bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12214: Large Left Atrial Infected Myxoma in a Healthy Patient With Intermittent Fever
Authors: Asturias Karla M , Pietrolungo Cara , Craft Colin
Published: December 2023

Introduction:
Infected myxomas represent a rare subset of cardiac myxomas. The diagnosis is classified as definite, probable, or possible based on microbiological and pathological findings. Prognosis is often favorable with early diagnosis and intervention.

Case description:
A 39-year-old female with a history of iron-deficiency anemia presented with three months of fever, poor exercise tolerance, 15-lb unintentional weight loss, and episodes of amaurosis fugax associated with upper extremity paresthesias. Her physical exam revealed tachycardia and a grade 3/6 apical holosystolic murmur. Her laboratory workup was notable for microcytic anemia, elevated inflammatory markers, and
Streptococcus sanguinis
bacteremia
.
Echocardiography showed left ventricular and left atrial dilation with normal systolic function and a 6.4x4.3 cm heterogenous left atrial mass adherent to the interatrial septum with prolapse across the mitral valve plane (Figure 1, panel A-B) associated with eccentric mitral regurgitation. She was managed with surgical resection and antibiotics. Pathology revealed myxomatous tissue and prominent plasma cell infiltrates, confirmatory of definite infected cardiac myxoma. Follow-up echocardiography showed residual mitral regurgitation due to mitral annular stretch from myxoma for which surgical intervention was deferred in the acute setting.

Discussion:
A definite diagnosis of infected myxoma is established with biopsy-proven myxoma, along with microorganism visualization or positive blood cultures with inflammatory cells on histopathology. Rare in occurrence, infected myxomas have been associated with a higher incidence of embolic events, sepsis, and shock compared to uninfected myxomas. Prognosis is favorable with prompt intervention. Increased awareness leading to earlier diagnosis and management is a priority for this subset of patients.
Abstract 12248: Anemia Impacts Mortality, Length of Stay and Resources Utilization on Patients Admitted With Primary Diagnosis of Ventricular Tachycardia: A Nationwide Analysis 2016 - 2020
Authors: Carvalhais Ricardo , Mahfooz Kamran , Ong Kenneth , Najeed Syed Ashfaq
Published: December 2023

Introduction:
Ventricular Tachycardia is a life threating arrhythmia with large admission amount. In this analysis, authors aim to investigate the impact of anemia in patients admitted due to ventricular tachycardia in terms of mortality, length of stay and total hospital charges.

Methods:
This is an analysis of the National Inpatient Sample Database of the years 2016-2020. Adult patients admitted non elective with a primary diagnosis of ventricular tachycardia, with or without a secondary diagnosis of anemia were identified using the ICD-CM codes. The primary outcome was mortality. Secondary outcomes were length of stay and resources utilization. Multivariate logistic analysis was performed, and outcomes were adjusted by age, gender, race, Charlson comorbidity index, hospital location, size, region, teaching status and insurance. Data was considered statistically significant with p-value <0.05.

Results:
Among 221720 patients who had a primary diagnosis of ventricular tachycardia, 17.56% had anemia. Adjusted mortality was significantly different in patients with secondary diagnosis of any anemia with odds ratio 1.95, p value < 0.001, 95% Confidence Interval 1.73 - 2.2. In terms of Length of Stay, patients with anemias of any type stayed 3.09 more days in the hospital when compared to general population, p value < 0.001, 95% Confidence Interval 2.78 - 3.41. Patients with anemia also had an increase on their total hospital charges by 61507.92 dollars, p value < 0.001, 95% Confidence Interval 53771.36 - 69244.48.

Conclusions:
Patients with anemia had 1.95 higher mortality rate, stayed 3.09 more days in the hospital and had a total hospital cost higher by 61507.92$. Anemia can be a risk marker within patients admitted with ventricular tachycardia, more studies needed to investigate if the treatment of anemia improves the outcome.
Abstract 12249: Activation of Prostaglandin E Receptor 4 Ameliorates Perivascular Inflammation and Pulmonary Hypertension in Rats
Authors: Kimuro Keiji , Abe Kohtaro , Imabayashi Misaki , Masaki Kohei , Imakiire Satomi , Hosokawa Kazuya , Kinugawa Shintaro
Published: December 2023

Introduction:
Perivascular inflammation is involved in the progression of vascular remodeling and pulmonary arterial hypertension (PAH). Activation of prostaglandin E receptor 4 (EP
4
) has recently been reported to reduce inflammation in ulcerative colitis and osteoarthritis, but there are no reports on perivascular inflammation in PAH.

Hypothesis:
EP
4
agonist ameliorate perivascular inflammation, vascular remodeling and pulmonary hypertension (PH).

Methods and Results:
We investigated the effects of EP
4
agonist (KAG-308) on hemodynamics and pulmonary artery remodeling in a monocrotaline (MCT)-exposed rat model of PH. Immunohistochemistry detected predominant expression of EP4 proteins in the macrophages and endothelial layer of pulmonary arteries in the lungs of normal and MCT-exposed rats. Compared to normal rats, MCT-exposed rats had increased nuclear factor kappa B (NFκB) activation and significantly higher interleukin 6 (
IL
-6) mRNA levels (1.0±0.4 vs 62.3±39.7,
p
< 0.05) in the lungs, and showed elevated right ventricular systolic pressure (RVSP; 29.7±1.8 vs 81.0±18.5 mmHg,
p
< 0.0001), total pulmonary vascular resistance index (TPRI; 91.0±12.1 vs 161.4 ± 37.0 mmHg/mL/min/g,
p
< 0.001) and RV hypertrophy (0.32±0.02 vs 0.57±0.10,
p
< 0.0001), together with medial wall thickening and perivascular macrophage accumulation on day 21 after MCT injection. Oral administration of EP
4
agonist KAG-308 (1 mg/kg, twice daily, by gavage, day 0 to 21) significantly reduced NFκB activation and interleukin-6 mRNA levels (6.8 ± 2.5,
p
< 0.05) in the lungs. Furthermore, KAG-308 prevented the elevated RVSP (53.1 ± 9.3 mmHg,
p
< 0.01), TPRI (112.0 ± 16.6 mmHg/mL/min/g,
p
< 0.05) and RV hypertrophy (0.47 ± 0.04,
p
< 0.05) by inhibiting medical wall thickening and macrophage accumulation.

