bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonconserved Long Intergenic Noncoding RNAs Associate With Complex Cardiometabolic Disease Traits
Authors: Foulkes Andrea S. , Selvaggi Caitlin , Cao Tingyi , O’Reilly Marcella E. , Cynn Esther , Ma Puyang , Lumish Heidi , Xue Chenyi , Reilly Muredach P.
Published: November 2020

Objective:

Transcriptome profiling of human tissues has revealed thousands of long intergenic noncoding RNAs (lincRNAs) at loci identified through large-scale genome-wide studies for complex cardiometabolic traits. This raises the question of whether genetic variation at nonconserved lincRNAs has any systematic association with complex disease, and if so, how different this pattern is from conserved lincRNAs. We evaluated whether the associations between nonconserved lincRNAs and 8 complex cardiometabolic traits resemble or differ from the pattern of association for conserved lincRNAs.

Approach and Results:

Our investigation of over 7000 lincRNA annotations from GENCODE Release 33–GRCh38.p13 for complex trait genetic associations leveraged several large, established meta-analyses genome-wide association study summary data resources, including GIANT (Genetic Investigation of Anthropometric Traits), UK Biobank, GLGC (Global Lipids Genetics Consortium), Cardiogram (Coronary Artery Disease Genome Wide Replication and Meta-Analysis), and DIAGRAM (Diabetes Genetics Replication and Meta-Analysis)/DIAMANTE (Diabetes Meta-Analysis of Trans-Ethnic Association Studies). These analyses revealed that (1) nonconserved lincRNAs associate with a range of cardiometabolic traits at a rate that is generally consistent with conserved lincRNAs; (2) these findings persist across different definitions of conservation; and (3) overall across all cardiometabolic traits, approximately one-third of genome-wide association study–associated lincRNAs are nonconserved, and this increases to about two-thirds using a more stringent definition of conservation.

Conclusions:

These findings suggest that the traditional notion of conservation driving prioritization for functional and translational follow-up of complex cardiometabolic genomic discoveries may need to be revised in the context of the abundance of nonconserved long noncoding RNAs in the human genome and their apparent predilection to associate with complex cardiometabolic traits.
Abstract 12729: Impact of Chilli-pepper Intake on All-cause and Cardiovascular Mortality - A Systematic Review and Meta-analysis
Authors: Kaur Manpreet , Verma Beni R , Zhou Leon , Kaur Simrat , Sammour Yasser , Lak Hassan Mehmood , Xu Bo
Published: November 2020

Background:
Chilli-pepper (CP) is well known for its anti-inflammatory, antioxidant, anticancer, and blood glucose regulation effects. However, the impact of CP on all-cause and cardiovascular mortality is not clear.

Methods:
A comprehensive search was performed using Ovid, Cochrane, Medline, Embase, and Scopus. We screened the studies from inception till January 16, 2020, and reported the outcomes of our interest after consumption of CP (Figure1a). The inclusion criteria were: all observational and randomized controlled trials reporting the outcomes of interest, and pediatric, animal studies, letters/case reports, reviews, abstracts, and book chapters were excluded. All-cause mortality was studied as the primary endpoint. Cardiovascular, cerebrovascular, and cancer-related deaths were studied as secondary outcomes.

Results:
From 4729 studies screened, four studies including 570,762 subjects met the inclusion criteria. Random-effects pooled analysis showed that there was a 25% reduction in the relative risk of all-cause mortality for regular CP consumers, compared to non-consumers (relative risk (RR): 0.75; 95% confidence intervals (CI): 0.64-0.88, p = 0.0004, Figure1b). Furthermore, there were a 26% and 23% reduction in the RR of death due to cardiovascular causes (RR: 0.74; 95% CI: 0.62-0.88, p=0.0006, Figure1c) and cancer (RR: 0.77; 95% CI: 0.71-0.84, p=0.0001, Figure 1d), respectively. However, there were no statistically significant differences in cerebrovascular accidents (RR: 0.76; 95% CI: 0.36-1.60, p=0.47).

Conclusion:
In a contemporary meta-analysis of 570,762 subjects, regular CP consumption was associated with a significant reduction in all-cause, cardiovascular, and cancer-related mortalities. Future studies are needed to better understand the potential mechanisms of the mortality benefits of CP consumption.
Abstract 12787: Meta-analysis of Dual Antiplatelet Theraphyversus Single Antiplatelet Theraphyafter Transcatheter Aortic Valve Implatation: A Popular Forecast
Authors: Costa GonÃ§alo , Gonçalves Lino , teixeira rogerio P
Published: November 2020

Background:
Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and affect survival. Recent guidelines recommend dual antiplatelet therapy (DAPT) in the initial period after TAVI. Explorative studies have suggested DAPT is associated with higher rate of major bleeding without a decrease in thromboembolic complications.

