bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15100: Influence of Human Immunodeficiency Virus Infection on the Management and Outcomes of Acute Myocardial Infarction With Cardiogenic Shock
Authors: Jain Vaibhav , Subramaniam Anna , Vallabhajosyula Saraschandra
Published: May 2021

Introduction:
Cardiovascular disease risks are significantly higher in patients with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). There are limited data on the management and outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in patients with HIV/AIDS>

Methods:
A retrospective cohort of AMI-CS during 2000-2017 from the National Inpatient Sample was evaluated for concomitant HIV and AIDS. Outcomes of interest included in-hospital mortality, use of cardiac procedures, hospital length of stay, hospitalization costs, use of do-not-resuscitate (DNR) status, and palliative care use. A sub-group analysis was performed for those with and without AIDS within the HIV cohort.

Results:
A total 557,974 AMI-CS admissions were included, with HIV and AIDS in 1,321 (0.2%) and 985 (0.2%), respectively. The HIV cohort was younger (54.1 vs. 69.0 years), more often male, of non-white race, uninsured, from a lower socioeconomic status, and with higher comorbidity (all
p
<0.001). The HIV cohort had comparable multiorgan failure (37.8% vs. 39.0%) and cardiac arrest (28.7% vs. 27.4%) (
p
>0.05). The cohorts with and without HIV had comparable rates of coronary angiography (70.2% vs. 69.0%;
p
=0.37), but less frequent early coronary angiography (hospital day zero) (39.1% vs. 42.5%;
p
<0.001). The cohort with HIV had comparable in-hospital mortality compared to those without (26.9% vs. 37.4%; adjusted odds ratio 1.04 [95% confidence interval 0.90-1.21];
p
=0.61). The cohort with HIV had longer duration of hospitalization (10.8±10.1 vs 9.9±11.4 days), higher hospitalization costs (158±155 vs. 143±182 x1000 USD) and was discharged home (48.6% vs 41.8%) more often as compared to those without HIV (all p <0.005). In the HIV cohort, AIDS was associated with higher in-hospital mortality (28.8% vs. 21.1%; adjusted odds ratio 4.12 [95% confidence interval 1.89-9.00];
p
<0.001). Secondary outcomes were relatively comparable between those with and without AIDS.

Conclusions:
The cohort with HIV had longer hospital stay and higher hospitalization costs; however these were comparable between those with and without AIDS.
Abstract 15110: Atherospectrum Identified Novel Foaming Programs and Monocyte Predictor Genes for Residual Cardiovascular Risk
Authors: Li Chuan , Qu Lili , Liu Yongmei , Vella Anthony , Murphy Patrick , Rodriguez Annabelle , Zhou Beiyan
Published: May 2021

Despite lipid-control therapies, substantial risk of major cardiovascular event remains. New approaches are needed to define and mitigate residual risks in a patient specific manner. Monocytes, critical player in CVD, transcriptionally respond to metabolic and inflammatory cues in the circulation and contribute to atherogenesis. However, previous studies of monocytes only found moderate associations to CVD events and with limited predictive power. Here we developed a novel computational approach, named AtheroSpectrum, which effectively depicted heterogeneity of foam cells. Our analysis revealed two distinct programs of plaque macrophages: the homeostatic-foaming and the inflammatory pathogenic-foaming, which we found to be associated with severity of atherosclerosis in multiple studies. Next, we screened the genes enriched in the pathogenic-foaming program using our original self-optimizing progressive machine learning algorithms, and identified 29 signature genes (including SOD2, SLC39A8, etc) that were strongly associated with cardiovascular events in 936 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) whose LDL levels were below 129 mg/dl, and were further validated in additional human data (gtexportal.org, GSE43292), while traditional risk factors (BMI, lipid profiles, smoking, etc) showed no significant association. We further developed a novel residual CVD risk score system that incorporated the newly identified 29 pathogenic foaming signature genes, gender, age, and the inflammation index (MPI) of AtheroSpectrum. Our scores presented strong prediction power for depicting residual cardiovascular risks (AUC 0.805) compared with the JAMA 2001 (AUC 0.620) and Framingham risk scores (AUC 0.650).In summary, we successfully identified pathogenic foam cell subpopulations with active inflammatory and lipid metabolic programs. Characterization of these subsets revealed novel feature-based key genes directly contributing to CVD residual risks and endowed creation of a CVD prediction score with high accuracy. Further optimizing this score system will facilitate both mechanistic investigations and development of therapeutic and prognosis strategies of CVD residual risk.
Abstract 15137: β2-adrenergic Signaling Promotes IL-6 Production From Cardiac Fibroblasts Through CREB/Arid5a Pathway and Induces Cardiac Hypertrophy via Paracrine System
Authors: Tanaka Shota , Maeda Makiko , Obana Masanori , Fujio Yasushi
Published: May 2021

Background:
β-adrenergic receptor (βAR) is involved in cardiac inflammation and hypertrophy. It has been revealed that βAR stimulation induces cardiac hypertrophy not only directly but also indirectly, for example, via cardiac fibroblasts (CFs). Interestingly, βAR signaling promotes the production of interleukin (IL)-6 from CFs. However, it has not been clarified the relationship between IL-6 released from CFs and cardiac hypertrophy after βAR stimulation.

Objective:
To elucidate the mechanisms by which βAR signaling promotes the production of IL-6 in CFs and the effects of CFs-secreted IL-6 on cardiac hypertrophy.

Methods:
CFs were isolated from adult mice. The expression of mRNA was measured by quantitative RT-PCR and the secretion of IL-6 into the medium was quantified by ELISA. Cardiac hypertrophy was assessed by echocardiography, cross-sectional area or cell surface area of cardiomyocytes.

