bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14225: Cardiovascular Structural and Functional Changes Become Apparent With Increased Waist Circumference in Childhood Obesity
Authors: Harada Kenji , Harada Yukiko
Published: December 2023

Background:
Higher waist circumference (WC) is associated with cardiovascular disease, however, little is known about the association between WC and cardiovascular functional change in children. The purpose of this study is to examine the relationships between numbers of cardiovascular risk factors and left ventricular (LV) geometry and function in children.

Methods:
Echocardiography was performed in 401 children aged 7 to 13 years. Left atrial (LA) diameter, LV end-diastolic volume, ejection fraction, mass, mass-to-volume ratio, and carotid artery intima media-thickness (IMT) were measured. Transmitral peak flow velocities during early and late diastole and mitral annular myocardial velocities during early (Em) and late diastole (Am) were measured. LA systolic force and aortic stiffness were calculated. Lipids, uric acid, fasting glucose, insulin, high sensitive CRP, and homeostasis model assessment for insulin resistance (HOMA-IR) were also assessed. Subjects were divided into 4 groups: A group, WC within normal range; B group, increased WC; C group, increased WC plus any one of the following individual factors of hypertension, dyslipidemia (low high-density lipoprotein-cholesterol and/or high triglyceride), and raised fasting glucose; D group, metabolic syndrome.

Results:
Compared with the A group, LA diameter, mass/volume ratio, HOMA-IR, and uric acid were greater in the B group (p<0.05 for all). With increasing number of metabolic syndrome disorders (C and D groups), dyslipidemia, increased Hs-CRP, decreased Em/Am, enhanced LA systolic force, increased IMT, and aortic stiffening were observed (Table).

Conclusions:
Higher WC is associated with insulin resistance, hyperuricemia, and concentric LV hypertrophy. Cardiovascular structural and functional changes become apparent with increasing number of metabolic syndrome disorders. Our findings suggest that primary prevention programs should be initiated in children with increased WC.
Abstract 14227: Fatty Acid-Binding Protein-3 and Renal Function Decline in Patients With Chronic Coronary Syndrome
Authors: Huang Chin-Chou , Yeh Jiunn-Tyng
Published: December 2023

Introduction:
Renal dysfunction is common in patients with coronary artery disease. To delay the development of end-stage kidney disease and improve chronic kidney disease prognosis, early detection and management of chronic kidney disease are crucial, especially for high-risk populations.

Hypothesis:
We hypothesized that the fatty acid-binding protein-3 (FABP-3) is a novel biomarker associated with renal dysfunction.

Methods:
This is a multicentre prospective cohort study. Patients with chronic coronary syndrome were classified into three groups based on the initial serum FABP-3 levels. The Modification of Diet in Renal Disease (MDRD) equation was used to estimate the patient’s renal function. Renal events were defined as >25% and >50% decline in estimated glomerular filtration rate (eGFR). Multivariable Cox regression was employed to delineate the correlation between FABP-3 and renal dysfunction.

Results:
A total of 1606 subjects were included. During a mean follow-up of 35.9 months, there were 274 patients with eGFR >25% reduction and 60 patients with >50% reduction. The Kaplan-Meier survival curves showed that increased levels of FABP-3 were significantly correlated with eGFR >25% reduction (
P
< 0.001) and >50% reduction (
P
< 0.001). Multivariate Cox regression model revealed that subjects with higher FABP-3 exhibited a greater risk of eGFR >25% reduction (Group 2: HR = 1.742, 95% CI = 1.222–2.483; Group 3: HR = 2.643, 95% CI = 1.847–3.784) and >50% reduction (Group 2: HR = 3.818, 95% CI = 1.261–11.564; Group 3: HR = 9.769, 95% CI = 3.291–29.002).

Conclusions:
Serum FABP-3 may serve as a novel biomarker to predict eGFR decline in patients with chronic coronary syndrome.

1
Abstract 14239: Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve
Authors: Lin Ying , Yang Qifan , Lin Xiaoping , Liu Xianbao , Kong Xiangmin , Zhu Lianlian , Zhou Bin , Wang Yidong , Peng Jinrong , Zhu Wei , Wang Jianan
Published: December 2023

Background:
Extracellular matrix (ECM) is involved in aortic valve development and aortic valve anomaly. ADAMTS gene mediated ECM dysfunction was reported to be related to aortic valve diseases.

Hypothesis:
The ADAMTS gene family members can contribute to aortic valve diseases.

Methods:
Morpholino based
adamts
gene-targeted phenotype-screening of outflow tract anomaly in zebrafish and the 19 ADAMTS family gene-targeted exon sequencing on a cohort BAV patients (304 BAV and 301 normal controls) were performed. Accordingly, both specific genetic tracing and different gene modified mouse models were generated to evaluate the role of specific genes in the aortic valve formation process. Movat’s pentachrome staining was used to describe the altered ECM maturation process. Bulk RNA-seq was performed on both mouse heart tissue and human iPSC-induced ECs to explore the potential molecular pathways, which was further confirmed in ex vivo embryonic outflow tract tissue culture studies.

Results:
We identified some novel
adamts
genes that resulted in cardiac outflow valve defects in zebrafish, while exon sequencing identified ADAMTS16 p.H357Q variant in an inherited BAV family. The generated
Ad
amts16-Cre;
Rosa26-tdTomato
mice showed
Adamts16
-expressing cells were primarily restricted to valvular endothelial cells (VECs) at E12.5 and then expressed in valvular mesenchymal cells (VICs) at E13.5. Both
Adamts16

+/-

and
Adamts16

+/H355Q

mice exhibited an R-NC-type BAV phenotype, with progressive aortic valve thickening. Conditional
Adamts16
mutant mouse models demonstrated that endothelial lineage cell deficiency in
Adamts16
recapitulated the BAV phenotype, which was associated with worse ECM deposition without ECM trilaminar structure. Bulk RNA sequencing unveiled enhanced FAK signaling, which was accompanied by elevated fibronectin levels. Both in vitro iPSC-ECs culture and ex vivo embryonic tissue explant studies validated the altered FAK signaling resulted in exaggerated cell proliferation.

