bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12227: Atherosclerotic Risk Factors Associated With Carotid Plaque Progression Are Different Depending on the Severity of Plaque Stage: A Longitudinal Study in General Population
Authors: Ojima Satoko , Kubozono Takuro , Kawasoe Shin , Kawabata Takeko , Salim Anwar A , Miyahara Hironori , Tokushige Koichi , Miyata Masaaki , Ikeda Yoshiyuki , Ohishi Mitsuru
Published: April 2022

Background:
Carotid plaque is a well-known prognostic factor for cardiovascular disease and stroke. However, it is unclear which atherosclerotic risk factors are related to plaque transformation in the non-pharmacological population.

Purpose:
To examine the atherosclerotic risk factors associated with the progression of carotid plaque according to the severity of atherosclerosis

Methods:
We investigated 738 male participants without medication who underwent the 1
st
and the 2
nd
health checkups (mean duration: 2.0±1.6 years). We measured carotid plaque thickness (PT) evaluated by using ultrasonography at three points of the right and left carotid artery. Plaque score (PS) was calculated by summing all the PT. We divided into three groups following previous reports: normal stage, PS<1.1 mm; early stage, 1.1 mm
<
PS<5.1 mm; advanced stage, PS
>
5.1 mm. We used the risk factors such as age, body mass index, systolic blood pressure (SBP), fasting blood sugar, low-density lipoprotein cholesterol (LDL-C), smoking habits, and exercise habits for analysis.

Results:
At 1
st
health checkup, 108 participants had already progressed to the advanced stage of carotid plaque, 454 participants had the early stage, and 176 participants had the normal stage. 14% of participants with the early stage at 1
st
health checkup had progressed to the advanced stage at 2
nd
health checkup, and 42% of participants with the normal stage at 1
st
health checkup had progressed the early stage at 2
nd
health checkup. In multivariate logistic regression analysis, SBP was an independent risk factor for progression of PS stage from the normal stage at 1
st
health checkup to the early stage at 2
nd
health checkup (SBP; OR 1.27, CI 1.01-1.60, p<0.05). In addition, LDL-C was an independent risk factor associated with further progression of carotid plaque from the early stage at 1
st
health checkup to the advanced stage at 2
nd
health checkup (LDL-C; OR 1.10, CI 1.00-1.21, p<0.05).

Conclusions:
SBP was associated with the carotid plaque progression of early atherosclerosis, while LDL-C was associated with the progression of advanced atherosclerosis. We should be aware of risk factors according to the stage of plaque progression.
Abstract 12245: Surface Lin28a Expression Indicative of Cellular Stress Directed Towards Senescence
Authors: Broughton Kathleen M , Esquer Carolina , Echeagaray Oscar , Sussman Mark A
Published: April 2022

Introduction:
Declining cellular functional capacity resulting from stress or aging is a primary contributor to impairment of myocardial performance. Molecular pathway regulation of biological processes in cardiac interstitial cells (CICs) is pivotal in stress and aging responses. Altered localization of the RNA binding protein Lin28A has been reported in response to environmental stress, but the role of Lin28A in response to stress in CICs has not been explored.

Hypothesis:
Lin28A redistribution is indicative of stress response in CIC associated with aging and senescence.

Methods and Results:
Localization of Lin28A was assessed by multiple experimental analyses and treatment conditions and correlated to oxidative stress, senescence, and ploidy in adult murine CICs. Surface Lin28A expression is present on 5% of fresh CICs and maintained through passage 2, increasing to 21% in hyperoxic conditions but lowered to 14% in physiologic normoxia. Surface Lin28A is coincident with elevated Beta-galactosidase (Beta-gal) expression in CICs expanded in hyperoxia, and also increases with polyploidization and binucleation of CICs regardless of oxygen culture. Transcriptional profiling of CICs using single cell RNASeq reveals upregulation of pathways associated with oxidative stress in CICs exhibiting surface Lin28A. Induction of surface Lin28A by oxidative stress is blunted by treatment of cells with the antioxidant Trolox in a dose-dependent manner, with 300uM Trolox exposure maintaining characteristics of freshly isolated CICs possessing low expression of surface Lin28A and Beta-gal with predominantly diploid content.

Conclusion:
Surface Lin28A is a marker of environmental oxidative stress in CICs and antioxidant treatment antagonizes this phenotype. The biological significance of Lin28 surface expression and consequences for myocardial responses may provide important insights regarding mitigation of cardiac stress and aging.
Abstract 12246: Significant Improvement In Atherosclerotic Risk Factors From Intensive Cardiac Rehabilitation Is Lost After Program Discontinuation
Authors: Vuppala Rohan , Miller Samuel A , Al Tibi Ghaith , Medina Samuel J , Webb Sadie K , Hu Huimin , Chen Xianyan , Chronos Nicolas
Published: April 2022

Introduction:
Intensive Cardiac Rehabilitation [ICR: Dr. Dean Ornish Program] is proven to reduce risk factors associated with CVD by facilitating stress management education, plant-based nutrition, and structured exercise. The present study aimed to determine if ICR programs can show sustained improvement in high-risk (elderly and rural) populations.

Hypothesis:
We assessed the hypothesis that ICR participants would not show sustained atherosclerotic risk factor improvement in a 7-14-month timeframe after program completion.

Methods:
Participants (n=65, mean age 75 +/- 6.5 (56% Male)) with a prior diagnosis of stable angina pectoris, secondary to CVD, completed a nine-week ICR program. Patients’ biomarker data was tracked in the range of 7-14 months following program completion. Eight biomarkers were evaluated including LDL, HDL, and Hb-A1c. The analysis utilized either parametric or nonparametric paired tests, with an adjusted
P
-value of 0.00625 as eight variables were tested. Serum labs were drawn at least five months before program commencement and at most one week following program completion. BMI was recorded at a separate date, with the
P-
value set at 0.05.

