bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11502: Elevations in Proinflammatory Cytokines Il-1β and Il-12 in the Transgenic (mren2)27 Rat: A Clinically-Relevant Animal Model of Metabolic Syndrome
Authors: McMullen Nathan P , Contillo Nicholas , Wolfe Stacey , Ryalat Fatima , Anzalone Anthony , Coffman Stephanie , Tschoe Christine , DIZ Debra I , xiang zhidan , Peterson Keyan , Jestus Jack
Published: March 2022

Introduction:
Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of strokes and carries a 40% mortality rate within one month. Neuroinflammation plays a key role in secondary brain injury after ICH and inflammatory pathways may represent important therapeutic targets. A major obstacle in developing novel therapeutics is the lack of a translatable animal model that recapitulates the comorbidities of patient’s that suffer from ICH. Hypertension, diabetes, and obesity are components of the metabolic syndrome often seen in ICH patients, and may modulate the neuroinflammatory response to ICH. Thus, we aimed to characterize peripheral markers of systemic inflammation in a transgenic hypertensive (mRen2)27 rat model of metabolic syndrome.

Methods:
Serum proinflammatory cytokines IL-1β and IL-12 were measured using ELISA in naïve male and female (mRen2)27 (n=15) and healthy SD rats at 32 weeks of age (n=14). Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. Statistical analyses of group differences were conducted using two-sample t-tests.

Results:
SBP (mm Hg) was significantly higher in the (mRen2)27 transgenic rats compared to SD rats, in both males (195 ± 4, n=8 vs. 125 ± 4, n=6, p< 0.05) and females (183±7, n=7 vs. 114±10, n=8, p< 0.05). Female (mRen2)27 rats had significantly higher serum concentrations (pg/mL) of IL-12 (1073±47, n=7 vs. 438±101, n=8, p< 0.05) and IL-1β (pg/mL) (11±3, n=7;. 4±1 , n=8, p< 0.05). Similarly, male (mRen2)27 rats had significantly higher levels of IL-12 compared to SD rats (825±58 , n=8 v. 582±90 , n=6, p< 0.05). IL-12 levels were higher in mRen female rats compared with males (1073±47, n=7 v. 825±58 , n=8, p< 0.05). Serum levels of IL-1β was not significantly different between male SD and (mRen2)27 rats.

Conclusion:
Compared to healthy SD rats, the pro-inflammatory cytokines IL-1β and IL-12 are elevated in a clinically-relevant animal model of spontaneous hypertension. These findings simulate human studies that have linked cardiometabolic disease with elevated levels of pro-inflammatory cytokines. Future studies using this animal model will seek to further characterize changes in perihematomal and peripheral levels of proinflammatory and inflammation-resolving cytokines following ICH.
Abstract 11505: Left Ventricular Mass Index and Risk of Cognitive Decline in a General Elderly Population (Tanushimaru Cohort Study)
Authors: Morikawa Nagisa , Adachi Hisashi , Enomoto Mika , Fukami Ako , Sakaue Akiko , Yamamoto Maki , Satou Hiromi , Fukumoto Yoshihiro
Published: March 2022

Introduction:
Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function. Recent cohort study suggested that higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels predicted incident dementia. However, there is little study of the longitudinal association between left ventricular (LV) structure and future cognitive decline.

Hypothesis:
LV structure is associated with cognitive decline.

Methods:
We recruited 1943 participants (mean age: 65.8±11.3 years, male 39.9%) as a population-based sample of Tanushimaru, Japan in 2009 and followed 837 adults in 2018 after excluding those with heart disease history. The subjects received 2-dimensional echocardiography to quantify LV mass index (LVMI) in 2009. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognitive function in 2009 and in 2018. We classified MMSE scores ≦23, 24-27, ≥28 as dementia, mild cognitive impairment (MCI) and normal cognition (NC). Multivariable logistic regression analyses were performed to examine the association between LVMI and cognitive decline.

Results:
Mean MMSE scores in 2009 and in 2018 among 837 participants were 28.1±2.0 and 28.4±2.3, respectively. Cognitive status progressed from NC to MCI/dementia in 19.3% (96/498) or from NC/MCI to dementia in 2.9% (24/826). Mean LVMI levels were 81.9±19.7g/m2 in men and 76.5±18.4g/m2 in women. Conversion from NC to MCI/dementia was not associated with LVMI, while larger LVMI was significantly associated with the progression from NC/MCI to dementia (p=0.002). Age, sex-adjusted odds ratio for progression to dementia was 1.50 (95% confidence interval, 1.16-1.97) as LVMI increased by 10 g/m2. The association was independent of body mass index, systolic blood pressure, and microalbuminuria. LVMI > 90.6 g/m
2
in men and > 99.9 g/m
2
in women accurately predicted progression to dementia (p < 0.0001). These cutoff points were smaller in men and larger in women than the current criteria for LV hypertrophy.

Conclusions:
Larger LVMI was not associated with early stage of cognitive decline, but can be a risk factor for progression to dementia. We recommend to carefully evaluate cognitive function among at-risk individuals with larger LVMI.
Abstract 11507: Radiation Reduction in Catheterization Laboratory: Single Center Experience
Authors: Shekhar Shashank , Ajay Abhishek , Kumar Anirudh , Kaur Manpreet , Isogai Toshiaki , Saad Anas M , Abushouk Abdelrahman , Abdelfattah Omar M , Lak Hassan Mehmood , Farwati Medhat , Wunderle Kevin , Ellis Stephen G , Khatri Jaikirshan , Krishnaswamy Amar , Kapadia Samir R
Published: March 2022

Introduction:
Radiation reduction measures were incorporated in the Cleveland Clinic Catheterization laboratories to mitigate the hazards from radiation exposure to patients and personnel during diagnostic and interventional coronary procedures. We report our experience with these improved systems over a 10-year period.

