bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13246: The Impact of Body-Mass Index Trajectories During Early Adulthood on Cardiac Mechanics in Middle Age: The CARDIA Study
Authors: Khan Sadiya S , Shah Sanjiv J , Liu Kiang J , Lewis Cora E , Shay Christina , Goff David C , Reis Jared P , Lloyd-Jones Donald M , Allen Norrina B
Published: July 2021

Introduction:
Obesity is a risk factor for left ventricular dysfunction and incident heart failure. We hypothesized that baseline body mass index (BMI) and trajectories in weight change through young adulthood are associated with abnormal cardiac mechanics in middle age.

Methods:
We examined 2,735 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. BMI was calculated at exam years 0, 2, 5, 7, 10, 15, 20, 25. 2D echo was performed with speckle-tracking analysis. Left ventricular ejection fraction (LVEF) and global longitudinal, circumferential, and radial strain (GLS, GCS, GRS, respectively) were measured at y25. Group-based modeling with latent class analysis (PROC TRAJ) was used to identify trajectories in relative changes in BMI (% change in BMI from baseline at each exam). Linear regression examined associations between baseline BMI and trajectory of BMI change and absolute GLS, GCS, and GRS at y25 adjusting for demographics, risk factors, and echo parameters.

Results:
Mean age at baseline was 25±4 years. Baseline BMI at y0 was significantly associated with mean GLS at y25 (p=0.01), but not GRS or GCS. We identified 4 distinct trajectories of relative BMI change: stable weight (36% of sample), mild increase (40%), moderate increase (18%), and major increase (6%) in weight (Figure). At y25, there was no difference in LVEF across the 4 BMI trajectory groups (P=NS). After adjustment for clinical variables and baseline BMI, absolute GLS was lower in groups with BMI increases (overall P<0.001). GRS and GCS were not significantly different between the groups.

Conclusion:
In conclusion, baseline BMI and increases in BMI during young adulthood are significantly associated with the presence of subclinical cardiac dysfunction in middle age despite normal EF. This novel characterization of BMI trajectories across young adulthood may assist in improving understanding of the impact of weight gain and obesity on cardiac dysfunction.
Abstract 13259: Electrophysiologic Mapping Identifies Stable Organized Tachyarrhythmias ("Rotors") in Both Atria during Spontaneous Atrial Fibrillation with Systolic Heart Failure
Authors: Nagarakanti Rangadham , Slee April , Saksena Sanjeev
Published: July 2021

Introduction:
Stable organized atrial tachyarrhythmias (ATs) /"rotors" that maintain AF have been identified in patients (pts) with paroxysmal atrial fibrillation (PAF) & persistent AF (PRAF) with no or minimal heart disease.

Hypothesis:
Biatrial ATs occur in AF pts with systolic heart failure (HF).

Methods:
We performed simultaneous contact catheter mapping of the RA & LA using 3 D non-contact mapping ) in 83 refractory AF pts during spontaneous AF episodes.Spontaneous atrial premature beats (APBs) & triggered ATs were analyzed. We also compared regional distribution of ATs & activation patterns in pts with & without HF.

Results:
24 HF pts, mean age of 62±9 years, 75% male with mean left ventricular ejection fraction (LVEF) 45.5±9% and mean left atrial (LA) size 4.35±0.8 cm were mapped. They had 42 APBs that triggered 26 distinct organized stable ATs/"rotors". Each pt had 1 to 4 RA or LA regions showing triggering APBs (mean 1.75/pt) initiating AT. APBs arose predominantly from the RA or LA septum (45%) & superior LA/PV (24%) regions (Fig 1a). A biatrial distribution of the stable ATs/"rotors" occcurred in HF pts (Fig 1b) with few focal ATs. Compared to pts without HF (n=59), HF pts (n=24) trended to have more PRAF (83% vs 66%, p=0.18). 78 organized stable ATs/"rotors" were compared for regional distribution in PRAF pts with HF (n=16) & without HF (n=32). Stable ATs with focal LA/PV origin were uncommon in both groups (7% vs. 15%). LA ATs/"rotors" were similar (26% vs. 17%; p=0.58) as were typical RA flutter and atypical RA ATs/"rotors" in both groups (Fig 1c).

Conclusions:
1. A majority of APBs initiating AF in HF pts originated from the septal and superior LA/PV regions. 2. While triggers are still frequently present with the LA/PV origin in HF pts, stable ATs/"rotors" had biatrial distribution & a lesser frequency of focal LA/PV ATs. 3. This spectrum of ATs/"rotors" was similar to PRAF pts without HF, potentially supporting similar ablative interventions in both pt groups.
Abstract 13284: A Novel Formulation of Vasoactive Intestinal Peptide Attenuates both Acute Hypoxic Pulmonary Vasoconstriction and the Development of Pulmonary Hypertension
Authors: Fraidenburg Dustin R , Tang Haiyang , Drennan Abigail , Yuan Jason X
Published: July 2021

Background:
Vasoactive intestinal peptide (VIP) is an endogenous hormone that is known to relax vascular smooth muscle and has established anti-proliferative and immunomodulatory effects in the pulmonary circulation making it an attractive therapeutic target in pulmonary arterial hypertension (PAH). In the current study, a polymer-based nanocarrier (protected graft copolymer - PGC) formulation of VIP, which has been shown to increase the potency and duration of action of VIP, is used to show both acute vasodilatory effects and chronic therapeutic effects in experimental animal models of pulmonary hypertension.

Methods:
The isolated perfused mouse lung preparation is utilized to test acute hypoxic pulmonary vasoconstriction (HPV) in mice. Two animal models of pulmonary hypertension are used in preventative experiments, chronic hypoxic pulmonary hypertension in mice and monocrotaline-induced pulmonary hypertension in rats. Right ventricular systolic pressure and Fulton’s index (weight ratio of RV/[LV+Septum]) are used for measures of pulmonary hemodynamics and RV hypertrophy respectively.

