bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13544: Cardiologist Underutilization of New Antihyperglycemic Medications in Diabetic Patients With Cardiovascular Disease
Authors: Desrosiers Gregory , Mohammed Alaa , Fort Daniel , Effron Mark B
Published: May 2021

Introduction:
Sodium Glucose Cotransporter-2 inhibitors (SGLT2i) and Glucose-Like Peptide-1 receptor agonists (GLP-1ra) showed significant reduction in cardiovascular (CV) events in type 2 diabetes (T2DM) patients (pts). The ADA and ACC recommend using SGLT2i/GLP-1ra in CV patients with T2DM (T2DM-CV). This study evaluated prescribing patterns in T2DM-CV to distinguish characteristics between those pts receiving SGLT2i/GLP-1ra from those not receiving SGLT2i/GLP-1ra.

Hypothesis:
SGLT2i/GLP-1ra are underutilized in T2DM-CV pts.

Methods:
Ochsner Health’s EPIC database was queried for T2DM-CV pts treated between Jan 2016 - Dec 2018. Baseline demographics and clinical characteristics were compared using ANOVA for numerical covariates, χ-square test for categorical covariates and multivariate logistic regression.

Results:
A total of 4,741 T2DM-CV pts were identified with approved indication for SGLT2i/GLP-1ra. Only 686 received a prescription for one of the approved SGLT2i/GLP-1ra with CV indication at the time of the study (empagliflozin, canagliflozin, liraglutide). Pts receiving SGLT2i/GLP1-ra were younger, had higher BMI, A1c, hypertension, hypercholesteremia, and/or commercial insurance or self-pay. Pts with CAD, atrial fibrillation, prior TIA or stroke, or heart failure were less likely to receive these drugs. (Table) Cardiologists rarely prescribed SGLT2i/GLP-1ra (2.2%) compared with primary care physicians (PCP) (45.6%) or endocrinologists (44.6%) (p<0.001).

Conclusions:
T2DM-CV pts rarely received guideline directed SGLT2i/GLP-1ra, and cardiologists rarely prescribed them. Younger pts with higher A1c, CV risk factors, and commercial insurance were more likely to be prescribed SGLT2i/GLP-1ra than pts with CV disease, despite reduction in CV events in randomized trials and societal guidelines. Cardiologists need to work with endocrinologists and PCPs to drive use of these medications to improve outcomes in T2DM-CV pts.
Abstract 13551: Identifying Left Main Coronary Artery Disease Using Coronary Artery Calcium Scans
Authors: Money Joel E , Muhlestein Joseph B , Mason Steve M , Bair Tami L , Knowlton Kirk U , Anderson Jeffrey L
Published: May 2021

Introduction:
The ISCHEMIA trial tested an invasive vs. an initial medical strategy in patients (pts) with stable coronary disease and evidence of ischemia. No significant difference between strategies in cardiovascular events was found at 3.2 years. However, pts were screened before randomization by coronary CT angiography (CCTA) to exclude ≥50% left main coronary stenosis (LMCS). CCTA adds complexity to routine medical practice, including time delays, expense, and safety concerns. We tested whether a coronary artery calcium scan (CACS), a simpler, less expensive test, could replace CCTA to exclude significant LMCS.

Methods:
We hypothesized that pts with ≥50% LMCS would have a LM CACS score>0. As a corollary, we postulated that a LM CACS=0 would exclude pts with LMCS. To test this, we searched Intermountain Healthcare’s electronic medical records database for all adult pts who had undergone non-contrast cardiac CT for quantitative CACS scoring prior to selective coronary angiography (SCA) and were found to have a LMCS ≥50%. Pts aged <50 and those with a heart transplant were excluded. Cases with incomplete (qualitative) angiographic reports for LMCS and those with incomplete or discrepant LM CACS results were reviewed and reassessed blinded to CACS or SCA findings, respectively.

Results:
Among 674 candidate pts with CACS followed by SCA, 24 qualifying pts were identified who had a quantitative CACS score and LMCS ≥50%. Their age averaged 71 ± 11 years, and 83% were men. Angiographic LMCS averaged 77% (range 50%-99%). A heavy burden of both total CAC and LM CAC was typically present. Total CACS score averaged 2,545 Agatston Units (AU), range 571-6,636. LM CACS score averaged 214 AU, range 47-610. Importantly, no LMCS pt had a LM CACS score of 0 vs. 57% (368/650) of non-LMCS controls (p<0.00001).

Conclusions:
Our results support the hypothesis that an easily administered, inexpensive, low radiation CACS can identify a large subset of pts with a very low risk of LMCS without the need for routine CCTA. Using CACS to exclude LMCS may efficiently allow for safe implementation of an initial medical therapy strategy in clinical practice for ISCHEMIA trial-like pts with at least moderate ischemia on stress testing. These promising results deserve validation in larger data sets.
Abstract 13552: Clinical Relevance of Endogenous Tissue-plasminogen Activator in Patients With Aortic Valve Sclerosis
Authors: Yang Ke , Chen Zhongli , Shen Ying , Zhang Yangyang , Lin Bo Wen , He Xiao Yan , Zhang Yi Bo , Shen Shutong , Yang Ying , Shen Wei Feng , Koch Walter J. , Liu Ye Hong
Published: May 2021

Introduction:
Impaired fibrinolysis featuring elevated tissue plasminogen activator (t-PA) induces cardiovascular outcomes. Aortic valve sclerosis (AVSc) shares similar aspects of pathophysiology with atherosclerosis and correlates with adverse cardiovascular events.

Hypothesis:
We investigated whether endogenous t-PA is associated with AVSc and clinical outcomes of these patients.

Methods:
Plasma levels of t-PA were measured in 155 AVSc patients and 140 non-AVSc counterparts. The composite major adverse cardio-cerebral events (MACCE), including cardiovascular death, nonfatal myocardium infarction, stroke, and re-hospitalization because of heart failure or unplanned revascularization were recorded during follow-up in 143 patients with AVSc (median, 6.5 years). Expression of t-PA was detected in human aortic valves with and without sclerosis by immunochemical analysis.

