bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13262: Improved Rabbit Model of Calcific Aortic Valve Disease Induces Severe Medial Calcification and Stenosis Equivalent to Human Disease
Authors: Anousakis-Vlachochristou Nikolaos , Mavroidis Manolis , Athanasiadou Dimitra , Varela Aimilia , Makridakis Manousos , Katsa Maria , Miliou Antigoni , Lali Dimitra , Carneiro Karina , Vlahou Antonia , Thomaidis Nikolaos , Anagnostopoulos Constantinos D , Cokkinos Dennis V , Tsioufis Costas , Toutouzas Konstantinos
Published: April 2022

Introduction:
Accurate animal models of calcific aortic valve stenosis (CAVS) are needed to get insights into the early stages. We had previously modified a rabbit model to achieve CAVS. Here, we sought to assess its ability to produce similar lesion to humans.

Methods:
New Zealand rabbits were randomized to normal diet or +1% cholesterol + 3500 I.U.s/kg Vitamin D2 daily. Aortic valve area was assessed with echocardiography. At 7 weeks, blood serum and valve cusps were retrieved from sacrificed animals. Valve cusps were ex-vivo imaged with 18F-NaF microPET/CT, snap-frozen or formalin-fixed. Cusps were homogenized with an optimized protocol. Pyrophosphate (PPi) was measured in serum and cusps, metabolites analyzed with LC-MS/MS. Phosphatase activity was detected with BCIP/NBT assay. Protein content was analyzed with immunohistochemistry, quantitative ELISA and proteomics analysis (LC-MS/MS), and compared to human databases. Fixed cusps were analyzed using FT-IR and imaged with atomic force, scanning and transmission electron microscope. EDX chemical maps were obtained from the regions of interest

Results:
Vitamin D and metabolites were validated in serum and tissue. Echocardiography confirmed significant valve stenosis. Sodium fluoride activity was quadrupled in experimental valves. Histology revealed severe medial calcification, positive for osteopontin, negative for TNAP, BSPII and osteocalcin. Endogenous phosphatase activity colocalized with calcification in the medium. Serum PPi levels were increased, and tissue PPi levels were decreased. Proteomics analysis revealed 96 differentially expressed proteins validating important proteins, including apolipoproteins, complement, osteonectin, matrix Gl(a), galectin-3, fetuin-A, sortiltin, and TGF-b axis proteins. Ultrastructural analysis revealed the pathognomonic calcified spherical particles composed predominantly of phosphorus in the experimental valves.

Conclusions:
The improved high-fat - vitamin D toxicity rabbit model produced severe phosphate-induced CAVS, with similar protein and ultrastructural content to human disease, related to TGF-b pathway. Further investigations are needed in the underlying molecular networks driving the lesion.
Abstract 13275: Eastern-European and African Immigrants Have Higher Risk of Out-of-Hospital Cardiac Arrest Compared to Other Danish Immigrants
Authors: Garcia Rodrigue , Rajan Deepthi , Barcella Carlo , Svane Jesper , Warming Peder , Jabbari Reza , Gislason Gunnar , Torp-Pedersen Christian , Folke Fredrik , Tfelt-hansen Jacob
Published: April 2022

Introduction:
American studies have pointed out racial disparities regarding Out-of-Hospital Cardiac Arrest (OHCA) occurrence, but to date, no data exists among immigrants in Europe.

Hypothesis:
The risk of OHCA may vary according to region of origin among immigrants.

Methods:
This nationwide study included all immigrants identified from the Danish Cardiac Arrest Register with OHCA with presumed cardiac cause between 18 and 80 years from 2001 to 2014. Regions of origin were defined as Asia, Western countries, Eastern Europe, Africa, South America, and Arabic countries.

Results:
Overall, among 940,207 immigrants present in Denmark, a total of 1,724 (0.2%) OHCA (median 62 (IQR 50,71) years 70% males) were recorded. History of myocardial infarction, heart failure, and diabetes were present in 23%, 18%, and 16% respectively. 217 OHCA occurred in Asians, 673 in Westerners, 347 in Eastern Europeans, 107 in Africans, 19 in South Americans, and 361 in Arabic immigrants.Crude incidence rate (/ 100 000 person-years) was 15.2 (95%CI 9.14-23.7) in South American, 19.4 (95%CI 16.9-22.2) in Asian, 22.8 (95%CI 18.7-27.5) in African, 24.7 (95%CI 22.2-27.3) in Arabic, 26.2 (95%CI 23.5-29.1) in Eastern European and 32.4 (95%CI 30.0-34.9) in Western immigrants.After Cox regression, factors associated with OHCA were Eastern European origin (HR 1.28, 95%CI 1.13-1.47; P<0.001), African origin (HR 1.31, 95%CI 1.07-1.61; P=0.01), male sex (HR 1.89, 95%CI 1.70-2.10; P<0.001), age (HR 1.05, 95%CI 1.04-1.06; P<0.001), ischemic heart disease (HR 52.02; 95%CI 39.41-68.67; P<0.001), diabetes (HR 7.04; 95%CI 5.42-9.16; P<0.001), and heart failure (HR 1.33, 95%CI 1.06-1.64; P=0.01).

Conclusions:
This is the first European study assessing the incidence of OHCA among immigrants according to their region of origin. Eastern European and African immigrants had a higher risk of OHCA compared to South American, Asian, Arabic and Western immigrants.
Abstract 13280: apoB-Containing Lipoproteins and Risk of Myocardial Infarction: Distinguishing Between Particle Concentration, Content, and Type
Authors: Marston Nicholas A , Giugliano Robert , Melloni Giorgio , Park Jeong-Gun , Ference Brian A , Stein Evan A , Ruff Christian T , Sabatine Marc S
Published: April 2022

Background:
Lipid management typically focuses on levels of LDL cholesterol (LDL-C) and, to a lesser extent, triglycerides (TG). Basic investigation and genetic studies, however, suggest that the atherogenic particle subpopulations (LDL & VLDL) are similarly important and that the number of particles is more important than their lipid content.

