bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P361: Inflammatory Burden May Partially Mediate the Relationship Between Everyday Discrimination and Carotid Plaque Height in Midlife Women
Authors: Suder Egnot Natalie , Barinas-Mitchell Emma , Orchard Trevor , Wassel Christina , Brooks Maria , Mulukutla Suresh , Thurston Rebecca
Published: July 2021

Introduction:
Self-reported experiences of discrimination have been associated with greater risk of incident cardiovascular events and all-cause mortality across racial/ethnic groups. However, questions remain regarding the potential mechanisms through which perceived discrimination may influence cardiovascular risk. Furthermore, the relationship between self-reported discrimination with markers of subclinical cardiovascular disease (CVD) such as atherosclerotic plaque presence, burden, and characteristics remains unclear. We hypothesized that perceived discrimination is associated with subclinical measures of carotid atherosclerosis indicative of greater CVD risk and that inflammation is a mechanism contributing to this relationship.

Methods:
Late peri- and postmenopausal women without clinical CVD (n=300) completed the Everyday Discrimination Scale, developed in order to assess day-to-day experiences of interpersonal mistreatment, and underwent B-mode ultrasound to assess carotid atherosclerosis. Associations between everyday discrimination and measures of carotid plaque presence, burden (total number of plaques, total plaque area), and characteristics (maximum height, grey-scale median, and calcification) were evaluated using linear and logistic regression models adjusted for demographics, as well as CVD and psychosocial risk factors. Overall circulating inflammatory burden, comprising C-reactive protein, interleukin-6, and fibrinogen was identified via exploratory factor analysis and was evaluated as a potential mediator of the relationship between everyday discrimination and subclinical CVD through the ratio of the natural indirect effect and the total effect by inverse probability weighting.

Results:
The sample was predominately white (72% white (n=216); 22% black (n=66)), nearly half the women (n=138) had at least one carotid plaque, and 40% (n=120) reported experiencing high levels of everyday discrimination. After adjustment, women who reported high levels of discrimination had a maximum carotid plaque height 0.29 mm higher (p=0.03) than those who reported lower levels of discrimination. Circulating inflammatory burden was identified as a partial mediator of the relationship between high discrimination and carotid plaque height explaining 31% of the relationship. There were no significant associations of plaque presence, burden, or other plaque characteristics with discrimination, and the results did not vary by race/ethnicity.

Conclusions:
These findings add to the growing evidence that perceived discrimination may be associated with elevated cardiovascular disease risk among women of various racial/ethnic groups. These results suggest that increased inflammatory burden may be a mechanism through which experiences of discrimination may be associated with the development of atherosclerosis in midlife women.
Abstract P363: Visceral, but Not Subcutaneous Adiposity by Computed Tomography is Associated With Increased Aortic Wall Thickness in Psoriasis Patients
Authors: Groenendyk Jacob W , Shukla Parag , Elnabawi Youssef A , Rivers Joshua P , Goyal Aditya , Belur Agastya D , Dey Amit K , Sadek Ahmed , Nanda Navya , Rodante Justin , Ahlman Mark A , Joshi Aditya A , Gelfand Joel M , Playford Martin P , Mehta Nehal N
Published: July 2021

Introduction:
Patients with psoriasis (PSO), an inflammatory skin disease, experience increased cardiovascular disease and obesity. Traditional measures of obesity, such as BMI and waist-to-hip ratio (WHR), do not fully capture the increased cardiovascular risk. Assessment of adipose tissue distribution via CT scan enables characterization of visceral adiposity (VAT) versus subcutaneous adiposity (SAT), which is clinically useful as excess VAT is known to be associated with cardiovascular events. Aortic Wall Thickness (AWT) is a validated measure of subclinical atherosclerosis. However, the relationship between adiposity distribution and AWT is unknown.

Hypothesis:
We hypothesized that VAT, but not SAT, BMI, or WHR, would be associated with increased AWT in PSO patients.

Methods:
Consecutive PSO patients (n=164) underwent quantification of VAT and SAT via CT, and AWT via MRI of the descending aorta. Interrelationships were analyzed via multivariable regression.

Results:
Patients were middle-aged (mean 50.4), predominantly male (56%), and were at low cardiovascular risk (median Framingham risk 3), despite high prevalence of hyperlipidemia (47%). VAT was significantly associated with AWT (β=0.18, p=0.04), SAT, BMI, or WHR did not demonstrate similar association. This association persisted beyond adjustment for SAT, Framingham score, insulin resistance, and systolic BP (β=0.30, p=0.03).

Conclusions:
Visceral adiposity demonstrated an association with AWT, a marker of early atherosclerosis, whereas subcutaneous adiposity, BMI, and WHR did not. These findings add to a growing body of literature that visceral fat and its assessment may provide incremental data for risk of subclinical CVD.
Abstract P372: Coronary Angiography Use, Results and Revascularization Trends in Olmsted County, Minnesota, 2000 to 2015
Authors: Gerber Yariv L , Weston Susan , Killian Jill , Fabbri Matteo , Manemann Sheila , Asleh Rabea , Roger Veronique
Published: July 2021

Background:
A decline in all forms of coronary revascularization has been previously reported. Whether the decline has continued after the turn of the century is unknown as well as whether it is influenced by trends in the use and results of coronary angiography.

Methods:
All diagnostic and therapeutic coronary procedures performed among Olmsted County, MN residents from 2000-2015 were analyzed. Standardized rates (per 100,000 population) were calculated applying the direct method and temporal trends compared using Poisson regression models. Trends in disease severity, defined as 3-vessel and/or left main coronary artery disease (CAD), were assessed using logistic regression models.