Methods:
Fluoroscopes were modified in 2013 by reducing the default fluoroscopic pulse rate from 10 to 7.5 pules/s, added default low-dose acquisitions, revised field-of-view dose factors, and instructed operators to use larger fields-of-view with appropriate collimation. A retrospective data analysis of all patients undergoing diagnostic catheterization from 2009 to 2012 (pre-initiative group), and 2013 to 2019 (post-initiative group) was done using Siemens CARE analytics software. The effectiveness of radiation reduction measures was assessed by comparing the total air kerma (K
a,r
), and fluoroscopy- and acquisition-mode air kerma in patients in the two groups after propensity matching them based on age, sex, BSA, and total fluoroscopic time.

Results:
The total fluoroscopic time for the pre-initiative group (N=18,181) was 8.02 seconds while that for the post-initiative group (N=25,868) was 8.05 seconds. After matching 18,181 patients in both the groups (mean age, 64 years; 62% males), a significant reduction (54.4%) in the mean K
a,r
was observed in the post- in comparison to the pre-initiative group (420.94 mGy vs. 921.21 mGy; p<2.2e
-16
). Further analysis revealed a reduction in the mean acquisition- (59.3%; 217.33 mGy vs. 533.50 mGy; p<2.2e
-16
) and fluoroscopy-mode (47.5%; 203.61 mGy vs. 387.71 mGy; p<2.2e
-16
) air kerma in the post-initiative group. A sub-analysis of patients matched on the basis of their exact fluoroscopy and acquisition times also revealed a significant reduction in K
a,r
, acquisition- and fluoroscopy-mode air kerma in the post-initiative group relative to the pre-initiative group (43.95%, 44.04%, 43.78% respectively).

Conclusions:
Optimization of imaging systems can significantly reduce patient radiation exposures which directly affect the radiation exposure of the Cath lab personnel. Similar algorithms can be applied in other labs to achieve a reduction in radiation exposure.
Abstract 11509: Social Media is Not Just for Posting Selfies Anymore: Social Media as a Medical Educational Tool Among Medical Trainees
Authors: Sreepathy Pranati , Gough Sophie , Pastapur Aishwarya , Shroff Adhir R
Published: March 2022

Introduction:
Social media (SoMe) platforms such as Twitter, Instagram, and Facebook are increasingly popular tools for dissemination of information. Currently, there is little research into SoMe and its utility in medical education (MedEd) at various training levels.

Hypothesis:
We hypothesize that residents will be more likely than medical students to use SoMe for MedEd and professional networking; that Twitter will be the dominant platform used by trainees for MedEd; that time constraints will be the primary barrier preventing trainees from using SoMe for MedEd; and that trainees who do use SoMe academically do so to network and collaborate.

Methods:
A survey based study was conducted at the University of Illinois College of Medicine. Surveys were sent to medical students and Internal Medicine residents and their responses recorded. Responses were anonymous. A Pearson Chi-Square analysis was used to analyze the categorical data.

Results:
Total of 294 responses were collected, 61 residents and 215 students. 51% (148) of responses were women. 50% (11/22) of medical students using Twitter use it for MedEd, vs 100% (9/9) of residents using Twitter use it for MedEd (p-value = 0.008). Only 22% (18/82, 7/31) of both residents and medical students using Instagram use it for MedEd. For residents and students alike, SoMe for MedEd was primarily used for up-to-date clinical guidelines rather than professional networking on both Twitter and Instagram (88% (14/16) and 67% (16/24) respectively). Among Instagram users, 71% (15/21) of trainees chose time constraint as the primary barrier to MedEd use. For Twitter, 100% (5/5) of trainees chose not knowing where to start as the primary barrier.

Conclusion:
Our study demonstrates that SoMe is a valid, but underutilized, education tool. Trainees most often utilized SoMe to keep up to date with clinical guidelines with Twitter being the most prominent platform for MedEd overall and engaging more residents than students. Targeted educational initiatives on these platforms may be a powerful platform to recruit trainees into the field of cardiology.
Abstract 11524: Ezetimibe Consistently Reduces LDL-C with Little Interindividual Variability in 14,970 Patients Post-ACS
Authors: Patel Siddharth M , Cannon Christopher P , Im KyungAh , Blazing Michael A , Mitchel Yale B , Sabatine Marc S , Giugliano Robert P , Bohula Erin A
Published: March 2022

Introduction:
Ezetimibe (EZE) added to statin further reduces LDL-C and CV events. Prior studies demonstrated large inter-individual variability in LDL-C reduction with statins. Whether similar variability exists with EZE has not been reported in a large study.

Methods:
We assessed the placebo (PBO)-adjusted LDL-C reduction from randomization to 4 months in IMPROVE-IT, a double-blind RCT of EZE vs placebo (PBO) added to simvastatin (SIMVA) post-ACS. Inter-individual variation in % LDL-C reduction was calculated via rank-ordered subtraction of PBO/SIMVA from EZE/SIMVA. Patients not on study drug or with missing LDL-C values at either timepoint were excluded. Using the overall distribution of PBO-adjusted LDL-C reductions with EZE, we modelled the % of patients anticipated to achieve guideline-recommended LDL-C targets at 4 months with the addition of EZE across a range of baseline LDL-C values.

