bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18622: The Role of MicroRNA-98 in the Context of Myocardial Ischemia-Reperfusion Injury During Late Pregnancy
Authors: Aryan Laila , Medzikovic Lejla , Li Min , Ruffenach Gregoire , Rahman Shadie , Esdin Leana , Bastanhagh Ehsan , Sun Wasila , Afshar Yalda A , Eghbali Mansoureh
Published: December 2023

BACKGROUND:
We have shown that the late-pregnant (LP) rodent exhibits a higher susceptibility to myocardial ischemia-reperfusion injury (IRI) compared to non-pregnant (NP). The molecular mechanisms remain unclear. The dysregulation of multiple microRNAs (miRs) in IRI suggests their potential as promising targets for therapeutic interventions.

Methods:
Female Sprague-Dawley rats in both NP and LP states underwent occlusion of the left anterior descending coronary artery (LAD) for a duration of 45 minutes, followed by reperfusion for 3 hours or 24 hours. Expression of miR was assessed via fluorescent
in situ
hybridization. MicroRNA-microarray profiling was conducted on hearts of NP and LP rats subjected to IRI. Female H9c2 rat cardiomyoblast cells were transfected with miR mimics and inhibitors, and subjected to hypoxia/reoxygenation. Blood samples were obtained from NP, LP, and ischemic heart disease (IHD) patients. MiR98 inhibitor was administered at the initiation of reperfusion.

Results:
MicroRNA-microarray analysis revealed upregulation of microRNA-98-5p (miR-98) in LV of LP at baseline, and a further upregulation after IRI. The expression of Stat3 and Pgc-1α were decreased in LV of LP rats compared to NP rats upon IRI. Fluorescent
in situ
hybridization revealed expression of miR-98 in cardiomyocytes in NP rats, which was increased in LP rats. Overexpression of miR-98
in vitro
in female H9c2 cells decreased Stat3 and Pgc-1α levels, and promoted apoptosis, oxidative stress, and inflammatory markers. MiR-98 inhibitor in LP rats at the onset of reperfusion reduced infarct size, apoptosis, oxidative stress, and inflammatory markers and was associated with upregulation of Stat3 and Pgc-1α. In humans, plasma miR-98 levels were significantly higher in healthy LP compared to healthy NP individuals and even higher in LP patients with IHD patients.

CONCLUSIONS:
We show the detrimental effects of miR-98 by promoting cardiomyocyte oxidative stress, inflammation, and apoptosis via its targets Stat3 and Pgc-1α in the context of late pregnancy. MiR-98 could be a novel cardio-protective strategy or biomarker in late pregnancy.
Abstract 18628: Focal Pericoronary Adipose Tissue Evaluated by Electron Density Numbers on Contrast Spectral Computed Tomography Was Associated With Coronary Arterial Plaques: A Site-by-Site Analysis
Authors: Funabashi Nobusada , Shukuya Atsushi , Asano Hiroki , Kawamura Akio , Mizuno Naoko
Published: December 2023

Introduction:
Inflammation in pericoronary adipose tissue (PCAT) around the coronary arterial wall causes coronary arterial sclerosis. Many studies evaluated the relationship between total PCAT volume and coronary arterial sclerosis on a patient-by-patient basis. Hypothesis: Inflammation in PCAT may occur focally in coronary arterial system to which coronary arterial plaques localize. Using novel spectral CT, based on electron density number (EDN) as a new parameter, the focal characteristics of PCAT were evaluated.

Methods:
17 patients (10 males, mean age 70 years) underwent cardiac spectral CT (7500, Philips, Tokyo, Japan). From contrast data, EDNs of PCAT were determined at a 1) right side site and 2) left anterior side site of a proximal portion of the right coronary arteries (RCA), 3) anterior side site of the left main coronary arteries, 4) left side site of a proximal portion of the left circumflex artery, and left side site of a distal portion of the RCA (five sites each patient). We also evaluated coronary arterial plaques on enhanced CT images at five corresponding sites for which EDNs were determined.

Results:
For a total of 85 sites among 17 patients using enhanced CT, 31 sites had no plaques (group 1), 14 sites had only non-calcified plaques (group 2), 20 sites had only calcified plaques (group 3), 16 sites had mixed plaques (group 4), and four sites had stent implantations (group 5). The mean of EDNS (%EDW) for 81 sites, excluding four sites with a stent implantation, were 93.7, 93.9, 94.0, and 94.3 in groups 1-4, respectively (P=NS). For a total of 81 sites, excluding four implantation sites, we evaluated the relationship between age and EDNs in groups 1-4. No correlations were observed in group 1 (R= 0.05), 3 (R= 0.09), and 4 (R= 0,15), however negative correlation was observed in group 2 (R= -0.42) between age and EDNs. No significant differences in EDNs were noted between males and females (P=NS).

Conclusions:
This is the first study in which focal PCAT was evaluated by EDNs and the relationship to coronary arterial plaques determined by site-by-site analysis. This new CT parameter may evaluate the status of PCAT and be a predictor of the future occurrence of coronary arterial plaques, which are related to PCAT inflammation.
Abstract 18629: Discriminative Accuracy of Cha
2
Ds
2
Vasc Score, and Development of Predictive Accuracy Model Using Machine Learning for Ischemic Stroke in Cardiac Amyloidosis
Authors: Ullah Waqas , Nair Abhinav , Warner Eric , Zahid Salman , Frisch Daniel , Rajapreyar Indranee , Alvarez Rene , Alkhouli Mohamad A , Yaddanapudi Sridhara , Maurer mathew S , Brailovsky Yevgeniy
Published: December 2023

Background:
Cardiac amyloidosis (CA) in conjunction with atrial fibrillation (AF) presents unique management challenges. CHA2DS2VASc score in these patients is believed to underestimate the risk of ischemic stroke, necessitating a better predictive model in these patients.