Conclusions:
Our present study identified a novel BAV-causing
ADAMTS16
p. H357Q variant. ADAMTS16 deficiency led to BAV formation.
Abstract 14317: Arterial Thromboembolism in a Patient With Primary Antiphospholipid Antibody Syndrome and a Mitral Valve Mass
Authors: Jandal Ali , Wark Tyler , Anwar Asad , MuthuKrishnan Anand , Hagerty Tracy , Barrett Trace
Published: December 2023

Background:
Antiphospholipid antibody syndrome (APLAS) is an immune-mediated thrombophilia with multisystem venous and arterial thrombosis. Valvular disease is the most common cardiac presentation of APLAS, usually involving the mitral valve, and rarely affects valve function. Arterial thrombosis leading to myocardial infarction (MI) and left ventricular dysfunction have been described but are rare. We present a challenging case of APLAS with mitral valve involvement complicated by MI and new decompensated heart failure.

Case:
A 48-year-old male with obesity, hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea, and triple-positive primary antiphospholipid antibody syndrome presented with a 3-day history of angina and dyspnea. He was started on rivaroxaban 9 years prior to presentation for breakthrough venous thrombosis while non-adherent to warfarin. During admission, he was found to have a mitral valve mass complicated by moderate mitral valve regurgitation, decompensated systolic heart failure, ST-segment elevation myocardial infarction, and multifocal strokes. Multimodality imaging (figure 1) in the setting of negative blood cultures suggested a non-infectious mitral valve mass with embolization as the culprit for his presentation. He ultimately underwent successful mechanical mitral valve replacement and bypass grafting with pathology confirming the diagnosis.

Discussion:
We highlight a case of a non-bacterial thrombotic mitral valve mass leading to moderate valvular regurgitation, acute heart failure, and arterial thromboembolic events in the setting of probable rivaroxaban failure. This case highlights the use of multimodality imaging and a team-based approach to correctly diagnose and treat a high-risk patient with APLAS and surgical valvular disease, as well as the inherent challenges of perioperative thrombotic and hemorrhagic risk assessment and monitoring.
Abstract 14318: Right Ventriculo- Arterial Coupling Assessment by High-Fidelity Hemodynamic Measurements in Patients Undergoing Left Ventricular Assist Device Implantation
Authors: Nicoara Alina , Culp Crosby , Cooter Mary W , Hunter Kendall , Krasuski Richard , Fudim Marat , Schroder Jacob , Milano Carmelo , Cherry Anne D , Podgoreanu Mihai V
Published: December 2023

Background:
The changes in RV function after LVAD placement are not fully understood. RV- PA coupling, defined as the ratio of RV end-systolic to arterial elastances (E
ES
/E
A
), offers unique insight into the cardiopulmonary unit and opportunity to address these knowledge gaps. We present early results from our study investigating RV adaptive changes after LVAD implantation by intraoperative placement of RV conductance catheters.

Methods:
Conductance catheter, echocardiographic, and hemodynamic data were gathered starting on the day of surgery. We used a 7Fr high-fidelity RV conductance catheter delivered through a 9Fr central venous sheath. P-V loop parameters were obtained before skin incision and after chest closure. Single- beat methods were used for E
ES
/E
A
determination. Early RVF was defined according to INTERMACS criteria. Intraoperative pre- and post-implantation echocardiographic and hemodynamic parameters were compared.

Results:
We present data on the first 14 patients who underwent successful placement of the RV conductance catheter. Moderate or severe RVF occurred in 3 patients (21.4%). Data are presented in the table. While overall E
Es
(1.2 vs 1.3, p=0.785), E
A
(1.1 vs 1.3, p=0.154), and RV-PA coupling (E
ES
/E
A
ratio 1.1 vs 1.0, p=0.129 ) remained unchanged, several patients underwent dramatic changes, either increase or decrease, in E
ES
and E
A
(Figure). Measures of energetic expense, such as stroke work ( SW, correlate of myocardial energy transferred) and pressure-volume area (PVA, correlate of myocardial oxygen consumption) significantly decreased after LVAD implantation.

Conclusions:
We have shown that RV function assessment using conductance catheters and 3D echocardiography is feasible and able to identify individual responses in RV-PA coupling after LVAD implantation. Continued accrual of data will help identify different phenotypes of RV adaptation and establish a cut-off level of RV-PA uncoupling at which RVF occurs.
Abstract 14320: The Utility of Zebrafish Cardiac Arrhythmia Model to Predict the Pathogenicity of
KCNQ1
Variants
Authors: Hayashi Kenshi , DENG Yaowen , Shihe Cui , Kobayashi Isao , Nomura Akihiro , Teramoto Ryota , USUDA KEISUKE , Kobayashi-Sun Jingjing , Tazaki Yuya , Sasaki Ayana , Kusayama Takashi , Tsuda Toyonobu , Tada Hayato , Kato Takeshi , Sakata Kenji , Fujino Noboru , Yamagishi Masakazu , Takamura Masayuki
Published: December 2023

Introduction:
Genetic testing for inherited arrhythmias and discriminating pathogenic or benign variants from variants of unknown significance (VUS) is essential for gene-based medicine.
KCNQ1
is a causative gene of type 1 long QT syndrome (LQTS) and familial atrial fibrillation (AF), and approximately 30% of the variants found in type 1 LQTS are classified as VUS.

Aims:
We studied the role of zebrafish cardiac arrhythmia model in determining the clinical significance of
KCNQ1
variants.