Results:
In 14,970 pts, the median baseline LDL-C in both groups was 80 mg/dL (IQR 65-96). The median change from baseline at 4 months was -37% (IQR -20% to -51%) in the EZE/SIMVA arm and -14% (IQR +7% to -31%) with PBO/SIMVA (
Panel A
). The PBO-adjusted median change in LDL-C at 4 months with EZE/SIM was -23% with low variability (IQR -19 to -27%;
Panel A)
. Based on this distribution, modelling predicts that fewer than half of patients would achieve the U.S. and European targets of <70 and <55 mg/dL when the baseline LDL-C is >91 mg/dL and >72 mg/dL, respectively, with the addition of EZE to statin therapy (
Panel B
).

Conclusions:
Addition of EZE to statin therapy results in a consistent median 23% reduction in LDL-C, with 75% of patients achieving at least a 19% reduction. The distribution of LDL-C reduction can be used to estimate how likely a patient will be to achieve guideline LDL-C targets with the addition of EZE to statin therapy.
Abstract 11526: Nardilysin is a Potential Biomarker for the Early Diagnosis of Non-St-Segment Elevation Acute Coronary Syndrome, A Multicenter Prospective Cohort Study, Nardi-ACS Study
Authors: Ohno Mikiko , shiomi hiroki , Yano Mariko , Aizawa Takanori , Nakano Yukiko , Yamagami Shintaro , Kato Masashi , Ohya Masanobu , Chen Po-Min , Nagao Kazuya , Ando Kenji , Kadota Kazushige , Yokomatsu Takafumi , Tsukasa Inada , kurokawa masato , Morimoto Takeshi , Kimura Takeshi , Nishi Eiichiro
Published: March 2022

Background:
Rapid and accurate diagnosis of acute coronary syndrome (ACS) is critical to prevent the fatal complication accompanied with the delay of the treatment. However, the diagnosis of non-ST-segment elevation ACS (NSTE-ACS), especially shortly after the onset, is not straightforward because even high-sensitivity cardiac troponin (hs-cTn) is sometimes not elevated at that phase. We previously reported in a retrospective study that serum nardilysin is a potential biomarker for the early detection of NSTE-ACS. Here, we present the results of the Nardi-ACS study, a multicenter prospective study conducted at six centers in Japan to clarify the significance of nardilysin for the early detection of ACS.

Methods and Results:
We analyzed serum nardilysin and hs-cTnI (Architect; Abbott) in the sequential 2 independent cohorts; phase I primary cohort (435 patients with chest pain who consecutively visited to the emergency room (ER)) and phase II validation cohort (486 patients with a strong suspicion of ACS who underwent coronary angiography). The frequency of non-ACS, STEMI and NSTE-ACS was 64.4, 22.5, and 13.1 (%) in the phase I, and 14.0, 60.0, and 25.9 (%) in the phase II cohort, respectively. The cutoff value of serum nardilysin was set at 1350.9 pg/ml (mean +2SD) obtained in 246 healthy volunteers, while the cutoff of hs-cTnI was set at 52 pg/ml. The initial blood test in the phase I cohort revealed that nardilysin was significantly elevated in ACS patients, compared to non-ACS patients (p<0.05). The sensitivity of hsTnI, nardilysin, and nardilysin combined with hsTnI for the diagnosis of NSTE-ACS was 52.6, 57.9, and 78.9 (%), and the negative predictive value (NPV) was 90.7, 88.7, and 92.4 (%), respectively. When focused on hsTnI-negative patients, the sensitivity and NPV of nardilysin in STEMI and NSTE-ACS were 64.7/91.4 and 55.6/91.4 (%), respectively. Furthermore, the sensitivity of nardilysin for the early detection of STEMI and NSTE-ACS patients, whose blood was examined within 3 hours after the onset was 77.6 and 60.4 (%), respectively, both of which were higher than that of hsTnI (51.2 and 56.3%).

Conclusion:
Nardilysin could be a potential biomarker for the early diagnosis of troponin-negative NSTE-ACS.
Abstract 11527: A Pilot of Food Insecurity and Its Sequelae on Health (FISH)
Authors: Ardoin Tiffany W , Dreznick Michael
Published: March 2022

Introduction:
Health outcomes data on community interventions addressing food insecurity is scarce.

Hypothesis:
The FISH Research study measures the effects of an 8 week Geaux Get Healthy Clinical Program (GGH), a program that provides food insecure community members with access to local resources including cooking classes, nutrition classes and grocery store tours. We proposed that addressing food insecurity with the GGH program can improve food insecurity and metabolic health.

Methods:
Eligible participants included patients who qualified for the GGH Program ages 18-65, were English-speaking and without audiovisual deficits. Upon enrollment, participants met with the Health Specialist and then at 8-12 weeks, and again at 6 months. Participants completed validated surveys regarding access to healthy foods, knowledge of a healthy diet, and motivation to prepare healthy meals; and the PHQ-9 (Patient Health Questionnaire-9) survey. At each visit, vital signs (including weight, height and waist circumference) and laboratory measurements (Hemoglobin A1C, lipid panel) were obtained. Patient data related to chronic disease and ER/hospital utilization was abstracted from the medical record.

Results:
At the time of this analysis, a total of 53 participants were enrolled. Participants’ average BMI was 34 (
SD
=9.06), 64% had diabetes/pre-diabetes and 55% had hypertension at time of enrollment. In the first 6 months, we had 11 (21%) FISH participants complete all assessments. The mean USDA Food Insecurity Scores were 6.9 (very low food security) at initial visit; 4 (low food security) at 8-12 weeks; and 2.7 (low food security) at 6 months. A non-parametric Friedman test of differences among the repeated measures of food security was conducted and resulted in a significant Chi-square value of 9.69 (
p
=0.008).