Conclusion:
EP
4
agonist ameliorated inflammation, vascular remodeling and PH in MCT-exposed rat. The EP
4
agonist KAG-308 is a potential therapeutic agent for the treatment of PAH.
Abstract 12253: Occludin as a Key Mediator in Adiponectin-Mediated Diabetic Vascular Protection
Authors: Duan Yanru , Du Yunhui
Published: December 2023

Background:
APN exerts its vascular protective effects through APPL1. However, the downstream target genes that mediate the protective effects of this signaling axis on diabetic vascular endothelium remain unclear.

Methods and Results:
APPL1knock-out mice were fed normal or high-fat-diet (HFD) for 10 weeks. 8 weeks after HFD, mice were randomized to receive vehicle or APN treatment for another two weeks. Aortic vessels were prepared for transcriptome analysis. Bioinformatics analysis indicates that the Tight Junction (TJ) pathway exhibited the most prominent changes. Using a global signaling transduction network showed that TJ-related genes had the highest degree values. Among these genes, PCR results indicated that Occludin was the sole gene inhibited in endothelial cells treated by HG/HL and promoted by APN treatment in an APPL1-dependent manner. The protein level of Occludin was reduced in diabetic condition, and APN treatment upregulated the expression of Occludin in APPL1-mediated manner in vivo and vitro. Endothelial specific OCLN knockdown blunted APN-mediated blood flow recovery after femoral artery ligation
in vivo
, and abolished APN’s effects upon HG/HL-induced permeability, and apoptosis
in vitro
. Mechanically, transcription factor expression and activity assay kits, and mass spectrometry techniques were employed to identify transcription factors involved in mediating the APN/APPL1 signaling axis. Through a comprehensive analysis, we discovered MYB, HDAC1, and FOXO1 play a role in the regulation of Occludin. This finding was validated by CHIP-QPCR. Western blot analysis revealed that the APN-induced increase in Occludin protein level was abolished after knockdown of MYB and FOXO1. However, knockdown of HDAC1 in endothelial cells did not alter the expression of Occludin mediated by APN. Finally, CHIP-qPCR showed that both MYB and FOXO1 participate in the enrichment of Occludin promoters mediated by APN.

Conclusion:
Our findings firstly indicate that the APN/APPL1 signaling axis promotes the expression of Occludin through MYB and FOXO1, ultimately exerting a protective effect on vascular endothelium.
Abstract 12256: The High FIB-4 Index is Independently Associated With an Increased Myocardial Extracellular Volume Fraction Quantified by Contrast-Enhanced Cardiac Magnetic Resonance Imaging
Authors: Miura Hiroyuki , Koseki Masahiro , Ide Seiko , nakao kazuhiro , Asaumi Yasuhide , Morita Yoshiaki , Ohta Yasutoshi , Fukuda Tetsuya , Tanaka Katsunao , Omatsu Takashi , Okada Takeshi , Noguchi Teruo , Sakata Yasushi
Published: December 2023

Introduction:
Liver fibrosis is associated with heart failure and left ventricular diastolic dysfunction. The fibrosis 4 (FIB-4) index is calculated from transaminases, age, and platelet count and can be used to screen patients with liver fibrosis. The myocardial extracellular volume fraction (ECVf) can be evaluated using contrast-enhanced cardiac magnetic resonance imaging (CMR).

Hypothesis:
ECVf is increased in patients with high FIB-4 index.
AIMS:
This study aimed to clarify the association between FIB-4 index and ECVf.

Methods:
A retrospective analysis was performed on patients aged ≥ 45 years with left ventricular ejection fraction (LVEF) > 40 % who underwent CMR at two Japanese institutions. Patients were divided into 3 groups according to the FIB-4 index: Low: FIB-4 index < 1.3; Intermediate: 1.3 ≤ FIB-4 index < 2.67; High: 2.67 ≤ FIB-4 index. The association between the FIB-4 index and ECVf was evaluated using multiple regression analysis, with the FIB-4 index treated as a continuous and nominal variable.

Results:
A total of 244 patients were included in the analysis, 136 of whom underwent contrast-enhanced CMR and could be evaluated for ECVf. The ECVf of the high FIB-4 index group was significantly higher than that of the other two groups (High: 31.0 ± 4.3 %; Intermediate: 27.9 ± 3.4 %; Low: 27.6 ± 3.7 %. High vs. Intermediate, p = 0.014; High vs. Low, p = 0.008; Intermediate vs. Low, p = 0.65). Multivariate analysis showed that both the FIB-4 index (continuous variable) and high FIB-4 index (nominal variable) were associated with higher ECVf (continuous variable, p = 0.043; nominal variable, p = 0.016).

Conclusions:
The high FIB-4 index was independently associated with increased ECVf. In contrast, patients with the intermediate FIB-4 index did not have increased ECVf. These suggested the usefulness of FIB-4 index as a cardiac fibrotic parameter.
Abstract 12259: Gas6 Binding With Sav1 to Restore Yap Transcriptional Activity in a Specialized Cardiomyocytes Population Contributes to Heart Regeneration
Authors: Fan Yi , Liu Yu , Zhang Zehao , Zhou Wenfeng , Lin Chengqi , Xie Wei , Ma Genshan
Published: December 2023

Introduction:
The neonatal mammalian heart possesses transient regeneration capacity following injury, during which certain cardiomyocytes (CMs) undergo self-proliferation and establish specific communication networks within the microenvironment. However, the characteristic of these CMs has not been elucidated.

