bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11432: The Impact of Regional Adipose Tissue Deposition on Physical Activity in Heart Failure with Preserved Ejection Fraction
Authors: Koepp Katlyn , Quicksall Zachary S , Reddy Yogesh , Obokata Masaru , Sorimachi Hidemi , Verbrugge Frederik , Egbe Alexander C , Bruhn Eric , Carter Rickey , Borlaug Barry A , Olson Thomas P
Published: March 2022

Introduction:
Obesity is common in heart failure with preserved ejection fraction (HFpEF) and is directly linked with lower levels of physical activity (PA). Visceral adiposity (VAT) is more common in HFpEF than controls and may play a role in its pathogenesis, characterized by impaired exercise capacity (peak VO
2
). The direct relationship between VAT and PA in HFpEF is unknown.

Hypothesis:
Compared to controls, HFpEF patients will have excess regional adiposity (VAT, subcutaneous (SAT), and intramuscular (IMAT)), and these fat depots will be associated with lower levels of chronic physical activity.

Methods:
HFpEF patients (n=51; age 70±9) and non-HFpEF controls (n=49; age 65±5) prospectively underwent body composition measurement by dual-energy x-ray absorptiometry and magnetic resonance imaging. Peak VO
2
was measured by standard cardiopulmonary exercise testing. PA was monitored continuously via accelerometry over two weeks. Data were binned in arbitrary accelerometry units, averaged and stored in 30-second epochs (counts per epoch, CPE). Models were adjusted for age, sex, and ideal body weight.

Results:
HFpEF were less active overall (3.15±0.80 vs 3.59±0.73 CPE), had less moderate intensity PA (10.13±0.04 vs 10.15±0.03 CPE), and less morning (3.83±1.15 vs 4.24±1.09 CPE) and afternoon (3.84± 1.20 vs 4.53± 0.97 CPE) (p<0.05 for all) PA. Patients with HFpEF spent a greater proportion of time sedentary (0.71±0.08 vs 0.67±0.08 CPE) and less time in moderate (0.04±0.03 vs 0.06±0.03 CPE) and vigorous (0.02±0.01 vs 0.03±0.03 CPE) PA (p<0.01 for all). Chronic PA was significantly associated with regional fat depots (VAT β= -0.003, 95% CI: -0.004-0.001; SAT β= -0.003, 95%CI: -0.004-0.001; IMAT β=-0.02, 95% CI: -0.04—0.01) as a combined cohort (p<0.01 for all). Muscle quality (β=0.28, 95%CI: 0.15-0.40), peak VO
2
(β=0.08, 95% CI: 0.03-0.13), and peak watts (β=0.01, 95% CI: -0.004-0.02) were associated with PA in HFpEF only (p≤0.01 for all).

Conclusions:
The amount and pattern of PA differs between HFpEF and controls, as do relationships between regional fat depots and PA, and the relationship of PA and peak VO
2
. Further investigation is needed to better understand the temporality and mechanisms related to the pathophysiology and severity of HFpEF.
Abstract 11436: Trends in Consumer Wearable Devices in a Primary Care Cohort
Authors: Al-alusi Mostafa A , Khurshid Shaan , Wang Xin , Reeder Christopher , Singh Pulkit , Venn Rachael , Pipilas Daniel , Philippakis Anthony A , Ashburner Jeffrey M , Ellinor Patrick T , Singer Daniel E , Atlas Steven J , Foulkes Andrea , Ho Jennifer E , Anderson Christopher D , Batra Puneet , Lubitz Steven A
Published: March 2022

Introduction:
Consumer wearable devices that record data relevant to cardiac health are widely available. However, whether providers find these devices relevant to clinical care, and in which patients, is unknown.

Methods:
We identified mention of wearable devices in provider notes between 2005 and 2020 in an EHR cohort of primary care patients in the Mass General Brigham healthcare system. Outpatient notes containing >250 characters were included. Search terms included “AliveCor,” “Apple Watch,” “Fitbit,” “Garmin,” “smartwatch,” “fitness tracker,” and alternative spellings. Demographics and cardiovascular comorbidities were compared between patients with and without device mentions. Notes with and without device mention were compared with respect to clinic type and diagnosis codes occurring on the same date. Incidence rates for device mention were calculated for each year.

Results:
The final sample comprised 494,254 patients and 27,221,019 notes. The mean age was 49.1 ± 17.0 years, and median follow-up was 6.9 (Q1 2.7, Q3 11.9) years. A total of 8,955 (1.8%) patients had ≥1 note mentioning a device. The proportion of notes mentioning devices increased over time (Figure), with increased incidence of device mention from 0.006 to 7.5 per 1000 person-years between 2005 and 2019. Most patients with device mentions were female (69.4%) and white (86.7%). At the time of first device mention, the mean age was 55.3 ± 14.0 years and 1,183 (13.2%) patients had prevalent atrial fibrillation (AF). Cardiology clinic notes comprised a greater proportion of notes with device mentions versus notes without device mentions (15.7% [5,336] vs 3.7% [996,971], p<0.001). A total of 9.3% (3,160) of notes with device mentions had same-day diagnosis codes for AF, versus 2.7% (730,614) of notes without device mentions (p < 0.001).

Conclusion:
Provider mention of consumer wearable devices in EHR notes has increased over time, and is associated with cardiology clinic notes and diagnosis codes for AF.
Abstract 11438: Texture Analysis Identifies Differences in Cardiac Magnetic Resonance T1 Maps of Pediatric Heart Transplant Patients with Rejection
Authors: Patel Devika , Mandell Jason , Cross Russell , Hamann Karin , Rossi Christopher , Kanter Joshua , Berger John T , Olivieri Laura , Doshi Ashish
Published: March 2022

Introduction:
Graft rejection is a significant contributor to morbidity and mortality in pediatric heart transplant recipients, despite surveillance by endomyocardial biopsy (EMB). Cardiac Magnetic Resonance (CMR) T1 mapping has shown potential for noninvasive diagnosis of rejection. However, variability in normative T1 values across field strengths, vendors, and individual scanners limits the utility of absolute T1 values to diagnose rejection across institutions. Texture analysis is an emerging method for quantifying spatial distribution of relative voxel intensities rather than using the absolute voxel intensities themselves and may serve as an additional method for evaluating T1 maps.

