of cardiovascular diseases. Previous studies have noted an increase in excess mortality among patients with chronic medical conditions during the pandemic. However, these trends have not been fully explored in patients with acute pulmonary embolism (APE) and cardiovascular disease.

Methods:
Death-certificate data from the CDC Wonder database were used to calculate death rates of APE, heart failure (HF), and myocardial infarction (MI) from 1999 to 2022. Training data from 1999 - 2019 were used to create a prediction model that was used to calculate excess mortality during the COVID-19 pandemic stratified by disease, year, sex, and race.

Results:
Between 1999 and 2022, the most common studied cause of death was HF followed by MI and APE. All studied causes of death occurred at higher rates during 2020 compared to 2019. For all included diseases, there was a positive correlation between monthly excess mortality and total US covid deaths. APE had the highest percent excess mortality (86.5%) followed by MI (31.6%), and HF (16.2%) (Figure 1). When stratified by sex and race, males and black individuals experienced greater cumulative excess mortality across all included diseases (Figure 2).

Conclusions:
COVID-19 has had a heterogenous effect on different cardiovascular diseases both directly through infection and indirectly through increased strain on the healthcare system. Understanding the impact of COVID-19 on CVD burden can help guide public policy in future health care-system stressors.
Abstract 11755: Efferocytic Regulator Rab11FIP1 Alleviates Inflammation and Cardiac Remodeling After Myocardial Infarction
Authors: zhuang lingfang , Zhang Ruiyan , Chen Kang , Yan Xiaoxiang
Published: December 2023

Introduction:
Defective efferocytosis drives cardiac dysfunction after myocardial infarction (MI); however, the underlying molecular mechanisms and regulators of macrophage efferocytosis remain unknown.

Hypothesis:
This study aimed to explore the modulator and its mechanisms of the continued clearance and degradation of phagolysosomal cargo during MI.

Methods:
Leveraging macrophage RAB11FIP1 knockout model, flow cytometry and PET-CT technologies, we examined the functional significance of RAB11FIP1 after MI. Moreover, a nanoliposome-linked ssDNA aptamer contained modified RAB11FIP1 mRNA was designed.

Results:
By comparing the transcriptomic signatures of our scRNA-seq data, we identified RAB11FIP1 was the most sensitively efferocytic gene among all phagosome-related signatures. RAB11FIP1 deficiency resulted in a considerable exacerbation in cardiac function, the accumulation of apoptotic cardiomyocytes and a reduced efferocytosis. RAB11FIP1-loss also led to increased infiltration of CCR2+ macrophages and neutrophils with upregulation of proinflammatory mediators, IL-1β, TNF-α, Ccl2 after MI. In mechanistic studies, RAB11FIP1 defect disabled the recycling of efferocytic receptor, Mertk, further impaired continued macrophages efferocytosis. Moreover, the scRNA-seq data revealed that the regulon activity of XBP1, which acted as the key ER-stress executor, was significantly activated in RAB11FIP1-null hearts, then, the activated XBP1 governed the transcriptional expression of pro-inflammatory mediators after MI. Finally, we constructed a nanoliposome-linked ssDNA aptamer to specifically target macrophages. RAB11FIP1-expressing phagocytes display a striking increase in efferocytosis and decline in inflammation, cardiac remodeling after MI.

Conclusions:
Collectively, these findings advance the relationship of RAB11FIP1 between macrophage efferocytosis, ER-stress response and the cardiac inflammation.
Abstract 11771: Validity of an Administrative Claims-Based Measure of Low-Value Carotid Revascularization
Authors: Navarro Matthew J , Han Jessica , Smith Michelle , Wu Kelly , Casale Paul N , Kini Vinay
Published: December 2023

Introduction:
Low value care is defined as care where harms or costs outweigh benefits. Researchers, payers, and policymakers commonly use administrative claims data to identify low-value care, but the validity of many claims-based algorithms has not been assessed.

Research Question:
What is the validity of a commonly-used claims-based algorithm to identify low-value carotid artery revascularization (CAR) procedures, compared to a reference standard of chart review?

Methods:
This was a retrospective cohort study of Medicare fee-for-service beneficiaries attributed to a large accountable care organization. We used administrative claims data linked to electronic health record data and identified all CAR procedures (endarterectomy or stenting) from 01/01/2020-12/31/2021. We excluded patients without claims history in the year prior to CAR. Using methods previously described by policymakers and researchers, we classified CAR as low-value by claims if patients did not have diagnosis codes for stroke, transient ischemic attack, or other neurologic symptoms such as vision changes or hemiplegia in the year prior to CAR. We then reviewed linked electronic health records to determine if cases were misclassified by the claims-based measure. Per recent guidelines, we classified CAR as low-value by chart review if it was performed in patients with less than 50% symptomatic stenosis or greater than 80% asymptomatic stenosis.