Conclusions:
We are encouraged that participating in the GGH program may lead to sustainable improvements in food insecurity, at least among those interested in signing up for the FISH research study. We are eager to see the future results of the GGH program’s effects on metabolic health.
Abstract 11531: Exploring Associative Pathways and Gender Effects of Racial and Weight Discrimination with Sleep Quality, Physical Activity, and Dietary Behavior in Adults with Higher Body Mass Index and Elevated Cardiovascular Disease Risk
Authors: Wittleder Sandra , Lee Linda , Patel Nikhil , Chang Jinhee , Geesey Emilie , Saha Sreejan , Merriwether Ericka , Orstad Stephanie L , Wang Binhuan , Seixas Azizi , Jay Melanie
Published: March 2022

Introduction:
Racial disparities in obesity and cardiovascular disease can partly be attributed discrimination. Racial discrimination (RD) and weight discrimination (WD) have been linked to higher psychological distress, lower sleep quality, less physical activity, and unhealthy diet, which can negatively impact weight. Better understanding the processes by which discrimination influences weight-loss factors would help create strategies for mitigating obesity disparities.

Methods:
This is a cross-sectional study of 745 primary care patients with a BMI ≥ 25 kg/m
2
(43.1% Female,

M
age

=51 years) who were enrolled in a weight-loss trial. To investigate the direct and indirect (via psychological distress) pathways by which RD and WD may be associated with sleep quality, physical activity, and diet, and to explore gender as a moderator, we used Ordinary Least Square regression with bootstrapping. Validated surveys included EOD, PROMIS-29, LDBQ, REAP-S, IPAQ-SF.

Results:
We found that RD and WD were indirectly associated with lower sleep quality via psychological distress (WD: indirect=2.11, CI[1.218;3.092]; RD: indirect=0.93, CI[0.057;0.134]). Further, we found that for men, RD and WD were indirectly associated with less physical activity via psychological distress (WD: moderated mediation=491.67, CI[75.565;1040.877]; RD: moderated mediation=22.60, CI[0.080;51.828]). Finally, we found that RD and WD were directly associated with unhealthy diet (WD: direct=0.195, CI[0.076;0.314]; RD: direct=0.007; CI[0.001;0.012]).

Conclusions:
Weight-loss factors were associated with both racial and weight discrimination through different pathways depending on gender and type of outcome. Lower sleep quality was associated with discrimination via psychological distress for both gender groups. Lower physical activity was also linked to discrimination via psychological distress, however for men only. Associations between unhealthy diet and discrimination were direct and could not be explained by increases in psychological distress. Although more research is needed, our findings suggest that interventions to address discrimination and its psychological impacts could mitigate obesity disparities and improve cardiovascular health.
Abstract 11533: Genetic Prediction Tool Using
LPA
Haplotypes Improves Identification of Patients with Elevated Lipoprotein(a)
Authors: Atri Deepak , Mukamel Ronen E , Loh Po-ru , Blankstein Ron , Gupta Rajat M
Published: March 2022

Introduction:
Multiple lines of evidence support the causal role of serum lipoprotein (a) [Lp(a)] in the pathogenesis of cardiovascular disease, including CAD/MI and ischemic stroke. Mendelian randomization studies demonstrate that genetic variation is the principal determinant of serum Lp(a) level, and that variants associated with higher Lp(a) are associated with higher vascular disease risk. Though 80-90% of variation in serum Lp(a) levels is genetically-determined, single nucleotide polymorphisms (SNPs) contribute a small fraction of this risk. SNPs, however, may be used to identify LPA alleles based on a reference panel. These LPA alleles are the primary genetic determinants of serum Lp(a). New methods that identify these alleles using extended SNP haplotypes may improve serum Lp(a) prediction and identify at-risk patients.

Hypothesis:
The use of reference panels of extended LPA haplotypes can identify patients with elevated Lp(a) in a genotyped, hospital-based cohort.

Methods & Results:
We identified all genotyped subjects in the Massachusetts General Brigham Biobank with a history of CAD or ischemic stroke for genetic prediction of serum Lp(a) (n = 3202). The majority of these patients (n = 2578, 80.5%) did not have a prior Lp(a) measurement as part of clinical care. We computed genetic predictions of Lp(a) in all patients by matching their SNP haplotypes to a reference panel of ~50,000 UK Biobank participants (and ~440,000 haplotypes) for whom LPA alleles had been matched to Lp(a) levels. The 90th percentile, 258 patients, had predicted Lp(a) of >75mg/dl (~159nM), equal to the 90th percentile of the general population. We observed strong correlation between predicted and clinically-measured Lp(a) (R2 = 0.75-0.92 across four clinical assays; p<0.0001 for all; n = 372).

Conclusions:
We demonstrate the validity of a serum Lp(a) genetic prediction with very high fidelity in a disease cohort using a new method of imputed SNP haplotypes. Using LPA alleles, as determined by SNPs, we identified patients who are likely to have elevated serum Lp(a) without a prior measurement. This method may be applied to biobank populations to identify patients at risk for cardiovascular disease mediated by elevated serum Lp(a).
Abstract 11534: Persistent Hopelessness is Reduced in Home Exercisers in a Primarily Rural Population of Adults with Ischemic Heart Disease
Authors: Dunn Susan L , Luong Anna , Bomgaars Debbie , Jensen Gwenneth A , White Lynn L , Van De Griend Kristin M , Kroeze Visser Angela , Goodyke Madison P , Gutierrez-Kapheim Melissa , Tintle Nathan L
Published: March 2022

Introduction:
Hopelessness and rurality are each associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining hopelessness in rural adults with IHD.