Hypothesis:
Analyzing communication networks of CMs involved in the microenvironment of neonatal heart regeneration will help identify heterogeneous populations of CMs and functional genes for regenerative treatment of adult myocardial infarction.

Methods:
CellChat was used to analyze communication networks in sc(n)RNA-seq datasets of postnatal mouse heart development and post-injury regeneration processes. Transcriptomic analysis was performed on Gas6-enriched CMs. Single-type cell isolation was used to assess Gas6 expression. CM-specific Gas6 loss- or gain-mice were generated using Cre-loxP system and Adeno-associated virus system. Adenoviral gene transfection, mass spectrometry, co-immunoprecipitation, domain truncation constructs, and dual-luciferase reporter gene assay were used to investigate the effect and mechanism of Gas6 in vitro.

Results:
The Gas pathway was identified among 2021 cell-cell pathways as contributing to the development and regeneration of CMs, with Gas6 being the functional gene involved. Gas6-enriched CMs exhibit heterogeneity in relation to proliferation and are abundant in neonatal hearts but disappear in adult hearts. CM-specific Gas6 gene knockout hindered myocardial proliferation in neonatal mice after apex resection. CM-specific Gas6 gene overexpression increased CM proliferation and protected cardiac function during postnatal heart growth and in injured adult hearts. In vitro studies revealed that the α-helical domain of Gas6 interacted with Sav1, inhibiting its recruitment to MST and subsequent phosphorylation cascade. Overexpression of Gas6 promoted Yap translocation into the nucleus and restored the transcription of genes involved proliferation and regeneration.

Conclusions:
Gas6-enriched CMs constitute a specialized population necessary for heart regeneration, in which Gas6 acts as a promoter of Yap transcriptional activity to enhance CM proliferation.
Abstract 12262: Tumor Plop Sound: A Unique Phonographic Finding of a Giant Atrial Myxoma Presenitng as an Acute Decompensated Heart Failure
Authors: Soodi Deepa , Nwaedozie Somto , Shah Milind
Published: December 2023

Introduction:
Atrial myxoma (AM) is the most common primary cardiac benign tumor, with the most common location being the left atrium (LA) near the fossa ovalis. As the tumor enlarges, hemodynamic changes similar to mitral valve stenosis can occur.

Case:
A 51-year-old female without cardiac history was admitted with an acute onset of shortness of breath, started a few minutes prior to arrival at the emergency department. Her blood pressure was 158/74 mmHg, and her heart rate (HR) was 99 bpm, with other vitals remaining stable. Physical examination revealed a tumor plop murmur in left lateral position (Fig.1). Lab work, including CBC, CMP, and high-sensitivity troponins, was unremarkable except for an elevated D-dimer and BNP. EKG indicated sinus rhythm (80 bpm) without ischemic changes. Chest x-ray revealed bilateral opacities, treated with antibiotics. CTA ruled out pulmonary embolism but detected a large hypodense mass in the LA extending to the mitral valve and partially into the left ventricle. Transthoracic echocardiogram measured the mass at 3.5 x 5.2 x 2.8 cm (Fig. 2). The mean diastolic transmitral gradient was 28 mmHg at a heart rate of 92 bpm. The patient was evaluated by cardiothoracic surgeon and underwent excision of the AM following a negative coronary angiogram. Left ventricular end-diastolic pressure was elevated (24 mmHg). Biopsy confirmed cardiac myxoma. The patient was discharged home in stable condition on postoperative day 5. The tumor plop murmur was absent postoperatively (Fig. 1).

Discussion:
AMs are predominantly found in the LA (75%) or the right atrium (25%). Thrombus, vegetation, or malignant tumors can be differential diagnoses. Presentation varies based on mass characteristics, with symptoms like flow obstruction, embolism, arrhythmias, valve dysfunction, heart failure, and syncope. Transthoracic/Transesophageal echocardiogram aids diagnosis, while cardiac MRI is the gold standard. Surgical excision is the primary treatment for AMs.
Abstract 12266: CCND2 Modified mRNA Activates the Cell Cycle in Cardiomyocytes and Improves Recovery From Myocardial Infarction in Small and Large Mammals
Authors: Sun Jiacheng , Wang Lu , Zhou Yang , Zhang Jianyi J
Published: December 2023

Background:
Experiments in mammalian models of cardiac injury suggest that the cardiomyocyte (CM)-specific overexpression of cyclin D2 (CCND2 in humans) improves recovery from myocardial infarction (MI). The primary objective of this investigation was to demonstrate that our Specific Modified mRNA Translation System (SMRTs) can induce CCND2 expression in CMs (CCND2-CMs) and replicate the benefits observed in other studies of CM-specific CCND2 overexpression for myocardial repair.

Methods:
The CCND2-CM SMRTs consists of two modRNA constructs: one codes for CCND2 and contains a binding site for L7Ae, and the other codes for L7Ae and contains recognition elements for the CM-specific microRNAs miR-1 and miR-208. Thus, L7Ae suppresses CCND2 translation in noncardiomyocytes but is itself suppressed by endogenous miR-1 and -208 in CMs, thereby facilitating CM-specific CCND2 expression. Experiments were conducted in both mouse and pig models of MI, and control assessments were performed in animals treated with an SMRTs coding for the CM-specific expression of luciferase or GFP, in animals treated with L7Ae modRNA alone or with the delivery vehicle, and in Sham-operated animals.

