bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P347: Association Between Sleep Patterns and the American Heart Association Life’s Simple 7 Among Women
Authors: Makarem Nour , St-Onge Marie-Pierre , Liao Ming , Aggarwal Brooke
Published: July 2021

Introduction:
The American Heart Association’s Life’s Simple 7 (AHA LS7) is a measure of cardiovascular health that evaluates seven lifestyle behaviors and clinical risk factors to track the population’s progress towards the AHA 2020 strategic goals. Sleep is an emerging lifestyle risk factor for cardiovascular disease that is not currently included in the AHA LS7. Our aim was to assess the relation of sleep with the AHA LS7 within a diverse sample of women.

Hypothesis:
We hypothesized that a longer sleep duration, good sleep quality, low risk for obstructive sleep apnea (OSA), and absence of insomnia and snoring would be associated with a higher global AHA LS7 score and its component scores, as measures of compliance to overall and individual AHA LS7 guidelines.

Methods:
Baseline data from the AHA Go Red for Women Strategically Focused Research Network cohort at Columbia University Medical Center, an ongoing prospective study, were examined (n=323, >50% minority/Hispanic, mean age: 39y, range: 20-76y). Sleep was self-reported using validated questionnaires. A standardized scoring system was used to compute the global AHA LS7 score using criteria for smoking, diet, physical activity, body mass index (BMI), blood pressure (BP), total cholesterol, and fasting glucose. Women received a score of 2 (optimal), 1 (average), or 0 (poor) based on their compliance with each AHA LS7 guideline. The seven component scores were summed to create the global AHA LS7 score. T-tests, Fischer’s exact test and multivariable-adjusted regression models were used to evaluate associations between sleep and the global AHA LS7 score and its components.

Results:
The median global AHA LS7 score was 10; 31.3%, 33.3% and 35.3% of women had a score of 0-8 (poor), 9-10 (average), and 11-14 (optimal), respectively. Participants with sleep duration ≥7 hours, lack of insomnia and snoring, and low risk for OSA were more likely to meet ≥4 of the AHA LS7 metrics (p≤0.04). Those with sleep duration ≥7 hours, good sleep quality, no insomnia and snoring, and at low risk of OSA were more likely to meet the AHA LS7 optimal guideline for physical activity, BMI, BP, glucose, and cholesterol (p≤0.04). In multivariable-adjusted linear regression models, a lower global AHA LS7 score was associated with a higher Pittsburgh Sleep Quality Index, indicative of poorer sleep quality (β=-0.08, p=0.019), higher insomnia severity index (β=-0.05, p=0.027), and higher risk for OSA (β=-0.84, p=0.016).

Conclusions:
In this cohort of women, better sleep habits were associated with meeting the AHA LS7 guidelines. Our results warrant confirmation in larger prospective studies and within other population groups, but nonetheless highlight the potential importance of screening for sleep habits in conjunction with other lifestyle behaviors to identify those at risk of cardiovascular disease.
Abstract P352: Racial Disparity in Post-stroke Readmission - a South Carolina Perspective
Authors: Chhatbar Pratik Y , Obeid Jihad S , Lackland Daniel T , Burns Suzanne P , Buie Joy N , Feng Wuwei , Magwood Gayenell S , Adams Robert J
Published: July 2021

Background:
Readmissions after acute hospitalizations are a cause of both risk and expense, and many of them are potentially preventable. Importantly, risk-standardized hospital readmission rates are sometimes used as a yardstick of the quality of care offered. However, racial variability in readmissions might involve factors beyond quality of care and has not been studied extensively. During our pilot investigation using 90-day post-stroke readmissions data at Medical University of South Carolina (MUSC), we found significant disparities between African Americans and Caucasians.

Objective:
To identify differences in readmissions between African Americans and other races and determine preventable readmissions from a pragmatic viewpoint.

Methods:
We obtained deidentified data from Health Sciences South Carolina (HSSC) Clinical Data Warehouse (CDW). The data was comprised of three institutions: Medical University of South Carolina (MUSC), Palmetto Health and Greenville Hospital System University Medical Center. The data consisted of on adult admissions with index diagnosis considered as an ischemic stroke (or closely related) using International Classification of Diseases, Ninth and Tenth Revision (ICD-9, ICD-10) codes between January 2011 and April 2017. Of these, we will determine readmission and reason for readmission over 90-day period. Readmission can be hospital or emergency room readmission.

Results:
Our database contains 32,548 patients who have been provided clinical care for stroke. Out of these patients 8,308 (25.5%), 23,085 (70.9%) and 1,155 (3.5%) are African Americans, Caucasians and others, respectively. We will present weekly readmission trends over 90 days and evaluate if there are disparities across races. We will apply chi-square test and Student’s t-test to determine statistical significance. For weekly readmission trends over 90 days, we will apply Kolmogorov-Smirnov test to identify difference in readmission patterns across races. We will also identify confounders like socioeconomic status and age and their influence in the racial disparity.

Conclusions:
From a single center retrospective data, we found that 90-days readmission rates involve African Americans in a disproportionate manner. This multicenter data analysis will further shed light on the etiology of readmission, confounders and the care offered.
Abstract P358: Relation of Microvascular Endothelial Function and Cognitive Performance in the ELSA-Brasil Study
Authors: Brant Luisa C , Bos Daniel , Araujo Larissa F , Ikram Arfan , Ribeiro Antonio L , Barreto Sandhi M
Published: July 2021

Introduction:
Microvascular endothelial dysfunction may be implicated in the etiology of cognitive decline. Yet, current data on this association are inconsistent.

Hypothesis:
More impaired endothelial function (EF) is related to worse cognitive performance in adults.

Methods:
In the ELSA-Brasil baseline examination, 1,521 non-demented participants underwent peripheral arterial tonometry (PAT) to quantify microvascular EF [PAT-ratio and mean baseline pulse amplitude (BPA)] and cognitive tests covering the domains of memory, semantic and phonemic fluency, and executive function. Linear regression and generalized linear models were used to assess the association between EF, global and specific cognitive performance. Adjustments were made for sex, age, level of education, alcohol intake, BMI, systolic blood pressure, antihypertensive use, diabetes mellitus, total/HDL cholesterol, smoking, prevalent cardiovascular disease, and use of neuroleptics.