Methods:
Data was obtained from the National Readmission Database (NRD). Outcomes between CA-AF and no-CA-AF were compared using multivariate regression analysis to calculate adjusted odds ratios (aOR). AutoScore; an interpretable machine learning framework, was used to develop a stroke risk prediction model, the predictive accuracy of which was evaluated with an area under the curve (AUC) using the receiver operating characteristic analysis.

Results:
A total of 11,860,804 (CA-AF 22,687 [0.19%] and no-CA-AF 11,838,117) patients were identified from 2015-2019. The adjusted odds of mortality (aOR 1.41 and 1.29), stroke (aOR 1.78 and 1.74), non-intracranial hemorrhage (aOR 2.10 and aOR 1.85), and intracranial hemorrhage (aOR 14.4 and aOR 4.26) were significantly higher in CA-AF compared with non-CA-AF at both index admission and 30-days, respectively. The CHA
2
DS
2
VASc score had a poor discriminative accuracy for stroke at 30-days in CA-AF (AUC 49%, 95%CI 47%-51%, p=0.54). The machine learning autoscore integrative model revealed that the predictive ability of our newly proposed E-CHADS score (end-stage renal disease (ESRD), congestive heart failure, hypertension, active cancer, dementia, and diabetes mellitus) for 30-day risk of ischemic stroke in CA-AF was excellent (for a cutoff of 52 points random forest score) with an AUC of 80% (95%CI 74%-86%)

Conclusion:
Cardiac amyloidosis carries a high risk of ischemic stroke that is not accurately predicted by the CHA
2
DS
2
VASc score. Our proposed model (E-CHADS) identifies 3 new variables (ESRD, dementia, and cancer) that have higher discriminative accuracy for ischemic stroke in these patients.
Abstract 18677: Residual Cardiovascular Risk Reduction Through a Digital App
Authors: Romano Letizia R , Curcio Antonio , Bruno Federica , Bartone Anna , Festa Miriam , Velato Letizia , Malizia Biagio , Scalzi Giuseppe , Augusto Florinda M , Indolfi Ciro
Published: December 2023

Introduction:
atherosclerotic cardiovascular disease (ASCVD) is the first cause of disability and death globally and represents the main etiological agent of myocardial infarction and ischemic stroke. The causal association between LDL cholesterol (LDL chol) and ASCVD is one of the most consolidated topics of modern medicine: it has gone from the demonstration that high levels of LDL Chol are a necessary condition for atherogenesis to the awareness that "the lower the better" and "the earlier the better" to underline the need for secondary and primary prevention to reduce atherosclerotic burden.

Hypothesis:
we hypothesized that motivational alerts sent through telemedicine to patients could affect escalation therapy in ASCVD patients.

Aim:
we evaluated the impact of a digital-APP in dyslipidemia management, and other CV risk factors, but focusing mainly on LDL chol.

Methods:
fifty dyslipidemic patients (APP_pts; 40 males; mean age 62±9 years; age range 40÷81 yrs) were followed through telemedicine-based APP from March 2022 to May 2023, in comparison with additional 50 dyslipidemic patients (ST_pts; 43 males; mean age 63±9 years; age range 40÷81 yrs) who underwent standard outpatient visits. Patients’ access to digital APP was remotely monitored and reports were used for therapy adjustments. Statistical analysis was performed with GraphPad Prism 7; comparisons were carried out by two-way ANOVA and by chi-square test.

Results:
baseline LDL chol values were 93,3±36,4 mg/dL, and 90,8±43,8 mg/dL, in APP_pts and in, ST_pts, respectively; six months after enrollment, both cohorts experienced significant reductions (APP_pts, 72,1±35,2 mg/dL, p=0,024; ST_pts, 76,7±38,6 mg/dL, p=0,008) vs baseline. We further subdivided both groups into ischemic and non-ischemic subjects (APP_pts: 26 vs 24; ST_pts : 33 vs 17). Remarkably, telemedicine control showed a 32% reduction in LDL chol for ischemic pts, while ischemic ST_pts gained only 11%. Overall, dyslipidemic control in non-ischemic pts appeared less beneficial (17 vs 15%). Finally, telemedicine-based APP resulted more effective than standard monitoring (p=0,04).

Conclusion:
aggressive lipid lowering therapies should be implemented with remote patients monitoring, mostly in the post-ischemic setting.
Abstract 18679: Sex Ed Can Never Be Bad With a VAD
Authors: Shelton Catherine , van Zyl Johanna , Carey Sandra , Warren Ann Marie , Whiteley Whitney , Afzal Aasim , Parker Lesia , Jamil Aayla , Felius Joost , Hall Shelley , Alam Amit
Published: December 2023

Introduction:
Little is known about the impact on sexual activity and sexual quality of life in patients with durable left ventricular assist devices (LVADs).

Objective:
To describe the impact of LVADs on sexual quality of life, depression, and anxiety in patients and their partners.

Methods:
This is a single-center, prospective, observational analysis from December 2021 to May 2023. Consecutive patients ≥4 months post-LVAD implantation and their partners completed the Sexual Activities in Left Ventricular Assist Device Patients Or PaRtners (SALVADOR) questionnaire to assess sexual quality of life, the Patient Health Questionniare 8 Item (PHQ-8) to assess symptoms of depression and the Generalized Anxiety Disorder 7 Item (GAD-7) to assess symptoms of anxiety.

Results:
61 patients and 58 partners completed the questionnaires. 87% patients and 14% partners were male. The median age of patients was 58 years with 87% living with their partner and 13% being single. 10% of patients and 19% of partners had a current diagnosis of a psychological condition, most frequently depression and/or anxiety. Overall, 50% of participants indicated that the VAD influenced their sexual activity. Disturbances from the driveline was the most common problem indicated. 24% of participants had scored in the mild to moderate depression range on the PHQ-8 and 29% scored in the mild to severe anxiety range on the GAD-7. The median total GAD-7 were comparable between patients and partners; whereas patients had a higher total PHQ-8 score. A preference to receive information regarding sexuality while on VAD support was indicated by 55% of participants and did not differ between patients and partners. Written resources was the most common preferred source of information.