Results:
CCND2 was abundantly expressed in cultured, post-mitotic CMs two days after transfection with CCND2-CM SMRTs, and the increase was accompanied by the upregulation of markers for cell-cycle activation and proliferation (e.g., Ki67 and Aurora B kinase). When the GFP-CM SMRTs was intramyocardially injected into infarcted mouse hearts, the GFP signal was observed in CMs but no other cell type. In both the mouse and pig MI models, CM proliferation (on Day 7 and Day 3 after treatment administration in mice and pigs, respectively) was significantly greater, left-ventricular ejection fractions (Days 7 and 28 in mice, Days 10 and 28 in pigs) were significantly higher, and infarcts (Day 28 in both species) were significantly smaller in animals treated with CCND2-CM SMRTs than in any other group that underwent MI induction.

Conclusion:
Intramyocardial injections of the CCND2-CM SMRTs promoted CM proliferation, reduced infarct size, and improved cardiac performance in small and large mammalian hearts with AMI.
Abstract 12288: Sex Differences in Cardiac Adaptation to Obesity During Adolescence: A Role of Cardiopulmonary Exercise Testing
Authors: Tsuda Takeshi
Published: December 2023

Introduction:
Heart size is known to increase in obese individuals as a physiological adaptation. Cardiac hypertrophy is also regarded as a risk factor for future adult cardiovascular disease. Sex differences of cardiac adaptation to obesity during adolescence are poorly understood.

Hypothesis:
Physiological cardiac responses to obesity are different between male and female adolescents.

Methods:
Anthropometric measurements, left ventricular mass index (LVMI; g/m
2.7
), and cardiopulmonary exercise testing parameters were analyzed. Peak oxygen consumption (VO2), ventilatory anaerobic threshold (VAT), and submaximal sloop parameters including ΔVO2/Δheart rate (HR) and ΔHR/Δwork rate (WR) were obtained. Data are shown as mean ± standard deviation. * denotes weight-indexed value.

Results:
Table 1 showed enrolled obese adolescents (19 males and 40 females). ΔVO2/ΔHR and ΔHR/ΔWR are surrogates of stroke volume and HR-dependency, respectively. Males showed significantly higher pVO2, pVO2*, VAT*, ΔVO2/ΔHR, and ΔVO2*/ΔHR but lower ΔHR/ΔWR and ΔHR/ΔWR* than females, suggesting males had higher peak exercise performance, higher stroke volume, and lower HR-dependency than females. Significant correlation was noted between LVMI and VAT* only in males (p = 0.045) and between LVMI and body mass index (BMI) only in females (p = 0.006), suggesting cardiac hypertrophy may not effectively contribute to exercise performance in females (Figure 1). Cardiac hypertrophy assessed by LVMI presented different physiological significance between obese males and females.

Conclusions:
Cardiac adaptation to obesity occurs differently between males and females during adolescence.
Abstract 12289: A Postpartum Diastolic Murmur
Authors: Han Joyce , Sheth Sameer , Isselbacher Eric M , Scott Nandita
Published: December 2023

A 44-year-old G3P1011 underwent uncomplicated Caesarian section for obstetric indications with delivery of a healthy girl. Several hours postpartum, she developed hypoxemia requiring transient supplemental oxygen. Cardiology was consulted for further evaluation.

Upon initial assessment, she appeared comfortable with an oxygen saturation of 93% on room air. She reports an otherwise uneventful pregnancy. Her past medical history is significant for chronic hypertension on propranolol. She was afebrile with a HR of 91, BP 147/66 (left arm) and 155/68 (right arm). Her JVP was 10-11 cm H20. There was a III/IV low-pitched decrescendo early-mid diastolic murmur, loudest at the left lower sternal border, radiating to the apex, and a systolic ejection murmur. EKG (panel A) showed normal sinus rhythm, with no ischemic abnormalities.

Due to the discovery of a new murmur, there was concern for valvular pathology as a cause for her suspected heart failure, particularly aortic regurgitation (AR). An urgent TTE (panel C-E) was requested and showed a dissection flap in the ascending aorta, effacement of the sinotubular junction, and severe AR. CT angiogram confirmed the diagnosis of type A aortic dissection (AD; panel B).

Twelve hours after the delivery of her baby, she underwent emergent aortic valve repair and aortic arch replacement. She recovered well and was discharged home post-op day 6. Though no human data exists, animal data suggests increased AD risk in breastfeeding animals with Marfan Syndrome. Due to her near catastrophic presentation, she elected to not breastfeed. Her genetic testing results are pending.

AD in pregnancy is rare. There is an increased risk of AD in pregnant compared to non-pregnant women. AD often occurs in the third trimester or postpartum, and most women are unaware of a preexisting arteriopathy. In this case, the detection of a diastolic murmur resulted in rapid diagnosis and treatment, essential in the management of this life-threatening condition.
Abstract 12294: Poldip2 Mediates Brain Vascular Permeability by Regulating ZO-1 Phosphorylation and Localization at the Interendothelial Border
Authors: Wang Keke , Hongyan Qu , Lassegue Bernard , Eaton Douglas C. C , Song Chang , Mu Jianjun , Griendling Kathy K , Hernandes Marina S
Published: December 2023

Introduction:
Poldip2 is a novel regulator of cerebral vascular permeability involved in aggravating blood-brain barrier disruption following ischemic stroke; however, the underlying mechanisms are incompletely understood. Tight junctions are crucial for the formation of endothelial barriers and are composed of transmembrane proteins and adaptor proteins such as ZO-1. Cerebral ischemia and inflammation lead to ZO-1 redistribution resulting in vascular permeability.

Hypothesis:
We hypothesized that Poldip2 may mediate ZO-1 phosphorylation and promote brain endothelial monolayer permeability following cerebral ischemia.

Methods:
Cerebral ischemia was induced in endothelial-specific Poldip2 knockout and control mice. Vascular permeability was assessed by Evans blue dye extravasation. For
in vitro
analysis, primary rat brain microvascular endothelial cells were used to investigate the effect of Poldip2 depletion by siRNA on TNF-α-induced permeability and trans-endothelial electrical resistance (TEER). Immunocytochemistry was carried out to investigate the effects of Poldip2 depletion or overexpression on ZO-1 localization.