Methods:
We performed a prospective cohort analysis in two populations: 1) 389,529 primary prevention patients w/o lipid-lowering therapy from UK Biobank, and 2) 45,708 statin-treated patients w/ established atherosclerosis from the FOURIER and IMPROVE-IT trials. Incident MI was assessed over a median follow up of 11.1 yrs in UKBB and 3.6 yrs in the trials. Adjusted HRs were calculated to determine whether lipid content (non-HDL-C & TG) or particle type (using LDL-C concentration as a surrogate for LDL, and TG concentration as a surrogate for TG-rich lipoproteins) offer predictive value beyond atherogenic particle concentration (apoB).

Results:
In the primary prevention cohort, apoB, non-HDL-C, and TG each individually predicted incident MI. However, when assessed together, only apoB remained a significant predictor (adj HR per 1-SD = 1.28 [95%CI: 1.16,1.42], p<0.0001) (
Fig, A/B
). Similarly, only apoB remained a predictor of MI in the secondary prevention cohort (
Fig, C/D
). Adjusting for apoB, there was no relationship between the ratio of TG to LDL-C (a surrogate for the ratio of TG-rich lipoproteins to LDL) and the risk of MI (p=0.32,
Fig, E
), implying that for a given concentration of apoB-containing lipoproteins, the relative proportion of particle subpopulations is not an independent predictor of risk.

Conclusion:
Risk for MI is best captured by the number of apoB-containing lipoproteins, independent from lipid content (cholesterol or TG) or type of lipoprotein (LDL or TG-rich). Therefore, therapeutic strategies should take into account lowering the overall concentration of all apoB-containing lipoproteins.
Abstract 13281: Idiopathic Ventricular Fibrillation Endophenotype Determines the Yield of Ultra-Rare
RYR2
Variants in Youthful Unexplained Sudden Cardiac Arrest
Authors: Stutzman Marissa J , Tester David J , Ackerman Michael J , Giudicessi John R
Published: April 2022

Introduction:
Loss-of-function variants in the RYR2-encoded cardiac calcium release channel underlie a small number of unexplained sudden cardiac arrest and death (SCA/SCD) cases.

Objective:
To determine if the yield of ultra-rare RYR2 variants in unexplained SCA patients with a default diagnosis of idiopathic ventricular fibrillation (IVF) depends on pre-defined IVF endophenotype and whether RYR2 variant-positive IVF cases have a discernible electrocardiographic phenotype.

Methods:
All SCA cases referred to Mayo Clinic’s Windland Smith Rice Genetic Heart Rhythm Clinic between 01/2000 and 04/2021 were reviewed. After exclusion of 116 cases where a probable SCA root cause was identified and/or
RYR2
genetic testing was not pursued, a total of 64 unexplained SCA cases (36% female; 26 ± 11 years at the time of SCA) were included. Clinical data was extracted from the medical record and patients classified as having i) IVF (no diagnostic clues), N=38 (59%) ii) PVC-triggered ventricular fibrillation (PTVF; documented short coupled PVC-triggered ventricular arrhythmias), N=19 (30%), or iii) early repolarization syndrome (ERS; J-point elevation ≥0.1 mV in ≥2 contiguous leads, excluding leads V
1
-V
3
), N=7 (11%). The yield of ultra-rare, non-synonymous
RYR2
variants (MAF<0.0001 in the Genome Aggregation Database) and electrocardiographic profiles were then compared.

Results:
Overall, a qualifying, ultra-rare
RYR2
non-synonymous variant was identified in 5 out of 64 (7.8%) unexplained SCA patients. Of note, the yield of ultra-rare
RYR2
missense variants was significantly higher in individuals with an PTVF endophenotype than those without [4/19 (21%) versus 1/45 (2.2%), p=0.02]. Interestingly, the majority of ultra-rare
RYR2
variant-positive unexplained SCA survivors [3/5 (60%)] displayed an exercise stress test pattern characterized by the onset of ventricular ectopy at ~120 bpm with suppression at heart rates ≥140 bpm.

Conclusions:
The burden of ultra-rare RYR2 variants is higher in unexplained SCA patients with documented PTVF. Collectively, this data suggests that i) a subset of PTVF may have an underlying genetic basis and ii) some IVF- and PTVF-associated RYR2 variants may result in an identifiable electrocardiographic profile.
Abstract 13282: Oxygen Uptake and Cardiac Output Exhibit Delayed Recovery After Maximum Incremental Ramp Exercise in Patients With Exercise Pulmonary Hypertension
Authors: Bhat Rohan R , Schoenike Mark , Christ Anastasia M , Farrell Robyn , Brooks Liana , Ho Jennifer E , Malhotra Rajeev , Lewis Greg
Published: April 2022

Introduction:
In individuals with dyspnea on exertion (DOE) and suspected exercise pulmonary hypertension (exPH), oxygen uptake (VO
2
), cardiac output (CO), peripheral oxygen extraction (Ca-vO
2
), and mean pulmonary artery pressure (mPAP) have been well characterized during incremental exercise but less is known about the kinetics of post-exercise recovery patterns.

Hypothesis:
Exercise recovery cardiac output kinetics are slowed in patients with exPH.

