bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10206: Misleading Transvalvular Hemodynamics for Patients With Moderate Aortic Stenosis
Authors: Mohanty Sharanya , Kherlopian Alec , Steinhauer Rachael , Downey Brian C , Pandian Natesa G , Apostolidou Eirini , Patel Ayan R , Wessler Benjamin S
Published: June 2023

Introduction:
Aortic stenosis (AS) is a progressive disease that leads to cardiac remodeling. Appropriate management depends on accurate assessment of AS severity. Transvalvular gradients are central to echocardiographic assessment of AS though can be impacted by any conditions that decrease transvalvular flow.

Hypothesis:
1) Decline in peak transvalvular gradient over time is associated with more significant cardiac remodeling and 2) Cardiac damage is associated with lower transvalvular flow and masks progression of AS.

Methods:
Retrospective single center study of patients with moderate AS (defined as peak gradient 25-40mmHg) from 2013-2020 with > 1 transthoracic echocardiogram (TTE). Each TTE was classified into established stages of cardiac damage: no damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage or subclinical heart failure (Stage 4).

Results:
Sixty patients with at least 1 follow-up TTE were included. The mean age was 73.5 +/- 11 years with 47% women (28/60) and median time of 381 days (IQR 12.7 months) between echocardiograms. On initial assessment, mean AVA and peak AV gradient were 1.2cm
2
+/- 0.33 and 37mmHg +/- 11.3 respectively. At follow-up, the mean AVA and peak AV gradient were 1.1cm
2
+/- 0.20 and 38mmHg +/- 12.6. Forty-three of 60 patients (72%) had evidence of cardiac damage on initial assessment compared to 55 of 60 patients (92%) on follow-up. Thirty-five (58%) patients displayed a decrease in peak AV gradient over time (average decrease -16% +/- 0.12). Twenty-one of the patients with declining peak gradients (60%) demonstrated progressive cardiac damage compared to 9 of 25 patients (36%) with increasing peak gradients (p= 0.06).

Conclusions:
Over half of patients with moderate AS demonstrated a decrease in peak AV gradient over time. Reliance on transvalvular gradients as a reflector of AS severity can be misleading as there was a trend toward more significant cardiac damage in this subset of patients. The presence of underlying cardiac damage can obscure traditional echocardiographic assessment and progression of AS and should be incorporated into assessments of disease severity and progression.
Abstract 10255: The Evolving Impact of Myocardial Injury in COVID-19 Patient Amid the Omicron Wave of the Pandemic
Authors: Case Brian C , Shea Corey , rappaport hank , Cellamare Matteo , Zhang Cheng , Zhu Mason , Kumar Sant , Medranda Giorgio A , Satler Lowell F , Waksman Ron , Rogers Toby , Waksman Ron
Published: June 2023

Introduction:
Coronavirus disease 2019 (COVID-19) with evidence of myocardial injury, defined as troponin elevation, has been demonstrated to be associated with worse outcomes. The temporal changes in outcomes in these patients during various phases of the pandemic remain unclear.

Hypothesis:
We sought to evaluate outcomes during the Omicron phase compared to previous phases of the pandemic.

Methods:
We analyzed COVID-19-positive patients with myocardial injury who presented to the MedStar Health system (11 hospitals in Washington, DC and Maryland) during Phase 1 of the pandemic (March 1 - June 30, 2020), Phase 2 (October 1, 2020 - January 31, 2021) and Phase 3 (Omicron) (December 1, 2021 - March 31, 2022) comparing their characteristics and outcomes. The primary end point was in-hospital mortality.

Results:
The cohort included 2079 COVID-19-positive admitted patients for whom troponin-I or high-sensitive troponin was elevated (Phase 1: n=150, Phase 2: n=854, Phase 3 [Omicron]: n=1075). Baseline characteristics were overall similar. Inflammatory markers were significantly elevated in Phase 1 as compared to Phase 2 and the Omicron Phase. The use of remdesivir and dexamethasone was most seen in Phase 2. In the Omicron Phase, 52.6% of patients were fully vaccinated. In-hospital mortality although high was lower in the Omicron Phase as compared to Phase 1 and Phase 2 (23.3% vs. 59.3% vs. 28.1%; p<0.001). Those vaccinated demonstrated even more favorable outcomes as compared to those patients unvaccinated (18.3% vs 24.2%, p = 0.042).

Conclusions:
COVID-19 patients with elevated troponin during the Omicron Phase still have significant mortality rates despite overall improved outcomes when compared to the first and second waves of the pandemic. This improvement in outcomes could be attributed to the implementation of the COVID-19 vaccine, advances in available COVID-19 treatment options, provider experience with the novel disease and less virulent variants.
Abstract 10263: “High Blood Pressure Comes From Thinking Too Much”: Health Beliefs Among Couples With Cardiometabolic Disorders and HIV in Sub-Saharan Africa
Authors: Conroy Amy A , Bidwell Julie T , Ruark Allison , Butterfield Rita , Neilands Torsten , Weiser Sheri , Mulauzi Nancy , Mkandawire James , Huwa Jacqueline
Published: June 2023

Introduction:
People living with HIV are at increased risk for cardiometabolic disorders (CMD) due to chronic inflammation, immune activation, and antiretroviral therapy. In high HIV prevalence areas of sub-Saharan Africa, little is known about how HIV patients and their partners understand CMD and how health services could leverage partner support.

Objective:
To explore health beliefs among HIV patients with CMD and primary partners

Methods:
We conducted a qualitative study with 25 couples recruited from 3 HIV care clinics in Zomba, Malawi. Patients managing HIV and CMD (hypertension and/or diabetes) were enrolled first, followed by their primary partners. Semi-structured interviews were conducted separately with partners to elicit health beliefs around causality, prevention, and management of CMD. Dyadic data were coded for patterns and themes within couples and between couples, and data matrices were created to compare and contrast the findings.