Results:
In unadjusted analyses, more impaired PAT measures was associated with worse global cognitive performance [difference per unit increase, BPA: -0.07 (95%CI: -0.11; -0.03), PAT-ratio: 0.11 (95%CI: 0.01; 0.20)]. Specifically, BPA and PAT-ratio were related to worse learning memory [difference per unit increase, BPA: -0.54 (95%CI: -0.78; -0.31), PAT-ratio: 0.96 (95%CI: 0.43; 1.48)], delayed memory [difference per unit increase, BPA: -0.26 (95%CI:-0.37; -0.14), PAT-ratio: 0.51 (95%CI: 0.25; 0.77)], and semantic fluency [difference per unit increase, BPA: -0.46 (95%CI:-0.77; -0.14), PAT-ratio: 0.72 (95%CI: 0.01; 1.43)]. However, adjustments for age, sex and level of education rendered the associations statistically non-significant.

Conclusions:
The association between microvascular EF and cognition are explained by age, sex, and educational level. Measures of microvascular endothelial function may therefore be of limited value with regard to preclinical cognitive deficits.
Abstract P364: Baseline and Change in Blood Pressure Are Associated With Central Arterial Stiffening and Pressure Pulsatility in Older Adults: The Atherosclerosis Risk in Communities Study - Neurocognitive Study (ARIC-NCS)
Authors: Meyer Michelle L , Tanaka Hirofumi , Palta Priya , Hughes Timothy , Kucharska-Newton Anna , Wei Jingkai , Matsushita Kunihiro , Folsom Aaron R , Hoogeveen Ron C , Heiss Gerardo
Published: July 2021

Background:
Greater central arterial stiffness and pulsatility predict target organ small vessel disease and all-cause mortality. Understanding change in artery stiffness and pulsatility and their determinants has implications for prevention. Reports of the temporal association of blood pressure with arterial stiffness and pulsatility are conflicting.

Objective:
Characterize the prospective association of blood pressure with changes in arterial stiffness and pulsatility in a population of older black and white adults.

Methods:
This is a preliminary analysis of 864 adults (508 women; 164 black; mean age 74 years) examined in both visits 5 (2011-2013) and 6 (2016-2018; n=4,215 expected) of the population-based ARIC-NCS. At both visits, certified staff measured arterial stiffness (carotid-femoral PWV (cfPWV), brachial-ankle PWV (baPWV)) and pulsatility (central pulse pressure (cPP)). Associations of baseline (visit 5) and annual change in SBP, diastolic blood pressure (DBP), and central SBP (cSBP) with the annual change in PWV and cPP were evaluated by multivariable linear regression. We adjusted for age, sex, race-center, and visit 5 heart rate, body mass index, smoking status, hypertension medication, and type 2 diabetes.

Results:
Over the 5 years between visits, cfPWV increased by 28 cm/s/y, baPWV increased by 28 cm/s/y, and cPP increased by 0.62 mmHg/y. Higher baseline SBP, DBP, and cSBP were associated with lower annual change in cfPWV, baPWV, and cPP (Table). Higher annual changes in SBP, DBP, and cSBP were associated with greater annual change in cfPWV, baPWV, and cPP. Their effect on annual change in cfPWV, baPWV, and cPP were ~double that of the baseline measures. Conversely, baseline PWV was not associated with annual changes in blood pressure.

Conclusion:
Annual changes in SBP, DBP, and cSBP are modifiable traits that were positively associated with change in arterial stiffness and pulsatility. Lowering blood pressure, therefore, may reduce the progression of arterial stiffness among older adults.
Abstract P370: Utility of Cardiovascular Risk Algorithms in Prediction of Subclinical Atherosclerosis in the Young
Authors: Geevarghese Alexi , Garshick Michael , Gianos Eugenia , Benenstein Ricardo
Published: July 2021

Background:
Prediction of cardiovascular risk in younger patients is particularly challenging. Most current risk estimators underestimate risk potentially leading to under-treatment in younger patients with significant risk factors for atherosclerosis.

Methods:
A retrospective analysis of patients age 20 to 50 (n = 274) referred to a cardiology clinic between 2013 and 2016 and undergoing carotid ultrasound for risk stratification and statin initiation was conducted. A medical history was obtained by chart review at the time of carotid ultrasound. The 2008 Framingham general risk score was used to calculate a 10-year cardiac risk. Carotid plaque was defined using standard definitions as carotid artery focal wall thickening 50% or greater than the surrounding vessel wall or a focal region > 1.5 mm protruding into the lumen.

Results:
Average age was 41 ± 7.9 years, 60% male, 77% Caucasian, 4% diabetes. Ten percent (n = 27) had carotid plaque noted on ultrasound. Those with plaque compared to those without were older (46 ± 4.3 vs. 41 ± 7.5, p < 0.01), more likely to have hypertension (HTN) (52% vs. 20%, p < 0.01), more likely to be active smokers (19% vs. 6%, p = 0.02) and had higher total cholesterol (222 ± 53 mg/dl vs. 202 ± 45 mg/dl, p = 0.04) and LDL-C (140 ± 40 mg/dl vs. 121 ± 43 mg/dl, p = 0.04). No differences were noted in gender, race, body mass index, diabetes or family history of early heart disease. The average cardiac risk score was 5.9 ± 3.5% for those with plaque and 4.2 ± 3.2% for those without (p < 0.01). When assessing the same population by number of risk factors, 93% (n = 25) of individuals with carotid plaque had ≥ 2 cardiac risk factors (one point each for age 40 to 50, smoking, family history of heart early disease, obesity, LDL > 160 mg/dl, DMII or HTN). This compared to 37% (n=10) who had carotid plaque on imaging and a risk score ≥ 7.5%. Receiver operator curve characteristics to predict plaque were similar for the cardiac risk score (AUC 0.674) and number of cardiac risk factors (AUC 0.674, p = 0.96).