Results:
RT-PCR revealed that β2AR and β3AR, but not β1AR, were mainly expressed in CFs. Salbutamol (SAL), a selective β2AR agonist, increased IL-6 mRNA by 20-fold, whereas CL-316243, a selective β3AR agonist, did only negligibly. Moreover, SAL, not CL-31243, upregulated the mRNA expression of AT-rich interaction domain 5A (Arid5a), an IL-6 mRNA stabilizing factor, by 4 times. CFs from
Arid5a
-null mice exhibited reduced expression of IL-6 mRNA and protein, compared with wild-type (WT) CFs, with or without SAL. SAL phosphorylated CREB, suggesting that SAL activated CREB pathway. The compound 666-15, a CREB inhibitor, suppressed SAL-induced IL-6 and Arid5a upregulation. Importantly, WT and
IL-6
-null mice were continuously treated with isoproterenol (ISO), a non-selective βAR agonist, for 2 weeks. Cardiac dilatation and cardiomyocyte enlargement were induced by chronic ISO treatment in WT mice, but to lesser extent in
IL-6
-null mice. Finally, conditioned media from WT CFs treated with ISO enlarged cultured neonatal rat cardiomyocytes by 10%, while not those from
IL-6
-null CFs.

Conclusion:
β2AR signaling induced IL-6 via CREB/Arid5a axis in CFs. Moreover, CFs-secreted IL-6 contributed to the enlargement of cardiomyocytes through paracrine signaling. β2AR signaling in CFs could be a therapeutic target against cardiac hypertrophy.
Abstract 15143: Painless Epicardial Implantable Cardioverter Defibrillator Net System With Electric Conductive Fibers
Authors: Akita Toshiaki
Published: May 2021

Introduction:
Current Implantable cardioverter-defibrillator (ICD) needs high CD shock (35J), which is not tolerable under consciousness. Our multi-physics computer-simulation demonstrated extra-low energy defibrillation (0.36J)can be possible if sheet electrodes are arranged upper (base) and lower (apex) side of the heart.

Hypothesis:
We developed the epicardial ICD net electrodes system (Ep-ICD) made of upper and lower parts with fine conductive fibers. The objective of this study was to test whether Ep-ICD can stop ventricular fibrillation with painless level (<0.7J) in large animal model.

Methods:
Ep-ICD was constructed by fine tungsten fibers using computer-assisted knitting machine (Shimaseiki Co., Japan). Middle part was knitted by polyester fibers. Upper and lower electrode nets were connected to RV and SVC coils of DF-1 lead (Medtronic), respectively. Five beagle dogs were used for this experiment. The Ep-ICD net was directly attached to the heart, and electrodes were connected to commercially available ICD system. DC discharges were controlled by telemetry controller. Vf was induced by attaching 9V battery onto the heart surface. Ten seconds after Vf induction, DC was delievered from minimal energy 0.4J (Medtronic Viva XT) or 0.1J (Boston Scientific Perciva). DC energy was gradually increased until defibrillation was accomplished. After 3 minutes of recovery, the ventricular fibrillation induction and defibrillation tests were repeated. Defibrillation threshold (DFT) was defined as 75% of success of defibrillation. To compare current ICD system, commercial ICD lead was inserted in one dog through internal juglar vein, and defibrillation test was conducted.

Results:
Defibrillation was accomplished by 0.1J~1J, All hearts recovered instantaneously to sinus rhythm. DFT were 0.6J for 4 dogs and 0.8J for one dog. Current ICD system needed 30J for defibrillation.

Conclusions:
Our preliminary results shows that the Ep-ICD accomplished defibrillation with painless level of DC energy (<0.7J). Extra-low energy DC can avoid electroporation which causes conduction abnormality or malignant arrhythmia. Ep-ICD can apply DC shock before losing consciousness, which has a huge merit for QOL.
Abstract 15151: The Prevalence of Covid-19 on the Door to Balloon Time in Patients With St-elevation Myocardial Infarction
Authors: matsubara yuki , Yamada Takeshi , Washimi Soichiro , Takahashi Akihiko , Hata Tetsuya , Nakajima Shunsuke , Taniguchi Norimasa , Hashimoto Sho
Published: May 2021

Background:
Patients with ST-elevation myocardial infarction (STEMI) should undergo primary PCI (percutaneous coronary intervention) as a standard of care. However, with the increase in the prevalence of COVID-19, all patients with suspected STEMI should be treated as possible COVID-19 cases. Therefore, more time may be needed to establish an acute MI diagnosis and to perform a COVID-19 status assessment. There has been a paucity of data regarding its influence on the primary PCI procedure.

Objective:
We sought to evaluate the impact of the prevalence of COVID-19 on the door-to-balloon time and clinical outcome in patient with STEMI.

Method:
Between January 2019 and May 2020, 157 patients with STEMI underwent primary PCI in 3 Japanese PCI centers. Mean age of patients was 70.4±12.9 years, and 71.6% were male. Right distal radial artery access was used in 110 patients (94.8%). We divided these patients into two groups: a group before the COVID -19 outbreak and another group during the pandemic, and were retrospectively analyzed. The following patients’ baseline characteristics were obtained: door-to-balloon time, duration in the emergency department, finding of CT scan if conducted, peak CK, 30-day mortality rate.

Results:
We evaluated patients with STEMI who underwent PCI between January 2019 and January 2020 (before the pandemic) and between February 2020 and May 2020 (during the pandemic). The number of patients was 119 before pandemic and 37 during pandemic. Mean door-to-balloon time was 35.8 ± 24.5 min before the pandemic and 41.2 ± 20.8 min after the outbreak (p<0.05). Induration at the emergency department was 22.6 ± 18.6 min before the pandemic and 21.3 ± 13.3 min after the outbreak (p=0.329). CT evaluation was performed before PCI was conducted in 41 patients (34.5%) and 14 patients (37.8%) (p=0.699). The peak CPK was 1956.2 ±2141.9 U/L and 2801.1 ± 2982.5 U/L (P=0.006). There was no significant difference in a 30-day mortality rate (5% vs 0%; P=0.699). Of the 37 patients after the outbreak, no patient underwent PCR examination for COVID-19 virus.