Purpose:
To compare DAPT (aspirin plus clopidogrel) versus single antiplatelet therapy (SAPT) (as aspirin) alone as antithrombotic treatment following TAVI for the prevention of cerebrovascular events, bleeding events and all-cause death.

Methods:
We systematically searched PubMed, Embase and Cochrane databases, in April 2020, for both interventional or observational studies comparing DAPT with (SAPT) following TAVI. Random-effects and meta-analysis for DAPT and SAPT were performed.

Results:
Nine studies were included (six registry-based or unrandomized studies and three randomized clinical trials) providing a total of 19389 patients, and 631 pooled stroke or transient ischemic attack. There was no statistically difference between DAPT and SAPT for the prevention of cerebrovascular events after TAVI (pooled OR 1.04 [0.85, 1.26], P=0.04, I
2
= 0%). Similarly, there was a similar rate of all-cause mortality (pooled OR 1.07 [0.81, 1.42], P=0.33, I
2
= 50%). Furthermore, the rate of major bleeding or life-threatening events was significantly higher for the DAPT compared with SAPT group (pooled OR 1.46 [1.19, 1.78], P<0.01, I
2
= 79%), although with a considerable amount of heterogeneity between studies in the magnitude of effect.

Conclusions:
Our pooled data suggests that after TAVI, the clinical benefit of DAPT compared to SAPT is questionable. The POPular-TAVI trial Cohort A is expected to clarify this research question during 2020.
Abstract 12818: Identifying Drivers of Hospital Readmission Through Analysis of Discrepant Predicted and Observed Readmission Status
Authors: Kratka Allison , Dalto Jodi , Beloff Jennifer , Salmasian Hojjat , Britton Kathryn
Published: November 2020

Introduction:
The Hospital Readmissions Reduction Program (HRRP) lowers Medicare payments to hospitals with excess readmissions for certain conditions. We analyzed FY2020 HRRP data for Brigham and Women’s Hospital (July 2015 to June 2018). We conducted an analysis to identify patients with a discrepant expected vs observed readmission status for AMI, HF and CABG, followed by a chart review to explain this discrepancy.

Methods:
We calculated the risk of readmission for each patient, which was a summed value of the weights associated with all recorded comorbidities in the CMS data. A negative risk score indicated a patient was unlikely to be readmitted and a positive score indicated the opposite. We then performed a chart review focused on patients who had a high risk of readmission but were not readmitted, and those who had a low risk of readmission but were readmitted.

Results:
For AMI, 18% (108/596) of patients were readmitted within 30 days, CABG 14% (50/357) of patients, and HF 27% (367/1382) of patients. For AMI, risk of readmission scores ranged from 2.75 to -0.095. 5/596 patients had a negative score, and none were readmitted. For CABG, scores ranged from 2.64 to -0.31, 58/357 people had a negative score, and 6 were readmitted. For HF, scores ranged from 1.94 to 0.055. There were no negative scores, but of the lowest 20/1382 scores, 2 were readmitted. We then performed a chart review of 37 patients whose readmission status was discordant with their risk score, and examined why this occurred. For patients who were low risk but were readmitted across all three conditions, 30% (range 10% - 54%) did not have a follow up appointment scheduled before discharge, 11% (range 0% - 29%) did not have an advanced care plan and 95% (range 86% - 100%) had not had a SIC. Patients who were high risk but not readmitted were evaluated but did not have any notable characteristics. We did not find any evidence of under-coding of risk comorbidities that would have led to falsely low risk scores.

Conclusions:
Patients with more comorbidities were more likely to get readmitted, and we found these risk factors to be accurately recorded. Clinical care insights from this project include the need for more SICs and palliative care consults and a more targeted effort to ensure patients have appropriate follow-up.
Abstract 12869: Association of Statin Therapy and Progression of Arterial Stiffness in the Multi-ethnic Study of Atherosclerosis
Authors: Nechyporenko Anatoliy , Tedla Yacob G , Korcarz Claudia E , Tattersall Matthew C , Greenland Philip , Gepner Adam D
Published: November 2020

Background:
Statin therapy may alter arterial stiffness by decreasing the low density lipoprotein cholesterol (LDL-C) content within blood vessel walls and reducing inflammation. Progression of arterial stiffness with prolonged statin treatment is not clear.