Conclusion:
In patients 50 years or younger, ≥ 2 cardiac risk factors revealed a higher percentage of carotid plaque than a Framingham cardiac risk score cut off value of ≥ 7.5%. In younger patients with cardiac risk factors, novel algorithms are needed to more accurately guide medication therapy.
Abstract 17016: The Role of Polymerase Delta-Interacting Protein 2 in Pulmonary Vascular Inflammation
Authors: Forrester Steven J , Xu Qian , Kikuchi Daniel S , Okwan-Duodu Derick , Lassegue Bernard , Sadikot Ruxana , Hernandes Marina S , Griendling Kathy K
Published: July 2021

Introduction:
Vascular inflammation is an underlying causative factor in the progression of various ailments including acute lung injury. In the inflamed lung, chronic endothelial cell (EC) activation facilitates leukocyte recruitment and extravasation into tissue beds, leading to end organ damage. Delineating the mechanisms of EC activation may uncover novel areas of therapeutic opportunity. Our laboratory has identified polymerase delta-interacting protein 2 (Poldip2) as a novel regulator of endothelial activation and permeability.

Methods:
Poldip2 +/- and +/+ mice were injected with either saline or lipopolysaccharide (LPS, 18 mg/kg) for either 6 or 18 hours to induce acute lung injury. Bronchoalveolar lavage (BAL) fluid was collected to assess leukocyte infiltration via flow cytometry and cytokine expression via ELISA. Evans blue staining was used to evaluate lung permeability, and tissue lysates were analyzed for inflammatory marker expression. For
in vitro
analysis, inflammatory marker expression, leukocyte adherence and cell permeability were tested in human pulmonary microvascular endothelial cells (HPMVECs) treated with saline or LPS (1 μg/mL). To test the efficacy of Poldip2 silencing in HPMVECs, siRNA was used at 100 nM (siControl vs siPoldip2). Comparisons between groups were analyzed with a one-way ANOVA followed by Tukey’s post-hoc test.

Results:
Compared to Poldip2 +/+, Poldip2 +/- mice treated with LPS exhibited significantly reduced mortality (80% vs. 20% survival), Evans blue staining, and leukocyte infiltration. FACS analysis of BAL fluid revealed a decrease in LPS-induced monocyte and neutrophil infiltration in Poldip2 +/- mice compared to Poldip2 +/+ mice. RT-qPCR analysis indicated a reduction in inflammatory gene induction in lung tissue. In HPMVECs, LPS induced increases in VCAM-1 protein expression, THP-1 leukocyte adherence and endothelial permeability, which were attenuated with siRNA-mediated knockdown of Poldip2 (
P<0.05
for all).

Conclusion:
Poldip2 is an important regulator of EC activation, leukocyte adherence and EC permeability. In scenarios of persistent vascular inflammation and endothelial barrier dysfunction, such as in acute lung injury, inhibition of Poldip2 may provide clinical benefit.
Abstract 17026: Effects of Supervised Exercise Therapy on Free-Living Physical Activity Among Patients With Symptomatic Peripheral Artery Disease
Authors: Schorr Erica , Whipple Mary , Treat-Jacobson Diane
Published: July 2021

Introduction:
Evidence supporting the effects of supervised exercise therapy (SET) on alleviating symptoms and improving walking ability for patients with symptomatic peripheral artery disease (PAD) is robust and well recognized. However, little is known about the impact of SET on free-living physical activity (PA). The aim of this study was to examine the relationship between participation in SET and changes in free-living PA among individuals in the the
EX
ercise Training to Reduce Claudication: Arm
ER
gometry versus
T
readmill Walking (
EXERT
) trial.

Methods:
In this randomized, controlled trial, 104 participants (mean age 68±9; 29% female) were allocated to receive treadmill (TM) exercise (n=41), upper body ergometry (UBE) exercise (n=42), or usual-care (UC) (n=21) for 12 weeks. Exercise participants attended SET three times per week; UC participants met with study staff weekly. PA was measured over 7 days via waist-worn ActiGraph accelerometers at baseline, 6, and 12 weeks. Steps per day was the primary outcome. Secondary outcomes were proportion of time in light and moderate to vigorous physical activity (MVPA), and sedentary time. PA was controlled for in TM participants by using SET logs. Results were analyzed using descriptive statistics, two-sample t-tests, and analysis of variance.

Results:
Regardless of randomization, average daily steps were low at baseline and 6 weeks (4,013 steps,
p
=.72; and 3,911 steps,
p
=.84, respectively), and slightly higher at 12 weeks (4,307 steps;
p
=.93). Although not statistically significant but perhaps clinically relevant, UBE participants exhibited greater increases in MVPA over 12 weeks (0.9% to 1.3%;
F
=.48,
p
=.62) compared to TM (1.2% to 1.3%;
F
=.35,
p
=.71) and UC (1.3% to 1.5%,
F
=.03,
p
=.97); similarly all participants exhibited reductions in sedentary time and increases in free-living PA between baseline and 12 weeks.

Conclusions:
These data suggest individuals with PAD attending SET replace sedentary time with light or moderate intensity PA regardless of exercise modality. Despite study participants meeting the recommended daily steps for adults with chronic conditions (3,500-5,500 steps), it is suspected that they did not reach the daily goal of 30 minutes of enhanced PA to reduce health risks. Future research should incorporate activity tracking devices that can provide feedback on PA as an approach to meet daily PA goals. Activity tracking devices used in conjunction with SET may further improve walking distance, symptom management, and quality of life among patients with symptomatic PAD.
Abstract 17051: Neurocognitive Disorders on Long-Term Follow up of Congenital Heart Disease Patients Undergoing Procedures in Childhood
Authors: Sterling Lee H , Liu Aihua , Guo Liming , Marelli Ariane J
Published: July 2021

Introduction:
Neurocognitive disorders (NCD) are a growing concern in congenital heart disease (CHD) patients. We hypothesized that early life cardiopulmonary bypass (CBP) as well as age at intervention (AAI) were risk factors for NCDs on long-term follow-up in CHD patients.

