bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9124: The Role of Mitochondrial Pyruvate Carrier on Myocardial Salvage Following Acute Myocardial Infarction
Authors: Visker Joseph R , LING JING , Kwak Hyoin , Shankar Thirupura S S , Velasco Jesse , Thodou Apasia S , Navankasattusas Sutip , Ducker Gregory , Rutter Jared P , Drakos Stavros G
Published: April 2024

Acute myocardial infarction (AMI) may progress to heart failure (HF). Ischemic-reperfusion injury (I/R) accounts for ~50% of the damage post-AMI. Currently, there are minimal interventions to mitigate I/R and prevent HF. Mitochondrial Pyruvate Carrier (MPC) is considered cardio-protective, and deletion causes HF. The purpose of this investigation was to determine if cardiac MPC deletion (MPC
-/-
) in mice limits myocardial salvage following I/R. We hypothesized MPC
-/-
mice would have more necrosis and less myocardial salvage compared to wild type (WT) littermates.MPC1 was targeted in C57Bl/6 mice by placing loxP sites in the introns flanking the exon 3-5 of MPC1. A cardiac-specific deletion was used by intraperitoneal injections of tamoxifen at 8 weeks old. Four weeks post injection, prior to development of HF, mice were intubated, ventilated, and the left anterior descending artery was occluded for 30 minutes then reperfused for 2 hours. Next, Evans-Blue was injected into the heart to define the ischemic area. Hearts of paired littermates between WT (n=6) and MPC
-/-
(n=6) were excised and cut into 1-mm transverse slices. Slices were stained with triphenyltetrazolium-chloride (TTC) to define myocardial salvage. Next, slices were imaged and quantified by independent researchers using planimetry. Paired t-tests with an α-level of 0.05 were used to compare groups.

Litters not subjected to I/R showed significant (p<0.001) MPC1 deletion (WT: 0.28±0.11 au vs. MPC
-/-
: 0.06±0.02 au). The area at risk (AAR) was comparable (p=0.12) between groups (WT: 46.7±5.9% vs. MPC
-/-
: 54.3±13.3), indicating equivalent coronary ligation-induced ischemia. Within the AAR, MPC
-/-
mice showed significantly (p=0.04) more necrosis (MPC
-/-
: 52.8±10.4% vs. WT: 42.7±17.4%) with less myocardial salvage (MPC
-/-
: 47.2±10.4% vs. WT: 57.3±10.6%). MPC
-/-
mice also had significantly (p=0.002) more absolute necrosis (28.4±7.8%) compared to WT mice (19.8±7.8%). There were no significant differences (p>0.05) in percent viable or salvageable tissue in relation to total area.

In conclusion, following I/R, MPC
-/-
mice showed more absolute and standardized necrosis with less myocardial salvage, suggesting when cardiac MPC is reduced it causes more myocardial damage leading to HF.
Abstract 9141: Cardiac Injury and Mortality Among Covid-19 Patients in a Predominantly Black Community of East Flatbush Brooklyn
Authors: Adomfeh Emmanuel C , Francois Jonathan , Priyan Harshith , Puskoor Anoop V , Wilson Clara , DaSilva Brandon , Adomfeh Jean
Published: April 2024

Introduction:
Black/African-American (AA) populations have been previously shown to have increased disease burden of COVID-19 and related deaths. However, not many studies have examined cardiovascular comorbidities and associated cardiac injury contributions to morbidity and mortality of COVID-19 in this population. In this study, we investigate the contributions of cardiac injury to mortality of COVID-19 in a predominantly AA population.

Study Design:
This is a retrospective cohort study of 572 laboratory confirmed COVID-19 patients admitted to SUNY Downstate HSC in East Flatbush, Brooklyn between March 12 and May 12, 2020. Patients with a documented troponin level above 0.15 μg/L were denoted as having cardiac injury. Of this group, 110 patients were in the cardiac injury group and 462 patients were in the no cardiac injury group. Statistical significance was designated at the p=0.05 level.

Outcome:
The primary outcome is 60-day mortality. Secondary outcomes included length of stay, non-invasive and invasive ventilation requirement, requirement of intensive care unit admission.

Results:
The median age was 69 years. 303 (52.97%) were males, and 515 (90.03%) were AA. When compared to patient’s non-cardiac injury group, the cardiac injury group tended to be older, and more likely to have comorbidities such as CHF, COPD, and ESRD. Patients with cardiac injury were also more likely to be smokers. In the cardiac injury group, laboratory data showed a higher white blood cell count, blood urea nitrogen, creatinine, and procalcitonin. Patients with cardiac injury had higher proportion of renal failure, were more likely to require intubation, and were more likely to be transferred to ICU. Notably in comparison to the non-cardiac injury group, patients with cardiac injury found to have a statistically significant two-fold increase in 60-day mortality (62.73% vs 32.90%), reduced mean survival time (33.57 vs 52.70) and a hazard ratio of 1.53 after controlling for confounders using the multiple adjusted Cox proportional hazard regression model.

Conclusions and Relevance:
The study results exhibit a statistically significant association between cardiac injury and mortality among COVID-19 positive individuals from a predominantly AA population.
Abstract 9150: Actigraphy-Derived Sleep Health Metrics and Biomarkers of Cardiovascular Disease Risk in Black/African American Smokers
Authors: Hoopes Elissa K , satti aditi , Brewer Benjamin , Blair Rachel , Davey Adam , Grandner Michael A , Farquhar William B , Patterson Freda
Published: April 2024

Introduction:
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in Black/African American (BAA) adults, and to a greater extent in BAAs who smoke cigarettes. Sleep is an emergent predictor of CVD, yet the independent role of sleep health on CVD risk in BAA smokers is unclear. Thus, we tested the hypothesis that better sleep health metrics would be independently associated with more favorable biomarkers of CVD risk in midlife BAA smokers.