Methods:
Upright maximum incremental ramp cycle ergometry cardiopulmonary exercise testing with invasive hemodynamic monitoring and serial blood gas measurements during exercise and recovery was performed in 50 consecutive patients referred for evaluation of DOE of unclear etiology. VO
2
, arterial and venous oxygen content (Ca-vO
2
), Fick cardiac output, and mPAP were analyzed from rest, peak exercise, and 2 minutes post-exercise. ExPH was defined in a consistent manner with recent consensus statements (ΔmPAP/ΔCO >3.0 mmHg/L/min) from rest to peak exercise.

Results:
Among 50 patients with DOE, [62% female, Age 61.7±11.8, BMI 30.7±8.2] 2-min post-exercise VO
2
was -56±11%, CO: -22±19%, Ca-vO
2
:-42±15% compared to peak exercise values. The % fall in CO at 2min was significantly lower in the 26 patients with exPH compared to the 24 patients without exPH (Table). The average mPAP remained elevated at 2 min post-exercise (>20mmHg) in exPH despite normal average resting values.

Conclusions:
Patients with exPH demonstrate slowed CO recovery kinetics in conjunction with persistent PAP elevation 2-min post-exercise. Persistent elevation in blood flow through the pulmonary circuit at a time conducive to non-invasive assessment of PAP (i.e. by echocardiography) may lend itself to non-invasive detection of exercise-PH in patients undergoing evaluation of dyspnea on exertion.
Abstract 13285: Sensitivity to Beta-Adrenergic Stimulation in Pediatric Failing Single Ventricle Myocardium
Authors: Nakano Stephanie J , Schwisow Jessica A , Neltner Bonnie , Stone Matthew , Stauffer Brian L , Sucharov Carmen , Bristow Michael , Miyamoto Shelley
Published: April 2022

Introduction:
Children with heart failure (HF) in the context of palliated single ventricle congenital heart disease (SV) are treated with various pharmacotherapies, all with limited efficacy. Specifically, outcomes with β-blockade for HF in SV children are disparate from those in adult HF, even with similar downregulation of β
1
-adrenergic receptors (AR) in both populations.

Hypothesis:
Downregulation of β
1
-AR in pediatric SV subjects results in a unique contractile phenotype.

Methods:
Hearts were obtained from SV children who underwent transplant between 2010-2020. Non-failing SV (SV-NF) subjects underwent primary transplantation and had no signs of HF at the time of transplant. Failing SV (SV-F) subjects required transplantation due to end-stage HF (including refractory protein losing enteropathy or plastic bronchitis). At the time of transplant, trabeculae are isolated from the right ventricle of the explanted SV heart and mounted in a multi-chamber muscle bath.
Ex vivo
contractile response of isolated trabeculae is measured in response to the non-selective β-agonist isoproterenol; only trabeculae with an appropriate isoproterenol response are included in analyses.

Results:
Although β
1
-AR density is decreased in both SV-NF and SV-F myocardium, trabecular contractility assessment demonstrates increased sensitivity to isoproterenol in SV-F compared to SV-NF. Maximal tension generation with isoproterenol is similar between SV-NF and SV-F. Isoproterenol sensitivity in SV-F is comparable to that of non-failing adult hearts (age <40, n=4).

Conclusions:
Pediatric SV-F trabeculae demonstrate increased sensitivity to β-adrenergic stimulation when compared to SV-NF, but is similar to that of non-failing adult hearts. The preservation of adrenergic responsiveness may suggest that chronic, adverse β
1
-AR signaling is not part of the pathophysiology of failing SV, which may limit the effectiveness of β-blockade for HF indications in this population.
Abstract 13305: The Relationship of Health Activation to Risk of Future Cardiovascular Disease Among Family Caregivers of Patients With Chronic Illness in Rural Dwellers
Authors: Lin Chin-Yen , Chung Misook L , Feltner Frances J , Rayens Mary Kay , Mudd-Martin Gia , Biddle Martha J , Miller Jennifer L , Lennie Terry A , Moser Debra K
Published: April 2022

Background:
Rural family caregivers experience high levels of stress, burden, and psychological distress related to caregiving and are at higher risk for cardiovascular disease (CVD) compared to non-caregivers. Health activation (known also as patient activation) is an indicator of engagement in self-care and is defined as an individual’s knowledge, skill, and confidence in managing health. Better health activation is associated with better health outcomes. Because rural individuals are at greater risk of CVD and have fewer supportive resources than those in urban environments, we wanted to determine the relationship of health activation with risk for future CVD in this population.

Objective:
The purpose of this study was to examine the association of health activation with risk for future CVD among rural family caregivers of patients with chronic illness.

Methods:
This was a cross-sectional study using baseline data from a randomized controlled trial of an intervention to reduce CVD risk for rural caregivers. We measured health activation using the Patient Activation Measure. The predicted10-year risk of CVD was assessed using the Framingham risk score. Covariates potentially related to cardiovascular risks among caregivers were collected including stress (Perceived Stress Scale-Cohen), anxiety (Brief Symptom Inventory), depressive symptoms (Patient Health Questionnaire-9), and caregiver burden (Zarit Burden Interview). Generalized linear regression was used to analyze data.

Results:
Of 217 caregivers (mean age 53 ± 13 years, 79% female), 48% were caring for a spouse, 20% were caring for a parent, and the remaining 32% were caring for a sibling, a child, or other relatives. Caregivers with higher health activation had a lower risk of developing CVD in the future based on their Framingham risk score (B = -0.081, SE= 0.039, 95% CI= -0.158 to -0.004, p=0.038), independent of the other covariates. Every 10-point increase in health activation score was associated with a nearly 1-point (0.81) decrease in Framingham risk score.

