bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11357: Sleep Modulates Heartbeat Waveform in Humans During a Predatory Virtual Competition
Authors: Araujo Queiroz Jonathan A , Brandao Daniel S , Ribeiro Sidarta , Barros Allan Kardec
Published: March 2022

Introduction:
Psychological stress modulates cardiac activity as a self-defense mechanism established across animal evolution and known as fight or flight response. However, the fact that our everyday fears differ from the ones that motivated this evolution represent a difficulty to the study of this response in humans. In this work, we are particularly interested in finding morphological cardiac markers that demonstrate the modulation of sleep to the human response of feeling like prey or predator.

Methodology:
Twelve individuals (10 men and 2 women) were recruited in pairs to attend to the laboratory, where they were randomly assigned in two groups: preys and predators. They played for 45 minutes a first person shooter electronic game against each other with close-combat weapons, but the predator had the advantage of being able to use a medium-range shotgun. After the match, they slept for 2 hours, followed by another 45 minutes match. We evaluated the ECG of the first 20 minutes of each of these 3 blocks in windows of 1 minute. We measured each cardiac cycle using variance, then estimated each resulting signal with Shannon entropy.

Result:
We verified that the Shannon entropy applied to the variance of cardiac cycles (H(V)) is larger in preys than in predators during the second game (Figure), with a p-value of 0.028 by the paired Wilcoxon signed-rank test. No statistical differences were found for the first game or sleep blocks.

Conclusion:
We hypothesized that prey and predator cardiac signals have their own characteristics and, therefore, have unique parameters for each of the different blocks. Thus, we believe that this tendency towards a standardization of roles (predator x prey) over time is due to the fact that in the first game, predators and prey are arbitrarily instituted and not biologically established, and that during sleep the memory of game events is consolidated towards their role goals, which modulates heartbeat waveform in the second game.
Abstract 11368: Association of New-Onset Atrial Fibrillation with the Development of Frailty in Older Veterans: A Propensity Matching Study
Authors: Ysea-Hill Otoniel , Fernandez Marlena , Torres Angelica , Pitteloud Marie , Azarbal Jilla , Vargas Gustavo , Cevallos Victor , Rodriguez Alexis P , Ruiz Jorge
Published: March 2022

Introduction:
Atrial fibrillation (AF) is the most common arrhythmia in older adults and has been previously shown to be associated with frailty. There is a lack of data regarding the trajectory of patients with new-onset AF and the development of frailty. The study aim was to determine the association between new-onset atrial fibrillation and the development of frailty over time in an older adult population.

Methods:
This is a retrospective cohort study using propensity score matching (PSM) among Veterans ≥60 years receiving primary care at Miami VAHS between July 2013-June 2014. Socio-demographic and clinical information was obtained from EHR and chart review. Patients were followed from their initial visit until onset of frailty, death, or end of study (June 2020). We assessed baseline and follow-up (FU) frailty using a 30-item VA Frailty Index (VA-FI). Veterans were categorized as non-frail (FI<.21) and frail (FI≥.21). Frail subjects at baseline were excluded. Patients with recent AF diagnosis were matched with controls using PSM with one-to-one nearest neighbor matching without replacement. Matching covariates used to calculate propensity score were age, race, ethnicity, and BMI, with a tolerance level of .01. Veterans were not matched for gender due to very small female population. Using a multivariate cox regression analysis, we determined the risk of developing frailty among patients with AF and controls.

Results:
After PSM, 415 Veterans with AF and 415 controls were included, mean age 78.58 (SD=8.54), 98.07% males, 76.02% Caucasian, 87.47% Non-Hispanic, 53.86% married, and mean BMI 29.21 (SD=6.85). Median FU was 4.05 (IQR=5.09) years. At the end of FU, 274 (34.99%) Veterans developed frailty, of those, patients with AF showed higher rates of frailty (42.89%, n=178), compared to controls (26.08%, n=96), p<.001. In comparison to controls, Veterans with AF were more likely to develop frailty, HR:3.15 (95%CI:2.42-4.10), p<.001.

Conclusions:
In this study, the risk of development of frailty was higher in older Veterans with AF, compared to controls without AF. Careful monitoring of older adults with AF for concurrent morbidity may reduce incident frailty in this population.
Abstract 11370: Track and Trigger System Based on Patient Analytics for Cardiac Arrest Risk Identification
Authors: Zaccagni Hayden , Asfari Ahmed , Hock Kristal M , Huskey Jordan , Tomczak Adam , Butler Evan , Borasino Santiago
Published: March 2022

Introduction:
Cardiac Arrest (CA) is a serious, yet not infrequent complication in the cardiacvascular intensive care unit (CVICU). A recent quality improvement project, Cardiac Arrest Prevention (CAP), showed a decrease in CA by applying a bundle to pre-identified patients at higher risk. Despite this success, CA still occurs among “low” risk patients. Automated risk analytics can offer patient-specific tools to identify risk periods in real time.

Hypothesis:

Methods:
Time series data including vitals and laboratory values were collected (6/2019 - 8/2020). These data were fed into a risk analytics algorithm [Etiometry Inc., Boston, MA] which uses a model of patient physiology to compute risk indices for various physiologic variables. Risk indices examined in this study include IDO2 (likelihood of SvO2 < 40%), HLA (likelihood of lactate > 4 mmol/L), and IVCO2 (likelihood of PaCO2 > 50 mmHg). Various criteria using these risk indices were retrospectively evaluated for categorizing risk status. Once criteria were met a 12-hour “watcher period” was established after a 1-hour assumed response period (figure 1A). CAP status was assigned on a daily basis.

