bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14870: Clinical Significance of Troponin Elevation in a Contemporary Hospitalized Population: Endotypes, Morbidity and In-hospital Mortality
Authors: Briscoe Michael , Sykes Robert A , Krysztofiak Thomas , Mangion Kenneth , Peck Oliver H , Berry Colin
Published: May 2021

Introduction:
Unplanned hospitalizations are commonly associated with a circulating troponin concentration >99
th
percentile upper reference limit (URL). In order to better understand the clinical significance of troponin elevation, we evaluated outcomes in hospitalized patients according to cardiac endotype.

Methods:
We prospectively screened consecutive hospitalized patients with elevated high-sensitivity troponin-I (hs-TnI) concentrations (Abbott ARCHITECT troponin-I assay; sex-specific URL, 99
th
centile: male: >34ng/L; female: >16ng/L) within a regional cardiac care network (population 650,000). A cardiology clinical team adjudicated individual patient records and assigned endotypes by consensus agreement according to the Fourth Universal Definition of Myocardial Infarction (MI). Endotypes were sub-classified into etiological category by inciting event(s). Characteristics and comorbidity were compared and outcomes recorded on virtual follow-up until June 2
nd
2020.

Results:
A total of 390 consecutive patients with ≥1 hs-TnI value >URL between March 1-April 15, 2020, were evaluated; 44 patients were excluded (
Duplicates: 2; Missing data: 41; Research patient: 1
). Of 346 who qualified for inclusion, an index diagnosis of Type 1 MI (T1MI), T2MI and myocardial injury were assigned in 115 (33.2%), 79 (22.8%) and 152 (43.9%) patients, respectively. Compared with T1MI, patients with T2MI and myocardial injury had lower peak hs-TnI values (median [IQR]: 86 [250-697]
vs
5020 [853-7774]ng/L; p< 0.01), lower estimated 10-year survival (40.2%
vs
53.4%; p=0.002), less frequently underwent coronary revascularization (1.4%
vs
45.2%; p<0.0005) and had longer inpatient stay (13.0
vs
6.1 days). Inpatient and overall mortality rates from admission to follow-up (median [range]: 71 [0-151] days) were higher among patients with T2MI and myocardial injury (19.9%
vs
7.8%; p=0.004; and 26.0%
vs
11.3%; Log rank (Mantel-Cox) X
2
= 1.927; p=0.003) independent of similar cardiovascular risk profiles.

Conclusions:
Despite lower peak circulating troponin concentrations, patients with T2MI and myocardial injury had higher inpatient mortality, lower estimated 10-year survival and longer in-hospital stay compared to those with T1MI.
Abstract 14875: Chronic Obstructive Pulmonary Disease Negatively Affects In-hospital Outcomes in Patients With Takotsubo Cardiomyopathy
Authors: Li Pengyang , Teng Catherine , Kranis Mark , Cai Peng , Dai Qiying , Pan Su , Dixon Richard A , Liu Qi
Published: May 2021

Introduction:
Chronic obstructive pulmonary disease (COPD) is a known comorbidity of takotsubo cardiomyopathy (TCM), and COPD exacerbation is a potential trigger of TCM. The association between COPD and in-hospital outcomes and complications in TCM patients is not well established.

Aim:
We aimed to assess the effect of COPD on hospitalized patients with a primary diagnosis of TCM.

Methods:
Using the latest National Inpatient Sample from 2016-2017, we conducted a retrospective cohort study in patients with a primary diagnosis of TCM with or without COPD. The diagnosis was identified by the ICD-10-CM coding system. We identified 3,139 patients admitted with a primary diagnosis of TCM; 684 of those patients also had a diagnosis of COPD. We performed propensity score matching in a 1:2 ratio (n=678 patients, matched COPD group; n=1,070, matched non-COPD group) and compared in-hospital outcomes and complications between TCM patients with and without a COPD diagnosis.

Results:
Before matching, the COPD group had worse outcomes compared with the non-COPD group in inpatient death (2.9% vs. 1.3%, p=0.006), length of stay (LOS) (4.02±2.99 days vs. 3.27±3.39 days, p<0.001), hospitalization costs ($55,242.68±47,637.40 vs. $48,316.97±47,939.84, p=0.001), and acute respiratory failure (ARF) (22.5% vs. 7.7%, p<0.001), respectively. After propensity score matching, the matched COPD group, compared with the matched non-COPD group, had a higher inpatient mortality rate (2.9% vs.1.0%, p=0.005), longer LOS (4.02±3.00 days vs. 3.40±3.54 days, p<0.001), higher hospitalization costs ($55,409.23±47,809.13 vs. $44,6469.60±42,209.10, p<0.001), and a higher incidence of ARF (22.6% vs. 8.2%, p<0.001) and cardiogenic shock (5.6% vs. 3.3%, p=0.024), respectively.

Conclusions:
Patients who are hospitalized for TCM and have COPD have higher rates of inpatient mortality, ARF, and cardiogenic shock, as well as a longer LOS and a higher cost of stay than TCM patients without COPD. Prospective studies are warranted to examine the effect of early intervention or treatment of COPD on short and long-term outcomes of TCM.
Abstract 14880: Single-cell Transcriptomes Identify Unique Endothelial Subpopulation (FABP4
+
TMEM100
-
) With Lipid Metabolism Dysfunction in Pulmonary Arterial Hypertension
Authors: LIU BIN , Dai Jingbo , Shuai Li , Yi Dan , Zhao Youyang , Dai Zhiyu
Published: May 2021

Introduction:
Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients.

Hypothesis:
We hypothesis that endothelial plasticity or distinct cell populations are critical for obstructive vascular remodeling in the pathogenesis of PAH.