Hypothesis:
We hypothesized that T1 maps from patients with rejection would exhibit differences in texture features from patients without rejection.

Methods:
This study included 19 cases from 17 pediatric transplant patients (mean age 11.8 ± 5 year, graft age 5.9 ± 4.7 years, 41% female) who underwent CMR imaging and EMB. 8 short axis slices of breath-held T1 mapping using Modified Look-Locker Inversion (MOLLI) recovery on 1.5T Siemens scanner were obtained. Left ventricular myocardium was semiautomatically segmented from T1 maps, excluding the blood pool and epicardial myocardium. Image texture analysis was performed on a single mid-ventricular slice from each case. Rejection was defined as acute cellular rejection (biopsy grade 1R or higher) or negative biopsy with decreased function requiring treatment. T-test analysis was performed to compare differences in texture analysis between patients with and without rejection.

Results:
Analysis of T1 maps showed differences (p-value ≤ 0.10) between patients with and without rejection in texture features of energy (0.062 ± 0.012 vs 0.091 ± 0.051), entropy (4.59 ± 0.23 vs 4.23 ± 0.60), and variance (0.031 ± 0.005 vs 0.025 ± 0.009).

Discussion:
In this small pilot study, texture analysis identified differences in tissue character between patients with and without graft rejection. Evaluation of tissue character via texture analysis may provide an additional method for diagnosis of rejection, given the variability in normative T1 values across institutions.
Abstract 11439: CD47 Functionalization of Bare Metal Stents Reduces In-Stent Restenosis in Hypercholesterolemic Rabbits
Authors: Inamdar Vaishali , Zviman Menekhem , Bratinov George , Fitzpatrick Emmett , Gardiner Kristin , Levy Robert , Stachelek Stanley J , Fishbein Ilia
Published: March 2022

Background:
Inflammatory mechanisms, which can be affected by altered metabolic profiles such as hypercholesterolemia (HC), contribute to the pathophysiology of in-stent restenosis (ISR). CD47 is a transmembrane protein that is known to inhibit immune cell and platelet activation. Previously in a rat model, we showed that immobilizing peptide sequences of CD47 (pepCD47) to stainless steel (SS) stent surfaces decreased platelet and leukocyte association, and significantly reduced ISR. In these current studies, we use HC rabbits to test the
hypothesis
that the pepCD47-modified stents will reduce ISR in a pro-atherogenic phenotype.

Methods:
PepCD47 was attached to SS using polybisphosphonate coordination chemistry and pyridyldithio/thiol conjugation. Bare metal (BM) and pepCD47 SS foils (n=6) were exposed to anticoagulated blood from normocholesterolemic (NC) or HC rabbits for 1 hr. The relative abundance of the surface-associated cells was determined fluorimetrically. Rabbits (n=4) were fed a HC diet for 4 weeks prior to placing BMS or pepCD47 stents bilaterally in the iliac locations. The diet was continued until sacrifice (4 weeks). After chemical dissolution of the stent struts, the segments were paraffin embedded, sectioned, stained and assessed morphometrically. The prevalence of peri-strut macrophages was determined by immunohistochemistry (IHC) as a percentage of a strut circumference infiltrated with macrophages.

Results:
An 8% decrease of platelet and leukocyte attachment to a pepCD47-derivatized SS compared to BM foils (p=NS) was observed with NC blood, while a significant 35% decrease of cell attachment (p<0.002) was found between the pepCD47 and BM foils exposed to HC rabbit blood. Lumen area increased (25%) whereas the neointimal area, % stenosis and neointima to media ratio decreased (23%, 25%, and 25% p=0.04, respectively) in the arteries treated with pepCD47 stents compared to BMS controls. IHC showed a 34% reduction of macrophage infiltration in the peri-strut area (p=0.048).

Conclusion:
These results are the first to show the anti-restenotic properties of pepCD47 modified stents in a translational HC rabbit model. The anti-restenotic effects are likely due to CD47-mediated reduction of stent-triggered inflammation.
Abstract 11448: Time from Blood Draw to Multiple Electrode Aggregometry and Association with On-Clopidogrel Platelet Reactivity
Authors: Hesselbarth David , Gjermeni Diona , Szabo Sofia , Vetter Hannah , Anfang Viktoria , Diehl Philipp , Moser Martin , Bode Christoph , Olivier Christoph
Published: March 2022

Background:
Guidelines consider platelet function testing to guide dual antiplatelet therapy (DAPT) de-escalation in selected patients. On-clopidogrel platelet reactivity as measured by multiple electrode aggregometry (MEA) varies according to patients′ characteristics but may also depend on pre-analytic factors.

Purpose:
This study aimed to analyze the association of time from blood draw to MEA results in patients undergoing percutaneous coronary intervention (PCI).

Methods:
In this observational single center cohort study, in patients undergoing PCI, all patients received DAPT with ASA and clopidogrel. Platelet aggregation (aggregation units, U) was quantified by MEA (Multiplate Analyzer) after stimulation with adenosine diphosphate (ADP; 6.4 μM in patients treated with ASA and clopidogrel following PCI. High on-clopidogrel platelet aggregation (HPR) was defined as ≥46 U. The manufacturer recommends performing the analysis within 30-180 min after blood draw. Thus, patients were grouped according to the time from blood draw to MEA: 1) 30-180 min 2) <30 min 3) >180 min.