Results:
A total of 127 CAR cases (mean age 77 years; 63% men; 87% white) with complete electronic health record data were identified, and 48 (38%) were classified as low-value by the claims-based algorithm. Only 11 of the 48 cases classified as low-value by claims were confirmed to be low-value by chart review. The positive predictive value of the claims-based algorithm was 23%.

Conclusions:
A commonly-used claims-based measure to identify low-value CAR procedures had poor accuracy with a positive predictive value of 23%. Using administrative claims to identify low-value CAR procedures might overestimate the number of procedures considered to be low-value. This has implications for the current system of quality reporting, particularly when quality is tied to financial incentives.
Abstract 11784: A Deep-Learning-Based Multi-Modal Phonocardiogram and Electrocardiogram Processing Framework for Screening Left Ventricular Systolic Dysfunction Using a Wearable Cardiac Patch
Authors: Zhang Wenli , Song Bei , Huang Qijia , Qu Xuezheng , Yu Jiwei , Mead Hardwin , Yan Xiaowei , Zhu Zhengbin , Quan weiwei , Zhang Ruiyan
Published: December 2023

Introduction:
Left ventricular systolic dysfunction (LVSD) is associated with poor health outcomes. Previous study has demonstrated the effectiveness of electromechanical activation time (EMAT) derived from phonocardiography (PCG) and electrocardiography (ECG) signals in identifying LVSD. However, high throughput and well-performed algorithm is needed in automatically detecting LVSD.

Hypothesis:
An artificial intelligence (AI) algorithm was developed and validated in detecting LVSD.

Methods:
Using ECG and PCG data collected by wearable patch from 1020 admitted patients in Ruijin hospital, we trained an AI algorithm to detect the LVSD, which was determined by ejection fraction <50% from echocardiogram. A separate 590 patients were taken as independent test set. The AI algorithm followed a two-step detection structure, where the first step is to use LSTM learning to quantify heartbeat and heartbeat interval in ECG, and the second step is to apply convolution neural network (CNN) in estimating optimal EMAT cutoff points in detecting LVSD. To overcome the challenge of multi-modal signal training, we develop an alignment-based contrastive learning approach that generates shared feature space embeddings for ECG and PCG signals.

Results:
Among training and test sets, 18.2% and 26.1% were LVSD, respectively. The AI algorithm yields an AUROC of 0.92 in detecting LVSD with sensitivity of 85.63%, and specificity of 79.39%. Among the test set, model yielded an AUROC of 0.86, sensitivity of 81.29%, and specificity of 77.13%.

Conclusions:
A wearable device incorporated with a high performed AI algorithm can be a viable, convenient, cost-effective tool in screening LVSD.
Abstract 11802: IRF2BP2 Regulates Hormone Sensitive Lipase and Lipolysis in Human Adipocytes and in Mice
Authors: Chen Yang , Liu Lin , Steger David , Cheng Lan , STEWART Alexandre F , Seale Patrick
Published: December 2023

Background:
IRF2BP2, a transcriptional co-factor, has emerged as a potential regulator of circulating lipid levels based on several coronary artery disease (CAD) genome-wide association studies (GWAS) studies. However, the role of IRF2BP2 in adipocytes, which regulate fat storage, energy expenditure, and fatty acid release, remains unexplored. Our aim is to investigate the role of IRF2BP2 in adipocyte function regulation.

Methods:
Human adipocyte stem cells (hASC) were differentiated into adipocytes for
in vitro
studies. We used the CRISPR system and lentiviral expression constructs to knockout (KO) and overexpress (OE) IRF2BP2. Control, IRF2BP2 KO and IRF2BP2 OE adipocytes were assessed by several methods, including RNA-seq, western blot analysis, and functional assessment of lipolysis and glucose uptake. IRF2BP2 chromatin immunoprecipitation (ChIP)-seq was performed
in vitro
. Adiponectin-Cre mice were crossed with Irf2bp2 flox/flox mice to generate adipocyte-specific KO (AKO) animals. We evaluated the effect of IRF2BP2 KO on adipose morphology and gene profiles. Circulating fatty acids were assessed in control and AKO mice.