Purpose:
This pilot study examined state hopelessness in a primarily rural population of adults with IHD living in West-Northcentral United States.

Methods:
A longitudinal design was used to collect data from 42 participants during their hospitalization with IHD and at a long-term recovery time point. Rural-Urban Commuting Area (RUCA) codes were used to stratify participants by rurality level, with 64% (n=28) categorized as rural. The relationships between changes in hopelessness and other variables were evaluated with both single- and multi-variable linear models.

Results:
A moderate to severe level of state hopelessness (>1.8 on the State-Trait Hopelessness Scale) was present in 47.6% (n=20) of participants during their hospitalization and persisted over time, with 57.1% (n=24) of participants reporting hopelessness between 200 to 540 days post-hospital discharge (p=0.42). Changes in state hopelessness levels from baseline to follow-up were not significantly associated with demographics, rurality, prior or current exercise, prior depression, depression score (measured by the Patient Health Questionnaire-8), or time to follow-up (p>0.05). However, participation in home-based exercise (measured by the Cardiac Rehabilitation Exercise Participation Tool) was associated with a significant decrease in state hopelessness among those reporting moderate to severe state hopelessness (n=20) at baseline, with an estimated decrease of 0.72 points in hopelessness levels (SE=0.32; p=0.04). There was no association for hospital-based exercise (p=0.91).

Conclusions:
Hopelessness symptoms were frequent and persistent in a primarily rural sample of adults with IHD, with a decrease in symptoms observed in the moderately to severely hopeless who participated in home-based exercise. Knowledge of hopelessness in rural IHD patients is important for health care professionals in acute care and outpatient settings so at-risk patients can be identified and interventions employed. Future work should replicate these findings in larger samples.
Abstract 11537: Progress Towards a Proteomic Surrogate Endpoint for Cardiovascular Outcomes
Authors: Williams Stephen A , Ostroff Rachel , Hinterberg Michael , Coresh Josef , Ballantyne Christie M , Matsushita Kunihiro , Mueller Christian , Walter Joan E , Jonasson Christian , Holman Rury H , Shah Svati H , Sattar Naveed , Taylor Roy , Lean Michael , Kato Shintaro , Shimokawa Hiroaki , Sakata Yasuhito , Nochioka Kotaro , Parikh Chirag , Coca Steven , Omland Torbjoern , Chadwick Jessica , Astling David , Hagar Yolanda , Kurieski Natasha , Primus Jeremy , Simpson Missy , Trujillo Nelson P , Ganz Peter
Published: March 2022

Introduction:
The critical path for novel treatment and prevention strategies, both pharmacological and non-pharmacological, requires clinical outcomes trials, which are slow, expensive and retard patient access to successful therapies. For marketed drugs, unreliable residual risk stratification hinders precision-directed therapy and facilitates payor reticence.

Hypothesis:
Large-scale proteomics and machine learning can identify a reliable, individualized, and dynamic surrogate of cardiovascular risk, synoptic for multiple biologic mechanisms, with a resulting multimarker model that is more robust than individual biomarkers. Avoidance of immutable prognostic factors (e.g. age, sex, medical diagnoses) will enhance sensitivity to change in risk.

Methods:
We quantified ~5000 proteins in >31,000 archived samples from >21,000 higher risk individuals in nine clinical datasets, generating ~150M plasma protein measurements. We derived and validated a 27-protein model encompassing 10 biologic processes to predict the four-year likelihood of myocardial infarction, stroke, hospitalization for heart failure or death. We assessed the association of model-predicted change with observed outcomes in a variety of conditions in four clinical intervention trials.

Results:
See table for details. In validation, observed event rates were 7.8 fold higher in quintile 5 than quintile 1 for proteins vs. 2.9 for an optimized clinical factor model; the Net Reclassification Index was +0.43. AUCs were 0.73 for proteins vs. 0.63 for clinical, and c-statistics 0.71 vs. 0.62. The protein model also responded concordantly with outcomes in four intervention studies.

Conclusions:
A 27-protein model is more prognostic than clinical factors in higher risk populations and has directionally concordant responsiveness to all mechanistic challenges to date. These features are consistent with surrogacy, and may prove useful in clinical trials and precision medicine.
Abstract 11546: Ten-Year Trends in the Nationwide Clinical Outcome After Percutaneous Coronary Intervention
Authors: Choi Jung-Min , Jang Yu Jeong , Lee Seung-Hwa , Choi Jin-Ho
Published: March 2022

Introduction:
We investigated the 10-year trends in the clinical outcome of percutaneous coronary intervention (PCI) in an unselected all-comer nationwide cohort.

Hypothesis:
Mortality following PCI is a key quality measurement in clinical practice and should be investigated within the context of the changing clinical comorbidities.

Methods:
Patients undergoing PCI for the first time between 2006 and 2015 from database of the National Health Insurance Service of Korea were included and followed until death or being censored by December 2016.

Results:
A total of 437,436 patients was included. Patients were divided into quartile subgroups according to a clinical score that predicting 1-year death risk. Over the decade, the annual number of PCI increased from 32,098 to 51,990 (p<0.001). The proportion of patients with higher risk quartiles increased, whereas lower risk quartiles decreased (p<0.001). The 1-year cumulative incidence rate of death did not change in the population with 1st (0.9% to 0.8%) and 2nd (1.3% to 1.3%) risk score quartiles, whereas it increased in the population with 3rd (3.4% to 5.1%) and 4th (15.5% to 19.4%) risk score quartiles (p<0.001 by restrictive mean survival time).