Results:
Platelet function of 273 patients with coronary artery disease undergoing PCI with DAPT were analyzed. The median age was 72 years (interquartile range, IQR 62-79) and 179 (66%) were male. Median ADP-induced aggregation was 25 (IQR 18-36) U. HPR was observed in 34 patients (12%). Median time to MEA was 65 (IQR 45-113) min and 245 measurements (90%) were performed within 30-180 min as recommend by the manufacturer of the aggregometer. Compared with measurements performed within the manufacturers′ recommendations (25 [IQR 18-36] U, median ADP-induced aggregation was not significantly different if performed outside these recommendations (<30min: 24 [IQR 20-28] U, p=0.54; >180min: 25 [IQR 21-40] U, p=0.31). For those analyzed within 30-180 min from blood draw, no relevant correlation of time from blood draw to MEA with ADP-induced platelet aggregation was observed (r= - 0.04; p=0.51).

Conclusion:
In patients undergoing percutaneous coronary intervention and treated with dual antiplatelet therapy, the time from blood draw to multiple electrode aggregometry does not correlate with ADP-induced aggregation.
Abstract 11454: Unsupervised Machine Learning Identified High-Risk Phenotype in Heart Failure Patients with Syncope
Authors: Chao Chiehju , Rattanawong Pattara , Sriramoju Anil , Tagle-Cornell Maria Cecilia , Koepke Laura , KoKo Nway , Fatunde Olubadewa , Shanbhag Anusha , Barry Timothy , Wu Han-Lun , Shen Win K
Published: March 2022

Introduction:
Syncope was reported to be associated with sudden cardiac death in heart failure patients regardless of the etiology of syncope. We attempted to use unsupervised machine learning to identify the prognostically distinct phenotypes in a large population of heart failure patients presenting with syncope.

Hypothesis:
Unsupervised machine learning can identify prognostically distinct phenotypes in a large population of heart failure patients presenting with syncope.

Methods:
Patients with a diagnosis of systolic or diastolic heart failure and syncope at Mayo Clinic sites were identified for baseline and follow-up data. Variables with ≥ 20% missing data were excluded; a total of 57 variables were used for k-means clustering analysis. Patients were grouped according to 4 distinct k-means determined clusters for statistical analysis.

Results:
A total of 3,557 patients with proper follow-up and echocardiography data were included in the final analysis. The median follow-up duration was 36.3 months, and 2908 (81.7%) patients died. Cluster 2 (n= 680) was identified as the cluster with the highest mortality (92%), which contained patients with high proportions of cardiovascular comorbidities, especially chronic kidney disease. The Kaplan-Meier survival curves are shown in Figure 1. In multivariate Cox regression analysis, the presence of CKD independently predicts mortality (HR 1.62, 95%CI 1.50-1.76, p <0.0001) after adjusting for age and sex.

Conclusions:
Unsupervised machine learning identified patients with CKD, CAD and DM are high-risk phenotypes in heart failure patients with syncope, and can be used to guide future studies in this highly heterogeneous, unexplored population.
Abstract 11456: Elevated Lipoprotein(a) is Associated with Statin Resistance
Authors: Ma Gary S , Schwartz Gregory G , Olsson Anders G , Willeit Peter , Tsimikas Sotirios , Yeang Calvin
Published: March 2022

Introduction:
LDL-C reduction by statins is the mainstay pharmacologic strategy for ASCVD risk reduction. Despite adherence, some patients fail to achieve LDL-C goals, a phenomenon known as statin resistance. Current LDL-C assays include cholesterol content on both lipoprotein(a) [Lp(a)] and LDL particles. Because statins do not lower Lp(a), Lp(a)-cholesterol may represent a statin insensitive pool within LDL-C.

Hypothesis:
Elevated Lp(a) contributes to statin resistance in patients treated with high-intensity statin therapy.

Methods:
A secondary analysis was performed on 2338 patients from the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial, randomized to receive atorvastatin 80mg or placebo; baseline and week 16 lipid parameters were analyzed.

Results:
In the atorvastatin group (n = 1092), mean (SD) baseline LDL-C, absolute LDL-C reduction, median percent LDL-C change from baseline (IQR), and Lp(a) were 123.8 (33.5) mg/dL, 52.2 (36.7) mg/dL, -47.6% (-59.1- -29.9%), and 10.6 (5.1-29.1) mg/dL, respectively. Median (IQR) baseline Lp(a) was higher [12.1 (5.9-38.1) vs 9.2 (4.4-22.4) mg/dL, p < 0.001] in patients with attenuated percent LDL-C reduction compared to group median. The median percent LDL-C reduction on atorvastatin was 42.3% (24.3-52.5%) in patients with baseline Lp(a) between 50 - 99 mg/dL, and 32.6% (11.5-43.7%) with Lp(a) > 100 mg/dL prevalent in ~10% of the population, both significantly attenuated compared to patients with Lp(a) <30 mg/dL (50.4% [33.3-61.1%]), p < 0.001. An LDL-C target of 70 mg/dL or less was achieved in 62.3% of patients with baseline Lp(a) <30 mg/dL, compared to 55.2%, 43.3%, and 24.1% of those with Lp(a) 30 - 49 mg/dL, 50 - 99 mg/dL, and > 100 mg/dL (p < 0.001), respectively [Figure 1].

Conclusions:
Elevated Lp(a) is associated with statin resistance and may identify patients who require additional or more potent lipid lowering therapies to achieve LDL-C goals.
Abstract 11457: Overexpression of Thioredoxin-1 Ameliorates the Progression of Diabetic Cardiomyopathy by Preservation of Cardiac Function, Increased Survivability and Decreased Fibrosis in Aged Transgenic Mice
Authors: Lim Sue-Ting , Pradeep Seetur R , Thirunavukkarasu Mahesh , Swaminathan Santosh , Accorsi Diego , Palesty J Alexander , Maulik Nilanjana
Published: March 2022

Introduction:
Increased production of reactive oxygen species contributes to the etiology of diabetic complications. It acts as an intracellular antioxidant by scavenging reactive oxygen species (ROS) and protect the cells against oxidative stress and cell death.