Methods:
BAA adults (n=226, 55.9±6.1y, 44% male) who were current smokers (≥1 cigarette in last month) without sleep-disordered breathing or severe lung disease completed 14 days of wrist actigraphy to assess sleep duration, efficiency, midpoint, and regularity (sleep midpoint standard deviation). Resting blood pressure (BP) and heart rate recovery (HRR; HR
peak
minus HR
1-min recovery
from submaximal exercise) were assessed. Hypertension was defined as resting BP ≥130/80 mmHg, or use of antihypertensives. Multivariable regression models of systolic BP, diastolic BP, hypertension (yes/no), and HRR were generated to test associations between sleep metrics and CVD risk markers after adjusting for key covariates (see Table).

Results:
In adjusted models, achieving a healthy sleep duration (6-8 h/night) was associated with 62% lower odds of hypertension (vs. <6 or >8h/night; OR=0.38, 95% CI=0.18-0.75). Later sleep midpoint was associated with higher systolic BP (B=1.97 mmHg per 1-h delay in midpoint, 95% CI=0.17-3.81); longer sleep duration (B=1.89 bpm per 1-h increase in duration, 95% CI=0.39-3.39) and greater sleep efficiency (B=0.27 bpm per 1% increase in efficiency, 95% CI=0.08-0.46) were associated with greater HRR.

Conclusions:
Better sleep health metrics are associated with a lower CVD risk profile in BAA smokers, independent of important confounding factors. Sleep health may represent an auxiliary intervention target for ameliorating the CVD burden experienced by this at-risk group.
Abstract 9162: Increased Ratio of B2/B1-like Lymphocytes in the Perivascular Adipose Tissue Could Contribute to Plaque Destabilization in Human Coronary Arteries: Preliminary Results
Authors: Farias-itao Daniela S , Pasqualucci Carlos Augusto , Andrade Renato A , da Silva Luiz Fernando F , Estevam Maristella Y , Campo Alexandre B , Suemoto Claudia K
Published: April 2024

Introduction:
B-lymphocyte density in the pericoronary adipose tissue (PvAT) was correlated with plaque size in human coronary arteries. However, the subtypes of B cells in the PvAT and atherosclerotic plaque composition have not investigated yet.

Hypothesis:
We hypothesized that B2 and the ratio of B2/B1-like lymphocytes in the PvAT will correlate with an increase in components related to plaque destabilization and a decrease in components related to plaque stabilization. B1-like lymphocytes will correlate with an increase of components related to plaque stabilization.

Methods:
Coronary arteries were freshly dissected with adjacent PvAT. The most important atherosclerotic plaque was selected from each main coronary artery. From 107 artery segments, we calculated the percentage of arterial obstruction, intima-media thickness, the minimum fibrous cap thickness, and the percentage of collagen, smooth muscle cells, fibrous cap, calcification, lipid, necrosis, and intraplaque hemorrhage. We considered B2-lymphocytes as CD20
+
CD43
-
and B1-like lymphocytes as CD20
+
CD43
+
using the immunohistochemistry double staining technique. The densities of B2, B1-like, and the ratio of B2/B1-like lymphocytes were correlated with plaque composition using linear, negative binomial, or Poisson regressions models with clustering for multiple measures in the same individual and adjusted for age, sex, hypertension, diabetes, body mass index, sedentary lifestyle, smoking, and alcohol consumption.

Results:
B2 and B1-like lymphocyte density in the PvAT were not correlated with plaque components. However, the increase of the ratio of B2/B1-like lymphocytes was associated with a decrease in intraplaque collagen (β= -0.19, 95%CI= -0.35; -0.03, p=0.01), calcification (β= -0.15, 95%CI= -0.28; -0.02, p=0.01), hemorrhage (β= -0.08, 95%CI= -0.15; -0.02, p=0.009), minimum fibrous cap thickness (β= -0.03, 95%CI= -0.04; -0.01, p<0.001), and an increase in the number of vasa vasorum in adventitia layer (β= 0.006, 95%CI=0.001; 0.01, p=0.006).

Conclusions:
An increase in the ratio of B2/B1-like lymphocytes in the PvAT could contribute to plaque destabilization by the decrease of atherosclerotic plaque components related to plaque stabilization.
Abstract 9187: Risk Factors for the Onset of Coronary Artery Calcium in Younger versus Older Persons
Authors: Razavi Alexander C , Allen Norrina B , Dzaye Omar , Michos Erin , Budoff Matthew J , Lima Joao A , Shikany James M , Liu Kiang , Post Wendy , Blumenthal Roger S , Blaha Michael J , Carr Jeffrey , Whelton Seamus P
Published: April 2024

Introduction:
Modifiable traditional atherosclerotic cardiovascular disease (ASCVD) risk factors (RFs) have a decreased predictive strength with higher ages. Whether the strength of relationship between these RFs and incident coronary artery calcium (CAC) changes with age is unknown.

Hypothesis:
Modifiable traditional ASCVD RFs will have a weaker association with incident CAC in older versus young adults.

Methods:
There were 5108 CARDIA and MESA participants without clinical ASCVD and baseline CAC=0. Repeat CAC scoring occurred 10 years later in CARDIA and 3-11 years later in MESA. Multivariable Cox proportional hazards regression calculated hazard ratios and C-statistics for RFs with incident CAC in young (32-45 years), middle-aged (46-64 years) and older adults (65-84 years).