Conclusions:
Health activation is a good predictor of future risk for developing CVD. Development and testing of interventions to promote health activation before people develop CVD is suggested to decrease the risk of future CVD.
Abstract 13308: Are Current Unplanned or Recent Hospitalizations Due to Non-Heart Failure Reasons Associated With Worse Outcomes After Implantable Cardioverter-Defibrillator Placement in Medicare Beneficiaries With Heart Failure?
Authors: Kuhrt Nathaniel , Akhabue Ehimare , Shalmon Uri , Bates Benjamin , Rua Melanie , Visaria Aayush , Lee Eileen , Dave Chintan , Gandhi Poonam , Setoguchi Soko
Published: April 2022

Introduction:
Elective ICD placement is efficacious for patients with chronic stable HF. ICD placement during or shortly after HF hospitalizations has been associated with worse outcomes. However, the impact of ICD placement in relation to non-HF hospitalizations is unknown.

Methods:
We identified all ICDs placed among older (age ≥ 66) HF patients without prior cardiac arrest using 20% random sample Medicare data (2008-2018). Setting of ICD was classified as: during unplanned 1) HF hospitalization or 2) non-HF hospitalization, within ≤ 3 months of 3) HF hospitalization or 4) non-HF hospitalization, or 5) electively during planned hospitalization or as outpatient. Non-HF hospitalization was defined as hospitalization without a primary or secondary HF diagnosis. We described patient characteristics and 3-yr mortality across these 5 settings. We estimated adjusted hazard ratios (HRs) using multivariable Cox regression with elective as reference.

Results:
Among 97,925 ICD patients (mean age 76, 67% male, 85% white), those getting ICDs during unplanned or after recent HF or non-HF hospitalizations were older and had more comorbidities vs elective patients (
Table
). The 3-year mortality after elective ICD placement was 21% but > 35% in non-elective groups. After adjustment, HR was significantly higher in unplanned HF (HR = 1.7), recent HF (HR= 1.6), unplanned non-HF (HR = 1.4), and recent non-HF (HR = 1.5) groups (
Figure).

Conclusions:
ICD placement during unplanned or after recent hospitalization is associated with worse outcomes, irrespective of hospitalization reasons. Randomized trials to understand appropriate settings of ICD placement are needed to maximize the benefit.
Abstract 13311: A Novel Senolytic Drug, Seno-7284 Ameliorates Age-Related Cardiometabolic Diseases
Authors: Katsuumi Goro , Suda Masayoshi , Shimizu Ippei , Yoshida Yohko , Hsiao Yung-Ting , Hsiao Chien Lun , Furuuchi Ryo , Minamino Tohru
Published: April 2022

Cellular senescence plays a pivotal role in aging and age-related disorders. Recently, it was shown that elimination of senescent cells, so-called "senolysis" has the potential to become a next generation therapy for age-related disorders including cardio-metabolic diseases. However, currently there is no senolytic drug available in clinical settings. The present study was aimed to identify a novel senolytic reagent effective for cardiometabolic diseases in compounds already available in clinical settings.

We demonstrate a compound called "Seno-7284" exhibits senolytic effect in murine models of type 2 diabetes, atherosclerosis, progeroid and chronological aged mice. Seno-7284 reduced the accumulation of senescent cells in visceral adipose tissue of diabetic mice as senescence-associated-beta-galactosidase (SA-beta-gal) staining exhibits. This associated with the suppression in systemic glucose intolerance, and adipose tissue inflammation in four weeks after the administration of Seno-7284. Administrating Seno-7284 for two weeks also suppressed the progression of atherosclerosis in ApoE-KO mice. This drug significantly improved the lifespan of Zm-KO mice by administering it from 12 weeks old. Administration of Seno-7284 from 50 week-old for 20 weeks improves physical function in chronological aged mice. Further analysis including single cell RNA-seq suggested that Seno-7284 stimulates endogenous senolytic function of NK cells and CD8+ T cells.

Our results indicate Seno-7284 mediates its biological effects by inducing senolysis in murine aging models. Seno-7284 would become promising therapies for age-related disorders.
Abstract 13320: APOO Knockout Elevates Plasma Cholesterol Levels Independent of LDLR and Accelerates Atherosclerosis in Mice
Authors: Chen Jin , Guo Xin , Hu Jiarui , yang yang , Qin Donglu , Tang Xiaoyu , Kuang Jie , Peng Daoquan , Yu Bilian
Published: April 2022

Introduction:
Apolipoprotein O (APOO), also known as MIC26, was first discovered through a functional genomics study aimed at identifying genes differentially regulated in the heart by obesity. While its physiologic role is incompletely understood, recent studies implicate a critical intracellular role for APOO in regulating lipid metabolism. The overall objective of the present study was to determine whether genetic deletion of APOO in mice would affect cholesterol metabolism and accelerate atherosclerosis.

Methods and Results:
Hepatic
Apoo
expression was induced in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (
Apoo
-/-
) model and liver-specific APOO knockout (

Alb
Cre
Apoo
fl/f

l
) model, we report here that APOO deletion elevates hepatic and plasma cholesterol levels. Then, we bred
Apoo
-/-
mouse onto both the
Ldlr
and
Apoe
KO hyperlipidemic mouse models. Female

Apoo
-/-
Apoe

-/-
mice and

Apoo
-/-
Ldlr

-/-
mice in both sexes displayed markedly elevated plasma cholesterol levels and more severe atherosclerotic lesions as compared to their littermate controls, implying the effect of APOO on cholesterol metabolism independent of LDLR and APOE. We demonstrate that APOO reduces cholesterol excretion through bile and feces. In addition, APOO deficiency led to hepatic triglycerides accumulation and decreased phospholipid unsaturation by inhibiting the expression of CYB5R3, which is responsible for hepatic fatty acid desaturation and elongation.

