bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P279: Workplace Facilities and Policies Associated With Bicycling to Work Among Adults
Authors: Porter Anna K , Kohl Harold W , Salvo Deborah
Published: July 2021

Introduction:
Bicycling to work is a mode of transportation that provides regular physical activity and has been associated with mental and physical well-being. Limited research has examined what facilities, such as bike racks, and policies within the workplace are associated with bicycling to work.

Hypothesis:
Access to workplace facilities and policies will be associated with higher odds of bicycling to work.

Methods:
In 2016/17, a convenience sample of adult residents of Travis County (Austin), Texas, and Jefferson County (Birmingham), Alabama who had ridden a bicycle at least once in the past year responded to an Internet-based questionnaire assessing correlates of bicycling. Participants who self-reported that a purpose of their bicycle trips was commuting to/from work were categorized as a bicycle commuter. Workplace facilities/policies included (a) bicycle lockers, (b) locked rooms/cages, (c) clothes storage, (d) bike racks, (e) showers, and (f) policies that supported bicycling to work. A summary score ordinal variable, (g) total facilitators, was derived by adding the total number of reported policies/facilities per participant. Multivariable logistic regression models adjusting for age, race, education, income, number of motor vehicles, relationship status, children in household, and sex were used to estimate the association between individual workplace facilities and policies, as well as total facilitators, and bicycle commuting. Interactions were tested between sex and each of the workplace variables. Analyses was limited to participants who were employed.

Results:
The final analytic sample was 771; 45% were categorized as a bicycle commuter (n=344). Access to workplace facilities/policies ranged from 7% (bike lockers) to 50% (bike racks). Bike lockers (OR 5.6; 95% CI 4.5,6.8), locked rooms/cages, (OR 2.2; 95% CI 1.4, 3.3), clothes storage (OR 2.0; 95% CI 1.5, 2.7), bike racks (OR 3.2; 95% CI 3.0, 3.3), and policies that supported bicycling to work (OR 3.3, 95% CI 2.5, 4.4) were associated with significantly higher odds of being a bicycle commuter. Only showers in the workplace showed a significant interaction by sex; showers were directly associated with being a bicycle commuter for males (OR 2.1; 95% CI 2.0, 2.1), but inversely associated with being a bicycle commuter for females (OR 0.9; 95% CI 0.8, 0.9). As compared to no facilitators, having 1 facilitator was associated with 2.1 times higher odds (95% CI 1.8, 2.6), 2 facilitators with 3.1 times higher odds (95% CI 2.1, 4.5), 3 facilitators with 4.4 times higher odds (95% CI 4.2, 4.8), and 4 or more facilitators with 7.9 times higher odds of being a bicycle commuter (95% CI 7.0, 9.0).

Conclusions:
The presence of workplace facilities/policies is associated with higher odds of bicycling to work. Workplaces should consider how the institutional environment can promote active transportation, and, in turn, employee health.
Abstract P348: Association Between Sleep Apnea and Blood Pressure Control Among African-Americans, the Jackson Heart Study
Authors: Johnson Dayna A , Thomas Stephen J , Abdalla Marwah , Yano Yuichiro , Guo Na , Rueschman Michael , Tanner Rikki , Wilson James , Mittleman Murray , Calhoun David A , Redline Susan
Published: July 2021

Background:
African-Americans have the highest prevalence of elevated blood pressure (BP) and poorer BP control than other racial/ethnic groups in the US. Untreated sleep apnea, common among minority populations, may explain the high prevalence of uncontrolled BP. We studied the association of objective measurements of sleep apnea severity with resistant hypertension and uncontrolled BP among African-Americans in the Jackson Heart Study (JHS) Sleep Ancillary study.

Methods:
Between 2012 and 2016, JHS participants (N=913) underwent an in-home sleep apnea study (measuring nasal pressure, abdominal and thoracic inductance plethysmography, oximetry, position, ECG); resting blood pressure; anthropometry; and completed questionnaires. Sleep apnea was defined as an apnea-hypopnea index
>
15 and nocturnal hypoxemia was quantified as % sleep time <90% oxyhemoglobin saturation (%Sat<90%). Elevated BP was defined as systolic BP ≥ 140 mmHg or diastolic BP
>
90mmHg. Controlled BP was defined as systolic BP <140mmHg or diastolic BP <90mmHg. Uncontrolled BP was defined as having elevated BP with use of
<
2 antihypertensive medications. Resistant hypertension was defined as having elevated BP while on 3-4 antihypertensive medications with one being a diuretic; or use of
>
4 antihypertensive medications. The study sample was limited to individuals with prevalent hypertension (N=613). Multinomial models were fit to determine the association between sleep apnea severity and resistant hypertension or uncontrolled BP (vs. controlled BP) adjusted for age, sex, education, smoking status, obesity (body mass index>30) and diabetes.

Results:
The study sample had a mean age of 54.8 years, were predominately female (69.8%), obese (57.8%), and college educated (52.7%). Approximately 40.5% had sleep apnea, which was untreated in 95% of individuals. Among the sample, 25.4% had uncontrolled BP and 4.9% were classified as resistant hypertension. After adjustment for confounders, individuals with sleep apnea had a 2.6-fold higher odds of resistant hypertension (95% confidence interval: 1.1, 5.9). A standard deviation higher %Sat<90% was associated with a 41% higher odds (1.1, 1.8) of resistant hypertension after adjustment for covariates. Sleep apnea and %Sat<90% were not related to uncontrolled BP.