Results:
The sample size was n=62. From baseline, patients’ LDL (11.8% decrease, 95% CI) and Hb-A1c (3.2% decrease, 95% CI) showed significant change (
P
<0.00625) using the paired Wilcoxon signed-rank test. During the follow-up period, the same methods were applied to a smaller sample size (n=30). This resulted in a significant change (
P
< 0.00625) for LDL (increased 13.4%) and HDL (increased 7.3%). With n=55, BMI showed significant change (3.9% decrease, 95% CI,
P<
0.05) using the paired Wilcoxon signed-ranked test directly after program completion. In the follow-up period, n=36 and BMI showed significant change (1.5% increase, 95% CI,
P
< 0.05) with the same method.

Conclusion:
Patients with atherosclerotic coronary disease optimized on medical therapy prior to enrollment in the ICR still showed improvement in biomarker levels with rehabilitation. However, these programmatic benefits were lost in the subsequent months due to a lack of structured supervision. In conclusion, we suggest long-term maintenance of ICR protocols and structured supervision in high-risk populations.
Abstract 12253: Fam210a Maintains Cardiac Mitochondrial Homeostasis by Promoting Ca
2+
Efflux
Authors: Yao Peng , Wu Jiangbin , Venkata Chinna , Chen Si , Hedaya Omar , Yan Chen
Published: April 2022

Mitochondria play fundamental roles in maintaining cellular metabolism and energetics and supporting normal myocardial function. Disturbed cardiac mitochondrial homeostasis causes
m
itochondrial dysfunction associated with
c
ardiomyopathy (MC) in humans and mice. Recent genome-wide association studies discovered that the mutations of FAM210A (family with sequence similarity 210 member A) are associated with sarcopenia. Intriguingly, FAM210A is most highly expressed in the heart, and multi-omics analyses in mouse hearts reveal Fam210a as a hub gene in cardiac hypertrophy and remodeling. However, the physiological and molecular functions of FAM210A in the heart remain elusive. Here, we discover that cardiomyocyte (CM) specific knockout (KO) of
Fam210a
in adult mice leads to progressive dilated cardiomyopathy and heart failure, ultimately causing mortality at ~10 weeks after
Fam210a
KO. The Fam210a deficient CMs exhibit severe mitochondrial morphological disruption and functional decline accompanied by myofilament disarray at the late stage of MC. Furthermore, we observed increased mitochondrial reactive oxygen species production, disturbed mitochondrial membrane potential, and reduced respiratory activity in CMs at the early stage prior to contractile dysfunction and heart failure. Transcriptomic, proteomic and metabolomic analyses from
Fam210a
KO hearts indicate that FAM210A deficiency activates chronic integrated stress response (ISR), resulting in metabolic and translational reprogramming in the heart. Therefore, persistent ISR activation contributes to the pathogenesis in MC and progression of heart failure. Mechanistically, interactome and biochemical analyses show that FAM210A binds to mitochondrial Ca
2+
/H
+
exchanger LETM1 (leucine zipper and EF-hand containing transmembrane protein 1) and promotes LETM1-mediated mitochondrial Ca
2+
efflux. Our evidence suggests that FAM210A is a novel mitochondrial Ca
2+
efflux regulator required for maintaining cardiac mitochondrial homeostasis and offers new targets for treating mitochondrial disease. This work uncovers important interplay among mitochondrial Ca
2+
signaling, metabolic reprogramming, and translational control in cardiac health and disease.
Abstract 12255: Prognostic Signals From Moderate Aortic Valve Disease: An Artefact of DICOM Structured Reporting?
Authors: Sen Jonathan , Moxham-Smith Ryan , Marwick Thomas
Published: April 2022

Background:
The use of Big Data in cardiac imaging research is usually based on DICOM structured reporting (SR) files. Default export settings from SR include all measurements, which may be misleading when diagnosis is based on peak measures. Validation of research datasets and remeasurements are seldom performed. We hypothesized that use of DICOM-SR outputs may lead to misclassifying patients with severe aortic stenosis (AS) as moderate.

Methods:
AS cases were filtered from an echocardiography dataset based on aortic valve area (AVA) <2 cm
2
, and peak velocity (V
max
) >2 m/s. Data validation was conducted i) by verifying each parameter, ensuring only appropriate values were considered and peak gradients acquired, and compared with ii) remeasurement. Outlier and erroneous captured values were excluded. Values of each parameter and definitions of AS were compared pre- and post-validation and remeasurements.

Results:
Of 919 validated echocardiograms with moderate or severe AS, up to 60% of echocardiographic parameter values, such as AVA, mean and peak gradient, or dimensionless severity index (DSI) had minimum 10% error pre- and post-validation (Table). Based on 2 of 5 criteria (AVA, AVAi, V
max
, MPG, and DSI) for classifying AS severity, 42% of echocardiograms changed degree of AS severity. Among echos identified as moderate AS pre-validation, 173/413 (41%) were reclassified as severe AS. The main reason for erroneous data was averaging of all repeated echo measures. These differences exceeded changes due to remeasurement in a subgroup of 262 echocardiograms by an order of magnitude (Table).

Conclusions:
Non-peak data in DICOM-SR led to incorrect categorisation of a high proportion of patients based on AS severity definitions. Standardisation of data fields, and curation to ensure that only peak values are considered in DICOM-SR data are essential.