Results:
Plasma t-PA was higher in patients with AVSc than in those without (median, 2163.10 pg/mL vs 1403.17 pg/mL, p < 0.001). After adjusting for confounding variables, t-PA level remained an independent risk factor for AVSc (OR=1.66, 95%CI: 1.18-2.34, P=0.004). Based on the optimal cut-off of 1787.8 pg/mL determined by X-tile program, AVSc patients with low t-PA displayed better survival free from MACCE than those with high t-PA (p=0.0018). After full adjustment, t-PA was independently associated with composite MACCE (HR=1.33, 95% CI: 1.07-1.66, p=0.009). The area under the curve of plasma t-PA for predicting composite MACCE within three years was 0.71(95%CI: 0.63-0.80). The expression of t-PA was three times higher in sclerotic compared to non-sclerotic aortic valves.

Conclusions:
Elevated endogenous t-PA in plasma may serve as an indicator of AVSc and is associated with poor clinical outcomes in patients with AVSc.
Abstract 13558: Caregiver Anxiety Reduced From Baseline to 12 Months After Surgery: Findings From the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Circulatory Support (
Sustain-it
) Study
Authors: Petty Michael , Andrei Adin-Cristian , Elenbaas Christian , Warzecha Anna , Yancy Clyde , Pham Duc , Kao Andrew , Spertus John , Hsich Eileen M , Dew Mary Amanda , Sciortino Christopher , HARTUPEE Justin , Cotts William , Pamboukian Salpy , Pagani Francis D , Lampert Brent , Johnson Maryl R , Murray Margaret A , Takeda Koji , Yusefpolskaya Melana , Silvestry Scott , Kirklin James , Collum Craig , Grady Kathleen L
Published: May 2021

Introduction:
Caregivers (CGs) of heart failure (HF) patients (PTs) who undergo heart transplantation (HT) or Destination Therapy Mechanical Circulatory Support (DT MCS) provide support to PTs before and after surgery, which may affect their own health-related quality of life (HRQOL). In SUSTAIN-IT, we previously reported that CG HRQOL was good at baseline (i.e., before HT and DT MCS surgery) and was impacted by CG comorbidities and CG anxiety. This report explores change in CG overall HRQOL, depression, and anxiety from baseline to 12 months after HT or DT MCS surgery.

Methods:
From 10/1/15-12/31/18, 13 U.S. centers enrolled 301 CGs of HF PTs: 193 awaiting HT (92 HT with MCS as a bridge to transplant [HT BTT] and 101 HT without MCS [HT non-BTT]), and 108 awaiting DT MCS. At baseline, 3, 6, and 12 months post HT or DT MCS surgery, CGs completed the following instruments: EQ-5D-3L (Visual Analog Scale [VAS]: 0 [worst] to 100 [best] imaginable health state), PHQ-8 (range=0-24; score ≥10=depressive symptoms requiring evaluation), and STAI-State (range=20-80, higher score=more anxiety). Analyses included unadjusted and baseline-adjusted linear regression models.

Results:
CGs were age 61.0±10.3 years; the majority were Caucasian (86%), female (86%), spouses (85%) of enrolled HF PTs. At baseline, CG EQ-5D-3L VAS and PHQ-8 average scores were 83.8 ± 13.99 (high) and 2.6 ± 2.85 (low), respectively, for the entire cohort. No significant interval changes in CG HRQOL and depressive symptoms were found within or between groups. DT MCS and HT non-BTT CG anxiety significantly decreased over time (baseline to 12 months) (Figure). Levels of CG anxiety were similar among all groups at 12 months after HT or DT MCS surgery.

Conclusions:
The demonstrated reduction in anxiety among CGs in the post-operative period provides clinicians with important information to share with CGs when PTs are considering surgical treatment options for HF.
Abstract 13574: A Rare Case of Giant Cell Arteritis With Coronary Artery Involvement
Authors: Nyange Christabel E , Toole Joseph , Chang William , Snyder Matthew , Fisher Perry
Published: May 2021

Introduction:
Coronary artery involvement in patients with systemic vasculitis is relatively rare, but can be life threatening. There is a well-known occurrence of coronary artery vasculitis in Kawasaki disease and Takayasu arteritis, however, coronary arteritis caused by giant cell arteritis (GCA) has been documented in only a handful of reports.

Case report:
A 65-year-old woman with a history of GCA complicated by cerebrovascular stenosis s/p bypass and coronary artery disease (CAD) s/p DES to mid-left anterior descending (LAD) 3 years prior, without cardiac risk factors, who presented with shortness of breath and 2-3 hours of progressive non-radiating pressure like midsternal chest pain. Vital signs were stable with an unremarkable physical exam. EKG showed new T-wave inversions in V4-V6, I, II, aVL. Labs were significant for Trop T 0.17 and CRP 2.02. Echocardiogram showed EF 30% with wall motion abnormalities (ECHO 9 months prior showed EF 69% with no wall motion abnormalities). Coronary angiography revealed 99% in-stent-restenosis (ISR) of mid-LAD, 50% tubular OM1 stenosis, and 100% RCA occlusion with right-to-right collateral (figure 2). The patient underwent CABG with a left internal mammary artery graft to LAD and saphenous vein graft to RCA. Post-operative EF was 50%, and she was discharged on post-operative day 5.

Discussion:
In patients with systemic vasculitis and no identifiable CAD risk factors presenting with acute coronary syndrome, there has to be a high suspicion for coronary arteritis. Our case strongly suggests that GCA can involve the coronary arteries given the rapid progression of ISR with triple vessel disease in the absence of cardiac risk factors. Although advancements in imaging techniques have led to improvements in the diagnosis of systemic vasculitis, standardized imaging for evaluating coronary vasculature is lacking. Larger retrospective case studies are needed in order to clearly delineate the association between GCA and CAD.
Abstract 13576: Anti-senescent Drug Screening by Deep Learning-based Morphology Senescence Scoring
Authors: Kusumoto Dai , Seki Tomohisa , Sawada Hiromune , Katsuki Toshiomi , Kimura Mai , Ito Shogo , Komuro Jin , Hashimoto Hisayuki , Fukuda Keiichi , Yuasa Shinsuke
Published: May 2021

Backgrounds:
Deep learning is currently being applied to many complex tasks. The accuracy of image classification, in particular, has improved with the development of convolutional neural networks (CNNs). Cellular senescence is a hallmark of ageing and is highly important for the pathogenesis of aging-related diseases. Furthermore, cellular senescence has been identified as a potential therapeutic target. Specific molecular markers are widely used to identify senescent cells, but senescent cells also show unique morphology, which can be identified by CNN.