Conclusions:
This real-world data analysis showed that the number, proportion, and the risk of high-risk patients increased over the decade in Korea.
Abstract 11553: Sudden Cardiac Death in Type 1 and Type 2 Diabetes
Authors: Norby Faye L , Reinier Kyndaron , Uy-Evanado Audrey , Nichols Gregory A , Stecker Eric , Jui Jonathan , Chugh Sumeet S
Published: March 2022

Introduction:
Diabetes is a known risk factor for sudden cardiac death (SCD). Whether type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) confer a similar risk of SCD remains unclear. Our aim was to determine and compare the association of T1D and T2D with SCD.

Hypothesis:
Given the differences in the pathophysiology, clinical presentation, and management, the likelihood of having SCD in T1D and T2D is different.

Methods:
Using data collected from 2002-19, we performed a case-control study of 2,771 cases of SCD (age ≥18 years) from the Oregon Sudden Unexpected Death Study and 8,313 control patients from Kaiser Permanente Northwest (matched for age, sex, and race/ethnicity) who did not have SCD or prior cardiac arrest. We used medical records to determine diabetes status and used logistic regression to evaluate the independent association between diabetes and SCD.

Results:
Our cases and matched controls had a mean age of 65 ± 16 years, were 33% female and 24% non-White race. In total, 37% (n=1,016) of cases and 24% (n=1,981) of controls had diabetes. In those with diabetes, the proportion of T1D was 6% (n=66) among cases and 2% among controls (n=40; P<0.001). The presence of diabetes was associated with a 1.5- times higher odds of SCD. Compared to those without diabetes, the odds ratio (OR) and 95% confidence interval (CI) for SCD was 4.36 (2.81–6.75; P<0.001) in T1D and 1.45 (95% CI, 1.30–1.63; P<0.001) in T2D after adjustment for age, sex, race/ethnicity, body mass index, and relevant comorbidities. Within the diabetic population (n=2,997), the odds of having SCD were 2.4 times higher in T1D than in T2D (adjusted OR: 2.41; 95% CI, 1.53–3.80; P<0.001).

Conclusions:
Individuals with T1D and T2D have a higher risk of SCD than those without diabetes. In the diabetic population, T1D is more strongly associated with SCD compared to T2D. These findings have implications for sudden death risk stratification in diabetics.
Abstract 11555: Prevalence of Depressive and Anxiety Related Symptoms Among Patients Living with Hypertrophic Cardiomyopathy
Authors: Asbeutah Abdul Aziz , Salberg Lisa , Jefferies John L
Published: March 2022

Introduction:
Hypertrophic cardiomyopathy (HCM) is a common heart condition that affects at least 1:500 individuals in the United States. Patients with HCM can suffer from life-threatening arrhythmias, requiring implantable cardiac devices and several limitations in daily life activities. Only limited data exist describing impacts on quality of life among these patients.

Hypothesis:
We hypothesize that patients living with HCM may suffer from an increased prevalence of depressive or anxiety related symptoms.

Methods:
Patients were approached via survey invitation on the Hypertrophic Cardiomyopathy Association (HCMA) website. Surveys were made accessible to all the members of the HCMA who had provided an active email address. Survey data were collected via the HCMA and de-identified for subsequent analyses. Demographic variables along with 40 questions assessing signs and symptoms of depression and anxiety were included. Answers to questions ranged from never to nearly always and were transformed on a Likert scale.

Results:
Survey invitations were sent to 1425 patients/families with HCM. Of these, 737 (52%) completed the survey adequately. Around 93% of respondents were Caucasian, with a mean age of 52.1 ±1.4, and composed of almost an equal number of men and women. Around 70% of patients with HCM reported that they never or rarely felt worthless, helpless, hopeless, anxious or depressed. Meanwhile, less than 3% reported depressive or anxiety related symptoms on a daily basis. On the contrary, around 52% of respondents found it difficult to engage in daily exercise or activities such as lifting items and helping with household chores.

Conclusions:
In conclusion, patients with HCM infrequently suffered from depressive or anxiety related symptoms, while many reported increased levels of exercise-related limitations. Further studies are warranted to better understand the effects of HCM on the physical and psychological well-being.
Abstract 11558: The Role of Oxidized CaMKII in Early Ischemia-Reperfusion Triggered Ventricular Arrhythmias
Authors: Haugsten Hansen Marie , Sadredini Mani , Hasic Almira , Anderson Mark E , Sjaastad Ivar , Stokke Mathis
Published: March 2022

Introduction:
Arrhythmias can complicate revascularization procedures after transmural infarctions and induce hemodynamic instability, but most cases can be adequately treated when they occur in hospital. However, arrhythmias that occur outside of hospital are potentially fatal. Arrhythmias in the early phase of reperfusion are caused by Ca
2+
overload and spontaneous diastolic release of Ca
2+
from the sarcoplasmic reticulum (SR). Indirect evidence suggests that reactive oxygen species (ROS) are important in this process by affecting the activity of key Ca
2+
handling proteins. Specifically, previous publications propose oxidation of the multifunctional Ca
2+
/calmodulin dependent protein kinase type II (CaMKII) to be a critical factor, and a potential therapeutic target. There is, however, a lack of data providing direct evidence for the importance of oxidized CaMKII (ox-CaMKII) for triggered arrhythmias in the early phase of reperfusion.

Hypothesis:
We hypothesized that ox-CaMKII increases diastolic SR Ca
2+
release events in the early phase of reperfusion.