Conclusion:
Among our sample of African-Americans in the JHS, sleep apnea was related to resistant hypertension but not uncontrolled BP. The study identifies the high burden of untreated sleep apnea in African-Americans and its association with resistant hypertension, a significant risk factor for stroke and heart disease. Research is needed on the impact of treating sleep apnea as a strategy for decreasing resistant hypertension, and thus, narrowing cardiovascular health disparities.
Abstract 17013: Preceding Contraction of Less Distensible Ventricular Compartment Plays a Key Role in the Pathogenesis of Mechanical Dyssynchrony in the Univentricular Heart
Authors: Hayama Yohsuke , Shimizu Shuji , Kawada Toru , Sugimachi Masaru
Published: July 2021

Background:
Septal flash motion is the key to mechanical dyssynchrony in the left bundle branch block in biventricular physiology. In univentricular Fontan circulations, however, morphological variations of systemic ventricles make it difficult to evaluate the negative impact of asynchronous contraction with widened QRS duration on hemodynamics.

Methods:
A computational simulation of Fontan circulation using a time-varying elastance chamber model combined with a three-element Windkessel vascular model was performed. Systemic ventricles were divided into two ventricular compartments (Vnt
1
, Vnt
2
) by large ventricular septal defects (VSD), which had various ratios of end-diastolic volumes (EDV
1
/EDV
2
, α) and contractilities (Emax
1
/Emax
2
, β). We introduced delayed contraction onset of Vnt
2
from Vnt
1
(T
dys
, ms) and simulated hemodynamic changes. We also studied 44 consecutive postoperative Fontan patients with wide QRS (28 male, 1-37 years; median age 16.2 years) and examined their clinical profiles including the analysis of focal ventricular wall motion with 2D speckle tracking echocardiography, hemodynamic parameters in cardiac catheterization, plasma levels of brain natriuretic peptide (BNP, pg/mL) and exercise capacities (peak VO
2
, mL/kg/min).

Results:
In
silico
, compared with the ventricles with α > 1 and β < 1, those with α < 1 and β > 1 exhibited significantly decreased cardiac output as T
dys
increased, and relatively impaired output reserve when tachycardia developed. These deteriorations were characterized by the increased reverse flow from Vnt
2
to Vnt
1
through VSD during mid-systole. Also in
vivo
, reverse flow during mid-systole via VSD, flash motion during isovolumic contraction time and lower peak systolic strain of smaller ventricular compartment were associated with higher central venous pressures, elevated BNP levels and decreased peak VO
2
(p < 0.05).

Conclusion:
Delayed contraction in more distensible ventricular compartment can exacerbate the mechanical dyssynchrony characterized by preceding “flash” contraction and subsequent dyskinetic dilation of less distensible compartment, which contributes to the pathogenesis of heart failure in the univentricular heart.
Abstract 17019: Secular Trends in Dilated and Hypertrophic Cardiomyopathy in an Epidemiological Cohort in Olmsted County, Minnesota
Authors: Masood Muhammad , Sherif Akil A , Jaliparthy Keerthi , Scott Christopher , Chamberlain Alanna , Ommen Steve R , Somers Virend K , Gersh Bernard , Lin Grace , Brady Peter A , Chahal Anwar A
Published: July 2021

Introduction:
Idiopathic Dilated (DCM) and hypertrophic cardiomyopathies (HCM) are leading causes of sudden cardiac death. The incidence and prevalence of both DCM and HCM were originally estimated in Olmsted County, MN over 1975-1984. Incidence was 6.0 and prevalence was 36.5 per 100,000 person-years, for DCM; with incidence and prevalence rates of 2.5 and 19.7 per 100,000 person-years for HCM. This study aims to determine the incidence and mortality rates of individuals diagnosed with HCM and DCM in Olmsted County, MN from 1984 to 2016.

Methods:
The Rochester Epidemiology Project is a validated long term medical record linkage system that collects and links medical information for the approximately 145000 residents of Olmsted County, Minnesota. Using this database and the Electronic Health Record systems at Mayo Clinic and Olmsted Medical Center in Rochester, MN, we manually reviewed and validated the medical records of 4440 patients. This cohort includes all patients with any mention of a cardiomyopathy based on ICD and HICDA codes during the period 1984 to 2016. Data were summarized with mean and standard deviation, frequency and percentage and compared between groups using two sample t-test for continuous data and chi-square for proportions. Survival was computed using Kaplan-Meier methods and compared to expected survival based on age and gender. Incidence was computed using Olmsted County population numbers during the time period and adjusted to the US 1980 white population to allow for comparison with the previous study.

Results:
The calculated crude incidence rate for DCM and HCM are 10.1 and 7.8 per 100,000 respectively. Incidence rates adjusted for comparison to US 1980 white population (age and sex adjusted) are 10.4 (95% CI: 9.3-11.4) and 8.0 (95% CI: 7.1-8.8) per 100,000 person-years, respectively. The observed number of deaths in this cohort (HCM and DCM) was 420 vs 194 expected.

Conclusions:
Calculated incidence, both crude and adjusted rates are higher than previously estimated rates. The crude incidence rate for HCM is almost 4-fold higher than that for DCM is 2.4 times higher than the original estimate by Codd et al. Individuals with cardiomyopathies were found to have a higher overall mortality rate than the general population with an observed to expected hazard ratio of 1.73 (95% CI 1.49-2.01, p<0.001) for DCM and 1.44 (95% CI 1.21-1.71, p<0.001) for HCM. Our findings suggest that previous studies may have underestimated the true burden of HCM and DCM in the population which has important implications for healthcare provision and cost.
Abstract 17020: Exercise With or Without Weight Loss and Functional Decline in Overweight or Obese Adults With Peripheral Artery Disease
Authors: Polonsky Tamar S , Zhang Dongxue , Bazzanno Lydia A , Criqui Michael H , Ferrucci Luigi , Guralnik Jack M , Kibbe Melina , Sufit Robert L , McDermott Mary M
Published: July 2021

Background:
Overweight or obese adults with PAD have greater functional decline than normal-weight adults with PAD. Walking exercise is first-line therapy for PAD. It is unknown whether weight loss+exercise is associated with less functional decline than exercise alone. Weight loss could worsen functional decline by decreasing muscle mass.