Results:
Most participants believed that the main causes of CMD were diet, aging, and genetics, but some believed CMD was sexually transmitted or caused by viruses such as HIV. Within couples, diet and stress were the most commonly agreed-upon cause, and over half of couples believed “thinking too much” due to stress or couple conflict was a cause of CMD. Prevention beliefs included a healthy diet, exercise, avoiding HIV, using condoms, and keeping stress levels low. Management beliefs included dietary changes, taking medication or herbs, exercising, and reducing stress. Within couples, the most agreed-upon belief was that diet, particularly salt reduction, was important for prevention and management; however, within-dyad disagreement and incorrect beliefs around other aspects of a heart-healthy diet were common.

Conclusion:
While lifestyle factors were correctly identified as important for prevention and management of CMD, misconceptions remained around transmission through a virus or sex. Partners often differed in their views of CMD, which could interfere with CMD management. Health education programs are critically needed and involving partners may offer an opportunity to solidify knowledge in couples and foster collaborative disease management around CMD.
Abstract 10270: High Shear Stress Decreases ERG Causing Endothelial to Mesenchymal Transition and Pulmonary Arterial Hypertension
Authors: Shinohara Tsutomu , Moonen Jan-Renier A , Okamura Kenichi , Szafron Jason , Taylor Shalina , Isobe Sarasa , Dong Melody L , Cao Aiqin , Wang Lingli , Marsden Alison L , Korbelin Jakob , Rabinovitch Marlene
Published: June 2023

Introduction:
Computational modeling studies indicated that pathological high shear stress (HSS) of 100 dynes/cm
2
is generated in pulmonary arteries (PA) (100-500μM) in patients with a ventricular septal defect or idiopathic pulmonary arterial hypertension (PAH) and occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH.

Hypothesis:
Pathological HSS induces EndMT, which contributes to the initiation and progression of PAH.

Methods:
We apply

the Ibidi perfusion system to human PA endothelial cells (EC), to determine whether HSS (100 dynes/cm
2
) induces EndMT, when compared to normal laminar shear stress (LSS) (15 dynes/cm
2
). We assessed the mechanism and targeted it to prevent PAH in a mouse with HSS resulting from an aortocaval (AV) shunt.

Results:
HSS induced EndMT, as assessed by an increase in transcription factors, SNAI1 and SNAI2, reduced BMPR2 (previously shown to inhibit EndMT), decreased EC markers PECAM1 and CDH5, and increased mesenchymal markers, ACTA2 and FSP-1. While the flow-induced transcription factors, KLF2 and KLF4 were similar in LSS and HSS, the co-transcription factor ERG was reduced with HSS. Indeed
ERG
siRNA under LSS caused EndMT whereas under HSS, transfection of
ERG
prevented EndMT. To address the significance of our observations in an animal model we created an AV shunt in mice and compared PAH in those sham operated vs transfected with an adeno-associated viral (AAV2- ESGHGYF) vector selectively targeting PAEC with a
luciferase
(control) or an
ERG
expressing construct (N=10 per group). Eight weeks after AV shunt, right ventricular systolic pressures was 21.9 ±0.6 mmHg in sham, 37.2±1.0 mmHg in AV shunt with luciferase vector (p<0.01 vs sham) and 29.2±0.8 mmHg in ERG-vector (p<0.01 vs both sham and luciferase). Muscularization of peripheral PA was similarly reduced in ERG-vector (p<0.01 vs luciferase) but not normalized (p<0.01 vs sham) as was immunohistochemical evidence of EndMT (p<0.01 vs luciferase).

Conclusions:
Our study is the first to document pathological HSS as an inducer of EndMT and PAH and to show that this results from reduced PAEC ERG. Agents that upregulate ERG could reverse HSS mediated PAH and occlusive vascular remodeling as a consequence of high flow or narrowed PAs.
Abstract 10296: Relation of Lipoprotein(a) to Progression of Coronary Artery Calcium: Results From a Pooled Cohort of Mesa, Cardia, and Framingham Offspring Studies
Authors: Wong Nathan D , FAN WENJUN , Hu Xingdi , Ballantyne Christie M , Hoogeveen Ron C , Tsai Michael Y , Browne Auris , Budoff Matthew
Published: June 2023

Background:
Lipoprotein(a) [Lp(a)] levels and coronary artery calcium (CAC) are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. Progression of CAC is also associated with greater ASCVD risk. Less well-established is the relation of Lp(a) with progression of atherosclerosis as assessed by progression of CAC.

Methods:
We included a pooled cohort of 9454 persons without ASCVD at baseline (mean age 55.6 years, 53.5% female, and 31% black) and with multiple measures of CAC (up to 4 over a mean of 7.3
+
3.3 years from baseline CAC measures) from the Multiethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Framingham Offspring Studies. Lp(a) was assessed continuously and by category (<15 mg/dL [reference], 15-29 mg/dL, 30-49 mg/dL, 50-69 mg/dL, 70-89 mg/dL, and
>
90 mg/dL) in relation to progression of CAC (annualized change in Agatston score) incorporating multiple CAC measures utilizing mixed model regression with time (in years), adjusted for age, sex, race, baseline CAC, and other covariates. Subgroup analyses were done separately in those with baseline CAC.

Results:
A 50 mg/dL increment of Lp(a) was associated with an adjusted annualized change in CAC score of 3.97 units. Compared to those with Lp(a) levels of <15 mg/dL, those with levels of 50-69 mg/dL, 70-89 mg/dL, and
>
90 mg/dL had a statistically significant annualized progression of CAC that was 3.09, 8.70, and 9.46 units greater in adjusted analyses. Progression was greater in those with baseline CAC>0 (Table).