Conclusion:
The COVID-19 pandemic changed the diagnostic procedure in the emergency department and affected door-to-balloon time in patients with STEMI.
Abstract 15156: Comparison of Left Atrial D
-
dimer Level in Patients With Atrial Fibrillation Administering Dabigatran, Apixaban and Edoxaban
Authors: Watanabe Tetsuya , Tachibana Kouichi , Shinoda Yukinori , Minamisaka Tomoko , Fukuoka Hidetada , Inui Hirooki , Ueno Keisuke , Hoshida Shiro
Published: May 2021

Introduction:
Atrial fibrillation causes cerebral infarction and systemic embolism. Increased D-dimer level indicates the hyperactivation of secondary fibrinolysis, showing thrombosis tendency in the vessel.

Hypothesis:
To clarify the effects of anticoagulation therapy, we planned to compare the D-dimer levels of peripheral and left atrial (LA) blood in patients scheduled for atrial fibrillation ablation during administration of dabigatran (D), apixaban (A) and edoxaban (E).

Methods and Results:
We analyzed 141 patients with non-valvular atrial fibrillation (D, n=30; A, n= 47; E, n=64; median age: 68[38-84] years, male: 60%) after exclusion of patients on dialysis. Peripheral venous blood was collected immediately before ablation and LA blood was collected immediately after the Brockenbrough method. We examined laboratory and echocardiographic parameters such as D-dimer and protein C levels, and LA diameter. Anticoagulation therapy was discontinued on the day of ablation. There were no significant differences in ejection fraction, LA diameter and peripheral C-reactive protein levels among the three groups treated with D, A and E. After adjusting for baseline characteristics, D-dimer level in the left atrium treated with E was significantly higher among the three groups (D, 0.550±0.078 vs. A, 0.603±0.052 vs. E, 0.774±0.046), although there were no significant differences in peripheral D-dimer levels (Table). Protein C levels of peripheral blood in group E were significantly suppressed among the three groups (D, 130.17±4.84 vs. A, 102.13±3.59 vs. E, 91.92±2.11, p<0.001).

Conclusions:
In the edoxaban group, the D-dimer level in the left atrium was higher than that in the apixaban group, suggesting that the anticoagulatory effect of left atrium is better in apixaban as compared to edoxaban in patient with non-valvular atrial fibrillation.
Abstract 15165: Routine Ambulatory Heart Rhythm Monitoring in Patients With Transthyretin Cardiac Amyloidosis
Authors: Dale Zack , Rashdan Lana , Chandrashekar Pranav , Elman Miriam , Heitner Stephen B , Nazer Babak , Masri Ahmad
Published: May 2021

Introduction:
Atrial fibrillation and flutter (AF/AFL) are common with transthyretin cardiac amyloidosis (ATTR-CM). These patients have higher risk for thromboembolism. Detection of AF/AFL may thus be especially important, but the role of routine ambulatory monitoring in asymptomatic patients is unclear.

Methods:
A single center observational study of patients seen at our Amyloidosis Center with wild-type or hereditary ATTR-CM diagnosed between 2005-2019. Records were reviewed to see if AF/AFL was present at baseline. In those without known AF/AFL, ambulatory monitor (duration 2-30 days) was done every 6 months when feasible as part of our routine practice. Patients with cardiovascular implantable electronic devices (CIED) instead had routine device interrogations.

Results:
Ninety-four patients with ATTR-CM (mean age 71.4±11.4 years, 88.3% male) had mean follow-up 2.2±1.9 years (200 patient-years). AF/AFL was seen in 62 patients (66.0%): 35 (56.5%) by symptoms, 18 (29.0%) incidentally by monitor or CIED, and 9 in whom method of AF/AFL diagnosis was unknown. Forty-one patients (66.1%) had AF/AFL before ATTR-CM diagnosis by of median 26.3 (IQR 4.3-40.9) months. New AF/AFL was diagnosed in 21/53 remaining patients with known ATTR-CM - 11 (52.4%) were incidentally diagnosed (Figure 1). Median time between ATTR-CM and AF/AFL diagnoses was 10.3 (IQR 7.0-25.8) months and 5.9 (IQR 2.2-22.3) months in symptomatic versus incidentally diagnosed patients (Mann-Whitney U=35, p=0.14). Anticoagulation (AC) was started in 9/11 (81.8%) due to incidental AF/AFL. One patient had AC for prior DVT; the other had no AC per patient preference. No strokes occurred in patients on AC.

Conclusions:
We found a high rate of incidentally diagnosed AF/AFL in patients with ATTR-CM. Detection of AF/AFL led to change in therapy. This finding affirms a need for routine ambulatory monitoring in asymptomatic patients with ATTR-CM. Optimal duration of monitoring needs further investigation.
Abstract 15170: In-hospital Utilization and Outcomes of Palliative Care Consultation in Patients With Advanced Heart Failure Complicated by Cardiogenic Shock Requiring Mechanical Circulatory Support
Authors: Grant Jelani , Vincent Louis , Ebner Bertrand , Maning Jennifer , Vaz Igor , olarte neal , Olorunfemi Odunayo P , Kavensky Elisse , Zaw Khin , Colombo Rosario A
Published: May 2021

Introduction:
Hospitalizations associated with advanced heart failure (HF) requiring mechanical circulatory support (MCS) are usually associated with a high morbidity, mortality and a protracted hospital course. Prior studies have shown that the early inclusion of palliative care specialist is associated with better end-of-life experiences.

Methods:
The National Inpatient Sample Database was queried from 2012 to 2017 for relevant International Classification of Diseases (ICD)-9 and ICD-10 procedural and diagnostic codes to identify patients above 18 years with advanced HF admitted with cardiogenic shock requiring MCS. Baseline characteristics and in-hospital outcomes were compared among patients evaluated by palliative care and those who were not. A p-value of <0.001 was considered statistically significant.