Methods:
Adults with PAD (ABI <0.90) and BMI ≥25 kg/m
2
underwent baseline testing 2002-2004. Mean follow-up was 3.4 years. Weight, six minute walk distance (6MWD) and self-reported exercise were measured annually. Weight loss was defined as ≥5 lb decrease compared to the prior year. Exercise was defined as walking ≥3 times/week for ≥30 min. To compare annual changes in 6MWD between groups (no exercise, exercise only, or exercise+weight loss) a mixed-effects linear regression analysis was used with a subject-specific random intercept, to account for the chance that a person’s annual change in 6MWD correlated with the prior annual change. Person-years for each group were summed from successive annual changes; adults could contribute person-years to ≥1 group. Analyses were adjusted for age, race, sex, ABI, smoking, comorbidities, lower extremity revascularization or hip/knee replacement during follow-up.

Results:
Among 271 adults (41% women, 15% black), mean age was 74±7.6 and ABI was 0.64±0.15. Mean baseline BMI was similar across groups (no exercise 30.7±4.6 kg/m
2
; exercise only 28.8±3.5 kg/m
2
; exercise+weight loss 30.1±4.3 kg/m
2
). PAD participants who walked for exercise and lost weight had less decline in 6MWD than those who walked without weight loss, or who neither exercised nor lost weight (p trend = 0.004) (Table).

Conclusions:
Overweight and obese adults with PAD who exercised and lost ≥5 lbs experienced less annual decline in the 6MWD than adults with only exercise or no exercise. A randomized trial is needed to determine whether weight loss+exercise improves functional outcomes for overweight or obese adults with PAD.
Abstract 17023: Early Incidence of First Myocardial Infarction in Adult Attention Deficit Hyperactivity Disorder Patients in the United States
Authors: Puli Pawan , Krovvidi Anila , Yandrapalli Srikanth , Kairam Ram
Published: July 2021

Background:
Behavioral patterns and pharmaceutical interventions in patients with attention deficit hyperactivity disorder(ADHD) might increase the risk of cardiovascular disease. Studies evaluating the differences in risk profiles and outcomes during first myocardial infarction in ADHD patients compared to the general population in the US are lacking.

Methods:
We performed a retrospective cohort analysis of the US National Inpatient Sample years 2005 - 2015 using appropriate ICD-9 codes to identify a weighted sample of hospitalizations for a first acute myocardial infarction (AMI) in adults. In this AMI cohort, patients with ADHD were identified. Differences in demographics, comorbidities, and outcomes were compared between patients with and without ADHD.

Results:
Of 4,285,185 first AMI cases, ADHD was present in 5379 (~1 in 1000). At the time of first AMI, patients with ADHD were 15 years younger (mean age 52 vs 67 years, p<.001) and were more likely to be men (72% vs 58%, p<.001) than those without. More patients with ADHD had private insurance and were in higher income categories; TABLE. Patients with ADHD had higher prevalence of substance abuse, smoking, obesity, dyslipidemia and depression whereas patients without ADHD had a higher prevalence of hypertension and diabetes mellitus. While the type of AMI was similar in both the groups, mechanical revascularization was more frequently performed in ADHD patients (69.4% vs 59.1%, p<.001). All-cause inhospital mortality during the first AMI was significantly lower in ADHD patients (1.3% vs 6.1%, p<.001).

Conclusion:
In the US, patients with ADHD had first AMI at a much younger age and had substantial differences in risk factor profile and outcomes compared to the general population. The influence of behavior patterns, underlying ADHD pathophysiology, and medical interventions in ADHD patients leading to the earlier AMI onset should be further explored.
Abstract 17037: Effect of Pregnancy on Long-Term Prosthetic Cardiac Valve Survival
Authors: Batra Jaya , Itagaki Shinobu , Egorova Natalia N , Chikwe Joanna
Published: July 2021

Introduction:
The effect of pregnancy on the lifespan of prosthetic heart valves is an important consideration in valve selection for women with valvular heart disease who may desire future pregnancy. Current evidence is mixed and limited to small, single-center studies.

Methods:
Retrospective analysis of 11,930 women ≤50 years of age who underwent 14,017 valve replacements in California, New Jersey, and New York State between 1990 and 2015. Patient were identified using state-run mandatory administrative databases. Average follow-up time was 9.4 years (SD 6.7 years). To evaluate the association between pregnancy and time to reoperation, time-dependent propensity scoring was used to match women with pregnancy at the time of earliest delivery with controls at risk for pregnancy within the same year after valve implantation. Controls were any woman with valve implantation and without exposure to pregnancy during the study period that was free from reoperation, death, or censoring at the time of matching.

Results:
Pregnancies in 417 women with 241 biologic valves and 217 mechanical valves were identified. After propensity score matching, there were no significant differences between the pregnant and control groups for both the cohorts with biologic and mechanical valves. Pregnancy was a significant risk factor for reoperation for both biologic (HR 2.5, 95% CI 1.6-3.8 after time-dependent propensity matching) and mechanical (HR 2.3, 95% CI 1.3-4.1 after time-dependent propensity matching) prostheses. For women with mechanical valves who experienced pregnancy and subsequently required reoperation, almost half of reoperations occurred within one year of delivery. Almost all were performed on valves at the mitral position (84.6%) and had diagnosis codes for valve-related complications, including valve thrombosis (76.9%).