Results:
Endothelial-specific Poldip2 deletion abolished Evans blue dye extravasation after cerebral ischemia induction (p<0.05). Poldip2 knockdown in vitro suppressed TNF-α-induced endothelial cell (EC) monolayer permeability (FITC-dextran and biotin-avidin assays, p<0.05 and p<0.001) and prevented decreases in TEER (p<0.01). Poldip2 depletion prevented TNF-α-induced ZO-1 disruption at interendothelial junctions (p<0.05). Poldip2 overexpression increased endothelial permeability (p<0.05), decreased TEER (p<0.05), reduced ZO-1 localization at cell-cell junctions (p<0.0001) and enhanced reactive oxygen species (ROS) production (p<0.05). Treatment with the antioxidant N-acetyl cysteine (NAC) abrogated Poldip2-induced ZO-1 disruption (p<0.0001). Immunoprecipitation studies demonstrated that Poldip2 overexpression induced tyrosine phosphorylation of ZO-1 (p<0.0001), an effect prevented by NAC treatment (p<0.01).

Conclusions:
Poldip2 induces ROS-mediated tyrosine phosphorylation of the TJ protein ZO-1 and promotes EC permeability following cerebral ischemia
Abstract 12341: Cardiometabolic Comorbidity Burden and Risk of Hospitalization in Heart Failure Patients
Authors: Hamo Carine , Li Xiyue , Ndumele Chiadi E , Mukhopadhyay Amrita , Adhikari Samrachana , Blecker Saul
Published: December 2023

Background:
Cardiometabolic comorbidities, obesity, diabetes, and hypertension, are highly prevalent in heart failure (HF). However, the implications of comorbidity burden on all-cause hospitalization, overall and among HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are unknown.

Hypothesis:
Higher cardiometabolic burden is associated with increased hospitalization in individuals with HF.

Methods:
In a retrospective EHR-based cohort of adults 18 with HF, we categorized individuals based on the number of cardiometabolic comorbidities present prior to 10/1/2021. Specifically, we defined presence of hypertension and/or diabetes mellitus by diagnosis code, and obesity by BMI 30kg/m2. Cox regression models were used to assess the association between number of cardiometabolic comorbidities and time to all-cause hospitalization within 1 year, adjusting for age, sex, race, and insurance status. Separate analyses were also conducted for HFpEF and HFrEF subgroups.

Results:
There were 26,800 individuals with HF in the study population (mean age 75 13.7, 46% female, 69% White) who experienced 4,284 (16%) hospitalizations over a 1-year period. Compared to those with absent comorbidities (n=3,420), there was an increase in risk for all-cause hospitalization with increasing number of comorbidities, with adjusted hazard ratio (HR) 1.19 (95% CI 1.05-1.34) for 1 comorbidity (n=7,988), HR 1.25 (95% CI 1.11-1.41) for 2 comorbidities (n=9,553), and HR 1.43 (95% CI 1.26-1.62) for 3 comorbidities (n=5,839). (
Figure
) A similar association was also seen for the HFpEF subgroup, but not for the HFrEF subgroup.

Conclusions:
Greater number of cardiometabolic comorbidities (hypertension, diabetes, and obesity) was associated with increased risk of all-cause hospitalization in HF, especially among patients with HFpEF. This suggests a possible role for targeting cardiometabolic comorbidities to reduce HF morbidity in HFpEF.
Abstract 12361: Predictors and Utilization of Ultrasound Enhancing Agents for Echocardiography in the Outpatient Setting
Authors: Strom Jordan B , Song Yang , Jiang Wenting , Lou Yingbo , Pfeffer Daniel N , Massad Omnya E , Russo Pierantonio
Published: December 2023

Background:
The national utilization of ultrasound enhancing agents (UEAs) for transthoracic (TTE) or stress (SE) echocardiography in the outpatient setting and their association with downstream utilization of care remains uncertain.

Methods:
In a set of large, all-payer claims databases (ACTICS Open and Closed Claims) encompassing 90% of the US population, we evaluated rates, predictors of use, and association of UEAs with downstream utilization using linear mixed effects models amongst adult outpatients receiving TTE or SE, 2019-2022. Amongst those with recent hospitalization for AMI, we evaluated the association of UEA receipt and downstream healthcare utilization.

Results:
A total of 11,270,268 individuals receiving TTE and 744,175 adults receiving SE across 2,407 sites were included (mean age 63, 54.8% female), of which 6.8% receiving TTE and 21.0% receiving SE received UEAs. Patients receiving UEAs were more frequently older, male, and had a greater number of comorbidities. Sites performing UEAs were more frequently large, rural, nonprofits, and teaching facilities. Use varied widely by state (
Figure;
19.7% in Minnesota vs. 1.1% in Delaware) and was not explained by patient or site characteristics (median odds ratios = 4.35). Amongst those receiving TTE after AMI, UEA use was associated with a reduction in cardiac non-stress imaging (adjusted RR 0.77, 95% CI 0.64-0.92, p = 0.004), but no substantial differences in cost, days alive at home, readmission rates, cardiac catheterization, or stress imaging (p > 0.05 for all).

Conclusions:
In this large, nationally representative cohort study, UEAs were used in 6.8% of TTEs and 21.0% of SEs performed in the outpatient setting but use varied widely across sites, unexplained by patient or site characteristics. Amongst outpatients, UEA receipt after AMI was associated with a reduction in cardiac stress imaging, but not other outcomes.
Abstract 12378: Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8-10 Years After Delivery
Authors: Countouris Malamo , Catov Janet M , Zhu Jianhui , de Jong Nikki , Brands Judith , Chen Xucai , Parks W. Tony , Berlacher Kathryn , Gandley Robin , Straub Adam C , Villanueva Flordeliza S
Published: December 2023

Introduction:
Hypertensive disorders of pregnancy (
HDP
) are associated with subsequent adverse cardiac remodeling and cardiovascular disease (
CVD
). The pathophysiologic mechanisms linking HDP to CVD, including the role of myocardial microvascular disease, are understudied.