Conclusions:
These data represent the first in vivo experimental validation of the association of APOO with plasma cholesterol metabolism independent of LDLR. These results demonstrate that APOO deficiency led to the decreased CRB5R3 expression and fatty acid unsaturation, which responsible for the decrease of cholesterol excretion and elevated plasma cholesterol levels.
Abstract 13331: Case Report Of Transient Right Bundle Branch Block With S1q3t3 Pattern In Acute Pulmonary Embolism
Authors: john sabu , MALLAPPALLIL MARY , Singh Kamal P , Budzikowski Adam
Published: April 2022

69 year old woman with hypertension, sleep apnea and who had a recent knee replacement, was brought in to the emergency room (ER) for syncope. She had her physiotherapy session earlier in the day and became symptomatic with dizziness and shortness of breath and passed out. In the ER she had a systolic blood pressure (SBP) of 90mmHg and an oxygen saturation (O2 sat) of 80% on room air. She was given fluid bolus with improvement of SBP to 110mmHg. O2 sat improved to 99% with 10L of oxygen. Treatment was started with full dose of Enoxaparin subcutaneously. A 12-lead electrocardiogram (EKG) showed sinus tachycardia (ST) at 117 beats per minute (BPM), right bundle branch block (RBBB) and S1Q3T3 pattern. A bedside echocardiogram showed right ventricular (RV) distension. A CT-angiogram showed bilateral main stem pulmonary emboli (PE) with signs of RV strain. Patient was admitted and remained hemodynamically stable. A repeat EKG done the following day showed ST at 110 BPM with resolution of RBBB. An echocardiogram done now showed normal RV size and function. Patent was eventually discharged home on full dose apixaban. Q3S1T3
Figure 1 - ST, RBBB, S1Q3T3 pattern Figure 2 - ST

Discussion:
The patient presented with new RBBB (Figure 1) due to RV strain from acute PE as shown by the CT-angiogram and bedside echocardiogram. The EKG also showed S1Q3T3 pattern. With the resolution of the RV strain the following day, as noted on the subsequent echocardiogram, the 12 lead EKG showed the resolution of the RBBB and the QRS complex became narrow (Figure 2). RBBB is thought to be caused by acute RV overload and dilatation, accompanied by subendocardial ischemia in the right bundle. The S1Q3T3 pattern is historically considered as a “classic” EKG pattern associated with acute PE, even though it is neither sensitive nor specific for acute PE.

Conclusion:
The RBBB along with the S1Q3T3 pattern and its resolution with improvement of RV hemodynamics, is the first reported case in the literature.
Abstract 13341: Enhanced External Counterpulsation Attenuates Coronary Microcirculation Dysfunction in Coronary Artery Disease With Diabetes: Primary Results of EECP-CMD Study
Authors: Liang jianwen , Wei Wenbin , Shi Jian , Huang Hui , Wu Jiansheng , Wu Guifu
Published: April 2022

Introduction:
Coronary microcirculation dysfunction (CMD) is recognized as a pivotal pathophysiological change of coronary artery disease (CAD) with diabetes, however, there is little evidence for CMD medication treatment. Though enhanced external counterpulsation (EECP), a non-invasive therapy to increase shear stress of coronary flow, has been proved to release angina and restore endothelial capacities, whether EECP could attenuate CMD remains unknown.

Hypothesis:
EECP could attenuate CMD in patients of CAD with diabetes.

Methods:
This is a single center, prospective, randomized, single blind, control clinical trial (ChiCTR1800019060). Forty-eight patients [age: (57.7±8.5) yrs, 30 males] diagnosed with CAD and diabetes were enrolled during March 2019 and October 2020 in the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China. The main exclusion criteria are as follows: type 1 diabetes or diabetes history≤3 years; ≥ 70 years old; acute coronary syndrome; chronic total occlusion lesions and contraindications for EECP. All accepted coronary angiography and index of microcirculation resistance (IMR) test with pressure wire, then were randomized to EECP (n=24) or control (n=24) group. All followed standard medication therapy as guidelines recommended, EECP group took 35 times of EECP (60 minutes per time, 5 times a week and 7 weeks for whole procedure) after IMR test. Another IMR test would be done at the end of 12-week follow-up, the occurrence of angina and the metabolic parameters, FMD, PWV, CPET and TTE would also be evaluated.

Results:
The baseline IMR displayed no significant difference in both groups [EECP: (26.56±3.70) vs. Control: (26.91±4.22),
P
=0.74], while IMR markedly decreased in the EECP group than control at the end of follow-up [(24.02±3.15) vs. (26.78±4.63),
P
=0.02]. After multivariate linear regression analysis, FMD and PWV were found to independently correlated with IMR change [FMD: (β=0.45,
P
=0.014); PWV: (β=-0.27,
P
=0.038)]. Apart from above, EECP reduced angina occurrence and improved exercise tolerance, early diastolic function of left ventricular.

Conclusion:
EECP attenuates CMD in CAD with diabetes through coronary microcirculation resistance decrease.
Abstract 13344: Racial Differences in Baseline Characteristics Among Adult Women Presenting With ST Elevation Myocardial Infarction
Authors: Senthil Kumaran Sriviji , Del Cid Fratti Juan , Desai Anjali R , Mungee Sudhir , Mukhopadhyay Ekanka , Kizhakekuttu Tinoy J
Published: April 2022

Background:
Race related differences in baseline characteristics among women presenting with ST Elevation Myocardial Infraction (STEMI) has not been well studied.

Methods:
We used the National inpatient sample database to identify women who were admitted with STEMI as the primary diagnosis from 2016 to 2018. We evaluated the differences in comorbid conditions among different races - Caucasians, African Americans, Hispanics, Asian and other minority races including native Americans.