Results:
IRF2BP2 deletion or OE in hASC-differentiated adipocytes did not affect adipocyte differentiation or glucose uptake. However, triglyceride lipolysis was markedly increased in KO cells. Conversely, IRF2BP2 OE suppressed lipolysis. RNA-seq analysis of control vs. IRF2BP2 KO or OE cells identified the enrichment of lipid catabolic pathways. Notably, IRF2BP2 KO upregulated, whereas IRF2BP2 OE downregulated the mRNA and protein levels of LIPE (i.e. hormone sensitive lipase, or HSL). Further, ChIP-seq analysis demonstrates strong binding of IRF2BP2 to a LIPE enhancer, suggesting direct regulation. In mice,
Irf2bp2
AKO increased circulating fatty acids, accompanied by a reduction of adipocyte size. LIPE mRNA and protein expression in adipose tissue was also elevated. Finally,
Irf2bp2
AKO induces massive adipose tissue inflammation, evidenced by F4/80 staining and chemotaxis gene markers expression.

Conclusions:
We established IRF2BP2, as a novel transcriptional regulator of adipocyte lipolysis, through the key lipolytic gene LIPE, which may shed light on deciphering the role of IRF2BP2 in CAD.
Abstract 11812: Cardiopulmonary Exercise Test and Atrial Fibrillation in Obstructive Hypertrophic Cardiomyopathy: A Study From Septal Myectomy Patients
Authors: Lu Tao , Wang Shuiyun
Published: December 2023

Background:
Cardiopulmonary exercise test (CPET )is currently used to quantify functional limitation and to evaluate the indications for surgery among patients with hypertrophic cardiomyopathy (HCM). Patients with HCM often have atrial fibrillation (AF) and their relationship is not clear.

Objective:
To investigate the function limitation among HCM patients who meet indications for septal myectomy and the association between it and AF. Method: We reviewed 565 consecutive patients who underwent myectomy from February 2019 to October 2021, of which 212 did CPET and 24h Holter before surgery.

Results:
In this cohort (median age: 50.55(37.6-58) years; male: 126(59.4%); left ventricular outflow tract gradient (LVOTG)≥ 50 mmHg: 190(89.6%)), there was a severely impaired function (Peak Oxygen consumption (Peak VO2): 16.44 ± 4.02 ml/min/kg, adjusted Peak VO2%: 58.27%). Comparing different groups divided by Peak VO2, the lowest group was characterized by older age (58 vs 50 vs 43.9 years, p < 0.001), more female patients (57.7% vs 38% vs 25.7%, p < 0.001), higher NT-proBNP level (1299 pg/ml vs 1049 pg/ml vs 742.5 pg/ml, p = 0.004), and larger left atrial diameter (46.8mm vs 43.77 mm vs 42.71 mm, p < 0.001). The incidence of AF also significantly increased (30.98% vs 14.08% vs 7.14%, p < 0.001). Among various indicators of CPET, Peak VO2 showed the strongest correlation with AF (point-biserial correlation coefficient: -0.347, p < 0.001; 0.2279, p = 0.011; -0.2502, p < 0.001; for Peak VO2, ventilatory efficiency, and anaerobic threshold, respectively). Additionally, the incidence of AF decreased with increasing severity of obstruction (60% vs 33.3% vs 16.2% vs 7.1% among non-obstructive, 30≥maximum LVOTG < 50 mmHg, 50≥LVOTG < 100 mmHg, >100 mmHg patients, respectively, p = 0.001). In multivariate regression analysis adjusting for age, sex, BMI, and left atrial diameter, Peak VO2 and LVOTG remained independently associated with the development of AF (OR 0.854, 95% CI 0.743-0.973, p = 0.021 and OR 0.969, 95% CI 0.949-0.987, p = 0.002, respectively).

Conclusions:
CPET indicator, particularly PeakVO2, was independently associated with the occurrence of AF in eligible surgical patients with HCM. We also found that the higher extent of obstruction, the lower the incidence of AF.
Abstract 11818: The Beneficial Effects of Ceramide on Human Microvascular Endothelial Function is Dependent on S1P/S1PR1 Signaling Axis
Authors: SenthilKumar Gopika , Zirgibel Zachary , Lindemer Brian J , Bordas-Murphy Henry , Freed Julie K
Published: December 2023