Results:
There were 748,360 patients hospitalized for advanced HF complicated by cardiogenic shock requiring MCS, of these a palliative care consult was placed in 118,015 (15.8%) patients. Patients evaluated by palliative care were older (70.6±14.9 vs. 64.9±16.3 years old, p<0.001) and had a higher prevalence of atrial fibrillation (39.3 vs. 35.1%,p<0.001) and chronic kidney disease (40.4 vs. 33.3, p<0.001), however had lower hypertension (57.4 vs. 59.7%, p<0.001), diabetes (35.4 vs. 36.5%, p<0.001), coronary artery disease (51.2 vs. 58.4%, p<0.001) and acute coronary syndromes (39.2 vs. 45.0%, p<0.001). Consulting palliative care was associated with a shorter length of stay (8.8±12.0 vs. 11.9±15.5 days, p<0.001), lower total hospital cost ($161,972±265,156 vs. $219,114±318,387, p<0.001) and higher Do Not Resuscitate (DNR) orders (30.8 vs. 5.8%, p<0.001). Mortality rates were higher in the palliative care cohort (73.4 vs. 29.4%, p<0.001).

Conclusions:
Despite the high morbidity and mortality associated with advanced HF patients with cardiogenic shock requiring MCS, the overall prevalence of palliative care consultation is exceedingly low. DNR orders were more prevalent in patients seen by the palliative care service. This study highlights the underutilization of palliative care services in this patient population, precluding any perceived benefit in end of life experiences.
Abstract 15183: Thrombopoietin Has a Protective Effect Against Apoptosis of Endothelial Cells Through Activating Pi3k/akt Pathway
Authors: Li Liang , Wang Junyan , zeng kuan , zhang hua , Yang Yanqi , Yang Mo
Published: May 2021

Introduction:
Thrombopoietin (TPO) is a hematopoietic growth factor for platelet lineage. TPO was found to be neuroprotective in hypoxic-ischemic neonatal rat brain models and treatment with TPO reduced brain damage and improved sensorimotor functions (Li L et al, Aging-US, 2020). However, the underlying mechanism of TPO in this model, and its role in neural cells and endothelial cells were still unclear.

Methods:
C17.2 cells were divided into control (0.5% FCS), Normal (10% FCS), TPO and TPO + LY294002 groups. Human umbilical vein endothelial (HUVEC) cells were divided in to normal, CoCl
2
, TPO and TPO + CoCl2 groups. The expressed of TPO and c-mpl was tested by RT-PCR. The cell viability and apoptosis of each group were tested by Cell Counter Kit 8 (CCK-8) assay and flow cytometry. The expression of Caspase-3 and mitochondrial membrane potential (MMP) were then determined by flow cytometry with Caspase-3-PE and JC-1. The effect of TPO in PI3K/AKT pathway was detected by using Western blot.

Results:
Both TPO and c-mpl are expressed in the neurons of the human CNS. TPO was also detected in human cerebrospinal fluid. TPO promoted C17.2 cell proliferation through activation of the PI3K/Akt signaling pathway. Via the Bcl-2/BAX signaling pathway, TPO exerted an anti-apoptotic effect by suppressing mitochondria membrane potentials. We also investigated the protective effect of TPO on human endothelial cells. CoCl
2
significantly inhibited the growth of HUVECs. The cell viability of HUVECs decreased gradually with the enhancement of CoCl2 at a gradient of chemical concentrations (r= -0.997). CoCl
2
dramatically increased apoptosis of HUVECs, whereas pre-treatment with TPO rescued cell apoptosis induced by CoCl
2
(P<0.001). Further investigation found that TPO decreased the expression of Caspase-3 and inhibited the reduction of MMP induced by CoCl
2
(P<0.05). TPO increased the activation of PI3K/AKT pathway in HUVECs.

Conclusions:
TPO has a protective effect against apoptosis of neural cells and endothelial cells through activating the PI3K/AKT pathway, thus decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.
Abstract 15185: Outcomes of Radiofrequency Catheter Ablation of Atrial Arrhythmias in Lung Transplant Recipients
Authors: Kochav Stephanie M , Wang Elizabeth , Goldenthal Isaac , Biviano Angelo B , Wan Elaine , Saluja Amardeep S , Dizon Jose , Morrow John P , Rubin Geoffrey , Waase Marc , Ehlert Frederick , Garan Hasan , Yarmohammadi Hirad
Published: May 2021

Introduction:
Atrial arrhythmias (AA) are common after lung transplant (LT) and may impact overall mortality. The majority of arrhythmias tend to be organized flutter, amenable to ablation; however the data is limited.

Hypothesis:
The purpose of this study was to investigate the outcomes of radiofrequency catheter ablation of AA in LT recipients.

Methods:
All LT recipients undergoing electrophysiology study at our institution between 2011-2018 were retrospectively reviewed. A total of 20 atrial ablations were identified in 16 patients. Mean follow-up was 4 ± 2.9 years.

Results:
Overall, mean age was 55 ± 13 years, 63% were male, 63% were status post bilateral (vs. single) LT, and mean LVEF was 57%. Transplant indications included interstitial lung disease (44%), COPD (19%), and cystic fibrosis (19%). Antiarrhythmics and beta blockers were used in 44% and 75%, respectively. Mean time from transplant to first ablation was 2.7 years. Of 20 ablations, macro-reentrant flutter (75%) and focal atrial tachycardia (15%) were common, particularly in double LT recipients (Figure). The most common ablation sites were pulmonary vein anastomosis/left atrial ridge (60%), mitral annulus (35%) and left atrial roof (30%). Restoration of sinus rhythm occurred in 19 of 20 procedures and only one complication occurred (e.g. small pericardial effusion without tamponade). Arrhythmia recurred in 10 (63%) patients, however, most were managed conservatively. Repeat ablation was needed in 4 patients, of which AAs originated from different locations. Beta blocker use was associated with a lower risk of SVT recurrence (p=0.04). Reduced LVEF and longer time to procedure post-transplant were associated with repeat ablation (p<0.05).