Objective:
We develop a strong-performing, morphology-based CNN system called Deep-SeSMo to identify senescent cells, and establish a novel quantitative scoring system to evaluate the probability that an endothelial cell is senescent.

Methods and results:
We induced cellular senescence in human umbilical vein endothelial cells (HUVECs) using three different stressors: ROS; an anti-cancer reagent; and replication stress, and demonstrated that CNN performed with high accuracy and generalizability. Then, we developed a “senescence score” based on the output of the pre-trained CNN, optimized it for the classification problem, and defined the overall average output probability calculated by the pre-trained CNN as the quantitative senescence score, namely Deep-SeSMo. Deep-SeSMo correctly evaluates the effects of well-known anti-senescent reagents; nicotinamide mononucleotide (NMN) and metrofmin. We screened for drugs that control cellular senescence using a kinase inhibitor library by Deep-SeSMo-based drug-screening and discovered four novel anti-senescent drugs. RNA sequence analysis revealed that those compounds commonly suppress senescent phenotypes through inhibition of the inflammatory response pathway.

Conclusions:
Using Deep-SeSMo, we demonstrated that the morphology-based CNN system can be a powerful tool for anti-senescent drug screening.
Abstract 13594: Adverse Right Ventricular Remodelling, Function and Stress Responses in Obesity: Implications for Severe Acute Respiratory Illness
Authors: Lewis Andrew J , Watson William , Mahmoud-Elsayed Hani , Moody William , Khan-Kheil Ayisha M , Senior Jonathan , ABDESSELAM Ines , Rayner Jennifer , Barker Graham , Colebourn Claire , Mahroof Razeen , Foley Paul , Byrne James , Borlaug Barry A , Neubauer Stefan , Steeds Richard P , Rider Oliver J
Published: May 2021

Introduction:
The mechanisms linking obesity to increased mortality in patients with coronavirus-disease 2019 (COVID-19) are unclear.

Hypothesis:
We hypothesised that obesity would be associated with adverse right ventricular (RV) remodelling and function which might be further exacerbated by COVID-19 associated increases in RV afterload/demand.

Methods:
We used echocardiography and computed tomography to establish links between RV dimensions and function and bodyweight in patients with severe COVID-19. In obese and non-obese participants without COVID-19, we used cardiovascular magnetic resonance to define the effects of obesity upon RV volumes, energetics, systolic function and stress reserve.

Results:
In patients with severe COVID-19, increasing bodyweight was associated with disproportionate RV dilatation (n=26, echocardiography, R=0.42, P=0.03, CT n=34, R=0.23, P=0.004) and impairment of RV systolic function (fractional area change (FAC) R=-0.45, P=0.04); obesity (BMI >30kg/m2) was associated with a 32% reduction in RV FAC (P=0.03). Similar associations were seen in a validation cohort (n=91, all P<0.05). In participants without COVID-19, class III obesity (n=54, BMI 47±4 kg/m
2
) was associated with RV remodelling, impaired cardiac energetics (PCr/ATP ratio 23% lower, P<0.001) and reduction in RV systolic function at rest (by 3±1%, P=0.01), which was related to reduced energetics (R=0.3, P=0.04). Participants with class I-II obesity (BMI 35±5 kg/m
2
, n=27) had impaired RV diastolic filling rate at rest (P<0.001) and blunted RV dobutamine stress systolic response (by 68%, P=0.03) and diastolic response (by 78%, P=0.008). Surgical weight loss in patients obesity (n=37, 34±15kg weight loss) was associated with improvement in RV volume (12±26 ml lower, P=0.006) and function (ejection fraction 2±5% higher, P=0.03).

Conclusions:
Increasing body weight is associated with both significant alterations in RV volumes, systolic function and stress responses which are mitigated with weight loss and also with disproportionate RV dilatation and dysfunction in severe COVID-19. RV dysfunction is a modifiable mechanism which might link obesity to adverse outcomes in patients with COVID-19 and other disorders stressing the right heart.
Abstract 13595: Association of Costal Cartilage Calcification With Cardiovascular Events and Risk Factors in Multi-Ethnic Study of Atherosclerosis (MESA); The MESArthritis Study
Authors: Shabani Mahsima , Pishgar Farhad , Akhtarkhavari Sepehr , Silva Thiago Q , Budoff Matthew J , Post Wendy S , Barr Graham , Wu Colin , Bluemke David A , demehri Shadpour , Lima João A.C.
Published: May 2021

Introduction:
Costal cartilage calcification (CCC) is an evident yet usually neglected finding in calcium scoring CT scans. Although CAC score is a well-known predictive marker for CVD, little is known about the potential association between CCC and CVD risk factors (RFs) and events.

Hypothesis:
CCC is associated with CVD RFs and is predictive of CVD events independent from CAC score.

Methods:
Cardiac CAC score images from Johns Hopkins Hospital field center acquired within the fifth exam of the MESA cohort (2010-2012) were re-analyzed as part of the MESArthritis ancillary study. The CCC was measured bilaterally for the first pair of cartilages at the superior end of image FOVs using calcium scoring package (VScore, Vitrea 7.11, Vital Images) with a 180 HU cut-off. Outlier values were excluded using the IQR-based outlier fence estimates. Association of CCC with CVD RFs, and CVD and mortality time-to-event was investigated by multivariable linear regression and Cox proportional hazard models, respectively.