Methods:
The subset of MESA participants (n=1,225) with comprehensive data on statin use who underwent B-mode carotid ultrasound at baseline (visit 1) and after (mean ± SD) 9.3±0.7 years (visit 5) was analyzed. Arterial stiffness was measured using carotid distensibility coefficient (DC) and Young’s elastic modulus (YEM) at MESA exam 1 and 5. Linear regression models evaluated associations of ten-year change in DC and YEM with statin treatment duration and intensity during visits 1-4. Models were adjusted for age, sex, ethnicity, systolic blood pressure (SBP), diabetes status, alcohol use, smoking, and lipid profiles.

Results:
At baseline, participants were 66.5±8.1 years of age, 41% female, 36% Caucasian, 30% African American, 13.7% Asian American, and 20.0% Hispanic, with LDL-C of 149.5±14.5 mg/dL; DC was 2.88×10-3±1.28×10-3 mmHg-1, YEM was 1659±1056 mmHg. Participants not on statin therapy at any visit had greater baseline arterial stiffness measures compared to participants who were treated at all visits (YEM: 1,724 ±993 mmHg vs 1,457 ±776 mmHg; p=0.0003; DC: 2.72 ±1.22×10-3 mmHg-1 vs 3.22 ±1.33×10-3 mmHg-1; p<0.0001). In unadjusted models, neither duration nor intensity of statin therapy was associated with changes in arterial stiffness measures over 10 years. Fully adjusted multivariable linear regression models showed associations with age and SBP but demonstrated no significant associations between DC and YEM and treatment duration or any statin intensity (table).

Conclusions:
Statin therapy was not associated with progression of carotid artery distensibility and elasticity over nearly a decade of follow up regardless of treatment duration or dose intensity.
Abstract 12872: Machine Learning on Dual-isotope Myocardial Semiconductor SPECT Can Predict Cardiac Prognosis in Patients With Congestive Heart Failure
Authors: Shimizu Masato , cho shummo , Misu Yoshiki , Ohmori Mari , Tateishi Ryo , Kaneda Toshio , Yamakami Yosuke , Shimada Hiroshi , Manno Tomoko , Isshiki Ami , Kimura Shigeki , Fujii Hiroyuki , Suzuki Makoto , Nishizaki Mitsuhiro , Sasano Tetsuo
Published: November 2020

Introduction:
Dual-isotope (201TlCl and 123I-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) ) single photon emission computed tomography (SPECT) is utilized to estimate not only in patients with ischemic heart disease but with congestive heart failure (CHF). We tried to construct predictive model for cardiac prognosis on the SPECT for cardiac death by machine learning.

Hypothesis:
Machine learning is a powerful tool to predict cardiac prognosis in patients with CHF

Methods:
Consecutive 310 patients who admitted with CHF (77.1±3.1 years, 164 males) were enrolled. After initial treatment, they underwent electrocardiography gated SPECT and observed in median 507 days [IQR: 165, 1032]. Multivariate Cox regression analysis for cardiac death was performed, and predictive model was constructed by ROC curve analysis and machine learning (Random Forest and Deep Learning). The accuracies (= [True positive + True negative] / Total) of the prediction models were compared with ROC curve model.

Results:
Thirty-six patients fell into cardiac death. Cox analysis showed Age, left ventricular ejection fraction (LVEF), summed rest score (SRS) of BMIPP, and mismatch score were significant predictors (Hazard ratio: 1.068, 0.970, 1.032, 1.092, P value: <0.001, 0.014, 0.002, <0.001, respectively). ROC curve analysis of them revealed the accuracy of the cut-off value was 0.479-0.773. Conversely, machine learning model demonstrated higher accuracy for cardiac death (Random Forest: 0.895, Deep Learning: 0.935). The top 4 feature importance of the random forest were LVEF (0.299), SRS BMIPP (0.263), Age (0.262), and mismatch score (0.160).

Conclusions:
Machine learning model on SPECT had powerful predictive value for predicting cardiac death in patients with CHF.
Abstract 12874: Thebesian Veins Are Common and Progress in Adult Patients Late After Fontan Operation
Authors: Tanaka Toshikatsu , Miki Yasunobu , Ogawa Yasuharu , Kido Sachiko
Published: November 2020

Introduction:
Thebesian veins (ThVs) are coronary veins that drain directly into the atrial or ventricular chamber. Angiographically detectable ThVs are a rare finding sometimes associated with myocardial ischemia due to coronary steal and volume overload of ventricles in adults. However, there are limited data concerning ThVs in the setting of congenital heart disease. The purpose of this study is to demonstrate presence, character, and changes with growth of ThVs in adult patients late after Fontan operation.