Results:
PGC-VIP decreased resting pulmonary artery pressure and attenuated acute HPV elicited by 1% inhaled oxygen tension in a dose dependent manner from 0.1 μM to 1.0 μM. After four weeks of chronic hypoxia, both RVSP measurements and Fulton’s index were significantly decreased in mice receiving 100 mg/kg intraperitoneal PGC-VIP every other day compared to vehicle control. Higher doses were associated with mortality in the treatment group. MCT-PH rats receiving subcutaneous PGC-VIP at a dose of 250 mg/kg failed to show improvement in RVSP or Fulton’s index compared to vehicle control.

Conclusion:
This novel formulation of VIP demonstrates both acute and chronic vasodilatory effects in the pulmonary circulation. Treatment with PGC-VIP can attenuate the development of hypoxic pulmonary hypertension, yet significant mortality is seen at higher doses. Subcutaneous injection failed to attenuate the development of experimental PH in rats, possibly due to an ineffective dose or route of administration. Further studies are underway to identify the ideal dosing strategy necessary to attenuate and potentially reverse experimental PH in animal models.
Abstract 13287: Dendritic Cells Play a Critical Role in the Initiation of Atherosclerosis
Authors: Jin Mengyao , Liu Peng
Published: July 2021

Introduction:
Dendritic cells (DCs) that are known as professional antigen-presenting cells have been found to pre-locate in non-inflammatory arterial wall and increasingly accumulate during atherosclerosis progression. Previous findings suggested that residential DCs in the intima are responsible for capturing modified lipids and forming foam cells during the initiation of atherosclerosis.

Hypothesis:
DC accumulation and enhanced DC-T cell interaction play a critical role in the initiation of atherosclerosis.

Methods:
We measured plaque formation, vascular DC accumulation and antigen-specific T cell proliferation mediated by isolated aortic cells in ApoE-/- mice, as well as DTR-CD11c/ApoE-/- or DTR-CD11b/ApoE-/- mice for conditional depletion of DCs or macrophages, respectively. A brief high-fat diet for 10 days was used as a model of initial atherosclerosis.

Results:
In addition to increased intimal DC accumulation and plaque formation in aortic roots, 10 days of HFD induced T cell infiltration in ApoE-/- mice, compared to those without HFD as the control. Isolated aortic cells from mice with 10-day HFD showed stronger capability in inducing antigen-specific T cell proliferation, compare to the control (HFD: 3.14±0.71%; no HFD: 1.56±0.36%; p=0.022). Single diphtheria toxin (DT) injection at day 1 yielded approximately 50% decrease in intimal DC accumulation, as well as 60% attenuation in plaque formation in DTR-CD11c/ApoE-/- mice after 10-day HFD. Capability of stimulating antigen-specific T cell proliferation was also impaired in aortic cells from DC-depleted mice (DT-treated: 1.62±0.30%; PBS-treated: 3.04±0.59%; p= 0.004), along with reduction in indirect conduction of T cell activation. In contrast, no significant changes were found in plaque formation and DC accumulation in DT-injected DTR-CD11b/ApoE-/- mice after 10 days of HFD, compared to control group. Furthermore, depletion of CD11b+ macrophages in either aortas or spleens didn’t alter capability of inducing antigen-specific T cell proliferation in DT-injected mice.

Conclusions:
These results suggested that vascular DCs rather than macrophages play a more important role in T cell activation and initiation of atherosclerosis.
Abstract 13311: Cardiac SIRT1 Deficiency Sensitizes Myocardium to Ischemia and Reperfusion Injury
Authors: Wang Jinli , Ma Yina , Sun Wanqing , Techiryan George , Wang Yanqing , Li Ji
Published: July 2021

Introduction:
A “longevity” gene, sirtuin 1 (SIRT1) is a conserved NAD
+
-dependent protein deacetylase that regulates life span extension. We have reported that SIRT1 is down-regulated in the aged heart which shows larger infarct size and deteriorative heart function during ischemia and reperfusion (I/R) compared with that of young heart.

Hypothesis:
Cardiac specific SIRT1 deficiency could increase the sensitivity of heart to ischemic insults caused by ischemia and reperfusion.

Methods:
Male SIRT1

flox/flox

mice and tamoxifen-inducible, cardiac-specific SIRT1 KO mice were subjected to I/R, which were induced by occluding the left anterior descending coronary (LAD) and subsequent releasing it. Langendorff-perfused heart model was used to monitor the heart function during I/R.

Results:
Adult cardiac-specific SIRT1 KO demonstrated significant cardiac hypertrophy, fibrosis and macrophage infiltration under normal physiological conditions versus the SIRT1

flox/flox

hearts by immunohistochemical staining (all p<0.05). The cardiac functions measured by the pressure-volume loop remained normal in SIRT1 KO mice as compared with SIRT1

flox/flox

mice under physiological conditions. The
ex vivo
heart perfusion results showed that the heart rate-left ventricular developed pressure product in SIRT1 KO hearts was decreased by 30% versus the SIRT1

flox/flox

hearts (p<0.05), and the infarct size of SIRT1 KO hearts was 1.7-fold larger than that of SIRT1

flox/flox

hearts (p<0.05). The immunoblotting data demonstrated that SIRT1 KO hearts had impaired responsive activation of AMP-activated protein kinase (AMPK) signaling during I/R versus the SIRT1

flox/flox

hearts. Furthermore, real-time qRT-PCR showed that cardiac SIRT1 KO resulted in up-regulation of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin-1 β and growth differentiation factor15 (GDF15), as well as a heart failure marker ANP (atrial natriuretic peptide) versus SIRT1

flox/flox

hearts during I/R.

