bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9398: Associations Between Blood Pressure, Race/Ethnicity, and Incident Stroke Type: A Pooled Cohort Analysis of ARIC, CARDIA, CHS, MESA, FOS, NOMAS
Authors: Johnson Kimson , Li Hanyu , Zhang Min , Springer Mellanie V , Galecki Andrzej , Whitney Rachael , Gottesman Rebecca F , Hayward Rodney A , Sidney Stephen , Elkind Mitchell S , Sacco Ralph L , Longstreth W T , Heckbert Susan R , Gerber Yariv , Sullivan Kevin J , Levine Deborah A
Published: June 2023

Introduction:
Stroke risk varies by systolic blood pressure (SBP) and race/ethnicity. Whether the relationship between cumulative mean SBP and first-time incident stroke type differs by racial/ethnic group is unknown. This study examines the relationship between cumulative mean SBP and first-time incident stroke among 3 major stroke types: ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and how race/ethnicity influences these relationships, using a pooled cohort analysis.

Hypothesis:
We hypothesize that race/ethnicity modifies the association between cumulative mean SBP and incident stroke type.

Methods:
Data were pooled from 38,325 participants with baseline age ≥18 and ≥1 SBP measurement before the first incident stroke from 6 US longitudinal cohorts from 1971 to 2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. A multivariable-adjusted Cox proportional hazard model was used to estimate the association between cumulative mean SBP, race/ethnicity, and time to incident stroke (overall, stroke type, and race/ethnicity*stroke type).

Results:
Median follow-up was 22.3 years. Mean (SD) baseline age was 53.2 (17.1) years, with 54.5% female, 24.9% Black, and 8.8% Hispanic. Baseline mean (SD) SBP was 136.8 (20.5) mmHg. Race/ethnicity modified the association of SBP with time to ICH (P-interaction=0.006) but no other stroke types. Compared to White participants, the association between higher SBP on ICH risk was greater in Black participants but not different in Hispanic participants (Table). A 10-mmHg higher SBP was associated with a higher risk of ICH than IS (Table).

Conclusions:
We found that race modifies the association between SBP and ICH risk, such that ICH risk is 19% higher per 10-mmHg for Black individuals than White individuals.
Abstract 9447: The Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations Study
Authors: Madhani Avni , Sabogal Natalia , Massillon Daniel , Paul Ludwine D , Rodriguez Carlos , Fine Denise , Helmke Stephen , Winburn Morgan , Kurian Damian , Raiszadeh Farbod , Teruya Sergio , Cohn Elizabeth , Einstein Andrew J , Miller Edward J , Connors Lawreen H , Maurer Mathew S , Ruberg Frederick L
Published: June 2023

Introduction:
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients aged > 60 years. While the V122I variant that is associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the US (or 1.5 million people), the phenotypic penetrance of this allele remains incompletely defined owing to age-dependent expression and limited methods for disease ascertainment.

Methods:
The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study is a currently accruing multisite cohort designed to determine the prevalence of ATTR-CM using Tc-99m-Pyrophosphate imaging in older (age > 60 years) Black and Hispanic individuals with HF.
TTR
genotype is determined by 4-exon targeted PCR, while functional, biochemical, and echocardiographic testing is performed. Data are presented here as an interim analysis performed using Kruskal-Wallis testing for the first 240 self-identified Black participants.

Results:
The prevalence of V122I was 6.7% (n=16 carriers of whom 7 had ATTR-CM), yielding a phenotypic penetrance of 44% (95% CI 20%, 70%) at a median age of 82 (IQR 74, 85) years. Allele carriers with ATTR-CM (Group 3) were older and more likely male, with lower 6-minute walk distance and LVEF, when compared to carriers without ATTR-CM (Group 2, Table) or wild-type, non-amyloid HF controls (Group 1). Other functional, biochemical, and echocardiographic parameters were predictably different between Group 3 and the other groups but similar between Groups 1 and 2 except for prealbumin levels (Group 1: 25 mg/dl vs. Group 2: 20.5 mg/dl, p < 0.05).

Conclusion:
The clinical penetrance of V122I among elderly Black individuals with HF and a median age of 82 years was 44%, suggesting that genotype alone is insufficient to infer ATTR-CM as the cause of HF in this clinical context. Prealbumin concentration may be useful to identify ATTR-CM in V122I carriers.
Abstract 9455: Sex Differences in Atrial Fibrillation Ablation Outcomes From the National Inpatient Sample Database 2016-2019
Authors: Shrestha Biraj , Diaz Fraga Julian , Poudel Bidhya , Donato Anthony
Published: June 2023

Background:
Research has shown mixed results when comparing in-hospital complications following atrial fibrillation ablation in women compared to men.

Objectives:
To better quantify sex differences and in-hospital outcomes in atrial fibrillation ablation procedures and identify factors associated with poorer outcomes.

Methods:
We queried the NIS database from 2016-2019 for hospitalizations with a primary diagnosis of atrial fibrillation ablation and excluded patients with any other arrhythmias, ICD/pacemaker placement. We assessed demographics, in-hospital mortality, and complications of women compared to men. Outcomes were adjusted for potential confounders using multivariable logistic regression analysis (Figure 1).

Results:
Admissions for atrial fibrillation were more common in females than males (849,050 versus 815,665; p<0.001). However, females were less likely to receive ablation (1.65% versus 2.71%, OR: 0.60; 95% confidence interval: 0.57-0.64, p<0.001) which persisted after adjusting for cardiomyopathy (adjusted OR: 0.61; 95% confidence interval: 0.58-0.65, p<0.001). The primary outcome of in-hospital mortality was not statistically different in univariate analysis (0.39% vs. 0.36%, OR: 1.09, 95% CI: 0.44-2.72, p=0.84), finding that did not change when adjusted for comorbidities (adjusted OR: 0.94, 95% CI: 0.36-2.49) (Figure 1). The total unadjusted complication rate was higher for females than males (9.58% vs. 7.09%, p=0.001); however, it was not significant when adjusted for risks (adjusted OR: 1.23, 95% CI: 0.99-1.53, p=0.06) (Figure 1).