Methods:
Here we applied single-cell RNA sequencing (ScRNA-seq) to profile the pulmonary cells in a severe mouse model (

Egln1
Tie2Cre

mice) of PAH. Human hPAEC from idiopathic PAH patients and healthy donors were used to measure FABP4 and FABP5 expression. siRNA mediated knockdown of FABP4 and FABP5 was performed to study cell proliferation and apoptosis. Mice with
Fabp4
and
Fabp5
deletion (

Fabp45
-/-

) and wild type (WT) mice were incubated with hypoxia (10% O
2
) to induced PAH.

Egln1
Tie2Cre

mice were bred with

Fabp45
-/-

mice to generate

Egln1
Tie2Cre

/

Fabp45
-/-

mice.

Results:
We identified five distinct EC subpopulations in both WT and

Egln1
Tie2Cre

mice via scRNA-seq. Unexpectedly, the number of Cluster (EC2, 49.8%) was markedly increased in

Egln1
Tie2Cre

lung compared with WT lung (2.8%). EC2 cluster (mainly from

Egln1
Tie2Cre

lung) was characterized by little expression of
Tmem100
,
Cldn5
,
Tspan7
,
Calcrl
and
Foxf1 and high expression of Fabp4, Cdh13, Sparl1 and Fabp5
. Fatty acid-binding protein (FABP) 4 and FABP5 (FABP4-5) were highly induced in PAECs from IPAH patients. Knockdown of FABP4-5 reduced EC proliferation and starvation-induced Caspase 3/7 activity.

Fabp45
-/-

mice were protected from hypoxia-induced PAH compared to WT mice. Moreover,

Egln1
Tie2Cre

/

Fabp45
-/-

mice also exhibited a reduction of RVSP and RV hypertrophy compared to

Egln1
Tie2Cre

mice.

Conclusions:
ScRNA-seq analysis identifies a unique endothelial population (FABP4
+
TMEM100
-
) highly enriched in the lung of severe PAH mice. Knockdown of FABP4-5 reduces EC proliferation starvation-induced injury. Genetic deletion of FABP4-5 protects from hypoxia and
Egln1
deficiency-induced PAH in mice.
Abstract 14896: Air Embolism and St Elevation Myocardial Infarction: A Systematic Review
Authors: Waheed Tayyab Ali , Nasir Usama , DONATO ANTHONY , NAZIR SALIK
Published: May 2021

Introduction:
Air embolism has rarely been associated with ST- elevation myocardial infarction (STEMI). Limited data exists on the risks, management and outcomes of this phenotype of STEMI to guide clinicians.

Method:
We queried EMbase, PubMed and Cochrane database for cases of air embolism associated with STEMI to better understand this association, its complications and outcomes.

Results:
We identified thirty-six cases of systemic air embolism events associated with STEMI. A mean age of fifty-nine with male predominance was identified. Patent foramen ovale was identified in 22%. Periprocedural air emboli occurred 66% (24/36) and miscellaneous causes including scuba diving and positive pressure ventilation accounted for 33% (12/36). Six patients reported chest pain, eleven developed shock and four suffered cardiac arrest. Neurological symptoms were reported in eighteen patients (50%). ST elevations were noted in all cases. CT angiography detected air bubbles in ten patients and seven were detected via cardiac catheterization. Transthoracic echocardiography detected air bubbles in a ventricular cavity in seven patients, and thirteen had air bubbles demonstrated on CT brain. Hyperbaric oxygen was delivered to eleven patients, nine of whom also received high flow oxygen. Seven were placed in Trendelenburg position and two had catheter aspiration of air bubbles. All patients received supportive treatment. Thirteen (36%) patients died.

Conclusion:
Patients with periprocedural STEMI and unexplained neurological symptoms should have air embolism considered in the differential. If identified, patients should be treated as per STEMI guidelines along with early delivery of 100% oxygen, in hyperbaric setting if available. If patient is hemodynamically unstable for catheterization, CT and echocardiographic imaging are reasonable alternatives to establish the diagnosis.
Abstract 15111: Aortic Pulsatility Index Predicts Heart Failure Rehospitalization: A Sub-analysis of the Escape Trial
Authors: Belkin Mark N , Alenghat Francis J , Besser Stephanie , Nguyen Ann , Chung Bow , Smith Bryan , Kalantari Sara , Sarswat Nitasha , Blair John , Kim Gene H , Grinstein Jonathan
Published: May 2021

Introduction:
Aortic pulsatility index (API), calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel hemodynamic measurement representing cardiac filling pressures and contractility.

Hypothesis:
API would predict heart failure hospitalizations in acutely decompensated heart failure participants in the Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness (ESCAPE) trial.

Methods:
From the ESCAPE trial individual-level data API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated, as well as reported routine invasive hemodynamics at baseline and after final hemodynamic-monitored optimization. Outcomes assessed were need for any rehospitalization and time to any first rehospitalization. Univariable analysis was conducted to assess rehospitalization. Negative binomial regression was used to analyze duration of time from discharge to first rehospitalization.

Results:
A total of 433 patients were enrolled in the ESCAPE trial. 189 patients had complete, accurate baseline hemodynamic data and were included in this analysis. No baseline hemodynamic measurements were associated with either outcome, except pulmonary artery (PA) diastolic pressure which predicted rehospitalization (OR 1.05 (95% CI 1.00-1.05, p= 0.02). Final API, OR 0.75 (95% CI 0.60-1.00, p= 0.03) and PAPI, OR 0.90 (95% CI 0.80-1.00, p= 0.03) predicted the need for any rehospitalization. Final API, OR 0.84 (95% CI 0.73-0.97, p= 0.02), and PA diastolic pressure, OR 1.03 (95% CI 1.01-1.06, p= 0.02), were associated with duration of time from discharge to any first hospitalization.