Conclusions:
SIRT1 plays a vital role in regulation of myocardial infarction, heart function and inflammation induced by I/R in the heart. SIRT1 specific agonists may have therapeutic potential for treatment of ischemic heart disease.
Abstract 13322: In-hospital Death and Stroke Following Surgical Aortic Valve Replacement: a Nationwide Perspective
Authors: Agarwal Shikhar , Garg Aatish , Parashar Akhil , Tuzcu E M , Kapadia Samir R
Published: July 2021

Significant heterogeneity exists in the current literature around the actual incidence of stroke following aortic valve replacement (AVR) among high-risk patients. We aimed to evaluate the risk of stroke in patients undergoing surgical AVR from a large national database.

Methods:
We used the 2002-2011 Nationwide Inpatient Sample for this analysis. All patients undergoing isolated AVR or AVR with coronary artery bypass grafting (AVR+CABG) were identified using ICD codes. In-hospital death and any adverse neurological event were co-primary outcomes. Based on predicted death estimates, the study population was classified into low (<8%) and high (≤8%) surgical risk

Results:
Incidence of in-hospital death was 3.0% and 5.1% among patients undergoing isolated AVR and AVR+CABG respectively. The incidence of adverse neurological event was 2.0% and 2.9% among patients undergoing AVR and AVR+CABG respectively. We demonstrated a progressive increase in the risk of in-hospital death and adverse neurological events with increasing age (Fig 1). The incidence of in-hospital death was as high as 5.7% and 7.4% among patients aged ≤ 85 years undergoing isolated AVR and AVR+CABG respectively. Similarly, the incidence of any adverse neurologic event was 3.2% and 3.6% among patients aged ≤ 85 years undergoing isolated AVR and AVR+CABG respectively.

We demonstrated a significantly higher risk of adverse neurological events among the high-risk cohort as compared to the low-risk cohort. Among patients undergoing isolated AVR, the incidence of any adverse neurological event was 1.8% and 4.8% in the low-risk and the high-risk cohorts respectively. Similarly, among patients undergoing AVR+CABG, the incidence of any adverse neurological event was 2.7% and 5.4% in the low-risk and the high-risk cohorts respectively.

Conclusions:
The incidence of in-hospital death and adverse neurological events was significantly higher among patients with advanced age and elevated surgical risk.
Abstract 13380: The Effects of Pre-LVAD Obesity on Post-LVAD Re-Hospitalizations
Authors: Mohamedali Burhan , Yost Gardner , Bhat Geetha
Published: July 2021

Introduction:
Obesity is a major risk factor for cardiovascular outcomes and it is prevalent in patients (pts) with advanced heart failure requiring left ventricular assist devices (LVAD). The understanding of high body mass index (BMI) after LVAD implantation outcomes continues to evolve. In this study, we investigated the effects of obesity on post-LVAD re-hospitalization.

Methods:
In this retrospective study, 288 pts with both HeartMate II and HeartWare HVAD, implanted for bridge to transplantation (BTT) and destination therapy (DT), were enrolled. Pts were stratified based on a BMI ≥ 30. Baseline demographics were obtained. Post LVAD incidence of readmissions and major adverse effects were tabulated.

Results:
The cohort was comprised of 95 (33%) obese and 193 (67%) non-obese pts, (63 (25%) women vs 225 (75%) men), BTT 48 (20%), vs DT 240(80%). The mean BMI in the obese group was 35.2 Kg/M2 compared to 24.3 Kg/M2 (p=<0.001) in the control group. There were no differences in the index length of stay and time to readmissions between the two groups. However, obese pts had a higher mean total number of hospitalizations compared to non-obese pts (4.2 vs. 3.4, p=0.03). Other than the incidence of post-LVAD heart failure and hemolysis being higher in the obese group, there were no other statistically significant differences between the two groups (Table 1). There was a trend towards higher thrombosis in the obese cohort.

Conclusions:
Obese pts had a higher number of total hospitalizations compared to non-obese pts. There was no difference in time to readmission between the groups. These readmissions appear to be mainly driven by heart failure and hemolysis. Further investigation to determine causality is indicated.
Abstract 13381: The Relationship Between PAD Symptomatology and Ischemia: a Mixed Method Evaluation
Authors: Schorr Erica , Treat-Jacobson Diane , Savik Kay , Lindquist Ruth
Published: July 2021

Introduction:
Classic claudication is only reported by 7.5% to 33% of patients with PAD. Atypical symptom reporting is common, but it is unknown if ischemic changes are occurring since the relationship between atypical symptoms and tissue oxygen saturation (StO
2
)

has not previously been reported. The purpose of this study was to measure calf StO
2
during treadmill exercise and recovery, and evaluate its relationship with self-reported symptoms.

Methods:
Adults diagnosed with PAD and experiencing exercise-limiting ischemic symptoms were asked to: (a) use a numeric rating scale (0 to 5) to rate symptoms during exercise and recovery; (b) provide symptom descriptors; and (c) wear a near-infrared spectroscopy device to obtain calf StO
2
during exercise and recovery. Data analysis included descriptive statistics, exploration of individual and grouped graphical trajectories, and multilevel modeling.

Results:
During three successive bouts of treadmill exercise, 40 participants (80% Caucasian males, mean age 68±9 years) provided 22 symptom descriptors in eight lower extremity locations. Only 69.2% of exercise tests were stopped due to discomfort in the calf and classic descriptors were used only half the time to describe maximum calf discomfort (55.4%). The most rapid decline in StO
2
during exercise occurred between the start of exercise and the onset of symptoms. The nadir StO
2
was often reached prior to the report of maximum discomfort. In the exercise model, changes in StO
2
were related to total exercise time (
p
<0.001), baseline StO
2
(
p
<0.001), exercise ratings (
p
<0.001) and ABI (
p
<0.05). During recovery, StO
2
increased steadily for most participants between maximum discomfort and full symptom recovery; changes in StO
2
were related to recovery ratings (
p
<0.001) and ABI (
p
<0.03).