Methods:
This study is single-center retrospective review of adults with Fontan circulation patients who had undergone cardiac catheterization for routine Fontan surveillance between 2009-2019. We assessed the presence of angiographically detectable ThVs from ascending aortography. After identification of the characteristic cases, we examined the ventricular morphology, the portion of ThVs drainage, and compared with previous findings of angiograms. We also reviewed clinical manifestation and findings of exercise stress ECG of the patients. Pulmonary atresia with intact ventricular septum was excluded because abnormal coronary arterial communications have been well documented in this condition.

Results:
Among 75 Fontan patients who had undergone catheterization, significant ThVs were observed in a total of 12 cases (16%). There were 6 right-dominant single ventricle, 4 left-dominant single ventricle, and 2 unbalanced two ventricles. In all cases, including left-dominant single ventricle, all ThVs drained into right ventricle cavity, never into left ventricle. The patients who underwent serial catheterizations demonstrated that ThVs dilation and tortuosity progressed over time. Among 6 patients who had underwent exercise stress ECG, only 1 patient showed ST segment depression, however, none had clinical history of chest pain.

Conclusions:
ThVs are common and progress in adult patients late after Fontan operation. Although the clinical significance of these findings remains uncertain, particular attention should be given to myocardial ischemia and volume overload for the future of adult Fontan patients who have prominent ThVs.
Abstract 12889: Clathrin-mediated Endocytosis Plays a Key Role in Stem Cell Therapy for Ischemic Heart Disease
Authors: Eguchi Shunsuke , Takefuji Mikito , Murohara Toyoaki
Published: November 2020

Background and Aim:
Cell therapy represents a potential frontier to transform the treatment and prognosis of heart failure and acute myocardial infarction (AMI). Extracellular vesicles (EVs) have come out as key mediators of intercellular communication to improve cardiac function in cell therapy. However, the mechanisms by which cardiomyocytes respond to EVs remain unclear. Here, we sought to clarify the effect of cardiomyocyte endocytosis on AMI.

Methods and Results:
Treatment with the culture supernatant of adipose-derived regenerative cells (ADRCs) prevented cardiomyocyte cell damage under conditions of hypoxia in vitro. In vivo, the injection of ADRCs in the heart simultaneous with coronary artery ligation decreased infarct area in the heart in a dose-dependent manner. In addition, the injection of ADRCs prevented cardiac rupture after AMI and significantly reduced apoptosis in cardiomyocytes at 1 and 2 days. To examine the efficacy of cardiomyocyte endocytosis, cardiomyocytes were cultured with EVs previously isolated from ADRC culture supernatant and labeled with the fluorescent dye, PKH67. Notably, hypoxic culture conditions increased the intensity of the labeled EVs in cardiomyocytes. An inhibitor of clathrin-mediated endocytosis (chlorpromazine), but not inhibitors of caveolae-mediated endocytosis, micropinocytosis, and phagocytosis (genistein, cytochalasin D, or amiloride), significantly suppressed the ADRC culture supernatant-induced decreases of hypoxia-damaged cardiomyocytes. Chlorpromazine treatment also decreased hypoxia-induced cardiomyocyte capture of labeled EVs secreted from ADRCs. To investigate whether communication between cardiomyocytes and ADRCs affords cardiac protection through clathrin-mediated endocytosis in vivo, mice were treated with ADRCs alone or in combination with chlorpromazine following coronary artery ligation. Chlorpromazine treatment failed to show ADRC-induced cardiac protection such as prevention of cardiac rupture and anti-apoptotic effect.

Conclusions:
Our results indicate that EVs secreted from ADRCs prevent cardiac rupture after AMI and that clathrin-mediated endocytosis plays a critical role in transporting the EVs into cardiomyocytes.
Abstract 12895: Tissue Sodium Content Increases With Severity of Chronic Heart Failure
Authors: Kolwelter Julie , Nagel Armin , Kannenkeril Dennis , Bosch Agnes , Striepe Kristina , Linz Peter R , Ott Christian , Bramlage Peter , Uder Michael , Achenbach Stephan , Schmieder Roland E
Published: November 2020

Introduction:
Heart failure is strongly linked to renal sodium and water retention as well as intravascular and interstitial fluid shifts. Experimental studies demonstrated a non-osmotic sodium storage, bound to proteoglycans, in the extravascular space. New sodium magnetic resonance imaging (
23
Na-MRI) enables us to quantify tissue (muscle and skin) sodium content in a reliable and accurate way.