Conclusion:
Female sex is not associated with increased complications or death in a real-world study of catheter ablation when results are adjusted for risks. However, females admitted with atrial fibrillation receive ablation less often than males during hospital admission. More study is needed regarding to identify factors contribute to later referral for females for catheter ablation.
Abstract 9457: Primary Cardiac Allograft Dysfunction Caused by Pretransplantation Amiodarone Therapy
Authors: Freundt Miriam , Eisen Howard J , Mahesh Balakrishnan , Dowling Robert D , Brehm Christoph , Soleimani Behzad
Published: June 2023

Background:
Primary graft dysfunction (PGD) is devastating. Amiodarone therapy prior to cardiac transplantation (TxP) is common but has recently been reported as potential cause of PGD.

Case:
66-year-old male with non-ischemic cardiomyopathy, severely reduced LVEF with LVAD, recurrent VT on amiodarone for 6 months presented with ICD shocks. Amiodarone was increased due to VT storm in the setting of Rhinovirus infection. Infusions with amiodarone and lidocaine were started but repeat IV boli of lidocaine and amiodarone were needed. VT-ablation was not feasible due to multiple morphologies. He underwent TxP with an ideal organ from a 28 yo donor. Paragonix SherpaPak was used for transport. Pre-explanation EF was 70% with serologies positive for EBV (+/+), Strongyloides (+/-), negative for Toxoplasmosis (-/-), CMV (-/-). Donor heart was arrested with appropriate cardioplegia and no distention occurred. Total ischemic time was 3 hours 10 minutes, warm ischemic time 40 minutes, crossclamp time in recipient 2 hours 2 minutes with total cardiopulmonary bypass time 2 hours 58 minutes. Coming off bypass both ventricles appeared markedly dilated with severely reduced function and due to high doses of inotropic and vasopressor support veno-arterial ECMO was placed. The chest was left open and during postoperative course in the intensive care unit pressor and inotropes could slowly weaned. Induction therapy was administered with ATG, Solumedrol and mycophenolate mofetil. Strongyloides infection was treated with four doses of Ivermectin. On postoperative day LVEF recovered to 40-45% with moderately reduced RV function and patient was successfully decannulated from VA ECMO with chest closure. Endomyocardial biopsies showed no signs of rejection throughout. After prolonged ICU and rehab stay patient has now recovered to independent life.

Conclusion:
Amiodarone associated PGD may be underreported and increasing awareness of this etiology may warrant early empiric discontinuation of the medication if transplantation remains a therapeutic option in the future.
Abstract 9462: Racial Disparities in Transcatheter and Surgical Aortic Valve Replacement Among Medicare Beneficiaries in the United States, 2012-2019
Authors: Gupta Aakriti , Mori Makoto , wang yun , Vahl Torsten , Nazif Tamim , Onuma Oyere K , Yong Celina M , Sharma Rahul , Kirtane Ajay J , Forrest John K , George Isaac , Kodali Susheel K , Chikwe Joanna , Geirsson Arnar , Makkar Raj , Leon Martin , Krumholz Harlan M
Published: June 2023

Background:
There are concerns that transcatheter or surgical aortic valve replacement (TAVR/SAVR) procedures are preferentially available to White patients.

Methods:
We stratified Medicare beneficiaries hospitalized with principal diagnosis of AS between 2012 and 2019 (n=299,976) by self-reported race/ethnicity (Black, Hispanic, Asian, Native American, and White). We evaluated AVR rates within 6 months of index hospitalization and associated procedural outcomes, including 30-day and 1-year mortality, and discharge disposition. We fitted Cox-proportional hazard models for outcomes, adjusting for demographics and comorbidities using race/ethnicity subgroup-specific-stabilized inverse probability weights.

Results:
Within 6 months of an index admission for AS, 86.8% (122,457 SAVR; 138,026 TAVR) patients underwent AVR. Overall, compared with White people, Black [HR 0.87 (0.85-0.89)], Hispanic [0.92 (0.88 - 0.96)], and Asian [0.95 (0.91 - 0.99)] people were less likely to receive AVR (Figure). Among patients who were admitted emergently/urgently, White patients (41.1%, 95% CI 40.7-41.4) had a significantly higher AVR rate within 6 months compared with Black (29.6%, 95% CI 28.3-30.9), Hispanic (36.6%, 95% CI 34.0-39.3), and Asian patients (35.4%, 95% CI 32.3-38.9). AVR rates increased annually for all race/ethnicities. There were no significant differences in 30-day or 1-year mortality by race. Black people were significantly more likely to be discharged to a facility compared with others.

Conclusion:
Within 6 months of AS admission, AVR rates are lower for Black, Hispanic, and Asian people compared with White people. These race-based differences in ultimate treatment of AS likely represent complex issues across the diagnosis and management of AS, warranting a comprehensive reassessment of the entire care spectrum for disadvantaged populations.
Abstract 9464: Adipocyte-Derived Fatty-Acid-Binding Protein 4 Impairs Human Dermal Microvascular Endothelial Cells Under Hypoxia Insults - A Mechanistic Clue to Impaired Wound Healing in Obesity
Authors: Wu Yen-Wen , Chen Jaw W , Chang Ting-Ting
Published: June 2023

Introduction:
Dermal white adipose tissue is found in the dermis of the skin, which may participate in the wound healing process. Obesity-mediated adipocyte hypertrophy has been related to adipose tissue hypoxia and chronic low-grade inflammation, which may impair wound healing by suppressing the vascularity. Fatty-acid-binding protein (FABP) 4 is a cytosolic fatty acid chaperone expressed in adipocytes, which may be involved in the pathogenesis of some vascular diseases and was found upregulated in skin tissue of obese animals. This study aimed to investigate the potential mechanistic impacts of adipocyte-derived FABP4 on vascular cells for wound healing under hypoxia insults.