Results:
A total of 61% of adults were women and 37% were African American. The proportion with incident CAC increased from young (22%) to middle-aged (33%) and older adults (45%). All modifiable traditional RFs were significantly associated with incident CAC except for diastolic blood pressure and HDL-C in young adults, whereas among older adults only a total cholesterol/HDL-C
>
3.5 (p=0.04) was significantly associated with incident CAC. Systolic blood pressure was the modifiable RF with the strongest association per 1 standard deviation change for incident CAC in young adults (HR=1.29, 95% CI: 1.13-1.48), conferring lower risks in middle-aged (HR=1.20, 95% CI: 1.06-1.36) and older adults (HR=1.10, 95% CI: 0.96-1.27). Modifiable traditional RFs provided a greater improvement in the C-statistic for incident CAC prediction in young versus middle-aged and older adults (
Table
).

Conclusion:
Modifiable traditional ASCVD RFs were stronger predictors of incident CAC for young compared to older adults, which may be due to their higher prevalence with increasing age. Further research is needed to examine whether nontraditional RFs improve incident CAC prediction in adults
>
65 years old.
Abstract 9191: Association of Cumulative Social Risk Score With Cardiovascular Outcomes in the Multi-Ethnic Study of Atherosclerosis
Authors: Hammoud Aziz , Chen Haiying , Ivanov Alexander , Yeboah Joseph , Cainzos-Achirica Miguel , Nasir Khurram , Bertoni Alain G , Khan Safi U , Blaha Michael J , Herrington David M , Shapiro Michael D
Published: April 2024

Introduction:
Although the importance of social determinants of health is well-established in atherosclerotic cardiovascular disease (ASCVD), there is a need for a validated polysocial risk construct in the current paradigm of ASCVD prevention and management.

Methods:
Data from the Multi-Ethnic Study of Atherosclerosis study were used to create an index of baseline Cumulative Social Risk (CSR) to explore its association with incident ASCVD (fatal/non-fatal myocardial infarction, stroke, definite angina, probable angina if followed by revascularization, or resuscitated cardiac arrest). CSR score was defined by assigning a point for the presence of each of 4 social factors: i) educational attainment less than a high school diploma, ii) household income less than the federal poverty level, iii) minority race/ethnicity (Black, Hispanic, or Asian), and iv) single-living status as a proxy for limited social support. Kaplan-Meier survival curves and log-rank tests were used to examine the univariate association between CSR score and ASCVD. Cox proportional hazards models were used to examine the association between CSR score and time-to-ASCVD with and without adjustment for traditional cardiovascular risk factors.

Results:
A total of 6,529 participants had available CSR scores (0, 24.3%; 1, 35.5%; 2, 25.5%; ≥3, 14.7%). In total, 947 ASCVD events over a median follow-up of 15.6 years were observed. There was a statistically significant difference between the survival curves according to CSR scores (overall log-rank p<0.01). CSR score was crudely associated with increased risk of incident ASCVD in a graded manner (Table 1); however, this association was attenuated in the fully adjusted models.

Conclusion:
CSR score was associated with incident ASCVD even after adjusting for age and sex; however, this association was attenuated after also adjusting for traditional cardiovascular risk factors, whose role as potential mediators should be explored in future work.
Abstract 9197: Lesion Size and Adverse Event Profile of the TactiFlex™ Ablation Catheter, Sensor Enabled™ in a Porcine Thigh Model
Authors: Overmann Jed , Ginn Greg , Ambrosius Nicholas , Geurkink Christopher , Thamavong Zada , Fish Jeffrey
Published: April 2024

Background:
Advanced irrigated catheters, such as the FlexAbility™ Ablation Catheter, Sensor Enabled™ (FlexAbility SE), improve safety during RF ablation. Integration of contact force sensing technology with FlexAbility SE is clinically desirable to further enhance procedural efficacy and safety.

Objective:
To compare lesion size and adverse events in a perfused porcine thigh model for the TactiFlex™ Ablation Catheter, Sensor Enabled™ (TactiFlex SE) and its market-released predecessor, FlexAbility SE.

Methods:
Power controlled RF ablations were performed in 5 swine at either a nominal (30W, 60s; N=88) or maximum (50W, 10s; N=74) setting (20 g, 13 ml/min irrigation rate for all). Trials were balanced between parallel and perpendicular tip orientations. Coagulum formation, steam pops, char and lesion depth and width were documented. At each setting, lesion depth and width were assessed for equivalence between catheters (linear mixed model). Results for both orientations were pooled and adverse events were evaluated for non-inferiority of TactiFlex SE compared to FlexAbility SE (logistic regression).

Results:
Lesion depth and width were equivalent between TactiFlex SE and FlexAbility SE for all conditions (pre-specified- equivalence interval = ±1.67mm). TactiFlex SE was non-inferior to FlexAbility SE for rate of coagulum and char (pre-specified upper -non-inferiority margin = 20% ). No steam pops occurred with either catheter.