Hypothesis:
To determine the long-term effect of streptozotocin (STZ) induced type 1 diabetes on aging Trx-1 transgenic mice related to survivability, heart function, fibrosis, and apoptosis up to 180 days (d) compared to its corresponding wild-type (WT C57Bl/6J).

Method:
WT and Trx-1 overexpressed mice (Trx-1
Tg/+
) (8-12 weeks old) were injected with STZ (i.p. 50mg/kg.body weight(bw)-male; 75mg/kg.bw-female for 5 consecutive days) for induction of diabetes (Dia). Fasting blood sugar level (FBS) was measured 30d after the final injection, and FBS >220mg/dL is used as the cut-off for diabetes. Echocardiography, Survival, FBS measurements were performed on 30, 60, 90, 120, 150, and 180d. Immunohistochemistry was performed on heart tissues (30, 90, and 180d).

Results:
Dia-Trx-1
Tg/+
mice maintained EF at 60d (61.14±2.3%), 120d (56.1±1.94%) and 180d (60.8±4.3%), when compared to 30d (64.4±1.94%) representing preserved cardiac functions. On the other hand, Dia-WT mice show significant progressive depression of EF at 60d (53.8±1.9%), 120d (48.8±2.1%), and 180d (48.9±1.5%), (p<0.05) when compared to 30d (68.4±6.1%) Dia-WT. Moreover, Dia-Trx-1
Tg/+
mice show significantly higher EF than their corresponding Dia-WT counterparts at each time point measured after diabetic induction (n=8-12, p<0.05). Dia-Trx-1
Tg/+
mice (n=71) also exhibited increased survival rate over Dia-WT (n=47) counterparts with a median survival of 150 days compared to 60 days (Log Rank test: p=0.004). Dia-Trx-1
Tg/+
mice also showed a significant reduction in cardiac fibrosis (4.18±1.08% vs. 17.5±5.1%; p=0.03, n=4) and TUNEL positive cells (3.81±1.49 vs. 7.66±1.46; p=0.03, n=4) when compared to their counterpart (Dia-WT) after 180d of diabetes.

Conclusion:
These results show that Trx-1
Tg/+
mice preserved cardiac functions, increased survival, decreased apoptosis and fibrosis up to 180d under diabetic conditions, and hence suggesting Trx-1 based treatment strategy could prevent heart failure in aging.
Abstract 11459: Mitochondrial Metabolites Predict Cardiovascular Outcomes and Heart Failure in Individuals with Type 2 Diabetes Mellitus: An Exscel Biomarker Substudy
Authors: Regan Jessica A , Mentz Robert J , Nguyen Maggie , Green Jennifer , Truby Lauren , Ilkayeva Olga , Buse John , Sourij Harald , Sjostrom David , Sattar Naveed , Hernandez Adrian F , Holman Rury , Shah Svati H
Published: March 2022

Introduction:
Metabolic substrate utilization is central to metabolic disease. Metabolic pathways linking type 2 diabetes (T2D) to major adverse cardiac events (MACE) and heart failure (HF) remain poorly understood and T2D drug effects on metabolite biomarkers could improve biological understanding and support precision medicine approaches.

Hypothesis:
Circulating metabolites characterizing mitochondrial dysfunction are predictors for MACE and hospitalization for HF (hHF), and are improved with exenatide.

Methods:
We performed targeted mass-spectrometry profiling of 60 metabolites on baseline and 12-month plasma samples from 978 participants from EXSCEL, a randomized trial of the GLP-1 receptor agonist, exenatide. Principal components analysis (PCA) was used; resultant metabolite factors were analyzed with univariate and multivariable logistic regression (adjusted for history of HF, coronary artery disease, BMI, HbA
1c
, eGFR, blood pressure) for association with MACE (CV death, non-fatal MI or stroke) and hHF. Results were validated in participants from TECOS, a randomized trial of the DPP-4 inhibitor sitagliptin. Metabolite changes by treatment arm were tested.

Results:
Of 12 PCA metabolite factors, two nominally associated with MACE in both univariate and multivariable models and two associated with hHF in univariate, but not multivariable models (
Table
). Individual metabolites remained associated with MACE in multivariable models and with hHF in univariate models. Similar results were seen in the TECOS validation cohort. Individual metabolites decreased to a greater extent in exenatide randomized individuals compared with placebo.

Conclusions:
Metabolites reporting on dysregulated mitochondrial fatty acid oxidation are increased in individuals with T2D who experience MACE. These biomarkers may improve CV risk prediction models, appear to be beneficially modified by exenatide, and highlight emerging risk mechanisms.
Abstract 11460: Antibodies to Citrullinated Protein Antigens Are Associated with Inflammatory Markers in a Multi-Ethnic Community-Living Population: The Multi-Ethnic Study of Atherosclerosis
Authors: Begur Maedha , Schenk Simon , Criqui Michael H , Corr Maripat P , Robinson William , Hughes-austin Jan M
Published: March 2022

Introduction:
Individuals with antibodies to citrullinated protein antigens (ACPA) have higher risk for cardiovascular disease (CVD). Cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα), have been identified as pro-atherogenic. While the association between ACPA and cytokines has been studied in rheumatoid diseases, it has not been studied in the general population. We hypothesized that ACPA are positively associated with IL-6, c-reactive protein (CRP), and TNFα; and that gender and race/ethnicity modify this association.

Methods:
In 1743 Multi-Ethnic Study of Atherosclerosis participants without clinical CVD, we evaluated the association between number of ACPA and IL-6, CRP, and TNFα using multivariable linear regression. We adjusted for demographics, CVD risk factors, and medication use; and tested for interactions by gender and race/ethnicity. ACPA was measured as an array of 38 individual ACPA with the cut-off for positivity for each antibody set at the 95
th
percentile. CRP, IL-6, and TNFα were measured in serum of fasting participants; values were log-transformed to reduce skewness.