Results:
After exclusion of 3 outliers, 329 participants (53% female) with a mean age of 70.1 (±8.75) were included. In cross-sectional analysis, in addition to age (β=8.86, p:.003) and gender (376.0, p<.001), CCC was associated with diabetes (141.42, p:.019) and glucose level (2.85, p:.006). CCC was correlated with Framingham global CVD risk score (FRS) (coefficient:0.39, p<.001), but not with CAC when adjusted for age and gender. In time-to-event analysis, adjusted CCC was positively associated with CHD (HR:1.17, p:.039) and CVD (1.14, p:.012) risk. Compared with CAC score (C-index: 0.76) and FRS (0.74) individually, models with CCC addition to FRS (0.85) and both CAC and FRS (0.84) had higher C-index for CHD prediction.

Conclusions:
CCC is associated with diabetes and can be used to predict CHD and CVD events and augment the predictive power of the highly validated CAC and FRS for CHD events. However, this scoring should be validated in other larger cohorts.
Abstract 13598: The G-protein BetaGamma Subunits Regulate Platelet Function
Authors: Alarabi Ahmed , Karim Zubair , Hinojos Victoria , Lozano Patricia A , Hernandez Keziah , Montes Ramirez Jean , Khasawneh Fadi T , Alshbool Fatima Z
Published: May 2021

Platelet activation involves tightly regulated processes to ensure a proper hemostasis response, but when unbalanced, can lead to pathological consequences such as thrombus formation. G-protein coupled receptors (GPCRs) regulate platelet function by interacting with and mediating the response to various physiological agonists. To this end, an essential mediator of GPCR signaling is the G protein Gαβγ heterotrimers, in which the βγ subunits are central players in downstream signaling pathways. While much is known regarding the role of the Gα subunit in platelet function, that of the βγ remains poorly understood. Therefore, we investigated the role of Gβγ subunits in platelet function using a Gβγ (small molecule) inhibitor, namely gallein. We observed that gallein inhibits platelet aggregation and secretion in response to agonist stimulation, in both mouse and human platelets. Furthermore, gallein also exerted inhibitory effects on integrin αIIbβ3 activation and clot retraction. Finally, gallein’s inhibitory effects manifested
in vivo
, as documented by its ability to modulate physiological hemostasis and delay thrombus formation. Taken together, our findings demonstrate, for the first time, that Gβγ directly regulates GPCR-dependent platelet function,
in vitro
and
in vivo
. Moreover, these data highlight Gβγ as a novel therapeutic target for managing thrombotic disorders.
Abstract 13599: A Truncated Mutation in Filamin C Reveals Non-myocyte Contributions to Hypertrophic Cardiomyopathy in Ipsc-derived Cardiac Fibroblasts
Authors: Argenziano Mariana A , yang jiajia , Burgos Angulo Mariana , Bertalovitz Alexander , McDonald Thomas V
Published: May 2021

Introduction:
Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disorder that affects 1:500 individuals and represents one of the main causes of sudden cardiac death in young adults. Several mutations have been associated with HCM, including
MYH7
and
FLNC
. The discovery of induced pluripotent stem cells (IPSC), has provided a unique patient- and disease-specific model to study cardiac disease. Although iPSC derived cardiomyocytes (IPSC-CMs) can provide a genetically diverse human model to study mechanisms of disease, the heart relies in a three-dimensional network of cells that actively participate in the development of hypertrophy.

Hypothesis:
We hypothesize that mutations causing HCM affect not only CMs, but other non-myocyte cell types such as cardiac fibroblasts contributing to the phenotype of the disease.

Methods:
IPSCs were reprogrammed from an HCM patient harboring a pathogenic mutation on
FLNC
(p. Ile616Aspfs*4) using Sendai virus. Cells were differentiated to cardiomyocytes (IPSC-CMs) and cardiac fibroblasts (IPSC-CFs) and cultured for 30 days before analysis. Gene expression, morphology and wound healing (WH) were analyzed in IPSC-CMs and IPSC-CFs.

Results:
We observed that IPSC-CFs show higher expression of
FLNC
than IPSC-CMs (CT CM: 1.04±0.19 vs CT CF: 4.05±0.97, **p<0.01). Besides,
FLNC
mutated (MT) IPSC-CFs showed lower expression of
FLNC
when compared to controls (CT), with no changes in expression in IPSC-CMs. Expression of the fibrotic markers
POSTN
,
SMA
and
THY1
was higher in IPSC-CFs from MT. Immunostaining revealed changes in morphology in IPSC-CFs of MT with accumulation of FLNC in the nucleus. Treatment with TGF-b showed upregulation of
CCL2
,
SMA
,
POSTN
,
COL1A1
and
FLNC
in MT IPSC-CFs. Wound healing assay revealed no changes in cell migration between CT and MT, although TGF-b treatment increased WH % in MT (MT: 22.5±1.5% vs MT TGF: 59.4±6.5% at 8hs, **p<0.01).

Conclusions:
Based on our results, we conclude that CFs play an important role on the development of HCM; with higher changes in gene expression, cell migration and morphology than those observed in CMs. Further functional studies will provide evidence of the effects of these changes on the phenotype of the disease.
Abstract 13790: Area Deprivation Index and Cardiac Readmissions: Evaluating Risk-prediction in an Electronic Health Record
Authors: Johnson Amber E , Zhu Jianhui , Garrard William , Thoma Floyd W , Mulukutla Suresh R , Kershaw Kiarri N , Magnani Jared W
Published: May 2021

Introduction:
Social determinants of health (SDOH) affect cardiovascular outcomes. Our objective was to examine the association between neighborhood-level SDOH, and risk of readmission and mortality for atrial fibrillation (AF), heart failure, (HF) and myocardial ischemia (MI).

Hypothesis:
We hypothesized that neighborhood-level SDOH 1) is associated with readmission and death, 2) would significantly contribute to risk-prediction.

Methods:
We conducted a retrospective analysis from a regional health center to test the predictive ability of the area deprivation index (ADI) on 30-day and one-year readmission and mortality among patients admitted to hospital. Covariates included age, sex, race, comorbidity, number of medications, length of stay, and insurance. We used Cox proportional hazards and log rank analyses. To evaluate the discriminative power of the prediction models, we used the C-statistic and net reclassification methods after adding ADI into the model.