Results:
Between 2000 and 2015, 11,691 coronary angiographies were performed (63% men; 54% ≥ 65 years of age). The age- and sex-standardized rates of angiography decreased over time (p
trend
< 0.001; Figure). Overall, 30% of the subjects had 3-vessel and/or left main CAD, and this proportion decreased over time (age- and sex-adjusted odds ratios (95% CI) for severe CAD: 0.68 (0.62-0.76) in 2005-2009 and 0.69 (0.63-0.77) in 2010-2015 compared with 2000-2004). Among 5,222 coronary revascularization procedures performed, 78% were PCI and 22% CABG. The age- and sex-standardized rates of any revascularization declined during the study period, reflecting temporal decreases in both PCI and CABG (all p
trend
< 0.001; Figure). The declines in angiography rates, CAD severity, and revascularization utilization were consistently greater in women than men (all P for interactions < 0.01).

Conclusions:
Declines in all forms of coronary revascularization, which were greater in women than men, have occurred in Olmsted County, MN, from 2000-2015. The declines occurred in the context of fewer angiograms performed in the population and reduced severity of anatomic CAD.
Abstract P377: Multicomponent Workplace Wellness Program Results in Weight Loss and Improved Cardiometabolic Indices
Authors: Bailey Ryan R , Fitzsimmons-Craft Ellen , Boeger Holley , Keenoy Katie , Hendrickson Sara , Welch Robinson , Wilfley Denise
Published: July 2021

Introduction:
Workplace wellness programs offer opportunities for decreasing obesity in adults. The effectiveness of such programs varies and is influenced by key intervention components (e.g. duration, intensity, content). We developed a multicomponent workplace wellness program, MyWay to Health (MW2H), which was adapted from an evidence-based weight loss intervention with demonstrated efficacy and meets the 2013 Guideline for the Management of Overweight and Obesity in adults. The purpose of this one-group pretest-posttest study was to evaluate program acceptability and effectiveness of MW2H on primary and secondary outcomes.

Hypotheses:
We hypothesized that MW2H would result in 1) clinically meaningful weight loss of ≥5%, and 2) improvements in cardiometabolic indices.

Methods:
During weeks 1-26, participants met privately with an interventionist for up to 24 weekly, 40-minute sessions, receiving training in eating and physical activity behavior change, self-regulation, and socioenvironmental strategies. During weeks 27-52, participants received maintenance support through phone calls, email, or in-person visits. Our primary outcome was percent weight loss. Secondary outcomes included improvement in BMI, waist circumference, HbA1c, cholesterol, and blood pressure. Outcomes were compared at baseline and 26 weeks; body weight only was measured at 52 weeks. Wilcoxin Signed Rank Tests were used to examine outcomes.

Results:
Participants (N=154) were mostly female (85%), White (75%), had a median age of 50 (Interquartile Range (IQR): 17) years, a median baseline BMI of 34.7 (IQR: 8.8), a median household income of $70,000 (IQR: $50,000), and 54% had a college degree or higher. Median number of in-person sessions attended was 19 (IQR: 4.0). Percent weight loss at 26 weeks (median [IQR]: 7.5% [6.8%]) was clinically meaningful, with 71% of participants achieving ≥5% weight loss. Statistically significant improvements in BMI, waist circumference, HbA1c, HDL cholesterol, and systolic and diastolic blood pressure (p<0.001 for all) were observed. At week 52, body weight data were available for 106 (69%) participants. Median percent weight loss from baseline was 7.0% (IQR: 9.3%). Of participants who achieved ≥5% weight loss at week 26, 94% maintained this level of weight loss at week 52.

Conclusions:
The MW2H workplace wellness program was acceptable to participants, evidenced by high program attendance, and resulted in clinically meaningful and statistically significant improvements in body weight and cardiometabolic indices. A majority of participants achieved ≥5% weight loss by 26 weeks, and nearly all participants for whom data was available maintained this level of weight loss at week 52. Additional research is needed to optimize intervention components, identify factors that contribute to weight maintenance, and examine MW2H effectiveness in a more diverse population.
Abstract P378: Excess Mortality Among Indiana Firefighters, 1985-2013
Authors: Muegge Carolyn M , Zollinger Terrell W , Song Yiqing , Wessel Jennifer , Monahan Patrick O , Moffatt Steven M
Published: July 2021

Introduction:
Firefighters are exposed to toxic agents in combustion products at fire scenes increasing their risk for cancer and cardiovascular disease. Inconsistent findings in previous research examining excess heart disease and cancer mortality have led to the need for further investigation of cause-specific death among firefighters.

Objective:
Using death certificate data, we tested the hypotheses that there is no difference in the likelihood of cancer and cardiovascular mortality between firefighters and a matched population of non-firefighters from the general population.

Methods:
Firefighter death records (n=2,818) were exactly matched to four non-firefighter (n=11,272) death records on age at time of death, sex, race, ethnicity and year of death between 1985-2013.Underlying cause of death was coded using the 9
th
and 10
th
revision of the
International Classification of Diseases (ICD
). Mortality odds ratios and 95% confidence intervals comparing firefighters to non-firefighters were calculated using conditional logistic regression to account for matching.

Results:
The risk of death due to all malignant cancers was significantly higher for firefighters than non-firefighters (OR: 1.19; 95% CI 1.08, 1.30). Firefighters had high risks of mortality due to malignancies of the buccal cavity and pharynx (OR 2.15, 95% CI 1.19, 3.79), other parts of the buccal cavity (OR 4.00, 95% CI 1.07, 14.96), pharynx (OR 2.26, 95% CI 1.05, 4.65), pancreas (OR 1.45, 95% CI 1.01, 2.06), and kidney (OR 1.84, 95% CI 1.17, 2.83). Deaths due to malignancies of other and unspecified sites (OR 1.27, 95% CI 1.02, 1.56) were also elevated among firefighters, due specifically to connective tissues (OR 2.5, 95% CI 1.01, 5.86) and brain and other parts of the nervous system (OR 1.98, 95% CI 1.23, 3.12). There was no difference in risk for heart disease deaths, including ischemic heart disease, between the two groups. However, the risks for undefined types of circulatory system deaths (OR 0.80, 95% CI 0.68, 0.94), specifically cerebrovascular disease (OR 0.82, 95% CI 0.67, 0.99) were significantly lower among firefighters than non-firefighters. Accidental poisoning deaths were also significantly lower (OR 0.43, 95% CI 0.43, 0.96) among firefighters.