Conclusions:
The novel hemodynamic measurement API better predicted rehospitalization and time to rehospitalization in the ESCAPE trial when compared to routine, and other advanced invasive hemodynamic measurements.
Abstract 15122: Il18 Uses Both Il18 Receptor and Na-cl Co-transporter to Support Islet β Cell Proliferation and Insulin Secretion
Authors: Zhang Xian , Luo Songyuan , Minjie Wang , Shi Guo-Ping
Published: May 2021

Introduction:
The regeneration of pancreatic β cells to restore insulin production is a promising therapeutic strategy for insulin-dependent type-1 (T1D) and type-2 diabetes (T2D). Plasma IL18 levels are increased in these patients. Prior studies suggest a role for IL18 in inducing islet insulin production. IL18 administration suppressed autoimmune diabetes in non-obese diabetic mice. We recently discovered that IL18 uses two receptors IL18r and NCC (Na-Cl co-transporter) with equal binding kinetics.

Hypothesis:
IL18r and NCC use different mechanisms to mediate IL18 activity in islet β cell insulin production.

Methods and Results:
Immunoblot and immunofluorescent staining localized IL18 on islet α cells, NCC on islet β cells, and IL18r on pancreas acinar cells. Development of T1D or T2D increased the α cell IL18 expression. From high fat diet (HFD)-induced T2D, deficiency of IL18r (

Il18r
-/-

) or NCC (

Ncc
-/-

), or combined deficiency of both receptors (

Il18r
-/-
Ncc
-/-

) reduced insulin secretion, exacerbated β cell failure, decreased α cell content, reduced islet size, reduced β cell proliferation, and decreased the expression of islet proliferation markers. Deficiency of IL18r in

Il18r
-/-

and

Il18r
-/-
Ncc
-/-

mice aggravated β cell content and size reductions and glucose metabolism and increased β cell apoptosis after streptozotocin (STZ)-induced T1D.

Il18r
-/-
Ncc
-/-

mice also showed increased macrophage accumulation in the islets from both T1D and T2D mice. Using α cell-selective IL18-deficient

Gcg
CreERT2
IL18
fl/fl

mice, acinar cell-selective IL18r-deficient

Mist1
CreERT2
Il18r
fl/fl

mice, and β cell NCC-deficient

Ins1
Cre
Ncc
fl/fl

mice, we demonstrated that these mice showed impaired insulin secretion and glucose metabolism, exacerbated β cell failure, and aggravated HFD-induced T2D. Mechanistic studies suggested that IL18 uses NCC on β cells to promote insulin secretion and uses IL18r on acinar cells to assist β cell development.

Conclusions:
Islet α cell IL18 uses NCC on β cells to promote β cell proliferation and uses IL18r on acinar cells to produce inflammatory molecules to assist β cell generation and insulin secretion. Both the IL18r and NCC signaling pathways are essential to β cell function in diabetic patients.
Abstract 15140: Older Participant Perspectives on Permanent Study Drug Discontinuation in an Ongoing Primary Prevention Trial of Statins: A Qualitative Study
Authors: Zhou Zhen , Nelson Mark R
Published: May 2021

Introduction:
Study drug discontinuation is commonplace in clinical trials of older populations and poses a major challenge to trial investigators. Little is known about why older participants discontinue the study drug. This study aimed to understand factors contributing to permanent study drug discontinuation among participants aged ≥70 years within an ongoing primary prevention trial of statins by tapping into their experiences and perceptions.

Methods:
Trial participants who had permanently discontinued the study drug within 2 years of randomization were purposively sampled based on age (<75 and ≥75 years) and sex to participate in semi-structured phone interviews between March 2019 and February 2020. Interviews were audio-recorded, transcribed and analyzed thematically.

Results:
Thirty participants took part (21 females; mean age, 77 years) and three themes were identified from the data. Perceived adverse events (AEs) and their impact on daily living (mobility, functional capacity, quality of life, etc.) were identified as the major factors leading to the participants permanently discontinuing their study drug. Muscle symptoms were the most commonly reported AE. Selected participant quotes which describe symptoms and their impact are presented in Table. For some, a challenging life circumstance further lowered their tolerance to the perceived AEs thus making discontinuation more likely. A few discontinuations were attributed to other factors (e.g. concerns about possible side effects, GP advice, unrelated illness).

Conclusion:
Among healthy older participants enrolled in a statin trial, perceived AEs and their related impact were key factors contributing to the permanent study drug discontinuation. Addressing anticipated participant-reported AEs and their concerns about drug-related side effects at trial entry and offering timely medical assistance and support when AEs occur may be useful to reduce drug discontinuation rates.
Abstract 15153: Functional Cardiac Adaptation to 60 Days Strict Head-Down-Tilt Bedrest
Authors: Hoffmann Fabian , Rabineau Jeremy , Mehrkens Dennis , Johannes Bernd W , Caiania Enrico G , Migeotte Pierre-Francois , Jordan Jens , Tank Jens
Published: May 2021

Background:
Reduced physical activity increases the risk for heart failure. Myocardial strain measurements capture subtle abnormalities in myocardial function. We tested the hypothesis that bedrest deconditioning produces cardiac dysfunction in healthy persons.

Methods:
In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (8 women) were submitted to 60 days strict -6°-head-down-tilt bedrest. 8 subjects each were included in a control group or groups subjected to continuous artificial gravity training on a short-arm centrifuge [30 minutes/day] or intermittent centrifugation [6x5 min/day]. We assessed cardiac morphology, function, strain and hemodynamics by cardiac-MRI (baseline, end of bedrest, recovery) and echocardiography (baseline, end of bedrest). Before and after bedrest, we assessed orthostatic heart rate responses as measure of cardiovascular deconditioning.