Methods:
Data source was the Quebec CHD database. We defined NCD based on ICD 9 and 10 codes including autism spectrum disorder, global developmental disorder, specific developmental disorder, attention deficit hyperactive disorder, intellectual disability or specific learning deficit. We compared NCD risk from 1983-2010 in 3 cohorts of patients undergoing procedures in childhood: percutaneous atrial septal defect (ASD) closure (no CBP group), surgical ASD closure (short CBP group), and complex CHD lesion repair surgeries (long CBP group). Patients were followed from intervention until NCD diagnosis, death, or administrative censoring whichever came first.

Results:
By 27 years of follow-up, the cumulative risk of NCD was significantly higher in the complex surgery group compared to the ASD surgery group (crude, 24.9% and 13.4%; p<0.0001) and with adjustments for AAI and sex (Cox regression, p=0.043). By 12 years of follow-up, the cumulative risk of NCD was significantly higher in the complex surgery group compared to the other two groups where the risk was almost identical. Cox models with different follow-up lengths identified younger AAI and male sex being significantly associated with increased risk in NCD.

Conclusions:
In long-term follow-up of CHD patients, younger AAI of CBP and male sex were associated with increased risk of NCD. Our findings suggest that CBP duration in a wide range of CHD lesions and cohort effects are important predictors of NCD. 
Abstract 17072: Discordance Between Lactic Acid Elevation and Invasive Hemodynamics in Decompensated Heart Failure
Authors: Narang Nikhil , Chung Bow , Nguyen Ann , Imamura Teruhiko , Kalantari Sara , Smith Bryan , Kim Gene H , Raikhelkar Jayant , Sarswat Nitasha , Jeevanandam Valluvan , Sayer Gabriel T , Uriel Nir
Published: July 2021

Introduction:
Elevated lactic acid (LA) levels carry a poor prognosis in patients admitted with shock. Data is lacking on the association of LA level with the severity of decompensated heart failure (HF). This study assesses the relationship between LA levels, invasive hemodynamics and clinical outcomes.

Methods:
Patients presenting to the cardiac care unit with decompensated HF between 2015-18 were prospectively enrolled into an invasive hemodynamics study. LA (normal 0.7-2.1 mmol/L) levels were obtained within 12 hours prior to right heart catheterization (RHC). No significant changes in therapy were made in the time between LA level collection & RHC. Patients were divided into 4 groups: 1) normal pulmonary capillary wedge pressure (PCWP) (< 18 mmHg)/ normal Fick cardiac index (CI) (≥ 2.2 L/min/m
2
), 2) normal PCWP/ low CI (< 2.2 L/min/m
2
) 3) elevated PCWP (≥ 18 mmHg )/ normal CI, 4) elevated PCWP / low CI.

Results:
80 patients were enrolled. Mean age 58±14 years; 78% male, left ventricular ejection fraction was 24±4%. Prior to RHC, 55% patients were on vasoactives and/or inotropes. Mean (SD) PCWP was 26 ± 8.8 mmHg and mean CI was 2.06 ± 0.61 L/min/m
2
. Overall 48 (60%) of the patients had high PCWP and low CI (group 4). 81% had normal LA (≤2.1 mmol/L) prior to RHC. There was no correlation between LA level and PCWP (R=0.12; p=0.30); there was a moderate inverse correlation between LA level and CI (R=-0.40; p<0.01). Only 25% of patients with the highest risk hemodynamic profile (elevated PCWP/low CI) had an elevated LA level (Figure A). 90- day all cause mortality was 33% When LA was stratified by tertile, there was no significant difference in mortality between the tertiles (Figure B).

Conclusion:
In patients with decompensated HF, normal LA levels do not exclude the presence of cardiogenic shock with profoundly impaired cardiac output. Invasive assessment of hemodynamics should not be delayed based on LA level alone.
Abstract 17078: Myocardial Stiffness by Intrinsic Wave Propagation Method: Comparison With End-Diastolic Pressure-Volume Relationship
Authors: Anupraiwan Orawan , Ionescu Filip , Petrescu Ioana , Pellikka Patricia A , Grogan Martha , Dispenzieri Angela , Pislaru Sorin V , Pislaru Cristina
Published: July 2021

Introduction:
Intrinsic wave propagation is a novel approach to measure myocardial stiffness (MS) as validated in animal studies.

Aims and Hypothesis:
1) To compare MS measured by the wave method with chamber stiffness (CS) derived from noninvasively estimated end-diastolic pressure-volume relationship (EDPVR) in patients; 2) To test the hypothesis that MS is superior to CS for predicting outcomes in patients with cardiac amyloidosis (CA).

Methods:
Prospective study in 56 patients with amyloidosis (CA: 38, noncardiac amyloidosis, NCA: 18; 90% AL-type; age 63 ± 10 yrs; ejection fraction 57 ± 11%) and 36 normal subjects (age 49 ± 13 years). Intrinsic velocity propagation of myocardial stretch (iVP), a measure of MS, was measured by ultra-high frame rate (250-465Hz) tissue Doppler imaging. Left ventricular (LV) EDPVR were reconstructed using the noninvasive single-beat method (Fig.A). Stiffness coefficients (α, β, load-independent) and CS (dP/dV) were calculated. End-diastolic pressure (EDP) was estimated from E/e’. Adverse events at follow-up (death, heart failure, stroke, significant arrhythmia) were recorded.