Despite the known damaging effects of elevated intracellular ceramides on human microvascular function, our recent work showed that loss of ceramide-formation through neutral sphingomyelinase (NSmase) promotes endothelial dysfunction in arterioles from healthy adults. This presents as a switch in the endothelial-derived mediator responsible for eliciting dilation to flow (flow-induced dilation; FID), from the vasoprotective nitric oxide (NO) to pro-inflammatory hydrogen peroxide (H
2
O
2
). The mechanism through which ceramide exerts beneficial effects on the vasculature remains poorly understood. One of ceramide’s metabolites, sphingosine-1-phosphate (S1P), has been shown to stimulate NO production through the activation of S1P receptor 1 (S1PR1). Thus, we hypothesize that ceramide promotes NO-mediated FID through its metabolism to S1P and activation of S1PR1. Arterioles (100-250μm) from healthy adults were dissected from discarded surgical adipose tissue. Vessels were cannulated in organ chambers, pre-constricted with endothelin-1, and changes in internal diameter in response to increases in flow or C2-ceramide was measured via videomicroscopy. Difference between mean % dilation ±SE with two-way ANOVA is reported. Agonism of S1PR1 (CYM5442, 1μM, 30min) during NSmase inhibition (GW4869, 4μM, 30min) restored dependency on NO for FID, as L-NAME (100μM; NO synthase inhibitor) diminished FID (GW+CYM, n=4 vs GW+CYM+L-NAME, n=4: -70.3±20.0, p=0.01). A similar switch to NO-mediated FID was seen with C2-ceramide (10μM)+GW4869 treatment (GW+C2, n=5 vs GW+C2+L-NAME, n=4: -52.5±5.9, p<0.001). Inhibition of S1PR1 (W146, 10μM, 30min) induced a switch from NO to H
2
O
2
mediated FID, as catalase (500U/ml; W146, n=5 vs W146+Catalase, n=4: -34.0±7.9; p=0.01) but not L-NAME (W146, n=5 vs W146+L-NAME, n=4; -1.4±9.9, p=0.89) impaired FID. Acute ceramide-induced dilation (1min) was diminished in the presence of L-NAME (C2, n=5 vs C2+L-NAME, n=4: -33.40±10.06, p=0.02) and W146 (C2, n=5 vs C2+W146, n=4; -39.7±5.9, p=0.01). Together, these data suggest that ceramide induces NO-signaling through the activation of S1PR1 and provide mechanistic insight into how ceramide may exert beneficial effects within the human microvascular endothelium.
Abstract 11882: Acute Cardiac Events Among Older Adults Hospitalized With Laboratory-Confirmed Respiratory Syncytial Virus
Authors: Woodruff Rebecca C , Melgar Michael , Pham Huong , Loustalot Fleetwood V , Daily Kirley Pam , Armistead Isaac , Kim Daewi , Openo Kyle , Ryan Patricia , Brown Chloe , Bye Erica , Shrum Davis Sarah , Barney Grant , Popham Kevin , Thomas Ann , Talbot H Keipp , Hill Mary , Sperling Laurence , Havers Fiona
Published: December 2023

Introduction:
Respiratory syncytial virus (RSV) can cause severe illness among older adults, but potential cardiac complications have not been comprehensively described. We evaluated the frequency and severity of acute cardiac events among older adults hospitalized with laboratory-confirmed RSV to inform recommendations for RSV vaccine candidates in development.

Methods:
The RSV-Associated Hospitalization Surveillance Network (RSV-NET) abstracted medical record data among all hospitalized patients identified with laboratory-confirmed RSV infection (clinician-ordered testing) in a population-based catchment area of 38 counties in 9 states. Among adults aged ≥50 years hospitalized with RSV during the 2015-16 to 2017-18 RSV seasons, we estimated the period prevalence and 95% confidence interval (CI) of acute cardiac events, identified from the patient’s discharge diagnoses and ICD-10 codes. Multivariable generalized estimating equation models estimated the adjusted risk ratio (aRR) of intensive care unit (ICU) admission and in-hospital death by acute cardiac event status.

Results:
Among 3959 adults aged ≥50 years hospitalized with RSV (mean age 73 years), 20.8% (CI, 19.5-22.1) experienced an acute cardiac event during hospitalization, most frequently acute heart failure (14.3%; CI, 13.2-15.4; Table). Acute cardiac events were common among adults aged ≥75 years (25.0%; CI, 23.1-27.0) and among those with underlying cardiac disease (30.4%; CI: 28.5-32.3). Compared to patients without an acute cardiac event, those with an acute cardiac event were more likely to experience ICU admission (16.8% vs 27.0%; aRR: 1.7, CI: 1.5-1.9) and in-hospital death (4.1% vs 8.8%; aRR: 2.0, CI: 1.6-2.5).

Conclusions:
One in 5 older adults hospitalized with RSV experienced an acute cardiac event, which was associated with approximately double the risk of severe outcomes. Adults at greater risk of cardiac complications from RSV may benefit from vaccines when available.
Abstract 11913: Prognostic Value of Right Ventricular-Pulmonary Arterial Coupling in Adults With Repaired Coarctation of Aorta
Authors: Karnakoti Snigdha , Abozied Omar , Younis Ahmed , Kandlakunta Sriharsha , Ahmed Marwan , Egbe Alexander C
Published: December 2023

Introduction:
Right ventricular (RV) systolic dysfunction and pulmonary hypertension is present in 20% of adults with repaired coarctation of aorta (COA). However, the prognostic value of RV to pulmonary artery (RV-PA) coupling in this population is unknown.