Methods:
We evaluated the propensity for early reperfusion arrhythmias in mice resistant to oxidation of CaMKII in the heart (homozygous CaMKIIδ M281/282V mice) and wild type control mice (WT), by the use of Langendorff-perfused hearts exposed to ischemia-reperfusion, confocal line scan imaging of isolated cardiomyocytes transiently exposed to hypoxia and ischemia-like conditions, and immunoblotting.

Results:
Langendorff-perfused hearts from CaMKIIδ M281/282V mice showed no significant difference in ventricular arrhythmias compared to WT during the early reperfusion phase, both at baseline and during beta-adrenoceptor stimulation with isoprenaline. Immunoblotting of left ventricular tissue from perfused hearts revealed no significant differences in the abundance or phosphorylation levels of Ca
2+
-handling proteins. Ca
2+
imaging experiments without isoprenaline showed no significant difference in the incidence of spontaneous transients, Ca
2+
waves or Ca
2+
sparks between CaMKIIδ M281/282V and WT mice.

Conclusions:
Initial data indicate that ablation of CaMKII oxidation does not protect mouse hearts against arrhythmias in the early phase of reperfusion after ischemia.
Abstract 11563: Frailty Predicts Hospital Outcomes in Patients With LVAD: A Nationwide Inpatient Analysis
Authors: ROMEO Francisco J , Aguilar-Gallardo Jose S , Correa Ashish A , Contreras Johanna P
Published: March 2022

Introduction:
Frailty is recognized as a major prognostic indicator in heart failure and is linked to perioperative morbidity and mortality. We sought to evaluate the prognostic value of frailty on hospital outcomes in patients with Left Ventricular Assist Device (LVAD) therapy.

Hypothesis:
Frailty portends a worse prognosis in patients with LVAD.

Methods:
This population-based, retrospective observational study extracted data of hospitalized adult patients with current LVAD therapy from the US Nationwide Inpatient Sample (NIS) database (2018). Participants were stratified into frail and non-frail using the Johns Hopkins (ACG) frailty-defining diagnosis indicator. Study endpoints were in-hospital mortality, sepsis, length of hospital stay, and total charges (u$$). Univariate and multivariate analyses were performed to determine associations between the endpoints and frailty.

Results:
A total of 23,210 weighted adult patients had the presence of LVAD therapy during index hospital admission. The mean age was 60 years old, 86% were men and a total of 13% of the patients with LVAD were considered frail. Of note, frail patients with current LVAD had an overall higher burden of comorbidities than those without frailty status. In addition, the prevalence of frailty steadily increased in groups with higher Charlson Comorbidity Index (CCI) scores (p-value <0.001). Hospital outcomes including mortality, sepsis, and LOS were higher among the frail populations as well as hospital costs (Table 1). Finally, after multivariate analysis for clinical variables, frailty at admission had a nearly 2-fold increase in mortality (OR 1.67, CI 95% 1.19-2.34, p-value 0.002).

Conclusions:
Frailty is a prevalent condition among patients with current LVAD therapy and portends a worse prognosis as well as higher hospital costs.

Table 1. In-Hospital outcomes
Abstract 11566: Use of Temporary Mechanical Circulatory Support Devices in Heart Failure Patients with Cardiogenic Shock
Authors: Malik Aroosa , BASU TANIMA , Shore Supriya
Published: March 2022

Objective:
Contemporary use of temporary mechanical circulatory support devices (tMCS) for heart failure (HF) without acute myocardial infarction (AMI) is not well described. Accordingly, we evaluated use patterns for tMCS in HF patients.

Methods:
This was a retrospective study of a large administrative claims dataset between 01/01/06 and 12/31/19. We included patients with HF or cardiogenic shock who received tMCS i.e. Impella, intra-aortic balloon pump (IABP) or extra-corporeal membrane oxygenator (ECMO) in the absence of AMI or coronary revascularization. Multinomial logistic regression model was used to identify predictors for type of tMCS device. Temporal trends in use of tMCS was also evaluated.

Results:
We included 2722 HF patients receiving tMCS: 1836 (68%) with ischemic cardiomyopathy (ICM) and 886 (32%) with non-ischemic cardiomyopathy (NICM). There were no gender or racial differences in device use. Table shows adjusted odds ratio for predictors associated with receipt of ECMO or Impella compared to IABP. After multivariable adjustment, patients with ICM or NICM placed on ECMO compared to IABP, had a higher comorbidity burden. For both groups, patients with valvular disease were more likely to receive IABP and patients with peripheral vascular disease an Impella. Over time, there was an increase in Impella and ECMO use with a decrease in IABP use (p <0.05; Figure).

Conclusions:
In a real world cohort of HF patients with cardiogenic shock without AMI, use of Impella and ECMO has increased over the last decade and IABP has decreased. Patients receiving ECMO have a higher co-morbidity burden, whereas patients receiving IABP are more likely to have valvular heart disease.
Abstract 11567: Congenital Heart Disease Classification Improves SRTR Risk Estimation of Waitlist and Early Post-Transplant Mortality for Pediatric Heart Transplantation
Authors: Butts Ryan J , Kirklin James , Cantor Ryan , Zhao Hong , Jaeger Byron , Nandi Deipanjan , Auerbach Scott R , St-Michele Emile Jean , Schumacher Kurt , WEST Shawn C , Conway Jennifer , Toombs Leah K , Peng David M
Published: March 2022

Introduction:
Risk estimation for waitlist and 1-year post-transplant mortality utilized by SRTR for pediatric heart transplantation dichotomizes patients based upon presence or absence of congenital heart disease (CHD).

Hypothesis:
Current SRTR risk estimations can be improved by adding further detail in categorization of CHD.