Results:
Our cohort of 31,633 adult patients followed was for 49.88 months (interquartile range 47.99). The cohort was 51.4% male and 90.6% white. Almost half (15,543, 49.1%) lived in neighborhoods in the two highest (worst) ADI quintiles. Patients living in areas with highest ADI were 28% less likely to be admitted within one year of index AF admission (HR=0.72, 95% CI [0.59, 0.87]). Patients in the highest ADI quintile were 30% more likely to be admitted within one year of index HF admission (HR=1.30, 95%CI [1.11, 1.52]). For MI, patients in the highest ADI quintile had a one-year risk for readmission that was twice that of those in the lowest quintile (HR=2.08, 95%CI [1.53, 2.81]). As ADI increased, risk of cardiac readmission and all-cause readmission increased at 30 days and one year. Reclassification of readmission risk was significantly improved when including ADI in the models. Patients in the highest ADI quintile were 46% more likely to die within 30 days when compared with those in the lowest quintile (HR=1.46, 95% CI [1.04, 2.06]) and 26% more likely to die within a year (HR=1.26 [1.10, 1.43]).

Conclusions:
Residence in disadvantaged communities predicts rehospitalization and mortality. ADI can be used to identify vulnerable cardiac patients after discharge.
Abstract 13815: Prognostic Impact of Sleep Disordered Breathing in Hospitalized Patients Following Acute Heart Failure
Authors: Ishiwata Sayaki , Kasai Takatoshi , Suda Shoko , Sato Akihiro , Mastumoto Hiroki , Shitara Jun , Yastu Shoichiro , Shimizu Megumi , Murata Azusa , Kato Takao , Hiki Masaru , Mastue Yuya , Naito Ryo , Daida Hiroyuki
Published: May 2021

Introduction:
Identifying hospitalized patients at a high risk for worse long-term clinical outcomes following acute heart failure (AHF) is important. However, limited data regarding influence of sleep-disordered breathing (SDB) and its treatment by positive airway pressure (PAP) on post-discharge clinical outcomes in hospitalized patients following AHF are available.

Hypothesis:
Presence of SDB may be associated with worse long-term clinical outcomes, which may be reversible by PAP therapy in patients with AHF. The aim of this study is to investigate relationship between SDB, its treatment by PAP and long-term clinical outcomes.

Methods:
After the initial improvement of AHF, overnight polysomnography was performed on consecutive hospitalized patients whose left ventricular (LV) ejection fraction ≤45% between May 2012 and April 2018. In the present study, SDB was defined as an apnea-hypopnea index ≥15. Patients with SDB were subdivided as those with or without PAP treatment. The incidence of deaths and re-hospitalizations due to exacerbation of heart failure until April 2019 were assessed by stepwise multivariable Cox proportional model.

Results:
Overall, 241 patients were enrolled. Among them, 73% had SDB and 29% were initiated into PAP. At a median follow-up of 1.7 years, 89 patients had clinical events (36.9%). In the stepwise multivariable analysis, SDB was associated with increased risk of clinical events (hazard ratio [HR], 2.20; P=0.007). Among SDB patients, stepwise multivariable analysis showed that PAP treatment was associated with reduced risk of clinical events (HR 0.45; P=0.022).

Conclusions:
In hospitalized patients following AHF, presence of SDB was associated with worse long-term clinical outcomes, which may be reversible by PAP therapy. Thus, following AHF, hospitalized patients with LV systolic dysfunction should be evaluated whether they have SDB and considered for SDB treatment before discharge.
Abstract 13873: Arterial Stiffness in Response to Eight Weeks of Exercise Training in African Americans versus Caucasians
Authors: Hwang Chueh-lung , Rader Melissa M , Thur Laurel A , Javier Jerome , Dambal Gaurav V , Severin Richard S , Drab Yuliya , Fernhall Bo , Phillips Shane A
Published: May 2021

Introduction:
Arterial stiffness predicts risks of cardiovascular disease in apparently healthy individuals. Exercise training decreases risks of cardiovascular disease, potentially via reductions in arterial stiffness. Compared with Caucasians, African Americans have higher risks of cardiovascular disease. However, lack of evidence supports the beneficial effects of arterial stiffness in African Americans. We hypothesize that arterial stiffness decreases in African Americans following eight weeks of exercise training and the effect is similar compared with Caucasians.

Methods:
A total of 13 African American and 10 Caucasian men and women, free of cardiovascular disease participated this study (age: 38±2 yrs; body mass index: 31.0±1.1 kg/m
2
; systolic blood pressures: 125±2 mmHg, diastolic blood pressure: 78±2 mmHg; mean±SE). Participants performed either aerobic exercise (65-85% of heart rate reserve) or resistance exercise (8-12 repetitions at 65-85% of 10-RM) for 30-45 minutes/time, three times/week for eight weeks. Arterial stiffness, assessed by carotid-to-femoral pulse wave velocity (cfPWV), and aortic blood pressure (BP) were measured by using the cuff-based SphygmoCor Xcel before and after the exercise training.

Results:
After the eight weeks of exercise training, cfPWV did not change in all participants, regardless of African Americans (6.7±0.3 vs. 6.5±0.3 m/sec; pre- vs. post-intervention) or Caucasians (6.3±0.4 vs. 6.0±0.3 m/sec; P=0.9 for raceхtime interaction, P=0.08 for time, and P=0.3 for race effect). Aortic systolic BP (African Americans: 123±5 vs. 120±3 mmHg and Caucasians: 111±2 vs. 110±3 mmHg; P=0.6 for raceхtime interaction, P=0.2 for time, and P=0.02 for race effect) and aortic diastolic BP (African Americans: 85±3 vs. 83±2 mmHg and Caucasians: 75±3 vs. 74±3 mmHg; P=0.6 for raceхtime interaction, P=0.5 for time, and P=0.01 for race effect) remained unchanged with the exercise training.