Conclusion:
Pregnancy accelerates time to reoperation for both biologic and mechanical prostheses. Mechanical valves, especially those in the mitral position, are at particular risk for near-term valve loss after delivery.
Abstract 17038:
Twist1
Modulates Smooth Muscle Cell Phenotypes in Atherosclerosis
Authors: Guerraty Marie A , Nurnberg Sylvia T , Shah Vraj , Rader Daniel J
Published: July 2021

Introduction:
Genome-wide association studies have identified rs2107595, a non-coding locus on chromosome 9 between HDAC9 and
Twist1
genes, as a risk allele for several vascular phenotypes, including Coronary Artery Disease (CAD). Rs2107595 has, more specifically, been associated with stable CAD over myocardial infarction phenotypes. Recent work has shown that rs2107595 risk allele increases
Twist1
expression in smooth muscle cells (SMCs) by creating an RBPJ binding site. In other cell types,
Twist1
is known to maintain cells in a de-differentiated state and to promote epithelial to mesenchymal transformation, driving tumor progression and metastasis.

Hypothesis:
Twist1
modulates SMC differentiation to promote an immature proliferative state over a differentiated (osteoblastic) state. This shift in phenotype promotes features of plaque stability
in vivo
.

Methods:
Twist1
expression plasmid (pCMV6-TWIST1) was transfected into A7r5 rat smooth muscle cells. To assess proliferation, cells were counted at 24, 48, 72, and 96 hours. To assess calcification, A7r5 cells were cultured in calcification media (2mM NaPhos) for 10 days and stained with Alizarin Red.
In vivo
studies were performed in Twist1 fl/fl tamoxifen-inducible MYH11-Cre C57BL/6 mice on ApoE-/- background fed a Western diet for 16 weeks to induce atherosclerotic lesions. Immunohistochemistry with SM22a identified lesion SMCs, and alizarin red was used to identify calcifications.

Results:
Ectopic overexpression of
Twist1
in A7r5 SMCs decreased proliferation at 48h and 72h (80%, p=0.014).
Twist
1 overexpression also decreased the total area of calcification (33% reduction, p=0.007).
In vivo
, both control and
Twist
1 KO mice show similar burden of atherosclerosis. However, there is a decrease in sub-endothelial SMCs in atherosclerotic lesions by SM22a staining in the
Twist1
KO. Additionally,
Twist1
KO mice have more prominent and larger focal calcifications.

Conclusions:
Twist1
promotes SMC proliferation and decreases calcification
in vitro
, and may affect the presence of subendothelial SMCs and calcification
in vivo
. This provides a compelling link that rs2107595 may promote plaque stability in CAD by increasing
Twist1
to modulate SMC phenotypes.
Abstract 17039: Neutrophil Subset in Blood Contributes to Acute Oxidant Signals in the Bone Marrow, Which Regulate Innate Immune Responses After Ischemic Tissue Damage
Authors: Thiruppathi Muthusamy , Barman Pijus , Fang Milie , Koh Timothy , Urao Norifumi
Published: July 2021

Blood neutrophils are short-lived and have distinct subsets. Aged (senescent) neutrophils are cleared by macrophages in multiple organs including bone marrow (BM), at least, in the steady state. It is unknown, after ischemic tissue damage, how these aged-type neutrophils regulate bone marrow microenvironment and impact on downstream bone marrow responses. In a mouse model of critical limb ischemia, we found that CD62L
lo
aged-type neutrophils that return to the BM, measured by in vivo circulating cell-labeling, are increased (2.1-fold) after acute limb ischemia, which is corresponded with acute increase in CXCR4, a major chemokine receptor promoting BM returning of blood neutrophils (31%). Interestingly, neutrophil uptake by macrophages is reduced (by 76%) in the BM after limb ischemia, suggesting increased retention of blood-derived CD62L
lo
neutrophils in BM microenvironment after ischemia. We also found, in the BM, that blood-derived neutrophils have higher reactive oxygen species (ROS) than other neutrophils (61% in MFI) and that limb ischemia indeed increases ROS (34%) and oxidized lipid microparticles (61%) in BM plasma in a Nox2 NADPH oxidase-dependent manner. These suggest that increased returning and retention of blood-derived CD62L
lo
neutrophils in the BM may contribute to oxidant signals in the BM after limb ischemia. Indeed, using aged neutrophils generated ex vivo and adoptive transfer of these cells, we found that aged neutrophils modulate BM innate immune responses after limb ischemia through ROS—reduced activation of hematopoietic stem progenitor cells (50%); increased acute activation of myeloid progenitor cells (4%); and increased acute but inhibited later Ly6C
hi
inflammatory monocytes/macrophages in the ischemic tissue (72% and 45%, respectively)—resulting in improved tissue recovery from ischemic damage (2.3-fold). In summary, an aged-type neutrophil subset in blood contributes to acute oxidant signals in the BM, which coordinate innate immune responses to promote tissue recovery from ischemic damage.
Abstract 17048: Dederivation and Validation of a Simple Heart Risk Score in 608,544 Thai Adults: HCUR Study
Authors: Chamnan Parinya , Mahawanakul Weera , Boongird Prasert , Nitiyanant Wannee , Aekplakorn Wichai ,   HCUR Investigators
Published: July 2021

Introduction:
Most heart risk prediction equations were developed in Western populations. These risk scores are likely to perform less well in Asian populations, who have different background risk.