Results:
We conducted a pooled analysis because cardiovascular responses to bedrest did not differ between groups. Supine heart rate (baseline: 64±9.6bpm; bedrest: 72.3±10.5bpm; recovery: 69.6±10.5bpm,
p
<0.0001) and diastolic blood-pressure (69.6±7.3mmHg; bedrest: 78.5±6.9mmHg; recovery: 70.3±6.3mmHg,
p
<0.0001) increased with bedrest. With head-up tilt, heart rate increased 22.8±10.5bpm before and 45.9±213bpm at the end of bedrest (
p
<0.0001) consistent with cardiovascular deconditioning. Cardiac-output decreased from 6.6±0.9l/min to 6±1l/min at end of bedrest (recovery: 6.8±1.2l/min,
p
=0.0096). Left ventricular ejection fraction and mass-index did not change. Echocardiographic global longitudinal strain (baseline: -19.90±2.1%; bedrest: -18.1±2.1%,
p
<0.0001) decreased, whereas global circumferential strain in MRI tended to increase (baseline: -18.6±1.7%; bedrest: -19.1±1.6%,
p
=0.0843). After four days of recovery MRI measurements had returned to baseline.

Conclusion:
In healthy persons, cardiovascular deconditioning through 60 days head-down-tilt bedrest does not lead to cardiac atrophy or sustained reductions in cardiac performance. The transient nature of cardiac strain changes suggests functional rather than structural changes in the heart.
Abstract 15168: Circulating Cell-free DNA Correlates With Markers of Disease Severity in the Rat Sugen/hypoxia Model of Pulmonary Arterial Hypertension
Authors: Zou Yvette , Brusca Samuel B , Jang Moon K , Kong Hyesik , Nelson Jasmine , Anderson Stasia , Chen Li-Yuan , Noguchi Audrey , Yu Zu-Xi , Sun Junfeng , Agbor-Enoh Sean , Solomon Michael A , Elinoff Jason M
Published: May 2021

Introduction:
Cell-free DNA (cfDNA) is released into circulation following tissue injury and cell turnover. In cancer and allograft rejection, cfDNA serves as a valuable biomarker for monitoring disease severity, progression, and response to therapy. The goal of the current study is to determine the temporal relationship between plasma cfDNA and disease severity in a PAH rodent model.

Methods:
Blood collection was performed weekly (weeks 4-11) in both sugen/hypoxia PAH rats (n=12) and age-matched, normoxia controls (n=12). cfDNA was isolated from plasma and concentration was determined by qRT-PCR. Cardiac MRI, cardiac catheterization and necropsy were performed at the end of study. Log-transformed concentrations of cfDNA were compared using linear mixed models. Pearson correlation coefficients were calculated to identify associations between rates of change in cfDNA and measures of disease severity.

Results:
Plasma cfDNA concentrations were significantly higher in PAH rats beginning at week 5 and continuing through week 10 (P < 0.05 for the comparison at each week; Figure 1). From weeks 4 to 11, there was an overall trend toward increasing cfDNA concentration over time in PAH rats (P = 0.07), whereas concentrations in control rats remained unchanged (P = 0.52). In PAH rats, the rate of change in log-transformed cfDNA concentration correlated inversely with RVEF (r = -0.80, P = 0.003), stroke volume index (r = -0.67, P = 0.02), and positively with total pulmonary resistance index (r = 0.62, P = 0.04). There were non-significant trends between the rate of change in cfDNA concentration and LV end-diastolic volume index (r = -0.54, P = 0.09), and Fulton index (r = 0.55, P = 0.08).

Conclusions:
Plasma cfDNA is elevated in the rat sugen/hypoxia PAH model and significantly correlated with markers of disease severity. Circulating cfDNA may reflect ongoing pulmonary vascular injury and remodeling, RV strain or both and thus may serve as a novel biomarker of PAH disease progression.
Abstract 15172: Murf1 Inhibitor Embl205 is a New Approach for Treatment of Heart Failure With Preserved Ejection Fraction in an Animal Model
Authors: Jannasch Anett , Schauer Antje , Kirchhoff Virginia , Draskowsi Runa , Dittfeld Claudia , Winzer Ephraim , Labeit Siegfried , Linke Axel , Tugtekin Sems-Malte , Adams Volker
Published: May 2021

Background:
The novel MuRF1 inhibitor EMBL205 attenuates effectively developing skeletal muscle atrophy and dysfunction in animals with heart failure with preserved ejection fraction (HFpEF, ZSF1 rat model). The impact of EMBL205 on myocardial function in the HFpEF setting is currently unknown and was evaluated in ZSF1 rats.

Methods:
20 wks-old female obese ZSF1 rats received EMBL205 (12 wks, conc. of 0.1% in chow; HFpEF-EMBL205). Age-matched untreated lean (con) and obese (HFpEF) ZSF1 rats served as controls. At 32 wks of age left ventricular (LV)-, aortic valve (AV) function and LV end diastolic pressure (LVEDP) was determined by echocardiography and invasive hemodynamic measurements. LV expression of collagen 1A (Col1A) and 3A (Col3A) was assessed by qRT-PCR, MMP2 expression was obtained by zymography and perivascular fibrosis was quantified in histological sections.

Results:
Development of HFpEF in ZSF1 obese animals is associated with cardiac enlargement and hypertrophy, as evident by increased myocardial weight, an increase in end diastolic volume (EDV) and LV anterior and posterior wall diameters. Diastolic LV-function is disturbed with elevation of E/é, an increased LVEDP and a preserved LV ejection fraction. AV peak velocity and peak gradient are significantly increased and AV opening area (AVA) significantly decreased. Col1A and Col3A expression are increased in HFpEF animals. EMBL205 treatment results in a significant reduction of myocardial weight and a trend towards lower EDV compared to HFpEF group. EMBL205 attenuates the increase in E/é, LVEDP, AV peak gradient and the decrease of AVA. EMBL205 significantly reduces Col3A expression and a trend for Col1A expression is seen. Increased perivascular fibrosis and MMP2 expression in HFpEF is extenuated by EMBL205 treatment (table 1).