Conclusion:
LVADs severely affect the sexual quality of life for patients and their partners. The presence of a driveline is a major cause for concern. Patients prefer receiving information on how to improve their sexual quality of life.
Abstract 18687: Cardio-Rheumatology: Coronary and Cerebrovascular Thromboses in Antiphospholipid Antibody Syndrome
Authors: Reejhsinghani Risheen
Published: December 2023

Description of Case:
A 27-year-old male with antiphospholipid antibody syndrome (APLS) with a high-risk antibody profile presented for cardiac evaluation. APLS was diagnosed after presentation with acute cardioembolic stroke requiring thrombolysis. Echocardiography showed a normal ejection fraction, with multiple small echo-densities attached to the anterior and posterior leaflet tips of the mitral valve suggesting non-bacterial thrombotic endocarditis (NBTE). The patient was treated with warfarin and aspirin was recommended but declined. As the patient reported lightheadedness, a cardiac rhythm monitor was placed and showed two episodes of non-sustained ventricular tachycardia (NSVT). A cardiac MRI was then obtained, showing multifocal, subendocardial and mesocardial delayed gadolinium enhancement suggesting fibrosis, in a distribution most consistent with a multivessel embolic event. A CT coronary angiogram was performed to further evaluate the coronary arteries, revealing normal coronary anatomy, free from atherosclerotic plaque or thrombus. Beta-blocker therapy was initiated for arrhythmic episodes, with resolution of symptoms and no recurrence of NSVT on follow-up monitoring. Left ventricular (LV) function continued to remain preserved on follow-up imaging, with no progression of mitral valve vegetations on anticoagulation.

Discussion:
Cardiac involvement in APLS has been well described but largely centers around valvular disease and de novo venous and arterial thromboses. This case of cerebrovascular and coronary pathology in APLS as a likely consequence of thromboembolic phenomena is an unusual presentation and highlights the potential downstream consequences of left-sided valvular NBTE. A high index of suspicion is required to specifically evaluate for myocardial scarring despite normal LV function on echocardiography. The presence of myocardial fibrosis in these cases can act as a focus for scar-related ventricular arrhythmias, which if diagnosed and treated in a timely manner can limit further cardiovascular complications for the patient.
Abstract 18695: C5ORF51/RIMOC1 - A Novel Regulator of Cardiogenesis
Authors: Zhang Xueyang , Gandhi Alay , Ratakonda Gayatri , Williams Charles H , Sun Lingfei , LI FENG , Ward Christopher W , Hong Charles C , Gladwin Mark T , Yechoor Vijay K , Liu Ruya
Published: December 2023

Introduction:
Adult human cardiomyocytes (CMs) have poor capacity for proliferation and functional recovery after heart attack, thus leading to the high morbidity and mortality of cardiovascular diseases. Thus, there is great need to understand the underlying mechanisms of adult CM turnover and maturation. While screening for modulators of TEAD1, the downstream transcriptional effector of Hippo pathway, my lab identified a novel factor—C5ORF51/RIMOC1—as a potential cardiomyogenic modulator. C5ORF51 (hereinafter referred to as C5x) is a previously uncharacterized protein of nearly unknown function, which appears to play critical roles in the regulation of CM homeostasis and heart size.

Hypothesis:
C5x is a novel cardiomyogenic regulator which determines CM turnover, maturation, and function.

Methods and Results:
(1) Ex vivo C5x deletion in mouse neonatal CMs leads to significantly increased percentages of cells in S-G2-M phases, suggesting that C5x mediates CM cell cycle arrest in a cell-autonomous manner; (2) In vivo CM-specific C5x-knockout mouse model shows significantly enhanced CM proliferation in adult mice as well as increased CM endowment and mononuclear diploid populations, indicating that C5x has an essential role in cell replication and division in vivo; (3) With age, C5x-CM-knockout mice develop systolic dysfunction, massive cardiomegaly, late-onset dilated cardiomyopathy, and premature mortality, demonstrating a critical role of C5x in maintaining normal cardiac function; (4) RNA sequencing analysis further reveals that C5x loss-of-function activates fetal gene expression while its gain-of-function suppresses fetal gene expression, suggesting C5x as a gatekeeper of the fetal gene program.

Conclusions:
C5x is required for CM cell cycle arrest, and its loss results in fetal gene activation leading to a primitive cell state and immature CM expansion.
Abstract 18709: Disparities in Socioeconomic Metrics Associated With Adverse Outcomes Among Medicare Beneficiaries Undergoing Peripheral Endovascular Intervention
Authors: Misra Shantum , Krawisz Anna , Carroll Brett , Secemsky Eric A
Published: December 2023

Background
Low socioeconomic status (SES) is associated with an increased incidence of peripheral artery disease, however there is a lack of granularity in the specific metrics that contribute to this discrepancy. We examine the association of community-level economic distress with adverse outcomes in patients undergoing peripheral endovascular intervention (PVI).

Hypothesis:
Socioeconomically distressed communities have non-healthcare-related, structural disparities that contribute to incident PVI and adverse outcomes.

Methods:
Medicare beneficiaries ≥66 years of age from 2016 to 2018 were evaluated to determine the incidence of femoropopliteal PVI. The Distressed Community Index (DCI) was used to categorize adults as distressed (DCI ≥80) or not distressed (DCI <80). Composite outcome of death and major amputation within 1 year of PVI were examined by level of distress using individual community-level metrics.

Results:
Socioeconomically distressed adults underwent 158 PVIs per 100000 distressed beneficiaries compared with 109 PVIs per 100000 non-distressed beneficiaries (risk ratio, 1.45 [95% CI, 1.42-1.48]; P<0.001). Distressed adults who underwent PVI were more likely to be female (45.5% versus 43.1%; P<0.001) and Black race (21.9% versus 10.1%; P<0.001) (Table I). There was a strong association between distress and the composite outcome at 1 year (incidence rate ratio, 1.11 [95% CI 1.07-1.16; P=0.0001]). Distressed adults lacked high school diplomas (11.88% versus 11.15%; P<0.001), had higher rates of unemployment (24.11% versus 22.76%; P<0.001), and greater housing vacancy rates (9.74% versus 9.31%; P<0.001).