Conclusions:
Deaths due to specific malignant cancers were found to be statistically higher in Indiana firefighters than non-firefighters. The study suggest the importance of early and effective health-promoting prevention strategies among firefighters.

Clinical Significance:
Firefighters need access to clinical evaluations focused on modifiable occupational and lifestyle risk factors. Biometric, fitness, psychological and self-reported data gathered during these examinations should be utilized for the development and assessment of specific occupational risk intervention programs.
Abstract P379: Adoption of Workplace Policies to Improve Heart Health: Results From the First and Second Year of the American Heart Association’s Workplace Health Achievement Index
Authors: Santana Adela , Poudel Remy , Calitz Chris , Driver Steven , Arena Ross , Nasir Khurram , Sanchez Eduardo , Fonarow Gregg
Published: July 2021

Background:
The American Heart Association’s Workplace Health Achievement Index (WHAI) uses a data-driven, quality improvement approach to assist companies in evaluating the quality of their current workplace health policies and promote a culture of healthy living in the workplace.

Objective:
The objective of this study was to use the WHAI to: 1) describe changes in adoption of workplace health strategies and employee health over time, 2) assess longitudinal differences in performance between smaller (<250 employees) and larger companies (250+ employees), and 3) identify the most and least adopted strategies among smaller and larger companies.

Methods:
The WHAI score is derived from 55 structure and process (SP) measures across 7 best-practice domains and performance metrics based on employee Life’s Simple 7 (LS7) data. The initial data collection period was Feb 1 – Mar 31, 2016 and the follow-up round of data collection occurred Apr 1 – Mar 31, 2017. Data were stratified according to smaller (n=26) vs. larger (n=119) company size. SP measure frequencies were tabulated to identify the most and least frequently adopted strategies by company size. Differences were assessed using Kruskal-Wallis rank sum tests and Chi-Square tests as appropriate.

Results:
From 2016-2017, company enrollment increased 49%, from 667 to 992. An estimated 82% (812 of 992) completed all 55 SP questions, an increase of 240% from the previous year. In addition, 36% (297 of 825) companies submitted employee health data, up from 15% to 37%. The median WHAI score increased from 89 to 197 points (p<0.01; max points = 217), with larger companies achieving a greater increase (120 vs. 104; p<0.05). Regarding improvements to SP scores, smaller companies did not significantly improve (p= 0.10) whereas larger companies did (p<0.01). In 2017, the median Heart Health Score (range: 0-10 points) was 7.49, 7.20 for smaller and 7.74 for larger companies (p=<.01). Larger companies 82% (482 of 589) were more likely than smaller companies 59% (120 of 204) to provide adequate tobacco cessation coverage (p<0.01). Conversely, compared to larger companies (75%, 441 of 589), managers at smaller companies (82%, 167 of 204) were more likely to allow employees time off during the day to engage in physical activity (p<0.05).

Implications:
WHAI enrollment and reporting of employee health data improved over time., Tthis may reflect quality improvement efforts, the larger sample size, or a combination of both. While total scores increased overall, smaller companies did not significantly improve their SP scores. Results indicate there are differences in workplace health strategies adopted among smaller and larger companies. Customized resources and technical assistance may help each group to efficiently address the specific gaps identified through the WHAI.
Abstract P382: Canola and High-Oleic Acid Canola Oils Improve Lipid/Lipoprotein Parameters Compared to an Oil Blend Characteristic of a Western Dietary Pattern in Individuals at Risk for Metabolic Syndrome: A Randomized Crossover Clinical Trial
Authors: Bowen Kate J , Kris-Etherton Penny M , West Sheila G , Fleming Jennifer A , Connelly Philip W , Lamarche Benoît , Couture Patrick , Jenkins David J , Taylor Carla , Zahradka Peter , Hammad Shatha S , Sihag Jyoti , Chen Xiang , Guay Valérie , Maltais-Giguère Julie , Perera Danielle , Wilson Angela , Castillo Sandra , Jones Peter J
Published: July 2021

Introduction:
Identifying dietary interventions for cardiometabolic disease prevention in individuals with metabolic syndrome is relevant to a significant portion of the population. Numerous studies have investigated the effects of canola oil on cardiovascular disease risk; however, no studies have compared canola oil diets to a control diet with a fatty acid composition characteristic of Western intakes in individuals with metabolic syndrome risk factors. The objectives of this study were to evaluate effects of canola oil, high-oleic acid canola oil (HOCO), and a control oil (blend of butter, safflower, coconut, and flaxseed oils formulated to represent a Western diet fatty acid profile) on lipids, lipoproteins, and apolipoproteins.

Hypothesis:
We tested the hypothesis that the two canola oil diets would elicit beneficial effects on the total lipid/lipoprotein profile compared to the Western (control oil) diet.

Methods:
In a multi-center, double blind, randomized, three-period crossover, controlled feeding clinical trial, 119 individuals with an increased waist circumference plus at least one additional metabolic syndrome risk factor consumed prepared isocaloric, weight maintenance diets containing canola oil [17.5% E from monounsaturated fatty acids (MUFA), 9.2% polyunsaturated fatty acids (PUFA), 6.6% saturated fatty acids (SFA)], HOCO (19.1% E from MUFA, 7.0% PUFA, 6.4% SFA), or control oil (11% E from MUFA, 10% PUFA, 12% SFA) for six-weeks each separated by 4-12 week washouts. The differences at the end of 42 days of feeding were tested.