Results:
665 encounters for 484 patients were included. 128 (19.2%) neonatal (<28days) encounters and 537 (80.8%) older patients, for a median age of 7.7 (IQR 2, 46) months. There were a total of 29 CA, of which 11 (38%) were captured by CAP. Figures 1B and 1C show two versions of Track and Trigger Systems (TTS) with their capture of CA events compared against CAP and when combined with CAP. TTSv1 and TTSv2 alone were able to capture 31% and 41% of the CA events. When combined with CAP these numbers increase to 55% and 62% respectively.

Conclusions:
A TTS based on risk indices could provide a patient/pathophysiologic status specific tool to increase our ability to identify patients at risk of CA when used in conjunction with CAP criteria. Further validation of these data in other cohorts and prospective application of the tool is warranted.
Abstract 11373: Computational Approach in Target Discovery and Its Validation: In Search for Inhibitors of Vascular Calcification
Authors: Tanaka Takeshi , Asano Takaharu , Okui Takehito , Kuraoka Shiori , Singh Sasha A , Aikawa Masanori , Aikawa Elena
Published: March 2022

Introduction:
Vascular calcification is cardiovascular disorder which has no therapeutic options. We previously reported that O-octanoyltransferase (CROT) suppression can inhibit calcification
in vivo
and
in vitro
through ameliorating mitochondrial function and fatty acid metabolism.

Hypothesis:
Small molecule compound inhibiting calcification via CROT-associated mechanisms will be excellent candidate for non-invasive treatment of vascular calcification. Here we used a computational approach to identify existing drugs that can inhibit vascular calcification through CROT.

Methods:
For screening of the compounds that reduce CROT expression, we utilized L1000 computational platform, which contains gene expression profiles in various cell lines and substances. We identified and tested 17 compounds in human primary smooth muscle cells (hSMCs) treated with calcification inducing osteogenic media. Niclosamide, an FDA-improved anthelminthic drug, inhibited calcification along with reduced CROT mRNA expression. To validate this compound
in vivo
, oral doses of Niclosamide (0 or 750 ppm admixed with diet) were given to Ldlr-deficient mice fed with high fat diet for 10 weeks. At sacrifice, the aortic calcification was visualized and quantified using optical molecular imaging employing near-infrared calcium tracer (Osteosense680) and then examined by histopathology. Samples from the aorta were collected to perform proteomics analysis at intermittent and terminal time points.

Results:
Molecular imaging and histological analyses of mouse aortas showed significant decrease of calcification after 10 weeks of Niclosamide treatment. Niclosamide improved fatty liver changes with decreased cholesterol levels in the liver along with decreased CROT expression, while plasma total cholesterol levels did not change. Proteomics analysis showed that lipid metabolism and transportation of fatty acid or cholesterol were increased with AMPK or Wnt pathways alteration.

Conclusions:
We identified a small molecule, which can inhibit calcification in vivo and in vitro with reduced CROT expression. Our computational strategy suggests that repurposing of an “old” drug could present novel treatment for vascular calcification.
Abstract 11381: Low Physical Activity is Associated with Poor Prognosis and Proteins Associated with Cardiovascular Disease Among Swedish Heart Failure Patients
Authors: Zaghi Amir , Holmes Hannes , Jujic Amra , Korduner Johan , Molvin John , Bachus Erasmus , Magnusson Martin
Published: March 2022

Introduction:
Several studies suggest that cardiac rehabilitation through physical exercise could reduce heart failure (HF) morbidity and mortality.

Hypothesis:
Here, we aimed to evaluate the association of physical activity with plasma levels of 92 proteins associated with cardiovascular disease (CVD) as well as risk of re-hospitalization and mortality in patients hospitalized for HF.

Methods:
Four-hundred-and-thirty-three patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 842 (IQR, 390-1433) and 155 (IQR, 42-583) days, respectively. Associations between baseline reported physical activity scores, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis. Plasma samples from 295 study participants were analyzed with a proximity extension assay consisting of 92 proteins. Associations between proteins and physical activity were explored using a false discovery rate of 5%, and significant associations were taken forward to multivariate analyses.

Results:
A total of 206 patients (48%) reported moderate and regular physical activity throughout the week. In the fully adjusted Cox regression model, absence of moderate to regular physical activity was associated with increased mortality (HR 1.50; CI95% 1.11-2.03; p=0.008), but not with re-hospitalization risk (HR 1.05; CI95% 0.84-1.32; p=0.684). Physical active time below 1 h throughout the week was associated with increased risk of mortality (HR 1.82; CI95% 1.36-2.43; p<0.001)as well as re-hospitalization irrespective of cause (HR 1.26; CI95% 1.01-1.58; p=0.049). Sedentary lifestyle was associated with elevated plasma levels of 24 proteins, whereof several implicated in myocardial fibrosis, migration and apoptosis.

Conclusions:
Low weekly physical activity is associated with increased risk of mortality and re-hospitalization in hospitalized HF patients, independently of traditional risk factors. Further sedentary lifestyle was associated with elevated levels of several proteins earlier linked to myocardial fibrosis, migration and apoptosis.
Abstract 11388: Multimorbidity Moderates Changes in Peak Oxygen Uptake in Cardiac Rehabilitation Patients
Authors: Chacin Suarez Audry , Medina-inojosa Jose R , Smith Joshua , Taylor Jenna L , Bonikowske Amanda R , Squires Ray W , Thomas Randal J , Olson Thomas P
Published: March 2022

Introduction:
Patients undergoing cardiac rehabilitation (CR) exhibit various degrees of illness severity and high prevalence of chronic conditions (CC). Cardiorespiratory fitness (CRF) is a key predictor of outcomes in patients with cardiovascular disease. Participation in CR is associated with increased CRF, reduced future cardiovascular events, and mortality. Peak oxygen uptake (VO
2
) is the gold-standard method to evaluate CRF; however, the burden of multimorbidity and its impact on CRF improvement has not been extensively studied.