Results:
iVP was higher in CA compared to NCA and controls, indicating higher MS (Fig. B). This was confirmed by EDPVR, which were steeper and shifted leftward (Fig. A). The slope (β) of EDPVR and CS (dP/dV) were higher and LV capacitance (V
30
, volume at 30 mmHg) was lower in CA (Fig. A) and correlated with iVP (β: r = 0.59; CS dP/dV, r = 0.43; EDP, r = 0.61; all p<0.0001). Patients with higher LV thickness (r = 0.66), lower LV longitudinal strain (r = -0.57) and elevated NT-proBNP (r = 0.69) had higher iVP. At follow-up (median 2.5 years), after adjusting for relevant confounders, an iVP >2.7 m/s was strongly associated with excess events (p<0.0001; Fig. C) and was superior to measures of CS (dP/dV: p = 0.28; β >6.5: p = 0.03; Fig. D).

Conclusions:
Myocardial stiffness by intrinsic wave method shows similar findings to chamber stiffness by EDVPR, but is more strongly related to outcomes in patients with amyloidosis.
Abstract 17082: ECG Screening in North Texas High School Students: A Randomized, Pilot Feasibility Study
Authors: Gordon Patti Karl , Cain Matthew , Daniels James , van Lanen Sander , Parizher Gary , Scott William , Link Mark S , Higgins John P , Drezner Jonathan A , Harmon Kimberly G , Lampert Rachel , Levine Benjamin D
Published: July 2021

Introduction:
The death of young athletes is devastating to families and communities. Despite routine pre-participation screening, 80–100/yr die or suffer cardiac arrest, with 65% occurring in high school athletes. AHA/ACC recommendations for pre-participation screening do not include routine electrocardiogram (ECG), in contrast to some international guidelines.

Methods:
We designed a pilot study to test feasibility of a larger trial, scaled to 1% of the estimated 800,000 participants required to power for detection of sudden death/arrest. Athletes and band members enrolled in eight high schools in two Texas school districts were randomized in block fashion to standard screening alone versus the addition of ECG. ECGs were interpreted using CardeaScreen software, over-read by an independent expert. Students with abnormal ECGs received cardiology evaluation at no cost. Text messages assessing for cardiac events or hospitalizations were sent to both groups biannually.

Results:
Of the ~8,000 eligible students, the intervention group enrolled 847 students who received ECG (21%); the non-intervention group enrolled 655 students (16%). CardeaScreen identified 20 of 847 ECGs as abnormal (2.4%) and the expert identified 19 as abnormal (2.2%) Six of 20 ECGs (30%) identified as abnormal by CardeaScreen were over-read as normal, and 5 of 827 ECGs (0.6%) identified as normal by CardeaScreen were over-read as abnormal (PPV 70%, NPV 99.4%). Twenty-five follow up visits were attempted, 22 were completed (88%), and specialist referrals were sent for 6 (29%). New diagnoses included Wolf-Parkinson-White syndrome, coronary anomaly, and depressed LV function. Follow up with SMS surveys yielded 737 responses at 6 months and 441 responses at 16 months. No sudden cardiac death or arrest was reported.

Conclusion:
Randomized ECG testing and follow-up of high school students is feasible, though with low enrollment and relatively low yield. Automated ECG interpretation is viable but leads to significant false + results. Low participation in enrollment and follow up present challenges to a large-scale ECG screening study powered for clinical events. Possible solutions include an “opt-out” enrollment strategy and use of alternate follow up methods such as social media.
Abstract 17086: External Support of the Cardiac Base in the Treatment of Functional Mitral Regurgitation & Heart Failure
Authors: Raman Jaishankar , Padmanabhan Chandrashekar , Saldanha Richard , Hote Milind , Deja Marek , Pibarot Phillipe
Published: July 2021

Introduction:
Ventricular dysfunction in the presence of normal mitral leaflets is characteristic of functional mitral regurgitation (MR). Surgical treatment with mitral valve repair or replacement, address mitral valve annulus and leaflets, not the ventricular muscle. We describe early and mid-term clinical experience with extra-cardiac treatment of FMR with a novel device that is implanted on a beating heart.

Hypothesis:
External and adjustable support of the cardiac base can effectively reduce functional MR & HF.

Methods:
The BACE (Basal Annuloplasty of the Cardia Externally) device is a broad belt/band of silicone that is implanted at the base of the heart, by means of slim polyester belt loops sutured on atrial and ventricular sides of the Atrio-Ventricular groove. Forty one patients (mean age 60.24 years) with functional and ischemic MR were evaluated at 10 multi-national centers between December, 2008 and June, 2018. All patients had moderately severe or severe MR (Mean MR grade 3.3) on trans-thoracic and/or trans-esophageal echocardiography, and impaired LV function (Mean EF 38.5%). Risk assessment by Logistic Euroscore showed a mean of 16.5%. Implantation of the BACE device, was performed, according to sizing performed along the base of the heart, overlapping atrial and ventricular surfaces of the atrio-ventricular groove circumferentially. Mean number of coronary grafts was 2.5. Five patients had stand-alone procedures without CABG. Procedures were performed on a beating heart with the majority of them performed off-pump. Intra-operative trans-esophageal echocardiography allowed customized inflation of specific chambers to selectively deform the annulus and sub-annular myocardium.

Results:
Three patients required peri-operative adjustment of the BACE device. There were no deaths related to the BACE device or device failures. The degree of MR improved from a mean of 3.4 to 0.88. This >2 class improvement in MR was sustained over the 12 month follow up period in all patients. LVEDD decreased from 5.9±0.6 to 5.5±0.6 cm.

Conclusions:
Ischemic and functional mitral valve regurgitation can be treated by epicardial implantation and dynamic adjustment of the BACE device. Ventricular stabilization may impact HF progression.
Abstract 17089: Cyclin D2 Overexpression Enhances the Potency of Human Induced-Pluripotent Stem Cell-Derived Cardiomyocytes for Cardiac Repair in a Porcine Model of Myocardial Infarction
Authors: Zhao Meng , Tang Yawen , Zhu Wuqiang , Zhang Jianyi
Published: July 2021

Introduction:
Stem-cell-based therapies provide promise for the treatment of ischemic myocardial injury, but the number of cells that remain engrafted at the site of administration is exceptionally low, which is believed to limit the effectiveness of treatment. In this study, we investigated whether the number of engrafted human induced-pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) can be increased via overexpression of the cell-cycle activator cyclin D2 (CCND2) and if so, whether this increase is accompanied by improvements in myocardial recovery. Experiments were conducted in a large-animal (swine) model of myocardial injury.