Hypothesis:
This study aimed to develop and validate a new risk algorithm for estimating 5-year risk of developing coronary heart disease (CHD) in a large retrospective cohort of Thai general population.

Methods:
This retrospective cohort was derived from the linkage of 2006 health checks data with diagnostic information from electronic health records of 608,544 men and women aged 20 years and above residing in Ubon Ratchathani. It was randomly and evenly divided into the derivation and validation cohorts. An outcome of interest was first recorded diagnosis of CHD over a period of 6 years between January 2006 and December 2012. A Cox proportional hazards model was used to estimate effects of risk factors on CHD risk and to derive a risk equation in the derivation cohort. Measures of discrimination, global model fits and calibration were calculated in the validation cohort.

Results:
The derivation cohort comprised of 304,272 individuals, who contributed 1,757,369 person-years of follow-up and 1,272 incident cases of CHD, while the validation cohort comprised of 304,272 individuals (1,757,312 person-years), with 1,290 incident cases of stroke. The risk equation was 0.0580 x Age (years) + 0.5739 x Sex (Male=1) + 0.3850 x Hypertension (present=1) + 0.7080 x Diabetes (present=1) + 0.0386 x Body mass index (kg/m
2
) + 0.2117 x Central obesity (present=1) - 0.1389 (if exercise 1-2 days/week) or -0.3975 (if exercise 3-5 days/week) or - 0.5598 (if exercise >5 days/week). The stroke risk equation had a reasonably good discriminatory ability in the validation cohort with the area under the receiver operating characteristic curve of 0.790 (95%CI 0.779-0.801). The risk equation had good global model fit as measured by Bayesian information criteria. The Gronnesby and Borgan test showed good calibration, with chi-square statistic of 809.45 (p<0.001).

Conclusions:
This simple heart risk score is the first risk algorithm to estimate the 5-year risk of CHD in a Thai general population. The risk score does not need laboratory tests and can therefore be used in clinical settings and by the public.
Abstract 17144: Cardioprotective Effect of Beta Blockers in Patients With Breast Cancer Undergoing Chemotherapy and Radiation Therapy: Is It a Myth or Reality?
Authors: Ivanov Alexander , Kancharla Pragnan
Published: July 2021

Background:
Breast cancer is the leading cause of cancer in women worldwide. Cardiotoxicity is a common complication of anthracycline based regimens. It has been suggested that use of beta blockers (BB) may have cardioprotective effect in patients with breast cancer undergoing therapy.

Methods:
A systematic search of 3 electronic databases was performed for all randomized clinical trials between 1990 and 2018 comparing BB and placebo in patients with breast cancer undergoing chemotherapy. Primary outcome was change in left ventricular ejection fraction (LVEF) , secondary outcome was change in LV diastolic function measured as difference in early (E) to late (A) ventricular filling velocities (E/A ratio). We used Cohen method for this meta-analysis.

Results:
Total of 6 studies evaluating 614 females, with mean age of 49 (±7) years were included. These patients were receiving anthracyclines with or without transtuzumab over weighted mean follow up of 8 (±3) months. There was a smaller LVEF decline in patients treated with BB compared to placebo with standardized mean difference (SMD) of 0.34% (0.18%-0.5%), p<0.01 and significant heterogeneity I
2
86%, p<0.01(Figure 1). There were only 3 studies reporting on e/a ratio. There was a significantly lower decline in e/a with BB therapy , SMD of 0.46 (0.23-0.7), p<0.01, with high heterogeneity I
2
85%, p<0.01 (Figure 2).

Conclusion:
Beta blockers can preserve left ventricular systolic and diastolic function in patient with breast cancer undergoing chemotherapy. Observed high heterogeneity indicates the need for larger trials.
Abstract 17166: Comparison Between Use of Vasoactive Medications in Patients Undergoing PVC and VT Ablation
Authors: Sandhu Amneet , Graham Jeffrey , Tumolo Alexis , Fleeman Blake , Mantini Nicholas , Rosenberg Michael , Tzou Wendy , Sauer William H , Nguyen Duy T
Published: July 2021

Background:
Societal guidelines have set prerequisites regarding procedures conducted in the EP lab. Despite metrics for management of EP cases, no clear guidelines exist for use of hemodynamic drugs to support complex ablations, particularly in setting of structural heart disease.

Objectives:
We sought to understand the variety and range of vasoactive medication use in patients undergoing PVC/VT ablation.

Methods:
Patients undergoing PVC or VT ablation, from January 2015 to December 2016, at our institution were analyzed. Demographics, echocardiography, and procedural details, including vasoactive medication use, were analyzed.

Results:
Sequential patients undergoing PVC or VT ablation (70 in each arm) were studied. Those undergoing PVC ablation (56 +/- 14 years, 30% female) had an average EF of 58% in comparison to 44% (p<0.01 for EF difference) in VT ablation patients (60 +/- 13 years, 20% female); more VT patients (62%) were under general anesthesia. Pressors were administered in 86% of cases with the significant majority (63%) consisting of alpha-agonists (phenylephrine, ephedrine, epinephrine). Importantly, 48% of cases required continuous drip initiation (Figure). Regardless of case type or abnormal EF, drip initiation with or administration of multiple bolus doses of alpha-agonists was much more frequent compared to inotropes (Figure). In a subset of patients with EF ≤ 35%, 96% received vasoactive medications with 73% receiving a continuous drip or multiple bolus doses of phenylephrine.