Results:
Average age was 64.7±9.7 years; 50% were women, 40% Caucasian, 13% Chinese American, 21% African American, and 26% Hispanic American. Approximately 31% (537) had at least one positive ACPA. In the fully adjusted analysis, each additional ACPA was associated with 0.3±0.1% (p=0.005) higher serum IL-6 and 0.6±0.2% (p=0.007) higher CRP. ACPA was not associated with TNFα. Associations of ACPA with CRP were modified by gender (p
interaction
= 0.000) and race/ethnicity (p
interaction
= 0.000). In men, each additional ACPA was associated with 0.4±0.1% (p=0.015) higher IL-6 and 0.7±0.2% (p=0.007) higher CRP. In women, this association was not observed. In Hispanic participants, each additional ACPA was associated with 0.3±0.2% (p=0.049) higher IL-6 and 0.8±0.3% (p=0.010) higher CRP; in Caucasian participants, each additional ACPA was associated with 0.4±0.2% (p=0.014) higher IL-6 and 0.6±0.3% (p=0.026) higher CRP. This association was not observed in Chinese or African American participants.

Conclusion:
In a multi-ethnic community-dwelling population, higher number of ACPA was associated with higher IL-6 and CRP.
Abstract 11461: Women with Coronary Artery Disease and Higher Cardiorespiratory Fitness Have Lower Coronary Artery Calcium Scores
Authors: Chedid Georges , Malik Abdulaziz , Welty Francine K
Published: March 2022

Introduction:
Higher coronary artery calcium (CAC) scores have been associated with increased cardiovascular (CVD) events and mortality. Women develop coronary artery disease (CAD) on average 10-15 years older than men and have worse outcomes than men when CVD events occur. The effect of exercise capacity on CAC scores in women with CAD is unclear.

Objective:
To determine if exercise capacity is predictive of CAC scores in men and women with CAD.

Methods:
A total of 203 men and 38 women with known CAD had CAC scores measured using noncontrast multidetector coronary tomography. All subjects underwent maximal exercise treadmill testing with calculation of metabolic equivalents of task (METs) achieved as a measure of cardiorespiratory fitness.

Results:
Mean (SD) age was not different in men and women: 62.7 (7.9) and 64.4 (6.8) years, P=0.239, respectively. CAC scores were significantly lower in women compared to men: median [IQR]: 114.0 [27.5, 321.0] Agatston units vs 535.3 [182.9, 1367.4] respectively, (P<0.001) and were lower in women than men at any given age (Fig 1A). Female CAC scores did not equal those of men until women were 20 years older (Fig 1A). After adjustment for age, METs were associated with CAC scores in both men and women (Fig 1B). However, after multivariate adjustment for age, LDL-cholesterol, waist circumference, diabetes status and hypertension,, METs remained an independent predictor of CAC score in women (P=0.011) but not in men (P=0.223).

Conclusions:
Despite having known CAD, female CAC scores did not equal those of men until women were 20 years older. The independent association of METs with CAC score in women supports counseling women to exercise to maximize their cardiorespiratory fitness to minimize CAC scores. Since higher CAC scores predict adverse CVD events and mortality, lower CAC scores should protect women from development of CVD events and possibly lower their worse outcome.
Abstract 11462: A Surprising Role of TNIK in Regulating Endothelial Interferon Signaling and Activation
Authors: Dominic Abishai , Abe Jun-ichi , Le Nhat-Tu
Published: March 2022

Background:
Endothelial cells (ECs) predominantly govern vascular tone and homeostasis. Activation of ECs is the central pathophysiological process in the initiation of atherosclerosis (AS). Interferon signaling (IFN Type I and II) is activated in ECs under inflammatory conditions such as systemic lupus erythematosus and is implicated in EC activation. Yet, the underlying mechanisms are still unknown. Through RNA sequencing and pathway analysis we have identified, TNIK, a Ste20 family of MAP kinases (MAP4K) to regulate IFN signaling in ECs. Our study is the first to report the role and function of TNIK in IFN and EC activation.

Hypothesis:
TNIK regulates IFNs through focal adhesion kinase (FAK) mediated STAT signaling in EC activation (Fig 1A).

Methods:
Cultured human aortic endothelial cells (HAECs) were treated with control or TNIK-targeted siRNA. Later cells were subjected to static, laminar or disturbed flow conditions. Total RNA was isolated and then RNA-sequencing was performed. The differential expression data were analyzed using CLC genomics and Ingenuity Pathway Analysis (IPA). Western blotting and qRT-PCR were performed to validate STAT activation and interferon-stimulated genes (ISGs)

Results:
We found >450 genes differentially expressed in siTNIK vs siCTRL treated ECs (fold change>2, FDR<0.05). IPA revealed that under static (ST) and disturbed flow (DF) conditions TNIK depletion led to inhibition IFN (-log P-value >11) and upregulation of eukaryotic transcription elongation factor signaling (eIF2, -log P-value >7) (Fig 1B, C). In addition, under DF, TNIK depletion led to downregulation of hypercytokinemia/hyperchemokinemia (-log P-value >8, Fig 1B). Validation through western blotting and qRT-PCR (Fig 1D, E) confirmed that TNIK regulates FAK and STAT phosphorylation and IFN stimulated gene targets.