Methods and Results:
Primary human dermal microvascular endothelial cells (HDMECs) and adipocytes were used. FABP4 and inflammatory protein expressions such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were upregulated under the hypoxic conditions. Treatment with conditioned medium from adipocytes under the hypoxic conditions significantly impaired cell function including migration and tube formation abilities in HDMECs. Furthermore, FABP4 and inflammatory protein expressions were upregulated, and angiogenic signaling pathways such as phospho-AKT/hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF)/ stromal cell-derived factor (SDF)-1 were downregulated in these conditioned medium treated HDMECs. Interestingly, administration of FABP4 inhibitor could reverse the conditioned medium-induced cell damages in HDMECs. On the other hand, FABP4 could directly impair cell functions with lower angiogenic and higher inflammatory protein expressions in HDMECs under the hypoxic conditions.

Conclusions:
Our pilot findings suggested that adipocyte hypoxia might lead to the secretion of inflammatory proteins and FABP4. Adipocyte-derived FABP4 could impair the migration and tube formation abilities of HDMECs via upregulating TNF-α/IL-6/IL-1β and downregulating phospho-AKT/HIF-1α/VEGF/SDF-1 signal pathways. Our findings provide a theoretical basis to the potential impact of FABP4 as a novel therapeutic target on wound healing in obese subjects with adipose tissue hypoxia.
Abstract 9499: Clinical Outcomes With Initial Thoracic Endovascular Aortic Repair versus Initial Medical Therapy for Acute Uncomplicated Type B Aortic Dissection in the United States
Authors: Weissler Hope , Osazuwa-Peters Oyomoare , Greiner Melissa , Hardy Natalie C , Kougias Panagiotis , OBrien Sean , Mark Daniel B , Jones William S , Secemsky Eric A , Vekstein Andrew , Shalhub Sherene , Mussa Firas , Patel Manesh R , Vemulapalli Sreekanth
Published: June 2023

Introduction:
Thoracic endovascular aortic repair (TEVAR) has increasingly been used for uncomplicated type B aortic dissection (uTBAD) despite limited supporting data. We compared outcomes after a strategy of initial TEVAR vs. initial medical therapy in patients with uTBAD.

Methods:
Index acute uTBAD admissions from 2011-2018 were identified using 100% Medicare inpatient claims. Initial TEVAR was defined as TEVAR within 30 days of admission. Complicated and non-acute TBAD were excluded. Outcomes included survival, cardiovascular hospitalizations, aorta-related and repeat aorta-related hospitalizations, and aortic interventions. Propensity score inverse probability weighting (IPW) was used to reduce the effects of treatment selection bias in the data. The primary analyses were landmarked at 30 days to avoid survival time bias; a sensitivity analysis used TEVAR status as a time-dependent variable to account for deaths in the first 30 days.

Results:
Of 7,105 patients with eligible index admissions for acute uTBAD, 1,140 (16.0%) underwent initial TEVAR. Receipt of initial TEVAR was significant associated with geographic region, non-Medicaid dual eligibility, and institutional TEVAR volume as well as certain comorbidities. After IPW, mortality was similar for the two strategies out to 5 years (HR 0.95, 95% CI 0.85 to 1.06), while aorta related hospitalizations were modestly increased with the TEVAR strategy (HR 1.12, 95% CI 0.99 to 1.27). In the sensitivity analysis including deaths within the first 30 days, initial TEVAR was associated with lower mortality over a period of 1 year (aHR 0.86, 95%CI 0.74-0.997, p=.045), 2 years (aHR 0.85, 95%CI 0.75-0.96, p=.01), and 5 years (aHR 0.87, 95%CI 0.79-0.97, p=.008).

Conclusions:
We found that a significant minority of uTBAD patients undergo initial TEVAR, which may be associated with lower risk of mortality when deaths within the first 30 days are included. These outcomes, and the reasons why some patients receive initial TEVAR while others do not, remain incompletely characterized. These findings, along with factors related to anatomy, peri-procedural complications, adequacy of medical therapy, patient preferences, and cost effectiveness, need to be assessed in a prospective trial in the US population.
Abstract 9502: Sexual Minority Adults’ Perceptions of a Multi-Component Intervention for CVD Risk Reduction
Authors: Pepe Vincent , Doan Danny , Sharma Yashika , George Maureen , Caceres Billy A
Published: June 2023

Introduction:
Sexual minority (SM; e.g., gay, lesbian, bisexual) adults have a higher prevalence of risk factors for cardiovascular disease (CVD) compared to heterosexual adults, which is attributed to their increased exposure to minority stressors (e.g., experiences of discrimination). Yet, there are no evidence-based interventions for CVD risk reduction tailored to the unique needs of SM adults. Our goal was to inform the development of a tailored intervention for CVD risk reduction in middle-aged (ages 40-64) SM adults.

Methods:
We conducted a qualitative descriptive study to understand the perceptions of SM adults on their risk of CVD and identify their preferences for an intervention. We recruited an online sample of middle-aged SM adults who lived in the United States and reported no history of CVD. During one-on-one semi-structured interviews, participants were presented a sample multi-component intervention that combined elements of existing interventions for minority stress and CVD risk reduction. Transcripts were independently coded using directed content analysis to create a codebook. Codes were grouped into cognitive, behavioral, and environmental themes guided by Social Cognitive Theory.