Methods and Results:
We generated homozygous
kcnq1
deletion zebrafish (
kcnq1
del/del
) using the CRISPR/Cas9 technique and expressed human Kv7.1/MinK channels in
kcnq1
del/del
embryos. We dissected the hearts from the thorax at 72 h postfertilization and measured the transmembrane potential of the ventricle or the atrium in the zebrafish heart. Action potential duration was calculated as the time interval between peak maximum upstroke velocity and 90% repolarization (APD90). The APD90 of the
kcnq1
del/del
embryonic ventricle was 280 ± 47 ms (n = 63), which was significantly shortened by injecting KCNQ1 wild-type (WT) cRNA and KCNE1 cRNA (162 ± 28 ms, n = 34, P < 0.01 vs.
kcnq1
del/del
). A study of two pathogenic variants (S277L and T587M) and one VUS (R451Q) associated with clinically definite LQTS showed that the APD90 of
kcnq1
del/del
embryonic ventricles with mutant Kv7.1/MinK channels (292 ± 40 ms for S277L, n = 27; 297 ± 63 ms for T587M, n = 25; 218 ± 49 ms for R451Q, n = 29, respectively) was significantly longer than that of Kv7.1 WT/MinK channels (P < 0.01). Regarding the pathogenic variant (S140G) associated with familial AF, the APD90 of the
kcnq1
del/del
embryonic atrium with mutant Kv7.1/MinK channel was 124 ± 21 ms (n=13), which was significantly shorter than that with Kv7.1 WT/MinK (148 ± 17 ms, n = 8, P < 0.05 vs.
kcnq1
del/del
with S140G Kv7.1/MinK channel).

Conclusions:
Functional analysis using in vivo zebrafish cardiac arrhythmia model may be useful for determining the pathogenicity of both loss-of-function variants in patients with LQTS and gain-of-function variants in patients with familial AF.
Abstract 14339: Guideline-Directed Intensive Management Improves Long-Term Survival and Compliance of Pulmonary Hypertension Patient
Authors: Guo Jiajun , Wang Jiaqi , Xu Yuanwei , chen yucheng
Published: December 2023

Introduction:
Although the overall survival of PH patients improved in the current era, better management of PH patients still needs further exploration.

Hypothesis:
We hypothesized that guideline-directed, nurse-led, and multidisciplinary intensive management of PH patients would improve the overall survival of PH patients.

Methods:
We prospectively enrolled patients with PH from October 2013 to December 2020. Patients were divided into intensive management group and usual care group voluntarily. Intensive management was nurse-led and delivered by multidisciplinary teams, including patient education, symptoms monitoring, and patient adherence improvement with careful outpatient assessment every 3 months and medicine prescription whenever needed. Patients with usual care were treated by primary cardiologists’ consultants and telephone follow-ups every year.

Results:
Overall, 413 PH patients were finally included with a median follow-up period of 25.2 months(interquartile range: 12.4-44.3 months). Both overall survival (p<0.001) and event-free survival (p=0.008) of the intensive management group were significantly higher than the usual care group. After adjustment of age and sex, intensive management was also an independent protective predictor for both primary [all-cause mortality, HR 0.378, 95% CI (0.214-0.668), p<0.001] and composite endpoints [all-cause mortality and re-hospitalization, HR 0.648, 95% CI (0.454-0.927), p=0.017].

Conclusions:
Guideline-directed, nurse-led, multidisciplinary intensive disease management strategy could be an ideal method to further improve the overall survival and event-free survival of PH patients.
Abstract 14343: Early Genetic Screening and Cardiac Intervention in Patients With Genetic Cardiomyopathies Within a Multidisciplinary Care Model
Authors: Sadasivan Chandu , Gagnon Luke R , Wang Kaiming , Hazra Deepan , Dzwiniel Tara , Christian Susan , Thomas Jissy , Chan Anita Y , Paterson David I , Tymchak Wayne , Oudit Gavin Y
Published: December 2023

Introduction:
Patients with genetic cardiomyopathies are a heterogeneous group of patients who experience significant morbidity and mortality. Early cardiac assessment and intervention coupled with access to genetic counselling and testing may improve clinical outcomes and prevent progression to end-stage heart failure.

Methods:
Our prospective cohort study was conducted at our multidisciplinary Cardiomyopathy Clinic and patients with suspected genetic cardiomyopathy (CM) or a family history of CM (
n
=405) were recruited. Patients with genetic analysis completed (
n
=228) were categorized into dilated cardiomyopathy (DCM) (
n=
118), hypertrophic cardiomyopathy (HCM) (
n=
55), infiltrative cardiomyopathy (CM) (
n=
18), and Stage A/at-risk for CM (
n=
37). Continuous variables were analyzed using Wilcoxon signed-rank test or paired
t
test, while categorical variables were compared using Pearson chi-square tests.

Results:
There was a median follow-up time of 13 months (IQR: 7 - 21 months) with an increase in genetic testing, cascade family screening, optimization of guideline-directed medical therapy, and usage of device therapies compared to prior to clinic enrolment. In patients with genetic testing, 29.4% (
n=
67) had positive genotypes (pathogenic or likely pathogenic variants), 11.8% (
n=
27) had variants of unknown significance (VUS), and 58.8% (
n=
134) had negative or inconclusive genotypes. Optimization of medical and device therapies resulted in improvements in left ventricular ejection fraction from 30.5% (20.8 - 42.5%) to 45.5% (34.0 - 48.5%,
P<
0.001), reduced left ventricular mass index from 121.2 g/m
2
(116.2 - 146.4 g/m
2
) to 107.0 g/m
2
(88.9 - 134.7 g/m
2
,
P<
0.001), and reduced E/e’ ratio from 12.6 cm/s (9.2 - 15.3 cm/s) to 10.9 cm/s (9.0 - 14.2 cm/s,
P=
0.015). These improvements were driven by patients with negative genotypes (no variants or VUS) relative to those with positive genotypes. Additionally, patients with normal blood pressure (SBP < 120 mmHg and DBP < 80 mmHg) at follow-up had improvement in LVEF (
P<
0.001) and LVMI (
P=
0.005).