Conclusions:
Vasoactive medication use during ventricular EP cases is common. Regardless of baseline EF, a propensity for use of alpha-agonists exists that may affect the treatment of patients with abnormal LV function. More studies are needed to assess the impact of pressor use on patient safety and procedural endpoints in the EP lab.

Figure:
Abstract 17169: Computationally-Engineered Analog of Stromal Cell-Derived Factor 1α Preserves the Mechanical Properties of Infarcted Myocardium Under Planar Biaxial Tension
Authors: Wang Hanjay , Wisneski Andrew , Paulsen Michael J , Wang Zhongjie , Lopez Hernandez Hector , Xuan Yue , von Bornstaedt Daniel , Steele Amanda N , Stapleton Lyndsay M , Lucian Haley J , Eskandari Anahita , Thakore Akshara D , Farry Justin M , Hironaka Camille E , Williams Kiah M , Wu Matthew , MacArthur John W , Woo Y. Joseph
Published: July 2021

Introduction:
Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, ultimately leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI.

Methods:
Male Wistar rats (n=46) underwent sham surgery (n=15) or permanent left anterior descending coronary artery ligation (n=31). Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n=15) or ESA (6 μg/kg, n=16), delivered at standardized peri-infarct sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Biaxial tensile testing of the anterior LV wall was performed using a strain-controlled biaxial load frame (Fig. 1A), producing up to physiologic circumferential and longitudinal strains (ε=20%, each). The modulus was determined along each axis, and maximum shear stress was calculated as a composite metric of the tissue’s response to physiologic strains. Data are expressed as mean±SEM.

Results:
At 4 weeks post-MI, ESA-treated hearts had smaller end-diastolic LV internal dimension (6.89±0.27 cm vs 7.69±0.22 cm, p=0.03) and improved ejection fraction (63.7±2.9% vs 49.4±4.4%, p=0.01) compared to saline-injected controls. Hearts treated with ESA exhibited lower moduli than saline controls in both the circumferential (269.4±33.2 kPa vs 431.5±55.6 kPa, p=0.02) and longitudinal axes (182.4±25.0 kPa vs 332.3±51.2 kPa, p=0.02, Fig. 1B). The maximum shear stress for ESA-treated hearts was significantly reduced compared to that for saline controls (5.8±0.8 kPa vs 9.0±1.2 kPa, p=0.03) and was similar to that for sham controls (Fig. 1C).

Conclusion:
Intramyocardial ESA injection mitigates post-MI tissue stiffening and preserves biaxial LV mechanical properties.
Abstract 17177: Cost of Hospitalizations Related to Hypertension (HTN) and Acute Myocardial Infraction (AMI) Related Events: Result From the 2014 Medical Expenditure Panel Survey
Authors: Veledar Emir , Saxena Anshul , Rubens Muni , Das Sankalp , McGranaghan Peter
Published: July 2021

Background:
Each year in the USA, more than 75 million adults are diagnosed with hypertension (HTN), but less than 54% have it condition under control. Mortality due to HTN or related complications was 410,000 in 2014 and resulted in close to $50 billion spent. Acute Myocardial Infarction (AMI) is the most dramatic manifestation of coronary artery disease. Every year, about 735,000 people are diagnosed with AMI and it is estimated that hospitals lose $4493-$7940 per AMI patient on hospitalization. We studied interplays of expenditures for all events associated with HTN and AMI in the US in 2014.

Methods:
We used all available subsets from Medical Expenditure Panel Survey (MEPS; 2014) to extract all cost and utilization events related to HTN and AMI, following procedures for complex surveys as described in MEPS specifications to define population influenced by HTN and AMI, number of events, and related costs. Patients were included in this analysis if they were ≥20 years.

Results:
In 2014, there were about 236 million weighted participants in MEPS. Out of these, about 4.9 million participants reported costs related to AMI and 61.8 million related to HTN. About 3.9 million people reported both. Out of 61 million with HTN, 4 million reported AMI, whereas out of 174 million without HTN, only 1 million had AMI (OR: 11.1; 7.9-15.5). Those who had events associated with AMI, with an average cost of $5328/event, adding to total expenditures of $26.6 billion. Cost of AMI, HTN and both were $6.8 billion, $4.1 billion, and $2.7 billion, respectively. The total cost of hospitalization due to both HTN and AMI was 31.4% of the total healthcare expenditure among these participants.

Conclusion:
Burden of AMI includes almost 5 million people who live and die with AMI, and pay a high cost to manage this condition. Evidence from this study suggests that there is a significant disparity between the cost of hospitalization due to AMI between people with HTN and without HTN, which has potential implications on outcomes, quality of care, and hospital sustainability for AMI population. Symptom management at primary care settings may decrease the number of AMI events resulting in lower spending and cost savings by hospitals.
Abstract 17182: The Role of ROS Sensitive TRPM2 Mediated Inflammation in Atherosclerosis
Authors: Yu Albert , Yue Zhichao , Feng Jianlin , Aguila Hector , Yue Lixia
Published: July 2021

Introduction:
A variety of cardiovascular diseases stem from the manifestations of subclinical atherosclerosis, whose growth is fueled by inflammatory cytokines produced by macrophage-derived foam cells. A better understanding of the mechanisms underlying atherosclerosis will provide novel insights on potential therapeutic approaches for atherosclerosis associated cardiovascular diseases. The Ca
2+
-permeable TRPM2 which is activated by various reactive oxygen species (ROS) under stress conditions, is highly expressed in monocytes and macrophages. Our objective is to understand how TRPM2 in monocytes/macrophages mediates inflammation in atherosclerosis. Our hypothesis is that monocyte/macrophage TRPM2 is activated in the oxidative environment of atherosclerosis, and blocking TRPM2 will attenuates initiation and progression of atherosclerosis, thereby mitigating atherosclerotic cardiovascular disease.