Table
. Differences in echocardiographic parameters pre- and post-validation of DICOM-SR or remeasurement
Abstract 12258: Associations Between Serum Perfluoroalkyl Substances and Vascular Function
Authors: Wittkopp Sharine , Wu Fen , Windheim Joseph , Robinson Morgan , Kannan Kurunthachalam , Katz Stuart D , Chen Yu , Newman Jonathan D
Published: April 2022

Introduction:
Perfluoroalkyl substances (PFA)s are ubiquitous synthetic organic compounds used in packaging, flame retardants and stain resistant fabric. The use of older, long-chain, persistent PFAs in the U.S. has been phased out due to cardiometabolic health effects and replaced with short-chain, less persistent, alternative PFAs for which little data on cardiotoxicity exists. We evaluated the relationships between serum PFAs and noninvasive measures of vascular function by carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART).

Methods:
We measured 14 serum PFAs using hybrid solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry in 94 adult outpatients without CVD from an urban medical center. Using medical records and questionnaires, we collected demographic and clinical data; and measured PWV and BART using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV.

Results:
Of the 14 measured PFAs, 10 were detectable in >50% of samples, and were included for analysis. Each standard deviation increase in perfluroheptanoic acid (PFHpA) was associated with -0.17 (-0.34, -0.002) decrease in log BART. The weighted index of PFAs in mixture 1 (Table) was significantly and inversely associated with log BART; each tertile increase in the weighted index of mixture 1 was associated with a -0.29 (-0.52, -0.06) decrease in log BART, with PFHpA having the greatest weight (0.73) in the mixture. In contrast, neither individual PFAs nor PFA mixtures were associated with PWV.

Conclusions:
Increasing concentrations of a new, short-chain PFA, PFHpA, are associated with impaired vascular function among outpatients without CVD. Our findings contribute evidence of potential adverse cardiovascular effects of currently used PFAs.
Abstract 12287: Clonal Hematopoiesis is Associated With Higher Risk of Stroke
Authors: Bhattacharya Romit , Zekavat Seyedeh , Haessler Jeffrey , Uddin Md Mesbah , Bick Alexander G , Niroula Abhishek , Gibson Christopher , Jaiswal Siddhartha , Libby Peter , Kooperberg Charles , Whitsel Eric A , Manson Joann , Ebert Benjamin , Natarajan Pradeep , Reiner Alex
Published: April 2022

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) is a newly recognized aging-related condition due to clonal expansion of mutated hematopoietic stem cells (HSC) that results in increased risk for coronary artery disease (CAD). The extent to which CHIP is associated with stroke risk is not well understood.

Methods:
CHIP genotypes were obtained from 6 cohort studies [the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), the Framingham Heart Study (FHS), the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), the Women’s Health Initiative (WHI)] and two electronic health record-based biobanks [UK Biobank (UKBB) and Massachusetts General Brigham Biobank (MGBB)]. Incident stroke was ascertained by physician adjudicators in the cohort studies, and by ICD codes in the biobanks. Cox proportional hazards models were fitted with adjustment for age, sex, diabetes mellitus, smoking status (never, past, current) and race. Fixed-effects meta-analysis was used to estimate pooled effect sizes.

Results:
A total of 74,306 participants from 8 studies were included. In the fixed-effects meta-analysis, CHIP mutations were associated with an increased risk of total stroke (HR= 1.17, 95% CI 1.05-1.28) (
Figure 1
). In analysis of stroke subgroups, the risk was greater for hemorrhagic (HR= 1.37, 95% CI 1.15-1.59) than ischemic stroke (HR= 1.13, 95% CI 1.00-1.26). Individuals with particularly expanded CHIP mutations (i.e. variant allele fraction >10%), showed similar effect estimates of association for total stroke, ischemic stroke, or hemorrhagic stroke were observed (HR
any stroke
= 1.21, 95% CI 1.09-1.34; HR
ischemic stroke
= 1.15, 95% CI 1.01-1.30; HR
hemorrhagic stroke
= 1.43, 95% CI 1.20-1.67) .

Conclusions:
CHIP is associated with incident ischemic and hemorrhagic stroke.
Abstract 12307: Differences in Outcomes Between Men and Women Enrolled in Chronic Disease Programs for Diabetes, Hypertension and Hyperlipidemia
Authors: Norsen Lisa , Anson Elizabeth , Lavigne Holly , Hoang Ging , Pesis-Katz Irena , Singh Renu
Published: April 2022

Ischemic heart disease (IHD) affects over 48 million women in the US and is the leading cause of death. Hypertension, diabetes and dyslipidemia are risk factors for the genesis of IHD in women. Disease management programs (DM) have proven effective, overall, in facilitating lifestyle change and adherence to treatment plan but little is known about the effectiveness of these programs for men versus women. The purpose of this program evaluation was to identify differences in outcomes between men and women who participated in DM programs for hypertension, diabetes and dyslipidemia.Between 2015 and 2019, 616 unique individuals completed one of these DM programs. Measures of height, weight, exercise minutes, sedentary lifestyle, healthy nutrition, sleep, hydration and medication adherence were taken at the first and last visit. The sample was primarily female (70%), white (76%), Married (67%), educated (93% had bachelor’s or better), and were 49.3 years old, on average. Analysis revealed that males and females differ in response to the DM programs. While there was significant decrease in BMI for all participants (p<.001), the decrease was significantly greater for males compared to females (-0.60 vs. -0.29, respectively, p<.01). While exercise minutes did not differ between males and females from pre to post measurement, males who had zero exercise minutes at pre-test increased exercise minutes post program by a significantly greater amount than females who were not exercising at pretest (p=.02). Decreases in the number of missed medication days were significantly greater for women than men (0.50 days vs. 0.17 respectively; p=.02). Interestingly, while males did decrease significantly (p=.02), the decrease in medication days missed were far more substantial for females (p<.001).Men and women differ in their response to DM programs focused on lifestyle modification. Interventions should be individualized based on sex and designed specifically for women in order to optimize outcomes.
Abstract 12308: Stress-Related Neural Activity Predicts Subsequent Heart Failure
Authors: Gharios Charbel , Abohashem Shady , Zureigat Hadil , Abbasi Taimur , Mezue Kenechukwu , Cardeiro Alexander , Osborne Michael , Tawakol Ahmed A
Published: April 2022

Introduction:
Higher stress-related neural activity (SNA) associates with subsequent risk of cardiovascular disease. We investigated whether heightened SNA predicts subsequent heart failure (HF).