Hypothesis:
Individuals with HDP history will have abnormal microvascular coronary flow reserve (
CFR
) 8-10 years after delivery and abnormal CFR will correlate with left ventricular (
LV
) remodeling.

Methods:
Individuals with pregnancies delivered 2008-2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity vs. time data were used to derive β, the rate of rise of video intensity, a correlate for myocardial blood flow. CFR was calculated as the ratio of β at peak stress to β at rest, averaged across LV myocardial regions of interest.

Results:
We studied 91 individuals (age 38±6, 9.1±0.9 years post-delivery), 19 with a history of HDP). Individuals with abnormal CFR (β ratio <2.0, n=13) had higher pre-pregnancy BMI, baseline heart rate, hemoglobin A1c, and a history of HDP (46.2% vs 16.7%;
p
=0.026). Association of CFR and HDP was attenuated after adjusting for pre-pregnancy BMI and hemoglobin A1c (
p
=0.114). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness>0.42) and HDP had the highest proportion of microvascular dysfunction (41.7% vs. +HDP-LV remodeling 14.3%, -HDP+LV remodeling 7.7%;
p
=0.0498).

Conclusions:
Individuals with HDP history may be more likely to have coronary microvascular dysfunction one decade after delivery. Larger studies are needed to determine if microvascular dysfunction may be a mechanism for development of CVD among individuals with HDP.
Abstract 12381: De Novo Multiple Myeloma in a Patient With Transthyretin Amyloid Cardiomyopathy
Authors: Chiou Andrew , Khedraki Rola , Mohan Rajeev
Published: December 2023

Background:
The development of de novo multiple myeloma in a patient with transthyretin amyloid cardiomyopathy (ATTR-CM) is rare and is often associated with poor prognosis. Early and definitive diagnosis is crucial to improve survival.

Case:
A 63-year-old male was evaluated for heart failure. He had a history of hypertension, sick sinus syndrome status post dual chamber pacemaker, non-sustained ventricular tachycardia requiring ablation in addition to bilateral carpal tunnel syndrome, spontaneous biceps tendon rupture, and lumbar spinal stenosis. Transthoracic echocardiogram showed progressive severe left ventricular hypertrophy with a septal thickness of 2.0cm with a normal left ventricular ejection fraction.

Decision-Making:
Given his history, an amyloid evaluation was performed. Serum and urine assessment for light chain amyloidosis revealed elevated kappa free light chains with kappa/lambda free light chain ratio of 19.30. Bone marrow biopsy at that time showed normocellular bone marrow with less than 3% plasma cells. An abdominal fat pad biopsy was inconclusive. A cardiac MRI was unobtainable given non-compatible pacemaker leads and a technetium-99m pyrophosphate scintigraphy was deferred given his abnormal light chains. An endomyocardial biopsy was performed and revealed wild-type ATTR deposition by mass spectrometry. Serum genetic test confirmed the absence of TTR gene mutation. The patient was started on Tafamadis. Six months later, he was noted to have progressive elevation in kappa free light chains on serial evaluation and underwent a repeat bone marrow biopsy. This showed plasma cell myeloma with 25-30% marrow cellularity and flow cytometry consistent with kappa light chain multiple myeloma. He was started on Daratumumab, Lenalidomide, and Dexamethasone. This resulted in normalization of his free light chain ratio and morphologic remission on repeat bone marrow biopsy.

Conclusion:
In patients who are found to have monoclonal gammopathy, an endomyocardial biopsy is crucial to evaluate for amyloid cardiomyopathy. These patients should also be monitored for the progression to multiple myeloma.
Abstract 12393: Pexidartinib Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats
Authors: Nishiura Kazuto , Yokokawa Tetsuro , Misaka Tomofumi , Miura Shunsuke , Tomita Yusuke , Sato Akihiko , Oikawa Masayoshi , Sugimoto Koichi , Nakazato Kazuhiko , Takeishi Yasuchika
Published: December 2023

Background:
Pulmonary arterial hypertension (PAH) is a life-threatening disease caused by pulmonary artery remodeling, inflammation, and altered immune responses. Lungs from PAH patients show that accumulation of perivascular macrophages is a key factor for the development of pulmonary artery remodeling, which leads to right ventricular failure. However, pharmacological inhibition of this pathway for treating PAH has not been thoroughly examined. Pexidartinib inhibits macrophage proliferation and polarization, thus can be a candidate for treating PAH.

Objective:
To investigate the effect of pexidartinib in PAH.

Methods:
Male Sprague-Dawley rats were divided into 4 groups: control, pexidartinib treated, monocrotaline (MCT)-exposed, pexidartinib treated and MCT-exposed rats. Right ventricular hemodynamic changes, right ventricular hypertrophy, and pulmonary artery morphological features were examined. Pulmonary artery perivascular macrophage infiltration was determined by immunofluorescence of CD68 and arginase-1 (M2 macrophage marker).

Results:
Immunofluorescence of lungs from MCT-exposed PAH rats showed perivascular CD68- and arginase-1-positive macrophage infiltration (P < 0.05, each) and muscularization of pulmonary arteries (P < 0.05) compared to controls. Treatment of pexidartinib inhibited perivascular CD68- and arginase-1-positive macrophage infiltration (P < 0.05, each) and attenuated right ventricular systolic pressure and the right ventricle to the left ventricle plus septum ratio (RV/LV+IVS) in MCT-exposed PAH rats (Figure 1).