Conclusions:
Higher levels of Lp(a) are associated with greater progression of atherosclerosis as measured by CAC scores.
Abstract 10318: Polyunsaturated Fatty Acids, EPA and DHA Possess a Potent P300-hat Inhibitor and Prevent Mi-Induced Development of Heart Failure in Rats
Authors: Sunagawa Yoichi , Funamoto Masafumi , Hamabe-Horiike Toshihide , Shimizu Kana , Shimizu Satoshi , Katanasaka Yasufumi , Hosomi Ryota , Hasegawa Koji , Morimoto Tatsuya
Published: June 2023

Introduction:
The histone acetyltransferase (HAT) activity of p300 has a crucial role in the development of heart failure. Although many studies have shown a cardioprotective effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 unsaturated fatty acids, little is known about the effects of these acids on cardiomyocyte hypertrophy. In this study, we investigated the effects of these acids on cardiomyocyte hypertrophy and the development of heart failure in rats with myocardial infarction (MI).

Methods and Results:
In cardiomyocytes, EPA and DHA (10 μM) significantly suppressed equally PE-induced cardiomyocyte hypertrophy, hypertrophy-response gene transcriptions, and acetylation of histone-H3K9. Furthermore, p300-induced hypertrophic responses were also suppressed by EPA and DHA. The result of an
in vitro
p300-HAT assay revealed that EPA and DHA directly inhibited p300-HAT activity (IC50: 37.8 μM, 30.6 μM) and induced allosteric inhibition of histones and competitive inhibition of acetyl-CoA
in vitro
. In addition, palmitic acid and stearic acid could not inhibit them. MI-operated rats (FS<40%) were randomly assigned to 3 groups; vehicle (saline), EPA, and DHA (1g/kg). One week after the operation, oral administrations were repeated for 6 weeks. The echocardiographic analysis demonstrated that both EPA and DHA treatments prevented MI-induced left ventricular remodeling with preserved FS. Furthermore, EPA and DHA significantly suppressed the MI-induced increase in myocardial cell diameter, perivascular fibrosis, mRNA levels of hypertrophic and fibrotic markers, and acetylation of histone H3K9. In the left ventricle, EPA contents were lower than those of the other fatty acids, and no difference in each group. The EPA group exhibited higher docosapentaenoic acid (DPA) and DHA content than the vehicle group. The DHA group increased DHA content but not DPA and EPA contents.

Conclusion:
These results suggested that both EPA and DHA suppressed MI-induced development of heart failure through the inhibition of p300-HAT activity. The cardioprotective effect of EPA on MI might be attributed to the conversion of DHA or EPA metabolites.
Abstract 104: Taurine As Biomarker And Therapeutic Target For Cardiac Arrest
Authors: Li Jing , Karfunkle Benjamin L , Justice Cody N , Kim Hajwa , Granado Misha N , Qin Kevin , Lee Chunpei , Kotini-Shah Pavitra , Lin Shaoxia , Zhu Xiangdong , Vanden Hoek Terry L
Published: June 2023

Introduction:
Out-of-hospital cardiac arrest (CA) is a leading cause of death with high mortality. Most patients die from post-CA syndrome due to ischemia/reperfusion injury-triggered responses. Taurine and glutamate, amino acids with cellular activities that are expressed primarily in heart and brain tissues, respectively, are released in response to CA.

Hypothesis:
Taurine and glutamate levels in blood reflect the extent of injury of CA. Taurine and glutamate could potentially regulate CA outcomes.

Methods:
Adult CA patients (n=51, 19 survivors, S and 32 nonsurvivors, NS; 35 received cooling treatment, C while 16 did not, NC) at an urban academic ED were enrolled from 2018-2019. Plasma taurine and glutamate collected at various time points including hospital arrival, 6, 24, 48 and 72 hours after arrival, and measured with commercially available assay kits. In a mouse model, 8-min asystolic cardiac arrest was induced with KCl, followed by initiation of CPR and randomized to blinded administration of taurine (50 mg/kg) or saline placebo at 90 second during CPR. Survival (4h) and mean arterial blood pressure (MAP) were evaluated. The Wilcoxon test and generalized estimating equation were used for comparison at each time point and longitudinal trend analysis for human data. Kaplan-Meier estimate and T-test were used for survival and mean comparison in mice.
p
<0.05 was considered statistically significant.

Results:
Plasma taurine and glutamate levels were highest at R0 and decreased over time in both S and NS, and were higher in NS than S. Taurine levels were significantly associated with survival (NS 66.24±41.36 vs. S 37.48±19.46 at 6h,
p
<0.05) while glutamate levels were not. Taurine levels in both C and NC groups demonstrated a significantly decreasing trend over time, but the C group showed more reduction (
p
<0.05), while glutamate levels showed no significant trend. In mice, compared to saline, taurine treatment markedly improved 4h survival and MAP post-ROSC.

Conclusions:
Decreased release of taurine into blood is correlated with CA survival and may regulate CA outcomes. It has high translational potential as a biomarker for predicting CA survival, guiding cooling treatment, and serving as a therapeutic target to improve CA outcomes.
Abstract 10401: Development and Pilot Implementation of Two Targeted Approaches to Ambulatory Clinical Decision Support for Cardiologists to Optimize Medical Therapy for Heart Failure
Authors: Mukhopadhyay Amrita , Reynolds Harmony , Xia Yuhe , Phillips Lawrence M , Aminian Rod , Diah Ruth-Ann , Nagler Arielle , Szerencsy Adam , Saxena Archana , Horwitz Leora , Katz Stuart D , Blecker Saul
Published: June 2023

Introduction:
Shortfalls in prescribing of proven therapies for patients with heart failure and reduced ejection fraction (HFrEF), particularly for mineralocorticoid receptor antagonists (MRA), account for several thousand preventable deaths per year nationwide. Electronic clinical decision support (CDS) is a potential low-cost and scalable solution to improve prescribing, but optimal timing and format of CDS tools are unknown.