Methods:
Individuals (N=2,112; median age 69 years; 48% female) enrolled in the Mass General Brigham Biobank without baseline HF who underwent clinically indicated
18
F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging were retrospectively identified. SNA was measured using validated methods, as amygdalar metabolic activity corrected for regulatory brain (i.e., medial prefrontal cortical) activity. Subsequent development of HF was determined via medical record review using International Classification of Diseases 10 (ICD-10) codes. Survival analyses using Cox and Kaplan-Meier models were performed.

Results:
Over a median follow-up period of 3.9 years after imaging, 210 individuals developed HF (57 systolic, 93 diastolic). Individuals with subsequent HF (versus no HF) had higher baseline SNA (mean Z-score 0.19 ± 1.07 versus -0.08 ± 0.99; p=0.005, adjusted for age and sex). SNA associated with subsequent HF when divided into tertiles (Figure) and as a continuous measure (standardized HR [95% CI]: 1.38 [1.11-1.70], p=0.003, adjusted for age, sex, hypertension, hyperlipidemia, diabetes and smoking). The association between SNA and HF subtype was stronger for diastolic HF (1.37 [1.00-1.88], p=0.047) than for systolic HF (1.14 [0.87-1.49], p=0.348) in models additionally adjusting for history of myocardial infarction.

Conclusion:
In this retrospective study of individuals with clinical FDG-PET/CT imaging, higher SNA predicted subsequent HF with a somewhat stronger association for diastolic HF. Understanding the link between heightened stress-associated neural activity and subsequent HF may provide important insights into better HF prevention and management strategies.
Abstract 12313: Gender and Racial Differences in Outcomes of Patients With Non-Acute Myocardial Infarction Cardiogenic Shock Receiving Extracorporeal Membrane Oxygenation With or Without Left Ventricular Unloading Devices
Authors: Sohal Sumit , Kurpad Krishna Prasad , Mehta Harsh , Visveswaran Gautam K , Cohen Marc
Published: April 2022

Introduction:
Cardiogenic shock (CS) is a state of end organ hypo-perfusion due to primary pump failure, 80% of which is due to acute myocardial infarction (AMI). Among patients with AMI-CS, women as well as black and Hispanic males have been found to have worse clinical outcomes with persistent sex disparities after receiving mechanical circulatory support (MCS). However similar differences in outcomes of CS in non-AMI patients with MCS are unknown.

Methods:
National Inpatient Sample database from years 2015 to 2018 was queried to identify patients admitted with non-AMI-CS. Gender and racial differences in baseline demographics and in-hospital outcomes were compared in patients who received VA-ECMO with or without LV unloading devices. Statistical significance was assigned at p<0.05.

Results:
178,605 patients met the criteria for non-AMI-CS out of which 2,190 (1.23%) patients received VA-ECMO alone, 965 (0.54%) received VA-ECMO plus Intra-aortic balloon pump (IABP) and 414 (0.23%) received VA-ECMO plus Impella. Gender and racial distribution of each cohort is shown in figure 1. On multivariate analysis, the in-hospital mortality rates in patients on VA-ECMO only or VA-ECMO plus Impella were non significantly higher for females as compared to males (OR: 1.29 (0.88-1.89), p=0.18), (OR: 1.97 (0.27-14.64), p=0.51) respectively, whereas in patients with VA-ECMO plus IABP they were non-significantly lower than males (OR: 0.74 (0.28-1.99), p=0.55). Furthermore, the in-hospital mortality was non significantly lower in African Americans when compared to Caucasians among patients on VA-ECMO with or without LV unloading devices.

Conclusions:
In patients admitted with non-AMI-CS requiring VA-ECMO with or without LV unloading devices no statistically significant gender or race-based differences occur in mortality outcomes.
Abstract 12512: Antithrombotic Strategies According to Age in Patients With Atrial Fibrillation and a Recent Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From the Augustus Trial
Authors: Guimaraes Patricia , Lopes Renato D , Wojdyla Daniel , Alexander John H , Goodman Shaun G , Aronson Ronald , Halvorsen Sigrun , Sinnaeve Peter R , Vinereanu Dragos , Storey Robert F , Berwanger Otavio B , Windecker Stephan , Mehran Roxana , Granger Christopher , Alexander Karen P
Published: April 2022

Background:
In AUGUSTUS, apixaban led to lower rates of bleeding and hospitalization than VKA, and aspirin caused more bleeding than placebo, in patients with AF and ACS and/or PCI treated with a P2Y12 inhibitor. We evaluated the safety and efficacy of different antithrombotic strategies by age in this population.

Methods:
Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were adjudicated ISTH major or clinically relevant nonmajor (CRNM) bleeding, ISTH major bleeding, death or rehospitalization, and death or ischemic events. The treatment effects of apixaban vs. VKA and aspirin vs. placebo were assessed across age categories using Cox models.

Results:
Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. All events, including bleeding, rehospitalization, and ischemic events, were more common with older age. Compared with VKA, apixaban was associated with lower rates of ISTH major or CRNM bleeding, ISTH major bleeding, and death or hospitalization, regardless of age (Fig). Apixaban was associated with greater absolute reduction in ISTH major bleeding than VKA in the older age groups, reflecting the higher bleeding risk in these groups. No differences were observed in rates of death or ischemic events between apixaban and VKA according to age. Patients who received aspirin had higher rates of bleeding than those receiving placebo in all age groups. Rates of death or rehospitalization and death or ischemic events were similar among patients receiving aspirin or placebo in different age categories.