Conclusion:
The TactiFlex™ Ablation Catheter, Sensor Enabled™ produced equivalent lesion sizes and a favorable adverse event profile when compared to the FlexAbility™ Ablation Catheter, Sensor Enabled™ in a perfused porcine thigh model.
Abstract 9199: A Novel Small Molecule Troponin Activator Increases Cardiac Contractile Function Without Negative Impact on Energetics or Diastolic Function
Authors: He Huamei , Baka Tomas , Balschi James , Motani Alykhan , Nguyen Khanh K , Liu Qingxiang , Slater Rebecca , rock brooke , Wang Chen , Hale Christopher , Karamanlidis Georgios , Hartman James J , Malik Fady I , reagan jeff D , Luptak Ivan
Published: April 2024

Background:
Current heart failure (HF) therapies improve cardiac energy balance and prolong survival by unloading the failing heart without targeting the underlying problem of reduced cardiac contractility. Traditional inotropic medications, also termed calcitropes, stimulate contractility via energetically costly augmentation of calcium cycling and worsen patient survival. Myotropes are a new class of agents that activate the sarcomere directly, independent of cAMP and calcium. We hypothesize that a novel myotrope, troponin activator (TA1), increases contractility without the deleterious myocardial energetic impact of calcitrope dobutamine (DOB).

Methods:
We determined the pharmacodynamics of TA1
ex vivo
and
in vivo
in anesthetized normal rats. Isolated rat hearts were perfused with incremental concentrations of TA1 or DOB to compare their effect on cardiac contractility and high-energy phosphate concentrations using
31
P NMR spectroscopy.

Results:
A dose dependent increase in contractility was observed
in vivo
by echocardiography after acute administration of TA1. In isolated hearts, increasing concentrations of TA1 and DOB similarly increased rate pressure product (RPP), which is a product of developed pressure (DevP) and heart rate (HR). At equivalent doses (DOB 120 nM, TA1 60 nM), TA1 increased DevP more and HR less compared to DOB. DOB decreased phosphocreatine (PCr) to ATP ratio and free energy of ATP hydrolysis (ΔG
~ATP
) and elevated left ventricular end-diastolic pressure (LVEDP). In contrast, the TA1 increased RPP without any effect on HR, LVEDP, PCr/ATP ratio or ΔG
~ATP
.

Conclusions:
Here we describe a novel myotrope, TA1, that increased myocardial contractility by sensitizing the sarcomere to calcium without impairing diastolic function or depleting the cardiac energy reserve. Since energetic depletion negatively correlates with long term survival, TA1 may represent a superior alternative to traditional inotropes in HF management.
Abstract 9200: In-Hospital Outcomes and Readmission Rates of Transcatheter Aortic Valve Replacement in Mixed Aortic Valve Disease
Authors: Rubin Phillip , Grant Jelani , Vincent Louis T , Chambers Sharde F , Ebner Bertrand , Maning Jennifer , Olorunfemi Odunayo , Colombo Rosario A , BRAGHIROLI JOAO F
Published: April 2024

Introduction:
Transcatheter Aortic Valve Replacement (TAVR) is indicated in patients with severe aortic stenosis (AS) and is increasingly performed in patients with combined AS and aortic regurgitation. We evaluated in-hospital outcomes and readmission rates after TAVR in patients with mixed aortic valve disease (MAVD).

Methods:
A total of 100,573 TAVR procedures were identified between 2011-2017 using ICD-9 and -10 codes from the Nationwide Readmissions Database (NRD). We separated patients into two cohorts, those with MAVD and those with pure AS. Primary outcome was post-TAVR all-cause inpatient mortality; secondary outcomes included rates of 30- and 90-day readmissions, paravalvular leak (PVL), permanent pacemaker (PPM) insertion, acute kidney injury, major bleeding, postoperative ischemic stroke, total cost of hospitalization and length of hospital stay.

Results:
A total of 3,260 patients had MAVD (median age 83 years, 43.5% women). In-hospital mortality (2.5% vs 2.6%, p=0.531), rates of PVL (1.0% vs 1.3%, p=0.056) and hospital length of stay (5.8±7.8 vs. 6.7±7.8, p=0.126) were similar between the MAVD and pure AS groups. 30- (0.5% vs. 8.8%, p<0.001) and 90-day readmission rates (0.8% vs. 16.0%, p<0.001), major bleeding (7.4% vs. 9.6%, p<0.001), acute kidney injury (12.9% vs. 15.1%, p<0.001), postoperative ischemic stroke (2.0% vs. 5.7%, p<0.001) and mechanical circulatory support use (1.9% vs. 4.5%, p<0.001) were less prevalent in the MAVD cohort. Using logistic regression, MAVD was not predictive of mortality in patients undergoing TAVR (adjOR: 1.25, 95% CI; 0.99 to 1.57, p=0.056), however MAVD was associated with: decreased odds of 30- (adjOR: 0.05, 95% CI; 0.03 to 0.08, p<0.001) and 90-day readmission rates (adjOR: 0.04, 95% CI; 0.03 to 0.06, p<0.001), and higher odds of PPM implantation (adjOR: 1.46, 95% CI; 1.29 to 1.65, p<0.001).

Conclusion:
Despite differences in the aortic valve and left ventricular anatomy (pressure versus volume related adaptive changes) in patients with MAVD and pure AS, TAVR appears safe and feasible. However, patients with MAVD were more likely to have permanent pacemakers implanted. The results of our study warrant further randomized controlled studies to confirm these findings.
Abstract 9213: Effect of Ai-Enabled Ecg Screening for Low Ef in Patients With Different Socioeconomic Status
Authors: Kurani Shaheen , Inselman Jonathan , Rushlow David R , McCoy Rozalina G , Thacher Thomas , Behnken Emma , Bernard Matthew , Rosas Steven L , Akfaly Abdulla , Misra Artika , Molling Paul , Krien Joseph , Foss Randy , Barry Barbara , Siontis Konstantinos , Kapa Suraj , Gersh Bernard J , Pellikka Patricia A , Lopez-jimenez Francisco , Attia Zachi , Halamka John D , Friedman Paul , Noseworthy Peter A , Yao Xiaoxi
Published: April 2024

Introduction:
Asymptomatic LV systolic dysfunction is often underdiagnosed, leading to missed opportunities for treatment. In a recently completed pragmatic RCT, an AI algorithm performed on the ECGs ordered as part of routine practice increased early diagnosis of low EF. The current study aimed to understand whether the effectiveness of the AI algorithm integrated into routine care differed by the socioeconomic status of the patient.