Objective:
We developed two CDS interventions to inform cardiologists of gaps in MRA therapy for patients with HFrEF and without contraindication to MRA therapy: 1) a best practice alert (BPA) that notifies cardiologists at the time of patient visit, and 2) an automated in-basket message that allows for review between visits.

Methods:
We designed CDS tools using an established CDS framework and findings from semi-structured interviews with cardiologists. We then pilot-tested both CDS tools at two cardiology practices for 12 weeks in a cross-over design, and further enhanced them based on additional semi-structured interviews.

Results:
Based on pilot testing (n=596 patients) and semi-structured interviews (n=11 cardiologists), in-basket messages were modified to reduce the number of patients listed, include future visits, and list date of next visit. The BPA was modified to improve noticeability, reduce extraneous information on guidelines, and include key information on contraindications. Final CDS interventions after incorporation of feedback are depicted in the Figure.

Conclusions:
Pilot testing and semi-structured interviews were instrumental in the development of CDS interventions and should be employed for other similar studies. We will compare the effectiveness of the BPA vs the in-basket message vs usual care on the primary outcome of MRA prescribing in The BETTER CARE-HF trial (Building Electronic Tools to Enhance and Reinforce CArdiovascular REcommendations for Heart Failure) (Clinicaltrials.gov NCT05275920)
Abstract 10420: Spontaneous Coronary Artery Dissection in a Young Man Taking Sumatriptan
Authors: Hirsch Eric , Mendapara Parrykumar , Akiyama Matthew
Published: June 2023

Introduction:
Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. There is an approximate 9:1 female predominance, and commonly cited risk factors include fibromuscular dysplasia, pregnancy, and cocaine use. We present a case of SCAD in a young man with migraines and triptan use, initially misdiagnosed as panic disorder.

Case:
A 25-year-old man with a history of migraines treated with sumatriptan presented with several months of intermittent chest pain and syncopal episodes. He had been evaluated in an emergency department at the onset of symptoms and diagnosed with panic disorder. His EKG now showed Q waves in leads V1-V2 and T wave inversions in leads I and AVL. Serial troponins were stable at 0.04 ng/mL. An echocardiogram showed left ventricular apical ballooning and large thrombus. Left heart catheterization revealed significant stenosis of the proximal LAD and 50% stenosis of the mid LAD (Fig. 1A). A follow-up CT angiogram showed intimal thickening and perivascular fat stranding in the proximal and mid LAD, confirming a diagnosis of SCAD (Fig. 1B). A full-body CTA showed no additional aneurysm or dissection. Inflammatory markers and autoimmune serologies were negative. Urine toxicology was negative for cocaine or amphetamines. Given an otherwise unrevealing workup, migraines and triptan use were identified as the significant risk factors for SCAD. He was discharged with clopidogrel, warfarin, and metoprolol and counseled against further use of triptans

Discussion:
Multiple studies have reported increased prevalence of SCAD in patients with migraines, particularly those using triptans. This phenomenon likely relates to stimulation of 5-HT1B and 5-HT1D receptors in the coronary vasculature. Greater recognition of SCAD and its risk factors is essential for timely diagnosis and treatment, particularly in young patients whose chest pain may be falsely attributed to non-cardiac causes.
Abstract 10429: When You Hear Hoofbeats, Think Zebras and Not Horses: A Case of Cardiac Tamponade Preceding the Diagnosis of Rheumatoid Arthritis
Authors: Tsay Annie J , Hoeger Christopher W , Gendelman Hannah , Stout Brian , Anagnostopoulos Anne-Marie
Published: June 2023

Introduction:
We present a case of a 50 year-old man who presented with one week of chest discomfort and ECG consistent with pericarditis (Fig. 1A) complicated by pericardial effusion. He rapidly developed cardiac tamponade with a pulsus paradoxus of 30mmHg and associated echocardiographic signs including RV diastolic collapse (Fig. 1B) and severe respiratory variation requiring pericardiocentesis (Fig. 1C). He was treated with high-dose indomethacin and colchicine 0.6mg twice daily with symptomatic improvement. Initial work-up for the etiology of pericardial effusion was notable for a borderline ANA of 1:40 and an RF of 20 IU/mL. CRP improved from 115.5 mg/L to 6.3mg/L with treatment. Two months later, he developed recurrent chest pain with new arthralgias and new morning stiffness in several joints after completing the course of indomethacin. A repeat ECG revealed normal sinus rhythm. He was restarted on high-dose indomethacin and referred to rheumatology clinic for further autoimmune work-up. This revealed an elevated anti-cyclic citrullinated peptide antibody IgG titer (>250), which is highly specific for RA. He was started on methotrexate 15mg weekly for treatment of newly diagnosed RA. To date, he remains asymptomatic.

Results:

Conclusions:
Cardiac tamponade as the initial presentation of RA has not been previously described, but has been seen in systemic lupus erythematosus. Few case reports of pericardial disease without tamponade as the initial finding of RA have been reported. Development of cardiac tamponade in RA is rare (<1%). New clinical symptoms and a high index of suspicion should prompt repeat and expanded work up for rheumatologic etiologies of pericardial disease. While cardiac involvement in RA is known to increase mortality, outcomes have been improving due to novel anti-inflammatory therapies. This case serves as an example of the collaboration needed between specialties to make the correct diagnosis in cardio-rheumatology patients
.
Abstract 10433: Inhibition of Plasminogen Activator Inhibitor Type 1 in Experimental Venous Thrombosis
Authors: Shaydakov Maxim E , Rainey Joshua , Lawrence Daniel A , Lurie Fedor , Diaz Jose A
Published: June 2023

Introduction:
Conventional treatment of deep vein thrombosis is suboptimal, requiring continuous improvement in knowledge about the disease and a search for new therapeutic approaches.