Conclusions:
The safety and efficacy of apixaban compared with VKA was consistent with the overall trial findings, irrespective of age. Aspirin compared with placebo increased ISTH major or CRNM bleeding in all age groups. Our findings support the use of apixaban plus a P2Y12 inhibitor without aspirin as the standard therapy for this patient population, regardless of age.

Figure:
Outcomes by Age
Abstract 12513: Post-GWAS Functional Analysis of the CDKN2A/B Locus Identifies CUX1 as a Regulator of Endothelial Senescence by Modulating the CAD-Associated p16
INK4A
Expression
Authors: Li Gang
Published: April 2022

Introduction:
Genome-wide association studies (GWAS) have validated a strong association of the
CDKN2A/B
locus with more than 10 different age-related diseases including atherosclerosis and its complications.

Hypothesis:
The
CDKN2A/B
locus is one of the most complicated genetic loci that harbors p16INK4a, one of the markers for cellular senescence. As a single locus associates with multiple different age-related diseases, this region may contribute to the progression of these diseases by promoting aging itself, perhaps through modulating cellular senescence.

Methods:
By coupling regulatory element-sequencing (Reel-seq) with SNP-specific DNA competition pulldown-mass spectrometry (SDCP-MS), two techniques recently developed in our lab, the disease-associated functional SNPs (fSNP) on
the CDKN2A/B
locus and the fSNP binding proteins were identified. The mechanism underlying the contribution of an atherosclerosis-associated fSNP rs1537371 to the pathogenesis of, and the susceptibility to atherosclerosis was revealed by contemporary techniques.

Results:
We demonstrate that the homeodomain transcription factor CUX1 specifically binds to the atherosclerosis-associated fSNP rs1537371 within the
CDKN2A/B
locus. Although it binds at a considerable distance (> 100 kb), CUX1 is shown to regulate the CDKN2A/B encoded genes p14
ARF
, p16
INK4A
, p15
INK4B
and
ANRIL
in endothelial cells (ECs). In-depth analysis demonstrates that endothelial CUX1 expression correlates with telomeric length and is induced by both DNA-damaging agents and oxidative stress. Moreover, induction of CUX1 expression triggers both replicative and stress-induced premature senescence via activating p16
INK4A
expression. Consistent with these findings, we also detect elevated expression of CUX1 and p16
INK4A
in the plaques of patients with carotid artery disease.

Conclusions:
CUX1 is a transcriptional regulator of p16
INK4A
expression. It regulates p16
INK4A
-dependent endothelial senescence via binding to the atherosclerosis-associated fSNP rs1537371.
Abstract 12542: Prevalence and Characterization of Occult Coronary Atherosclerotic Disease Among Middle Aged Individuals Free of Clinical Cardiovascular Disease - Results From Miami Heart Study (MiHeart) at Baptist Health South Florida
Authors: Nasir Khurram , Cainzos Achirica Miguel , Budoff Matthew , Cury Ricardo C , Valero Elizondo Javier , Ali Shozab S , Arias Lara , Shapiro Michael D , Blaha Michael J , Blankstein Ron , Ziffer Jack A , Feldman Theodore , Fialkow Jonathan
Published: April 2022

Introduction:
While prior population-based cohorts have extensively described burden of coronary artery calcification (CAC) among asymptomatic individuals, there is paucity of occult coronary atherosclerotic disease (CAD) assessment with coronary computed tomography angiography (CCTA) in the general population. The aims were to determine prevalence, burden and coronary plaque characteristics in the ongoing prospective Miami Heart Study (MiHeart) using both CAC and CCTA.

Methods:
MiHeart enrolled 2,549 middle-aged 40-65 years free of clinical cardiovascular disease participants (49% females, mean age 53, 47% Hispanic/Latino) from general population of Greater Miami Area (Florida, USA). Final study consisted of 2491 (98%) among whom non- cardiac-gated CT for CAC testing and contrast-enhanced CCTA cardiac-gated were performed.

Results:
In this study 58% had CAC=0, 13% had CAC≥100, and 45% had detectable plaque on CCTA. 143 (6%) participants had significant (≥50%) stenosis and 44 (2%) had severe (≥70%) stenosis. Overall, 26% participants had exclusive non-calcified plaque whereas 7% demonstrated high-risk plaque features (HRP) with positive remodeling being most frequently observed (5%). Among participants with CAC=0, 15% had any plaque on CCTA (62% in 1 segment); 1% had obstructive CAD and 2% any HRP, respectively. Burden of CAD (plaque segmental score, subtype, stenosis) as well as HRP on CCTA was strongly associated with increasing CAC scores (table). Overall, 31% and 20% with CAC≥100 had significant stenosis and HRP, respectively.

Conclusions:
In the first US general population based CCTA study, we demonstrate high burden of diverse coronary atherosclerotic plaque features in a middle-aged general population free of established CVD. Future studies in MiHeart will focus on biological associations and clinical implications of of coronary atherosclerotic disease severity and features on CCTA among asymptomatic individuals.
Abstract 12546: Artificial Neural Network Models for Lipid Profile Prediction in the US General Population
Authors: RANA Juwel , Chowdhury Townim Faisal , Rahman Shafin , Oldroyd John , Islam Rakibul
Published: April 2022

Introduction:
Hyperlipidemia is a major risk factor for cardiovascular disease. Tests of blood lipid concentrations require a blood sample to be taken in a clinical setting, which is costly, time-consuming, and may preclude measurements in a large number of people at risk.