Conclusions:
An eight-week exercise training may not improve arterial stiffness in African Americans, and the effect appears to be similar in Caucasians.
Abstract 13889: The Influence of Depression on Dementia Risk in Patients With Atrial Fibrillation
Authors: Bunch T Jared , Bair Tami L , Knight Stacey , Steinberg Benjamin A , Anderson Jeffrey L , Muhlestein Joseph B , Knowlton Kirk U , Horne Benjamin , May Heidi T
Published: May 2021

Background:
Atrial Fibrillation (AF) is a significant risk factor for multiple forms of dementia. Although late-life depression may be a manifestation of dementia, earlier-life depression is a risk factor for dementia. The influence of earlier-life depression in patients with AF as a risk factor for dementia is unknown.

Methods:
AF patients (January 1, 1990-August 8, 2016) with no history of dementia and at least 3 years of follow-up derived from the Intermountain Healthcare Registry were included. Patients were compared by the presence or absence of depression at baseline. The primary endpoints were the development of dementia (total)imer’s disease.

Results:
Among 132,703 AF patients, 19,757 (14.9%) had a history of depression. Of these, 10,044 (50.8%) had SSRI use prior to AF diagnosis. The mean time from depression diagnosis to AF diagnosis was 5.0±4.8 years. AF patients with a history of depression were younger, more often female, and had higher rates of hypertension, diabetes, and heart failure. Patients with depression had a significantly higher multivariable-adjusted risk of dementia at 3 years (HR: 1.74 (1.59, 1.90), p<0.0001) and 5 years (HR: 1.73 (1.61, 1.86), p<0.0001), independent of the length of time between depression and AF diagnosis. Landmark analysis showed patients with depression and AF have much higher rates of dementia after 3 years (HR 1.51 (1.40, 1.63), p<0.0001) and after 5 years (HR 1.47 (1.34, 1.61), p<0.0001), Figure. These relative risks with depression are greater than composite risks of AF and dementia alone (HR 1.36) derived from multiple population-based studies.

Conclusions:
Patients with a history of depression prior to AF diagnosis have much higher rates of dementia after the onset of the arrhythmia. The presence of earlier-life depression should be recognized as an important risk factor for dementia in AF patients and may represent a therapeutic target to lower risk of cognitive decline.
Abstract 13895: Machine Learning-based Prediction Model With Contribute the Optimal Recipient Selection for the Regenerative Therapy in ICM and Non-ICM Patients
Authors: Sakashita Yuji , Asanoi Hidetsugu , Miyagawa Shigeru , Kainuma Satoshi , Kawamura Ai , Kashiyama Noriyuki , Kawamura Takuji , Yoshioka Daisuke , Ueno Takayoshi , Toda Koichi , Kuratani Toru , Sawa Yoshiki
Published: May 2021

Background:
Although transplantation of patch-shaped autologous skeletal muscle-derived cells has been introduced to ischemic cardiomyopathy (ICM) or non-ICM patients, we found responders or non-responders to this treatment exist and how to predict the responsiveness to this treatment is crucial for the improvement of the effectiveness. In this study, we revealed the clinical features associated with the responders using a machine learning based-model, which was discriminated between the responder and the non-responders in this treatment.

Methods and Results:
We used the retrospective databases of 23 ICM patients and 23 non-ICM patients undergoing autologous myoblast patch transplantation to develop machine learning models to discriminate 3-year VAD free survival. Sixty-nine pre-transplantation clinical futures were selected to train the models. In ICM models, there were 4 VADs or deaths, and in non-ICM models, there were 10 VADs or deaths during the 3-year follow-up periods. Using these databases, we trained multiple machine learning models and evaluated the models with the leave-one-out method. In ICM, k nearest neighbor demonstrated the best performance, showing the accuracy was 95.7%, and the AUC was 0.95. The features associated with 3-year VAD free survival in ICM were NYHA classification, cardiac index, and left ventricular ejection fraction. In non-ICM, k nearest neighbor demonstrated the best performance among the trained classifiers, demonstrating the accuracy was 95.7%, and the AUC was 0.93. The features associated with 3-year VAD free survival in non-ICM were pulmonary capillary wedge pressure, pulmonary vascular resistance, and albumin.

Conclusion:
We found the features associated with 3-year VAD free survival in autologous myoblast patch transplantation in ICM and non-ICM. Focusing on these features may facilitate optimal candidate selection in ICM and non-ICM for regenerative therapy.
Abstract 13908: Prevalence and Implications of Junctional Rhythm During Transcatheter Aortic Valve Replacement
Authors: Angsubhakorn Natthapon , Anderson Maria , Akdemir Baris , Bertog Stefan C , Garcia Santiago , Adabag Selcuk
Published: May 2021

Introduction:
Cardiac conduction abnormalities are among the most frequent complications of transcatheter aortic valve replacement (TAVR). A small case series has raised the possibility that junctional rhythm (JR) following TAVR may be associated with poor outcomes. However, the prevalence and implications of JR during TAVR have not been systematically studied.

Methods:
We retrospectively reviewed intra-procedural continuous 6-lead telemetry of 300 consecutive patients undergoing TAVR between April 2015 and April 2019 to identify JR that
occurred after deploying the valve
. Forty-two patients with pre-existing permanent pacemaker (PPM) were excluded. JR was defined as regular rhythm without P waves but with QRS morphology that was identical to baseline.

Results:
A total of 258 patients fulfilled the inclusion criteria (mean age of 77.5±8.5 years and 99% men). During TAVR, 79 (30.6%) patients developed new JR. The mean ventricular rate was 74.6±31.0 bpm. Patients who developed JR had similar baseline characteristics compared to those without JR (Table). After TAVR, 57 (22.1%) patients required PPM for complete atrioventricular block. There was a trend for a higher rate of PPM implantation in patients with rapid JR (39%) vs. slow JR (26%) vs. no JR (19.0%, p=0.10). In logistic regression analysis, patients who had a rapid JR (rate >100 bpm) were 2.71 times (95% CI 0.98-7.52, p=0.055) more likely to require PPM than those without JR.