Conclusion:
Pexidartinib treatment prevented MCT-induced PAH and right ventricular hypertrophy by inhibiting perivascular macrophage infiltration and M2 macrophage polarization in rat pulmonary arteries. Therefore, pexidartinib may be a promising drug for the treatment of PAH.
Abstract 12424: Left Atrial Strain and Incident Heart Failure in Older Adults
Authors: Mannina Carlo , Ito Kazato , Jin Zhezhen , Yoshida Yuriko , Russo Cesare , Nakanishi Koki , Elkind Mitchell , Rundek Tatjana , Homma Shunichi , Di Tullio Marco
Published: December 2023

Introduction:
The prevalence of heart failure (HF) is rising, particularly in older adults. Left atrial (LA) dysfunction is commonly seen in HF, but it is unclear if it predicts onset or contributes to its development.

Hypothesis:
LA strain reduction is associated with incident HF in the general elderly population, independent of other risk factors and even in the presence of normal LA volume.

Aims:
We aimed to investigate the association between reduced LA strain (LAε) and strain rate (LASR) and incident HF in older adults without history of HF or atrial fibrillation (AF), adjusting for HF risk factors and echocardiographic parameters.

Methods:
We examined 795 participants aged ≥55 from the Cardiovascular Abnormalities and Brain Lesions (CABL) study with no history of HF or AF. LAε
pos
, LASR
pos
, LASR
early-neg
, and LASR
late-neg
were assessed using speckle-tracking echocardiography for global, reservoir, conduit and pump function, respectively. Incident HF was detected through standardized interviews, in-person visits, active hospital surveillance of admission and discharge ICD-9 codes. LA strain's association with incident HF was assessed using a cause-specific hazards regression model, adjusting for HF risk factors, including incident AF.

Results:
Mean age was 70.9±9.2 years (297 men, 498 women). During a mean follow-up of 11.4 years, 215 participants (27.0%) developed new-onset HF; incident AF occurred in 98 (12.3%). Left ventricular ejection fraction and global longitudinal strain were not associated with new-onset HF (p=0.06 and p=0.23, respectively). All LA strain measures at baseline were significantly associated with new-onset HF (all p<0.01). In multivariable analysis, only LASR
late-neg
(adjusted HR per SD decrease 2.31, 95% CI 1.12-4.43) remained independently associated with new-onset HF, after adjusting for LA volumes, left ventricular systolic function, and incident AF. LASR
late-neg
was especially associated with incident HF in participants with normal LA size (HR 8.64, CI 3.10-24.08).

Conclusion:
Reduced LA strain during atrial contraction is independently associated with new-onset HF in older adults. LA strain measurement may improve HF risk stratification in older adults, even in the presence of normal LA volume.
Abstract 12452: Risk Stratification in Cardiogenic Shock Patients With Venoarterial Extracorporeal Membrane Oxygenation Using Lung Computed Tomography Density and Model for Endstage Liver Disease Score
Authors: Hada Tasuku , Seguchi Osamu , Nana Kitahata , KOMEYAMA SHOTARO , Mochizuki Hiroki , Tadokoro Naoki , Kainuma Satoshi , Watanabe Takuya , Fukushima Satsuki , Tsukamoto Yasumasa
Published: December 2023

Background:
End-organ dysfunction often occur in patients receiving femoro-femoral veno-arterial extracorporeal membrane oxygenation (VA ECMO) and it has been reported to be associated with poor prognosis. This study aimed to elucidate the ability to risk stratification in patients with cardiogenic shock (CS) who received VA ECMO using lung computed tomography (CT) density and Model for End-stage Liver Disease exclude INR (MELD-XI) score.

Methods:
This is a single-center retrospective observational study targeted 65 CS patients who has had available chest CT images on VA ECMO support followed by MCS escalation from 2012 to 2021. The average density of lung CT images in the lung field at the level of tracheal bifurcation was measured using region-of-interest methods. MELD-XI scores were also calculated. The primary endpoint was 180-day all cause death after MCS escalation.

Results:
Twenty-two patients (34%) died within 180 days during the follow-up period [659 (78-1,544) days]. According to the Cox regression analysis higher MELD-XI scores (≥ 18) (HR; 2.68; 95% CI, 1.05-6.86; p=0.039), and higher lung CT density [≥ -481 Hounsfield unit (HU)] (HR, 5.64; 95% CI, 1.95-16.28; p=0.001) were independently associated with all cause death. Moreover, combination of both lung CT density and MELD-XI score further refine risk stratification in current patient population : group A, high lung CT density (≥-481 HU) and high MELD-XI score (≥18); group B, high lung CT density (≥-481 HU) or high MELD-XI score (≥18); and group C, low lung CT density (<-481 HU) and low MELD-XI score (<18) (group A:31.3% vs. group B:65.2% vs. group C:88.5%, log-rank p<0.001).

Conclusions:
Combination of higher lung CT density and higher MELD-XI score is a useful predictor of prognosis in patients with VA ECMO requiring escalation of MCS.
Abstract 12461: Early Use of Tocilizumab Following Cytokine Release Syndrome During CAR-T Therapy for Multiple Myeloma May Be Associated With Fewer Short and Long Term Adverse Cardiovascular Events
Authors: Golec Sophia , Pileggi Brunna , Moshier Erin , Peleg Ariel , Rossi Adriana , SAHNI GAGAN
Published: December 2023

Background:
Chimeric antigen receptor-T cell (CAR-T) therapies have recently been approved for multiple myeloma (MM). Patients with MM have a higher burden of cardiovascular (CV) disease compared to other hematologic malignancies due to higher prevalence of CV risk factors, potentially cardiotoxic therapies and older age. Retrospective studies of CAR-T therapy in other hematologic malignancies demonstrated a 20-30% CV event rate following higher grades of cytokine release syndrome (CRS). Early use of the interleukin-6 antagonist, tocilizumab, to reverse CRS has been reported to lower rates of major adverse CV events (MACE).