Methods:
We included 618 patients who were ≥ 18 years old and underwent cardiopulmonary exercise testing prior to and after CR at Mayo Clinic. Using the Rochester Epidemiology Project records- linkage system, we assessed the prevalence of 18 CC defined by the US Department of Health and Human Services. To evaluate changes in peak VO
2
in patients with multimorbidity (categorized as ≥6 CC), we created logistic regression models adjusting for age, sex, and baseline peak VO
2
.

Results:
Mean age was 61.5 ± 11.0 years and 75.5% were male. Most patients (81.2%) attended ≥18 CR sessions. Half (50.4%) of patients had at least 6 CC (median 6; range 0-13). Overall, peak VO
2
at baseline was 20.7 ± 6.3 mL/kg per min and the percent change in peak VO
2
following CR was 11.4% ± 21.6%,
Figure 1A
. Multimorbidity was associated with lower improvement in peak VO
2
following CR compared to patients with <6 CC (7.5% vs 11.4%, p=0.0001). Furthermore, across categories of CRF improvement (i.e., 1%, 5%, and 10% percent change in peak VO
2
) lower multimorbidity was associated with a 1.5-2-fold increase in CRF when compared to those with higher multimorbidity (≥6 CC),
Figure 1B
.

Conclusions:
Patients entering CR have a high multimorbidity burden. Our results suggest that multimorbidity in CR patients attenuates improvement in peak VO
2
. Individualized interventions should focus on managing and reducing multimorbidity to minimize the negative impact on CRF improvement.
Abstract 11390: Exercise Intensity, Minutes Walked for Exercise, and Improved Walk Performance in Peripheral Artery Disease: The Lite Randomized Clinical Trial
Authors: Slysz Joshua , Spring Bonnie , Rejeski W. Jack , Manini Todd , Guralnik Jack , Forman Daniel E , Tian Lu , Zhao Lihui , Zhang Dongxue , McDermott Mary M
Published: March 2022

Introduction:
Recent evidence showed that among people with peripheral artery disease (PAD), walking exercise conducted at a pace inducing ischemic leg symptoms improved six-minute walk distance (6MW), while walking exercise conducted at a pace without ischemic leg symptoms had no effect on 6MW. This report describes associations of walking exercise intensity and minutes walked for exercise among participants with PAD with the change in 6MW.

Method & Results:
In the LITE clinical trial, 305 participants with PAD (69±4 years, 181 (59%) Black, 146 (48%) female) were randomized to: 1) walking exercise conducted at a pace without ischemic leg symptoms (low-intensity: LI), 2) walking exercise conducted at a pace eliciting ischemic leg symptoms (high-intensity: HI), or 3) an attention-control group for 12-months. Participants in both exercise groups were asked to walk in or around the home for up to five days/week for up to 50 minutes/session. Measurements of walking intensity and exercise minutes per week were determined individually for each participant in each exercise group using an Accelerometer. Participants in each exercise group were categorized into quartiles according to exercise minutes per week and exercise intensity, respectively (4
th
quartile indicated greatest minutes or intensity). Within the LI and HI groups, more minutes of exercise per week were associated with greater 6MW improvement [(LI: 4
th
vs 1
st
Q: +54 m, 95%CI:16, 92; P=0.018), (HI: 4
th
vs 1
st
Q: +54 m, 95% CI: 12, 96; P=0.010), Table 1]. Within the LI group, but not the HI group, greater exercise intensity was associated with greater 6MW improvement [(LI: 4
th
vs 1
st
Q: +80 m, 95% CI: 31, 128; P=0.002), Table 1].

Conclusion:
While high intensity exercise improves 6MW in PAD, exercising for a greater duration offers greater benefit. Additionally, there is benefit in exercising at low intensity, focusing on increased duration of exercise, if patients are unable to exercise at high intensity.
Abstract 11392: Sex Differences in Fat Deposition: The Relationship with Exercise Capacity and Symptom Severity in a Case-Control Model in Heart Failure with Preserved Ejection Fraction
Authors: Koepp Katlyn , Reddy Yogesh , Obokata Masaru , Sorimachi Hidemi , Verbrugge Frederik , Omote Kazunori , Egbe Alexander C , Bruhn Eric , Borlaug Barry A , Olson Thomas P
Published: March 2022

Introduction:
Obesity is prevalent in HFpEF, a syndrome that disproportionality affects women, and is associated with poor exercise tolerance (VO
2
), reduced quality of life, and greater symptoms. Visceral adipose tissue (VAT), more than general obesity, is related to metabolic and cardiovascular dysfunction common to HFpEF. While fat deposition varies between sexes, these differences and the relation to exercise tolerance remain unclear in HFpEF.

Hypothesis:
Compared to sex-matched controls, HFpEF patients will demonstrate reduced lean mass, excess VAT, subcutaneous, visceral, and intramuscular fat, and will be associated with reduced VO
2
.

Methods:
HFpEF females (F) and males (M) (n=78; 37 F/41 M; age 70±9) and non-HFpEF controls (n=50; 30 F/20 M; age 65±5) prospectively underwent body composition measurement via dual-energy x-ray absorptiometry and magnetic resonance imaging (MRI) and cardiopulmonary exercise testing for measurement of peak oxygen consumption (peak VO
2
). Muscle quality calculated as peak Watts (W) achieved divided by MRI thigh lean mass.