Results:
The sample included 23 participants with a mean age of 52.0 (±7.2) years. Approximately 52% were female and 61% were White. Cognitive theme: Participants acknowledged the importance of their sexual identity and cardiovascular health but lacked insight into the elevated CVD risk that has been observed in SM adults. Behavioral theme: They were willing to join an intervention to reduce their CVD risk if it did not require dramatic lifestyle changes. Environmental theme: Participants preferred a virtual, synchronous, group intervention no longer than 12 weeks. They indicated convenience, socialization, and comprehensiveness were main factors informing intervention delivery preferences. All participants approved of the sample intervention, particularly stress-reduction components.

Conclusions:
Gaps in knowledge related to CVD risk among SM adults were identified. Findings provide important knowledge that should be considered in designing tailored interventions for CVD risk reduction in SM adults.
Abstract 9515: Cariporide, a Selective Na+-H+ Exchange Inhibitor, Enhances Cardiac Positive Inotropic and Lusitropic Responses to Dobutamine in Heart Failure: Assessment by Pressure-Volume Analysis
Authors: Cheng Che Ping , Li Tiankai , Zhang Xiaowei , Zhang Zhi , Zhao David X , Herrington David M , Kitzman Dalane W , Cheng Heng-Jie
Published: June 2023

Background:
Inability of failing hearts to respond to positive inotropic agents such as dobutamine (DOB) represents a major clinical problem. We have shown previously that in addition to intracellular acidosis, various signaling pathways such as endothelin-1 and angiotensin II also activate cardiac Na
+
-H
+
exchange (NHE). In heart failure (HF), increased stimulation of NHE decreases myocardial calcium sensitivity. We hypothesized that blocking NHE with cariporide (CAR), a NHE-1-selective inhibitor, may improve β-adrenergic inotropic responsiveness in HF and enhance left ventricle (LV) positive inotropic and lusitropic responses of DOB.

Methods:
We compared the effect of clinically relevant doses of CAR (3.5 μg/kg, iv) on LV functional performance and LV contractile response to DOB (6 μg/kg/min, iv, 10 min) in 6 instrumented, conscious dogs after pacing-induced HF. LV contractile performance was measured by pressure (P)-volume (V) analysis. Animals received DOB first. After stopping DOB for 30 minutes, both DOB and CAR were infused.

Results:
After HF, DOB caused a 17% increase in E
ES
(5.3 ±1.5 vs 4.4±0.8 mmHg/ml), a16% increase in M
SW
(53.8±4.9 vs 45.3±3.7 mmHg), and an 11% decrease in the time constant of LV relaxation (τ) (40.4±2.6 vs 45.8±2.5 ms). DOB followed by CAR resulted in significantly greater effects with a 42% increase in E
ES
(6.1±2.3 vs 4.3±1.9 mmHg/ml) and a 37% increase in M
SW
(61.4±5.9 vs 45.1±3.2 mmHg), and a 23 % decrease in τ (34.1±3.6 vs 44.5±2.4 ms). Compared with DOB alone, DOB plus CAR caused no significant changes in heart rate (126±11 vs 130±12 bpm) and LV end-systolic P (110±8.6 vs 112±6.5 mmHg), but significantly decreased mean left atrial P (27.2±5.0 vs 32.9±5.4 mmHg), and increased stroke volume (32%, 13.3±1.7 vs 10.1±2.7 ml). DOB plus CAR also produced about 28% increased LV mechanical efficiency, measured as the ratio of stroke work to total P-V area (0.59±0.15 vs 0.46±0.17) (
p
<0.05).

Conclusions:
In pacing-induced HF, Na
+
-H
+
exchange inhibition by cariporide enhances LV positive inotropic and lusitropic responses to DOB. This suggests that combination therapy with intravenous cariporide and DOB may be appropriate in HF, thus providing a potential method of enhancing β-adrenergic responsiveness of the failing myocardium.
Abstract 9552: Optimal Sensing Vector for Maximal Pwave Amplitude, Implications for Insertable Cardiac Monitor (ICM) Implantation
Authors: Pitman Bradley M ,   Amy Zanker,   Matthew Lim,   Joshua McLoughney,   Jade Spinelli,   Rachel Tarone,   Kristie McInnes,   Kyle Heath,   Mahsa Gieve,   Shaun Evans,   Christopher X Wong,   Prashanthan Sanders, Lau Dennis H
Published: June 2023

Introduction:
Pwave visibility on electrograms (EGMs) obtained by Insertable Cardiac Monitor (ICM) can enhance the diagnostic accuracy of atrial arrhythmias.

Objective:
To assess the optimal sensing vector for maximal Pwave amplitude obtained on sinus rhythm strips from the precordial region of patients undergoing cardiac investigation.

Methods:
150 participants each had 12 separate tracings of single-lead surface EKG acquired using Northeast Holter (DR200/HE) placed to mimic ICM recordings. 3M electrodes were positioned at different vector length (75mm & 45mm) for each of three angles (vertical, oblique, horizontal) repeated in two postures (upright & supine). Impedance-based body fat percentage (BF%) was measured. Fifty patients also received ICM implant in 1:1 recruitment (Medtronic LINQ:Biotronik Biomonitor IIIm) with device EGM attained. All EKG and EGM were uploaded into DigitizeIt software for offline analysis by blinded technicians who measured calibrated Pwave amplitude. The minimum amplitude for readily visible Pwave on ICM has previously been reported as .015mV, and this threshold was used to define acceptable Pwave amplitude.