Conclusion:
Socioeconomic distress is associated with higher rates of PVI-incidence and post-PVI adverse outcomes. This may be driven by structural inadequacies inherent to low SES communities that need to be addressed in order to narrow the gap in care among distressed adults undergoing PVI.
Abstract 18714: Myocardial Infarction With Non-Obstructive Coronary Artery Disease in a Young Woman - The Cardinal Role of Coronary Reactivity Testing in Unveiling the Underlying Etiology
Authors: Kolimas Amie M , Beverly Joshua K , Kashif Mohammad , Acharya Tushar , Vangala Adarsh , Corban Michel T
Published: December 2023

43-year old female presented to the emergency department with substernal chest pain. She had similar symptoms years ago without obstructive CAD on coronary angiogram and was diagnosed with myocarditis. Presenting ECG revealed new anterolateral T wave inversions (Fig 1), and high-sensitivity troponins peaked at 322 ng/L consistent with NSTEMI. TTE was significant for global hypokinesis of the left ventricle with a reduced ejection fraction of 35 to 40%. Invasive coronary angiogram showed no obstructive CAD or spontaneous coronary artery dissection however there was reduced flow in the mid to distal LAD raising suspicion for endothelial and microvascular dysfunction. Contrast-enhanced cardiac MRI showed myocardial edema in the anterior and anteroseptal walls with elevated myocardial T1 and T2 values, and early enhancement post gadolinium administration showed an acute LAD territorial infarct (Fig 2). Findings were consistent with myocardial infarction with non-obstructive coronary artery disease (MINOCA). She was started on carvedilol for empiric treatment of coronary artery spasm and microvascular dysfunction, along with aspirin and atorvastatin. Losartan was added for heart failure management. Outpatient invasive coronary reactivity testing showed severe epicardial (70% vasoconstriction) and microvascular (80% decrease in coronary blood flow) endothelial dysfunction in response to acetylcholine (Fig 3 and Fig 4) as underlying etiology of recent MINOCA. CFR was normal. L-arginine (NO precursor) was added to the medical regimen. Patient has not had recurrence of chest pain or ACS at 1 year follow-up and LVEF normalized on repeat echocardiogram. This case shows the importance of cardiac MRI in confirming the diagnosis of MINOCA in patients with no obstructive CAD, and the crucial role of coronary reactivity testing in diagnosing and treating severe coronary endothelial dysfunction, which is aligned with the AHA/ACC MINOCA consensus document.
Abstract 18721: Increased Predisposition to Hypertrophic Cardiomyopathy in Mitochondria Gene
CYP2E1
Rare Variant Carriers
Authors: Huang Qiya , Zhang Channa , Lu Minjie , Bo Xiaochen , Wang Jizheng , song lei
Published: December 2023

Introduction:
With a prevalence of up to 1 in 200, hypertrophic cardiomyopathy (HCM) is the most common monogenic hereditary cardiovascular disease. Previous studies have observed that mitochondrial dysfunction and mitochondria-associated metabolic remodeling are major metabolic features in HCM. However, the impact of mitochondrial gene mutations on HCM were poorly understood.

Methods and Results:
We selected 2272 mitochondrial genes from the Mitocarta database 3.0 and screened rare variants from the whole-exome sequencing data in 985 HCM patients (excluding patients with HCM phenotypes, including mitochondrial myopathy) and 759 non-HCM controls. We found that
CYP2E1
rare variants were significantly enriched in HCM patients (OR = 9.56, Bonferroni corrected P = 0.001). Patients with or without
CYP2E1
rare variants shared similar demographic and echocardiographic variables at baseline. With a median follow-up time of 5.31 years in 735 HCM patients, we revealed that HCM patients with
CYP2E1
rare variants were more likely to experience myocardial infarction (HR 14.1, P < 0.001).

Conclusion:
We demonstrated that rare variants in the mitochondrial gene
CYP2E1
might increase the risk of HCM onset and may be associated with the occurrence of myocardial infarction endpoints in HCM. We hypothesize that the mechanism is related to the extensive and complex mitochondrial metabolic processes in which
CYP2E1
is involved. Our findings provided new evidence for the association between mitochondrial gene variants and HCM, and more multi-center evidence is needed to confirm this association in the future.
Abstract 18729: cBIN1 Gene Therapy Improves Recovery of Peri-Infarction Muscle in a Canine Model of Chronic Ischemic Heart Failure
Authors: Khan Muhammad S , Ishidoya Yuki , Smego Douglas , Li Jing , Offei Emmanuel , Ruizcastillo Sofia , Hirahara Annie , Gharbia Omar , Seamons Benjamin , Palatinus Joseph , Krueger Lauren , Hoareau Guillaume , Hong Tingting , Ranjan Ravi , Selzman Craig , Dosdall Derek J , Shaw Robin M
Published: December 2023

BACKGROUND:
Heart failure (HF) due to ischemic dilated cardiomyopathy (IDCM) is a major cause of morbidity and mortality. In failing hearts, loss of T-tubule microdomains is central to impaired calcium transients and loss of cardiac function. Cardiac bridging integrator 1 (cBIN1), a membrane scaffolding protein that organizes T-tubule microdomains, is transcriptionally reduced in failing hearts.

Hypothesis:
cBIN1 gene therapy will improve cardiac function in ischemic cardiomyopathy.
AIM:
Evaluate the effectiveness of catheter-based delivery of cBIN1 gene therapy in preserving bipolar voltage (an assay of muscle health) and LVEF in a canine model of IDCM.