Objective:
The purpose of this study was to assess the relationship between RV-PA coupling and clinical outcomes (heart failure hospitalization and all-cause mortality) in this population.

Methods:
Retrospective cohort study of adults with repaired COA and normal RV systolic function defined as RV-free wall strain ≥-24%. RV-PA coupling was assessed using tricuspid annular plane systolic excursion/ RV systolic pressure (TAPSE/RVSP) ratio.

Results:
Of 509 patients (median age 32 [20-45] years; men 290 [57%]), the average TAPSE and RVSP were 22±5 mm and 33±9 mmHg, respectively, and TAPSE/RVSP ratio was 0.78 (0.56-0.96) mm/mmHg. Of 509 patients, 51 (10%) died and 43 (8%) were hospitalized for heart failure. TAPSE/RVSP was associated with all-cause mortality (hazard ratio 0.82, 95% confidence interval 0.78-0.86, per 0.1 mm/mmHg), and heart failure hospitalization (hazard ratio 0.86, 95% confidence interval 0.79-0.83, per 0.1 mm/mmHg) after adjustment for anatomic lesions, cardiovascular interventions, comorbidities, and echocardiographic indices. The inclusion of TAPSE/RVSP ratio in the risk models improved the prognostic power of the models to predict all-cause mortality (C-statistics difference 0.046, p<0.001), and heart failure hospitalization (C-statistics difference 0.031, p=0.007).

Conclusions:
TAPSE/RVSP ratio was associated with outcomes in COA patients with normal RV systolic function, suggesting that abnormal RV-PA coupling may be present prior to the onset of overt RV systolic function in this population.
Abstract 11918: Simultaneous Presentation of Pyogenic Pericarditis, Coronavirus Infection, and Endocarditis: A Challenging Triad in a Single Patient
Authors: Casey Bradley , Bahekar Amol A , Patel Divyang , Bhandari Manoj , Jyothidasan Amudhan , Guddeti Raviteja , Younus Usman , Chapa-Rodriguez Alejandro
Published: December 2023

Background:
Pyogenic pericarditis is a rapidly progressive infection with high mortality near 100%. In the present antibiotic age, bacterial pericarditis is an uncommon cause of acute pericarditis. The reported incidence of pyogenic pericarditis is less than 1% of all pericarditis cases.

Case:
54 year-old male patient that presented with complaints of generalized weakness, fatigue, and fever. He was diagnosed with Coronavirus 229E by PCR. He was in respiratory distress, and CT chest showed concern for large pericardial effusion. Transthoracic echocardiogram showed large pericardial effusion (Image) without tamponade effect. Patient decompensated overnight and bedside point of care ultrasound overnight showed concern for tamponade effect. Pericardial window was performed and 800 ml thick purulent drainage evacuated. While in the ICU patient underwent transesophageal echocardiogram that showed Small hyper-mobile echo-density on the aortic valve concerning for endocarditis (image). Patient also had Type 1 Bicuspid aortic valve with heavily calcified raphe. Cultures on the pericardial effusion grew methicillin sensitive Staphylococcus Aureus. Patient will need 6 weeks of IV antibiotics and aortic valve replacement. Infectious disease recommended lifelong suppression therapy for MSSA.

Decision-making:
It is not uncommon for bacterial endocarditis and viruses to cause pericardial effusions. It is uncommon for a patient to have bacterial endocarditis, Coronavirus, and be diagnosed with pyogenic pericardial effusion. Cardiac tamponade is a clinical emergency, and evacuation of pericardial fluid to assist reduce the pressure surrounding the heart is used to treat cardiac tamponade.

Conclusion:
Here we present a case to our knowledge that has never been described before. This is a case of a patient that had infective endocarditis with confirmed Coronavirus that resulted in a pyogenic pericardial effusion.
Abstract 11919: Cardiac Conundrum: A Novel Case of Isolated Cardiac Scleromyxedema
Authors: Murphy Brittany , Weinand Nicholas , Liu Angela , Zalawadiya Sandip
Published: December 2023