Hypothesis:
Blood flow affects the composition of an acute venous thrombus (VT).
Aim 1:
Compare VT composition under flow and stasis conditions.
Aim 2:
Evaluate the antithrombotic properties of the novel PAI-1 inhibitor MDI-2268 in-vivo.

Methods:
C57BL/6 mice, 10-12w, 20-25g were used in electrolytic (EIM) and ligation (LM) models of venous thrombosis.
Aim 1:
The thrombus weight (TW) and the microstructure of an acute VT (Day 2) in the EIM (n=5) and the LM (n=5) were compared. Expression of PAI-1, tPA, and uPA in the vein wall and plasma levels of D-dimer were investigated.
Aim 2:
Five EIM groups (n=5) were studied: MDI-2268 1.5 mg/kg (Group 1), MDI-2268 3 mg/kg (Group 2), enoxaparin 7.3 mg/kg (Group 3), MDI-2268 3 mg/kg plus enoxaparin 1.8 mg/kg (Group 4), and DMSO controls (Group 5). TW and bleeding time (BT) on Day 2 were measured.

Results: Aim 1:
VT within the EIM was smaller compared to the LM (6.2.5±3.6 vs. 26.2±3.6, P<0.05). VT formed within the EIM had a significantly higher amount of plasminogen. The level of D-dimer was 23.4±12.5 and 4.5±1.3 ng/mL/mg in the EIM and LM, respectively (p<0.05).
Aim 2:
TW was 6.9±3.3 (p>.05), 5.5±1.6 (p=.035), 3.8±1.3 (p=.005), and 4.8±2.4 mg (p=.035) for groups 1,2,3, and 4; compared to 12.7±5.7 mg in the controls. BT was not affected by the MDI-2268.

Conclusions:
Blood flow pattern significantly affects VT composition. Non-occlusive thrombus has a higher potential to be targeted by the fibrinolytic system due to a higher plasminogen content. MDI-2268 demonstrates strong antithrombotic properties in-vivo and may be associated with a lower risk of bleeding compared to enoxaparin. This data may contribute to a better understanding of the disease process, different outcomes after venous thrombosis, and new therapeutic targets.
Abstract 10438: Genetically Determined Levels of Apolipoprotein B and Low-Density Lipoprotein Are Not Associated With Increased Mortality in Heart Failure
Authors: Shaikh Preet , Qian Chenao , Kvikstad Erika , Maranville Joseph , Zhao Lei , Chang Ching-Pin , Gordon David A , Ramirez-Valle Francisco , Javaheri Ali , Chirinos Julio
Published: June 2023

Introduction:
Increased levels of low-density lipoprotein cholesterol (LDL-C) and its constituent apolipoprotein B (ApoB) are associated with atherosclerotic coronary disease, a risk factor for heart failure (HF). However, among patients with established HF, increased LDL-C has been associated with a lower risk of death. The potential causality of this association is unclear.

Hypothesis:
This study investigated the relationship between ApoB/LDL-C and adverse outcomes in participants with HF.

Methods:
We measured ApoB levels using the SomaScan assay among participants in the Penn Heart Failure Study (PHFS, n=1268). We performed one-sample Mendelian Randomization (MR) for ApoB and two-sample MR for ApoB and LDL-C.

Results:
Measured ApoB levels were inversely associated with the risk of death (Fig 1A) or death and heart failure hospital admission (DHFA; Fig 1B). One-sample MR revealed no significant association between genetically determined ApoB and the risk of death (HR 0.497, [95% CI, 0.20-1.2], p=0.125) or DHFA (HR 0.653, [95% CI, 0.35-1.2], p=0.182). Two-sample MR analyses were also consistent with a non-significant association between ApoB (Fig 2) or LDL-C (Fig 3) and risk of death or DHFA.

Conclusions:
ApoB is associated with the risk of death or DHFA in established HF. However, MR does not support a causal link between ApoB/LDL-C and the risk of adverse outcomes in this population.
Abstract 10451: Efficacy and Safety of Ebronucimab, a Monoclonal Antibody Against Pcsk9, in Patients With Hyperlipidemia: Result From a Phase 2, Randomized, Double-Blind, Placebo-Controlled Study
Authors: Zhen Wang , Pei Zhaohui , Chen Jiyan , Zhang Guogang , Li Dongye , Xia Yu , Li Baiyong , Wang Max , Ni Xiang , Wang Guoqin , Ge Junbo
Published: June 2023

Introduction
Elevated low-density lipoprotein cholesterol (LDL-C) is a well-recognized risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to Low-density lipoprotein receptors (LDL-R) and triggers their degradation. Inhibiting PCSK9 activity results in lowering LDL-C levels and further reduceing the risk of cardiovascular events. Ebronucimab (AK102) is a novel fully human immunoglobulin G1 (IgG1) monoclonal antibody against PCSK9.

Objectives
To evaluate the safety, efficacy of ebronucimab and further identify the optimal dosing scheme in patients with hyperlipidemia.

Methods
A total of 260 Chinese patients with hyperlipidemia (≧18 years, male or female) were planned to be enrolled, and randomized to receive ebronucimab 450 mg every 4 weeks (q4w), 300 mg q4w, 150 mg q2w, 75 mg q2w or matching placebo via subcutaneous injection. The patients were treated up to 12 weeks (day 85). Serum samples were collected at preselected timepoints to analyze the lipid profiles.