Methods:
Nine healthy adult mongrel dogs (30±3 kg) underwent LAD ligation, developing IDCM and HFrEF (LVEF < 40% and NT-proBNP >900 pmol/L) over 3-4 months. Animals received a single treatment at 20 sites by intramyocardial injection of either AAV9-GFP (control, n=3) or AAV9-cBIN1 (n=6) using a MyoStar catheter-mediated subendocardial injection. Low voltage LV regions were quantified as percent of total endocardial area with bipolar voltage <1.5 mV on the day of the treatment (pre-therapy) and the terminal study (5-10 weeks post-therapy).

Results:
In control-treated dogs, low voltage areas did not change significantly (19.5±3.4 vs. 28.7±9.8%, p=0.143,
Figure A
), whereas in the cBIN1-treated cohort, the low voltage areas surrounding infarction zones decreased significantly (18.9±10.9 vs. 13.4±9.1%, p=0.038,
Figure B
). Control therapy was associated with an additional 9.2% loss LV myocardium, whereas cBIN1 therapy caused a 6.5% recovery of myocardium (p=0.024,
Figure C
). Post-therapy week 5, LVEF decreased in control animals (36±2 vs. 29±3%, p<0.001) yet improved in the cBIN1-treated animals (37±2 vs. 41±3%, P=0.003).

CONCLUSION:
Intramyocardial injection of cBIN1 gene therapy can halt and reverse expansion of peri-infarction low voltage areas and improve LVEF in a preclinical IDCM model of chronic HF.
Abstract 18734: Comparison of Hypertension Prevention Education Among Community Health Students, Online Chat-Based Artificial Intelligence Model, and Physician
Authors: Visaria Aayush , Vijayakumar Eesha , Aseervatham Christopher , Arredondo Andrew , Chidananda Anshruta , SHAH PRIYANSHI , Pinas Angeles , Saad Pierre , Moon Seung Jae
Published: December 2023

Introduction:
Health literacy and preventive education remain the core of hypertension management. Emerging language processing, artificial intelligence (AI) tools have the potential to provide effective preventive information. We sought to compare the quality of responses to commonly asked questions about hypertension by community health students, a physician, and an AI tool.

Methods:
Through a structured, student service-learning program, 270 trained undergraduate students conducted 56 health fairs across 19 locations in NJ from Jan 2022 - March 2023. We identified the 10 most commonly asked questions related to blood pressure and asked a physician, a trained student, and ChatGPT to answer them in paragraph format within 200 words. Four independent, blinded expert reviewers graded each response from 1 to 3 (3=best, 1=worst response relative to others). We assessed the reliability across responses using the Fleiss' Kappa statistic. We used ANOVA with post-hoc pairwise comparisons to determine differences in average response score.

Results:
Among 30 responses, there was a significant difference in score by response type (physician, 2.0 [SD, 0.6]; student, 1.8 [0.5]; ChatGPT, 2.2 [0.6], p=0.001). Post-hoc, pairwise comparisons revealed student scores were significantly lower than ChatGPT scores (p=0.0038), but there was no difference between physician and ChatGPT responses (p=0.81). Scores were moderately reliable across expert reviewers (kappa = 0.56). Qualitatively, student and physician scores were rated to be more empathetic and personalized, but less comprehensive and actionable.

Conclusions:
A language-processing, AI-based tool performed as well, if not better, than a physician and trained community health students to provide preventive education related to blood pressure. Further quality improvement initiatives need to be done to better understand the utility of AI tools to augment preventive education and to more effectively train students/physicians to provide comprehensive and actionable strategies.
Abstract 18755: Engineered Nanoparticles for the Oral Delivery of Cardioprotective Small RNA Therapeutics
Authors: Yamaguchi Shukuro , Miyamoto Kazutaka , Jones Xaviar M , Ciullo Alessandra , Marban Eduardo , Ibrahim Ahmed G
Published: December 2023

Background:
RNA drugs have been applied to cardiovascular conditions including hypercholesterolemia and amyloidosis, but such drugs are deliverable only by parenteral routes. The ability to deliver RNA drugs orally would be highly desirable. Here we describe the development of a casein-chitosan-based formulation (dubbed C2) for the oral delivery of TY1, a 24-nucleotide chemically-modified Y RNA which we are exploring as a therapeutic candidate for cardiac fibrosis.

Materials and Methods:
We characterized the size distribution of C2-encapsulated TY1 (C2-TY1) micelles by nanoparticle tracking analysis. qPCR quantified the number of TY1 copies per micelle, as well as the presence of exogenous RNA in intestinal tissue from animals fed C2-conjugated RNA. Using a mucin precipitation assay, we assessed the ability of C2 micelles to adsorb onto mucin. We then tested the resistance of C2-TY1 micelles to degradation through incubation with proteinase K and RNase. To assess safety, healthy animals were fed C2-TY1 (0.15mg/kg, comparable to doses effective intravenously), or vehicle (H
2
O), twice weekly and evaluated at four weeks. Finally, we gauged the therapeutic potential of orally-administered C2-TY1 in a rat model of myocardial infarction.

Results:
C2 micelles are 100-500 nm in size and efficiently encapsulate TY1 (~10
4
TY1 copies per particle; n=3 technical replicates). After oral gavage, C2 efficiently delivered exogenous RNA to intestinal tissue within 60 minutes, as verified by qPCR (n=9). Chitosan played a significant role in the mucoadhesive property of C2 (n=6). C2 protected TY1 from enzymatic degradation compared with other formulations (p<0.01; n=3 per group).
In vivo
, animals fed C2-TY1 had stable weight, exercise endurance, CBC and blood chemistry relative to controls, with no histologic abnormalities in vital organs (n=3-5 per group). When administered orally 20 minutes after reperfusion, C2-TY1 reduced infarct size (p<0.01) and decreased circulating levels of troponin I (p<0.05; n=3-6 per group). Preliminary findings show similar oral efficacy of two other, chemically-unrelated, small RNA drugs encapsulated in C2.