Results:
HFpEF had greater VAT, subcutaneous (SAT) and intramuscular (IMAT), and poorer muscle quality than controls (all p<0.01). Exercise performance was lower in HFpEF (peak VO
2
: 14±4 vs. 22±6; peak W: 69±29 vs. 116±34; both p<0.01). HFpEF demonstrated increased odds for VAT (OR: 2.02, 95% CI: 1.22-3.37), SAT (OR: 2.05, 95% CI: 1.20-3.49), and IMAT (OR: 2.04, 95% CI: 1.35-3.39) (all p<0.01). Sex-stratification revealed increased odds of excess VAT in HFpEF females (OR: 2.76, 95% CI: 1.16-7.72, p=0.03), SAT in HFpEF males (OR: 3.64, 95% CI: 1.10-12.07, p=0.03), and IMAT in HFpEF females (OR: 2.38, 95%CI: 1.10-5.29, p=0.03) with a trend in males (OR: 1.67, 95%CI: 0.97-2.86, p=0.06). Impaired VO
2
was associated with all AT depots as a combined cohort and among controls (all p<0.01) and linked to poor muscle quality individually for men and women in HFpEF and controls (all p<0.01).

Conclusion:
HFpEF patients have significantly altered body composition profiles and reduced exercise tolerance compared to controls. Sex differences in regional fat deposition impact peak VO
2
and may serve a distinct role in the pathophysiology of HFpEF.
Abstract 11398: Association of Electronic Nicotine Delivery Systems Use with Circulating Angiogenic Cell Levels
Authors: Amraotkar Alok R , Owolabi Ugochukwu S , Malovichko Marina , Benjamin Emelia J , Fetterman Jessica L , Hirsch Glenn A , Srivastava Sanjay , Bhatnagar Aruni , Hamburg Naomi , Keith Rachel J
Published: March 2022

Background:
Circulating Angiogenic Cells (CAC) are known to aid in endothelial repair and are a promising marker of vascular function. Electronic Nicotine Delivery Systems (ENDS) have been hypothesized to impact vascular health, however the association between ENDS and CACs is unknown.

Hypothesis:
We hypothesize that ENDS use, sole or dual, will be significantly associated with CAC levels.

Methods:
We analyzed CAC levels of 314 human participants enrolled in the Cardiovascular Injury due to Tobacco Use study, which is a multi-center cross-sectional study of healthy participants 21-45 years age, without known cardiovascular disease or cardiovascular disease risk factors. Four study groups were determined
a priori
- non-smokers (n=62), sole cigarette users (n=207), sole ENDS users (n=17), and dual users (cigarette and ENDS) (n=28). A total of 15 CACs were measured via a standardized flowcytometry protocol using four cell surface markers - CD146 (endothelial), CD34 (stem cell), CD45 (leukocyte), and ACC133 (early progenitor/stem cell). Regression analysis was conducted using a General Linear Model with gamma distribution and log-link. Model was adjusted for age, sex, race, ethnicity, and enrollment site.

Results:
Among sole ENDS users, two CACs were significantly higher and four CACs were significantly lower, as compared to referent non-smokers (all P<0.05) (Figure 1-A). Similarly, among dual users, seven CACs were significantly higher and one CAC was significantly lower, as compared to non-smokers (all P<0.05) (Figure 1-B).

Conclusion:
CACs are sensitive to ENDS use, including dual use. Although CACs with endothelial surface markers were most commonly associated with ENDS/dual use, CACs with stem and early progenitor surface markers were also associated with ENDS/dual use. CACs are promising biomarkers of vascular function and further research is needed to quantify the effect of individual CAC on vascular function.
Abstract 11401: The Association of Carotid-Femoral Pulse Wave Velocity with Coronary and Extra-Coronary Calcification: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ding Ning , Kim Esther , Cainzos Achirica Miguel , Tanaka Hirofumi , Howard-Claudio Candace M , Butler Kenneth R , Wagenknecht Lynne , Coresh Josef , Folsom Aaron R , Meyer Michelle , Blaha Michael J , HEISS Gerardo M , Matsushita Kuni
Published: March 2022

Introduction:
Increased carotid-femoral pulse wave velocity (cfPWV) is considered the standard non-invasive measurement of central arterial stiffness and is associated positively with cardiovascular disease. However, its relationship with coronary artery calcium (CAC) and extra-coronary calcification (ECC) in older adults is unclear.

Hypothesis:
cfPWV has a stronger relationship with aortic calcification as it is a large conduit artery, compared to small end-organ coronary arteries.

Methods:
In 1,409 ARIC participants aged 74-91 without prior coronary heart disease at visit 7 (2018-19), we quantified associations of cfPWV and high CAC or ECC using multivariable logistic regression models. PWV test was conducted at either visit 6 (2016-2017) or 7, and 725 participants completed PWV test at visit 6. cfPWV was measured using VP-1000plus (Omron Healthcare) and was categorized into tertiles. High CAC and ECC (aortic valve, aortic valve ring, mitral valve, ascending aorta, and descending aorta calcification) >75th percentile of Agatston score were analyzed separately as dependent variables.

Results:
Those in the highest (vs. lowest) tertile of cfPWV were significantly more likely to have high CAC (adjusted OR 1.66 [1.19, 2.33]) (Table). The strongest association was seen for high descending aorta calcification, with adjusted ORs of 3.53 (2.47, 5.03) for the highest tertile of cfPWV and 1.90 (1.33, 2.71) for the middle tertile, compared with the lowest tertile. High mitral valve calcification but not aortic valve calcification was significantly associated with cfPWV.