Methods and results:
CCND2-overexpressing hiPSC-CMs (CCND2
OE
CMs) were constructed via lentiviral transfection; then, myocardial infarction (MI) was surgically induced in swine, and the animals were randomly assigned to treatment with CCND2
OE
CMs (i.e., the MI+CCND2
OE
CM group), wild-type hiPSC-CMs (the MI+CCND2
WT
CM group), or neither experimental treatment (the MI group); the cells were injected into five sites (6х10
6
cells/site) surrounding the infarct. Four weeks after MI, measurements of the heart-weight to bodyweight ratio (HW/BW), cardiac function (determined via magnetic resonance imaging), and vascularity (CD31 staining) were significantly better in MI+CCND2
OE
CM animals than in the CCND2
WT
CM group. HW/BW was also significantly lower in both cell-treatment groups than in MI animals, and CCND2 overexpression was associated with increases in both hiPSC-CM engraftment (mRNA levels) and cell-cycle activity (ki67 and phosphorylated histone 3 levels).

Conclusion:
Experiments in a large-animal MI model indicated that CCND2 overexpression in transplanted hiPSC-CMs was associated with increases in cell-cycle activity and the number of engrafted cells, as well as improvements in cardiac function, hypertrophy, and vascularity.
Abstract 17096: The Efficacy of Renal Sympathetic Denervation in End-Stage Renal Disease Patients
Authors: Kim Chan Joon , Chang Kiyuk , Kim Daewon , Park Man Won , Her Sung-Ho
Published: July 2021

The efficacy of renal sympathetic denervation in end-stage renal disease patients under hemodialysis

Chan Joon Kim, Kiyuk Chang, Daewon Kim, Manwon Park, Jung Sun Cho, Sung-Ho Her

Introduction:
The end-stage renal disease (ESRD) patients who are under under renal replacement therapy, have often have uncontrolled, resistant hypertension. Renal sympathetic denervation (RDN) with radiofrequency ablation catheter has shown promising results in resistant hypertension. The purpose this pilot study is to assess the efficacy of RDN in resistant hypertension in ESRD patients.

Method:
Patients who are under renal hemodialysis and inter-dialytic SBP > 160 mmHg despite of three or more antihypertensives were eligible for enrollment. 8 patients were allocated to either medical therapy group or RDN group by randomization. RDN was performed with Symplicity RDN catheter (Medtronic®).The primary outcome was change in SBP change in an inter-dialytic day in 3 months. The secondary outcome was change in DBP in 3 months, left ventricular mass index (LVMI).

Results:
The baseline SBP/DBP were 172.2 ± 9.5/ 88.7 ± 12.1 mmHg for the intervention group and 164.0 ± 6.9/84.7 ± 13.4 for medical group. Baseline ambulatory SBP was 164.8 ± 4.4 for the intervention group and 162 ± 8.4 mmHg for medical therapy group. The 3 month SBP/DBP were 155.5 ± 12.2/80.2 ± 7.7 for the intervention group and 167.5 ± 10.3/83.6 mmHg for medical therapy group. The mean change in SBP was 18.4 ± 4.5 mmHg for the intervention group and 2.8 mmHg ± 3.8 mmHg for the medical group (
p
=0.03). The mean LVMI 194.3 ± 10.4 g/m2 for the intervention group and 187.4 ± 11.5 g/m2 for the medical therapy group. The mean change in LVMI was 41.4 ± 3.5 g/m2 for the intervention group and 1.1 g ± 4.4 g/m2 for the medical group (
p
=0.03).

Conclusion:
This pilot study suggests that RDN may have therapeutic effect in resistant hypertension in ESRD patients and may have a role in regression in left ventricular hypertrophy.
Abstract 17129: Trends of Inpatient Malignancy Admissions Among Patients With a History of Heart Transplant: Analysis of National Inpatient Sample Database
Authors: Fugar Setri , Uchenna Mbachi C , Okoh Alexis K , Olakanmi Olagoke , Solomon Alfred , Akthar Tauseef , Gomez Jorge O , Vafah Atefeh , Sreenivasan Jayakumar , Yirerong Juliet A , Al-Ogaili Ahmed , Fuentes Harry
Published: July 2021

Introduction:
Heart transplantation is associated with prolonged survival and improved quality of life in patients with advanced cardiac disease albeit with an increased risk of malignancies due to the use of immunosuppressant medications. Our study aimed to determine the types and trends of in patients’ hospitalization for malignancies among heart transplant patients.

Methods:
We queried the 2005 to 2014 National Inpatient Sample(NIS) database to identify all patients with a history of heart transplant (ICD-9 codes V412, 99683) who were hospitalized with a diagnosis of cancer. The main outcome was the trend in cancer admissions. Secondary outcome were inpatient mortality, total charge and length of stay. Cochran’s and Mantel-Haenszel test was used to assess trends of cancer admissions. Adjusted OR were used to compare the incidence of death between the two groups.

Results:
A total of 36543(weighted national estimate of 177,604) patients were admitted with a history of heart transplantation over the study period, out of which 2347(6.4%) had a diagnosis of a malignancy. Cancer patients were older (Mean age 66±12 Vs. 61.1±18 P-Value <0.001) and were more likely to be male. There was an increasing trend in the rate of cancer admissions over the study period from 60 per 1000 patients in 2005 to 70 per 1000patients in 2014(P-Vale <0.0001). Overall the most prevalent cancer was Non-Hodgkin’s 20.9% followed by lung Cancer 19.1%. ninety-seven patients(4.1%) had a 2 or more cancers. Patients with a diagnosis of cancer were more likely to die while inpatients as compared those without a diagnosis of cancer (6.6% vs. 3.1%, adjusted OR 2.42 95%CI 1.53-3.38 P-value <0.001). Lastly, patients with cancer had an increased total median coast and a longer length of stay(Total charge(39735 vs, 32,035, P value =<0.001 and 5 vs. 4. P-value <0.001).