Results:
150 participants [55.5% male, median age 59years (IQR 35 - 73)] each had 12 EKG strips obtained (total 1,800). Median Pwave was 45% larger for 75 vs. 45mm (.042 vs. .029mV, p<.001). Good correlation was seen for EKG and EGM, with Pwave ICC .74 (95%CI .58 - .84). In total, 79% (n=1,415) of EKG had sufficient Pwave visibility (≥.015mV), with a greater proportion seen for 75 vs. 45mm vector (84% vs 73%, p<.001). Overall, Pwave amplitude was lower for higher BF% patients. Among the top third BF% (figure), Pwaves were twice [OR 2.03 (95%CI 1.04 - 3.95)] as likely to be of visible amplitude for 75mm vector (oblique angle) compared to the best 45mm vector (vertical).

Conclusion:
Longer sensing vector provides superior Pwave amplitude, particularly for high BF%, which is important when factoring ICM device selection for patients.
Abstract 9570: Different Distribution of CD163 Positive Macrophages in Thrombus Retrieved From Infarct-Related Artery: Atherothrombosis vs. Cardiogenic Thrombosis, Pathological Analyses From the MITO Study
Authors: Koizumi Tomomi , Kato Noriyuki , Inadome Yukinori , Nakano Koji , Yamada Yuu , Abe Yuto , Tabata Fumimasa , Yamazaki Tomosato , Ono Masao ,   MITO study Investigators
Published: June 2023

Introduction:
Diagnosis of cardiogenic thrombosis is important because anticoagulant therapy is recommended for its secondary prevention. However, it is difficult to make a clear distinction in the pathogenesis between atherothrombosis and cardiogenic thrombosis.

Hypothesis:
Role of macrophage in thrombus formation is different between atherothrombosis and cardiogenic thrombosis.

Methods:
The Macrophage in Thrombus (MITO) study is a prospective observational study examining pathological and biological differences of arterial thrombus between atherothrombosis and cardiogenic thrombosis. Patients with ST elevation myocardial infarction (STEMI) or acute ischemic stroke (AIS) whose solid thrombus could be retrieved from the infarct-related artery were enrolled. Patients were divided into 2 groups as follows; STEMI with sinus rhythm: Group A (presumed atherothombosis) and AIS with atrial fibrillation (presumed cardiogenic thrombosis): Group C, and compared macrophage score as follows; 1:almost no macrophages detected byх40; 2:difficult to detect the macrophages in х20 but detected by х40; and 3:easy to detect macrophages in х20 in the thrombus. Serum levels of soluble CD163 were measured all the patients.

Results:
The score for CD163 positive macrophage of Group C (n=33) was significantly higher than that of Group A (n=32) (p<0.01): Figure. Serum level of soluble CD163 in Group C (median 603 ng/ml, IQR 405, 788) tended to be higher than that in Group A (median 520 ng/ml, IQR: 314, 634); p=0.08.

Conclusions:
CD163 positive macrophages are more involved in the thrombus formation of cardiogenic thrombus than that of atherothrombosis. Detection of CD163 positive macrophages are likely to help discriminate between atherothrombosis thrombus versus cardiogenic thrombus.
Abstract 9575: TOTUM-070 Hypocholesterolemic Effect Linked to Intestinal Cholesterol Absorption Inhibition. An in vivo and in vitro Study
Authors: Langhi Cedric , Otero Yolanda F , Le Joubioux Florian , Guigas Bruno , PELTIER Sébastien , Sirvent Pascal
Published: June 2023

TOTUM-070 (T070) is a patented blend of five plant extracts designed to act in combination to prevent hypercholesterolemia. Previous study in dyslipidemic hamster model fed a High Fat High Cholesterol (HFHC) diet for 12 weeks demonstrated that supplementation with T070 at 3,5% to 5% in the diet (n=16 per group) reduced serum non-HDL cholesterol compared to HFHC group (-38%, p<0,001 and -47%, p<0,001, respectively) as well as serum triglyceride levels (-30%, n.s and -46%, p<0,05, respectively). We aimed to decipher the mechanisms of action of T070 both in vivo and in vitro. First, the chemical characterization of T070 by HPLC-UV/MS analyses led to the identification and quantification of 37 biomolecules such as oleuropein, oleanolic acid or chlorogenic acid. Total RNA sequencing analysis of livers from the HFHC and T070 5% supplemented groups highlighted 511 genes with significant different expression level between groups. Among canonical pathways identified, 19 genes implicated in metabolism were differentially regulated with T070. Several functional tests were performed in hamster fed with T070 5% for 12 weeks in comparison to HFHC group (n=14 per group). Dosage of lipoprotein lipase activity ex vivo did not show any difference between groups. Results from hepatic triglyceride production test detected no effect of T070. However, an oral fat tolerance test showed that post-prandial hypertriglyceridemia was significantly reduced by 40% (p<0,01) in T070 group following olive oil gavage compared to the HFHC hamsters. Finally, in vivo intestinal [4-
14
C]-Cholesterol absorption test demonstrated a 12% reduction (n.s) with T070 5% compared to HFHC group. In vitro investigations were assessed on differentiated human enterocyte Caco2 cells. Incubation with T070 at 1g/l for 1h acutely reduced [1,2-
3
H(N)]-cholesterol uptake by 30% in Caco2 cells (p<0.01). Pharmacological inhibition of cholesterol transporter NPC1L1 abolished the effect of T070 on cholesterol uptake. There was no effect of T070 on NPC1L1 protein expression in Caco2 cells, suggesting T070 blocked directly NPC1L1 activity. Altogether, our results demonstrate that hypocholesterolemic effect of T070 is mediated by inhibition of intestinal cholesterol absorption.
Abstract 9592: The Super Relaxed State of Myosin Contributes to the Pathogenesis of Right Ventricular Dysfunction in Pulmonary Hypertension
Authors: Waddingham Mark T , Tsuchimochi Hirotsugu , Asano Ryotaro , Sonobe Takashi , Higuchi Takahiro , Aoyama Kohki , Shirai Mikiyasu , Pearson James T , Ogo Takeshi
Published: June 2023