Results:
Of 208,223 female patients with STEMI, 75.7% were Caucasians, 11.3% African American, 7.4% Hispanic, 2.4% Asian, and 4.3% other races. African Americans had the highest percentage of obesity (23%), Obstructive Sleep Apnea (6%) and Tobacco use. Overall, Diabetes mellitus was more common among the racial minorities with the highest among Hispanics (52.3%) followed by Asians (47.8%) and then African Americans (41.2%). All racial minorities had higher incidence of Chronic kidney disease (CKD) when compared to Caucasians. Despite similar prevalence of Coronary artery disease, Asians had lower rates of prior revascularization procedures compared to other subgroups.

Conclusion:
The differences in prevalence of the various comorbidities among racial subgroups is crucial to note. This will determine outcomes in these patients. CKD is a key association that plays an important role in the pathogenesis of multiple cardiac diseases, including STEMI. Our study underscores the increased prevalence of CKD among racial minorities. Our findings will help guide the management of these populations and make long term management more patient centered.
Abstract 13362: Patient-centered Assessment Of Risk Of Stroke Vs. Bleeding In Patients With Atrial Fibrillation
Authors: Sargsyan Davit , Duan Yajie , Kostis William J , Ananth Cande , Kostis John B , Cabrera Javier ,   for the Myocardial Infarction Data Acquisition System (MIDAS) Study Group
Published: April 2022

Introduction:
Clinicians use CHA
2
DS
2
-VASc to predict stroke at one year and HAS-BLED to predict bleeding at one year in patients with atrial fibrillation. However, the scores do not consider the fear of the two outcomes in the individual patient.

Hypothesis:
A new algorithm predicting the relative risk of stroke versus bleeding at one year implemented as a web application will classify individual patients with high degree of precision.

Methods:
Using the Myocardial Infarction Data Acquisition System (MIDAS) database, we developed an algorithm that considers the preferences of each individual patient as estimated from data from history in predicting the risk of bleeding or stroke from CHA
2
DS
2
-VASc and HAS-BLED. Given the patient demographics and comorbidities, the confidence intervals of predicted risks of the outcomes were first obtained by fitting a multinomial regression model. The estimates were fed into a Deming regression model to correlate the risks of the outcomes in subgroups of patients with similar risk factors. The line of best fit between the two outcomes represented the objective relationship between the outcomes. Each patient would state their fears of the outcomes on a 0 to 100 scale and adding up to 100, e.g. 20 vs. 80 for fear of stroke vs. fear of bleeding respectively. A prediction region around the line of best fit was then calculated based on the patient’s fears.

Results:
Based on the predicted risks of stroke and bleeding and the patient’s fears of bleeding, the algorithm produces a graph with two regions corresponding to whether the patient should be treated with anticoagulants. Thus, patients who feared stroke more than bleeding would be more likely to receive anticoagulation compared to a decision based on objective data.

Conclusions:
The algorithm shown in the figure and implemented as a web application helps clinicians make decisions on whether to prescribe anticoagulants or not based on objective data modified by individual patient preferences.
Abstract 13402: Continuous Rhythm Monitoring in Patients After Embolic Stroke of Undetermined Source Yields High Evaluation Burden
Authors: von Falkenhausen Aenne Solvejg S , Feil Katharina , Schönecker Sonja , Müller Johanna , Becker Regina , Clauss Sebastian , Kellert Lars , Kaab Stefan , Sinner Moritz F
Published: April 2022

Introduction:
Embolic stroke of undetermined source (ESUS) accounts for up to 20% of ischemic strokes. Undetected atrial fibrillation (AF) represents one important underlying cause. Once diagnosed, initiation of oral anticoagulation is recommended for secondary stroke prevention. Yet, detection of paroxysmal AF is tedious. Implantable loop recorders (ICM) have evolved as the diagnostic gold standard. Prior studies have indicated that ICM implantation and remote monitoring in particular result in a relevant financial and personnel burden in unselected patients. ESUS patients are considered at higher risk of an AF diagnosis.

Hypothesis:
We hypothesized that AF diagnosis by ICM and remote monitoring puts considerable strain on health care providers, even in patients at high risk for AF after ESUS.

Methods:
We investigated all patients of our hospital-based, prospective, single-center, observational ESUS cohort that were equipped with an ICM after ESUS between January 2018 and December 2019. Follow-up was performed through July 2020.

Results:
Overall, 179 patients were eligible for analysis. Of these, 38 patients (22,1%) were diagnosed with AF by ICM and remote monitoring. During the study period a total of 11,975 episodes were transmitted through remote monitoring, of which 3,766 were alarms for AF. Response to alarms resulted in 307 on site visits and 132 telephone calls to inquire about symptoms, to inform about the diagnosis of AF, and to initiate a change in antithrombotic regimen from antiplatelet therapy to oral anticoagulation. On average, a single ESUS patient generated 40.9 episodes per year for review, triggered one additional on-site visit, and every other patient required additional telephonic follow-up. The number needed to diagnose one ESUS patient with AF within one year was 5.

Conclusions:
ICM and remote monitoring can successfully diagnose AF in a high-risk cohort after ESUS. Yet, the number of alarms other than for AF, and alarms inappropriately suggesting AF by far exceed appropriate AF diagnoses. Even in a cohort at high risk for AF and with an immediate therapeutic consequence upon AF diagnosis, the resulting burden on personnel and health care resources is high. An optimization of diagnostic ICM algorithms is therefore desirable.
Abstract 13403: Data Nuggets for Matching Large Clinical Datasets: Application in a 350,000 Record Perinatal Database
Authors: Tryputsen Volha , Ananth Cande V , Sargsyan Davit , Kostis John B , Kostis William J , Cabrera Javier
Published: April 2022

Introduction:
Research based on observational designs often include examination of outcome assessments across sub-populations. The sub-populations can be small, thereby potentially losing representativeness of the target population. The exact, approximate, and propensity score matching are popular methods to address this issue but become inefficient for large data sets.