Conclusion:
Development of cancer among patients with a history of transplant adds significant morbidity and mortality. Further studies are needed to determine effective ways to reduce morbidity in this patient cohort.
Abstract 17142: Parkin Deficiency Shortens Life Span and Accelerates Cardiac Aging: Role of Telomere Dysfunction and Mitochondrial Genome Instability
Authors: Ren Jun , Zhang Yingmei
Published: July 2021

Background:
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulated autophagy and mitochondrial integrity. Telomere dysfunction plays a complex role in life span and cardiac aging although the interplay between mitophagy and telomere function remains elusive.

Method:
This study examined the impact of global Parkin ablation on lifespan and cardiac aging, and the mechanisms involved with a focus on telomere function and mitochondrial integrity. Echocardiography, cardiomyocyte mechanical function, telomerase activity, mitochondrial respiration and mitochondrial genome stability were assessed in young (4-5 months) and old (18 months) WT and Parkin-/- mice.

Result:
Our results revealed that Parkin ablation shortened lifespan (by 12.4%) and accentuated aging (18 months)-induced unfavorable changes in cardiac function, cardiac remodeling (heart weight, LV wall thickness, LV systolic and diastolic diameters, and cardiomyocyte cross-sectional area) and intracellular Ca
2+
handling. Advanced aging disturbed autophagy, mitophagy and mitochondrial integrity as evidenced by increased p62, decreased levels of beclin-1, Atg7, LC3B, PTEN-induced putative kinase 1 (PINK1), Parkin, UCP-2, PGC-1α and aconitase activity, the effects of which were accentuated by Parkin deficiency. Aging triggered telomerase dysfunction and mitochondrial instability including PGC1α, NRF1, and TFAM, the effect of which was accentuated by Parkin deficiency.

Conclusion:
Our work revealed that Parkin ablation exacerbates aging-induced cardiac dysfunction and mitochondrial injury, possibly in association with telomere dysfunction and mitochondrial instability.
Abstract 17154: Machine Learning Outperforms ACC/AHA CVD Risk Calculator in MESA Offering new opportunities for Short-Term Risk Prediction and Early Detection of the Vulnerable Patient
Authors: Kakadiaris Ioannis A , Vrigkas Michail , Yen Albert , Kuznetsova Tatiana , Budoff Matthew , Naghavi Morteza
Published: July 2021

Introduction:
Machine learning (ML) is poised to revolutionize healthcare. Current national guidelines for prediction and prevention of atherosclerotic cardiovascular disease (ASCVD) use ACC/AHA Pooled Cohort Equation Risk Calculator which relies on traditional risk factors and linear statistical models. Unfortunately, this approach yields a low level of sensitivity and specificity. The low sensitivity results in missing high-risk individuals who need intensive therapy and the low specificity results in millions of people unnecessarily recommended drugs such as statin. We aimed to utilize Machine Learning (ML) to create a more accurate predictor of ASCVD events and whom to recommend statin.

Methods:
We developed and validated a ML Risk Calculator based on Support Vector Machines (SVMs) using the latest 13-year follow up dataset from MESA (Multi-Ethnic Study of Atherosclerosis) of 6,459 participants who were free of cardiovascular disease at baseline. We provided identical input to the ACC/AHA and ML risk calculators and compared their accuracy. We also validated the ML model in another longitudinal cohort: the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO).

Results:
According to the ACC/AHA Risk Calculator and a 7.5% 10-year risk threshold, 46.0% would be recommended statin. Despite this high proportion, 23.8% of the 480 “Hard CVD” events occurred in those not recommended statin, resulting in sensitivity (Sn) 0.76, specificity (Sp) 0.56, and AUC 0.71. In contrast, ML Risk Calculator recommended statin to 11.4%, and only 14.4% of “Hard CVD” events occurred in those not recommended statin, resulting in Sn 0.86, Sp 0.95, and AUC 0.92. Similar results were seen in prediction of “All CVD” events.

Conclusions:
The ML Risk Calculator outperformed the ACC/AHA Risk Calculator by recommending less drug therapy, yet missing fewer events. Additional studies are underway to validate the ML model in other cohorts and to explore its ability in predicting short-term (1-5 years) events with additional biomarkers including imaging. Machine learning is paving the way for early detection of asymptomatic high-risk individuals destined to a CVD event in the near future, the Vulnerable Patient.
Abstract 17179: Blunted Vasoreactivity and Loss of Flow Reserve Contribute to Impaired Arteriogenesis in Diabetic Peripheral Artery Disease
Authors: Wang XinLu , Simons Michael , Sessa William , Zhuang Zhen W
Published: July 2021

Introduction:
Given the uncertainty around the exact pathophysiological mechanisms of diabetic peripheral artery disease (PAD), patients continue to have extremely poor prognoses. Our study attempted to address this critical unmet need.

Hypothesis:
We hypothesize that vasoreactivity in the feeding artery and impaired peripheral flow reserve are two primary causes of impaired arteriogenesis in these patients.

Methods:
The distal right femoral artery was ligated 2 weeks after streptozocin (STZ, n=12) or citrate buffer (n=12) treatment in wild-type (WT) mice. The contralateral hindlimbs were used as a negative control. 2 weeks post-hindlimb ischemia (HLI), the endothelial (EC)-dependent and EC-independent vasodilatation of the feeding artery was investigated using a Vevo 770 preclinical ultrasound scanner. Peripheral flow reserve was also assessed by pulse wave Doppler after 60 ul adenosine (3mg/ml) was administered systemically. A microCT angiography was performed to quantify collateral arteries. Gastrocnemius muscles were taken both for immunohistochemical examination in the evaluation of angiogenesis.