Conclusions:
Application of EMBL205 attenuated the development of pathological myocardial alterations associated with HFpEF in ZSF1rats due to antifibrotic effects.
Abstract 15173: Association of Specific Statins With Cardiovascular Disease, All-cause Mortality, and Disability-free Survival in Initially Healthy Older Adults
Authors: Zhou Zhen , ofori asenso richard , Chowdhury Enayet K , Curtis Andrea J , Breslin Monique , Wolfe Rory , McNeil John J , Murray Anne M , Ernst Michael E , Reid Christopher M , Ryan Joanne , Woods Robyn L , Tonkin Andrew M , Nelson Mark R ,   ASPREE Investigator Group
Published: May 2021

Background:
The effectiveness of specific statins for the primary prevention of cardiovascular disease (CVD) in older adults is not well-characterized.

Objective:
To assess whether specific statin subclasses according to type, potency and solubility are associated with lower risk of CVD, all-cause mortality and improved disability-free survival in older adults.

Methods:
The cohort included 18,090 subjects from a primary prevention trial of aspirin, aged ≥70 years, initially free of CVD, disability and dementia, and followed for a median of 4.7 years. Outcomes included major adverse cardiovascular event (MACE, definition see
Table
), all-cause mortality and disability-free survival (a composite of persistent physical disability, all-cause mortality or dementia). Three multivariable Cox models were used to estimate hazard ratios (HRs) for each outcome comparing participants taking specific statin subclasses at baseline with baseline statin nonusers.

Results:
At baseline, participants’ median age was 74.2 years and 5,623 were using statins (31%). Atorvastatin (38%) was the most widely used, followed by simvastatin (30%), rosuvastatin (26%) and other statins (7%, mainly pravastatin). Compared with nonusers, the risk of MACE was significantly lower for atorvastatin (HR: 0.68, 95% CI: 0.48-0.96) and rosuvastatin users (0.59, 0.37-0.94), but not for simvastatin (0.82, 0.57-1.17) or other statin users (1.02, 0.54-1.93). A significant risk reduction in MACE was also seen for high-potency statin users and for both lipophilic and hydrophilic statin users but not for low/moderate-potency statin users. None of the specific statin subclasses was associated with improved disability-free survival or reduced all-cause mortality. (
Table
)

Conclusions:
In healthy older adults, specific statin subclasses were associated with varying cardiovascular benefits but none was associated with improved disability-free survival or reduced all-cause mortality.
Abstract 15180: Myeloid Differentiation Factor 2 Inhibitor Improves Left Ventricular Function And Heart Rate Variability Via Attenuating Cardiac Mitochondrial Dysfunction In Pre-diabetic Rats
Authors: Sumneang Natticha , Thun Oo Thura , jaiwongkam thidarat , Arunsak Busarin , Apaijai Nattayaporn , Liang Guang , Chattipakorn Siriporn , CHATTIPAKORN Nipon
Published: May 2021

Introduction:
Systemic inflammation is known as a key mediator of left ventricular (LV) dysfunction in pre-diabetic models including obese-insulin resistance. In obese rats, lipopolysaccharide activates myeloid differentiation factor 2 (MD2)/toll-like receptor 4 complex, leading to systemic inflammation. Previously, MD2 inhibitor L6H21 (20 mg/kg) was shown to effectively reduce systemic inflammation in obese mice. However, its potential benefits on the heart and the underlying mechanisms in pre-diabetic obese-insulin resistant rats are unknown.

Hypothesis:
L6H21 exerts cardiometabolic protection in pre-diabetic rats by improving LV function and heart rate variability (HRV) via reducing cardiac mitochondrial dysfunction.

Methods:
Male Wistar rats were fed either a normal diet (n=8) or high-fat diet (HFD, n=40) for 12 weeks. In HFD group, rats were divided into 5 groups (n=8/group): 1) vehicle (1% Na-carboxymethyl cellulose), 2) metformin (300 mg/kg, positive control), 3-5) L6H21 at 10, 20, and 40 mg/kg. After 4 weeks of treatments, LV function and HRV were examined. Heart tissue was assessed for mitochondrial function.

Results:
Pre-diabetic rats had impaired glucose tolerance, depressed HRV, and decreased LV ejection fraction (LVEF), indicating cardiac autonomic imbalance and LV dysfunction. Cardiac mitochondrial dysfunction was also observed, shown by increased mitochondrial ROS levels, mitochondrial depolarization, and mitochondrial swelling. Although L6H21 at 20 and 40 mg/kg improved insulin sensitivity, cardiac autonomic balance, LV function, and mitochondrial function, L6H21 at 40 mg/kg exerted the highest cardioprotective effects, compared to metformin, in pre-diabetic rats by restoring LV function, HRV, and cardiac mitochondrial function
(Fig)
.

Conclusions:
L6H21 exerted cardiometabolic protection in pre-diabetic rats by improving insulin sensitivity and cardiac mitochondrial function, leading to restoring LV function.
Abstract 15181: The National Pediatric Cardiology Boot Camp Training Program - Five Years’ Evidence of Consistent Educational Benefit
Authors: Sacks Loren D , Motonaga Kara S , Krawczeski Catherine D , Axelrod David M , Su Lillian , Bishop Robert , Arunamata Alisa , Kwiatkowski David M , Olson Inger , Maskatia Shiraz A , Kipps Alaina K , Lopez Leo , SHENOY Rajesh U , Grossfeld Paul D , Weidenbach Michael , Kelle Angela M , Patel Sonali S , Pass Robert H , Romero-Villanueva Lupe , Lewin Holly , Ceresnak Scott R
Published: May 2021

Introduction:
The transition from residency to subspecialty fellowship in pediatric cardiology is challenging, with the daunting requirement to rapidly acquire a broad scope of knowledge and skill. In 2015, a pediatric cardiology boot camp was designed as an educational tool to help prepare trainees for this transition.

Hypothesis:
A national pediatric cardiology boot camp consistently improves knowledge and decreases anxiety for prospective fellows.