Results
Efficacy Ebronucimab showed significant and dose-dependent LDL-C reductions from baseline. At week 12, the mean reductions in LDL-C were 65.48 %, 48.14%, 63.69% and 37.39% for 450 mg q4w, 300 mg q4w, 150 mg q2w and 75 mg q2w dose groups, respectively. Patients in the 450 mg q4w and 150 mg q2w groups achieved higher and more sustained LDL-C reduction compared with other dose groups. Similar trend was observed in serum levels of total cholesterol (TC), apolipoprotein B (ApoB), lipoprotien (a) (LP[a]).

Safety
A total of 49.6% (130/262) patients experienced at least 1 treatment-emergent adverse event (TEAE), 109 patients (109/210 [51.9%]) in ebronucimab groups and 21 patients (21/52 [40.4%]) in the placebo group. Most TEAEs were mild and moderate. No adverse events were apparently dose dependent with ebronucimab. The overall incidence of serious adverse events (SAEs) was 3.4 % (9/262).

Conclusions
Ebronucimab was generally safe and well tolerated in Chinese patients with hyperlipidemia. Patients treated with ebronucimab achieved a significant reduction in serum levels of LDL-C and other lipids, especially in 450 mg q4w and 150 mg q2w treatment groups.
Abstract 10490: Sex Disparities in Cardiovascular Research Are Influenced by Senior Investigator Gender
Authors: Veizades Stefan , Auer Natasha , Sandifer Jaylen , Mueller Adrienne , Vera Carlos D , Nguyen Patricia K
Published: June 2023

Introduction:
The clinical presentation and management of cardiovascular diseases has been shown to be sex-specific, yet, historically, cardiovascular research participants have been predominantly male. One cause for this discrepancy could be gender-based bias on the part of studies' senior investigators.

Methods:
We screened 749 randomly selected clinical research articles from 8 top cardiovascular research journals, published between 2015 and 2020. We predicted the gender of senior investigators by using the genderize.io gender-coding algorithm. We then used t-tests to determine the relationship between putative senior author gender and number of study participants of each sex.

Results:
Cardiovascular research cohorts were 39.74% female. Compared to studies senior-authored by men, cohorts of female senior-authored studies included 11.36% more female participants (p<0.0001, 37.84% vs 49.44%). This difference was preserved across several study types (
Fig. 1A
). Only 15.49% of articles were written by female senior authors and the proportion of female to male senior authors did not change over time (p=0.93;
Fig. 1B
). The proportion of female participants in a study did however significantly increase between 2015 and 2020 (p=0.011,
Fig. 1B
).

Conclusions:
In cardiovascular research, the gender of the senior author of a study is predictive of the study’s sex composition: female senior authors are more likely to author studies that include higher proportions of female participants. Over time, the proportion of female to male participants in cardiovascular research studies is increasing.

Figure 1.
Percentage of women in study cohorts, (
A
) segregated by study type and gender of senior author and (
B, right
) segregated by senior author gender and year. (
B, left
) Percent of female seniors by year. Bars represent mean and standard error. p>0.05=ns, p≤0.05=*, p≤0.01=**, p≤0.001=***, p≤0.0001=****.
Abstract 10542: The Utility of Repeat Coronary Angiography in Patients With Non Ischemic Cardiomyopathy
Authors: Elkhapery Ahmed , Boppana Hemanth Krishna , Eisa Mahmoud , Chand Swati , Mohamed Mohamed Salah , Jain Deeptanshu , Hashem Anas , Abbas Syed Faiz , Mohamed Amr , baibhav bipul
Published: June 2023

Introduction:
Up to 20% of angiograms reveal no coronary artery disease (CAD). Repeat studies are often done for chest pain, dyspnea, or reduction in ejection fraction (EF), but little is known about the diagnostic yield of this practice.

Methods:
Retrospective cohort of patients with no or minimal CAD on their first angiography (<30% stenosis) and a repeat angiography in the last 5 years were included in the study.

Results:
There were 17 patients with no CAD and 26 patients with mild CAD on initial angiography, with 58 incidences of repeat angiography over an average follow-up of 5.4 years. The average time between procedures was 3.07 ± 1.83 years. Of these, 13 (30.2%) patients had demonstratable progression of CAD, and 8 (18.6%) patients ultimately required PCI. Findings on initial angiogram were associated with CAD progression (p=0.01) but not with intervention requirement (p=0.18), with the odds of new CAD in those with normal coronaries on first angiogram 0.07 (95% C.I. 0.008-0.634, p=0.005). Neither a low EF (<50%) (n=21) nor a drop in EF by >10% (n=17) was associated with CAD progression or PCI.

The 8 patients that required PCI presented with STEMI (n=3), NSTEMI (n=3), and unstable angina (n=2). Only one patient with normal coronaries on initial angiography required PCI, after presenting with a STEMI 4 years later and found to have distal LAD thrombotic occlusion with otherwise no coronary atherosclerosis.

Conclusions:
Repeat angiography had a low yield in our patient population. A drop in EF by >10% was not associated with new findings on repeat angiography or revascularization. Larger studies are needed to investigate if a drop in EF requires invasive testing.
Abstract 10551: Air-Ortitis
Authors: Chan Marvyn Allen G , Oyenubi Olamide , Gruen David S , Benjamin Patrick , Teweldemedmedhin Bisrat , Boy Gerald Kristoffer E , Jesmajian Stephen H
Published: June 2023

Background:
Vascular graft infections (VGI) are serious complications of open and endovascular types of surgery with 30-60% perioperative mortality and 40-60 % morbidity. High index of suspicion is necessary in patients with multiple risk factors for graft infection to ensure early detection and intervention. This is a patient who presented with occult graft infection 4 years after endovascular aortic aneurysm repair (EVAR).