Conclusion:
Our findings demonstrate the efficacy of a combined cardiovascular genetics clinic in improving the clinical trajectories of patients with genetic cardiomyopathies.
Abstract 14418: Prevalence, Characteristics, and Factors Associated With Atrial Fibrillation and Flutter in Patients With Transthyretin Cardiac Amyloidosis
Authors: Chan Nicholas , Teruya Sergio , Mirabal Alfonsina , De Los Santos Jeffeny , Guadalupe Samantha , Rodriguez Carlos , Helmke Stephen , Cuomo Margaret , Smiley Dia , Biviano Angelo B , Dizon Jose , Wan Elaine Y , Yarmohammadi Hirad , Maurer mathew S
Published: December 2023

Introduction:
Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized form of restrictive cardiomyopathy in older adults. Adverse chamber remodeling from amyloid infiltration predisposes these patients to tachyarrhythmias such as atrial fibrillation/flutter (AF), which increase the risk of thromboembolic events. The goal of our study was to explore the prevalence, phenotypic characteristics, and factors associated with AF in ATTR-CA patients.

Methods:
This is a retrospective cohort study of 419 patients diagnosed with ATTR-CA comparing demographics and clinical characteristics between patients with and without AF at baseline. AF was ascertained based on review of prior electrocardiogram, long term monitors when performed, pacemaker interrogations if applicable, and charted history. Binary logistic regression was then performed to determine factors associated with prevalence of AF.

Results:
AF was prevalent in 58% (n=244) of ATTR-CA patients on initial presentation. Compared to those without AF, individuals with AF were older, of white race, exhibited NYHA class III-IV symptoms, and less frequently had variant disease (ATTRv-CA). They also had more prior stroke/TIA, chronic kidney disease, implanted pacemakers, and need for loop diuretics at baseline (Table 1). AF patients more consistently had Columbia stage II-III disease as per established biomarker cutoffs and greater left atrial volume index on echocardiogram (LAVI). On multivariable logistic regression, per point increase in Columbia score (OR 1.48, 95% CI 1.25-1.75) and per mL/m
2
increase in LAVI (OR 1.05, 95% CI 1.02-1.08) were predictive of prevalent AF, while ATTRv-CA (OR 0.19, 95% CI 0.07-0.55) was protective, all p<0.05.

Conclusions:
More than half of ATTR-CA patients have preexisting AF. Wild-type ATTR-CA, greater Columbia staging, and a dilated LA are the main clinical factors associated with prevalent AF.
Abstract 14422: Accuracy of a Popular Online Chat-Based AI Model in Providing Recommendations on the Management of Atrial Fibrillation in Accordance With the 2019 AHA/ACC/HRS Guidelines: A Patient versus Physician-Centered Approach
Authors: Kassab Joseph , El Hajjar Abdel Hadi , El Dahdah Joseph , Chedid El Helou Michel , Layoun Habib , Nakhla Shady , Saliba Walid I , Kanj Mohamed H , Kapadia Samir R , Harb Serge C
Published: December 2023

Introduction:
Atrial fibrillation (AF) is associated with reduced QOL and numerous CV events. AF patients often seek additional information beyond what their physician provides, often turning to Internet sources for guidance.

Hypothesis:
The rise of online chat-based AI interactions raises the question of whether this technology can assist in patient education and provide guidelines-based recommendations. We sought to evaluate if ChatGPT 4.0 could provide accurate patient and physician-centered recommendations for AF.

Methods:
We created 2 sets of 15 questions, one from a patient (PA) and another from a physician’s (PH) perspective. PA questions were formulated after querying “Google Trends” for the most searched terms related to AF. PH questions were formulated by expert cardiologists. Each question was submitted to the AI online model. Each cardiologist received 1 set of 30 answers and graded each answer as "accurate," "accurate with missing information (MI)," or "inaccurate." An answer was considered “accurate” if it included appropriate and complete information found in the currently published guidelines, “inaccurate” if false information was provided, or “accurate with MI” if essential information was missing according to the PH clinical expertise. Discrepancies in the PH gradings were identified and resolved.

Results:
13/15 (87%) PA answers were graded as accurate. The remaining 2/15 were accurate but with MI. No PA answers were inaccurate. 6/15 (40%) PH answers were accurate. 7/15 (46%) were accurate with MI and 2/15 (13%) were inaccurate. The AI chatbot provided significantly more accurate answers to PA questions vs PH questions (p<0.05, Fisher’s exact test).

Conclusions:
ChatGPT 4.0 provided largely accurate answers to PA questions, showing promise as a tool to assist in patient education on AF. However, the accuracy of answers to PH questions was suboptimal, reinforcing that this tool should not be used by physicians for clinical support in AF.
Abstract 14435: Psoas Muscle Index as a Tool to Predict Outcomes in a Pulmonary Hypertension Population Undergoing Pulmonary Thromboendarterectomy
Authors: Hopkins Steven , Hall Jillian , Lee Madeline , Vaidya Anjali , Forfia Paul R , Oliveros Estefania
Published: December 2023

Introduction:
Sarcopenia is defined as an overall decline in skeletal muscle mass and has been associated with a range of cardiac pathologies. Psoas Muscle Index (PMI) has emerged as a metric of sarcopenia. We investigated the prognostic value of PMI on six-minute walk distance (6MWD), and length of stay (LOS) in pulmonary hypertension patients following Pulmonary Thromboendarterectomy (PTE).

Hypothesis:
Sarcopenic patients will have lower 6MWD meters and increased LOS compared to non-sarcopenic patients.

Methods:
Retrospective chart review of 65 patients with CTEPH who had undergone PTE with CT scans of the abdomen between 2017-2022. Psoas muscle area was measured at the L3 level on CT scan. PMI was calculated using the formula (left psoas area + right psoas area)/height
2
. Patients in the 1
st
quartile PMI for their gender were classified as sarcopenic. 1
st
quartile PMI values were calculated as 5.34 cm
2
/m
2
for males, and 3.30 cm
2
/m
2
for females.