Conclusions:
Higher cfPWV was robustly associated with high calcification of some, but not all, vascular beds examined, especially descending aorta calcification. Our findings further support unique pathophysiological processes across different vascular beds. The robust association between cfPWV and mitral valve calcification warrants future investigation.
Abstract 11404: Disparities in Anticoagulation for Atrial Fibrillation: A Systematic Review of Recent Literature
Authors: Daly Danielle , Wasfy Jason
Published: March 2022

Atrial fibrillation (AF) causes 1 in 7 strokes as it is the most prevalent arrhythmia in the United States.
1
Previous work has shown that even with significant recurring AF and high CHA
2
DS
2
VASc scores, there are various disparities that occur within the prescription, type, and quality of anticoagulation control. One previous systematic review published in 2018 discusses disparities within anticoagulation for AF. Given the importance of health equity for this highly efficacious intervention, we aimed to review recent data on disparities with respect to anticoagulation for AF published after 12/31/17. This systematic review used the PubMed database to identify 19 articles that discuss disparities within anticoagulation for AF. We limited our search to articles published after 12/31/17. The search string consisted of 7 phrases that combined AF, anticoagulation, and disparities involving sex, race, ethnicity, income, socioeconomic (SE) status, etc. Articles were excluded if they focused on anticoagulation for conditions other than AF, if they did not discuss anticoagulation as a treatment for AF, and/or lack of inclusion of data referring to disparity as defined above. We found 7 articles on race and anticoagulation, 6 articles on anticoagulation and sex/gender, 3 articles that discussed SE status and anticoagulation, and 5 articles that discuss other types of disparity related to anticoagulation. Results showed that black populations were much less likely to be given anticoagulation than other patients. Black patients were more likely to be given warfarin over DOACs. Women were less anticoagulated than men even when their stroke risk was higher. Some studies in this review found that there were not statistically meaningful differences in anticoagulation use in women and men. Lower income and less educated patients were less likely to receive DOAC compared to warfarin. Compared to a prior systematic review, focusing on articles after 2017 revealed much more information about DOAC use. Disparities first noted in the warfarin era have persisted with DOACs. Given that we have identified disparities in anticoagulation with respect to race, sex, and SE status, more work is needed to identify mechanisms of these disparities and identify potential solutions.
Abstract 11410: One Drop’s Multicondition Program is Associated with Blood Pressure Reduction in Employees with High Blood Pressure and Maintenance for Employees with Blood Pressure in Range
Authors: Sears Lindsay , Hoy-Rosas Jamillah , Prenger Kai , Printz Alison , Lyle Archer , Sanchez-Madhur Rachel , Nagra Harpreet , Goldner Dan , Dachis Jeff
Published: March 2022

Background:
Studies of mobile apps to reduce and manage blood pressure (BP) show mixed results. One Drop’s (OD) multicondition program incorporates a mobile app, health predictions and insights, in-app coaching, connected devices (glucometer, blood pressure cuff, scale) and integration with thousands of apps & devices to support management of pre-diabetes, diabetes and hypertension. This study evaluated BP outcomes for employees in a large healthcare organization.

Methods:
Participants were employees identified as having hypertension, enrolled and participated in an OD hypertension program for 30+ days and had at least two systolic/diastolic BP measurements (SBP, DBP; via manual entry or Bluetooth cuff). For employees starting with high BP (Stage 1: SBP 130-139 mmHg, Stage 2: SBP 140-179 mmHg), Wilcoxon signed rank and t-tests evaluated BP change, and ANCOVA assessed program engagement level and duration effects. For in range (SBP < 130 mmHg) and high BP groups, McNemar’s test evaluated risk change.

Results:
Participants (N = 94) tended to be male, in their 40’s, white and non-hispanic. For the high BP group (N = 45), baseline SBP/DBP was 144.6±11.3/87.8±10.7 mmHg. OD yielded significant reduction in SBP (-16.5±13.2 mmHg, p < .01), DBP (-9.3±12.3 mmHg, p <.01), SBP risk category (p = .01) and marginal reduction in DBP risk category (p = .06). The greatest reduction was within Stage 2 (N = 27; SBP -21.4±13.2, p < .01; DBP -12.2±13.8, p < .01). SBP/DBP change did not vary by engagement level (p = .63/.86) or duration (p = .10/.57), suggesting BP outcomes may be achieved for individuals through varied strategies and timelines. For the in range BP group (N = 49), baseline SBP/DBP was 117.6±9.5/77.7±8.5 mmHg. Of those starting in range, 81.6% stayed in SBP range at follow-up (73.2% for DBP). Of those starting with high BP, 57.8% moved in range at follow-up (43.4% for DBP).

Conclusions:
For employees with high BP, One Drop’s multicondition program is associated with -16.5/-9.3 mmHg SBP/DBP reduction, and -21.4/-12.2 mmHg reduction for those at Stage 2 hypertension. Employees with hypertension and BP in range were 4.4 times more likely to stay in range. Future studies should validate BP reduction results and explore patterns of engagement and outcomes in additional populations.
Abstract 11412: Methyltransferase Smyd2 Mediate Atherosclerotic Plaque Calcification
Authors: Sharma Shaligram , Guan Xiaoqing , Hou Yuning , Goodlett Bethany
Published: March 2022

Introduction:
Clinical manifestation of atherosclerosis is marked by calcification of vasculature, including the expression of mineralization regulating proteins (Sox9, Msx2, and Runx2) by vascular smooth muscle cells (VSMCs). This pathogenic remodeling of VSMCs into osteochondrogenic cell types is accompanied by increased proliferation, migration, and secretion of extracellular matrix proteins. This study aimed to determine the spatiotemporal role of SMYD2 in atherosclerotic plaque progression and calcification.