Conclusions:
Ischemic symptoms extended beyond classic locations and descriptors. Interestingly, participant perception of maximum discomfort frequently occurred after the nadir StO
2
. Similarly, most reports of full symptom recovery occurred prior to complete resolution of ischemia. Further research is necessary to explore mechanisms that could explain this objective-subjective mismatch to better understand the full range of ischemic symptoms associated with PAD.
Abstract 13387: Highly Sensitive Troponin I and Coronary Computed Tomography Angiography Assessment of Stenosis and High-risk Plaque Permit Rapid Classification of Acute Coronary Syndrome Risk in Chest Pain Patients: Results from the ROMICAT II Trial
Authors: Ferencik Maros , Liu Ting , Mayrhofer Thomas , Puchner Stefan B , Lu Michael T , Maurovich-Horvat Pal , Pope J. Hector , Truong Quynh A , Udelson James E , Peacock W. Frank , White Charles S , Woodard Pamela K , Fleg Jerome L , Nagurney John T , Januzzi James L , Hoffmann Udo
Published: July 2021

Introduction:
Highly sensitive troponin (hsTn) and coronary computed tomography angiography (CCTA) are promising diagnostic tools for triage of acute chest pain patients in the emergency department (ED). We determined whether a diagnostic strategy of initial hsTn I followed by early CCTA improves classification of ACS risk.

Methods:
We included ED patients with acute chest pain, negative electrocardiogram and conventional troponin who were enrolled in the ROMICAT II trial, randomized to CCTA and had hsTn I (hsVista, Siemens Diagnostics) measured at the time of presentation. The patients were categorized as having hsTn I < the limit of detection (<0.5 pg/mL), > 99th percentile (>49 pg/mL), or intermediate. Core lab readers assessed CCTA for the presence of ≥50% stenosis and high-risk plaque features (positive remodeling, low CT attenuation <30 HU, napkin ring sign, spotty calcium).

Results:
Overall, 160 patients met inclusion criteria (mean age 53±8 years, 40% women, ACS during index hospitalization 10.6%, n=19). The ACS rate was 0% (n=0/9) for patients with HsTn I < the limit of detection 8.6% (n=12/139) for patients with intermediate HsTn I and 53.8% (n=7/12) for patients with hsTnI > 99th percentile. No coronary plaque was present in 68 (42.5%), non-obstructive CAD in 70 (43.8%), ≥50% stenosis in 22 (13.8%), and high-risk plaque in 61 (38.1%) patients. The figure shows ACS risk stratification based on hsTn I followed by CCTA. The addition of CCTA increased the number of patients categorized as low risk from 9 to 96 and high risk from 12 to 25 and re-classified 63% of patients (n=100). The net gain in reclassification proportion was 0.47 (95%CI 0.16-0.78; p=0.003) for patients with ACS and 0.59 (95%CI 0.46-0.72; p <0.001) for patients without ACS, and net reclassification index was 1.06 (95%CI 0.73-1.40; p <0.001).

Conclusions:
A strategy of initial hsTn I at the time of ED presentation followed by early CCTA improved classification of ACS risk in patients with acute chest pain.
Abstract 13424: Dendritic Cell Surface Proteoglycan Binding-mediated Internalization of the Apob-100 Peptide P210 Increases Cd8+ T Cell Cytolytic Function
Authors: Zhao Xiaoning , Dimayuga Paul C , Zhou Jianchang , Yano Juliana , Lio Wai Man , Cercek Bojan , Shah Prediman K , Chyu Kuyang-Yuh
Published: July 2021

Background:
We have reported that immunization with the apoB-100 derived peptide p210 reduces atherosclerosis and aortic aneurysm formation/rupture, through modulation of CD8+ T cells. It remains unclear how an exogenous peptide like p210 enters dendritic cells for antigen presentation by MHC-I to CD8+ T cells. The p210 peptide sequence is located within the proteoglycan (PTG) binding site of apoB-100, which is a known alternative mechanism for cell internalization of LDL. Antigens internalized by cell surface PTG binding are cross-presented on the MHC-I molecule. We therefore tested the mechanism of p210 internalization by dendritic cell (DC) surface PTG binding and investigated the CD8+ T cell function in response to p210 antigen presentation.

Methods and Results:
Bone marrow derived DCs from apoE-/- mice were primed with fluorescently tagged p210 (FITC-p210) for 4 hours in vitro. There was significantly increased FITC internalization in DCs treated with FITC-p210 compared to FITC alone (24.3±2.7% vs. 6.6±0.8%; P<0.001; N=8 each) assessed by flow cytometry. Heparin significantly reduced internalization of FITC-p210 compared to no treatment (14.0±4.0%, N=4 vs. 29.9±6.7% N=9; P<0.01). Treatment of DCs with p-nitrophenyl-β-D-xylopyranoside, an inhibitor of cell surface heparan sulfate chain addition, significantly reduced FITC-p210 internalization (10.5±1.5% vs. 22.8±10.0% P<0.05, N=5 each) confirming the role of PTG binding. Adoptive transfer of p210-primed DCs into recipient apoE-/- mice significantly reduced CD8+CD25+FoxP3+ regulatory cells compared to unprimed DC controls (0.26±0.04% vs. 0.37±0.05%; N=5 each; P<0.01). Cytolytic activity against target DCs was significantly higher in CD8+ T cells from p210-primed DC recipient mice compared to controls (1.6±0.3% vs. 1.0±0.4% specific lysis; N=5 each; P<0.05). There were no significant differences in CD8+ T cell activation markers.

Conclusion:
Internalization of p210 is mediated in part by DC surface PTG binding, resulting in significantly reduced CD8+CD25+FoxP3+ regulatory T cells and increased cytolytic activity, suggesting unopposed CD8+ T cell effector function. Our results support the mechanism of p210 internalization by DC surface PTG increasing CD8+ T cell function.
Abstract 13447: Risk of Subsequent Cardiovascular Events Following a Respiratory Viral Infection
Authors: Knight Stacey , Miller Russell R , Bair Tami L , Horne Benjamin D , Lopansri Bert K , Anderson Jeffrey L , Muhlestein Joseph B , Carlquist John F
Published: July 2021

Background:
Studies have found that respiratory viral infections (RVI) can trigger acute cardiovascular (CV) events. These studies are based on self-reported symptoms and outdated antibody testing. The purpose of this study is to determine the risk of subsequent CV events in subjects with confirmed RVI based on molecular polymerase chain reaction or direct immunofluorescence assay.