Case Presentation:
A 41-year-old woman with history of diabetes, inferior STEMI with RCA PCI, and HFmrEF was transferred to our hospital with worsening cardiogenic shock on ionotropic support. She was admitted to an outside facility one month prior with worsening dyspnea on exertion, peripheral edema, paroxysmal nocturnal dyspnea, pre-syncope, and weakness. TTE demonstrated LVEF of 30-35% (40-45% previously) with severe inferior and posterior wall hypokinesis. Cardiac MRI revealed LVEF of 23%, prior RCA infarct, full-thickness late gadolinium enhancement in the left ventricular basilar wall, global abnormal parametric mapping parameters of both native T1, T2 and ECV, and severe biventricular dysfunction concerning for infiltrative cardiomyopathy. Left heart catheterization revealed nonobstructive CAD. Right heart catheterization showed severely elevated right sided filling pressures and endomyocardial biopsy revealed frequent deposits of interstitial mucin (Figure 1), later confirmed by electron microscopy; a Congo red stain was negative for amyloid deposition. Additional work up included serum protein electrophoresis, which was negative for monoclonal proteins. She had no dermatologic disease. A diagnosis of isolated cardiac scleromyxedema was made.

Discussion:
Scleromyxedema is a rare mucinous disorder typically characterized by cutaneous mucin deposits and fibroblastic proliferation. It is commonly associated with monoclonal gammopathies, specifically IgG lambda; however, there are rare cases without paraproteinemia. Systemic mucinous infiltration has been reported and cardiac involvement specifically has been described in up to 20% of patients, although it has never been reported without cutaneous manifestations or monoclonal gammopathy as demonstrated with our patient. The patient received IVIg treatment, however required two additional hospitalizations over the next four months for decompensated heart failure.
Abstract 11956: Arumenamide-787 Suppresses Arrhythmogenesis Associated With the J Wave Syndrome as Well as Hypothermia
Authors: Abdelsayed Mena , Di Diego Jose M , Barajas-Martinez Hector , Cox Robert H , Robinson Victoria , Jung Joseph , Patocskai Bence , Fouda Mohamed , Ruben Peter C , Antzelevitch Charles
Published: December 2023

Background:
The J-wave syndromes (JWS), comprised of Brugada (BrS) and early repolarization syndromes (ERS), increase the risk of life-threatening ventricular arrhythmias in patients resulting in sudden cardiac death. There are limited therapeutic strategies to treat these life-threatening conditions. Present management is via an implantable cardioverter defibrillator and/or medication, including quinidine. However, these treatments may have serious side-effects. Thus, novel therapies are needed to treat JWS. In this study, we investigate the effects of ARumenamide-787 (AR-787) in suppressing the electrocardiographic and arrhythmic manifestations of JWS and hypothermia.

Methods:
We studied the effects of AR-787 on sodium current (I
Na
) and the delayed-rectifier potassium current (I
Kr
) in HEK-293 cells stably expressing the α- and β1-subunits of the cardiac (Na
V
1.5) sodium channel or the hERG channel. In addition, we studied its effect on the transient outward potassium current (I
to
) and calcium current (I
Ca
) from dissociated canine ventricular myocytes, along with action potentials and ECG from coronary-perfused right (RV) and left (LV) ventricular wedge preparations. The I
to
agonist, NS5806, I
Ca
blocker, verapamil, and sodium current (I
Na
) blocker, ajmaline, to induce the electrocardiographic and arrhythmic manifestations of JWS (prominent J waves/ST segment elevation, phase 2 reentry, and polymorphic VT/VF) in right and left canine ventricular wedge preparations.

Results:
AR-787 exerted pleiotropic effects on the cardiac ion channels. The predominant effect was an inhibition of I
to
and enhancement of I
Na
, with subtle effects to inhibit the I
Kr
and augment I
Ca
. AR-787 diminished the electrocardiographic J wave and prevented and/or suppressed all arrhythmic activity in canine RV and LV experimental models of BrS, ERS and hypothermia. We observed no arrhythmogenic effects of AR-787 on I
Kr
.

Conclusions:
Our findings point to AR-787 as a promising candidate for the pharmacologic treatment of JWS and hypothermia. AR-787 suppresses the electrocardiographic and arrhythmic manifestations of JWS and hypothermia without significant prolongation of the QT interval, as with the classic BrS drug, quinidine.
Abstract 11958: Incidence and Predictors of In-Hospital Complications After Myocardial Infraction in Contemporary Clinical Practice: Findings From the FRENCHIE Myocardial Infarction Cohort
Authors: Lemesle Gilles , Cayla Guillaume , Gallet de Saint-Aurin Romain , Nekrouf Celia , Rousseau Alexandra , DUCROCQ Gregory , Angoulvant Denis , COSTE Pierre , Boccara Franck , Lhermusier Thibault , Baronne Rochette Gilles , Dubreuil Olivier , Steg Philippe G , Danchin Nicolas , Simon Tabassome
Published: December 2023

Introduction:
It is important to identify patients presenting with myocardial infarction eligible for early hospital discharge in order to avoid prolonged hospitalizations and reduce costs.