Methods:
SMC-specific SMYD2 knockout was generated in ApoE
-/-
mice (SMYD2

ΔSMC

ApoE
-/-
). Age and body weight-matched mice were fed with Western diet (WD) for 18 or 26 weeks. The distribution of atherosclerotic plaque was examined by En-face Oil-Red-O staining (ORO) of freshly collected aorta. Atherosclerotic plaque burden was determined by Hematoxylin & Eosin (H&E) staining. Collagen content and calcification of atherosclerotic plaque were determined by Masson's trichrome staining and von Kossa staining, respectively. The calcification-regulatory genes (MGP1, AGG and transcription factors SOX9, MSX2, BMP2, and RUNX2) in the aorta were analyzed by RT-qPCR.

Results:
SMC-specific deletion of SMYD2 protected mice from atherosclerotic plaque calcification. En-face ORO and H&E analysis of Brachiocephalic artery demonstrated a significant decrease in ORO positive area, total plaque size, and necrotic core area in SMYD2

ΔSMC

ApoE
-/-
mice as compared to ApoE-/- mice, with no change in the distribution of collagen fibers. Von Kossa staining showed hydroxyapatite depots at the medial lining of the vasculature (microcalcification) in ApoE
-/-
mice fed with 18-week Western diet, while a smaller depot of macrocalcification was observed in SMYD2

ΔSMC

ApoE
-/-
mice compared with ApoE
-/-
mice when fed with 26-week WD. mRNA analysis of key calcification transcription factors showed significant suppression of SOX9 and MSX2 genes in aortas of SMYD2

ΔSMC

ApoE
-/-
mice compared with ApoE
-/-
mice, with downward trends of BMP2 and RUNX2 in both 18- or 26-week WD.

Conclusion:
SMYD2 ablation attenuates atherosclerotic plaque formation and calcification, suggests targeting SMYD2 can be a potential therapeutic strategy for atherosclerosis.
Abstract 11416: The Prognostic Impact of Myocardial Fibrosis Biomarkers for Atrial Fibrillation in a Heart Failure Population
Authors: Holmes Hannes , Jujic Amra , Magnusson Martin
Published: March 2022

Introduction:
Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis of atrial fibrillation (AF).

Hypothesis:
Here, we aimed to evaluate the prognostic impact of myocardial fibrosis biomarkers for atrial fibrillation in a heart failure (HF) population

Methods:
Three-hundred-and-twenty-one patients hospitalized for HF (mean age 75 years; 32% women) were screened for co-existing AF and a proximity extension assay including estimation of 7 proteins associated with myocardial fibrosis; Metalloproteinase inhibitor 4 (TIMP-4), Soluble interleukin 1 receptor-like 1 (ST-2), Galectin 3 (Gal-3), Growth/differentiation factor 15 (GDF-15) and Matrix metalloproteinase 2, 3 and 9 (MMP-3, MMP-3 and MMP-9 respectively). Associations between AF and proteins were cross-sectionally studied in multivariable logistic regression models. Furthermore, associations between protein plasma levels, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis adjusted for age sex, prevalent diabetes, smoking, body mass index (BMI), systolic blood pressure (SBP) and New York heart association classification (NYHA-class).

Results:
One-hundred-and-ninety-seven patients (61%) had prevalent AF at hospitalization. In multivariate logistic regression models, the prevalence of atrial fibrillation was significantly associated with increased plasma levels of TIMP-4, GDF-15, ST-2, MMP-2 and MMP-9. In the fully adjusted Cox regression model, increased plasma levels of 5 proteins yielded significant associations with mortality; TIMP4 (p=0,022 HR;1,46 CI95%1,06-2,01), GDF 15 (p=0,028; HR1,29; CI95% 1,03-1,63), Gal-3 (p=0,017; HR1,64;CI95% 1,09-2,47), ST2 (p=0,002; HR;1,43; CI95%1,14-1,80) and MMP3 (p=0,011; HR;1,29; CI95% 1,06-1,58). Further, increased levels of TIMP4 was significantly associated with rehospitalization (p=0,001; HR 1,58; C95% 1,19-2,08).

Conclusions:
We have demonstrated that increased plasma levels of plasma proteins related to myocardial fibrosis are associated with the risk of mortality in hospitalized HF patients, independently of traditional risk factors.
Abstract 11419: Outcomes of Transcatheter Aortic Valve Replacement in Patients with High Comorbidity versus Low Comorbidity Burden
Authors: Ashraf Muddasir , Zlochiver Viviana , Carnahan Ryan , Jan M. Fuad
Published: March 2022

Introduction:
Transcatheter aortic valve replacement (TAVR)’s on-par performance with surgical aortic valve replacement in clinical trials has led to its successful adoption in patients with high and low mortality risk. Here we evaluate if a correlation exists between comorbidity burden and in-hospital mortality (IHM) in TAVR patients and examine the factors associated with increased IHM.

Methods:
Using the National Inpatient Sample database, 148,315 adult patients who underwent TAVR from 2016 through 2018 were included in the study. The Elixhauser Comorbidity Index 2020 was used to identify comorbidities. All comorbidities were weighted equally. Patients with <3 comorbidities were assigned to the low comorbidity group (LCG) and those with ≥3 comorbidities to the high comorbidity group (HCG). The primary outcome of interest was IHM in the HCG versus the LCG. Secondary outcomes were average length of stay (LOS) and average hospital charges.

Results:
The overall IHM rate in our sample was 1.52%. Unadjusted and adjusted IHM odds were not different between groups (unadjusted odds ratio=1.024, P=0.7994; adjusted odds ratio=1.022, P=0.8225). Female sex, non-elective admission for TAVR, and transapical access were found to be independent predictors of IHM when adjusted for other factors (Table). The adjusted average LOS was significantly higher in the HCG than the LCG (3.07 vs. 2.7 days, P<0.0001). The adjusted average total hospital charges billed and average actual cost of hospital services were significantly higher in the HCG than the LCG (213,507 vs 208,019 USD, P=0.0032 and 55,284 vs 54,278 USD, P=0.0078; respectively).