Methods:
In late spring each year (2015-2019), a 2.5-day intensive program was provided for trainees prior to beginning fellowship in July. Hands-on, simulation-based experiences were provided on topics including anatomy, auscultation, echocardiography, catheterization, cardiovascular intensive care, electrophysiology, heart failure, pulmonary hypertension, and cardiac surgery. Knowledge based exams and surveys were completed by each participant pre- and post-training. Pre- and post-training exam results were compared via paired t-tests and survey results were compared via Wilcoxon rank sum.

Results:
Over 5 years 144 participants (72 female, 50%) completed the course, representing 40 fellowship programs in the United States and Canada. In aggregate, significant improvement was seen in participants’ knowledge assessment (pre 45 ± 11% vs. post 71 ± 9%; p<0.0001). Post-intervention tests showed significant increases in knowledge every year, with a similar mean rate of improvement from year to year (25±10%; p=0.15). Participants in 2015 did score higher on both pre and post testing (pre 55±10%, post 85±7%; p<0.0001), but the improvement rate remained consistent. Pre- and post-program surveys showed significant improvement in 38 of 38 domains assessing comfort and anxiety (p<0.001 for each domain). All participants strongly agreed (97%) or agreed (3%) that the boot camp was a valuable learning experience and 98% strongly agreed (66%) or agreed (32%) that boot camp alleviated anxieties about starting fellowship.

Conclusions:
The Pediatric Cardiology Boot Camp provides a significant and reproducible educational benefit to participants nationwide. This intensive program simultaneously improves learners’ knowledge and alleviates anxiety as they transition to subspecialty training.
Abstract 15182: Acute Complications of Type B Aortic Intramural Hematoma Compared With Classic Aortic Dissection
Authors: Miyoshi Yutaro , Kaji Shuichirou , Masumoto Akiko , Toyota Toshiaki , Okada Taiji , Kim Kitae , Kitai Takeshi , Ehara Natsuhiko , Kobori Atsushi , Kinoshita Makoto , Furukawa Yutaka
Published: May 2021

Introduction:
Although acute type B aortic intramural hematoma (B-IMH) is a variant of acute aortic syndrome having similar clinical demographics to type B classic aortic dissection (B-AD), early clinical course including acute complications are not well investigated. The purpose of this study was to investigate early clinical course and acute complications of B-IMH in comparison with that of B-AD.

Methods:
Clinical features and early clinical course including acute complications were retrospectively analyzed in 270 B-IMH and 177 B-AD consecutive patients who were admitted to our hospital between 1991 and 2020. Acute complications were defined as rupture, impending rupture, re-dissection, and visceral and leg ischemia.

Results:
As compared with B-AD, B-IMH presented at older age (72±11 vs 62±15 years; p<0.001), predominantly in females (37% vs 25%). During in-hospital courses, limb ischemia and mesenteric ischemia were less common in patients with B-IMH than those with B-AD (0.4% versus 5.1%, p=0.003, 0.4% versus 2.8%, p=0.03; respectively). In contrast, spinal ischemia was more common in B-IMH patients (2.4% versus 0.6%, p=0.05). Aortic rupture and impending rupture were comparable between B-IMH and B-AD patients (5.9% versus 7.3%. p=0.28). Besides, re-dissection was also comparable between two groups (2.2% versus 5.1%, p=0.06). As a result, prevalence of acute complications was significantly lower in patients with B-IMH (8.8% versus 17%, p=0.008). In-hospital mortality rate in B-IMH was significantly lower than that in B-AD (0.4% versus 9.0%, p<0.001).

Conclusions:
Although patients with B-IMH had lower in-hospital mortality rates than patients with B-AD, significant portion of B-IMH patients had fatal complications including spinal ischemia or aortic rupture. Patients with B-IMH should be carefully observed as well as patients with B-AD patients.
Abstract 15187: Very Low-density Lipoprotein Signals Through Sphingosine-1-phosphate Receptors Upon Binding to Scavenger Receptor Class B, Type I in Human Adrenocortical Cells
Authors: Chowdhury Shinjini , Choudhary Vivek , Choudhary Mrunal , Bollag Wendy B
Published: May 2021

Aldosterone is considered to be a link between hypertension and obesity; obese individuals have high serum levels of both very low-density lipoprotein (VLDL) and sphingosine-1-phosphate (S1P). VLDL has been shown to stimulate aldosterone production in multiple zona glomerulosa cell models. S1P is transported in blood bound to lipoproteins such as VLDL, low-density lipoprotein, and high-density lipoprotein (HDL); the VLDL particle contains the highest levels of S1P. S1P in HDL has been shown to promote interactions between scavenger receptor class B, type I (SR-BI) and S1P receptor 1 (S1PR1). We hypothesized that like HDL, VLDL will signal through S1PRs upon binding to SR-BI; therefore, VLDL-induced aldosterone production will be inhibited by S1PR antagonists. Human adrenocortical cells (HAC15) were treated with VLDL and/or an S1PR1 antagonist (Ex26) for 24 h. The expression of steroidogenic genes and aldosterone production were monitored by qRT-PCR and radioimmunoassay, respectively. Ex26 inhibited VLDL-induced increases in CYP11B2 (22-fold) and StAR (1.5-fold) expression by 43% and 10%, respectively. Ex26 had no effect on VLDL-stimulated increase in NR4A1 expression. In addition, the VLDL-induced 5-fold increase in aldosterone levels was significantly inhibited by Ex26 (36%). Our results indicate that like HDL, VLDL likely signals by binding to SR-BI and activating S1PR1, such that an S1PR1 antagonist reduces VLDL-induced aldosterone production. Further investigation into these steroidogenic signaling pathways is warranted and may lead to the identification of therapeutic targets such as S1PR1 to potentially treat obesity-associated hypertension.
Abstract 15194: The Distribution of Anti-factor Xa Activity Values, Prothrombin Time and Activated Partial Thromboplastin Time Assessed at Multiple Points in Patients on Edoxaban Therapy
Authors: Ono Ryohei , Fukushima Kenichi , Takahashi Hidehisa R , Hori Yasuhiko , Kobayashi Yoshio
Published: May 2021

Introduction:
Edoxaban is one of the direct oral anticoagulants (DOACs) used for non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Chromogenic anti-factor Xa activity (AXA) is the appropriate assay to measure the pharmacodynamics of a factor Xa inhibitor and to estimate plasma drug concentrations. Although patients taking DOACs do not require routine coagulation monitoring, the distributions of AXA values have not been assessed at multiple points in the previous study.