Results:
Femoral diameters at rest were similar between both control and diabetic models. In the non-ischemic limb, diabetes markedly blunted endothelial and smooth muscle cell (SMC) vasodilation reaction in the proximal femoral artery when compared with control mice [[acetylcholine (Ach): 286.3 ±16 μm versus 370±30 μm; sodium nitroprusside (SNP): 285±24.5 μm versus 350±30 μm, p<0.01]. In the ischemic hindlimb, chronic ischemia impaired vasodilation in diabetic mice when compared with control mice (Ach: 255±16 μm versus 330±40 μm; SNP: 340±50 μm versus 253±22 μm, p<0.05). In diabetic mice, peripheral flow reserve was impaired (1.27±0.27 in controls vs 0.87±0.13 in diabetes, p<0.05), with arteriole rarefaction and increased capillary/muscle ratio.

Conclusions:
This study demonstrated that chronic hyperglycemia negatively affects collateral development at different levels:
1
) dysregulation of the feeding artery;
2
) impaired arteriogenesis and increased angiogenesis; and
3
) loss of peripheral flow reserve.
Abstract 17184: Nearly One Third of GWAS CAD Are Putative SMC Klf4 or Oct4 Targets in Advanced Atherosclerotic Lesions
Authors: Alencar Gabriel F , Haskins Ryan , Venkata Vamsidhar M , Bjorkegren Johan , Bekiranov Stefan , Owens Gary K
Published: July 2021

Atherosclerosis is a disease of chronic inflammation and the leading cause of morbidity and mortality worldwide. Despite decades of research, our understanding of the mechanisms regulating plaque stability remains poor. Until recently, smooth muscle cells (SMCs) were thought to play an athero-protective role in lesion pathogenesis. However, rigorous lineage tracing has shown a significant portion (>80%) of SMC-derived cells within an advanced atherosclerotic lesion did not express detectable SMC markers. Furthermore, SMC-specific conditional KO of Klf4 resulted in reduction of several indices of plaque instability and SMC-derived macrophage-like cells. In contrast, conditional KO of Oct4 in SMCs presented a reduction of SMC and increased of Lgals3+ cells within lesions, as well as increase of several indices of plaque instability. Taken together, SMCs can have a beneficial or detrimental effect in lesion pathogenesis.

Hypothesis:
Combinatorial analysis of Oct4/Klf4 ChIP-seq and RNA-seq of advanced atherosclerotic lesions from our SMC-Klf4 and SMC-Oct4 mice provide a unique opportunity to identify genes that play a critical role in regulating beneficial or detrimental changes in SMC phenotype.

Results:
SMC-Oct4 target genes are enriched for migration pathways, while SMC-Klf4 target genes are enriched for inflammation pathways. Further, atherosclerosis pathway, among others, presented significant opposite patterns (SMC-Oct4-KO up-regulation and SMC-Klf4-KO down-regulation), and presented strong significant gene anti-correlation, corroborating our phenotypic observations. Remarkably, we cross-reference our ChIP-seq datasets with CAD GWAS and found that 54 of the 161 human loci were either Klf4 and/or Oct4 SMC targets, highly suggesting that CAD GWAS genes might be affecting SMC function in lesion development/pathogenesis. To validate our results, we used the STARNET dataset, and we observed that both Oct4 and Klf4 are significantly up-regulated in aorta of CAD patients compared to controls. In addition, co-expression analysis shows that one of the Klf4 network is highly related to human GWAS CAD, including genes such as LDLR, APOE, PCSK9, TRIB1, and others. Surprisingly, more than 35% of genes in this network also are present in our SMC Klf4 ChIP-seq dataset.

Conclusions:
our results suggests that: late stage atherosclerotic lesions of mouse and humans seems to be more similar than previously thought; and nearly 1/3 of CAD GWAS loci appear to be affecting SMC function and are potentially Klf4/Oct4-dependent.
Abstract 17185: Modest Performance of Heart Failure Clinical Prediction Models: A Systematic External Validation Study
Authors: Upshaw Jenica N , Nelson Jason , Wessler Benjamin , Koethe Benjamin , Lundquist Christine , Lutz Jennifer , van Klaveren David , Steyerberg Ewout , Kent David M
Published: July 2021

Introduction:
Most heart failure (HF) clinical prediction models (CPMs] have not been independently externally validated. We sought to test the performance of HF models in a diverse population using a systematic approach.

Methods:
A systematic review identified CPMs predicting outcomes for patients with HF. Individual patient data from 5 large publicaly available clinical trials enrolling patients with chronic HF were matched to published CPMs based on similarity in populations and available outcome and predictor variables in the clinical trial databases. CPM performance was evaluated for discrimination (c-statistic, % relative change in c-statistic) and calibration (Harrell’s E and E
90
, the mean and the 90% quantile of the error distribution from the smoothed loess observed value) for the original and recalibrated models.

Results:
Out of 135 HF CPMs reviewed, we identified 45 CPM-trial pairs including 13 unique CPMs. The outcome was mortality for all of the models with a trial match. During external validations, median c-statistic was 0.595 (IQR 0.563 to 0.630) with a median relative decrease in the c-statistic of -57 % (IQR, -49% to -71%) compared to the c-statistic reported in the derivation cohort. Overall, the median Harrell’s E was 0.09 (IQR, 0.04 to 0.135) and E
90
was 0.11 (IQR, 0.07 to 0.21). Recalibration of the intercept and slope led to substantially improved calibration with median change in Harrell’s E of -35% [IQR 0 to -75%] for the intercept and -56% [IQR -17% to -75%] for the intercept and slope. Refitting model covariates improved the median c-statistic by 38% to 0.629 [IQR 0.613 to 0.649].

Conclusion:
For HF CPMs, independent external validations demonstrate that CPMs perform significantly worse than originally presented; however with significant heterogeneity. Recalibration of the intercept and slope improved model calibration. These results underscore the need to carefully consider the derivation cohort characteristics when using published CPMs.