Results:
The canola oil and HOCO resulted in lower endpoint total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), the TC: high-density lipoprotein-cholesterol (HDL-C) ratio, apolipoprotein (apo) B, the apoB: apoA1 ratio, and non-HDL-C compared to control oil (
P
<0.0001 for treatment effect), with no differences between HOCO and canola oil for these parameters. Endpoint apoA1 did not significantly differ between the two canola oils and control, but was higher after the HOCO compared to canola oil (1.46 ± 0.02 g/L vs. 1.43 ± 0.02 g/L,
P
= 0.0462). There were no differences among the three diets in endpoint triglycerides or HDL-C.

Conclusions:
Incorporating canola or high-oleic acid canola oils into the diet improves blood lipids and lipoproteins compared to a contemporary Western diet in individuals with at least two criteria for metabolic syndrome.
Abstract 17021: Disruption in Circadian Rhythms Triggers Arrhythmias & Sudden Death in LQT3 Mice
Authors: Schroder Elizabeth A , Stumpf John L , Seward Tanya , Esser Karyn A , Delisle Brian P
Published: July 2021

Introduction:
The autosomal dominant long QT syndrome type 3 (LQT3) is caused by gain-of-function mutations in the pore-forming cardiac sodium channel α-subunit Na
V
1.5 (
Scn5a
). A major challenge for treating LQT3 patients is predicting when or if a potentially life-threatening cardiac event (syncope or cardiac arrest) will strike. For example, longitudinal data from five LQT3 families with the Δ1505-1507KPQ mutation show only 33% of patients are symptomatic, and most symptomatic patients suffered only a single event (n = 46 patients; average age = 41 ± 23 years; average QTc interval = 510 ± 50 ms). The data suggest external stressors play a key role for triggering cardiac events in LQT3.

Hypothesis:
Disruptions in circadian rhythms can act as an external stressor to trigger LQT3-releated cardiac events.

Methods:
We disrupted the circadian rhythms in older wild type (WT) or
Scn5a
+/ΔKPQ
mice using an established model of chronic jet lag (chronic light phase advance or CPA). The light cycle was advanced 6 hours every 4 days for 65 days. Mice were monitored using in vivo telemetry before and during CPA. Heart size and cardiac fibrosis were measured using immunohistochemistry.

Results and Conclusions:
Actograms for both WT and
Scn5a
+/ΔKPQ
mice showed that CPA disrupted diurnal activity patterns. Before starting CPA, the
Scn5a
+/ΔKPQ
mice had longer heart rate corrected QT (QTc) intervals compared to WT mice (Pre-WT = 45 ± 2 ms vs. Pre-
Scn5a
+/ΔKPQ
= 54 ± 7 ms, n = 5, p<0.05). Twenty days after CPA, the QTc intervals in
Scn5a
+/ΔKPQ
mice became even longer (CPA-WT = 47 ± 2 ms vs. CPA-
Scn5a
+/ΔKPQ
= 63 ± 6 ms, p<0.05 compared to Pre-WT and Pre-
Scn5a
+/ΔKPQ
). Shockingly, all 5 of the
Scn5a
+/ΔKPQ
mice undergoing CPA died within 65 days. Most deaths occurred after repeating patterns of premature contractions or prolonged episodes of bradycardia. In contrast, none of the age-matched control
Scn5a
+/ΔKPQ
mice died (n = 5). Compared to the hearts of control
Scn5a
+/ΔKPQ
mice, the hearts from CPA
Scn5a
+/ΔKPQ
mice did not show changes in size or thickness but had more fibrosis (control = 9 ± 2%, CPA = 15 ± 2%; p<0.05). These data show that chronic disruption of circadian rhythms in
Scn5a
+/ΔKPQ
mice exacerbates QTc prolongation, increases arrhythmias, and causes premature mortality.
Abstract 17027: Racial Disparities in Transcatheter Aortic Valve Replacement Access: Geographic Analysis Suggesting Disparate Access to Care
Authors: Ganim Nidal , Monlezun Dominique J , Garcia-Sayan Enrique D , Balan Prakash
Published: July 2021

Background:
Transcatheter aortic valve replacement (TAVR) has ample randomized trial evidence that it can reduce mortality and cost for patients with aortic stenosis. Yet racial disparities in procedure access are poorly understood.

Methods:
This case-control prospectively enrolled TAVR subjects at a single high-volume quaternary academic medical center in Houston, Texas, USA, from 11/8/11-3/28/18. Neural network machine learning-supported binomial probability testing was conducted comparing the Houston population versus the center’s TAVR rates by race, with mortality and cost extrapolations. The IOM definition of health inequities was applied using the rank and replace method for counterfactual comparison (matching subjects by insurance and Society of Thoracic Surgery [STS] risk score for TAVR eligibility).

Results:
Compared to the Houston population, TAVR subjects (N=1641) were significantly more likely to be Caucasians (51.93% vs 77.26%), and less likely to be African Americans (14.80% vs 6.02%), Hispanics (23.63% vs 15.02%), or other races (9.50% vs 1.70%), all p<0.001. Among TAVR subjects with private insurance, the large majority were Caucasian (832, 85.60%), with the minority being African American (34, 3.50%), Hispanic (96, 9.88%), and other (10, 37.04%) (private insurance by Caucasian versus non-Caucasian, p<0.001). Based on TAVR mortality and cost savings in the PARNTER trial, access disparities for racial minorities over 5 years may result in 858 excess deaths, $130,000 per patient excess costs, and $111.5 million excess costs per the overall sample of eligible presenting Houston subjects. The predicted versus actual racial distribution of TAVR for each minority group matched to Caucasians by insurance and STS score was significantly greater than the actual (each group comparison to Caucasians, p<0.001).