Conclusions:
The majority of AAs in LT recipients are atrial flutter originating near the pulmonary vein anastomosis sites. Despite a high immediate procedural success rate, recurrence is high and 25% of patients require multiple ablation attempts.
Abstract 15197: Lipopolysaccharide-Nuclear Factor-kappa B Pathway and Lipoprotein Apheresis Effects in Patients With Familial Hypercholesterolemia and Coronary Artery Disease
Authors: Liu Huihui , Zhu Cheng-Gang , Cui Chuan-Jue , Cao Yexuan , Jin Jinglu , Wu Na-Qiong , Guo Yuan-Lin , Gao Ying , Sun Jing , Dong Qian , Li Jian-Jun
Published: May 2021

Introduction:
Inflammation may play an important role in atherosclerosis in familial hypercholesterolemia (FH). Lipopolysaccharide (LPS)-nuclear factor-kappa B (NF-κB) pathway is a routine signal process activated in inflammatory status.

Hypothesis:
We assessed the hypothesis that LPS-NF-κB axis is markedly activated and lipoprotein apheresis has an inhibitory effect on this pathway in patients with FH and coronary artery disease (CAD).

Methods:
In this matched case-control study a genetically diagnosed FH cohort who presented stable CAD (n=63) was compared with 63 non-FH CAD and 63 non-FH non-CAD controls matched by sex and age. Plasma LPS levels and NF-κB activity were compared among the three groups. In addition, we studied in vitro LPS-induced interleukin-6 production by mononuclear cells from 16 FH cases without previous statin use and compared them with their respective matched control groups. Subsequently, these 16 FH patients underwent lipoprotein apheresis. Blood samples were taken immediately before and regularly after apheresis for measuring LPS and NF-κB.

Results:
FH plus CAD had higher LPS levels and NF-κB activity than CAD and non-CAD controls (all
p
<0.01). LPS-induced interleukin-6 production by mononuclear cells of FH plus CAD was also much higher compared with CAD and non-CAD controls (both
p
<0.01). Moreover, plasma LPS levels (
p
<0.001) and NF-κB activity (
p
<0.01) were dramatically reduced after apheresis in FH patients.

Conclusions:
In conclusion, genetically confirmed FH patients with CAD had a marked activation of LPS-NF-κB axis, while lipoprotein apheresis significantly attenuated this key inflammatory pathway, suggesting that inflammation may be an important therapeutic target for FH patients.
Abstract 15205: MANP: A Novel ANP Analog for Hypertension Associated With Obesity and Metabolic Syndrome
Authors: McKie Paul M , Iyer Seethalakshmi R , Scott Christopher , Bailey Kent , Johnson Bradley K , Benike Sherry L , Chen Horng , Miller Wayne L , Volpi Riccardo , Cabassi Aderville , BURNETT John C , Cannone Valentina
Published: May 2021

Introduction:
Atrial natriuretic peptide (ANP) plays an important role in blood pressure (BP) regulation via the second messenger cGMP. ANP also induces lipolysis by increasing plasma levels of non-esterified fatty acids (NEFA). MANP is a new Mayo Clinic designed ANP analog consisting of the native ANP with a novel 12-amino-acid C-terminus extension. In experimental models, MANP is more potent than ANP in reducing BP and inducing natriuresis. These actions are mediated by the activation of the pGC-A receptor and generation of cGMP. To date, the BP pressure lowering, cGMP generating and lipolytic actions of MANP remain unexplored along with its safety and tolerability in subjects with hypertension (HTN) associated with metabolic disease.

Hypothesis:
In subjects with HTN, obesity and metabolic syndrome (MS), MANP administration is safe, well tolerated, activates cGMP and exerts BP lowering and lipolytic properties.

Methods:
Double-blind, placebo-control clinical trial in 22 subjects (17 receiving MANP) with HTN, obesity and MS involving a single subcutaneous (SQ) injection of MANP (2.5 μg/Kg) or placebo. Subjects were monitored and cardiovascular, cGMP and metabolic parameters were collected during 24 hours after the injection.

Results:
In all subjects, MANP was safe and well-tolerated with no serious adverse side effects. MANP increased mean cGMP plasma levels after 30 minutes (delta: 4.8 ± 2.0 pmol/mL, p=0.02) and 1 hour (delta: 2.9 ±1.3 pmol/mL, p=0.03) when compared to baseline. Six hours after MANP injection systolic BP decreased by 5.7 ± 2.9 mmHg (p=0.06) whereas subjects receiving placebo had no decrease in blood pressure values compared to baseline. During fasting period, one hour after the administration of MANP, NEFA plasma levels increased by 108.2 ± 37.4 μM (p=0.01).

Conclusions:
In subjects with HTN, obesity and MS, SQ MANP is safe, well tolerated and activates the pGC-A receptor as measured by a significant increase in the second messenger cGMP. Subjects receiving MANP showed a borderline significant decrease in systolic BP and a significant increase in NEFA circulating levels supporting anti-hypertensive and lipolytic properties. Our findings support MANP as a potential novel therapy for HTN associated with metabolic disease.
Abstract 15206: Stethaid: Automated Point-of-care Recognition of Innocent Still’s Murmur in Children
Authors: Doroshow Robin , John Titus , Ambati Ravi Tej , Shekhar Raj
Published: May 2021

Introduction:
Still’s murmurs are difficult to distinguish from other heart murmurs at the primary care level. This leads to an estimated 400,000 children being referred to pediatric cardiologists each year for evaluation of heart murmurs in the United States. The murmur is ultimately diagnosed as innocent Still’s murmur in approximately 90% of these children. This diagnosis requires no specialty referral, cardiac testing, exercise restrictions or cardiology follow-up. These unnecessary referrals and associated tests waste healthcare resources, add to healthcare costs, and are a source of avoidable anxiety in children and families while waiting to see a pediatric cardiologist.