Hypothesis:
At our institution, tocilizumab is usually administered as early as grade 1 CRS. We hypothesized that our patients would have lower rates of CV toxicity compared to studies where tocilizumab was administered late or not at all.

Methods:
We conducted a retrospective chart review of adult patients undergoing CAR-T therapy for MM between 2017 and 2023. The primary outcome was MACE (composite of myocardial injury, new heart failure, stroke, new arrhythmias and CV death) over a median period of 12 months. A Kaplan-Meier curve was used to analyze probability of developing MACE.

Results:
Of the 145 patients studied, the demographics included median age of 61, male (61%), prior anthracycline use (25%), and carfilzomib use (47%) within 1 year. CV co-morbidities included 57% with hypertension, 35% hyperlipidemia, 23% diabetes mellitus type 2, 17% coronary artery disease, and 14% left ventricular dysfunction. CRS occurred in 121 (83%) patients, of which 99 had grade 1 (82%), 19 (16%) had grade 2 and 3 (2%) had grade 3. Of those with CRS, 108 (89%) received tocilizumab, on average within the first day of CRS. Within 1 year of CAR-T therapy, 14 patients (10%) experienced MACE. The Kaplan-Meier estimates for incidence of MACE were 6% at 30 days, 8% at 6 months and 11% at 12 months.

Conclusion:
The occurrence of MACE in MM patients following CAR-T therapy with early administration of tocilizumab was lower compared to previously published retrospective studies of CAR-T therapy for other hematologic malignancies despite high CV burden. Further prospective studies are needed to validate these findings.
Abstract 12464: Family Caregiving Support and Sleep Duration Among African American Family Caregivers
Authors: Irani Elliane , Griggs Stephanie , Aldossary Heba , Still Carolyn H , Hickman Ronald L
Published: December 2023

Background:
African Americans family caregivers are at risk for poor sleep health and cardiovascular disease. Psychological health (i.e., depressive symptoms) and social determinants of health (i.e., social interactions) are associated with sleep health (i.e., sleep duration) and are important contextual drivers of cardiovascular health. Recently, the American Heart Association recognized sleep duration as a component of cardiovascular health. However, there is limited literature on psychological and social determinants of sleep duration among African American family caregivers.

Aim:
The purpose of this cross-sectional study was to examine the contribution of depressive symptoms and family caregiving support to sleep duration among African American family caregivers. We hypothesized that higher levels of depressive symptoms and lower levels of family caregiving support would be associated with shorter sleep duration.

Methods:
African American family caregivers (
n
= 55) of adults with chronic illness were recruited through community-engaged strategies. Demographic, depressive symptoms, family caregiving support, and sleep duration data were based on self-report measures, whereas body mass index (BMI) data were based on objective height and weight assessments. Hierarchical linear regression was used to determine the contributions of depressive symptoms and family caregiving support on sleep duration, controlling for age, gender, and BMI.

Results:
On average, participants were 60.67 years old (SD = 12.04) and had a BMI of 34.61 (SD = 7.55). The majority self-identified as female (87.3%). Mean self-reported sleep duration was 5.87 hours (SD = 1.35) per night, which is below the recommended sleep duration of 7-9 hours for adults. In the final model, lower levels of family caregiving support were associated with shorter sleep duration (
b
= -.46,
p
= .046), controlling for caregivers’ age, gender, BMI, and depressive symptoms.

Conclusion:
Family caregiving support is a modifiable target to promote sleep and cardiovascular health equity for African American family caregivers. Multilevel interventions may optimize the support that caregivers receive from other family members and friends as well as professional and community-based sources.
Abstract 12471: Use of Traditional Heart Failure Medications in Patients With Cardiac Amyloidosis and Heart Failure is Safe but Does Not Improve Mortality or Hospitalization
Authors: Yan Crystal L , Gallo Ryan A , Vasquez Moises , Rivera Rodriguez Beatriz , Trujillo Luis , Rivera Nina , hoffman james
Published: December 2023

Background:
Randomized controlled trials have demonstrated mortality benefit for several medication classes in patients with heart failure (HF), especially with reduced ejection fraction. However, the benefit of these traditional HF therapies in patients with HF from cardiac amyloidosis is unclear.
Objective:
The aim of this study was to evaluate the safety and efficacy of traditional HF therapies in patients with cardiac amyloidosis and HF with reduced ejection fraction (HFrEF) or HF with mid-range ejection fraction (HFmrEF).

Methods:
We conducted a single-center retrospective study. Patients were included if they were diagnosed with cardiac amyloidosis and HFrEF or HFmrEF between January 2012 and 2022. The primary outcomes of interest were medication use patterns (for beta blockers (BB), angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitors (ARNI), and mineralocorticoid receptor antagonists (MRA)); potential medication side effects (symptomatic bradycardia, fatigue, hypotension, lightheadedness, and syncope); hospitalization; and death. The associations of BB, ACEI/ARB/ARNI, and MRA use with clinical outcomes were evaluated using Kaplan Meir and Cox proportional hazards regression.

Results:
82 patients met study criteria. At time of cardiac amyloidosis diagnosis, 63.4% were on a BB, 51.2% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. At last follow up, 51.2% were on a BB, 35.4% were on an ACEI/ARB/ARNI, and 43.9% were on a MRA. There were no statistically significant differences in rates of potential medication side effects in patients on the medication class compared to those who were not. There was no association with mortality for baseline or follow-up BB, ACEI/ARB/ARNI, or MRA use. There was an association with hospitalization for baseline and follow-up MRA use, but this effect was lost after controlling for pre-specified covariates.

Conclusions:
BB, ACEI/ARB/ARNI, and MRA use is not infrequent in patients with concomitant cardiac amyloidosis and HFrEF or HFmrEF. These traditional HF therapies may be safely used in this population. However, their use does not appear to improve mortality or hospitalization.