Hypothesis:
Data Nuggets will produce matching results that are similar to conventional methods while performing the matching orders of magnitude faster.

Methods:
Data Nuggets is a novel data reduction technique that preserves the structure of the data by creating a collection of representative data points and contains the information about the centers, scale and weight for each group represented by a nugget. Observational data and simulations were used to show that matching data nuggets instead of individual patients is more efficient due to using data that is orders of magnitude smaller than the original and corrects for bias. We tested a Data Nuggets matching algorithm in a perinatal database with over 350,000 records with varying number of nuggets (between 100 and 800) against a conventional matching and full model fitting. We fit models to examine the association of preeclampsia on gestational duration, after adjusting or matching on age, race and body mass-index, and infant sex. All variables were scaled before fitting the models.

Results:
Models with a few hundred data nuggets produced results similar to those using conventional matching. Estimates of coefficients predicting gestational age via pre-eclampsia ranged from -0.73 weeks (100 nuggets) to -0.71 weeks (1,200 nuggets) compared to -0.72 (SE = 0.01) in the approximate matching and -0.80 (SE = 0.01) in the full (unmatched) data model (figure).

Conclusions:
Data Nuggets matching achieved results similar to those produced by the conventional matching method and is preferable for large data sets because of speed and efficiency.
Abstract 13411: Vasodilatory Capacity With Regadenoson Myocardial Perfusion Imaging In Patients With End Stage Liver Disease
Authors: Nguyen Thuy , Bradley William , Hernandez Pampaloni Miguel
Published: April 2022

Introduction:
The sensitivity and specificity of myocardial perfusion imaging in end stage liver disease (ESLD) patients ranges between 35-37% and 63-88%, respectively. Despite high levels of endogenous catecholamines and angiotensin, ESLD induced arterial vasodilation may exhaust the vasodilatory capacity of common pharmacologic stress agents. Reduced heart rate (HR) response to vasodilator stress test has been associated with increased major adverse cardiac events (MACE) in pre-transplant end stage renal disease patients but there is limited data in ESLD. We hypothesize that the hemodynamic response, measured as a change in HR and systolic blood pressure (SBP), during regadenoson stress test will be more robust when associated with low level exercise.

Method:
Forty-five subjects with ESLD referred for pre-transplant risk stratification were assigned to 1 of 3 groups: regadenoson alone or associated with low level treadmill or bicycle maneuver. Regadenoson was injected 2 minutes after low level exercise in the treadmill and bicycle groups. Myocardial perfusion images and hemodynamic changes were performed and interpreted as part of the standard clinical protocol.

Results:
There were 21 subjects in the regadenoson alone group, 10 in the low level treadmill group, and 14 in the bicycle maneuver group. There were no perfusion abnormalities in any of the groups and LVEF were greater than 50%. There was a statistically significant difference in HR response between the 3 groups (p = 0.015), but not in percentage SBP change between the 3 groups (p = 0.4). Pairwise comparison of regadenoson alone vs. low level treadmill percentage HR change showed statistical significance (p = 0.011). There was no MACE at 6-month follow-up.

Conclusions:
Low level exercise achieved a higher HR response than the other groups with a similar SBP response. The increased HR response may represent a more physiologic assessment of the true vasodilatory capacity remaining in ESLD patients.
Abstract 13422: The Impact of Cardiac Resynchronization Therapy With Defibrillator in Patients With Nonischemic Cardiomyopathy
Authors: Patel Harsh P , Thakkar Samarthkumar J , Kowlgi N. Gurukripa , Kumar Ashish , Parikh Rohan , Lee Justin Z , Parikh Vishal , Feitell Scott , Dani Sourbha , Desimone Christopher V , Deshmukh Abhishek
Published: April 2022

Introduction:
Real-world data on the significance of adding a defibrillator to cardiac resynchronization therapy (CRT-D) in patients with nonischemic cardiomyopathy (NICM) are limited.

Hypothesis:
CRT-D is associated with a lower risk of mortality and heart failure (HF) readmissions compared to CRT-P in NICM.

Methods:
We identified patients with NICM who underwent CRT-D and CRT without an ICD (CRT-P) by analyzing the nationwide readmission database from October 2015- December 2018 and using appropriate ICD-10 CM codes. Propensity score matching was performed to adjust for the confounders. Kaplan Meier curves were utilized for time to event analysis. Cox proportional hazard regression was used to generate hazard ratios. All-cause mortality at 6 months was the primary outcome whereas readmission due to HF and any other cause at 6 months were defined as secondary outcomes.

Results:
Post-PSM, 3054 patients with NICM underwent CRT-P, and 2863 patients underwent CRT-D placement. CRT-D did not show any benefit over CRT-P in reducing all-cause mortality at 6 months (2.92% vs. 2.79%, HR: 0.84, 95% CI: 0.61-1.16, p=0.29). Similarly, there was no difference in terms of readmissions due to other causes among both groups of patients (36.25% vs. 31.85%, HR: 0.98, 95% CI: 0.89-1.08, p=0.77). However, patients with CRT-P implantations had a lower risk of HF readmissions compared to the CRT-D group (10.05% vs. 14.25%, HR: 0.67, 95% CI: 0.58-0.79, p<0.0001).

Conclusions:
The addition of a defibrillator to CRT failed to show a survival benefit in patients with NICM. Moreover, HF readmissions were higher in CRT-D patients compared to CRT-P.
Abstract 13424: Lack of Improvement in Prevalence of Overtly Uncontrolled Blood Pressure Over the Past Decade and Its Association With Social Determinants
Authors: Visaria Aayush , Setoguchi Soko
Published: April 2022

Introduction:
Despite improvements in treatment strategies, BP control continues to be a public health challenge. We determined the 20-year national trends for overtly uncontrolled BP (OUBP).