Methods:
The main findings of the RCT were previously published. Clinicians in the intervention group had access to AI results (i.e., a positive or negative screening result, with positive results indicating a high likelihood of low EF). When a positive result was found, clinicians in the intervention group received an alert that encouraged them to order TTE if considered clinically appropriate. Clinicians in the control group did not have access or received alerts. Area deprivation index (ADI) was used to measure area-level social determinants of health. This study included 16,992 patients (control 8,225; intervention: 8,767) who had ECG performed for any indications between 8/5/2019 and 3/31/2020, no prior HF, and a valid address to derive ADI. The primary endpoint was a new diagnosis of EF≤50% within 3 months.

Results:
The mean age was 60.5±17.6 y. AI increased the diagnosis of low EF in the overall cohort (OR 1.42 [1.13, 1.78], p=0.01). The magnitude of benefit was greater in patients with higher socioeconomic status, e.g., living in an area that is less deprived (OR 1.88 [1.16, 3.05]), with higher median income, lower poverty rate, higher education level, better housing conditions, and higher proportion of white-collar workers, although the interaction was not statistically significant (Figure).

Conclusions:
AI enables early diagnosis of low EF and the magnitude of benefit might be numerically greater in patients with higher socioeconomic status, possibly due to variations in access to or referral for subsequent testing.
Abstract 9234: Effects of a 26-Week Randomized, Controlled Exercise Intervention on Arterial Stiffness, Endothelial Function, and Cognition in Adults Atrisk for Alzheimer Disease
Authors: Pewowaruk Ryan , Gaitan Julian M , Mitchell Carol , Lose Sarah , Dougherty Ryan , Boots Elizabeth , Cook Dane B , Okonkwo Ozioma C , Gepner Adam D
Published: April 2024

Introduction:
Arterial stiffness progresses with age and is associated with cardiovascular disease (CVD) events and cognitive decline. Alzheimer’s disease (AD) risk factors like physical inactivity overlap significantly with progression of arterial stiffness. Aerobic exercise training reduces arterial stiffness and may bolster cognition at a time of life when the risk of AD heightens.

Hypothesis:
Following a 26-week aerobic exercise intervention, improvements in cognitive function will be significantly correlated with improvements in carotid artery stiffness and endothelial function.

Methods:
Late-middle-aged adults with normal cognition and parental history of AD were randomized to a 26-week exercise training intervention designed to increase physical activity (PA) levels (Enhanced PA; n=11) or maintain Usual PA (n=12). At baseline and following the intervention we used ultrasound to measure local stiffness of the right common carotid artery, brachial artery flow mediated dilation, and tested cognitive function. Pre- and post- intervention changes in outcome variables were compared between groups using independent sample t-tests or ANCOVA and results are presented as mean ± standard deviation. The association between pre-post intervention changes in arterial stiffness and cognitive function were assessed using Pearson correlation coefficients.

Results:
The pre-post intervention changes for Usual PA vs Enhanced PA were not different for carotid artery stiffness (Young’s Elastic Modulus: (219 ± 1088 mmHg vs -131 ± 384, p=0.12) or endothelial function (0.49 ± 1.69 vs 0.47 ± 1.71, p=0.32). Improvements in cognitive function were not significantly correlated with changes in arterial stiffness or endothelial function (r = -.27-.25, p = .24-.81).

Conclusions:
The findings of this pilot study do not support the hypothesis that improved cognition following exercise would be associated with improved carotid artery stiffness and endothelial function.
Abstract 9289: Use of Oral Anticoagulants for Atrial Fibrillation Drops by 20% Upon Entering the Medicare Coverage Gap
Authors: Harrington Josephine L , Carnicelli Anthony , Wilson Lauren , OBrien Emily , Curtis Lesley , Pokorney Sean , Melloni Chiara , Lopes Renato D , Granger Christopher B
Published: April 2024

Introduction:
Medicare Part D beneficiaries enter a coverage gap when prescription costs for a given year exceed $3300-3700. While in this gap, patients are responsible for a substantially increased portion of their medication costs until those costs exceed $4850-5000, at which time patients exit the coverage gap. For patients with atrial fibrillation (AF), the impact of this increased cost on oral anticoagulant (OAC) medication fills (“fills”) is unknown.

Hypothesis:
We hypothesized that for patients with AF who enter the coverage gap, OAC fills would decrease while in the gap, particularly for non-vitamin K antagonist OACs (NOACs) due to high costs.

Methods:
Using the Centers for Medicare and Medicaid Services claims data from 2016-2018, we assessed OAC fills (using proportion of days covered [PDC]) in patients with AF before, during, and after the coverage gap. We compared PDC for NOACs versus warfarin by coverage gap status.

Results:
We analyzed OAC PDC in patients with AF across 182,192 patient-years. For patients entering the gap, median time to enter was 174 days. For patients who entered and remained in the coverage gap, median PDC dropped significantly from 0.92 to 0.76 (p=<0.001) upon entering the coverage gap (Figure). For patients who entered and exited the coverage gap, PDC did not improve upon exiting the coverage gap, but rather continued to drop significantly despite having nearly full financial drug coverage (0.95 to 0.88 to 0.70; p=<0.001). This pattern was similar for patients on NOACs and on warfarin.