Conclusion:
The C2 formulation enables efficient and effective oral delivery of small RNA drugs for cardioprotection.
Abstract 18758: Pain and Quality of Life in Older Adults With Advanced Heart Failure
Authors: Byun Jun Yeong , Azuero Andres , Bakitas Marie A , Wells Rachel
Published: December 2023

Background:
Over 80% of people with advanced heart failure (HF) experience pain; however, little is known about the relationship between pain and quality of life (QoL).
Research Objectives:
Examine the relationships between: 1) Total Pain Theory constructs and 2) pain and QoL across time.

Methods:
A secondary analysis of usual care participants in the ENABLE CHF-PC, a palliative care RCT (ClinicalTrials.gov: NCT02505425). Primary outcome was pain (PROMIS Pain Intensity & Interference). Total Pain constructs include physical and mental health (PROMIS Global Health 10), social support (Multidimensional Scale of Perceived Social Support), and spirituality (Negative Religious Coping). Mixed models assessed the relationships between pain and Total Pain constructs. Cross-lagged path analysis examined the temporal relationship between pain and QoL (baseline, 24-weeks, 48-weeks).

Results:
Of 205 usual care participants, mean age was 64.15 (SD 9.14), 108 (52.7%) men, and 111 (54.1%) African American. At baseline, participants’ QoL was poor (35.98, SD 10.7) with greater pain interference (54.5, SD 10.70) but not pain intensity (45.09, SD 10.47) compared to the general population. Among Total Pain constructs, only physical health was significant. As physical health decreased, pain intensity (b = -0.80, SE = 0.09, CI = -0.99, -0.62, p < .001) and pain interference (b = -0.69, SE = 0.10, CI = -0.89, -0.49, p < .001) increased. An unadjusted path analysis suggested variable magnitude temporal relations: a significant, large relationship between pain intensity and QoL at baseline (standardized cov. = 0.53), but medium-sized across baseline to 24-weeks (B = 0.28), and across 24- to 48-weeks (B = 0.32). Relationship between pain interference and QoL was also significant at baseline (standardized cov. = 0.54) and across baseline to 24-weeks (B = 0.41).

Conclusions:
Variability in magnitude of relationships between pain intensity and interference and QoL demonstrates the complex nature of pain in advanced HF.
Abstract 18801: Impact of COVID-19 Pandemic on Cardiovascular Diseases Hospitalisation, Management and Mortality in Brazil
Authors: Fagundes Antonio A , Passaglia Luiz , Pinheiro Pedro , Nascimento Bruno R , Brant Luisa C , Ribeiro Antonio L
Published: December 2023

Introduction:
The COVID-19 pandemic led to a reduction in cardiovascular (CVD) hospital admissions in many countries. We aimed to assess the effect of the COVID-19 pandemic on CVD hospitalizations, management, and mortality in Brazil.

Methods:
Hospitalization data for the years 2020 and 2021 for Brazil and regions were analyzed using the Datasus hospital admission system. We analyzed the number of hospitalizations, the number and proportion of intensive care unit (ICU) utilization, and the number and proportion of in-hospital deaths. The observed data were compared to the average of the previous three years (2017 to 2019). Absolute differences and risk ratios (RR) were calculated, with the RR obtained by dividing the observed values by the expected ones for each period studied.

Results:
There was a reduction in CVD hospital admissions, with 184,727 (95% CI 157,579 to 211,876) fewer hospitalizations than expected, representing a decrease of 16.2% (RR 0.838; 95% CI 0.836-0.839). There were two valleys of reduction in CVD hospitalizations, the first before the first peak of Covid-19 hospitalizations and the second simultaneous to the second peak of Covid-19 hospitalizations in 2021. There was a 9% decrease in the absolute number of CVD admissions in the ICU (RR 0.910; 95% CI 0.907-0.912), associated with a 4.7% absolute decrease in the number of CVD admissions that resulted in in-hospital deaths (RR 0.953; 95% CI 0.949-0.957). However, there was an 8.6% increase in the proportion of ICU admissions due to CVD (RR 1.086; 95% CI 1.084-1.088) and a significant increase of 14.4% in the proportion of admissions due to CVD that resulted in in-hospital death.

Conclusions:
Brazil′s data reveal that the Covid-19 pandemic reduced the number of CVD hospitalizations, but with a higher proportion of ICU use and higher in-hospital mortality.
Abstract 18806: How Well Does Left Atrial Remodeling Predict Adverse Outcomes in Patients With Chronic Severe Aortic Regurgitation?
Authors: El Dahdah Joseph , Akintoye Emmanuel , Braghieri Lorenzo , Badwan Osamah , Patel Hardik , Dabbagh M. Marwan , Kassab Joseph , Chedid El Helou Michel , Jellis Christine L , Desai Milind Y , Rodriguez L L , Grimm Richard A , Roselli Eric E , Griffin Brian P , Popovic Zoran B
Published: December 2023

Introduction:
Aortic regurgitation (AR) leads to left ventricular (LV) remodeling by increasing LV load. We recently showed that LV dimensions, widely adopted marker of severe AR, are not reliable predictors of adverse CV outcomes in older patients and female sex. Here we sought to study the effects of chronic severe AR on left atrial (LA) size and function as a prognostic adjunct to LV dimensions.

Methods:
Adult patients with ≥3+ AR on routine surveillance with serial echocardiograms between 1/2010 and 12/2016 were included in this study. We assessed longitudinal trends of LA volume indexed to body surface area (LAVI) and LA reservoir strain (LAr) stratified by age and sex. Clinical endpoints included the occurrence of heart failure hospitalization, urgent aortic valve surgery, or all-cause mortality and were used to assess the prognostic value of our studied parameters.

Results:
A total of 525 patients with 1,687 serial echocardiograms conducted over a median (IQR) follow-up duration of 2.0 (1.0-3.6) years were included. As shown in figure 1, we observed a substantial increase in LAVI (1.0 [95% CI: 0.76-1.2] mL/m2 per year of follow-up) and a decrease in LAr (-1.3% [95% CI: -1.6 to -0.92%]) over the study period. There was no significant interaction related to sex or age (p ≥0.17). 210 adverse events were recorded and were significantly predicted by both LA parameters. Optimal discriminatory threshold for LAVI was determined to be 37 mL/m2 and LAr at 35% and were both found to be consistent across categories of sex and age.