Hypothesis:
From a contemporary French nationwide MI cohort, we aimed to analyze incidence and correlates of in-hospital MI complications.

Methods:
French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing MI registry, which collects data from all patients admitted for MI < 48h of symptom onset in 21 French centers. In-hospital complications were collected and patients who experienced complications were compared to those who did not.

Results:
Overall, 9692 patients presenting with MI were enrolled (5325 STEMI (55%) and 4367 NSTEMI). Among these, 2755 (28%) presented at least one complication during hospitalization. The median length of stay was 4 days [3-7]. The complications were: high degree AV block (2.4%), atrial arrhythmias (7.7%), ventricular arrhythmias (5%), reinfarction (including stent thrombosis) (0.9%), stroke (0.6%), mitral valve and chordae rupture/tear (1.4%), ventricular free wall rupture (0.1%), ventricular septal defect (0.2%), tamponade (0.2%), heart failure (Killip class >1) (15.4%) including cardiogenic shock (3.2%) and need for assistance (1.3%), LV thrombus (1.5%), acute renal failure (4.2%), major bleeding (0.7%) and in-hospital death (2.9%). Independent predictors of the absence of any complications were: younger age (OR=0.97 and 95%CI=[0.96-0.97]), absence of PAD (1.4 [1.2-1.8]), absence of AF (2 [1.6-2.5], absence of HF (2.3 [1.7-3.1]), presentation as NSTEMI (as compared to STEMI) (1.6 [1.4-1.8]), successful PCI (0.6 [0.5-0.7]), heart rate (0.98 [0.98-0.99]), systolic blood pressure (1.01 [1.00-1.01]), creatinine (0.98 [0.97-0.99]), hemoglobin (1.06 [1.03-1.10]), leucocytes (0.94 [0.93-0.96]) and CRP (0.99 [0.99-1.00]).

Conclusions:
In-hospital complications after MI are still frequent (more than 1/4 of patients) and driven by atrial arrhythmias and heart failure. Patients presenting with inaugural NSTEMI successfully revascularized, with no history of cardiovascular disease, and normal heart rate, systolic blood pressure and biology parameters may be targeted for early discharge.
Abstract 11996: National Survey of Coronary Artery Bypass Grafting in Adult Patients With Coronary Artery Lesions Caused by Kawasaki Disease in Japan
Authors: Tsuda Etsuko , Kitagawa Tetsuya , Mitani Yoshihide , Kumamaru Hiraku , Motomura Noboru
Published: December 2023

About 50 years have passed since the first report of Kawasaki disease (KD), and adult patients with coronary artery lesions caused by KD have increased. The national results of coronary artery bypass grafting (CABG) in adult KD patients who had undergone CABG between 2008 and 2019 in the National Clinical Database of Japan were investigated. A total of 343 patients were identified. Furthermore, the outcomes of the 167 patients (49%) after discharge were surveyed by questionnaires. There were 264 male (77%) and 79 female (23%) patients. The median age at operation was 39 (5
th
-95
th
percentile, 13-72 years). The numbers of emergent operations was 37 (10%). Previous CABG and previous percutaneous coronary intervention were performed in 16 (5%) and 50 (15%) patients, respectively. Acute myocardial infarction was found in 64 patients (19%), and cardiogenic shock was found in 10 patients (3%). The mean numbers of grafts and anastomosed vessels were 2 each. The grafts used were as follows. internal thoracic artery 316; saphenous vein grafts 118; gastroepiploic artery 52, and radial artery 56. The anastomosed vessels were as follows. left anterior descending artery 305, right coronary artery 209, left circumflex 145, and diagonal branch 73. Mitral valve surgery and aortic valve surgery were performed in 10 and 9 patients, respectively. The coronary risk factors were as follows: Previous smoking 124 (36%), dyslipidemia 126 (37%); hypertension 124 (36%); and diabetes mellitus 35 (10%). Antiplatelet agents after CABG were administered after CABG to all patients, and coumadin was given to 133 patients (39%). Statins and beta-blockers were given to 143 (42%) and 198 patients (58%), respectively. Three patients (0.8%) died in hospital, and 7 patients died in the late period. Survival rates after CABG at 1, 5 and 10 years were 98%, 94% and 93%, respectively (n= 343). Survival rates at 5 years depending on the values of the preoperative left ventricular ejection (LVEF) were as follows. bad (<30%, n=24), 72%, medium (≧30% but < 60%, n=140), 93% good (≧60%, n=189), 97%. There were significant differences among the 3 groups (p<0.01). The preoperative LVEF affected on the outcome after CABG.
Abstract 12001: To Bleed or Not to Bleed: The Challenging Management of Saddle Pulmonary Embolism in a Patient With Widely Metastatic Breast Cancer
Authors: Patel Zeel K , Shah Keneil , Hossain Afif , Palani Arthi , Solanki Pallavi
Published: December 2023

Introduction:
In patients with high-risk pulmonary embolism (PE), anticoagulation (AC) is the mainstay of treatment before and after systemic thrombolysis and/or catheter-directed therapy. Our case highlights a challenging clinical decision where AC had to be initiated due to hemodynamic instability despite its controversial role in patients with CNS metastases.