Conclusions:
Upon entering the coverage gap, OAC fills decrease significantly in patients with AF. In AF patients who exit the coverage gap, OAC fills do not increase but rather continue to decrease. This pattern was consistent for NOACs and warfarin. Coverage gap status may have important and persistent impacts on OAC use in patients with AF.
Abstract 9303: Delay in Coronary Artery Bypass Grafting for ST Elevated Acute Myocardial Infarction Patients is Associated With Beneficial Outcomes: Further Evidence and Opportunities
Authors: Guite Jessica W , Tang Jing , Rao Jyotsna , Bhambere Sailee , Mahmood Shaikh D , Singerman Richard W , Hsieh Christine
Published: April 2024

Introduction:
Coronary artery bypass grafting (CABG) surgery for patients with acute ST Elevated Acute Myocardial Infarction (STEMI) in the first 24 hrs of admission is associated with greater hospital morbidity and mortality. Delaying CABG >24 hrs may provide opportunities to improve patient outcomes. This study replicates and extends recent research and considers practice implications.

Hypothesis:
Patients with STEMI undergoing non-elective CABG surgery <24 hrs after admission will have worse outcomes than patients receiving later non-elective or elective CABG surgery.

Methods:
Patients age >= 30 yrs undergoing CABG <7 days of admission from the National Inpatient Sample 2016-2017 were examined. Non-elective and elective CABG was compared with 4 subgroups examined: Non-elective admission, STEMI diagnosis, CABG <24 hrs (Group A); CABG in 2-3 days (Group B); CABG in 4-7 days (Group C) and elective admission, CABG <7 days (Group D). Outcomes included postoperative complications (bleeding, cardiac, renal, respiratory), in-hospital mortality, post-operative and total hospital length of stay (LOS), and total hospital cost.

Results:
Patients with STEMI (n=2793, age=65.9±9.7 yrs) non-electively hospitalized (group A=47.2%, B=25.7% and C=27.0%) and elective admissions without STEMI (n=28096, mean=63.8 ±10.8 yrs, group D) were analyzed. Complication rates did not consistently differ for groups A, B, and C, however group A rates were significantly higher than group D. Group A had the highest mortality (6.06%) — significantly greater than groups B (3.62%) and C (3.32%) — with all non-elective groups greater than the elective group D (1.01%). Group A had significantly longer postoperative and total LOS. Total median hospitalization cost was lowest for elective group D ($135,446) but not significantly different between groups A ($191,344) and B ($203,944).

Conclusions:
STEMI cases typically need urgent intervention and CABG surgery can be critical for management. Delaying non-elective CABG >24 hours after admission is associated with better outcomes. Elective CABG has the best outcomes. More pre-surgical time provides opportunities to better prepare patients and caregivers with tailored coaching and content which can further improve outcomes.
Abstract 9305: Association of Silent Myocardial Infarction on Electrocardiogram and Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis
Authors: Singleton Matthew J , German Charles A , Soliman Elsayed Z , Burke Gregory L , Yeboah Joseph
Published: April 2024

Introduction:
Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood.

Hypothesis:
SMI on ECG is predictive of elevated CAC.

Methods:
Eligible participants from the Multi-Ethnic Study of Atherosclerosis (MESA) had ECG and CAC scoring at study enrollment (2000-2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross-sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression.

Results:
Among 6,705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0 - 261.7] vs. 0 [0 - 81.5]; p < 0.0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48 - 3.20, p < 0.0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06 - 2.16, p = 0.02).

Conclusions:
An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk-stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed.
Abstract 9313: Clinician Training, Implicit Bias, and Self-Efficacy in Treating African American Patients: A Substudy of the HYpertension and VALUEs Trial
Authors: Pham Vy A , Blair Irene , Helmkamp Laura , Maertens Julie A , Hanratty Rebecca , Vupputuri Suma , Steiner John , Havranek Edward P , Dickinson Miriam L , Daugherty Stacie L
Published: April 2024

Background:
Implicit bias among clinicians is believed to contribute to health disparities. Clinicians have racial biases comparable to others in society, leading to calls for trainings in cultural awareness. However, whether such trainings improve clinician self-efficacy or reduce bias is not well known. We assessed the relationships between prior cultural awareness training, perceived efficacy in caring for African American patients, and implicit race bias.

Methods:
As part of a larger trial, a sample of primary care clinicians (PCPs) completed a race implicit association test (IAT) and survey regarding prior training in cultural awareness, and perceived efficacy in caring for African American patients (i.e., preparation to care for, and skill in developing positive relationships and overcoming bias). IAT d-scores measure racial implicit bias with scores >+0.15 indicating “pro-White” race bias, scores <-0.15 indicating “pro-Black”race bias and scores between -0.15 to +0.15 indicating “no bias”. Groups were compared using chi-squared tests for categorical variables and t-tests for continuous variables

Results:
Among 137 PCPs (63% female, 61% White, 51% ≤10 years in practice), 65% showed implicit pro-White race bias (mean IAT d-score = 0.34 (SD 0.44)) and 79% reported prior training in cultural awareness. Though 67% of participants felt “very prepared” to care for and 59% felt “very skilled” in developing a positive relationship with African American patients, only 26% felt “very skilled” in overcoming implicit racial bias. Prior training in cultural awareness was not associated with perceived efficacy in caring for African American patients (all p >0.05). IAT scores were similar between clinicians who had training in cultural awareness and those without prior training (Mean(SD)=0.32(0.47) vs. 0.42(0.35), p=0.32).