Conclusion:
In-hospital mortality in TAVR patients is not significantly correlated with comorbidity burden. Female sex and procedural characteristics like transapical access and non-electiveness are more important in determining IHM. Resource utilization is higher in the HCG than the LCG.
Abstract 11421: The M2 Gene is a Determinant of Reovirus-Induced Myocarditis
Authors: Dina Zita Marcelle , Phillips Matthew B , Stuart Johnasha D , Snyder Anthony J , Venugopal Gopinath , Kumarapeli Asangi R , Danthi Pranav , Weinkopff Tiffany , Boehme Karl W
Published: March 2022

Although a broad range of viruses can cause myocarditis, the mechanisms that underlie virus-induced cardiac inflammatory disease are poorly understood. Here, we use mammalian orthoreovirus (reovirus) to examine mechanisms of viral myocarditis. We found that the M2 gene is a determinant of reovirus myocarditis in neonatal mice. The M2 gene encodes viral outer capsid protein μ1, which mediates host membrane penetration during viral entry. A recombinant reovirus in which the M2 gene from strain T3D was substituted into an otherwise strain T1L genetic background (T1L/T3DM2) caused significantly more myocarditis than the parental T1L strain. T1L was non-lethal in wild-type mice, whereas greater than 90% of mice succumbed to T1L/T3DM2. T1L/T3DM2 produced higher viral loads at the site of inoculation and disseminated with more rapid kinetics than T1L. T1L/T3DM2 also produced higher peak viral titers compared to T1L, most notably in the heart where T1L/T3DM2 viral loads were approximately 50-fold higher than T1L. Hearts from T1L-infected animals contained small purulent lesions, consistent with previous reports that T1L is mildly myocarditic. In contrast, hearts from T1L/T3DM2-infected mice were grossly abnormal, with extensive pericardial inflammatory infiltrate. Histological analysis revealed that T1L/T3DM2-infected hearts had larger and more frequent heart lesions containing necrotic cardiomyocytes with pyknotic debris than animals infected with T1L. T1L/T3DM2 also induced more lymphocyte and histiocyte infiltration than T1L. More cells with activated caspase-3 were found in hearts infected with T1L/T3DM2. Flow cytometry profiling of cardiac immune cells revealed that T1L/T3DM2 induced significantly more lymphoid cell (CD4
+
and CD8
+
T cells) and inflammatory monocyte infiltration than T1L. Together, our findings indicate that the M2 gene, and by extension the μ1 protein, promotes reovirus replication in the heart, leading to increased cardiac inflammation and enhanced myocarditis.
Abstract 11424: SARS-CoV-2 B.1.1.7 Variants Do Not Increase Risk of Subsequent Cardiovascular Disease
Authors: Knight Stacey , Larsen Gabriel , Sinclair Will , Rupper Ryan , Bair Tami L , May Heidi T , Lopansri Bert K , Carlquist John F
Published: March 2022

Background:
The SARS-CoV-2 B.1.1.7 variant, also known as the UK or alpha variant, carries the spike 69/70 deletion mutation and has been reported to be more contagious and possibly more virulent than other variants. This study examines follow-up cardiovascular outcomes for patients infected with deletion-carrying SARS-CoV-2 alpha variant.

Methods:
From October 2020 to May 2021, all positive SARS-CoV-2 samples at Intermountain Healthcare were tested for the 69/70 deletion (n=92822). Patient characteristics, COVID-19 treatments, and follow-up outcomes were extracted from Intermountain records. Cox hazard regression analysis with multivariable adjustment was used to determine risk of subsequent major cardiovascular adverse event outcomes (MACE), which included all-cause death, heart failure (HF), and hospitalization for coronary artery disease (CAD) or atrial fibrillation (AF).

Results:
Overall, 4.2% of patients testing positive for the SARS-CoV-2 virus carried the deletion mutation with prevalence increasing with time, ranging from 1.3% in October to 61.0% in May. Baseline characteristics, treatments, and outcomes stratified by non-mutant and deletion mutation status are shown in the Table. While the mutation did result in higher rates of COVID hospitalization (adjusted OR=1.68, p<0.001), there was no difference in overall MACE after adjustment by baseline characteristics and risk factors. There was a non-significant trend toward an increased rate of all-cause death in patients carrying the mutant variant (adjusted HR=1.90, p=0.12).

Conclusions:
The SARS-CoV-2 deletion mutant, while resulting in an increased risk of COVID hospitalization and a trend toward increased death, did not increase the risk of subsequent CVD. Because of the recent emergence of the variant the long-term effects are not known. Thus, it remains important to minimize risk of exposure. Moreover, long-term surveillance of subsequent CVD risk is warranted.
Abstract 11426: Signs of Depression Predict Mortality Among Swedish Heart Failure Patients
Authors: Holmes Hannes , Molvin John , Korduner Johan , Jujic Amra , Bachus Erasmus , Magnusson Martin
Published: March 2022

Introduction:
Anxiety and depression are common comorbid conditions in heart failure (HF), and there is growing evidence that they increase the risk of adverse outcomes, including rehospitalization and functional decline.

Hypothesis:
We aimed to determine if symptoms of anxiety and depression would predict mortality and rehospitalization in a Swedish prospective HF patient cohort.