Results:
17 (26%) patients were classified as sarcopenic. There were no significant differences between sarcopenic and non-sarcopenic groups comparing hemodynamics (mean PA 45 vs 42 mmHg, PVR 9 vs 8 WU, CI 2 vs 2.1-l/min/m
3
), age (61.2 vs 59.7-years), female sex (52.9 vs 55.3%), ethnicity or comorbidities. Regarding 6 minute walk distance (6MWD), the sarcopenic group had significantly lower meters walked than the non-sarcopenic group pre-PTE (220 vs. 322-meters, p=0.049). Following PTE, there was less distinction between groups in 6MWD (347.1 meters vs 345.1, p=0.970). The sarcopenic group increased their 6MWD more than the non-sarcopenic group (137.3 meters vs 43.7, p=0.055). The sarcopenic group had significantly longer overall length of stay (LOS) (27 vs 14-days, p=0.001), and intensive care unit stay (19 days vs. 6-days, p=0.002) than the non-sarcopenic group.

Conclusions:
Sarcopenia is prevalent in patient with CTEPH. Sarcopenic patients with CTEPH had lower pre-PTE 6MWD, longer ICU stays and overall hospital LOS.
Abstract 14459: Endothelial Cell Specific Expression of HIV-Nef Induces Endothelial Senescence and Reduced Cardiac Output
Authors: Noda Moraima , Chelvanambi Sarvesh , Clauss Matthias A
Published: December 2023

Introduction:
People living with HIV experience increased cardiovascular comorbidities despite immediate prescription of combined antiviral therapy (ART) upon HIV diagnosis. Previously, we reported that the virally encoded HIV-Nef protein persists in extracellular vesicles (EV) of aviremic HIV patients on ART and endothelial-specific transgenic expression of HIV-Nef in murine models causes increased endothelial surface expression of the pro-apoptotic protein EMAPII. Co-culture with HIV-Nef expressing T cells induced endothelial senescence which could be completely abrogated by using EMAPII-neutralizing antibodies.

Hypothesis:
Here we hypothesize that endothelial Nef expression in transgenic mice induces EMAPII-associated endothelial senescence after intermittent exposure to hypoxia.

Methods:
Female (n=5) transgenic mice with endothelium-specific Nef expression using VE-Cadherin promoter were challenged with 4 weeks of mild hypoxia (10% O
2
) followed by 8 weeks of normoxia and then evaluated for cardiac function using non-invasive echocardiography with INVEVO2100.

Results:
We observed decreased cardiac output (Nef= 15.10 ul/min vs WT= 21.46 ul/min, p<0.05). Subsequently, we observed a 3.5-fold increased frequency of senescent endothelial cells using the senescence-associated marker p16INK4α (Nef= 0.54% vs WT= 0.15%, p<0.05) from the heart using flow cytometry. Furthermore, we also observed a 3.5-fold increase in the frequency of EMAPII+/P16INK4α+ cells (Nef= 0.50% vs WT= 0.14%, p<0.05).

Conclusions:
Transgenic endothelial HIV-Nef expression leads to upregulation of endothelial cellular senescence and EMAPII expression. EMAPII-neutralizing antibodies and senolytic agents are likely tools to reduce HIV-Nef-induced senescence. Endothelial cell senescence could affect cardiac circulation to impair heart function. Future studies will evaluate sex differences in HIV-Nef induces cardiac output at various ages.
Abstract 14589: Impairment of Endothelial Function by Chronic Cannabis Use: An Interim Analysis of the CANDIDE Study
Authors: Mohammadi Leila , Navabzadeh Mina , Han Daniel D , Reagan Emma , Naughton Jordan , Zhou Lylybell , Almeida Rahul , Park Kathryn , Uyemura Keith , Goyal Natasha , Rao Poonam , Hellman Judith , Cheng Jing , Marcus Gregory M , Springer Matthew L
Published: December 2023

Background:
Increasing cannabis legalization has led to a surge in cannabis use. To understand the consequences for cardiovascular health, we have initiated the CANnabis: Does It Damage Endothelium (CANDIDE) study. Here, we report results of an interim analysis.

Aims:
To investigate the effects of chronic cannabis product use on endothelial function.

Approach:
We recruited 44 healthy non-tobacco smokers/vapers, 21-50 yrs, in 3 groups based on chronic cannabis use: cannabis smokers, THC edible users, and nonusers. Participants underwent assessment of brachial artery flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (PWV). Human umbilical vein endothelial cells (ECs) were exposed to sera from each individual with and without VEGF to determine serum effects on endothelial NO production. Human lung microvascular ECs were also exposed to the individual sera and cell permeability was measured by electric cell-substrate impedance sensing.

Results:
FMD and VEGF-stimulated NO levels were both significantly lower in cannabis smokers than nonusers (5.7±3.3% vs 12.0±8.0%, p=.037, and 1.1±0.3 nM vs 1.5±0.3 nM, p=.018, respectively; figure), comparable effects to what we have reported for tobacco smokers. In contrast, FMD, but not VEGF-stimulated NO levels, was lower in the THC edible users than nonusers (5.0±4.1% vs 12.0±8.0%, p=.031, and 1.6±0.3 nM vs 1.5±0.3 nM, p=.54). There were no significant differences in other functional properties (p>.48). CD31 and IL-1β, which are circulating inflammatory biomarkers that we showed are elevated in tobacco smokers, were not elevated in cannabis smokers. The inflammatory biomarker PTX3 was lower in cannabis smokers than nonusers (p=.038).

Conclusion:
Chronic cannabis use impairs endothelial function but may reduce inflammation. Our findings suggest that the impairment caused by smoking cannabis vs edible THC use occurs via distinct mechanisms differing in the involvement of endothelial NO production.
Abstract 14607: Management of Inappropriate Sinus Tachycardia: A Promising Breakthrough
Authors: Pham Nicholas K , Ahmed Adnan , Bawa Danish , Ghazal Rachad , Kabra Rajesh , romeya ahmed , Pothineni Krishna , Darden Douglas J , Gopinathannair Rakesh , Lakkireddy Dhanunjaya R
Published: December 2023

Introduction:
Inappropriate Sinus Tachycardia (IST) is a cardiac dysautonomia with limited treatment options. This case highlights the effectiveness of a novel sinus node-sparing hybrid surgical ablation (SNSHA) for IST.