Conclusions:
Our study elucidates the unique role of TNIK in regulating FAK-STAT mediated IFN signaling and subsequently EC activation.
Abstract 11480: Machine Learning Discovers a Prediction Model for Contractile Function of Circulatory Death Donor Hearts Based on Microvascular Flow Shifts During Ex-Situ Hypothermic Cardioplegic Machine Perfusion
Authors: Saemann Lars , Kohl Matthias , Veres Gábor , Korkmaz-Icoez Sevil , Karck Matthias , Simm Andreas , Wenzel Folker , Szabo Gabor
Published: March 2022

Introduction:
Hearts, procured from circulatory death donors (DCD) are predominantly resuscitated and maintained ex-vivo by machine perfusion (MP) with warm donor blood. Currently, DCD-heart function is evaluated by the course of lactate and by visual inspection. We have shown in an experimental research series that MP with the cardioplegic, crystalloid Custodiol-N solution is superior to blood perfusion to maintain DCD-hearts. However, no method has been developed yet to predict contractile function of DCD-hearts after continuous cardioplegic MP.

Hypothesis:
We hypothesize that the shift of microvascular flow during continuous MP with a cardioplegic preservation solution predicts contractile function of DCD-hearts.

Methods:
In a pig model, DCD-hearts were harvested and maintained by MP with hypothermic, oxygenated Custodiol-N solution for 4 h while myocardial microvascular flow (LDF) was measured by Laser-Doppler-Flow technology in the left ventricular wall. Subsequently, hearts were perfused with blood for 2 h and left ventricular contractility was measured with a balloon catheter after 30 and 120 min. Various novel parameters which represent the LDF-shift, were computed. Bivariate prediction models based on two combined LDF-shift parameters were identified based on machine learning algorithms.

Results:
Highest r
2
for ESP was 0.77 (p=0.027), for dp/dt
max
was 0.73 (p= 0.037) and for dp/dt
min
was 0.75 (p=0.032) after 30 min of reperfusion. After 120 min of reperfusion, highest r
2
for ESP was 0.81 (p=0.016), for dp/dt
max
was 0.90 (p=0.004) and for dp/dt
min
0.58 (p=0.115). Identical prediction models were identified for dp/dt
max
and for dp/dt
min
at both time points of reperfusion. Lactate remained constant during MP and therefore was unsuitable for prediction.

Conclusions:
Contractile function of DCD-hearts after continuous MP with a cardioplegic preservation solution can be predicted by the shift of LDF during MP.
Abstract 11481: Non-Invasive Electrocardiographic Mapping of the Human Heart Through a Novel 'Cardiac Magnetic Resonance-Electrocardiographic Imaging' Solution for High Throughput Use
Authors: Webber Matthew , Joy George , falconer Debbie , Tao Xuyuan , Pierce Iain , Moon James , Hughes Alun , Lambiase Pier , Rudy Yoram , Orini Michele , Captur Gabriella
Published: March 2022

Background:
Electrocardiographic imaging (ECGI) non-invasively maps the heart’s electrical activity through multiple leads on the body surface. Cardiologists need a safe, quick, affordable and re-usable ECGI method to apply to patients undergoing cardiovascular magnetic resonance (CMR), but current solutions are not suitable for high-throughput use. We developed a CMR-ECGI vest for high-throughput use and report the first
in vivo
results.

Methods:
We designed and fabricated the CMR-ECGI vest from cotton, containing 256 square (2x2cm) dry textile electrodes each tagged with a localisation marker (
Fig 1
). Body surface potentials were recorded and co-registered with heart-torso geometries obtained from CMR (
Fig 2
). Epicardial unipolar potentials were reconstructed using state-of-the-art ECGI algorithms (YR Lab) and local activation and repolarization times were computed using standard methods.

Results:
Ten healthy volunteers with normal resting ECGs were recruited (34±10years; 60% male). A recumbent 5-minute ECGI recording was performed (preparation time ~15 minutes for montage and doffing). 3 Tesla CMR provided baseline parameters (left ventricular ejection fraction [LVEF] 75±5%, right ventricular [RV] EF 57±5%, native T1 1275±23ms, T2 42±1ms) and showed no clinically significant late gadolinium enhancement. ECGI showed that the sites of earliest and latest activation were the basal RV (
Fig 3A
) and basal-lateral LV respectively (
Fig 3B
). Total duration of epicardial activation and repolarization was 73.3±8.9ms and 195±35.2ms, respectively. These epicardial activation patterns in health are in line with previously described ECGI data.

Conclusions:
We have developed a re-usable and high-throughput CMR-ECGI solution that is safe and well-tolerated
in vivo
. This technology is now available for large-scale clinical research use to provide deeper insights into the pathophysiology of arrhythmogenesis, through seamless integration with CMR.
Abstract 11484: Subclinical Renal Impairment and Inflammation in Cognitive Frailty in Older Adults (Tanushimaru Cohort Study)
Authors: Morikawa Nagisa , Adachi Hisashi , Enomoto Mika , Fukami Ako , Sakaue Akiko , Maki Yamamoto , Sato Hiromi , Fukumoto Yoshihiro
Published: March 2022

Introduction:
Sarcopenia or slow gait speed (SGS) strongly interact with cognitive impairment (CI), that is cognitive frailty, possibly because of reinforcing common underlying pathophysiologies. We previously reported that renal impairment (RI) was associated with CI and inflammation is said to be important in the association. Associations of RI and inflammation with cognitive frailty has been understudied.

Hypothesis:
RI and inflammation are associated with cognitive frailty.

Methods:
We conducted a cross-sectional study in 1368 population-based sample (mean age: 68.7±11.3 years, men:40.5%) of Tanushimaru, Japan in 2018. We measured urinary albumin-creatinine ratio (ACR) and high-sensitivity C-reactive protein (hsCRP) and assessed cognitive function by Mini-Mental State Examination (MMSE) and 5m walking time. RI was defined as ACR ≧30mg/dL and inflammation was defined as higher than median log-hsCRP. MMSE scores ≦27 out of 30-points was classified as CI and SGS was defined as <1m/s. Multivariable logistic regression analyses were performed to examine an association of RI and inflammation with CI and SGS.