Conclusions:
In this sample of PCPs, prior cultural awareness training was not associated with either implicit bias or preceived efficacy in caring for African American patients. This study suggests that cultural awareness trainings may need to be further developed and expanded to target implicit bias and improve clinician self-efficacy.
Abstract 9334: Clonal Hematopoiesis is Associated With Incident Severe Aortic Stenosis
Authors: Raddatz Michael A , Silver Alexander J , Farber-Eger Eric , Xu Yaomin , Wells Quinn S , Savona Michael R , Lindman Brian R , Bick Alexander G
Published: April 2024

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) has been linked to increased risk of cardiovascular disease, mediated in part through inflammation. Like CHIP, aortic stenosis (AS) has a strong association with aging and involves pathologic inflammation. A prior study found that AS patients with CHIP have worse outcomes (Mas-Peiro,
Eur Heart J
, 2020); however, whether CHIP is associated with incident AS is presently unknown.

Methods:
We tested the association of CHIP and incident severe AS by echocardiography (defined by aortic valve area (AVA) ≤ 1 cm
2
or aortic valve peak jet velocity (V
max
) ≥ 4 m/s) in 6,866 patients over 40 years of age in the Vanderbilt University Medical Center BioVU repository. Analyses were performed using Cox proportional hazards models adjusted for age, sex, self-reported race, ethnicity, type 2 diabetes, hypertension, and hyperlipidemia.

Results:
CHIP mutations were identified in 3.5% of patients (n = 241 of 6,866 patients;
DNMT3A
, n = 97;
JAK2
, n = 48;
TET2
, n = 41;
ASXL1
, n = 33; mutations in multiple genes, n = 22). Severe AS by V
max
and AVA was seen in 2.7% (180/6,732) and 8.8% (359/4,088) of patients, respectively. Patients with CHIP mutations were older (63.9y vs 61.9y; P = 5.8 x 10
-3
) and more often white (93.8% vs 87.5%; P = 5.1 x 10
-3
). Presence of CHIP mutation was associated with increased risk of incident severe AS by V
max
(hazard ratio [HR] = 1.82 [1.03-3.20]; P = 0.039,
Figure
) and AVA (HR = 1.65 [1.07-2.54]; P = 0.023).
DNMT3A
mutations, specifically, were associated with incident severe AS (V
max
: HR = 2.42 [1.013-5.18]; P = 0.022; AVA: HR = 2.27 [1.27-4.05]; P = 5.4 x 10
-3
).

Conclusions:
We found that the presence of a CHIP mutation is associated with an increased risk of incident severe AS. This finding underscores the need for preventative cardiovascular care for patients with CHIP and suggests a role for immunobiology in AS pathophysiology.
Abstract 9356: The Effect of Intraoperative Oxygenation on Vascular Reactivity in Human Resistance Arterioles
Authors: Lopez Marcos G , Pandey Arvind K , Shotwell Matthew S , Harrison David G , Billings Frederic T
Published: April 2024

Introduction:
Hyperoxia during surgery is common and may promote oxidative stress. Oxidative stress uncouples endothelial nitric oxide synthase and may impair vascular reactivity, a key regulator of tissue perfusion.

Hypothesis:
Hyperoxia during cardiac surgery impairs vascular reactivity compared to normoxia.

Methods:
We isolated resistance-level arterioles from mediastinal fat collected from subjects in a clinical trial of hyperoxia versus normoxia during cardiac surgery. Tissue was obtained at the end of surgery, and arterioles from 24 subjects were mounted on a wire myograph. After norepinephrine contraction, we measured the endothelium-dependent response to acetylcholine and the endothelium-independent response to sodium nitroprusside. To further identify if hyperoxygenation impairs nitric oxide mediated vasodilation via oxidation of the soluble guanylyl cyclase heme moiety, we measured the response to the heme-independent soluble guanylyl cyclase activator cinaciguat. We compared relaxation to increasing doses of each vasodilator in normoxia vs. hyperoxia treated arterioles using repeated measures ANOVA and nonlinear mixed effects regression.

Results:
The acetylcholine response was uniformly impaired (P=0.98,
Figure
). The sodium nitroprusside response was selectively impaired in hyperoxia treatment vs. normoxia as reflected by a higher EC50 (EC50: 50.1±6.3 x10-8 M for hyperoxia vs. 7.9 ± 0.8 x 10-8 M for normoxia, P=0.02) and decreased peak response. In striking contrast to the response to sodium nitroprusside, vasodilation evoked by cinaciguat was not impaired and was slightly enhanced for hyperoxia vs. normoxia (EC50: 7.9±0.8 x10-8 M vs. 15.8±6.2 x10-8 M; P=0.07, Figure).

Conclusions:
Intraoperative hyperoxia impaired human arteriole vasodilation likely via oxidation of the soluble guanylyl cyclase heme moiety. These data provide additional mechanistic insight into potential harmful effects of intraoperative hyperoxia.
Abstract 9373: Cinnamamide Derivative Reduces Left Ventricular Dysfunction by Modulating Mitochondrial Dynamics in Prediabetic Rats
Authors: Sumneang Natticha , Oo Thura Tun T , Arunsak Busarin , Pratchayasakul Wasana , Apaijai Nattayaporn , Liang Guang , Chattipakorn Siriporn , Chattipakorn Nipon
Published: April 2024

Introduction:
Chronic high-fat diet (HFD) consumption induces prediabetes via increased systemic inflammation by activating myeloid differentiation factor 2 (MD2)/toll-like receptor 4 pathway, resulting in left ventricular (LV) dysfunction. Cinnamamide derivative was shown previously to reduce inflammation in lipopolysaccharide-induced septic mice by targeting MD2. However, the effects of cinnamamide derivative, 2i-10, on the LV function in prediabetes are not known.