Methods:
We studied Intermountain Healthcare patients from Jan 2007 to Dec 2013 tested for RVI with either positive (cases, n=9397) or negative (controls, n=27011) results. RVI included influenza A (seasonal or H1N1) or B, human metapneumovirus, parainfluenza, adenovirus, rhinovirus, respiratory syncytial virus, and coronavirus. A second control group (n=33210) seen for routine general medical examination were 1:5 matched using sex, age at visit (±5 yrs), time of presentation (±1 month), and history of CV disease to 6642 cases. All cohorts were followed for 90 days to determine subsequent CV events (including CV death, myocardial infarction, and stroke). Multivariable logistic regression was used to examine associations with combined outcome of any CV event.

Results:
A total of 130 (1.4%) positive RVI cases had a subsequent CV event compared to 617 (2.3%) of the negative RVI controls. About half of the events were CV death (49% & 48% for positive and negative RVI, respectively), followed by non-fatal strokes (34% & 34%) and non-fatal MI (18% & 19%). After adjusting for age, Intermountain mortality risk score, history of CV disease, presence of pneumonia, tobacco use, heart rate, respiratory rate, BMI, and patient type (ED, outpatient or inpatient), positive RVI cases were less likely compared to negative RVI controls to have a subsequent CV event (OR=0.63, 95% CI: 0.52, 0.77; p<0.0001). After similar adjustments, positive RVI cases had the same risk of a CV event as compared to matched general healthy controls (OR=1.30; 95% CI: 0.70, 2.41; p=0.41).

Conclusion:
Our study based on modern testing for RVI found positive RVI cases were at decreased risk of CV events within 90 days compared to negative RVI controls and similar risk as the general healthy controls. The decreased risk for the positive RVI may be due to the infection prompting changes in care that influence the 90 day CV outcomes.
Abstract 13452: Serum Apolipoprotein B-48 levels Are Significantly Correlated with Plaque Score of Carotid Arteries
Authors: Masuda Daisaku , Okubo Manabu , Hanada Hiroyuki , Matsui Masahiro , Hidaka Yoh , Sakata Yasushi , Yamashita Shizuya
Published: July 2021

Introduction:
Fasting hypertriglyceridemia is a “residual risk” factor for atherosclerotic cardiovascular diseases and related to postprandial hypertriglyceridemia (PHTG). Intestine-derived lipoproteins such as chylomicrons and chylomicron remnants (CM-Rs), which contain one apolipoprotein(apo) B-48 molecule per one particle, are accumulated in patients with PHTG. Basic studies showed that CM-R had an atherogenic nature and apoB-48 molecule was observed in atherosclerotic plaque twice as many as apoB-100 molecule histologically. We established a CLEIA for measuring serum apoB-48 concentrations and reported that high apoB-48 concentrations correlated with the prevalence of dyslipidemia, diabetes mellitus, metabolic syndrome, chronic kidney disease and coronary heart disease.

Hypothesis:
We investigated whether serum apoB-48 concentration correlated with subclinical carotid atherosclerosis.

Methods:
A total of 163 subjects who received ultrasonography of carotid arteries in Osaka University were enrolled. Blood pressure (BP) at the supine position and serum concentrations of apoB-48, plasma glucose, HbA1c, TC, TG HDL-C and LDL-C were measured. Intima-media thickness (IMT) of carotid arteries was measured and plaque score (PS) were calculated in all subjects.

Results:
All subjects were classified into 4 groups by apoB-48 concentration quartiles: 1st (0-2.2 μg/mL, n=41), 2nd (2.3-3.5 μg/mL, n=39), 3rd (3.6-6.7 μg/mL, n=42) and 4th quartile (≧6.8 μg/mL, n=41), respectively. TG concentrations, prevalence of high BMI (≧25), max-IMT and PS were increased as apoB-48 concentrations were increased. Max-IMT and PS had significant correlations with age, eGFR, systolic BP, log-TG and log-apoB-48 levels and a multiple regression analysis indicated that the age, eGFR, and log-apoB-48 concentrations (p<0.05) were a significant determinant of an increased max-IMT and PS. In subjects whose TG concentrations were <150 mg/dL, max-IMT and PS were significantly higher in subjects of the 4th quartile than those of other quartiles.

Conclusions:
High serum apoB-48 concentrations strongly correlated with increased max-IMT and PS, indicating that the accumulated CM-Rs might be one of the increased risk for subclinical carotid atherosclerosis.
Abstract 13479: Identification of microRNAs that Target mRNA Encoding Atrial Natriuretic Peptide
Authors: Wu Connie , Arora Pankaj , Goumans Marie Jose , Hu Dongjian , Domian Ibrahim , Jiramongkolchai Pawina , Vickers Kasey C , Hata Akiko , Buys Emmanuel , Newton-Cheh Christopher , Wang Thomas J , Bloch Donald B , Bloch Kenneth D
Published: July 2021

Introduction:
The minor allele of a common variant (rs5068) in the 3’UTR of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with increased plasma ANP levels, lower blood pressure, and reduced risk of hypertension. A microRNA (miR-425) expressed in the human heart binds to a sequence spanning rs5068 for the major but not the minor allele leading to reduced ANP biosynthesis. mRNAs typically contain multiple miR-binding sites, and binding of different miRs often coordinately regulates the function of any given mRNA.

Hypothesis:
We hypothesize that miRs, in addition to miR-425, target NPPA mRNA and that interference with miR-based silencing of NPPA mRNA using miR antagonists (antimiRs) could be used to increase ANP biosynthesis.