Hypothesis:
We have developed a novel mobile technology to discriminate Still’s murmur from all other murmurs. A smartphone application (app) that could quickly distinguish Still’s murmur from all other murmurs with high accuracy at the point of care could reassure pediatricians in their identification of Still’s murmur, significantly reducing the current rate of unnecessary referrals to cardiologists.

Methods:
Our current prototype is StethAid, a smartphone app which accepts heart sound recordings, and a cloud-based deep learning algorithm for discriminating Still’s murmur from other murmurs. The algorithm was independently developed and evaluated using archived heart sounds, recorded by one of the authors (RWD), made using an electronic stethoscope (3M Littmann Model 4100).

Results:
Our algorithm offers a sensitivity (Still’s murmurs correctly identified) of 90% with a specificity (Non-Still’s murmurs correctly identified) of 99% on 5-fold cross-validation over the Murmur Library. The area under the curve was 0.99446. The algorithm’s result is available in real time at the point-of-care (< 1 min).

Conclusions:
The described point-of-care mobile technology could automatically distinguish Still’s murmur from all other murmurs with high accuracy. The technology could lower the current high rate of specialist referrals associated with Still’s murmur and reduce the related financial and emotional costs. Future directions will include further improvement of the technology and validation through multi-center clinical trials.
Abstract 15210: Do Idiopathic Ventricular Fibrillation and Brugada Syndrome Patients Have Favor Outcomes in the Targeted Temperature Management Era?
Authors: Kagawa Eisuke , Kato Masaya , Oda Noboru , Kunita Eiji , NAGAI Michiaki , YAMANE AYA , Shiota Haruko , Dote Keigo
Published: May 2021

Introduction:
Idiopathic ventricular fibrillation (IVF) including Brugada syndrome (BS) is one of causes of cardiac arrest without prior overt cardiac dysfunction.

Hypothesis:
We assessed the hypothesis that patents of IVF had favor outcomes than those of non-IVF after cardiac arrest treated with targeted temperature management (TTM).

Methods:
Patients who were treated with TTM after cardiac arrest between 2000 and 2019 were enrolled in the study. Patients were divided into 2 groups according to whether the patients were diagnosed as IVF or not. The patients treated with TTM were routinely performed coronary angiography.

Results:
Among the study patients (N = 306), 35 (11%) patients were IVF and 7 were BS. The patients of the IVF group were significantly younger (median 53 y vs. 64 y) than those of the non-IVF group. The prevalence of initial rhythm was shockable (69% vs. 47%, P = 0.02) was significantly higher in the patients of the IVF group than those of the non-IVF group. Among the patients in the non-IVF group, 114 patients (42%) were diagnosed as acute coronary syndrome and 93 patients (35%) were treated with coronary revascularization. The prevalence of male sex (77% vs 74%, P = 0.70) and witnessed to arrest (80% vs. 81%, P = 0.87), and low-flow time (29 min vs. 38 min [20 - 43 min vs. 21 - 52 min, P = 0.15]) were similar between the 2 groups. The prevalence of performing extracorporeal resuscitation (9% s 43%, P < 0.001) were lower in the patients of the IVF group. The 8-y survival rate were shown in the figure. All of the BS patients were witnessed arrest and were discharged without severe neurological deficit. The IVF as the cause of arrest was independently associated with 8-y survival.

Conclusions:
The patients of IVF had favor outcomes than those of non-VF. One of causes may be the lower prevalence of requiring extracorporeal circulatory support due to less cardiac dysfunction. The patients of BS had the tendency toward higher survival rate than those of non-BS IVF patients.
Abstract 15214: Food Insecurity and Cardiovascular Disease in NHANES (National Health and Nutrition Examination Survey) 2011-2016
Authors: DELSON MONICA M , Bell Janice F , Porter Tequila S , Bidwell Julie T
Published: May 2021

Background:
Adherence to a heart-healthy diet is foundational for the prevention, management, and treatment of cardiovascular disease (CVD). Despite the fact that adhering to dietary guidelines may be challenging in the context of food insecurity, little is known about the likelihood of food insecurity in persons with CVD.

Hypothesis:
We hypothesized that persons with CVD (hypertension, coronary artery disease, heart failure, or stroke) would have significantly higher odds of food insecurity.

Methods:
This was an analysis of data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional study of health in the United States. All adults aged 19 years or older with food insecurity data were included across 3 cycles of NHANES (2011-2016). Food insecurity was measured using the 10-item Food Security Scale. CVD diagnosis was measured by self-report. Risk for food insecurity by CVD diagnosis was examined using multivariable logistic regression models, incorporating NHANES sample and person weights, and controlling for common sociodemographic confounders (age, gender, race/ethnicity, education, marital status).

Results:
The sample consisted of 17,175 persons (weighted study
N
=229,247,659). Slightly more than half were male (51.9%), and most were non-Hispanic white (65.1%). Just under half (45.6%) were in early adulthood (19-44 years), 35.3% were in middle adulthood (45-64 years), and 18.6% were in late adulthood (≥65 years). One quarter (25.9%) were food insecure. Consistent with our hypothesis, diagnosis of any CVD (stroke, heart failure, coronary artery disease, or hypertension) was significantly associated with higher likelihood for food insecurity (stroke: OR=2.18; 95% CI 1.83-2.60; p<0.001; heart failure OR=1.94, 95% CI 1.46-2.57, p<0.001; coronary artery disease: OR=1.90, 95% CI 1.49-2.43, p<0.001; and hypertension: OR=1.25, 95% CI 1.10-1.42, p=0.001).