Conclusions:
This study indicates that LA remodeling, unlike LV remodeling, shows a similar rate of progression across different categories of sex and age among patients with chronic severe AR. Furthermore, LA parameters provide an added prognostic value over LV parameters and may therefore be better suited to inform the timing of AR intervention.
Abstract 18811: Heart Failure in a Carrier of Danon Disease
Authors: Mohammad Yasmeen , Brink Benjamin , levine daniel
Published: December 2023

Background:
Danon Disease is a rare X-linked dominant genetic condition characterized by hypertrophic cardiomyopathy, skeletal muscle myopathy, and intellectual disability, among other serious complications. The disease is a lysosomal storage disorder in which a mutation in the LAMP-2 gene causes a defect in the lysosome membrane and an accumulation of glycogen in vital tissue including cardiac muscle cells. It occurs more commonly in males, who are also more severely affected than females with this condition. There are no specific treatments available, although studies involving gene therapy have been ongoing. Patients with Danon Disease often require heart transplantation as treatment for end-stage heart failure.

Description of Case:
A 37-year-old female with a known family history of Danon Disease was discovered to be a carrier of the LAMP-2 mutation after presenting to the hospital with dizziness and palpitations. An echocardiogram obtained at the time of diagnosis revealed left ventricular hypertrophy and left ventricular apical thrombus with normal ejection fraction. She was started on anticoagulation and began following closely with a heart failure clinic. Since diagnosis, she has had multiple echocardiograms which have shown a steady decline in her ejection fraction to 25% and biventricular failure. An ICD was placed, with no shocks ever administered. She has had multiple hospital admissions for exacerbations of heart failure since diagnosis. Telemetry monitoring during these admissions revealed frequent premature ventricular contractions attributed to the patient’s severe cardiomyopathy. Despite continuation of guideline-directed medical treatment, this patient’s systolic heart failure is anticipated to continue worsening. She will likely require heart transplant, for which evaluation has already been initiated.

Discussion:
Danon Disease is a rare lysosomal storage disorder that often involves progressively worsening cardiomyopathy. Individuals with a known family history of this condition should be referred early for genetic testing. If found to have the condition or be a carrier, they should begin following with a heart failure specialist and consideration for advanced therapies, like transplant, should be initiated.
Abstract 18813: Economic Burden of Pregnancy Among Privately Insured Women With Congenital Heart Disease
Authors: Agarwal Anushree , Duan Rong , Sobhani Nasim C , Sabanayagam Aarthi , Marcus Gregory M , Gurvitz Michelle Z
Published: December 2023

Background:
Women with congenital heart defects (CHD) are increasingly reaching childbearing age. Understanding their healthcare costs in pregnancy may inform resource allocation, financial planning, and pre-conception counseling.

Methods:
We used 2010-2016 US commercially insured beneficiaries’ data within the IBM
®
MarketScan® database to identify pregnancies among 18-55-year-old women with CHD and matched controls without CHD. We assessed baseline characteristics, cardiac and noncardiac conditions, pregnancy related conditions, birth outcomes, and cesarean section. We estimated total and out-of-pocket (OOP) costs, compiled and adjusted to 2016 medical component of the consumer price index. Negative binomial mixed model was used.

Results:
There were 6385 pregnancies in 5077 women with CHD (672 pregnancies among severe and 5713 among nonsevere) and 9438 pregnancies in 7737 controls. Compared to controls, pregnancies with CHD were more likely to be 35+ years of age at delivery, resided in the Northeast and West regions, had flexible insurance plans, cardiac conditions, noncardiac conditions, birth outcomes, pregnancy related conditions and cesarean sections, while there was no difference in the year of delivery and gestational diabetes rates. After adjusting for all covariates, having CHD was an independent predictor of higher adjusted pregnancy-related cost ratio for total (1.49, 95% confidence interval [CI] 1.40, 1.59) and OOP costs (1.27, 95% CI 1.19, 1.35). The adjusted mean total and OOP cost difference for pregnancy per patient for any CHD, severe CHD, and nonsevere CHD was significantly higher than controls (Figure). Total expenditure and OOP cost of CHD pregnancies during the study period were $162.5 and $15.7 million dollars respectively.

Conclusions:
We provide novel estimates of economic burden of pregnancy among privately insured CHD patients for clinical and financial counseling and planning for patients, payors and policymakers.
Abstract 18815: Spectral CT Study to Evaluate Left Atrial Remodeling Using Anatomic and Electron Density Numbers in Patients Scheduled to Undergo Pulmonary Vein Isolation
Authors: Funabashi Nobusada , Shukuya Atsushi , Asano Hiroki , Kawamura Akio , Nakamura Kohki
Published: December 2023

Introduction:
Left atrial (LA) wall remodeling, such as fibrosis and inflammation, may occur in patients with atrial fibrillation (AF) to cause a low voltage AF wave and thickened LA wall. To date, an invasive biopsy has been used to evaluate LA wall remodeling. Hypothesis: Using novel spectral CT with an effective atomic number (EAN) and electron density number (EDN), which are new parameters in addition to CT attenuation, LA anterior wall characteristics can be evaluated.

Methods:
A total of 13 patients (eight males, mean age 69 years) scheduled for pulmonary vein isolation (PVI) underwent cardiac spectral CT (7500, Philips, Tokyo, Japan). This revealed AF in four patients and a sinus rhythm in nine. From non-contrast, and early and late phase contrast data, EAN and EDN (%EDV) of the LA anterior wall were determined.