Conclusion:
Multi-year data from our high-volume center suggest Houston racial minorities are less likely to undergo TAVR, potentially translating into a growing number of preventable excess early deaths and costs as disease incidence increases. Additional studies are underway to determine and reduce the degree of preventable race-related disparities independent of known access predictors.
Abstract 17031: Incidence of Life-Threatening Events in Children With Wolff-Parkinson-White Syndrome
Authors: Janson Christopher M , Millenson Marisa E , Dai Dingwei , Tan Reina Bianca , Iyer V. Ramesh , Vetter Victoria L , Vogel R. Lee , Shah Maully J , O’Byrne Michael L
Published: July 2021

Introduction:
Life-threatening events (LTE) in patients with Wolff-Parkinson-White Syndrome (WPW) are rare, with considerable variation in published rates. Existing data on LTE incidence represent selected populations or tertiary referral-based cohorts. Access to large observational datasets allows, for the first time, measurement of the risk of LTE in an unselected, contemporary WPW population.

Methods:
A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan
®
) to identify all WPW patients (aged ≤18 years) from both inpatient and outpatient encounters between January 2013 and December 2016. Prevalence of WPW was measured. A composite outcome, LTE, was defined as an episode that included ventricular fibrillation or cardiac arrest. Secondary outcomes included diagnoses of atrial fibrillation (AF) and supraventricular tachycardia (SVT). Factors associated with LTE were evaluated by creating multivariable models.

Results:
The prevalence of WPW in the study population was 0.025% (4,717/18,884,579). Subjects with WPW were 57% male, had a median age of 13 yrs (IQR 7-16 yrs), with coincident Ebstein’s anomaly in 1.9%, other congenital heart disease (CHD) in 12%, and cardiomyopathy (CM) in 2%. Over the study period, SVT was reported in 20.3% (n=957/4,717), and AF in 1.3% (n=61/4,717) of subjects. Patients with AF were 79% male (n=48/61), with median age 16 yrs (IQR 14-17 yrs), with CHD in 25% (n=15/61) and CM in 7% (n=4/61). LTE occurred in 23 subjects: 70% male (n=16/23), at median age 16 yrs (IQR 7-17 yrs), with CHD in 9% (n=2/23) and CM in 13% (n=3/23); AF was reported in 3 patients with LTE. The incidence of LTE was 1.4 events per 1000 person years of follow up (23/16,514). In a multivariate model including age, gender, CHD, and CM, the only independent predictor of LTE was CM (OR 10.2, 95% CI 2.4-31.1, p<0.001).

Conclusions:
Use of a large claims dataset allowed for evaluation of LTE risk in an unselected pediatric WPW population. This WPW-related LTE estimate of 1.4/1000 person years can serve as a benchmark for assessment of risk reduction interventions on a population level. Incidence of LTE in this unselected contemporary cohort is consistent with observed rates in prior reports from selected populations.
Abstract 17041: Increased Transvalvular Gradients Precede Clinical Diagnosis of Bioprosthetic Valve Thrombosis
Authors: Ionescu Filip , Petrescu Ioana , Nkomo Vuyisile T , Pellikka Patricia A , Connolly Heidi M , Pislaru Sorin V , Egbe Alexander C
Published: July 2021

Introduction:
Bioprosthetic valve thrombosis (BPVT) is increasingly being recognized as a cause of prosthetic valve dysfunction within the first years after surgical implantation. However, in the absence of changes in clinical status, current guidelines recommend cardiac imaging only after 10 years post bioprosthetic valve implantation .

Hypothesis:
We hypothesized that an increase in prosthetic valve gradient is detectable months before a formal diagnosis of symptomatic BPVT.

Methods:
Eighty-three patients diagnosed with BPVT and treated medically at our institution between 2002 and 2017 were retrospectively identified. Transvalvular gradients recorded on TTE immediately post implantation, at time of clinical BPVT diagnosis, and within a 12-month period prior to BPVT diagnosis were available in 45 patients: 18 for the aortic position, 11 for mitral, and 16 for tricuspid. When more than one study was conducted in the 12 months’ timeframe, the latest value was used in the analysis. Data are reported as mean (95% CI).

Results:
For all valve positions, an increased gradient was detectable within 12 months prior to formal BPVT diagnosis: mean increase vs. baseline of 17 (10-23) mmHg, p < 0.0001 for aortic prostheses; 5 (2-8) mmHg, p = 0.004 for mitral prostheses, and 2 mm Hg (1-3) mmHg, p = 0.003 for tricuspid prostheses. The figure presents the evolution of prosthetic valve gradients (normalized to the baseline, immediately post-implantation value) in patients with aortic (left), mitral (middle), and tricuspid (right) valve .

Conclusions:
Elevated gradients precede formal clinical diagnosis of BPVT. Closer monitoring of transvalvular gradients may prove useful for BPVT diagnosis before patients become symptomatic. With recent evidence supporting the efficacy of anticoagulant therapy in BPVT, earlier diagnosis may lead to an increased rate of response and better clinical outcomes.
Abstract 17042: Ketone Body Utilization is Suppressed in Patients With Ischemic Heart Disease
Authors: Arima Yuichiro , Izumiya Yasuhiro , Ishida Toshifumi , Takashio Seiji , Ishii Masanobu , Sueta Daisuke , Yamamoto Eiichiro , Sakamoto Kenji , Kanazawa Hisanori , Fujisue Koichiro , Araki Satoshi , Hanatani Shinsuke , Yamabe Hiroshige , Kaikita Koichi , Tsujita Kenichi
Published: July 2021

Introduction:
Ketone bodies (acetoacetate, acetone, and β-hydroxybutyrate [βOHB]) are well-known energy substrates. Recent reports revealed that heart failure augmented the utilization of ketone bodies. However, little is known about the effects of an ischemic condition on the utilization of ketone bodies.