Conclusions:
Junctional rhythm after deploying the valve is common in TAVR. There was a trend for higher PPM implantation risk among patients who developed rapid JR. Further investigation of these observations in larger cohorts is needed.
Abstract 13913: Single Dose Safety, Pharmacokinetics, and Pharmacodynamics of a Potent PCSK9 Synthesis Inhibitor, AZD8233, in Subjects With Elevated Ldl Cholesterol
Authors: Nilsson Catarina , Monia Brett P , Ryden-Bergsten Kristina , Rekic Dinko , Hurt-Camejo Eva , Bhanot Sanjay , Tsimikas Sotirios , Geary Richard , Hofherr Alexis , Crooke Rosanne M , knöchel jane , Wernevik Linda , Arfvidsson Cecilia , Isaksson Rikard , Carlsson Bjorn , Han David , henry scott
Published: May 2021

Background:
AZD8233 is a chemically modified 16-mer antisense oligonucleotide linked to N-acetyl galactosamine (GalNAc) for efficient targeting of PCSK9 mRNA in hepatocytes to prevent the synthesis of PCSK9. We are reporting preliminary data from the first in human study. The aim with the study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single doses of AZD8233 in subjects with LDL-C ≥100 mg/dL.

Methods:
This was a randomized, single-blind, placebo-controlled; single ascending dose study (NCT03593785) of AZD8233 administered subcutaneously (SC) to 56 subjects enrolled in 7 cohorts (6 on active and 2 on placebo in each cohort). Doses studied ranged from 4 to 120 mg. Serial blood samples were collected to assess PK, PCSK9 and LDL-C profiles after administration of AZD8233. PK parameters were calculated using non-compartmental methods.

Results:
After SC administration, AZD8233 was generally well tolerated, no clinically relevant safety and tolerability findings were observed and no serious adverse events were reported. Peak plasma concentrations were achieved within 1 to 3 hours after dosing. After peaking, plasma concentrations declined biphasically with a terminal half-life of 2 to 3 weeks. A dose dependent decrease in plasma levels of PCSK9 and LDL-C was observed. The largest mean percent reductions from baseline were >90 % for PCSK9 and 70% for LDL-C. PCSK9 and LDL-C levels slowly returned to baseline or close to baseline levels over the 16 weeks post dose follow up period.

Conclusions:
The safety, PK and PD support further evaluation of AZD8233 in multiple ascending dose studies. The PD data indicate that a high level of PCSK9 and LDL-C reduction can be maintained over a dose interval of once monthly or less frequent at a dose below 100mg.
Abstract 13917:
O
-GlcNAc Levels Are Regulated in a Time and Tissue Specific Manner Independently of Dietary Intake
Authors: DUPAS Thomas , DENIS Manon , Dontaine Justine , Persello Antoine , Bultot Laurent , Erraud Angelique , Vertommen Didier , Bouchard Bertrand , tessier Arnaud , Lebreton Jacques , Montnach Jérôme , De Waard Michel , Gauthier Chantal , Burelle Yan , Olson Aaron K , Rozec Bertrand R , Des Rosiers Christine , Bertrand Luc , Issad Tarik , Lauzier Benjamin
Published: May 2021

Background:
O
-GlcNAcylation (
O
-GlcNAc) is a post-translational modification involved in the stress response. A single pair of enzymes,
O
-GlcNAc transferase (OGT) and
O
-GlcNAcase (OGA) controls the
O
-GlcNAcylation. Due to the contribution of energy-linked metabolites (e.g. glucose, glutamine, etc.) to produce UDP-GlcNAc, the substrate used by OGT,
O
-GlcNAc is considered as a nutrient sensor. Metabolic sources vary from carbohydrates
in utero
, to fatty acids after birth then a mix once adult. Yet the link between diet composition and
O
-GlcNAc has never been explored.

Purpose:
Evaluate changes in
O
-GlcNAc levels and regulatory mechanisms throughout development.

Methods:
Organs were harvested from Wistar rats (n=6-8 for each group) before and after birth (D-1 and D0), in suckling animals (D12), after weaning with a standard (D28) or a carbohydrate free diet (D28F), and adult (D84).
O
-GlcNAc levels and regulatory enzymes were evaluated by Western blots. Mass spectrometry (MS) was performed to quantify known regulators of
O
-GlcNAc (n=6-8) and identify cardiac
O
-GlcNAcylated proteins at D0 and D28 (n=2).

Results:
O
-GlcNAc levels fell after birth in the heart, brain and liver (2.5, 1.5 and 1.3-fold, respectively). Interestingly, while
O
-GlcNAc levels decrease progressively from D0 to D84 (5.75-fold p<0.05) in the heart, the
O
-GlcNAc changes are opposite and of much smaller magnitude in liver and brain. Regulatory mechanisms appear to be in accordance in heart with a decrease in OGT (4.5-fold; p<0.05), an increase in OGA (125-fold; p<0.05) expression and decrease in UDP-GlcNAc (3-fold; p<0.05) over time. Yet changes in expression of OGT, OGA and UDP-GlcNAc do not follow
O
-GlcNAc levels in brain and liver.
O
-GlcNAc levels are unaffected by weaning diet in any tissues. MS analyses identified changes in cardiac levels of specific
O
-GlcNAcylated proteins, namely those involved in the energy metabolism, such as ACAT1, which is only
O
-GlcNAcylated at D0.

Conclusion:
We demonstrate that
O
-GlcNAc levels are not linked to dietary intake and are regulated in a time and tissue-specific manner during postnatal development. We have identified by MS proteins with a particular
O
-GlcNAc signature across the development process suggesting specific role for those proteins.
Abstract 13919: Race and Gender Specific High Sensitivity Troponin-t Cutoff Values Improve Detection in Patients’ With Ischemic Heart Disease
Authors: Kong Nathan , Chua Rhys , Besser Stephanie , Heelan Louise , Nathan Sandeep , Spiegel Thomas , van Wijk Xander , Tabit Corey E
Published: May 2021

Introduction:
Death rates from acute coronary syndrome events (ASCE) are 30% higher in African Americans than in Caucasians. A potential reason for this disparity is the underdiagnosis of ACSE due to race-specific differences in blood levels of cardiac troponin-T (cTnT), the biomarker of choice for the exclusion of myocardial injury.