Methods:
ApoE-deficient mice with
Trpm2
deletion (APOE-TRPM2 double knockout: DKO) mice were fed with a high fat diet (HFD) to generate atherosclerosis. TRPM2 activity was measured by patch-clamp electrophysiology using peritoneal macrophages (PMs) obtained from DKO mice fed with HFD. Peripheral blood cells were collected from the tail vein and analyzed by flow cytometry.

Results:
We found that atherosclerosis plaque area was significantly reduced in HFD-fed DKO mice in comparison with the HFD-fed ApoE-KO mice (p<0.001). The TRPM2 channel activity and TRPM2 mediated Ca
2+
entry in macrophages were markedly higher in ApoE-KO mice fed with HFD than the ApoE-KO mice fed with normal chow, suggesting that TRPM2 may play a role in the atherosclerosis (p<0.05). Moreover, TRPM2 deletion drastically reduced IL-β production in PMs induced by LPS. Furthermore, we found that Trpm2-KO led to a 17% reduction of the inflammatory circulating myeloid cells in the ApoE-TRPM2 DKO mice compared to ApoE-KO mice fed with HFD (p<0.005).

Conclusions:
Our results indicate that deletion of TRPM2 reduces atherosclerotic plaques. Both inflammatory cytokine IL-1β production and inflammatory macrophages are reduced by TRPM2 deletion, indicating that the mechanisms by which TRPM2 inhibition deletion reduces atherosclerosis is through inhibiting inflammation during the atherosclerosis. As oxidative stress is a hallmark of atherosclerotic plaques, targeting monocyte/macrophage TRPM2 may serve as a novel approach to halt initiation and progression of atherosclerosis, as well as atherosclerotic cardiovascular diseases.
Abstract 17187: The Association of Longitudinal Patterns of Metabolic Syndrome With Elevated hs-cTnT: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Vakil Rachit M , Adesiyun Tolulope , Kwak Lucia , Sharma Kavita , Nambi Vijay , Michos Erin D , Neeland Ian J , Blumenthal Roger , Ballantyne Christie , Selvin Elizabeth , Coresh Josef , Ndumele Chiadi E
Published: July 2021

Background:
Longitudinal increases in metabolic syndrome (MS) components are associated with increased heart failure (HF) risk, but the association of MS change over time with subclinical myocardial injury is unknown.

Hypothesis:
Greater progression and duration of MS is associated with subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin T (hs-cTnT).

Methods:
We studied 8,170 participants (mean age 63, 59% female) without coronary heart disease, HF or diabetes at ARIC Visit 4 (1996-1998) with available data on MS components from the first four ARIC visits and hs-cTnT data at Visit 4. We defined MS using AHA/NHLBI criteria for high waist circumference (WC), hyperglycemia, elevated blood pressure (BP), low HDL-C and hypertriglyceridemia, with a diagnosis of MS made by ≥ 3 components. Using data on MS components from Visit 1 (1987-89) through 4, we used logistic regression models adjusted for demographics and cardiovascular risk factors to evaluate associations of changes in MS components over time and duration of MS with elevated hs-cTnT (≥ 14 ng/L) at Visit 4.

Results:
3,644 (45%) of Visit 4 participants had MS. Greater number of MS components at Visit 4 was associated with a higher likelihood of elevated hs-cTnT, with the highest odds seen for those with 5 MS components (OR 2.32; 95%CI: 1.39-3.87) compared to those with none. Among MS components, the strongest associations were seen for elevated BP and high WC. Among participants without MS at V1, those with no MS components at both Visits 1 and 4 had the lowest odds of elevated hs-cTnT (reference), with progressively higher likelihood of elevated hs-cTnT for those increasing to 1-2 (OR 1.12; 95%CI 0.61-2.06), 3 (OR 1.90; 95%CI 1.04-3.45) and 4-5 (OR 2.64; 95%CI 1.41-4.92) MS components by Visit 4. MS duration was also significantly associated with elevated hs-cTnT, with an OR of 1.08 (95%CI: 1.06-1.11) per year of MS duration.

Conclusions:
Greater MS severity and progression, and longer duration of MS, are associated with a higher likelihood of subclinical myocardial injury. This may have mechanistic implications for the association between MS and HF, and underscores the need to refine strategies to prevent MS onset and progression.
Abstract 17191: Intraprocedural Dobutamine Use is Independently Associated With Prolonged Length of Stay (LOS) Following Ventricular Tachycardia (VT) Ablation
Authors: Graham Jeffrey D , Rosenberg Michael , Sandhu Amneet , Tumolo Alexis , Tzou Wendy , Sauer William , Borne Ryan , Nguyen Duy
Published: July 2021

Introduction:
Use of inotropes such as dobutamine remains controversial in the management of heart failure (HF) due to uncertain efficacy and lack of mortality benefit. Furthermore, vasoactive drugs are frequently utilized during VT ablations despite minimal data regarding their effects on outcomes. Vasoactive drugs may impact factors such as long-term VT recurrences and hospital length of stay.

Hypothesis:
We sought to evaluate the hypothesis that the use of dopamine, dobutamine or phenylephrine have differential effects on outcomes after VT ablations.

Methods:
A retrospective analysis was completed for all VT ablations from 2013-17 at our institution. Patient characteristics and procedural details were collected for 149 VT ablation cases.