Hypothesis:
Myocardial ischemia suppresses ketone body utilization.

Methods:
We retrospectively enrolled 171 consecutive patients who were planned to undergo acetylcholine (ACh) provocation test. Lactate and βOHB concentrations at the aortic root and coronary sinus were simultaneously measured. Coronary lactate production (CLP) was defined lactate concentration at the coronary sinus was greater than that in the aortic root and indicated enhancement of anaerobic metabolism. Subjects were divided into two groups according to the CLP at baseline (CLP (+): n=32, CLP (-): n=121). Subsequently, to assess the acute effect of myocaridal ischemia, subjects of CLP (-) at baseline were further grouped into two groups according to CLP after ACh provocation test (Provoked-CLP (+), n=81; Provoked-CLP (-), n=40). βOHB extraction rate as follows; {[Concentration at aortic root]-[Concentration at coronary sinus or femoral vein]}/ [Concentration at aortic root] х 100.

Results:
Concentration of βOHB at the aortic root, femoral vein and coronary sinus was significantly higher in patients with CLP (+) than CLP(-) at baseline [129-494 (226) vs 43-236 (105) μmol/L, p=0.0003; 58-412 (131) vs 27-163 (53) μmol/L, p=0.0004; 74-323 (149) vs 26-158 (63) μmol/L, p<0.0001, respectively]. CLP at baseline was related to a decreased coronary βOHB extraction rate [CLP (+): 23.8-33.7% (29.9%) , CLP (-): 33.2-44.0% (38.5%)].

Conclusions:
Concentrations of βOHB were elevated in patients with myocaridal ischemia. βOHB extraction rate in the coronary circulation was suppressed by acute and chronic ischemic stresses.
Abstract 17079: MYBPC3 Truncation Mutations Cause Contractile Dysregulation in iPSC-Derived Cardiomyocytes
Authors: Helms Adam S , Tang Vi , Hernandez Jonathan , Wauchope Mick , Arora Akul , Friedline Sabrina , Previs Michael , Day Sharlene
Published: July 2021

The mechanism of
MYBPC3
(encoding cardiac myosin binding protein C, MyBP-C) truncation mutations, the most common genetic cause of hypertrophic cardiomyopathy, has been incompletely resolved.
We hypothesized
that truncating MYBPC3 mutations cause myofibrillar protein assembly defects and/or contractile dysfunction.

Methods and Results:
Control iPSCs were CRISPR/Cas9-edited to create cell lines with homozygous (homCT) and heterozygous (hetCT) C-terminal MYBPC3 truncation mutations and heterozygous MYBPC3 promoter knock-out (hetPROM). HetCT was further edited to add an N-terminal flag tag (FhetCT). Purified cardiomyocytes were assayed at day ~25. RNAseq showed a 50% reduction in MYBPC3 mRNA in hetCT (p<0.01). Full ablation of MyBP-C was demonstrated in homCT but MyBP-C content was not reduced in hetCT or hetPROM by quantitative mass spectrometry. Immunofluorescence and co-IP of FhetCT showed no truncated MyBP-C. Sarcomere assembly, quantified by aligned myofilament number after replating onto 7:1 rectangular micropatterns, did not differ between lines; homCT (23±3), hetCT (23±3), hetPROM (22±3 myofilaments), control (22±3), p=NS. Quantitative mass spectrometry demonstrated that the stoichiometry of other major thick and thin filament proteins was not altered (all p=NS). Maximum force was reduced in homCT (866±366 uN, p<0.001) and hetCT (1213±545 uN, p=0.03) vs controls (1509±441 uN), and not significantly different for hetPROM (1238±360 uN, p=0.07), when measured in single micropatterned iPSC-CMs on 8.7 kPa hydrogels by traction force microscopy. Time to peak contraction was shorter in homCT (0.27 s, p=0.02) vs control (0.42 sec), but not in hetCT (0.46 s) and hetPROM (0.49 s). Contractile deceleration time was reduced only in homCT (0.12 s vs 0.25 s, p=0.002).

Conclusions:
Heterozygous MYBPC3 truncation mutations result in haploinsufficent mRNA with steady state compensation of MYBP3 protein and no MYBPC3 truncated peptide. Even complete ablation of MyBP-C loss does not alter the overall stoichiometry of other sarcomeric thick and thin filament proteins. MyBP-C ablation and heterozygous truncating mutations impair maximal contractile force, strongly implicating contractile dysregulation as the primary mechanism of MYBPC3-HCM.
Abstract 17085: Metabolic Signature of Human Right Ventricular Heart Muscle in Pulmonary Arterial Hypertension and Comparison to Two Animal Models
Authors: Davogustto Giovanni E , Talati Megha , Penner Niki , Tomasek Kelsey , Su Yan Ru , Hemnes Anna , Brittain Evan
Published: July 2021

Introduction:
Molecular studies of the human right ventricle (RV) in pulmonary arterial hypertension (PAH) are lacking. Metabolic changes in the failing RV vary across different animal models and have not been directly compared with the human RV. We hypothesized that the BMPR2 murine model of PAH would closely recapitulate metabolic changes in the human PAH RV

Methods:
We performed metabolomic profiling of 596 compounds (Metabolon) on: RV specimens from patients with PAH and non-PAH controls (n=3 per group), BMPR2 mice (n=15), wild-type mice after pulmonary artery banding (PAB) (n=7), and wild-type control mice (WT) (n=7). Normalized metabolites per group were compared by Welch’s t-test between two groups, and two-way ANOVA for >2 groups, followed by adjustment for multiple comparison analysis