Results:
Prevalence of CI and SGS were 29.3% and 44.3%, respectively. SGS was more prevalent in participants with CI than those with normal cognition (64.4% vs 35.7%, p<0.0001). 15% of participants had RI and they had higher serum hsCRP than those with normal renal function (0.067mg/dL vs 0.047mg/dL, p<0.0001). Higher log-ACR was significantly associated with CI and SGS, while higher log-hsCRP was associated with only SGS. Age, sex-adjusted odds ratio (OR) of RI was 1.85 (95% confidence interval (CI): 1.19-2.87) in the group with CI and SGS compared to the group with normal cognition and gait speed, while OR of inflammation was 1.52 (95%CI: 1.10-2.10) in the group with CI and SGS. (Fig 1).

Conclusions:
RI and inflammation were associated with cognitive frailty, especially inflammation was strongly associated with frailty.
Abstract 11487: Individualizing the Cardiovascular Benefits of Intensive Blood Pressure Reduction Using Computational Phenomaps of the SPRINT and ACCORD Trials
Authors: Oikonomou Evangelos K , Suchard Marc , Khera Rohan
Published: March 2022

Introduction:
Intensive systolic blood pressure (SBP) control reduces major adverse cardiovascular events (MACE) in patients without type 2 diabetes mellitus (T2DM). However, these benefits are less clear in T2DM. We evaluated an application of machine learning to clinical trials of patients without and with T2DM in assessing a personalized cardiovascular benefit of intensive SBP control.

Methods:
In SPRINT, a trial of intensive (n=4678, SBP<120 mmHg) versus standard (n=4683, SBP<140 mmHg) SBP control in 9361 patients without T2DM, we created a topological representation of the trial patients using 59 baseline variables (trial phenomaps). Within each patient’s 5% topological neighborhood, we calculated hazard ratios (HR) for recurrent MACE (cardiovascular death, acute coronary syndrome, stroke, acute decompensated heart failure). We trained an extreme gradient boosting algorithm to predict the personalized effects of intensive SBP control using features linked to topological benefit. We then tested this machine learning tool in the ACCORD BP trial of patients with T2DM (n=2362 & 2371 in the intensive and standard arms respectively).

Results:
In SPRINT (age 68±9 years, 36% women) there were a total of 1046 recurrent MACE endpoints. The median individual patient HR was 0.58 [IQR, 0.38-0.82] (
A
). We developed a 10-variable tool in SPRINT (
B
) and subsequently tested in ACCORD BP (age 63±7 years, 48% women) where it identified individual patients with a higher benefit with intensive vs standard SBP control (adj. HR for time-to-MACE 0.77 [95% CI 0.61-0.98] in individuals with above median predicted benefit [high responders] (
C
) vs 0.97 [95% CI 0.77-1.23] (
D
) for below median predicted benefit [low responders]).

Conclusions:
We present a clinical trial-based, machine learning tool that identifies an individual’s personalized benefit from intensive versus standard SBP goals in patients with and without T2DM and may be used to guide clinical decision-making.
Abstract 11490: Coronary Computed Tomography Angiography with Fractional Flow Reserve Outperforms Single-Photon Emission Tomography Myocardial Perfusion Imaging in the Observation Unit
Authors: Patel Sahishnu , Snippen Janessa , Soma David , Smith Aaron A , Sharma Abhinav
Published: March 2022

Introduction:
Coronary Computed Tomography Angiography (CCTA) and SPECT myocardial perfusion imaging (SPECT-MPI) are equally safe in evaluating patients presenting to the emergency department with acute chest pain. However, no study has compared the use of CCTA with Fractional Flow Reserve (FFR-CT) to SPECT-MPI in a chest pain observation unit (OU). We compared the performance of CCTA (with FFR-CT as needed) to SPECT-MPI for change in coronary artery disease (CAD) specific treatment (statins, antianginals, antiplatelets, and coronary revascularization) as well its impact on length of hospital stay (LOS).

Methods:
In 2020, our institution implemented an algorithm-based protocol in the OU to select patients appropriate for CCTA with explicit guidelines for management based on the results. We performed a retrospective analysis of 105 patients (52 SPECT-MPI patients from the period prior to initiation of the OU CCTA protocol who met criteria for CCTA, and 53 CCTA patients after CCTA protocol initiation). We performed two-tailed t-tests and chi-squared analyses to compare changes in treatment and LOS in both groups.

Results:
Patients in the CCTA group were younger (61 vs. 67 years, p=0.007), but there were no significant differences in CAD risk factors amongst the two groups. CCTA led to significant increase in statin, antianginal, and antiplatelet therapies, cardiac catheterization and revascularization within 6 months. There was no increase in LOS. Finally, CCTA did not increase acute kidney injury at follow up (Table 1).

Conclusion:
CCTA with FFR-CT significantly improved patient care by increasing appropriate preventative CAD treatment compared to SPECT-MPI while increasing the rate of revascularization without compromising length of stay or kidney function. In conclusion, protocol-based use of CCTA with FFR-CT is a more effective tool when compared to SPECT-MPI for chest pain patients admitted to the OU.
Abstract 11492: Relationship Between Coronary Artery Calcium and Thoracic Spine Bone Mineral Density: The Multi-Ethnic Study of Atherosclerosis
Authors: Manubolu Venkat Sanjay , Mao Song , Kinninger April , Gao Yanlin , Carr Jeffrey , Dailing Christopher , Roy Sion , Budoff Matthew
Published: March 2022

Background:
Traditionally, osteoporosis and coronary artery disease were considered unrelated. Beyond age, these two conditions appear to share common etiologies that are not yet fully understood.

Objective:
We sought to evaluate the relationship between thoracic spine bone mineral density (BMD) and severity of coronary artery calcium (CAC) score.

Methods:
MESA is a cohort study of 6,814 men and women from six U.S. cities between the ages of 45 and 84 years, who were free of clinical CVD. Included participants had thoracic spine BMD and CAC that was assessed by non-contrast chest CT, using methods previously described by Budoff et al 2010. Multivariate regression analysis was performed to examine the association of thoracic spine BMD and CAC score after adjusting for conventional risk factors of atherosclerosis including age, gender, BMI, race/ethnicity, diabetes, hypertension medications, lipid lowering medications, smoking history and family history of CAD.