Conclusions:
Diagnoses of hypertension, stroke, coronary artery disease, and heart failure were all significantly associated with higher risk for food insecurity. Given the necessity of dietary modification in CVD, further efforts to study food insecurity in CVD alongside other social determinants of health are urgently needed.
Abstract 15223: Comparison of Net Clinical Benefit Between Clopidogrel-based and Ticagrelor-based Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention in China
Authors: chen yundai , Wang Daowen , Li Dandan , Sun Yang , Ye Xiaoran , Li Lanting
Published: May 2021

Introduction:
Dual antiplatelet therapy (DAPT) increases the bleeding risk, which might outweigh the benefits of reduction in ischemic events in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). This study aimed to evaluate the difference in net clinical benefits of clopidogrel-based DAPT compared with ticagrelor-based DAPT in ACS patients undergoing PCI in a real-world setting in China.

Method:
This study was conducted on three pre-existing PCI patient databases, two were from nation-wide studies with similar prospective designs and time-span: the BRIC-ACS(I) study and the COSTIC study, and other was from a tertiary hospital-maintained PCI patient database. The primary endpoint was net adverse clinical and cerebral event (NACCE), which was a composite of all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke and BARC ≥ 2 (excluding BARC 4) bleeding within 12 months after discharge. The efficacy outcome, major adverse cardiovascular events (MACE), was defined as a composite of all-cause death, non-fatal MI, and non-fatal stroke. The safety outcome was defined as BARC ≥ 2 (excluding BARC 4) bleeding. Kaplan-Meier survival curves, and Cox regression were applied to analyze the difference between the two groups after propensity score matching (PSM).

Results:
A total of 7,236 adult ACS patients who underwent PCI in the period of Jan 2014 to Oct 2017 were analyzed. Of them, 4,330 patients were included in post-PSM analyses. Patients prescribed clopidogrel and aspirin had a significant lower risk of NACCE within 12 months after discharge relative to those prescribed ticagrelor and aspirin [5.4% vs. 8.3%, hazard ratio (HR) = 0.63, 95% CI: 0.50 - 0.80]. While the two groups did not vary significantly in the risk of MACE (2.9% vs. 3.1%, HR = 0.91, 95% CI: 0.64 - 1.28), clopidogrel-based DAPT was associated with a significant lower risk of BARC ≥ 2 (excluding BARC 4) bleeding (2.9% vs. 5.5%, HR = 0.50, 95% CI: 0.37 - 0.68) compared to ticagrelor-based DAPT.

Conclusion:
In this real-world study, post-PCI ACS patients prescribed clopidogrel-based DAPT were associated with a reduction in NACCE and bleeding events without significant difference in MACE, compared to patients treated with ticagrelor-based DAPT.
Abstract 15227: Egln1 Deficiency Induce Alveolar Macrophages Accumulation and Polarize Lung Interstitial Macrophages to a Pro-pah State Mediating Obliterative Pulmonary Vascular Remodeling and Severe PAH
Authors: Dai Jingbo , Dai Zhiyu , Zhu Mengqi , Dong Daoyin , Zhao Youyang
Published: May 2021

Introduction:
Previously we identified a mouse model (Tie2Cre-mediated disruption of
Egln1
) of Pulmonary arterial hypertension (PAH) with progressive obliterative vascular remodeling including vascular occlusion and plexiform-like lesions and right heart failure. Tie2Cre-meidated disruption of
Egln1
in bone marrow contributes to the severity of PAH indicating the importance of the immune cells in the pathogenesis of PH.

Hypothesis:
Macrophage accumulation and polarization due to Egln1 deficiency contributes to obliterative pulmonary vascular remodeling and severe PAH in Egln1
Tie2Cre
mice.

Methods:
Egln1
Tie2Cre
mice with macrophage Fas-Induced apoptosis (MaFIA) transgene were generated (Egln1
Tie2Cre
/MaFIA) and received AP20187 treatment to deplete the macrophages during the development of PAH afterwards the RVSP and RV/(LV+S) ratio were measured as the indicator of diseases severity. Flowcytometry and immunostaining were used to quantify different types of macrophages. Bulk RNA-seq and single cell RNA-seq were used to identify PAH-related pathway changes and population changes of lung macrophages in
Egln1
Tie2Cre
mice. BrdU staining was used to measure the smooth muscle cell (SMC) proliferation co-culturing with macrophages isolated from
Egln1
Tie2Cre
mice.

Results:
We observed that CD206+ Alternative Activated Macrophages (AAMs) are accumulated in the pulmonary vessel adventitia of IPAH patients as well as
Egln1
Tie2Cre
mice. These macrophages are
Egln1
deficient and express elevated level of pro-PAH factors and thus promote SMC proliferation
in vitro
. Moreover, genetic depletion of total macrophages using the

Egln1
Tie2Cre

/MaFIA mouse model markedly inhibited obliterative pulmonary vascular remodeling and PAH. Single cell RNA-seq revealed that lung resident alveolar macrophages (Siglec-F+/Cd11c+) accumulated due to hyper-proliferation while recruited lung interstitial (Cx3cr1+/Aif1+) macrophages polarize to a pro-PAH state in

Egln1
Tie2Cre

mice.

Conclusions:
Egln1
deficiency in the HCs induced proliferation/accumulation of alveolar macrophages and polarized the recruited interstitial macrophages to AAM state which contributes to the vascular remodeling by secreting pro-PAH factors.
Abstract 15242: Increased Mortality Among African American Patients With Heart Failure Caused by Hereditary Transthyretin Amyloid Cardiomyopathy
Authors: Zareh Meena , Levine Alina , Berk John L , Siddiqi Omar K , Gopal Deepa M , Connors Lawreen H , Fine Denise , Chiuzan Codruta , Maurer Mathew S , Ruberg Frederick L
Published: May 2021

Introduction:
Hereditary transthyretin amyloid cardiomyopathy (pV142I hATTR-CM) is an under-recognized cause of heart failure (HF) in elderly patients of African origin. While we have previously demonstrated that the endogenous TTR ligand retinol binding protein 4 (RBP4) identifies patients with hATTR-CM, its capacity to predict outcomes is unexplored. Further, comparative data are lacking describing clinical outcomes in hATTR-CM vs. matched patients with HF.