Methods:
Luciferase reporter assays were used to screen 10 miRs that are predicted in silico to interact with the NPPA 3’UTR. The expression levels of validated miRs in human atria were determined. Human cardiomyocyte progenitor cells (hCMPCs) or human embryonic stem cell (HUES 9)-derived cardiomyocytes (hESC-CMs) were transfected with antimiRs targeting the validated miRs, and the levels of NPPA mRNA were measured.

Results:
Of the 10 miRs predicted in silico to interact with the NPPA 3’UTR, we identified 3 miRs (miRs-103, -105, and -107) that reduced luciferase activity in cells containing a luciferase-NPPA 3’UTR construct (miR-103, p=0.034; miR-105, p=0.0009; and miR-107, p=0.021), but the miRs had no effect on luciferase activity in cells containing a luciferase construct in which the predicted miR-binding site in the NPPA 3’UTR was mutated. Using qRT-PCR, the three miRs were detected in human atria. Transfection of an antimiR directed against miR-103, miR-105, or miR-107 increased NPPA mRNA levels in hCMPCs (antimiR-103, p=0.024; antimiR-105, p=0.039; and antimiR-107, p=0.036). Similar results were observed in hESC-CMs.

Conclusions:
Our studies suggest that miRs-103, -105, and -107 regulate NPPA expression in human cardiomyocytes. AntimiRs directed against these miRs increased NPPA mRNA in human cardiomyocytes. AntimiR-based methods to increase ANP levels may represent a novel approach to the treatment of hypertension.
Abstract 135: In Vitro Activity of Antimicrobial Drugs Against Clinically Relevant Bacterial Pathogens Under Mild Hypothermic Conditions
Authors: Wallmüller Christian , Birger Herold , Sterz Fritz , Makristathis Athanasios , Ramharter Michael
Published: July 2021

Aim:
Infections are a common problem in cardiac arrest survivors. Antimicrobial drugs are often administered in routine care during treatment of patients with mild therapeutic hypothermia. Since there is to date no evidence for the pharmacodynamics of antimicrobial drugs under mild therapeutic hypothermia conditions, we investigated the in vitro activity of common antimicrobials against clinically relevant bacterial pathogens.

Methods:
Activities of antimicrobial drugs against clinically relevant bacterial pathogens were assessed in vitro by disc diffusion and broth microdilution assays at normothermic (37°C) and hypothermic (32°C) conditions.

Results:
73 bacterial isolates were tested in disc diffusion and 15 in broth microdilution assays. Mean differences in zone diameters and minimal inhibitory concentration ratios were 0.6 mm (95% confidence interval: 0.3-0.9 mm) and 0.98; (95% confidence interval: 0.95 - 1.02), respectively, meeting predefined criteria for equivalence of in vitro antimicrobial activity.

Conclusion:
The presented data provide reassuring evidence that the intrinsic activity of antimicrobials seems to be unaltered in mild therapeutic hypothermia. However, further studies evaluating the pharmacokinetics including target site concentrations of the respective drugs and in vivo pharmacodynamics are necessary to complement our understanding of the appropriate use of antimicrobials in mild therapeutic hypothermia
Abstract 13514: Apoptogenic Protein is a Novel Phenotypic Marker of the Contractile Vascular Smooth Muscle Cells
Authors: Yasuda Osamu , Soejima Hirofumi , Miyata Keishi , Yasuda Hisayo , Rakugi Hiromi , Oike Yuichi , Mitsuyama Shoukei-Kim , Ogawa Hisao
Published: July 2021

Introduction:
Apoptogenic protein (Apop) is a mitochondrial protein originally identified in the atherosclerotic cells cultured from thoracic aortas of ApoE-deficient mice. Functional analysis revealed that the expression of Apop using an expression vector induces apoptotic death of smooth muscle cells (SMC) in culture through the release of cytochrome c from mitochondria, followed by the activation of the caspase cascade. Here, we show that Apop is expressed in the contractile SMC, and can be a novel phenotypic marker of the SMC.

Methods and Results:
Human aortic smooth muscle cells (HASMC) and human coronary atery smooth muscle cells (HCASMC) were cultured in HuMedia-SB2 supplanted with hEGF, hFGF, insulin and 5% FBS. Differentiated HASMC were cultured on laminin-coated dishes in HuMedia-SD2 supplemented with heparin and 1% FBS. Gene expression level was analyzed by real time PCR. SM2 and SMemb were used as differentiation marker and synthetic SMC marker, respectively. The differentiated SMC showed a higher level of expression of SM2, and the ratio of SM2/SMemb was higher compared to the synthetic SMC. Apop gene expression was higher in differentiated HASMC compared to the synthetic phase cells. Similarly, HCASMC showed a higher level of Apop and SM2 expression and SM2/SMemb expression ratio in differentiated cells compared to the cells in synthetic phase. These results indicate that Apop is expressed in differentiated SMC at a higher level than synthetic SMC. CArG box, which is often present in phenotypic marker genes expressed in differentiated SMC, exists in the intron1 region of Apop gene. Serum response factor (SRF) binds to CArG box, and regulates the expression of the genes expressed in differentiated SMC. The silencing of SRF using siRNA reduced the expression of Apop in differentiaed HASMC, indicating that SRF regulates the expression of Apop in differentiated cells. Moreover, immunostaining using human atherosclerotic coronary artery specimens revealed that Apop gene is co-expressed with the differentiation marker, SM2 in the coronary artery SMC.

Conclusion:
These results indicate that Apop is a novel phenotypic marker of the differentiated SMC, and may be a novel therapeutic target for the prevention of the development of atherosclerosis.
Abstract 13522: Vascular Healing in Drug-Eluting Stents: Differential Response of Limus-Eluting Stents in a Preclinical Model of Stent Implantation
Authors: Tajiri Kazuko , Sato Akira , Hoshi Tomoya , Kimura Taizo , Seo Yoshihiro , Sakai Satoshi , Hiroe Michiaki , Aonuma Kazutaka , Watanabe Shigeyuki
Published: July 2021

Introduction:
Recently, several clinical studies suggest that second-generation cobalt-chromium everolimus-eluting stents (CoCr-EES) lead to more favorable vascular healing than first-generation sirolimus-eluting stents (SES). However, it remains unclear the difference of vascular responses between CoCr-EES and SES.