Case Description:
A 52 years old female with ER+/PR+/HER2- breast cancer with widespread brain & vertebral metastases presented after a syncopal event. She had tachycardia and hypotension necessitating IV fluids and vasopressors. Echocardiogram showed RV dilation with reduced systolic function & septal wall motion concerning for RV pressure overload. CTA of chest showed large saddle PE with extension into bilateral segmental arteries and enlarged RV. Significant labs: Troponin-I 1.64 ng/mL, BNP 186 pg/mL, hemoglobin 8 g/dL, and platelets 54,000/μl. She was initiated on IV heparin but given worsening hemodynamic instability, she underwent catheter-based thrombectomy with improvement in hemodynamics. Serial CT head showed no evidence of intracranial hemorrhage but she developed diffuse alveolar hemorrhage necessitating intubation. Her bleeding eventually resolved, and she was extubated and discharged on DOAC.

Discussion:
This patient had high-risk PE given her hemodynamic instability, elevation in cardiac biomarkers, and RV strain on imaging. Treatment includes AC followed by systemic thrombolysis or catheter-directed therapy followed by AC. This patient’s management was complicated due to widespread metastases, thrombocytopenia and anemia. AC was nonetheless initiated due to her hemodynamic instability and patient eventually required thrombectomy.

Conclusion:
Brain metastases are an absolute contraindication to systemic thrombolysis, but the role of systemic AC is controversial. Our case highlights the importance of personalized decision-making regarding AC.
Abstract 12041: Coronary Artery Calcium and All-Cause Mortality in the Multicenter Aids Cohort Study: MACS
Authors: Suzuki Takahiro , Haberlen Sabina , Peterson Tess E , Palella Frank , Budoff Matthew , Witt Mallory D , Magnani Jared W , Post Wendy S
Published: December 2023

Introduction:
People living with HIV (PLWH) have more subclinical cardiovascular disease than people without HIV (PWOH), but few studies have evaluated risk for mortality based on coronary artery calcium (CAC) among this population.

Purpose:
This study aimed to determine the association between CAC and all-cause mortality among male PLWH and PWOH and to identify a potential interaction with HIV serostatus.

Methods:
The study population was derived from the MACS, a US prospective observational cohort study including male PLWH and PWOH. Participants underwent cardiac non-contrast computed tomography from July 2004 to November 2013. Men with atrial fibrillation, coronary heart disease, or coronary revascularization were excluded. Cox proportional hazards model was used to calculate adjusted hazard ratios [aHR] for all-cause mortality among men with vs. without baseline CAC (Agatston score>0) and per standard deviation (SD) increment in continuous Agatston score [log (CAC+1)], controlling for demographic and cardiac risk factors. CAC differences by HIV serostatus were evaluated using multiplicative CACхHIV interaction terms.

Results:
Among 1344 males (mean age 50 years, CAC prevalence 46%, 823 (61%) PLWH), we observed 110 deaths (13%) among PLWH and 41 deaths (8%) among PWOH during the follow-up period (median: 13.4 years). Among PLWH, 62% had an undetectable plasma HIV viral load, the median CD4 cell nadir was 284 cells/μL, and 17% had a history of clinical AIDS. The age-adjusted mortality rate was 13.5 (95% CI: 11.0-16.5) among PLWH and 7.8 (5.4-10.9) among PWOH per 1000 person-years. CAC presence was associated with all-cause mortality among all participants (aHR=1.47, 95% CI: 1.02-2.11, p=0.04), and among PLWH (aHR=1.61, 1.04-2.47, p=0.03). In PWOH, we found no significant association (aHR=1.27, 0.63-2.59, p=0.50), although the interaction was not significant (p= 0.49). Higher log (CAC+1) was also associated with all-cause mortality among all participants (aHR=1.37 per SD, 1.15-1.63, p<0.001) and among strata (PLWH, aHR=1.40, 1.13-1.73, p=0.002; and PWOH aHR=1.38, 1.00-1.91, p=0.049).

Conclusion:
CAC predicts all-cause mortality in a large cohort of PLWH and PWOH, with no significant difference in this association by HIV serostatus.