Methods:
387 patients hospitalized for HF (mean age 75 years; 32% women) were assessed using the Hospital Anxiety and Depression Scale (HADS) to measure symptoms of anxiety (HADS Anxiety) and depression (HADS Depression). The median follow-up time to death and rehospitalization was 665 (range,1737; interquartile range, 811) and 316 (range, 2069; interquartile range, 348) days, respectively. Relations between baseline HADS scores, mortality and rehospitalization risk were analyzed using multivariable Cox regression analysis adjusted for age, sex, body- mass index, smoking, prevalent atrial fibrillation, educational level, prevalent diabetes, NYHA-class at hospitalization and systolic blood pressure.

Results:
A total of 30 patients (8%) had signs of depression according to HADS Depression score >11 points. In the fully adjusted Cox regression model using continuous standardized values per 1 SD change, higher score on HADS Depression scale (HR,1.42; CI, 1.16-1.75; p=0.001) yielded significant associations with increased mortality whereas no associations were found for HADS Anxiety scale (HR, 1.04; CI, 0.86-1.26; p=0.719). Rehospitalization risk (n = 246; 64%) was not significantly associated with higher scores on HADS Depression scale (HR, 1.08; CI, 0.94-1.25; p=0.274) or HADS Anxiety scale (HR, 0.95; CI, 0.82-1.09; p=0.449).

Conclusions:
Higher scores on HADS Depression scale indicated increased mortality risk in hospitalized HF patients, independently of traditional risk factors. However, higher scores on HADS Anxiety scale did not herald increased risk of mortality or rehospitalization.
Abstract 11433: Protein-Energy Malnutrition is Associated with Higher Mortality and Adverse Clinical Outcomes in Patients with Systolic Heart Failure with History of Atrial Fibrillation
Authors: Fatuyi Michael , Pereira Leanne , Zain elabidin Awfa , Namdarizandi Vahid , Tappuni Bassman , Akuna Emmanuel , Kaseer Belal , Otulana Rukayat , Sharma Vivek , Ansari Asimul H , Shemisa Kamal
Published: March 2022

Introduction:
Poor nutritional status worsens clinical outcomes in multiple disease states. Protein-Energy Malnutrition (PEM) worsens outcomes for patients with systolic heart failure (SysHF). Similarly, Atrial Fibrillation (AF) worsens outcomes of SysHF. The impact of PEM on patients with SysHF & AF is not known. Therefore, our study sought to measure the effect of PEM on clinical outcomes in patients with SysHF & AF.

Methods:
We queried the National Inpatient Sample (NIS) between 2016 & 2017. NIS was searched for adult patients hospitalized with SysHF with a history of AF as a principal diagnosis with & without PEM as a secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality, while secondary outcomes were the length of stay (LOS), total hospital charge, cardiac arrest, cardiogenic shock, & respiratory failure. A multivariable logistic & linear regression analysis was applied to estimate the odds for the clinical outcome. A p-value <0.05 was considered significant.

Results:
There were 270,580 SysHF with history of AF admissions, approximately 5.4% (14,611) had PEM. PEM vs No PEM cohorts include; (Mean Age of 77 vs 75 years], Males [57.8% vs 60.9%], Whites [76.5% vs 76.4%], Black [11.8% vs 13%].

PEM resulted in increased LOS (10 days vs 5.4 days, Adjusted LOS 3.6 days [3.1-4.3, P = <0.0001], Increase in hospital charge (PEM $117,969 vs No PEM $50,050, Adjusted charge $59,322 [$46,633-$72,012, P = <0.0001].

Conclusion:
In conclusion, PEM raised the risk of adverse clinical outcomes & increased hospital expense in patients hospitalized with SysHF & AF. Assessing nutritional status will aid in risk assessment & help guide cardiovascular treatment. Whether treating protein malnutrition will improve cardiovascular outcomes is unknown.
Abstract 11434: Emergency Department Disposition for Patients with Low-Risk Acute Pulmonary Embolism: A Nationwide Analysis
Authors: Elkaryoni Ahmed , De Sirkar Sovik , Collins Matthew , Krepostman Nicolas , Sutherland David , Walsh Kevin , Allen Sorcha , Newman Joshua , Bunte Matthew C , Darki Amir
Published: March 2022

Background:
Outpatient management has been shown to be safe and effective for patients presenting to the emergency department (ED) with low-risk acute pulmonary embolism (PE). The degree to which outpatient management for PE has evolved in contemporary clinical practice is uncertain, as is an understanding of whether certain patient or hospital factors are associated with outpatient PE management.

Methods:
Using the Nationwide Emergency Department Sample, we identified hospitalizations with primary or secondary PE between 2006-2018. We excluded patients who were <18 years old, died during ED visit, received systemic or catheter-directed thrombolysis, or had any of the following: acute coronary syndrome, heart failure, atrial fibrillation, chronic kidney/lung disease, gastrointestinal bleeding, or respiratory failure. Multivariable regression models were utilized to identify patient and hospital factors that predicted discharge to home from the ED.

Results:
Among 516,670 ED visits with acute PE, 92,108 (17.8%) patients were discharged to home. As compared to those admitted, patients who were managed as an outpatient were younger (median 52, interquartile range (IQR) 26-78 vs 61 IQR (35-87) years, P<0.001), and more female (57.9% vs 53.1%, P<0.001). In more recent years there was a significant increase in discharge from ED to home (9.2% in 2016 to 29.7% in 2018 (relative increase 69.0%, P<0.001))
Panel A.
In a sensitivity analysis, when PE was only a primary diagnosis, the rate of home disposition increased from 4.8% to 27.7%, P<0.001. Patient and hospital factors associated with an increased likelihood of home discharge are listed
Panel B
.

Conclusion:
Outpatient management of patients with low-risk PE has become increasingly common, with more than one-quarter of patients evaluated in the ED now discharged to home. Patient demographics, seasonal variation, and hospital characteristics were associated with a differential effect on the home disposition.