Methods:
A total of 42 stents (14 bare-metal stents [BMS], 13 CoCr-EES, and 15 SES) were deployed in the iliac arteries of 31 Japanese White rabbits. Qquantitative real-time reverse-transcription polymerase chain reaction (QRT-PCR) analyses of the neointima were performed on days 30 and 90 after the stent implantation.

Results:
On day 30, the gene expression of the angiogenic growth factors (hepatocyte and basic fibroblast growth factors) and proteoglycans (decorin, biglycan and lumican) were more upregulated in the BMS than in the SES. However, at 90 days after stenting, the gene expression of proteoglycans and collagen was more upregulated in the SES than in the CoCr-EES and BMS.

Conclusions:
In contrast to CoCr-EES and BMS, SES strongly suppresses the vascular healing-related gene expression in the early phase, and then upregulates it in the late phase. These differences may lead to different clinical outcomes in humans.
Abstract 13539: Physiological Basis of Discordance Between Coronary Flow Reserve and Hyperemic Microvascular Resistance to Evaluate Coronary Microvascular Dysfunction in Patients Without Atherosclerotic Obstruction
Authors: Yamanaga Kenshi , Tsujita Kenichi , Komura Naohiro , Sakamoto Kenji , Ishii Masanobu , Tabata Noriaki , Miyazaki Takashi , Akasaka Tomonori , Arima Yuichiro , Ono Takamichi , Kojima Sunao , Tayama Shinji , Kaikita Koichi , Hokimoto Seiji , Nakamura Sunao , Ogawa Hisao
Published: July 2021

Introduction:
Although coronary flow reserve (CFR) has been the only physiological way to evaluate the coronary microvascular (MV) function until recently, hyperemic MV resistance (hMR) have been developed as a newer modality measuring directly coronary MV function. Discordance between CFR and hMR may reflect various coronary hemodynamic situations.

Hypothesis:
Simultaneous measurement of CFR/hMR in pts without coronary obstruction could provide us deeper appreciation of hemodynamic functional alterations in coronary microvasculature.

Methods:
In 44 pts without coronary stenosis (diameter stenosis >50%), CFR and hMR were measured utilizing a dual sensor (Doppler velocity and pressure)-equipped guidewire. To evaluate coronary MV hemodynamics, pts were categorized into four CFR/hMR quadrants using a cutoff values of CFR≥2.0 and hMR<1.7 (median value of all study subjects) (Figure).

Results:
Discordance results between CFR/hMR was present in 39% of patients (17 of 44), with CFR≥2.0 and hMR≥1.7 in 30% (13 of 44) and CFR<2.0 and hMR<1.7 in 9% (4 of 44). There were significantly negative correlation between hMR and
hyperemic
average peak velocity (APV) (r=-0.73, p<0.0001), CFR and
baseline
APV (r=-0.66, p<0.001) despite no correlation between CFR and hyperemic APV (r=0.25, p=0.1). Baseline APV and hyperemic APV were significantly different among these groups (baseline APV; group 2 vs. group 3, 12.0±5.7 vs. 30.5±7.2, p=0.02, group 2 vs. group 4, 12.0±5.7 vs. 21.3±8.5, p=0.002, hyperemic APV; group 1 vs. group 4; 51.2±10.4 vs. 28.7±10.2, p<0.0001, group 1 vs. group 2, 51.2±10.4 vs. 32.5±13.6, p=0.03). Four CFR/hMR quadrants thus represent 4 different types of coronary blood flow-perfusion pressure relationship (Figure).

Conclusions:
In pts without coronary obstruction, CFR was related to coronary autoregulation state and hMR to hyperemic state. Simultaneous CFR/hMR measurement might provide new physiological insight about coronary MV hemodynamics.
Abstract 13544: Differences in the Population of Muscular Dystrophy Patients With Respect to Ventricular Tachycardia, Heart Failure and Use of Implantable Cardioverters Defibrillators
Authors: Punnoose Ann R , Kaltman Jonathan , Spurney Christopher
Published: July 2021

Introduction:
As the treatment of the respiratory and skeletal muscle complications associated with muscular dystrophy (MD) has improved, males with MD are living longer and are more likely to develop cardiac disease. The impact of sudden cardiac death related to ventricular arrhythmias and heart failure and the indications for ICD implantation are not well established.

Hypothesis:
We evaluated the hypothesis that VT is a significant contributor to mortality in hospitalized patients with MD and this is improved with ICD implantation.

Methods:
We searched the Pediatric Health Information System (PHIS) database for males with discharge diagnosis codes of MD and different combinations of heart failure (HF), ventricular arrhythmias (VT) and ICD placement between 2003 and 2013.

Results:
There were significant differences in the mean length of stay and mean age between MD patients with HF and/or VT versus all hospitalized male MD patients (p<0.05). Out of a total of 76 deaths in MD patients, 32% (n=24) were related to HF. Of those, 30% (n=7) also had a diagnosis of VT. Isolated VT without HF was only 1% (n=42) of admissions and the cause of death in 2 patients. However, ICD’s were implanted in 12% (n=5) of MD/VT patients compared to 5% (n=5) of MD/HF/VT patients. No deaths were seen in patients with ICD’s. Only 1 ICD was placed prior to 2009.