Purpose:
To clarify the distribution of AXA values at two-hour intervals in patients taking edoxaban.

Methods:
Sixteen patients (66.8 ± 9.6 years, 11 males) with NVAF or VTE on edoxaban therapy were enrolled in the study. We measured AXA, using chromogenic assay with the HemosIL Liquid Heparin kit, at two-hour intervals (from immediately before the intake of edoxaban to 8 hours after the intake). The dosage of edoxaban was 30 mg (n=11) once daily (OD) or 60 mg (n=5) OD according to the prescribing information.

Results:
The distributions of AXA values of 30 mg OD at 0, 2, 4, 6 and 8 hours after the intake of edoxaban were 0.12±0.08, 0.80±0.48, 0.94±0.48, 0.72±0.34 and 0.53±0.32 (IU/mL), respectively. The distributions of AXA values of 60 mg OD at 0, 2, 4, 6 and 8 hours after the intake of edoxaban were 0.17±0.04, 1.59±0.76, 1.43±0.34, 1.29±0.32 and 0.96±0.21 (IU/mL), respectively.

Conclusions:
Our findings reveal that the peak time of AXA values might be different depending on the dosage. The peak time of 30 mg OD is between 0 to 4 hours, whereas that of 60 mg OD is between 2 to 6 hours after the intake of edoxaban. In addition, the AXA values of 60 mg OD are almost twice as much as that of 30 mg at each point.
Abstract 15216: Longitudinal Changes in Peak Aortic Valve Velocity in Late Life: Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ravnkilde Kirstine , Claggett Brian , Skali Lami Hicham , Konety Suma , Kitzman Dalane , Mosley Thomas , NAMBI VIJAY , Matsushita Kunihiro , Shah Amil M
Published: May 2021

Background:
Aortic stenosis (AS) is a growing health problem within the aging population. We aimed to quantify longitudinal changes in aortic valve hemodynamics in late life.

Methods:
We studied 2,512 community-based elderly participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent uniform echocardiographic imaging at study visits 5 (2011-2013) and 7 (2018-2019). Peak aortic valve (AV) velocity was assessed by continuous wave spectral Doppler from the apical 5 chamber view. Participants with heart failure or in atrial fibrillation at either echocardiographic examination were excluded.

Results:
Mean age at Visit 5 was 74 ± 4 years, 41% were male, 24% black, and the mean AV velocity at Visit 5 was 1.27 ± 0.28 m/s. Over median 6.6 [IQR: 6.1-7.0] years, AV velocity increased by 0.15 ± 0.32 m/s and the mean velocity at Visit 7 was 1.43 ± 0.43 m/s. Of 2,454 participants with peak AV velocity < 2.0 m/s at Visit 5, 123 (5%) developed a peak AV velocity > 2.0 m/s at Visit 7 (mean 2.45 ± 0.46 m/s). In models accounting for blood pressure and heart rate at both study visits, Visit 5 predictors of transitioning to a peak AV velocity > 2.0 m/s included age, male sex, white race, BMI, higher NT-proBNP and hs-troponin T, and greater LA volume index and E/e’ ratio (
Table
).

Conclusions:
Peak AV velocity increases over 6 years in late life, with ~5% developing a peak velocity > 2.0 m/s. Demographics, higher cardiac biomarkers, and worse diastolic function predict increases in peak AV velocity in late life. These data have important implications for the development of age-related aortic stenosis.
Abstract 15218: Structural and Functional Alterations in a Premature Ventricular Contractions-induced Cardiomyopathy Model
Authors: Balderas Villalobos Jaime , Samso Montserrat , Lynch Christopher , Torrado Juan , Ramirez Rafael J , Tan Alex Y , Kaszala Karoly , Huizar Jose F , Eltit Jose M
Published: May 2021

Introduction:
Previous studies of premature ventricular contractions (PVC)-induced cardiomyopathy (PVC-CM) in canines have showed reduction in L-type Ca
2+
current and Ca
2+
transient amplitude in isolated ventricular myocytes, concomitant with eccentric hypertrophy and a decline in left ventricular (LV) ejection fraction.

Objectives:
Assess potential alterations of PVC-CM related to: 1) the efficiency of the Ca
2+
recycling machinery in the sarcoplasmic reticulum (SR), and 2) the overall ultrastructural integrity of myocytes.

Methods:
Modified pacemakers were implanted in healthy canines to reproduce PVC-CM after 3 months of bigeminal PVC (50% burden at 200-220 ms coupling interval). Animals were randomized to either 50% PVC or no PVC (sham). Ventricular cardiomyocytes were isolated and paced to measure Ca
2+
transients using Fura2. Permeabilized cardiomyocytes loaded with Fluo-5N were used to assess SERCA2 activity
in vitro
. Additionally, expression of SERCA2, and phosphorylated versus total phospholamban (PLN) were measured with Western blot (WB). LV wall muscle was fixed, en-block stained with uranyl acetate, and thin-sectioned for electron microscopy (EM).