Case:
A 79M with DM, hypertension, coronary artery disease s/p bypass surgery and angioplasty, and abdominal aortic aneurysm s/p EVAR 4 years ago, presented with mild central abdominal pain associated with nausea and loss of appetite. He denied change in bowel habits, fever, or rectal bleeding. Initial workup showed WBC 10,000/ml with left shift of 90%, together with anemia of 7g/dl. Urinalysis showed pyuria and initial blood cultures grew gram negative bacilli later revealed to be Klebsiella pneumonia. Abdominal CT then showed an aortoiliac stent in place with an air-fluid level in the native aortic aneurysm, 6.4 cm in diameter. There was immediate concern for an aorto-enteric fistula and the patient underwent exploratory laparotomy which instead revealed an infected endograft with purulent drainage to the aortic sac. The post operative period was complicated with respiratory failure, requiring intubation for a few days. Tissue culture isolated multidrug resistant Klebsiella pneumoniae necessitating a 6-week course of meropenem. After a long hospital stay, his family opted for comfort care and was discharged to a hospice facility.

Conclusions:
Surgical treatment of VGI is challenging and involves debridement of infected periprosthetic tissues, excision of the infected graft and secondary revascularization usually in a critically ill patient. VGI have exceedingly high mortality rates; thus, early identification, and screening of high-risk patients with infectious focus for VGI is needed.
Abstract 10554: Major Cardiac Side Effects of BTK and BCR-ABL Kinase Inhibitor Therapy in Cancer Patients: A Global WHO Database Analysis
Authors: Karthikeyan Badri , Pokharel Saraswati , Sharma Umesh C
Published: June 2023

Introduction:
Bruton’s tyrosine kinase (BTK) and BCR-ABL kinase inhibitors have transformed the treatment for hematological cancers, such as mantle cell lymphoma and chronic myelogenous leukemia. However, these therapies present unique cardiac events that remain underexplored.

Hypothesis:
We hypothesize that the two groups of targeted therapies commonly used to treat hematological cancers will differ in cardiac side-effect profiles.

Methods:
The World Health Organization database, VigiBase ®, contains over 20 million Individual Case Safety Reports and is maintained by the Uppsala Monitoring Centre. Reports for unique cardiac events associated with the use of BTK and BCR-ABL kinase inhibitors were analyzed. Reporting odds ratios (ROR), 95% confidence intervals (CI) and chi-squared tests were used to compare differences in cardiac side-effect profiles between the two groups of therapies.

Results:
A total of 24,385 adverse cardiac events from the use of BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib) and BCR-ABL kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) have been observed based on records obtained to-date. Compared to BCR-ABL kinase inhibitors, BTK inhibitors have significantly increased reporting for atrial fibrillation (ROR: 6.995; 95% CI: 6.493-7.537; P < 0.001) and ventricular tachycardia (ROR: 1.829; 95% CI: 1.342-2.493; P < 0.001). However, BCR-ABL inhibitors have significantly increased reporting for myocardial infarction (ROR: 2.077; 95% CI: 1.863-2.316; P < 0.001) but similar reporting for congestive cardiac failure (ROR: 0.949; 95% CI: 0.852-1.058; P = 0.343). The median onset of ventricular tachycardia from the use of BTK inhibitors is 176 days (interquartile range: 48-636 days). For BCR-ABL kinase inhibitors, the median onset of ventricular tachycardia is similar at 137 days (interquartile range: 92-396 days), P = 0.741 from nonparametric tests.

Conclusion:
We conclude that BTK inhibitors are associated with arrhythmic events, while BCR-ABL kinase inhibitors are associated with myocardial infarction. Both groups have similar reporting for congestive cardiac failure. Research is underway to study the mechanisms behind these novel side-effect profiles.
Abstract 10558: Association Between Concurrent Use of Diltiazem and DOACs and Risk of Bleeding in Atrial Fibrillation Patients
Authors: Shurrab Mohammed , Jackevicius Cynthia , Austin Peter , Tu Karen , Qiu Feng , Singh Sheldon , Crystal Eugene , Caswell Joseph , Michael Faith , Andrade Jason , Ko Dennis T
Published: June 2023

Introduction:
Diltiazem is a commonly used pharmacotherapy in patients with atrial fibrillation (AF) with potential for a drug-drug interaction (DDI) with direct oral anticoagulants (DOACs). We aimed to assess the risk of bleeding after co-prescription of diltiazem and DOACs among adults with AF.

Methods:
We conducted a population-based, nested case-control study in Ontario, Canada. The study population included all patients with AF > 66 years on a DOAC between April 1, 2011-March 31, 2018. Cases were patients admitted with major bleeding (index date). Controls were matched in a 2:1 ratio to cases. We categorized exposure to diltiazem before the index date as: a) current users (diltiazem within 7 days); b) past users (diltiazem within 8 to 90 days); and c) unexposed (no diltiazem prescription or diltiazem prescription >90 days before index date). Conditional logistic regression models were used to examine the association between bleeding and diltiazem co-prescription.

Results:
Among 86,679 AF patients on a DOAC, we identified 2,766 cases (3.2%) admitted with major bleeding. The median age of AF patients was 80 years (interquartile range 75-85); 48.3% were women. After multivariable adjustment, there was a significant association between major bleeding and current use of diltiazem (adjusted odds ratio (aOR) 1.37; 95% confidence interval (CI) 1.08-1.73, p<0.009) but no significant association between major bleeding and past use of diltiazem (aOR 1.19, 95% CI 0.99-1.42, p=0.06) as compared with the unexposed group (Figure).

Conclusions:
Among older patients with AF on a DOAC, there was 37% increased odds of current use of diltiazem in those with versus without major bleeding.
Abstract 10559: Causes of Early Mortality After Transvenous Lead Removal
Authors: Tan Min Choon , Lee Justin Z , Deshmukh Abhishek , Sorajja Dan , Valverde Arturo M , Srivathsan Komandoor , Scott Luis , Kusumoto Fred , Friedman Paul , Asirvatham Samuel , Mulpuru Siva K , Cha Yong-Mei
Published: June 2023

Background:
Recognition of the causes of early mortality after transvenous lead removal (TLR) is an essential step for the development of quality improvement programs.