Methods:
A retrospective analysis of the Pediatric Heart Transplant Society (PHTS) database of pediatric (<18yo) heart transplant listings from 2010 to 2020 was performed, excluding patients listed for retransplantation. Cox hazard models were developed for waitlist mortality during the first year following listing (WaitDeath) and one year post-transplant mortality (TxDeath). The initial model was constructed using covariates included in the current SRTR model and a second model was developed by adding CHD classifications (SRTR+) including: single ventricle vs. biventricular heart disease, ventricular morphology, and surgical interventions.

Results:
The WaitDeath model included 5,790 patients in which 722 of which died. In the SRTR WaitDeath model, CHD had a HR of 1.8 (95%CI of 1.4-2.3) compared to cardiomyopathy patients. Where as in SRTR+ model, patients with different types of CHD had HR’s that ranged from 1.5 to 2.1 (Table 1). The TxDeath model included 4,185 patients in which 304 which died. (Table 1) In the SRTR model of TxDeath, patients with CHD had a HR of 3.9 (2.9-5.1) compared to cardiomyopathy patients, whereas in the SRTR+ model patients with different types of CHD had HRs that ranged from 2.4-5.3 (Table 1).

Conclusions:
Inclusion of granular CHD data may improve waitlist and post-transplant mortality risk estimation in pediatric heart transplant patients, allowing for more refinement in allocation policies and understanding of difference in post-transplant outcomes across sites. This data supports further refinement of current SRTR risk adjustment models.
Abstract 11571: Defining the Distance Between the His Bundle and Septal Perforator Arteries
Authors: Bocchese Matthew , Gannon Michael , Patil Pravin , Vandecker William , Whitman Isaac R , Cronin Edmond
Published: March 2022

Introduction:
Left bundle branch pacing (LBBP) is an emerging pacing modality in which the LBBP lead is screwed through the interventricular septum towards the left bundle branch in the left septal subendocardium. Damage to a septal perforating branch of the left anterior descending coronary artery is a potential complication.

Objective:
To define the distance between the His bundle and the first septal perforator artery to guide safe LBBP lead placement.

Methods:
Clinically indicated coronary CT angiograms (CCTA) at our institution were reviewed. The intersection of the tricuspid annulus and the base of the non-coronary cusp of the aortic valve represented the location of the His bundle. The intersection of a line joining the His bundle location with the RV apex with the first septal perforator was determined. The distance between the His Bundle and this intersection was measured and recorded. Values were analyzed using standard statistical methods. T-tests were used for continuous variables.

Results:
A total of 50 consecutive CCTAs were included in this study, 30 men and 20 women, average age 55.4 ± 14.1 years. Medical history included HTN (64%), and diabetes (50%) and CAD (10%). LVH was present in 9 patients (18%) but was mild in all cases. Heart failure was present in 9 patients (18%), 4 of whom had systolic dysfunction with an average EF for the study being 57.0%. The mean left ventricular internal diameter at end diastole (LVIDd) and interventricular septum thickness (IVS) were 46.7 mm and 10.2 mm, respectively. The mean distance from the His Bundle to the first septal perforator was 27.2 ± 7.7 mm, median 26.9 mm, range 13.0 to 44.7 mm. There was no significant difference by gender for mean distance (28.1 mm men vs 25.6 mm women, p=0.26). There was no significant association between LVIDd or IVS and the His Bundle-Septal Perforator distance (r
2
=0.02 and r
2
=0.002, respectively).

Conclusions:
Using CCTA, we defined the distance between the His bundle and the first septal perforator. Operators implanting LBBP leads can use these measurements to guide safe lead placement.
Abstract 11572: Plasma Proteomic Signature Implicates Impaired Calcium Handling and Cell-Matrix Adhesion in Repaired Tetralogy of Fallot with Right Ventricular Volume and Pressure Overload
Authors: Lan Ingrid , Zhu Aihua , Van Eyk Jennifer E , Reddy Sushma
Published: March 2022

Introduction:
Patients with repaired tetralogy of Fallot (TOF) are subject to chronic volume and pressure loading leading to a 40% probability of right ventricular (RV) failure by the 3
rd
decade of life. We sought to identify a non-invasive, circulating signature of the systemic response to right heart stress to better understand the mechanisms of RV failure and to develop novel therapies.

Methods:
High throughput mass spectroscopy was used to assess circulating plasma proteins in controls with structurally normal hearts (N=14) and in TOF s/p repair (N=74): no residual lesion (N=4), severe right heart volume overload (N=28), severe right heart pressure overload (N=20), and moderate right heart volume and pressure overload (N=22). Ingenuity pathway analysis was used to identify enriched biological processes using proteins with log2 fold change>0.6, and q value <0.05.

Results:
Mean age in controls was 15±2yrs, 50% male and in TOF s/p repair 17±14yrs, 34% male. The RV was moderately dilated with normal function in those with volume and/or pressure overload. We identified (i) excellent proteomic coverage identifying >1500 proteins/sample; (ii) unique subset of proteins distinguishing control from tetralogy of Fallot with residual defects (Fig 1); (iii) upregulated pathways involved signal transduction (CREBBP), catabolic processes (NT5M), cell death and aging (FUCOA 2-fold); (iv) downregulated pathways involved immune response (IGHV4), complement and coagulation activation (VWF), regulation of calcium handling (S100A 12-fold) and cell-extracellular matrix adhesion.

Conclusion:
Patients with TOF s/p repair with RV volume and pressure overload have a distinct proteomic profile implicating heightened cell death pathways and impaired calcium handling which may predispose to heart failure and arrhythmias. These data suggest peripheral blood proteins can provide insight into the mechanisms of RV failure and can be used for monitoring disease progression.