Results:
Principal component analysis (PCA) revealed markedly different metabolic profiles between PAH and controls (
Figure 1A
), with significant changes in 131 biochemicals in PAH. We observed an increase in glycolysis as evident by lactate accumulation and reduction in glycolytic intermediaries. We also observed a substantial reduction in fatty acid oxidation in the PAH RV, characterized by markedly reduced acylcarnitines and accumulation of long chain fatty acids, lysolipids, and glycerol compounds (
Figure 1B
). The BMPR2 model significantly reproduced the direction of difference in 43/131 metabolites and the PAB model 29/131. Both models were associated with an increase in glycolysis but only the BMPR2 model showed evidence of impaired fatty acid oxidation (accumulation of long-chain fatty acids, lysolipids, glycerol, and monoacylglycerols), as observed in the human PAH RV (
Figure 1C
)

Conclusions:
The failing RV of patients with PAH has a distinct metabolic signature characterized by increased glycolysis and impaired fatty acid oxidation. The BMPR2 model of PAH recapitulates more of the key metabolic changes observed in humans compared with a model of isolated pressure overload. The BMPR2 model may be preferable for metabolic studies of the failing RV
Abstract 17087: Competent p53 Stabilized iPS-Cardiomyocyte Transplantation in Ischemic Myocardium of Mice Reduce Fibrosis Through Exosomal miRNA-26a
Authors: Kannappan Ramaswamy , Miller Jessica M , Mardhekar Nikhil M , Zhang Jianyi
Published: July 2021

Introduction:
With the growing field of myocardial repair through transplantation of cardiomyocytes (CM) derived from human induced pluripotent stem cells (iPSC) calls for a method for reducing fibrotic tissue development at the site of cell transplantation. We tested the hypothesis whether transplanting CMs derived from p53 stabilized (p53S) iPSCs could reduce the recruitment of fibroblast and reduce fibrosis at the site of transplantation.

Methods:
Transcription factor p53 functions are inflammation dependent: inducing apoptosis in inflammatory and transformed cells while promoting cell cycle in normal cells. Utilizing this discriminating nature of p53 we selected iPSCs that express less inflammatory and more anti-inflammatory markers and differentiated them into CM. Control CM (ctrl-CM) and p53S-CMs were tested for transplantation induced fibrosis in a mice model.

Results and Discussion:
The inflammatory markers such as accumulation of ROS, superoxide and DNA damage were significantly lesser in p53S cells. RNA sequencing revealed that, in p53S-CMs, the anti-inflammatory and anti-fibrosis signaling pathways are upregulated compared to ctrl-CMs. Transplantation of both CMs into the myocardium of ischemia induced mice resulted in cell engraftment and fibrosis around the transplantation site. However, fibrotic area was significantly reduced in p53S-CM transplanted sites evidenced by COL1 and COL4 accumulation and Sirus red staining of fibrotic tissue. In vitro treatment of human fibroblast with p53S-CM exosomes (p53S-Exo) resulted in reduced expression of fibrotic markers than ctrl-CM exosomes (Ctrl-Exo) treatment. miRNA analysis of exosomes showed that the anti-inflammatory miRNA26a is upregulated and the inflammatory miRNA101 is downregulated in p53S-Exo. Overexpression of miRNA26a mimic in ctrl-Exo abrogated the fibrosis inducing property of ctrl-Exo. Interestingly, in migration study, fibroblasts preferentially migrated towards the ctrl-CMs.

Conclusion:
Our results clearly shows that anti-inflammatory cells can be isolated from a population of heterogeneous cells by activating p53. Transplanting p53S-CMs attracted reduced fibroblast to the engraft site and oppose fibrosis through exosomal expression of miRNA26a.
Abstract 17094: The Curcumin Analogue GO-Y030 Effectively Suppresses Cardiac Hypertrophy and Systolic Dysfunction Through p300-HAT Inhibition
Authors: Shimizu Kana , Funamoto Masafumi , Sunagawa Yoichi , Katanasaka Yasufumi , Miyazaki Yusuke , Genpei Mai , Shimizu Satoshi , Sari Nurmila , Shibata Hiroyuki , Wada Hiromichi , Hasegawa Koji , Morimoto Tatsuya
Published: July 2021

Introduction:
We previously found that a natural p300 histone acetyltransferase (HAT) inhibitor, curcumin, suppresses the development of heart failure. However, curcumin has low bioavailability; therefore, it is important to find analogues to it to enhance its therapeutic potential. In the present study, we focused on C
5
-curcuminoids, which possess stronger anti-cancer activity than curcumin, and investigated whether they inhibit p300-HAT activity, and therefore whether they may be useful as therapeutic agents for heart failure.

Methods & Results:
First, an
in vitro
p300 HAT assay revealed that the IC
50
value of GO-Y030, one of the C
5
-curcumin analogues investigated, was 1.1 μM, while that of curcumin was 9.4 μM. Moreover, the assay revealed that both mono-ketone moiety and 4 alkoxy groups (3, 3’, 5, 5’) were important for the enhancement of p300-HAT inhibition of GO-Y030. Second, cultured cardiomyocytes were treated with GO-Y030 or curcumin and then stimulated with phenylephrine (PE). 1 μM of GO-Y030 suppressed the following effects to the same extent as 10 μM of curcumin: PE-induced histone H3K9 acetylation, increases in the mRNA levels of ANF and BNP, and an increase in the surface area of cardiomyocytes. Third, C57BL/6j male mice were subjected to transverse aortic constriction (TAC) or sham operation. One day after the operation, TAC mice were randomly assigned to five groups: vehicle, 1 or 50 mg/kg curcumin, and 0.1 or 0.5 mg/kg GO-Y030. Oral administrations were repeated for 6 weeks. Echocardiographic analysis showed that 0.5 mg/kg GO-Y030 prevented a TAC-induced increase in posterior wall thickness and systolic dysfunction to the same extent as 50 mg/kg curcumin. Moreover, 0.5 mg/kg GO-Y030 suppressed increases in HW/BW ratio, myocardial cell diameter, perivascular fibrosis, mRNA levels of ANF and BNP, and histone H3K9 acetylation to the same extent as 50 mg/kg curcumin.