Introduction:
Patients with pulmonary hypertension (PH) often succumb to right ventricular (RV) failure yet little is known regarding the underlying pathological mechanisms. Recently, the transition of myosin from the disordered relaxed (DRX) to the super relaxed (SRX) state during diastole has been identified as a pathological feature contributing to myocardial dysfunction in heart failure. Using synchrotron radiation (SR) x-ray diffraction (SAXS), the proximity of myosin heads relative to actin in the
in situ
beating rat heart can be evaluated in different layers of the myocardial wall. We performed SR SAXS at different timepoints post-PH induction with simultaneous PV-loop acquisition to assess if SRX transition contributes to progressive global RV dysfunction in a rat model of PH.

Methods:
PH was induced in rats using the Sugen5416/3-week 10% hypoxia method, with rats being returned to normoxia for 3- (SuHx3wk) or 6-weeks (SuHx6wk) after the hypoxic period. SR SAXS was performed at BL40XU, SPring-8 Synchrotron, Japan. Global and site-specific RV myofilament phosphorylation status was also examined.

Results:
Compared to control rats (n=7), SuHx3wk (n=7) and SuHx6wk (n=7) rats exhibited progressive increases in RV size, RV end systolic pressure (ESP), RV dP/dt
max
and dP/dt
min
(all P<0.05 vs. Control). In the deeper subendocardial layer of the RV free wall, there were virtually no myosin heads within the proximity of actin at end diastole in SuHx6wk rats, whereas in the control and SuHx3wk rats, around 30-50% of myosin heads were in proximity to actin (P<0.05, SuHx6wk vs. Control and SuHx3wk). No significant differences in diastolic sarcomere length were found, suggesting a transition of myosin from DRX to SRX in the SuHx6wk rats. Importantly, indices for global RV function (ESP, dP/dt
max,
dP/dt
min
) significantly correlated with diastolic myosin mass transfer values. Analysis of RV myofilament phosphorylation revealed a progressive and significant reduction in MLC-2v phosphorylation over the time course of PH in rats.

Conclusion:
PH is associated with progressive changes in global RV function, which may be attributed to a transition from DRX to SRX state of myosin in the RV. Reduced MLC-2v phosphorylation may underlie the DRX to SRX transition in PH.
Abstract 9603: An Examination of Differences in Ideal Cardiovascular Health Between Gender Minority and Cisgender Adults in the Behavioral Risk Factor Surveillance System
Authors: Sharma Yashika , Vohr Mackenzie , Jackman Kasey , Belloir Joseph , Caceres Billy A
Published: June 2023

Introduction:
Gender minority (e.g., transgender, gender nonbinary) adults have been shown to be at higher risk of cardiovascular disease (CVD) compared to cisgender adults. However, prior research has primarily examined differences in individual cardiovascular health (CVH) metrics rather than composite measures. We examined gender identity differences in ideal CVH using the American Heart Association’s Life’s Simple 7, which includes three health behaviors (i.e., tobacco use, diet, and physical activity) and four health factors (i.e., body mass index, hypertension, diabetes, and total cholesterol).

Methods:
We analyzed self-reported data from the Behavioral Risk Factor Surveillance System (2015-2019). Participants received a score of 0 (nonideal) or 1 (ideal) for each CVH metric and scores were summed to calculate ideal CVH scores (continuous; range 0-7). We ran regression models, adjusted for demographic and clinical factors, to compare ideal CVH scores and the odds of meeting criteria for ideal CVH (i.e., ≥5 CVH metrics with score of 1) between gender minority and cisgender adults. We separately compared all groups of gender minority participants (i.e., transgender women, transgender men, gender nonbinary) to both cisgender women and men.

Results:
The sample included 368,541 participants, of which 99.6% were cisgender, 0.3% were transgender, and 0.1% were nonbinary. Transgender women (
B
= -0.22,
p
<0.01) and gender nonbinary (
B
= -0.42,
p
<0.01) participants had lower ideal CVH scores than cisgender women. No differences in ideal CVH scores were found when comparing gender minority adults to cisgender men. Transgender women (AOR 0.54, 95% CI = 0.50, 0.76) and gender nonbinary (AOR 0.46, 95% CI=0.30, 0.71) adults were less likely to meet criteria for ideal CVH than cisgender women. In contrast, transgender men were more likely to meet criteria for ideal CVH than cisgender men (AOR 1.61, 95% CI = 1.10, 2.36).

Conclusions:
Findings indicate that transgender women and gender nonbinary participants are at higher risk of CVD than cisgender women. Transgender men had a lower risk of CVD than cisgender men. Future research is needed to examine factors that may contribute to the CVH disparities observed among transgender women and gender nonbinary adults.
Abstract 9614: Association Between Myocardial Contraction Fraction and Heart Failure Subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Sutton Alexandria J , Chen Haiying , Abdalla Marwah , Shimbo Daichi , Ac Lima Joao A , Kitzman Dalane W , Bertoni Alain G
Published: June 2023

Introduction:
Myocardial contraction fraction (MCF) is a non-ejection fraction volumetric measure of myocardial shortening which has been associated with incident heart failure (HF) including in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. However, less is known regarding MCF’s prediction of HF subtypes.