Conclusions:
VT was a frequent cause of death in hospitalized male patients with MD and HF, however isolated VT without HF was not. No deaths were found in the small number of patients with ICD’s. Further prospective studies are needed to validate the importance of ICD use in MD patients
Abstract 13566: Pitavastatin Regulates mTOR Complex 1 Signaling Through Inhibition of Rheb in T Cells
Authors: Tajiri Kazuko , Shimojo Nobutake , Sakai Satoshi , Machino-Ohtsuka Tomoko , Imanaka-Yoshida Kyoko , Hiroe Michiaki , Kimura Taizo , Sato Akira , Aonuma Kazutaka
Published: July 2021

Accumulated evidence has shown that statins have anti-inflammatory and immunomodulatory effects; however, the mechanism has not been fully elucidated. Here we report that pitavastatin inhibited mTOR complex 1 (mTORC1) activity by inhibiting the farnesylation of the small GTPase Rheb in murine T cells. As a result of The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibition, statins regulate the biosynthesis of cholesterol and isoprenoid farnesylpyrophosphate (farnesyl-PP) that mediates the farnesylation and membrane association of Rheb. Pitavastatin-treated T cells failed to differentiate into T helper (Th)1 and Th17 cells, and this failure was rescued by adding farnesyl-PP. Pitavastatin and a farnesyltransferase inhibitor affected the transcription of T-bet and RORγT which have critical roles in the development of Th1 and Th17 cells respectively. In a mouse model of experimental autoimmune myocarditis, a CD4+ T cell-mediated disease, pitavastatin treatment ameliorated the pathophysiological severity of myocarditis associated with reduced Th1 and Th17 responses and mTORC1 signaling. We conclude that statins reduce the inflammatory functions and pathogenic activity of T cells through inhibition of mTORC1 signaling, and that this pathway may be a potential therapeutic target for Th1- and Th17-related diseases.
Abstract 13583: Left Ventricular Remodeling After Type a Aortic Dissection Surgery: a Comparison Between Different Surgical Techniques
Authors: Regeer Madelien V , Versteegh Michel I , Klautz Robert J , Schalij Martin J , Bax Jeroen J , Ajmone Marsan Nina , Delgado Victoria
Published: July 2021

Introduction:
Type A aortic dissection (AADA) requires emergency surgery with different options including valve-sparing aortic root replacement (VSRR), supracoronary ascending aorta replacement (SCR) and aortic valve and root replacement (AVRR). Recurrence of aortic regurgitation (AR) and extent of left ventricular (LV) remodeling in patients with AADA was compared between these surgical techniques.

Methods:
A total of 120 patients (59 ± 12 years, 63% male) with AADA who underwent VSRR (n=22), SCR (n=62) or AVRR (n=36) were included in the present retrospective evaluation. AR grade and LV volumes and ejection fraction were assessed postoperatively (before hospital discharge) and during follow-up. Estimated marginal means ± standard error of the mean were obtained using linear mixed models.

Results:
Patients who underwent VSRR were significantly younger (49 ± 6 years) and more often male (84%). There were more patients in SCR group with hypertension compared to VSRR and AVRR (67% vs. 27% and 47%; p=0.006). The EuroSCORE II was highest in patients who underwent AVRR. After a median follow up of 53 months, the mean AR grade was 1.2 ± 0.2 in VSRR vs. 1.8 ± 0.2 in SCR vs. 0.2 ± 0.1 in AVRR (p<0.001). LV end-diastolic and end-systolic volumes remained stable in VSRR, while a significant increase was observed in SCR (table). The ejection fraction remained stable in all groups, however, a trend towards improvement was observed in VSRR (p=0.055).

Conclusions:
Patients with AADA who underwent SCR experienced more AR compared to AVRR resulting in larger LV volumes during follow up. Despite higher AR grade during follow up in patients who underwent VSRR compared to AVRR; there was no deterioration in LV volumes and function after VSRR.
Abstract 13596: The Prognostic Impact of Spontaneous Coronary Artery Dissection in Younger Female Patients with Acute Myocardial Infarction; Report from Angina Pectoris-Myocardial Infarction Multicenter Investigations in Japan
Authors: Nakashima Takahiro , Yasuda Satoshi , Noguchi Teruo , Haruta Seiichi , Yamamoto Yusuke , Oshima Shuichi , Nakao Koichi , Seki Atsushi , Uchida Tatsuro , Omura Nobuhiro , Yamaguchi Junichi , Taniguchi Yasuyo , Kikuchi Migaku , Tsuchihashi Kazufumi , Kimura Kazuo , Ogawa Hisao , Miyazaki Shunichi
Published: July 2021

Introduction:
Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute myocardial infarction (AMI). It is postulated that the patients with SCAD have good clinical prognosis because they have few coronary risk factors (CRF). However, a recent report studying the US patients with SCAD aged 18~78 years suggested that the rate of recurrence was higher than we expected. In the present study, we therefore have focused on prognostic impact of SCAD on younger female populations.

Methods:
A total of 16,233 AMI patients registered by 10 institutes from 1991 to 2012 were retrospectively studied. The definition of SCAD was based on the presence of medial dissection or intramural hematoma that was recognized by angiography before any catheter intervention.

Results:
There were 27 patients diagnosed as SCAD (male/female 1/26, age 45±9 [SD] years). The overall prevalence of SCAD was 0.17% of AMI patients. SCAD developed after physical or emotional stress in 11 patients (40.7%). The left anterior descending artery was involved in 17 patients (62.9%), among whom 4 patients had multi-vessel SCAD (14.8%). Recurrences of SCAD were shown in 9 patients (33.3%). In 4 of 9, recurrence was seen in previously unaffected coronary arteries. In young population of AMI patients (age <50), we compared clinical parameters of SCAD (n=21) with those of Non-SCAD groups (atherosclerotic, n=35). In SCAD group, the number of CRF was significantly lower than in Non-SCAD groups (SCAD, 1.0+/-0.8 vs Non-SCAD, 2.2+/-1.1, P<0.0001). In Kaplan-Meier analysis, younger female AMI patients with SCAD showed significantly higher rate of cardiac event (death, AMI and heart failure) in comparison with those without SCAD (SCAD, 11/21 vs Non-SCAD, 4/34; P=0.0002) during a median follow-up of 1557 (1-8172) days.

Conclusions:
The present multicenter study demonstrated that younger female AMI patients with SCAD, characterized as minimum accumulation of CRF, seem to be prone to cardiac events.