Objective:
To describe a novel hybrid surgical approach for management of IST.

Case Description:
A 43 y/o female presented with history of palpitations/tachycardia for 5 years. A comprehensive evaluation directed towards the diagnosis of IST with resting heart rates (HR) above 100 bpm and HR changes greater than 30% with minimal exertion. A trial of ivabradine & beta blockers along with lifestyle modifications offered limited relief. Patient was offered the novel SNSHA after a shared decision-making process.

Methods:
The SNSHA is a minimally invasive procedure performed by a CT surgeon in conjunction with an electrophysiologist involving thoracoscopic epicardial ablation of the sympathetic connections from the SVC to the IVC. The thoracoscopic approach allows for safeguarding of the phrenic nerve and sinus node followed by endocardial ablation along the lateral wall.

Results:
Intraprocedural pre and post ablation electroanatomic map (EAM) and electrogram (EGM) demonstrated an immediate drop in HR as shown in the Figure 1(a-d). An ILR was implanted during the procedure. On 45-day post-op visit, the patient experienced significant symptom relief and improvement in her HR as well as HR variability on ILR as shown in Figure 1(e).

Conclusion:
SNSHA offers a reasonable treatment option for patients with drug resistant IST. This procedure provided symptom alleviation and improvement in HR without increasing the risk of complications in comparison to sinus node modification ablation, which has previously been shown to be associated with higher incidence of pacemaker implantation.
Abstract 14613: Sex Differences in Protein Biomarkers and Measures of Fat Distribution
Authors: Pan Abigail S , Ramirez Fernandez Del Castillo Mariana , Parekh Juhi K , Owunna Ndidi , Roshandelpoor Athar , Murabito Joanne M , Levy Daniel , Ho Jennifer E , Lau Emily S
Published: December 2023

Background:
Sex differences in obesity and fat distribution have been well described and may explain differences in subsequent cardiovascular risk in men vs women. Underlying mechanisms are not fully elucidated and warrant further investigation.

Objective:
This study aims to examine sex differences in the associations of obesity and fat distribution measures with cardiovascular disease (CVD) protein biomarkers reflecting key pathways including inflammation, adiposity, fibrosis, and neurohormonal regulation.

Methods:
We measured 71 circulating protein biomarkers in 3,143 participants with available computed tomography measures of adiposity in the Framingham Heart Study. We examined whether sex modified the association of obesity (body mass index [BMI] and waist circumference [WC]) and fat distribution measures (visceral adipose tissue [VAT]) with protein biomarkers using multiplicative interaction terms in multivariable linear regression models. Sex-stratified analyses were performed as appropriate.

Results:
Among 3,143 participants (mean age 50 years, 48.7% women), we found that sex modified the association of BMI with 8 protein biomarkers including AGP-1, adipsin, IGFBP-1, IGFBP-2, ADM, KLKB1, MCP-1, and ucMGP (FDR-q
int
< 0.05 for all,
Figure 1
). For example, BMI was associated with higher MCP-1 levels in women, but not in men (ß 0.132, SE 0.025, p < 0.0001 in women vs ß 0.036, SE 0.028, p = 0.20 in men, FDR-q
int
0.03). We found that sex also modified the association of WC and VAT with key CVD protein biomarkers including AGP-1 and A1M.

Conclusions:
We found that sex modified the association of obesity and adipose traits with cardiovascular risk as ascertained using biomarkers of CVD. These findings highlight potential biological pathways that may contribute to obesity-related cardiometabolic disease uniquely in men versus women.
Abstract 14660: The Effect of Sacubitril/Valsartan Therapy on Hospitalization and Mortality in Patients Non-Respondent to Cardiac Resynchronization Therapy
Authors: Szabo Krisztina Maria , Toth Anna Zsofia , Racz Vivien , Nagy Attila Csaba , Barta Judit , Borbely Attila , Csanadi Zoltan
Published: December 2023

Background:
Non-responders to Cardiac Resynchronization Therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcomes of heart failure patients with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials; however, limited data are available on the specific cohort of CRT-NRs.

Aim of the study:
We have compared heart failure hospitalization (HFH) and mortality rates in three patient cohorts: CRT-NR patients on S/V versus on ACEi/ARB and general HFrEF patients on S/V.

Methods:
275 HF patients, including 70 CRT-NRs receiving S/V at least for 6 months (Group I); 70 CRT-NRs on ACEi/ARB treatment (Group II); and 135 HFrEF patients without CRT indication on S/V therapy at least for 6 months (Group III) were included. CRT-NR was defined as a less than 10% improvement in left ventricular ejection fraction (LVEF) 6 months after device implantation. Rates of HFH and the composite of all-cause mortality/heart transplantation/LVAD therapy were compared with a mean follow-up of 21.5 months. A subgroup analysis was also performed in patients on S/V (Groups I and III) who demonstrated a more versus less than 10% increase in LVEF after 6 months of S/V treatment (S/V super-responders versus S/V moderate responders, respectively).

Results:
HFH rates were similar in Groups I and III (28.5% vs. 28.1%, respectively; p>0.05), while significantly higher (54.2%) in Group II (p=0.02). No significant difference in the composite mortality endpoint was demonstrated between the three groups (22.8% vs. 24.2% vs. 22.2%, p=0.08). On S/V treatment, 13 out of the 70 (18.5%) CRT-NR patients (Group I) and 24 out of the 135 (17.8%) HFrEF patients (Group III) were found to be SV super-responders. Comparing these 37 patients with the 168 S/V moderate responders, neither the HFH (24.3% vs 30.9%, p=0.07), nor the composite mortality rates (24.3% vs 23.2%, p=0.53) demonstrated significant differences.