Hypothesis:
2i-10 improves LV function in prediabetic rats by reducing cardiac inflammation, mitochondrial dysfunction, and mitochondrial dynamics imbalance.

Methods:
Prediabetic rats were induced by feeding HFD for 12 weeks, and were divided into 3 groups; vehicle, 2i-10 (40 mg/kg), or metformin (300 mg/kg). Normal diet fed rats received vehicle. Rats orally received their assigned treatment for 4 weeks. Then, LV function, cardiac inflammation, and mitochondrial function and dynamics were examined.

Results:
Prediabetic rats had impaired LV function, as shown by reduced %LV ejection fraction. Moreover, impaired mitochondrial function and dynamics were observed, as shown by increased reactive oxygen species (ROS), mitochondrial depolarization, swelling, increased mitochondrial fission (p-Drp1/Drp1) and decreased mitochondrial fusion (OPA1). NF-κB phosphorylation was increased in these rats, indicating inflammation. Treatment with 2i-10 significantly reduced cardiac inflammation, mitochondrial dysfunction, mitochondrial dynamic imbalance, and improved LV function in prediabetic rats (Fig 1). Similar benefits were observed in metformin-treated rats.

Conclusions:
Chronic treatment with 2i-10, effectively suppressed cardiac inflammation, mitochondrial dysfunction and mitochondrial dynamics imbalance, leading to improved LV function in prediabetic rats. These findings suggest that targeting MD2 could be a novel treatment to protect the heart in prediabetes.
Abstract 9383: Dapagliflozin, an Sglt2 Inhibitor, Reduces Expression of Myd88, Nlrp3 and Nf-kb During Exposure to Doxorubicin and Trastuzumab in Cellular Models
Authors: Maurea Nicola , Paccone Andrea , Iovine Martina , Buccolo Simona , Cerrone Francesca , Quagliariello Vincenzo
Published: April 2024

Introduction:
The cumulative incidence of cardiac events in women treated with anthracycline and trastuzumab at 1 year after the diagnosis of breast cancer was 16.4%, at 2 years 23.8 %, and at 3 years 28.2%. Sodium glucose cotransporter 2 inhibitors, reduces HF hospitalization and cardiovascular mortality.

Hypothesis:
We hypothesize that dapagliflozin could exerts cardioprotective effects in cellular models of doxorubicin and trastuzumab-induced cardiotoxicity

Methods:
Human cardiomyocytes (HL-1 cells) were exposed to subclinical concentration of doxorubicin and trastuzumab (100 nM) alone or in combination with dapagliflozin at 50 nM for 48h. Cell viability, apoptosis and necrosis were performed. Quantification of malondialdehyde, 4-hydroxynonenal and intracellular Ca
2+
were performed through spectrophotometric methods. Anti-inflammatory studies were also performed (expression of NLRP3 inflammasome, TLR4/MyD88 pathways, nuclear expression of NF-kB). Intracellular concentration of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF were also performed.

Results:
Dapagliflozin increased cell viability during exposure to doxorubicin and trastuzumab. Dapagliflozin reduces intracellular Ca
2+
overload ( -47,6% vs cells treated only to anticancer drugs; p<0,001), lipid peroxidation (mean reduction of 35-43 % compared to cells exposed only to anticancer drugs; p<0,001). The expression of Myd88, NLRP3 and NF-kB was significantly reduced after treatment with dapagliflozin (-37,5, -28 and -37 % vs cells exposed only to anticancer drugs, respectively; p<0.001). A specific set of cytokines, such as IL-1α, IL-1β, IL-6, IL17-α, TNF-α and IL-18 were significantly reduced after treatment with dapagliflozin indicating its anti-inflammatory, anti-fibrotic and cytoprotective properties which could prevent arrhythmic and myocardial events.

Conclusions:
Dapagliflozin exerts significant cardioprotective properties mediated by iCa
2+
content that consequently reduces peroxidation and NLRP3- Myd88 expression; inhibition of NLRP3 inflammasome by dapagliflozin decreased the expression of cytokines involved in cardiotoxicity.
Abstract 9385: Sacubitril-Valsartan (lcz-696) Improves Ejection Fraction and Longitudinal Strain in Mice Exposed to Doxorubicin Through Nlrp3 Inflammasome, Myd88 Myddosome and Chemokines
Authors: Maurea Nicola , Paccone Andrea , Buccolo Simona , Iovine Martina , Rea Domenica , Barbieri Antonio , Cerrone Francesca , Quagliariello Vincenzo
Published: April 2024

Introduction:
Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril-valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction.

Hypothesis:
we hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function and cardiac inflammation in preclinical models

Methods:
Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (200 nM) alone or in combination with LCZ-696 (100 mM) for 72 h. After the incubation period, we performed the following tests: cell viability, apoptosis and necrosis; expression of MDA and 4HNA and concentration of intracellular Ca
2+
. Moreover, pro-inflammatory studied were also performed (activation of NLRP3; expression of TLR4/MyD88; mTORC1 Fox01/3a; NF-κB). C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), LCZ-696 at 60 mg/kg (LCZ, n=6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3, Myd88, NF-kB and chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified.

Results:
LCZ-696 exerts cardioprotective effects, enhancing cell viability of 48-55% compared to only doxorubicin-treated cells (p<0,001 for all); LCZ 696 decreased NLRP3, MyD88 and NF-kB expression in cardiac cells. In preclinical study, LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88 and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (p<0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696.

Conclusions:
LCZ-696 reduced inflammation and cytokine expression involved in doxorubicin-mediated cardiotoxicity, improving cardiac functions.