Methods:
This analysis included men and women aged 45-84 free of clinical cardiovascular disease who underwent cardiac magnetic resonance imaging (cMRI) during the baseline MESA examination and who had data regarding incident adjudicated definite or probable HF events. MCF was calculated using cMRI measurements and defined as the ratio of stroke volume to myocardial volume. HF subtypes were divided into HF with ejection fraction (EF) < 50% (HF EF < 50%, including HF with reduced EF (EF ≤ 40%) and HF with mildly reduced EF (EF 41-49%) and HF with preserved EF (HFpEF, EF ≥ 50%). Cox proportional hazards regression was used to examine the association between MCF and incident HF subtype per decile increase in MCF. Event time was defined as time of first defined HF subtype, and censoring occurred at death or end of follow-up. After an incident HF event, participants were not at risk for another HF subtype. Covariates adjusted for were age, gender, race-ethnicity, education, body-mass index, tobacco and alcohol use, systolic blood pressure (BP), diabetes, physical activity, total cholesterol, and BP and lipid lowering drug use.

Results:
Among 4,983 participants (mean age 61, 52% female, 61% non-White) over a maximum of 18 years follow-up, there were 275 incident HF events (142 HF EF < 50%, 113 HFpEF, 20 unknown EF). MCF differed across HF status (p<0.001)
.
Participants without incident HF had a higher mean MCF (0.65) compared to HFpEF (0.62), HF EF < 50% (0.53), and unknown EF (0.52). The adjusted risk of any HF was reduced (HR 0.86, 95% CI 0.82, 0.91) per decile increase of MCF. MCF was strongly associated with incident HF EF < 50% (adjusted HR 0.80, CI 0.74, 0.86) but was not associated with HFpEF (adjusted HR 0.98, CI 0.91, 1.05).

Conclusions:
In a multi-ethnic cohort, increasing MCF is associated with a decreased risk of incident HF EF<50%. MCF is not significantly associated with incident HFpEF, suggesting different etiologic pathways for these two HF subtypes.
Abstract 9618: Prolonged Arterial Phase is the Culprit Pathology in Patients With Chest Pain, Elevated Troponin Level, Abnormal Thallium Scan and Patent Coronary Arteries: An Angiographic, Machine Learning Analysis for a Personalized Preventive Medicine Approach
Authors: Nguyen Thach N , Hsu Che Wei , Le Phuc X , Nguyen DUC , PHAM THIEN , Vu Quang Phuc , Huynh Duong , Ha Quang Dat , Vu LOC , Tran Nghi , Le Thoa , Hoang Thanh , Nguyen Cardy , Aggarwal Sarthak , Mihas Imran , Nguyen Huu Duc
Published: June 2023

Introduction:
Many patients with acute coronary syndrome (ACS) presented with elevated troponin level and reversible changes in the thallium scan. When they patients underwent coronary angiogram, the results showed patent coronary arteries. WHY?

Hypothesis:
Could abnormal coronary flow explain ACS, abnormal thallium and patent coronary arteries?

Methods:
Patients with newly diagnosed ACS and abnormal Thallium scan underwent a new dynamic coronary angiogram. 10 patients without ACS, normal EF and no coronary artery disease served as control. In this new technique, the contrast and blood flow were recorded at 15 images per second. The first image was of the index artery completely filled with contrast. The subsequent images showed the blood in white color moving in over a background of black contrast. The arterial phase started when the blood began moving in and ended when the contrast disappeared from the distal arterial vasculature as the contrast was replaced by blood. The machine learning (ML) program had 2 models (built on Python). Model 1 was built based on U-net and Densenet-121 for vessel segmentation. Model 2 was used for classification of flow. The model 2 was trained based on the convolutional neural network. The data to be collected was the duration of the arterial phase and the recurrence of ACS within one year follow-up

Results:
45 patients with ACS (elevated troponin level (50-100mg), reversible stress thallium), underwent coronary angiogram. The angiograms of 10 control patients showed a normal arterial phase (AP) of 1.56 sec. It was prolonged at 2.5sec in 45 patients with ACS (p<0.05). After 1 year follow-up, 35 patients had no further ACS if their LDL cholesterol was well controlled (<75mg%), blood pressure (BP<130mmHg) and the patients stopped smoking. In 10 patients who continued to have uncontrolled LDL, high BP and especially smoking, they developed ACS including death.

Conclusions:
In ACS patients, a prolonged arterial phase associated with reversible change in nuclear scan and normal coronary arteries identified the patients of high risk. Aggressive treatment of risk factors protected these patients of new ACS. Failure to control risk factors lead to repeat ACS. New trials are needed to confirm and guide new personalized medicine approach.
Abstract 9696: Long-Term Outcomes With Abandoning versus Extracting Sterile Leads: A 10-Year Population-Based Study
Authors: Talaei Fahimeh , tan Min-Choon , Srivathsan Komandoor S , Sorajja Dan , Valverde Arturo M , Scott Luis R , Asirvatham Samuel , Kusumoto Fred , Mulpuru Siva K , Cha Yong-Mei , Lee Justin
Published: June 2023

Background:
Long-term outcomes of lead management strategies of lead abandonment (LA) or transvenous lead extraction (TLE) during cardiac implantable electronic devices (CIED) procedures requiring lead addition or replacement remain unclear.

Hypothesis:
We hypothesized that there is no difference in long-term (10-year) outcomes of LA versus TLE during CIED procedures requiring lead addition.

Methods:
We performed a retrospective cohort study of a population residing in seven adjacent counties of southeastern Minnesota with follow-up at the Mayo Clinic and its health systems. Patients who underwent LA or TLE for sterile leads from January 1, 2000, to January 1, 2011, and had follow-up for at least 10-years or until their death were included. Outcomes were identified through a detailed chart review of the electronic health record from within the Mayo Clinic system.