Conclusion:
S/V treatment in CRT-NRs improved hospitalization rates similarly to what was observed in a general HFrEF population. No benefit in mortality rates was demonstrated in this cohort. The extent of change in LVEF on S/V was not predictive of a better response on HFH or mortality.
Abstract 14693: Combined Tele-Cardiology Tools for Cardiovascular Risk Stratification in Primary Care: Data From the PROVAR+ Study
Authors: Cardoso Clareci S , Ribeiro Isabely S , silva gabriela , de Morais Bessa Allan M , Vinhal Wanessa C , da Mata Coimbra Mariela M , Silva Cássia Aparecida , Nunes Maria D , Fraga Lucas L , Diniz Marina G , Ferreira Alexandre M , Silva Mauro Henrique A , Barbosa Marcia , Costa Beatriz , Fava Henrique L , Diamante Lucas C , Ribeiro Antonio L , Sable Craig A , Nascimento Bruno R
Published: December 2023

Introduction:
Tele-cardiology tools are valuable strategies to improve risk stratification, especially in low-resourced settings. We aimed to evaluate the accuracy of tele-electrocardiography (ECG) in remote sites to predict abnormalities in screening echocardiography (echo) in primary care (PC).

Methods:
In 17 months, 6 healthcare workers at 16 PC units were trained on simplified handheld (GE VSCAN) echo protocols. Tele-ECGs were recorded with dedicated software with measurement and magnification tools, with final diagnosis by a cardiologist. Consented patients with major ECG abnormalities by the Minnesota code, and a 1:3 sample of individuals without abnormalities underwent a clinical questionnaire and screening echo interpreted remotely. Major heart disease (HD) was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion or wall-motion abnormalities. Association between major ECG and echo abnormalities was assessed by logistic regression, in 4 models: 1): unadjusted, 2): model 1 adjusted for age and sex; 3): model 2 plus cardiovascular risk factors (hypertension and diabetes); 4: model 3 plus history of cardiovascular disease (Chagas, Rheumatic Heart Disease, ischemic heart disease, stroke and heart failure).

Results:
At total 1,411 patients underwent echo; 1,149 (81%) with major ECG abnormalities. Mean age was 67 (IQR 60-74) years, 51.4% were males; 76.3% had hypertension, 37.7% diabetes and 22.3% ischemic heart disease. Among those with major ECG abnormalities, 78% had abnormal echo. Major ECG abnormalities were associated with a 2.2 higher chance of major HD in echo in bivariate analysis: OR=2.15; (95%CI: 1.76 - 3.39), and remained significant after adjustments in models (p<0.001) 2: OR=2.57 (95%CI 1.84 - 3.65), model 3 (OR=2.52 (95%CI 1.80 - 3.58), and model 4 (OR=2.23 (95%CI 1.59 - 3.19). Age (OR=1.07 (95%CI 1.06 - 1.09), p<0.001) and heart failure (OR=5.18 (95%CI 2.43 - 11.87), p<0.001 were also independent predictors of major HD on echo.

Conclusions:
Tele-ECG abnormalities increased likelihood of major HD on screening echo, even after adjustments for demographic and clinical variables. The combination of tele-cardiology tools and clinical data may improve risk stratification in PC.
Abstract 14696: Blockade of CD47 Using a Novel Anti-CD47 Molecule, BRB-002, Attenuates Atherosclerosis in an ApoE Mouse Model
Authors: Yun Rui , Feng Dongdong , Ardoin Caiaphas , Mata Ofelia , Chen Sharline , Cheruvu Pavan , Leeper Nick J , Basson Craig , YI B Alexander
Published: December 2023

Atherosclerosis is characterized by the deposition of lipoproteins in the vessel wall leading to inflammatory response, neointimal thickening, and occlusive plaque. Emerging data suggests that the cell surface marker CD47 is upregulated in atherosclerotic lesions. CD47 produces a ‘don’t eat me’ signal that prevents efficient clearance of diseased vascular cells by phagocytes (a process referred to as ‘efferocytosis’), and it has been hypothesized that dysregulated CD47 may contribute to expansion of atherosclerotic lesions by allowing the accumulation of inflammatory debris in the necrotic core. Blockade of CD47 has been shown to reverse this defect in efferocytosis and attenuate atherosclerosis in mouse models. Here, we evaluated the efficacy of BRB-002, a novel hybrid protein biologic inhibitor of CD47, in a mouse model of atherosclerosis. Four-week-old apolipoprotein E-deficient (ApoE -/-) male mice were fed a high fat diet for 12 weeks during which they were treated with BRB-002 at 2.5 mg/kg, BRB-002 at 10 mg/kg, or IgG isotype control (10 mg/kg) three times a week. Animals were monitored by serial measurements of hematologic parameters, pharmacokinetics, and CD47 receptor occupancy. After 12 weeks, mice were injected with a cathepsin B fluorescent probe and then necropsied to examine their descending aortas. Probes of cathepsin B activity have been used to detect atherosclerotic lesions and shown to correlate with areas of active inflammation and plaque burden. BRB-002 was generally well tolerated in ApoE -/- mice with similar hemoglobin, hematocrit, and red blood cell count between groups. Evaluation of aortas by cathepsin B activity showed that animals treated with BRB-002 at both 2.5 mg/kg and 10 mg/kg dose groups showed significantly decreased cathepsin B activity compared to mice treated with isotype control. These results suggest that blocking CD47 with BRB-002 can attenuate inflammation and atherogenesis in mice.
Abstract 14699: Effects of Papillary Muscle Approximation and Annuloplasty Ring Sizing for Functional Mitral Regurgitation Repair in Enlarged Ventricles
Authors: Gaidulis Gediminas , Dasi Lakshmi , Padala Muralidhar
Published: December 2023

Introduction:
Our recent large animal study showed that papillary muscle approximation (PMA) repairs functional mitral regurgitation (FMR) and increases valve coaptation in enlarged left ventricles without negatively affecting ventricular function. However, since PMA does not reduce mitral annular dilation, addition of annuloplasty ring might be beneficial for such repair. In this study, we used computational modeling to investigate the benefit of the addition of annuloplasty to PMA and the effects of ring sizing on FMR repair in enlarged ventricles.