Results:
There was a non-statistically significant trend towards a reduction of SR-Ca
2+
reuptake efficiency in PVC-CM vs sham, evidenced by a 21% slower decay of the electrically-evoked cytosolic Ca
2+
transient and a 23% slower maximal rate of SR Ca
2+
uptake (PVC-CM n=42 cells, 4 animals vs sham n=50 cells, 3 animals). WB analysis showed a 23% reduction in SERCA2 expression (0.76 ± 0.18 vs 1 ± 0.25, P =0.002, n=6 animals each), a 40% increase in PLN expression (1.4 ± 0.18 vs 1 ± 0.1, P <0.0001, n= 3 animals each), and a 64% reduction in phospho-PLN (0.35 ± 0.15 vs 1 ± 0.18, P <0.0001, n=3 animals each) in PVC-CM vs sham. In addition, EM showed intact dyads, regularly shaped SR, but noticeable myofibril disorder in the PVC-CM derived samples.

Conclusions:
In PVC-CM, there is impaired electrically-evoked Ca
2+
cycling due to a combination of reduced L-type Ca
2+
channels and reduced SERCA-mediated SR Ca
2+
uptake. This combined with the apparent ultrastructural remodeling, underscore long-term cellular adaptations leading to LV systolic dysfunction associated to the chronic exposure to PVC.
Abstract 15240: Evaluation of the Performance and Safety of Wideband Cardiac MRI in Patients With a Cardiac Implantable Electronic Device (CIED)
Authors: Schwartz Sarah M , Pathrose Ashitha , Serhal Ali , Avery Ryan , Ragin Ann , Charron Jessica , Knight Bradley P , Passman Rod S , Kim Daniel
Published: May 2021

Introduction:
Wideband late gadolinium enhancement (LGE) CMR is capable of suppressing image artifacts induced by cardiac implanted electronic devices (CIEDs). We implemented our own wideband segmented (seg) breath-hold and wideband single-shot (SS) free-breathing LGE pulse sequences and used them clinically since 2016. The purpose of this study was to evaluate image quality and CMR safety of wideband LGE compared to standard LGE.

Methods:
We retrospectively identified 54 consecutive patients (mean age: 61±15 years; 31% females) with CIED (33 t-ICD, 4 s-ICD, 15 pacemaker, 1 CRT-D, 1 CRT-P) who underwent CMR at 1.5T (Avanto, Siemens). Standard seg, wideband seg, and wideband SS LGE used standard imaging parameters. 16 myocardial segments were scored for scar/myocardial conspicuity and presence of any visual artifact on a 5-point Likert scale (1:worst; 3:acceptable; 5:best). Distance between center of the heart and CIED (CXR D) was measured on chest X-ray. Whole-body specific absorption rate (SAR) was read from DICOM metadata. Device changes were calculated from pre- and post- device interrogation measurements.

Results:
Both wideband seg and SS LGE consistently produced better image quality than standard LGE (Figure 1A). Median conspicuity and artifact scores were significantly better for wideband seg (F=20.6, p<0.001) and wideband SS (F=24.2, p<0.001) LGE compared to standard LGE. There was a trend in conspicuity and artifact scores with CIED distance for standard LGE (rho=0.476, p=0.02), but not wideband LGE scans (Figure 1B, 1C). Whole-body SAR averaged for both wideband scans (0.15±0.04 W/kg) was one order of magnitude below the 2.0 W/kg FDA limit. Device parameters (sensing, impedance, threshold, battery level) did not differ before and after CMR including wideband LGE.

Conclusions:
Both wideband seg and SS LGE scans produced improved image quality compared to standard LGE while maintaining CMR safety. *The first two authors (SS and AP) contributed equally
Abstract 15250: The Correlation Between the Amounts of Exosomes and Functional Parameters of Myocardial Perfusion Imaging in the Patients With Coronary Artery Disease
Authors: Chang Sheng Nan , Liu Chia-Ju , Chen Jien-jiun , Hsiao Wen-Pin , Jhong Yao-De , Chang Yi-Cheng , Lin Jou-Wei , Hwang Juey-Jen
Published: May 2021

Introduction:
Exosomes were found to be involved in the pathophysiological process of coronary artery disease (CAD). The study investigated the relationship of the exosome amounts and imaging markers of myocardial perfusion in patients with CAD.

Methods:
Peripheral blood was collected from patients who had more than 70% luminal stenosis of coronary arteries on coronary angiography. Plasma exosomes were extracted by chemical precipitation and flow cytometry (CytoFLEX BB10068). Further confirmation of exosome surface markers was performed by Western blot. The myocardial perfusion imaging (MPI) of single photon emission computed tomography performed less than 6 months before coronary angiography were retrospectively reviewed. Perfusion deficits of MPI were scored visually by a nuclear medicine physician. Functional parameters of MPI were generated from gated images by QPS/QGS software (Cedars-Sinai), including ejection fraction (EF), diastolic function, shape index of heart, etc. The amounts of exosomes were correlated with the perfusion deficits and functional parameters of MPI using Spearman’s correlation. Comparison of the exosome amounts between patients with normal or abnormal functional parameters was performed by Mann-Whitney U test.

Results:
Exosome amounts and MPI images from 40 patients with CAD were analyzed. Exosome amounts have poor correlation with perfusion and functional parameters of MPI (all R value <0.5). However, patients with abnormal post-stress ejection fraction (<50%) had significantly higher amounts of exosome in size of 100nm and 100 to 200nm ( p = 0.046, 0.030, respectively). The mean amounts of exosome in size of 100nm and 100 to 200nm were 67793.8 ± 45498.3 and 19394.1 ± 10995.9 million particle/ml in patients with abnormal EF, compared to 43885.0 ± 24678.4 and 13604.2 ± 8381.3 million particle/ml in patients with normal EF.

Conclusions:
CAD patients with abnormal systolic function have increasing amounts of exosomes. Exosomes may participate in the dysfunction process of ischemic heart disease. The exact casual relationship and mechanism needs further investigation.