Results:
Correlation coefficient, r, was -0.29 (p<0.0001), indicating inverse relationship between CAC and BMD. BMD was categorized as normal (T-score>-1), osteopenia (-2.5<T-score=<-1) or osteoporosis (T-score<=-2.5). Prevalence of CAC >0 was 36% in normal group, 49% in the osteopenia group and 68% in the osteoporosis group. In adjusted regression models, the odds of CAC were significantly higher in those with osteoporosis (OR: 1.57 95% CI: 1.31,1.88) p<0.0001 and trending higher in those with osteopenia (OR: 1.15; 95% CI:1.00,1.32) p=0.049. Analysis stratified based on gender, the odds of CAC in men with osteoporosis is higher (OR: 1.61; 95% CI: 1.24,2.09) p=0.0004 compared to women with osteoporosis (OR: 1.48; 95% CI: 1.15,1.90) p=0.002.

Conclusion:
The prevalence of CAC was significantly higher in osteoporosis group compared to normal BMD. There is an inverse relationship between BMD and CAC independent of cardiovascular risk factors.
Abstract 11494: Patient Characteristics, Management and Outcomes of Acute Heart Failure Hospitalizations in Japan
Authors: Kim Jung Hyun , Jiang Jenny , Shen Sophie , Chaudhary Anuj , Setoguchi Soko
Published: March 2022

Introduction:
In Japan, the prevalence of heart failure (HF) was approximately 0.8% in 2005 and is projected to increase. Yet, studies of real-world HF patients are limited. Thus, using a large multi-institutional database, we described in-hospital management and outcome of acute HF hospitalizations.

Methods:
We conducted a retrospective cohort study of adult patients (age ≥18) using the Medical Data Vision (MDV) database in Japan. MDV consists of ~ 35million medical records from > 400 hospitals across all regions in Japan providing data on diagnosis, procedures, pharmacy claims, and laboratory data. Acute HF hospitalizations were defined as primary HF diagnoses + use of intravenous diuretics within 48 hours. We described patient characteristics, in-hospital management, length of stay (LOS), in-hospital death, and 30-day all-cause readmissions. We included published results from AHA’s Get With The Guidelines (GWTG)-HF for benchmarking.

Results:
Table includes results from 120,921 hospitalizations in Japan and GWTG-HF publications. Mean age was higher but weight and BMI were lower in Japan. Laboratory values were similar but Hemoglobin A1c, B-type natriuretic peptide, and creatinine levels were lower in Japan. Mean LOS was 24 in Japan vs.4 in the US but 44% had cardiac rehab during hospitalization. In-hospital mortality was > 3 times higher but the 30-day readmission rate was lower in Japan.

Conclusion:
In a large multi-institutional real-world data of acute HF hospitalizations, compared to published US GWTG-HF data, Japanese patients were older but had less comorbidities. They had longer LOS and lower readmission rates. While hospital death was higher in Japan, this is not directly comparable to the US data due to the large LOS difference. Further studies to understand the reasons for the population and practice differences may generate hypotheses for potential interventions to improve HF outcomes.
Abstract 11496: Increased Pulmonary Microvascular Endothelial Permeability by E-Cigarette Aerosol: The Pathway from Lung to Peripheral Blood Vessels
Authors: Mohammadi Leila , Han Daniel D , Fang Xiaohui , Xu Fengyun , Derakhshandeh Ronak , Hellman Judith , Gotts Jeffrey , Springer Matthew L
Published: March 2022

Background:
We reported that permeability of cultured microvascular endothelial cells is increased by incubation in e-cigarette (e-cig) users’ serum relative to that from smokers or non-users. It is unclear whether this is a direct effect of aerosol chemicals that reach the circulation, or an indirect response mediated by the e-cig users’ pulmonary epithelium.

Hypothesis:
Vaping increases microvascular endothelial permeability indirectly by signaling from alveolar epithelium.

Methods:
E-cig aerosol condensates were derived from e-liquids with and without nicotine (12 mg/mL free base), each containing menthol, vanillin, ethyl maltol, or cinnamaldehyde (2 mg/mL). Cell permeability was measured in human lung microvascular endothelial cells (HMVEC-Ls) using electric cell-substrate impedance sensing. Human Type II lung alveolar epithelial cells (ATII) were grown in serum-free air-liquid interface and exposed to e-cig aerosols with 0, 18, or 36 mg/mL nicotine (free base and salt), or air, 1 h/day for 3 days in an exposure chamber inside a CO
2
incubator.

Results:
Incubation of HMVEC-Ls with 0.3% v/v e-cig aerosol condensates from most e-liquids, with and without nicotine,
decreased
cell permeability (in contrast to the increased permeability that we reported from incubation with e-cig user serum). The exception was menthol + nicotine, which increased permeability (but reduced viability). When HMVEC-Ls were instead incubated with supernatant collected from ATII cells after exposure to e-cig aerosols, permeability was
increased
when supernatants were from exposure to aerosol with 36 mg/ml nicotine salt, but not 36 or 18 mg/mL freebase nicotine. Supernatants from similarly exposed ATII cells contained higher levels of the proinflammatory proteins MCP-1, IL-8, GROα, and MIP-1β when aerosol contained 36 mg/mL freebase nicotine (3/6 wells) or nicotine salt (5/6), but not 18 mg/ml nicotine (0/6).

Conclusion:
HVMEC-L permeability was not directly increased by e-cig aerosol condensate, but was increased by supernatant of alveolar epithelial cells exposed to high-nicotine aerosol, potentially mediated by elevated ATII cytokine production, indicating a potential indirect mechanism by which vaping increases pulmonary microvascular permeability.