Hypothesis:
Reduced survival is associated with pV142I hATTR-CM when compared to an age, race, sex matched patients with HF.

Methods:
Retrospective, single center, cohort study of self-reported African American patients ≥ 60 years of age with normal
TTR
genotype, HF, and LV wall thickness ≥ 12mm (n=84) were compared to a cohort with biopsy-proven pV142I hATTR-CM (n=30). Patients did not receive ATTR-specific therapies, as study occurred prior to FDA approvals. Baseline laboratory values were measured. All-cause mortality was estimated and compared between groups based on a median followup of 45.4 months. Analyses were conducted with Fisher Exact, Kruskal Wallis, and Kaplan-Meier with log-rank testing.

Results:
hATTR-CM patients were slightly older but less likely to have concomitant HTN or DM (Table 1). Baseline RBP4 concentration was lower while troponin level higher in patients with hATTR-CM (Table 1). hATTR-CM patients had a higher hazard of all-cause mortality after adjusting for age (HR=3.5, 95% CI: 1.8 – 6.7, p<0.001). Baseline RBP4 was not a significant predictor of mortality (p-value=0.195).

Conclusions:
Patients pV142I hATTR-CM demonstrate significantly reduced survival (a 3.5-fold increased risk of death, 43% 4-year survival) compared to control subjects with HF in the absence of amyloidosis. Baseline RBP4 concentration did not associate with survival. These data suggest that hATTR-CM recognition is essential to permit implementation of available therapies that can improve survival.
Abstract 15253: Significant Discrepancies in Quantification of Regurgitant Volume in Primary Mitral Regurgitation Observed on Multimodality Imaging: Is It Time for Reappraisal?
Authors: Fava Agostina M , Miyasaka Rhonda , Gillinov Marc , Wierup Per , Popovic Zoran B , Rodriguez Leonardo , Griffin Brian P , Desai Milind Y
Published: May 2021

Introduction:
Mitral valve regurgitation volume (RV) can be quantified using proximal isovelocity surface area (PISA) or stroke volume (SV). SV method incorporates mitral annulus (MA) diameter (assumed circular) on 2D transthoracic echo (2D TTE). However, MA area (MAA) can be precisely measured using 3D transesophageal echocardiographic (3DTEE) or computed tomography (CT).

Hypothesis:
We sought to compare RV obtained using a) PISA b) standard SV using MA diameter on 2D echo and c) modified SV using MAA on 3D TEE and d) MAA on CT.

Methods:
37 patients (63±9 years, 81 % men) with severe primary mitral regurgitation (MR) undergoing surgery were prospectively recruited. RV was calculated using a) PISA b) standard SV method using MA diameter on 2D echo (0.785*diameter
2
MV
*VTI
MV
-0.785*d
2
LVOT
*VTI
LVOT
) c) & d) modified SV methods where MAA (on 3D TEE and CT) were incorporated instead of MA diameter.

Results:
The mean MAA (cm
2
) by 2DTTE, 3DTEE & CT were 10.7±3, 10.9 ±3 & 15.9 ±3. Mean RV (cc) by standard SV method, modified SV (3D TEE & CT) & PISA were 294±126, 276±82, 355±127 & 91±51, respectively. Correlations & agreements of SV-based RV are shown in Figure 1. RV was highest using CT-based MAA. The closest agreement was between 2D TTE & CT with a mean error (ME) of -61 cc. There was a large discrepancy in RV derived from PISA vs all SV methods, with a systemic overestimation using SV methods with root mean square errors (RMSE) ranging from 156 to 293 cc Figure 2.

Conclusions:
In severe MR,calculating RV using SV vs PISA yields vastly different values. The differences are exaggerated using modified SV method incorporating more accurate MAA on 3D TEE or CT. These techniques should not be interchanged to quantify MR.
Abstract 15292: Acute Coronary Syndrome in Patients With Severe Aortic Stenosis Undergoing TAVR: A Retrospective Analysis
Authors: Amin Saad M , Mehta Harsh , AMIN AKHTAR
Published: May 2021

Introduction:
Transcatheter aortic valve replacement (TAVR) has been increasingly utilized in patients with Aortic Stenosis (AS). The purpose of this study is to document the incidence of acute coronary syndrome (ACS) in patients with a history of severe Aortic Stenosis (AS) undergoing TAVR.

Methods:
Using the Nationwide Inpatient Sample (NIS) for years 2015 to 2017, we performed a retrospective analysis of adults over 18 years of age who underwent TAVR and their inpatient course was complicated by ACS. We further analyzed the comorbidities and complications associated with patients who developed ACS during the same hospitalization.

Results:
We divided a total of 69,584 patients with ACS, who underwent TAVR into two groups: patients with ACS (2.11%) and patients without ACS (97.89%). From 2015 to 2017 there was a decline in the incidence of ACS in patients undergoing TAVR from 2.62% to 1.93%. There were no demographic differences between the two groups. Comorbidities like diabetes, peripheral vascular disease, end-stage renal disease and chronic liver disease were more prevalent in ACS group (Table 1). Patients with ACS had a higher history of previous PCI (4.42% vs 2.64% p-0.08). Complications like cardiogenic shock (11.9% vs 1.29% p-<0.05), acute respiratory failure (25.17% vs 4.1% p <0.05), acute kidney injury requiring dialysis (1.7% vs 0.46% p<0.05) and cardiac arrest (4.08% vs 0.78% p<0.05) were more prevalent in the ACS group. Overall, in-hospital mortality (3.41% vs 1.42% p< 0.05) and length of stay (12.22 days vs 4.20 days p<0.05) was higher in the ACS group.

Conclusions:
A steady decline was noted in the number of cases complicated by ACS undergoing for TAVR over 3 years. ACS in TAVR cases was associated with higher rates of complications, prolonged hospitalizations and higher mortality.