Results:
The cohort was 81% male, and 67% had cardiomyopathy of which 53% were ischemic with a mean EF of 29% (CI 26.7- 31.4). Average procedure time was 368 minutes (CI 347-388). Vasoactive drugs were used in 87% of patients undergoing VT ablation: phenylephrine (67%), dopamine (40%), dobutamine (37%). The median LOS for all patients was 5 days (mean 7 days, range 1 - 56 days, IQR 2 - 9 days). After adjusting for inducibility, HF and procedural time, the dose of dobutamine, but not dopamine or phenylephrine, was significantly associated with increased length of stay (Fig. 1a). Inducible VT at the end of the procedure also correlated with increased LOS (5.4±0.3 vs 8.6±0.3, p < 0.0001). Procedural time did not associate with increased LOS. Of all covariates, only the number of VTs induced during the procedure was significantly associated with increased VT recurrence (HR 1.22/VT morphology (CI 1.11-1.34, p < 0.001)).

Conclusions:
Dobutamine, but not phenylephrine or dopamine, was significantly associated with increased length of stay after adjusting for HF, procedural time and inducibility of VT. More research is needed regarding vasoactive drug use in VT ablations and their significance to procedural and post-procedure outcomes.
Abstract 17200: Plasma BNP Declines in the First Two Years After Transplant and is Elevated at the Time of Treated Rejection
Authors: Valikodath Tom J , Jorgensen Neal , Albers Erin , Hong Borah , Friedland-Little Joshua , Kemna Mariska , Law Yuk
Published: July 2021

Introduction:
Plasma B-type natriuretic peptide (BNP) is a biomarker used to diagnose and monitor ventricular dysfunction and heart failure. However, the response of the allograft to produce BNP from ventricular wall stress and inflammation may be different, particularly in an understudied population such as pediatric recipients.

Hypothesis:
BNP levels decrease over time after transplant as the allograft recovers; but BNP will be higher during rejection.

Methods:
Enrolled all heart recipients from January 2007 to December 2016. Rejection surveillance included serial echocardiography, annual biopsy, and BNP q 1-3 months. Rejection is defined as requiring augmentation of immunosuppression from biopsy grade ≥ 2R or ≥ pAMR2 or from clinical diagnosis.

Results:
Among 114 patients studied, 60% were male with age at transplant 5.8 ± SD 6.5 yrs. Follow-up was 3.7 ± 2.7 yrs and 37 patients (32%) experienced 75 episodes of rejection. A total of 8358 BNP samples were obtained. BNP decreased linearly after transplant leveling off after 2 years (Fig 1). BNP was 671 ± 1115 (n=75) at rejection vs. 187 ± 423 pg/mL (n=501) without rejection confirmed by biopsy. By multivariable analysis, Ln BNP was associated with rejection (RR 1.56; 95% CI 1.35-1.80). Figure 2 shows the relationship between change in BNP and risk of rejection. Multivariable longitudinal Cox proportional model incorporating BNPs leading to 1
st
rejection showed Ln BNP to be associated with rejection (HR 2.22; 95% CI 1.53-3.23, p<0.001).

Conclusion:
BNP continues to decrease in the 1
st
2 years after transplant. At rejection, BNP is elevated, and this test can be further developed to screen for rejection.
Abstract 17203: Exosomes From Induced Pluripotent Stem Cell-Derived Cardiomyocytes Salvage the Injured Myocardium by Modulation of Autophagy
Authors: Santoso Michelle R , Tada Yuko , Ikeda Gentaro , Jung Ji-Hye , Vaskova Evgeniya , Sierra Raymond G , Gati Cornelius , Goldstone Andrew B , Bornstaedt Daniel V , Shukla Praveen , Wu Joseph C , Wakatsuki Soichi , Woo Joseph , Yang Phillip C
Published: July 2021

Background:
Induced pluripotent stem cells (iPSCs) and their differentiated cardiomyocytes (iCMs) have tremendous potential as patient-specific therapy for myocardial injury (MI). Our previous work showed that the iCMs restore the injured murine myocardium through secretion of paracrine factors, modulating apoptotic pathways to restore the murine peri-infarct region (PIR).

Hypothesis:
iCM-derived exosomes (iCM-Ex), a major constituent of the iCM secretome, may salvage the injured cardiomyocytes in the PIR.

Methods:
iCM-Ex were precipitated from iCM supernatant and characterized using various molecular analyses. Immunodeficient mice sustained MIs and received iCMs, iCM-Ex, or PBS control via direct intramyocardial injection into the PIR. Cardiac MRI assessed LV ejection fraction (LVEF) and viability at 2- and 4-week post-injection. iCMs, iCM-Ex, and PIR tissue were isolated for molecular and histological analyses.

Results:
iCM-Ex measured approximately 142 nm and expressed CD63 and CD9. iCM and iCM-Ex miRNA profiles had significant overlap, indicating that exosomal content was reflective of the parent cell.
In vitro
iCM apoptosis was increased significantly by hypoxia and exosome biogenesis inhibition while iCM-Ex or rapamycin reduced iCM apoptosis (p<0.05, vs. control). Mice treated with iCMs or iCM-Ex had significantly improved LVEF and LV viability compared to the control (p<0.05). Apoptosis and fibrosis were significantly reduced in iCM- and iCM-Ex treated mice. Autophagy and associated mTOR signaling pathway were significantly enhanced in iCM-Ex treatment group.

Conclusions:
iCM-Ex demonstrated similar efficacy as the iCMs in improving post-MI cardiac function by regulating autophagy and apoptosis of hypoxia injured cardiomyocytes. This finding represents the potential of cell-free, patient-specific biologic to treat ischemic cardiomyopathy by stimulation of an endogenous repair mechanism.