Methods:
3D echo images were obtained in 3 pigs with heart failure, enlarged ventricles, and FMR. Each echo dataset was segmented, and computational model of the mitral valve was developed. To mimic PMA repair, the papillary muscles were drawn together in diastole. A true-sized annuloplasty ring of 40 mm and two downsized-rings of 38 mm and 36 mm were then added to each model. Leaflet closure was simulated and mitral valve geometry and biomechanics in peak systole were evaluated (
Fig A-B
).

Results:
On average, compared to pre-repair, PMA increased coaptation area by 30.6%, while the addition of annuloplasty increased this area by 85.1% with 40 mm, 138.1% with 38 mm, and 190.6% with 36 mm ring. Tenting area was reduced by 45.8% after PMA, 64.1% with the addition of 40 mm ring, 70.6% with 38 mm, and 76.5% with 36 mm ring. PMA reduced tension forces in chordae by 19.8%, while adding true-sized ring reduced forces by 16.4%. Annular downsizing allowed to reduce chordal forces by 31.2% with 38 mm, and 43.0% with 36 mm ring. Peak leaflet stress was observed on the P2 cusp, and PMA reduced it by 26.9%. True-sized ring reduced peak stress by only 10.7%, while 38 mm ring by 29.9%, and 36 mm by 43.7% (
Fig C
).

Conclusions:
Addition of true-sized ring to PMA further improved systolic valve geometry but not biomechanical parameters. Annular downsizing added to PMA was more beneficial for FMR repair, as it improved both mitral valve geometry and biomechanics.
Abstract 14724: Health Status and Long-Term Outcomes After Acute Myocardial Infarction in Patients Without Standard Modifiable Risk Factors
Authors: Ikemura Nobuhiro , Nguyen Dan , Sawano Mitsuaki , Lu Yuan , Gosch Kensey , Krumholz Harlan M , Spertus John
Published: December 2023

Background:
Prior studies examining patients who experienced acute myocardial infarction (AMI) as their initial presentation of coronary disease have shown that those without Standard Modifiable Risk Factors (SMuRF; diabetes, dyslipidemia, hypertension, and smoking) had worse in-hospital but better long-term survival than those with SMuRFs. However, the health status outcomes, patients’ symptoms, function, and quality of life among those without SMuRF are unknown.

Research questions:
Are there differences in long-term health status and mortality between patients who survived hospitalization following AMI with and without SMuRFs?

Methods:
We analyzed data from two prospective registries, PREMIER and TRIUMPH, comprising patients hospitalized to 31 US hospitals with AMI between 2003-2008. We compared the clinical characteristics, 1-year health status (with the Seattle Angina Questionnaire [SAQ]), and 5-year all-cause mortality between patients with and without SMuRFs. Patients with prior coronary artery disease were excluded. We used hierarchical linear mixed models for health status outcomes and Cox-proportional hazard models for mortality, adjusted for clinical and sociodemographic characteristics, including baseline SAQ scores.

Results:
Among 4076 patients with AMI (mean age 58.4±12.4 years, 34% female, 22% Black), 569 (13.9%) presented without SMuRFs. Despite similar mean age, patients without SMuRFs were more likely to be male, Non-Hispanic White, have higher income and education, fewer depressive symptoms, and higher SAQ Summary Scores at baseline (83.5±13.2 vs. 79.6±16.5). At 1-year follow-up, patients without SMuRFs had higher SAQ Summary Scores (93.9±10.1 vs. 89.9±14.7), although the difference between groups was attenuated after adjustment (1.69 points, 95% CI 0.40-1.97). Furthermore, there were no significant differences in all-cause mortality over 5 years between groups (adjusted HR= 0.83, 95% CI: 0.59-1.16). Notably, besides sex or race category, a higher incomes and better depression status were negative independent predictors for health status and clinical outcomes.

Conclusions:
AMI survivors, both with and without SMuRFs, had comparable long-term health status and survival after rigorous adjustment.
Abstract 14745: Stem Cell Factor Associated With Critical Limb Ischemia in Patients With Peripheral Artery Disease
Authors: Bonaca Marc P , Morrow David , Giugliano Robert , Scirica Benjamin , Creager Mark A , Jarolim Petr , Bellavia Andrea , Murphy Sabina A , Sabatine Marc S
Published: December 2023

Introduction:
Critical limb ischemia (CLI) and related amputation (AMP) are severe manifestations of peripheral artery disease (PAD). The pathobiology of CLI/AMP is multifactorial including chronic ischemia in the context of large vessel and microvascular disease. Novel biomarkers may identify potential pathways for new therapies to prevent and treat CLI.

Hypothesis:
Exploration of the proteome will yield insights into new proteins and hence pathways relevant in the pathogenesis and complications of PAD.

Methods:
A nested case-control study including 50 patients with CLI/AMP and 83 without was assembled from patients with PAD in the TRA2P-TIMI 50 trial for proteomic exploration using the Olink CVDII panel. Candidate markers were identified based on a false discovery rate (FDR) p-value <0.05 and then validated among 7,077 patients with PAD from TRA2P-TIMI 50 and FOURIER trials. Biomarkers were evaluated continuously & by quartile and analyses adjusted for age, sex, diabetes mellitus, and prior peripheral revascularization.

Results/Data:
A total of 12 protein biomarkers were significantly associated with CLI/AMP in the case-control sample at an FDR of 5% (Fig-Panel A). Three remained significantly associated with CLI/AMP in the validation step, the strongest of which was stem cell factor (SCF), a cytokine expressed by endothelial cells and involved in vasculogenesis. There was a significant inverse association between SCF and CLI/AMP (p-Bonferroni 0.00047). Examined by quartiles and adjusting for baseline differences (Panel B), a graded inverse association between SCF and CLI/AMP was observed (Q4 vs Q1 Adjusted OR 0.52, 95% CI: 0.34, 0.77; p=0.002).

Conclusions:
A proteomic approach to identifying novel biomarkers associated with CLI/AMP revealed a strong inverse risk relationship with SCF levels. These data suggest that SCF and its effects on vasculogenesis warrant further investigation as a pathway to prevent and treat CLI/AMP in patients with PAD.