Results:
Mean EANs for the LA anterior wall were 7.35 in patients with AF, and 7.38 in patients with a sinus rhythm, respectively (P=NS), during the non-contrast phase; 8.18 and 8.17, respectively (P=NS), during the early phase; and 8.59 and 8.51, respectively (P=NS) during the late phase. Mean EDNs (%EDW) were 102.7 in patients with AF, and 103,1 in patients with a sinus rhythm, respectively (P=NS) during the non-contrast phase; 102,6 and 103.4, respectively (P=NS) during the early phase; and 103.7 and 103.5, respectively (P=NS) during the late phase. In patients with AF, both LA anterior thickness on CT and LA volume determined by transthoracic echocardiogram had a significant negative correlation with the voltage of AF waves (V2 lead) (R= -0.87 and -0.46, respectively). The EDN, but not EAN, in non-contrast, and early and late phases after contrast material showed a significant negative correlation with the voltage of AF waves (R= -0.74, -0.75, respectively).

Conclusions:
This is the first study in which characteristics of the LA anterior wall were evaluated by EAN and EDN on spectral CT. As well as LA anterior wall thickening and an enlarged LA volume, the EDN was an indicator of characteristic changes of the LA anterior wall that related to the low voltage of AF waves. This new parameter determined by spectral CT may evaluate characteristics of the LA anterior wall and be a predictor of future occurrence of LA remodeling that is related to the effectiveness of PVI.
Abstract 18847: Apples to Apples: Cardiopulmonary Exercise Testing Findings in Healthy Athletes versus Equally Fit Patients With Hypertrophic Cardiomyopathy
Authors: McHugh Cliodhna , Gustus Sarah K , Petek Bradley J , Wasfy Meagan M
Published: December 2023

Introduction:
CPET is often used when athletes present for clinical evaluation of suspected pathology, including HCM. While lower than expected peak oxygen consumption (pVO
2
) may raise suspicion for HCM, athletes with HCM frequently display normal or supranormal pVO
2
, limiting the diagnostic utility of this parameter.

Hypothesis:
We hypothesize that there will be differences in other CPET parameters between healthy athletes and equally fit individuals with established HCM.
Aim:
The aim of this study was to compare CPET parameters in healthy athletes and equally fit individuals with established HCM.

Methods:
Healthy athletes and HCM patients (percent predicted pVO
2
(ppVO
2
) >90%, non-obstructive, no nodal agents) were identified who had cycle ergometer CPETs for research or clinical evaluation in a single lab. CPETs were compared between HCM patients and athletes matched (2:1 ratio) for age, sex, race, height, weight, and cardiorespiratory fitness (ppVO
2
).

Results:
Consistent with matching, HCM (n=30, 43.6 ± 14.2 years) and athletes (n=60, 43.8 ± 14.9 years) groups had similar, supranormal pVO
2
(40.4 ± 9.0 vs. 41.2 ± 8.9 mL/kg/min, 125% vs. 124% predicted, n.s.). While many CPET parameters were similar between groups, HCM patients had worse ventilatory efficiency with lower end-tidal CO
2
at the ventilatory threshold (VT) (42.9 ± 6.4 vs. 45.7 ± 4.8, p= 0.02), higher early VE/VCO
2
slope (through VT, 25.4 ± 4.7 vs. 23.4 ± 3.1, p=0.02), and higher nadir of VE/VCO
2
(27.3 ± 4 vs. 25.2 ± 2.6, p<0.001). When stratified by ppVO
2
, these differences remained significant for those with ppVO
2
< and ≥100%. Using the recommended cut-off of <30, HCM patients were more likely to have abnormally high VE/VCO
2
nadir than athletes (20% vs. 5%, p= 0.03).

Conclusion:
Amongst equally fit individuals, ventilatory efficiency was worse in patients with HCM than in healthy athletes. Our results suggest ventilatory efficiency may be useful to integrate in with other diagnostic testing in “gray zone” clinical cases in which the diagnosis of HCM is being debated in athletes with LVH. Given ventilatory efficiency has been increasingly recognized as a key prognostic CPET parameter, future work should establish the prognostic value of VE/VCO
2
in HCM patients with intact cardiorespiratory fitness.
Abstract 18855: Comparison of Hospital Outcomes in Sick Sinus Syndrome Patients With and Without Pacemaker- A Nationwide Inpatient Sample Analysis
Authors: Abbasi Ayesha , Jamshed Aneeza , AZIZ IMRAN , KHANAL SMRITI , Yilmaz Mahir , Shoura Sami , Atluri Ramtej
Published: December 2023

Introduction:
Sick sinus syndrome refers to degenerative fibrosis of the sinoatrial node, leading to bradyarrhythmias with or without tachyarrhythmias. Pacemaker implantation is a common therapeutic intervention in patients with symptomatic sick sinus syndrome (SSS). We aimed to analyze the periprocedural outcomes for patients with SSS who undergo pacemaker implantation.

Hypothesis:
Pacemaker implantation is associated with lower odds of mortality in patients with sick sinus syndome.

Methods:
Retrospective cohort study with data from 2016-18 combined National Inpatient Sample database. ICD-10 codes used to include admissions with SSS and dichotomized based on permanent dual chamber pacemaker implantation. The primary and secondary outcomes were studies between the two cohorts. Multivariate linear and logistic regression were used to adjust for confounders

Results:
Out of 190,625 sick sinus syndrome, admissions in 2016-18 NIS database, 115,195 (60%) received a permanent pacemaker. Permanent pacemaker implantation in SSS patients was associated with lower adjusted odds of inpatient mortality (aOR 0.22, 95% CI 0.17-0.29, p<0.001), decrease in mean LOS by 0.31 days (5.55 vs 5.86, p<0.001) and higher adjusted THC by a difference of 35,489 USD (116,474 USD vs 80,985 USD, p< 0.001). Secondary outcomes are shown in Fig.

Conclusions:
Pacemaker implantation in sick sinus syndrome patients is associated with 80% decrease in mortality, shorter length of stay, and significantly lower odds of inpatient complications including sepsis, pulmonary embolism, ventricular fibrillation, acute kidney injury when compared to patients without a pacemaker.