Hypothesis/Objective:
This study aimed to develop artificial neural network (ANN) models to predict lipid profiles of the US general population using noninvasive and low-cost diagnostic features.

Methods:
We used the most recent cycle of the National Health and Nutrition Examination Survey (NHANES) 2017-2018. The participants with missing values in outcomes: total cholesterol (TCH), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), and aged<18 years were excluded. We developed ANN-based prediction models using various combinations of eight features: age, gender, race/ethnicity, body mass index, waist to hip ratio, waist to height ratio, systolic and diastolic blood pressure with three to thirty hidden neurons in one layered feed-forward ANN. We trained ANN models 100 times for seven different input combinations. The performances of these prediction models were evaluated by mean accuracy (ACC), R-squared (R
2
), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE).

Results:
Of 5176 participants, 51.8% were females with a mean (range) age of 52 (18-80) years. Results show that the ANN models can predict these outcomes with high mean ACC, (TCH 96.69%, HDL 95.11%, LDL 93.47%, TG 91.35%), average R2 (TCH 0.022, HDL 0.186, LDL -0.019, TG 0.158), average MSE (TCH 0.048, HDL 0.056, LDL 0.152, TG 0.268), average RMSE (TCH 0.220, HDL 0.237, LDL 0.389, TG 0.518), and average MAE (TCH 0.171, HDL 0.192, LDL 0.287, TG 0.410).

Conclusions:
ANN is an effective diagnostic tool for predicting lipid profiles for the US general population, and can be used to predict lipid profiles for clinical diagnosis using noninvasive and low-cost features.
Abstract 12549: Population Patterns of Clustering in Cardiovascular Health Metrics and Associations With Cardiovacular Disease: A Latent Classpopulation Patterns of Clustering in Cardiovascular Health Metrics and Associations With Cardiovacular Disease: A Latent Class Analysis
Authors: Ning Hongyan , Siddique Juned , Khan Sadiya , Perak Amanda M , Allen Norrina , Wilkins John T , Lloyd-jones Don
Published: April 2022

Background:
Cardiovascular health (CVH) is defined by 7 health behaviors (smoking, diet, physical activity) and factors (body mass index, blood pressure, total cholesterol, glucose). we sought to explore how CVH components cluster in individuals and examine associations of clusters with cardiovascular disease (CVD).

Methods:
Participants aged 20-79 years were included from four longitudinal cohorts. Levels of each CVH metric were classified as ideal, intermediate, or poor using AHA definitions. Among sex and race subgroup, we applied latent class analysis (LCA) models on CVH metrics and individuals were assigned to a class based on the highest posterior probability of membership. Cox regression model was conducted to estimate the association of cluster and the CVD events.

Results:
Among 9270 White and 3913 Black women, and 7773 White and 2875 Black men, 6004 CVD events occurred during 19.5 years’ follow-up. Three common classes were observed (Figure 1): Suboptimal (unfavorable behaviors and factors), Mixed (diverse levels of behaviors and factors), and Favorable factors. One additional class of Unfavorable Behaviors (with relatively favorable factors) was identified in Whites. Compared with Favorable factors, other classes had significantly higher risk for CVD (Figure 2), except in Black women.

Conclusions:
We observed three common clusters of CVH component, with an additional class of Unfavorable Behaviors (only) in White participants, that were significantly associated with incident CVD across subgroups. Given that 27-47% of participants were in the Suboptimal group, multifaceted primordial prevention strategies will be needed to bend the CVD epidemic curve.
Abstract 12552: Juxta-Purkinje Ventricular Myocytes Are the Cellular Trigger of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Blackwell Daniel , Faggioni Michela , Matthew Wleklinski , Gomez-Hurtado Nieves , Venkataraman Raghav , Baudenbacher Franz J , Gong Shiaoching , Fishman Glenn I , Pfeifer Karl , Knollmann Bjorn C
Published: April 2022

Introduction:
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic arrhythmia syndrome caused by mutations that render intracellular calcium release channels hyperactive during adrenergic stress. Hyperactive calcium release has also been identified as a cause of ventricular arrhythmia in acquired heart diseases such as heart failure. What remains unknown is the cellular source of ventricular arrhythmia triggered by inappropriate calcium release – Purkinje cells in the cardiac conduction system or ventricular cardiomyocytes in the working myocardium.

Methods:
To investigate the cellular origin, we used a genetic approach in mice to knock out cardiac calsequestrin (Casq2) either in Purkinje cells or in ventricular cardiomyocytes (Panel A). Total loss of calsequestrin in the heart causes a severe CPVT phenotype in mice and humans. Immunostaining and western blotting were used to examine protein expression and arrhythmias were induced by administration of isoprenaline.

Results:
Loss of Casq2 only in ventricular myocytes produced a full-blown CPVT phenotype, whereas mice with loss of Casq2 only in Purkinje cells were comparable to wild-type mice (Panel B). Subendocardial chemical ablation or restoration of Casq2 expression in subendocardial cardiomyocytes neighboring Purkinje cells was sufficient to protect against catecholamine-induced arrhythmias (Panels C, D).

Conclusion:
Our data indicate that subendocardial ventricular myocytes juxtaposed to Purkinje fibers are the source of ventricular arrhythmias triggered by intracellular calcium release and hence identify a novel cellular target for arrhythmia prevention.
Abstract 12557: Echo-Guided vs. Device-Based Strategies for Optimization of Cardiac Resynchronization Therapy and Long-Term Clinical Outcomes: A Meta-Analysis
Authors: Ali-ahmed Fatima , Friedman Daniel , Allen Lapointe Nancy , Dalgaard Frederik , Kosinski Andrzej S , Mulpuru Siva K , Jackson Kevin P , Sanders Gillian , Al-Khatib Sana M
Published: April 2022

Introduction:
CRT optimizations has the potential to improve the 30% non-response rate. Randomized trials (RCTs) comparing device and echo-guided CRT optimization have been overall small and results have been conflicting.