Objective:
This study sought to determine the causes of early mortality after TLR and to further understand the circumstances surrounding death after TLR.

Methods:
We performed a retrospective analysis of all patients undergoing TLR from January 1, 2001, to January 1, 2021 at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a detailed chart review of the electronic health record from within the Mayo Clinic system and outside records when available. The causes of death were further characterized based on whether it was related to the TLR procedure.

Results:
A total of 2,319 patients were included in the study. The overall 30-day all-cause mortality rate was 3%. Among all 30-day deaths, infection was the most common primary cause of death (42%). This was followed by decompensated heart failure (17%), procedure-related death (10%), sudden cardiac arrest (7%), and respiratory failure (6%). The 30-day mortality rate directly due to complications associated with the TLR procedure was 0.3% due to vascular tear and cardiac perforation. A third of deaths (33%) occurred after discharge from index hospitalization, among which 43% were readmitted before their death, 35% died at home or a nursing facility, and 22% were discharged on comfort care and died in hospice. The main reasons for readmission prior to death were sepsis and decompensated heart failure.

Conclusions:
The majority (90%) of 30-day mortality after TLR was not due to complications associated with TLR procedures. The primary causes were infection and decompensated heart failure. This highlights the importance of further research to reduce postoperative mortality from these factors, including deaths after hospital discharge.
Abstract 10567: Sepsis-Related Early Mortality After Transvenous Lead Removal
Authors: Tan Min Choon , Lee Justin Z , Deshmukh Abhishek , Sorajja Dan , Valverde Arturo M , Srivathsan Komandoor , Scott Luis , Kusumoto Fred , Friedman Paul , Asirvatham Samuel , Mulpuru Siva K , Cha Yong-Mei
Published: June 2023

Background:
Recognition of the infectious characteristics among the sepsis-related early mortality after transvenous lead removal (TLR) is an essential step to improving patient outcomes.

Objective:
This study sought to understand the infectious characteristic and circumstances among the sepsis-related early mortality after TLR.

Methods:
We performed a retrospective analysis of all patients undergoing TLR from January 1, 2001, to January 1, 2021 at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Patient details were identified through a detailed chart review of the electronic health record from within the Mayo Clinic system and outside records when available.

Results:
A total of 2,319 patients were included in the study. The overall 30-day sepsis-related mortality rate was 1.25% (n=29). Among the sepsis-related deaths, 24 patients (83%) had systemic cardiac implantable electronic device (CIED) infection, and 4 patients (14%) initially had isolated pocket infection. The average time from admission to TLR was 11 days. MSSA was the most common organism (n=8, 28%), and this was followed by MRSA (n=4, 14%) and Candida (n=3, 10%). Twenty of these patients (69%) had vegetation on the echocardiogram: vegetation on lead only in 9 patients, vegetation on both valve and lead in 8 patients, and vegetation on valve only in 3 patients. Among valvular vegetations, 5 patients had tricuspid valve vegetations, 3 patients had aortic valve vegetations, 2 patients had mitral valve vegetations, and 1 patient had both mitral and aortic valve vegetation. The average size of vegetation was 1.3±0.8 x 1.1±0.6 cm.

Conclusions:
The 30-day sepsis-related mortality rate was 1.25%. Among the sepsis-related early deaths, MSSA was the most common organism, and more than two-thirds (69%) of the patients had vegetations on cardiac imaging. This highlights the importance of further research to improve the infection outcome in TLR patients.
Abstract 10617: Non-Alcoholic Fatty Liver Disease, Heart Failure, and Long-Term Mortality: Insights From the National Health and Nutrition Examination Survey
Authors: jain vardhmaan , Minhas Abdul M , Pandey Ambarish , Khan Sadiya S , Fudim Marat , Fonarow Gregg C , Butler Javed , Khan Mohammad S
Published: June 2023

Objective:
To evaluate the association between non-alcoholic fatty liver disease (NAFLD), heart failure (HF), and all-cause mortality.

Background:
Both NAFLD and HF are increasing in prevalence due to shared risk factors.

Methods:
We used data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 to identify non-pregnant individuals aged ≥20 years with HF and NAFLD and linked with the cause of death data from the National Center for Health Statistics. The associations between NAFLD, HF, and all-cause mortality were assessed using logistic regression and Cox proportional hazard modeling as appropriate.

Results:
There were 82,358,893 weighted eligible participants of whom 3,833,667 (4.7%) had NAFLD. The mean (SE) age was 51.5 (0.35) years, 45.1% women, 63.0% Non-Hispanic White and 11.8% Non-Hispanic Black. Cardiovascular comorbidities were more common in participants with NAFLD; they were more likely to have hypertension (81.7% vs 53.5%), diabetes (65.1% vs 17.1%), stroke (7.3% vs 4.1%), coronary artery disease (14.9% vs 8.4%), or HF (10.5% v s 3.5%) compared with participants without NAFLD. In multivariate logistic regression models adjusting for age, race/ethnicity and sex, participants with NAFLD were 3.5 times more likely to have HF [aOR, 95% CI: 3.47 (1.98-6.06)]. Older age, male sex, presence of diabetes and coronary artery disease were associated with higher odds of HF in participants with established NAFLD. At the end of the follow-up period, participants with NAFLD had higher all-cause mortality compared with participants without NAFLD [HR(95% CI): 1.93 (1.24-2.99), p<0.001].

Conclusion:
In this analysis of US adults, ambulatory participants with NAFLD were ~3.5 times more likely to have HF, and twice as likely to experience mortality compared with participants without NAFLD. Further studies are needed to identify the possible linkage between NAFLD and HF beyond the shared risk factor pathogenesis.