Hypothesis:
Race- and gender-specific high-sensitivity cTnT (hs-cTnT) cutoff values will improve the detection of myocardial injury.

Methods:
Emergency Department encounters at the University of Chicago from June 2018 through April 2019 with at least 1 hs-cTnT value were included. Race- and gender-specific 99
th
percentiles for hs-cTnT were determined for patients without a history of hypertension, heart failure, coronary artery disease, diabetes, or chronic kidney disease, and used as the threshold for a positive result. These threshold values were compared against manufacturer’s recommended gender-only values (male ≥ 22 ng/dL, female ≥ 14 ng/dL). Confusion matrices were used to calculate test characteristics. The presence of ischemic heart disease was determined by the corresponding International Statistical Classification of Diseases.

Results:
Among 10,934 included encounters, 89.9% were African American. The 99
th
percentile values for African American were lower than for matched white counterparts. Race and gender specific cutoffs had higher specificity (83.1% vs 75.2%), greater positive predictive value (91.9% vs 90.7%), and lower false negative rates (16.9% vs. 24.8%) compared with traditional gender-only cutoff values. During the 10 months of data collection, race- and gender-specific cutoffs would have correctly identified 215 additional encounters as having ischemic heart disease, all of them African Americans. The net reclassification rate was +7.91%.

Conclusions:
Using race-specific, in addition to traditional gender-specific, hs-cTnT cutoff values resulted in higher specificity, greater positive predictive value, and lower false negative rates. Nearly 8% of patients with eventual diagnosis of ischemic heart disease would have been correctly reclassified using race- and gender-specific cutoffs. These findings suggest that race- and gender-specific cutoffs should be further explored.
Abstract 13935: Steroids Wean Failures After Heart Transplantation - Does It Lead to Mortality?
Authors: Skorka Rafael , Nishihara Keith , Shen Adriana , Patel Jignesh K , Chang David H , Kittleson Michelle M , Kransdorf Evan P , Czer Lawrence S , Kobashigawa Jon A
Published: May 2021

Introduction:
It is estimated that approximately 90% of heart transplant (HTx) patients who are low risk can be weaned off steroids after 6 months post-transplant. However, for those 10% who fail weaning subsequent outcome is not known. There is concern that failure to wean off steroids may lead to subsequent greater morbidity/mortality.

Methods:
Between 2010 and 2014, 178 HTx patients at low rejection risk were initiated to be weaned off steroids after 6 months post-transplant. Our protocol includes decreasing prednisone by 1mg per month from a baseline of 5mg daily. Monthly heart biopsy or use of Allomap are used to exclude rejection during weaning. 15 patients failed the corticosteroid wean due to either rejection (n=8), abnormal echocardiogram (n=2) or severe corticosteroid withdrawal symptoms (n=5). Study endpoints include subsequent 5-year survival, freedom from cardiac allograft vasculopathy (CAV) and non-fatal major adverse cardiac events (NF-MACE); and 1-year freedom from any treated rejection (ATR), antibody-mediated rejection (AMR), acute cellular rejection (ACR).

Results:
The failed wean group compared to the successful wean group had a trend for lower subsequent 5-year survival. There was no significant difference between the two groups in subsequent 5-year freedom from CAV or NF-MACE. Subsequent 1 Year freedom all rejection (ATR, ACR, AMR) were significantly lower in the failed steroid wean group compared to the successfully weaned group.

Conclusions:
HTx patients who are deemed low risk who failed corticosteroid weaning may be at risk to develop more rejection with compromised 5-year outcome, including a possible lower survival rate. It is unclear whether the act of corticosteroid weaning activated a deleterious response in these patients. Caution must be given to those patients who fail corticosteroid weaning.
Abstract 13937: QT Monitoring in Early Stage Asymptomatic/Paucisymptomatic Covid-19 Subjects on Hydroxychloroquine/Azithromycin Off-label Regimen -
Iwatch
ECG
Authors: Sabatini Antonella
Published: May 2021

Introduction:
Covid-19 has disrupted our quality of life worldwide. Among off-label therapeutic approaches for early stage non-hospitalized asymptomatic/paucisymptomatic COVID-19 subjects, the use of hydroxychloroquine (HCQ)/azithromycin (AZM) regimen is currently widely used in Italy. One concern is how to easily evaluate cardiac toxicity by monitoring ECG QT-interval at base and during follow-up.

Purpose:
The purpose of this work is to illustrate a validation method by comparing a 12-lead ECG and the simultaneous Apple iWatch Lead-I ECG function for QT monitoring.

Methods:
2 asymptomatic subjects underwent 2 ECGs: • The 12-lead and the Apple iWatch Lead-I ECGs were read and QT evaluated: • QT-segments were scanned and digitized by DigitizeIt (www.digitizeit.de, ver. 2.2.2) • Pearson correlation coefficient was calculated (12-lead ECG QT-segment and Apple iWatch Lead-I ECG function QT-segment). • Comparison of QT-segments and correlation coefficient of the QT-segments in the 12-ECG and the Apple iWatch Lead-I ECG function are in Table.

Results:
Table.

Conclusions:
Based on our data: 1. Pearson Correlation Coefficient (R) reflects the correlation of the QT-segments of the ECGs performed by the Apple iWatch Lead-I ECG function and the 12-Lead ECG in the male subject (R=0.8). 2. The coefficient R reflects poor correlation, hence indicating the 2-hours difference and different conditions in the female subject 2 ECGs (R= -0.03). 3. QT-segment evaluation obtained by the Apple iWatch Lead-I ECG function approaches the value of the QT-segment obtained by the 12-lead ECG machine. Hence, considering the emergency situation produced by COVID-19, and assuming still critically difficult situations in the various health systems globally, clinicians using off-label hydroxychloroquine/azithromycin regimen for asymptomatic/paucisymptomatic early stage COVID-19 subjects may find appropriate to monitor cardiac toxicity risks by Apple iWatch Lead-I ECG function.