Methods:
We searched the EMBASE and MEDLINE databases from January 2008 through September 2020 for RCTs and prospective observational studies that randomized patients to either echo-guided or device-based CRT optimization. Included studies had to report on at least one of the following outcomes of interest: all-cause mortality, heart failure hospitalization (HFH), NYHA class improvement, mean EF at follow up, LVEDD, 6MWD, and QoL. A meta-analyses on the outcomes of interest was performed using random effects models.

Results:
We included seven RCTs representing a total of 2,730 patients. Of those, 1,113 patients were randomized to echo-guided optimization, and 1,617 were randomized to device-based optimization. The mean age of patients was 64.5 years, and they were predominantly men (60%). In the device-based optimization group, there was 93 deaths (5.7%) and 142 HFH (5.1%). In the echo-guided optimization group, there was 57 deaths (10.2%) and 112 HFH (12.4%). On random effects meta-analysis, the device-based optimization group had a lower rate of HFH compared with the echo-guided optimization group (OR 0.81, 95% CL 0.70-0.95, Figure). However, differences in the following outcomes between the two groups were not statistically significant: all-cause mortality, mean follow up EF, LVEDD, NYHA class improvement, 6MWD improvement range or QoL.

Conclusions:
This meta-analysis suggests that echo-guided optimization of CRT is equivalent to device-based optimization in relation to the clinical outcomes of death, EF, LVEDD, NYHA and 6MWD but suggests that device-related optimization could reduce HFH. The latter merits further investigation in relation to different device-base optimization algorithms.
Abstract 12826: Genetic Variation in
SLC5A2
Mimicking SGLT2-Inhibition Lowers Risk of Cardiovascular Disease and All-Cause Mortality
Authors: Bechmann Louise E , Emanuelsson Frida , Nordestgaard Borge G , Benn Marianne
Published: April 2022

Background:
Treatment with sodium-glucose co-transporter 2 (SGLT2)-inhibitors reduces risk of hospitalization for heart failure and all-cause mortality, but the mechanisms are unclear.

Hypothesis:
We hypothesized that a functional genetic variant in
SLC5A2
, encoding SGLT2, mimics pharmacological SGLT2-inhibition on risk of cardiovascular disease and all-cause mortality.

Methods:
112,745 individuals from two similar studies of the Danish general population were included and genotyped for a common variant causing familial renal glucosuria, rs61742739 (c.1961A>G; p.Asn654Ser) in
SLC5A2
. This variant was examined for association with risk of heart failure (N=6,260), myocardial infarction (N=5,778), ischemic heart disease (N=12,504), and all-cause mortality (N=16,410) during a median of 42 years of follow-up, and for potential mediators of these associations related to glycemic control, body mass, blood pressure, circulating blood volume, and lipids.

Results:
The rs61742739 variant lowered risk of heart failure by 31%, myocardial infarction by 21%, ischemic heart disease by 16%, and all-cause mortality by 22%, and was associated with lower plasma glucose and lipoprotein(a). Lower plasma glucose mediated 4.2% (95%CI:1.3-10.2%; p=0.01) of the effect of genotype on risk of heart failure, 5.3% (1.5-21.2; p=0.02) on risk of myocardial infarction, 7.5% (2.2-25.1; p=0.01) on risk of ischemic heart disease, and 10.5% (3.0-26.8; p<0.01) of the effect on risk of all-cause mortality. Similar estimates for lipoprotein(a) lacked statistical significance.

Conclusion:
A functional genetic variant in
SLC5A2
, encoding SGLT2, is causally associated with a 31% lower risk of heart failure, a 21% lower risk of myocardial infarction, a 16% lower risk of ischemic heart disease, and a 22% lower risk of all-cause mortality. These effects were partly mediated through lower plasma glucose.
Abstract 12839: A Standardized and Regionalized System of Care Network for Cardiogenic Shock: Insights From the Inova-Shock Registry
Authors: Tehrani Behnam N , Sherwood Matthew W , Rosner Carolyn , Baghchi Pramita , Truesdell Alexander G , Bakhshi Hooman , Damluji Abdulla , desai mehul , Desai Shashank , Epps Kelly C , Flanagan Michael , Gattani Raghav , Genovese Leonard , Howard Edward , Ibrahim Nasrien , Kasarabada Aditya , Kennedy Jamie , Lantry James , Moukhachen Hala , Ofosu-Somuah Araba , Petro Kathleen , Psotka Mitchell , Qion Xaioxiao , Ryan Liam , Sarin Eric , Shah Palak , Singh Ramesh , Sinha Shashank , Speir Alan , Tang Daniel , Welch Timothy , Young Karl , Defilippi Christopher , O'Connor Christopher M , Batchelor Wayne B
Published: April 2022

Introduction:
Recent studies have demonstrated improved short-term outcomes with cardiogenic shock (CS) at centers using standardized protocols. Whether these benefits may be extended across systems of care networks is unknown.

Objective:
To investigate clinical characteristics & short-term outcomes of CS patients initially managed at spoke hospitals & transferred, & those admitted directly to the hub.

Methods:
Observational study of 520 consecutive CS patients (1/3/2017-12/31/2019) treated in a regionalized network of 34 spoke hospitals across 600 sq miles. Presenting location, clinical characteristics, mechanical circulatory support (MCS) use & outcomes were compared. Multivariate logistic regression was employed to determine factors associated with 30-day mortality.