Conclusions:
These results indicate that the curcumin analog GO-Y030 strongly inhibits p300-HAT activity compared to curcumin and its derivatives
in vitro
, and that a low dose of GO-Y030 prevented both cardiomyocyte hypertrophy and the development of heart failure. These findings suggest that GO-Y030 may be more effective than curcumin for heart failure therapy.
Abstract 17103: A Novel Approach to an Old and Unrecognized Disease- Intricacies of Cardiac Sarcoidosis
Authors: Aldweib Nael , Popeck Michael , Trivedi Rohan , Doyle Mark , Raina Amresh , Thosani Amit , Biederman Robert , Poornima Indu
Published: July 2021

Introduction:
Appropriate referral of patients to advanced imaging for suspected cardiac sarcoidosis (CS), and prognosis of patients based on imaging results is not well understood. We sought to define clinical predictors associated with an imaging diagnosis of CS and compare outcomes in the CS group, based on imaging characteristics

Methods:
Study population comprised 164 consecutive patients, referred for FDG-PET or MRI imaging based on clinical suspicion for CS. Imaging diagnosis of CS was based on prior MRI results or current FDG-PET results, classified as scar+ inflammation (group1), scar-only (group2) and inflammation-only (group3). Follow-up was 2.3±1.3 years

Results:
Among 164 patients, 61% were male (mean age 59±10 years, 82% white) and 86 (52%) were diagnosed as CS (68 by PET and 18 by MRI). Clinical presentation of VT (32/86-37% vs 7/78-10%) and conduction system disease i.e. AV block and sinus node dysfunction (14/86-16% vs 6/78-6%) was more likely in CS (p<0.05). Prior diagnosis of extracardiac sarcoid was less frequent in CS (49% vs 69% p=0.03). LVEF was similar in both groups (45±18 in CS vs 51±19 in controls). In a multivariable model including the above variables, presentation with VT (OR5.64; CI-1.98-16.10) and conduction system disease (OR 2.13; CI-1.03-9.94) remained significant predictors of imaging diagnosis of CS. The distribution of FDG-PET results was: Group 1 (29%), Group 2 (32%) and Group 3 (38%). Group 1 had the highest incidence of VT at presentation (55% vs 41% vs 19%). Mean LVEF was 44±14, 23±14 and 52±12 across 3 groups respectively (p<0.003). Steroids and immunosuppressants were more commonly used in Groups 1 and 3 vs 2 (75%, 69% vs 18% p<0.0001). In a multivariable model that included LVEF and presentation with VT/conduction system disease, use of immunosuppressants (OR 2.57; CI 1.05-6.25) and LVEF (OR 0.97; CI 0.94-0.99) significantly predicted the outcome of death or recurrent VT (chi-sq 9.57; p=0.008)

Conclusions:
In a population being referred for imaging diagnosis of CS, presentation with VT or conduction system disease is more likely to identify those with disease. Among those with imaging diagnosis of CS by FDG-PET, presence of inflammation and therefore use of immunosuppressants and low LVEF were predictive of death or VT.
Abstract 17138: Are Patients With Diabetes Mellitus at Increased Risk for Adverse Outcomes After Left Ventricular Assist Device Implantation? A Systematic Review and Meta-Analysis
Authors: Khan Muhammad S , Colombo Paolo C , Lateef Noman , Usman Muhammad S , Khan Safi U , Garan Arthur R , Yuzefpolskaya Melana , Demmer Ryan T
Published: July 2021

Background:
Patients with diabetes mellitus (DM) are known to have reduced life expectancy and be at increased risk for multiple morbidities including serious infection. However, published data on DM outcomes after left ventricular assist device (LVAD) implantation are sparse, inconsistent and individual studies are small with limited power. We conducted a systematic review and meta-analysis to compare survival and adverse events post-LVAD in DM versus non-DM (NDM) patients.

Methods:
Medline, Scopus and Cochrane Central databases were searched for studies comparing outcomes in DM and NDM patients undergoing LVAD implantation for advanced heart failure (HF) from inception-February 2018. Outcomes included all-cause mortality (30-day and one-year), device-related infection, ischemic stroke, hemorrhagic stroke and major bleeding. Results were reported as random effect risk ratios (RR) with 95 % confidence intervals.

Results:
We identified 5 retrospective cohort studies, at low risk of bias, reporting on 1,351 patients (n=488 DM). There was a borderline significant, increased 30-day mortality (RR: 1.57 [1.00, 2.47]; p=0.05; I
2
=0%) among DM vs. NDM. The DM and NDM groups did not differ significantly in terms of 1-year mortality (RR: 1.15 [0.98, 1.35]; p=0.08; I
2
=39%), device-related infection (RR: 1.05 [0.92, 1.19]; p=0.88; I
2
=0%), ischemic stroke (RR: 1.29 [0.91, 1.83]; p=0.69; I
2
=0%), hemorrhagic stroke (RR: 1.10 [0.42, 2.83]; p=0.85; I
2
=69%), and bleeding (RR: 1.06 [0.80, 1.40]; p=0.70; I
2
=27%).

Conclusion:
Following LVAD implantation, patients with DM, versus patients without, have a modestly elevated 30-day mortality rate. However, 1-year mortality rates, device related infection, and bleeding rates were not different.