Results:
A total of 172 patients were included in the study with 153 patients who underwent LA and 19 who underwent TLE for sterile leads. In long-term follow-up, indications for subsequent lead extraction arose in 9.1% (n=14) of patients with initial LA and 5.3% (n=1) in patients with initial TLE, after an average of 7-years. Moreover, out of 14 patients, who required secondary extraction in the LA cohort, 28.6% did not proceed with the extraction. Of the remaining 10 patients, 60% had clinical success and 40% had a clinical failure with the extraction. Subsequent device upgrades or revisions were performed in 18.3% of patients in the LA group and 31.6% in the TLE group, with no significant differences in procedural challenges such as requiring balloon venoplasty or serial dilation (5.2% vs. 5.3%, P=1.0). There was no difference in 10-year survival probability among LA group and TLE group (P=0.64).

Conclusion:
Indications for subsequent extraction arose in 9.1% of patients with the initial LA approach for sterile leads after an average of 7.3 years and 28.6% did not proceed with the extraction. Of the patients who underwent the subsequent extraction, 60% had clinical success and 40% had a clinical failure. There was no difference in 10-year survival probability between patients with the initial LA approach or TLE approach.
Abstract 9700: Totum-070 Reduces Hypercholesterolemia in Western Diet Fed Mice and Increases Cholesterol Fecal Excretion
Authors: Langhi Cedric , Otero Yolanda F , Le Joubioux Florian , Guigas Bruno , PELTIER Sébastien , Sirvent Pascal
Published: June 2023

Lowering blood cholesterol level reduces the incidence of cardiovascular diseases. Totum-070 (T070) is a polyphenol-rich active substance composed by the association of 5 plant extracts. We tested the effect of supplementation of T070 in dyslipidemic mice and characterized the mechanisms of action. C57Bl/6 mice were fed with either a normal diet (ND) or a western diet (WD) for 6 weeks. Mice fed WD were split in different groups (vehicle, T070 1g/kg and T070 3g/kg) depending on the treatment received daily by gavage (n=14 per group). Compared to WD-fed mice, the concentration of total cholesterol was decreased after 3 weeks of supplementation by -9% (p<0.05) and -12.7% (p<0.01) with 1 g/kg T070 and 3 g/kg T070, respectively. At the end of the study, total cholesterol was reduced by -7.3% (n.s) and -11% (p<0.01) with 1 g/kg and 3 g/kg T070 compared to WD-fed mice. Mice receiving 1g/kg T070 exhibited similar body weight gain than mice from the WD group. On the contrary, WD-fed mice receiving 3 g/kg T070 had reduced body weight gain by 29.5% compared to WD-fed mice (p<0.01). The supplementation of T070 reduced hepatic steatosis in a dose-dependent manner with a 17.4% drop at 1 g/kg T070 (p<0.05) and a 40% reduction at 3g/kg T070 (p<0.0001) compared to WD-fed mice. Hepatic and intestinal gene expression were altered by WD feeding compared to ND, while supplementation with T070 tended to restore normal levels of expression on several genes implicated in lipid and lipoprotein metabolism. Fecal neutral sterols were quantified in feces collected at the end of the study. Sterol quantity was increased by 16% in feces from the 3g/kg T070 group compared to the WD group. Furthermore, a significant 13% increase in feces production was observed in mice supplemented with T070 3 g/kg compared to the mice fed with WD alone (p<0.01). Fresh feces were harvested of the mice and composition of microbiota was assessed by 16S rDNA sequencing. WD induced a decrease in richness (Chao) and diversity (Shannon) indexes, compared to ND. T070 supplementation was able to partially restore diversity index, compared to WD. In conclusion, T070 supplementation is a promising strategy to prevent hypercholesterolemia though increased of fecal cholesterol excretion and amelioration of gut microbial imbalance.
Abstract 9744: Declining Relative Use of Mitral Valve Repair in Australia Despite Superior Outcomes: A Statewide Population-linkage Study
Authors: Cheng Yeu-Yao , Shun Matthew Wei Shun , Vijayarajan Vijayatubini , Hsu Arielle , HYUN Karice , Brieger David , Chow Vincent , Kritharides Leonard , Ng Austin Chin Chwan
Published: June 2023

Introduction:
Mitral valve (MV) repair (MVr) has superior survival outcomes to MV replacement (MVR) for primary MV diseases. MVr cases has increased in other developed nations but is unknown in Australia. We assessed temporal trends in the total and relative MVr volume and compared MVr and MVR outcomes over 17 years.

Method:
Patients who had isolated MV surgery (MVSx) between 2001-2017 were identified from the New South Wales statewide Admitted Patient Data Collection registry. Mortality outcome was tracked to Dec 2018.

Results:
A total of 5693 patients (MVr: n=2020 [35%]; mechanical MVR: n=1656 [29%]; bioprosthetic MVR: n=2017 [35%]) were identified; median age [interquartile range] were 67y [59-75y] vs 64y [55-71y] vs 75y [68-80y], respectively (all P<0.001). Median follow-up for the cohort was 6.3yrs. Annual MVSx cases increased over the study period but relative use of MVr declined from 44% (110/252 MVSx) in 2002 to 27% (165/601 MVSx) in 2017 (Fig1). Crude in-hospital and 1-yr mortality steadily declined for all groups between 2001 and 2017. MVr had the best outcome, with 1.2% in-hospital, 2.5% 1-yr, and 21.6% total cumulative mortality. Compared to MVr, after adjusting for age, sex, referral source, and comorbidities, the adjusted hazard ratios for long-term mortality were 1.41 (95% confidence interval [CI]=1.24-1.61) for mechanical MVR and 1.73 (95% CI=1.53-1.95) for bioprosthetic MVR (Fig 2).

Conclusion:
In this statewide Australian cohort study, relative use of MVr decreased over 17 years and are lower than reported by other international studies, despite having superior outcome compared to MVR. Factors driving the relatively low use of MVr should be explored.