Results:
Fifty five percent (n=287) initially presented to a spoke. They were more likely to have CS due to acute myocardial infarction (50.5% vs 31.8%;
p
< 0.01) & be supported initially with an IABP (32.1% 17.2%;
p
<0.01). They were also more likely to require escalation to Impella + VA-ECMO at the hub. Hub patients had higher index lactates (2.7 vs 2.3 mg/dL;
p
=0.04). No differences were seen between the hub and spoke cohorts in regard to 30-day mortality (39.1% vs 36.4; p=0.60), major bleeding (19% vs 23%; p=0.23), stroke (9.4% vs 7.0%; p=0.33), & 30-day readmissions (24% vs 21%; p=0.53) (Figure 1) Independent factors associated with 30-day mortality were age, diabetes, baseline lactate
>
2.0 mg/dL & index SCAI shock stages D & E. Initial presentation to a spoke was not (aOR 0.81; 95% CI 0.49-0.38;
p
=0.38 )

Conclusions:
Despite differences in CS etiology and initial MCS use, the hub and spoke cohorts had similar 30-day mortality & associated short-term outcomes. Creating a regionalized system of CS care across a multi-hospital network with dedicated protocols & expedited transfer algorithms may provide similar benefits for patients initially presenting to either hub or spoke shock care centers.
Abstract 12843: Amyloidosis is Associated With Increased Risk of Atrial Fibrillation. A Forgotten Link Between Uncommon and Common Cardiac Conditions. Analysis From the National Inpatient Sample
Authors: Salama Amr , Abdullah Abdullah , Hussein Ahmed , Corteville David , Rao Mohan , Alweis Richard
Published: April 2022

Objective:
This study aims at identifying the relationship between amyloidosis and atrial fibrillation

Background:
Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of stroke, heart failure, and mortality. Recent advances in cardiac imaging have increased the frequency of diagnosis of cardiac amyloidosis. Data is limited on the role of cardiac amyloid in patients with AF.

Methods:
This is a retrospective cohort study of patients with amyloidosis from the National Inpatient Sample (NIS) 2014. The primary outcome was diagnosis of AF in the amyloidosis vs. non-amyloidosis population. Logistic regression models were used to assess predictors of AF among the study population.

Results:
5, 872,587 health encounters from the NIS were identified. Of these, 4,287 subjects had a diagnosis of amyloidosis. AF was found in 28.7% of the amyloidosis vs. 13.4% % of the non-amyloidosis group, p < 0.001. The average age of the amyloidosis is 71 yrs. old, female represents 55.9% of the study population. Systolic heart failure (8.5% vs. 3.9%, p < 0.001), diastolic heart failure (14.7% vs. 4.6%, p < 0.001), ischemic stroke (6.3% vs. 1.9%, p < 0.001) and chronic kidney disease (42.3% vs. 14.4%, p < 0.001) were more prevalent in the amyloidosis vs. non-amyloidosis group. Amyloidosis was associated with the black ethnicity (19.4% vs. 14.1%, p < 0.001). In addition, diabetes mellitus, hypertension, and obesity were common in the amyloidosis group. On multivariate analysis, amyloidosis was a strong predictor of AF (OR 1.37 (95% CI 1.28-1.47, p < 0.001))

Conclusion:
AF and amyloidosis are mutually associated identities. High suspicion should be maintained for the diagnosis of amyloidosis in patients presenting with AF. This may allow early recognition and treatment of underlying amyloidosis in patients with AF.
Abstract 12848: Patient-Specific
in silico
Models Demonstrate Hemodynamic Effect of LAMPOON in Transcatheter Mitral Valve Replacement
Authors: Kohli Keshav , Wei Zhenglun Alan , Perdoncin Emily , Sadri Vahid , Siefert Andrew W , Blanke Philipp , Greenbaum Adam , Khan Jaffar , Lederman Robert , Babaliaros Vasilis , Yoganathan Ajit P , Oshinski John N
Published: April 2022

Introduction:
The purpose of this study was to investigate the hemodynamic impact of LAMPOON (Laceration of the Anterior Mitral leaflet to Prevent Outflow ObstructioN) in transcatheter mitral valve replacement (TMVR) using patient-specific
in silico
modeling.

Methods:
Eight subjects from the LAMPOON investigational device exemption trial were included. All subjects were at prohibitive risk of outflow tract obstruction from TMVR based on computed tomography (CT), and underwent successful LAMPOON immediately followed by TMVR. A validated computational fluid dynamics (CFD) model was used to compare simulated hemodynamics and 3D flow patterns between two modeled conditions: 1) TMVR with LAMPOON and 2) TMVR without LAMPOON. Using the post-procedure CT scans, anatomical models of TMVR with LAMPOON were created for each subject. The open transcatheter valve cells were then
virtually closed
to model TMVR without LAMPOON for each subject. Finally, CFD was performed for each condition to simulate the systolic flow fields.

Results:
As compared to TMVR without LAMPOON, TMVR with LAMPOON resulted in lower peak velocity, lower peak LVOT gradient, and higher peak LVOT effective orifice area by 13
±
6% (p=0.004), 28
±
14% (p=0.008), and 15
±
8% (p=0.002), respectively. LAMPOON provided flow communication through exposed cells of the transcatheter valve, thereby decreasing the flow constriction and reducing flow stasis in the vicinity of the neo-LVOT (Figure). The hemodynamic benefit of LAMPOON was observed to be greater in subjects with a smaller neo-LVOT area measured post-implant (p<0.001).

Conclusions:
In silico
modeling allowed for a quantitative patient-specific comparison of TMVR with and without LAMPOON, which is impossible to study clinically. The LAMPOON procedure improved simulated hemodynamics in all subjects, with a greater hemodynamic impact observed in subjects with a smaller post-implant neo-LVOT area.