Methods:
In this serial cross-sectional study, we included adults with 3 consecutive BP measurements from the 1999-2018 National Health and Nutrition Examination Surveys. OUBP was defined as mean SBP≥160 or DBP≥100. We calculated crude, age-adjusted, and covariate-adjusted prevalence estimates using multivariable logistic regression, and determined the effect of covariates on OUBP trends.

Results:
Among 44,622 participants (mean age 47 years, 51% female, 69% White), 2,613 (4%) had OUBP. OUBP individuals in 2015-18 were more likely to be male, non-Hispanic Black, diabetic, and lack insurance compared to those from earlier cycles (Table). There was a decreasing trend in multivariable-adjusted OUBP prevalence from 6.0% in 1999-2002 to 3.0% in 2007-10 (p<0.001), followed by an insignificant increase to 3.4% in 2015-18 (Figure). Although the downward trend in OUBP persisted after multivariable adjustment, family income, education, and insurance coverage modestly attenuated the trend (change in slope [95% CI] from 1.3% [0.9-1.7] to 1.0% [0.7-1.4] decrease/year). Lack of insurance was increasingly associated with OUBP (OR [95% CI]; 1999-2002=1.19 [0.61, 2.30], 2007-2010=1.83 [1.19, 2.82], 2015-2018=2.70 [1.64, 4.45]).

Conclusions:
Although OUBP prevalence has overall significantly decreased, it has remained stagnant since 2011. Social determinants, including insurance, income, education, and race may be playing increasingly important roles in OUBP prevalence.
Abstract 13447: Mental Health and Substance Use in the Psychosocial Assessment for Ventricular Assist Devices
Authors: Siry-Bove Bonnie , Mayton Caitlin , Latimer Abigail , Khazanie Prateeti , Knoepke Chris
Published: April 2022

Introduction:
A ventricular assist device (VAD) is a final treatment option for advanced heart failure (HF) but continues to have high mortality and requires ongoing support post implantation. VAD candidacy includes a psychosocial evaluation by social workers (SW) assessing domains including mental health and substance use (MH/SU). No universal psychosocial assessment exists, yet MH/SU are often cited as dealbreakers to receiving a VAD as higher psychosocial risks (e.g., substance use, lack of caregiver, etc) are linked to poorer outcomes. SWs have a crucial role in VAD candidacy determination and how they perceive their role in evaluations is understudied.

Methods:
Ongoing semi-structured interviews, currently with 18 SWs explored the structure and process of the psychosocial evaluation. The use of inductive thematic analysis led to emergent themes. Interviews were read in entirety prior to codes being categorized.

Results:
Three themes with sub themes emerged: 1) SW’s perceived role and structure of the evaluation itself, including that MH/SU is used to describe patient deficits and MH/SU is of minimal import, 2) Variability across sites with respect to methods and resources available for MH/SU assessment, and 3) The assessment process impacted SWs’ moral distress (Table).

Conclusions:
SWs provided insight into assessment variability, both across sites and within programs. Assessment subjectivity allows responsiveness to patient population needs but may limit reliability in predicting improved patient outcomes. Given the reality that these decisions deny life saving treatment, without national standards or evidence-based recommendations, the impact of assessments may affect clinician well-being. National clinical acceptance of strengths-based approaches to psychosocial assessment templates may provide evidence-based structure and increase objectivity aimed to improve patient selection and mitigate distress. Table 1.
Abstract 13455: Endothelium-Derived Hydrogen Sulfide Modulates Endothelial-Mesenchymal Transition in Heart Failure
Authors: Li Zhen , Xia Huijing , Sharp Thomas E , Lapenna Kyle , Elrod John W , Pfeilschifter Josef , Beck Karl-Friedrich , Goodchild Traci T , Lefer David J
Published: April 2022

Introduction:
Hydrogen sulfide (H
2
S) is a critical endogenous signaling molecule that exerts protective effects in the setting of heart failure (HF). Cystathionine γ-lyase (CSE), one of three H
2
S producing enzyme, is predominantly localized in the vascular endothelium. The interaction between endothelial cell derived H
2
S and endothelial-mesenchymal transition (EndoMT), an important pathological process contributing to the formation of fibrosis, has yet to be investigated.

Methods:
Endothelial cell specific CSE knockout (EC-CSE KO) and overexpressing (EC-CSE Tg) mice were subjected to transverse aortic constriction (TAC) to induce HF with reduced ejection fraction (HFrEF). Cardiac function, vascular reactivity, and treadmill exercise capacity following TAC were measured to determine the severity of HF. Histological analysis was performed to investigate changes in cardiac fibrosis. Vimentin and Von Willebrand factor co-immunostaining were utilized to investigate EndoMT activation.

Results:
EC-CSE KO mice exhibited reduced circulating H
2
S level, which was accompanied by increased EndoMT in the myocardium, resulting in increased perivascular fibrosis in the heart, impaired cardiac and vascular function, and worsened exercise performance. In contrast, genetic overexpression of CSE in endothelial cells elevated circulating and myocardial H
2
S, led to decreased EndoMT and subsequent fibrosis, preserved cardiac and endothelial function, and improved exercise capacity.

Conclusions:
Our data demonstrate that endothelial CSE modulates endothelial-mesenchymal transition to ameliorate the severity of pressure overload - induced heart failure. These data further suggest that endothelium-derived H
2
S is a potential therapeutic for the treatment of heart failure with reduced ejection fraction.