Hypothesis:
We hypothesised that the increase of tissue sodium content is dependent on the severity of chronic heart failure (CHF).

Methods:
We investigated patients with stable CHF before initiating treatment with an SGLT2-inhibitor within a prospective, placebo-controlled study. We here report the baseline data of 64 patients with CHF, defined as patients with reduced (HFrEF) or mid-range ejection fraction (HFmEF). In each patient, tissue sodium content of the lower leg was assessed non-invasively by a clinical 3.0T
23
Na-MRI. The median NT-proBNP plasma level at baseline was 493.3pg/ml (IQR: 225.8-1122.0pg/ml) and was used as cut off value of CHF severity.

Results:
Our patients (men: n=54) were 66.9±8.9 years old and had NYHA class II-III; mean muscle sodium content was 19.1±3.8mmol/l and mean skin sodium content was 22.5±5.9mmol/l. Our reference for young healthy subjects are 18.7±2.0 mmol/l for muscle sodium content and 19.6±3.1 mmol/l for skin sodium content. Patients with CHF and NT-proBNP levels above the median showed higher muscle (20.2±3.5 vs 17.9±3.7mmol/l, p=0.008) and skin sodium content (24.1±6.8 vs 20.8±4.4mmol/l, p=0.005) than patients with CHF and NT-proBNP levels below the median. No difference in plasma sodium levels between the two groups (138.0±3.7 vs 138.8±2.1mmol/l, p=0.527) was observed, but patients with NT-proBNP levels above the median had lower urinary sodium excretion over 24 hours (167.0±78.8 vs 172.3±63.4mmol/l, p=0.009). Age was different in the two groups (69.88±8.2 vs 63.8±8.7, p<0.001) with no difference in gender. The number of diagnosed coronary heart disease was similar in the two groups (62.5% vs 59.4%, p=0.802).

Conclusion:
Concluding, tissue sodium content in patients with stable CHF as assessed by
23
Na-MRI increases with the severity of CHF. A decrease of tissue sodium content might be a future therapeutic goal.
Abstract 13231: Fibromuscular Dysplasia Screening in Patients With Spontaneous Coronary Artery Dissection
Authors: Thompson Elizabeth W , Fitzsimmons Elliot , Cook Tessa , Lewey Jennifer
Published: November 2020

Introduction:
Spontaneous coronary artery dissection (SCAD) is commonly associated with fibromuscular dysplasia (FMD), a vascular condition that can lead to aneurysm and dissection in any arterial bed. SCAD and FMD are increasingly being diagnosed, especially in women. Our objective is to describe screening patterns of FMD over time among patients with SCAD.

Methods:
We conducted a retrospective cohort study, identifying patients treated for SCAD in the University of Pennsylvania Health System from 2005-2019 using ICD-9 (414.12) and ICD-10 (I25.42) codes. Charts were manually reviewed and clinical data were abstracted. Screening modalities included CT angiogram (CTA) or MR angiogram (MRA) of the head, neck, or abdomen; carotid or renovascular ultrasound; or renal angiography. Complete screening was defined as having head, neck, and abdominal imaging. We indexed cases by date of SCAD event. Time categories were calculated by quartiles of patients. We used Fisher’s exact test to compare proportions and Cochran-Armitage trend test to compare trends over time.

Results:
We identified 121 patients with SCAD with ≥ 6 months of follow-up prior to the COVID-19 pandemic. FMD screening rates by any modality were higher among patients with SCAD in 2018-2019 compared to 1993-2011 (62% vs. 28%, p=0.009 for trend), see Figure. Rates of complete screening remained low and did not change over time (p=0.451 for trend). In 2018-2019, only 41% of patients were screened with CTA or MRA of the abdomen, 26% with CTA or MRA of the neck, and 15% with CTA or MRA of the head. Patients undergoing complete screening had higher rates of FMD diagnosis compared to those undergoing any screening (63% vs. 37%, p=0.036).

Conclusions:
While overall FMD screening in SCAD patients has increased, complete screening rates remain low. FMD was diagnosed more often in patients undergoing complete screening, highlighting the importance of head, neck, and abdominal imaging in all patients with SCAD.
Abstract 13289: Incidence of Heart Failure Hospital Admissions Among Type 2 Diabetes Mellitus Patients and the Potential Impact of SGLT2 Inhibitors in Japan: A Population-based Study From the Shizuoka Kokuho Database
Authors: Nishimura Shiori , Kumamaru Hiraku , Kohsaka Shun , Shoji Satoshi , Nakatani Eiji , Yamamoto Hiroyuki , Ichihara Nao , Miyachi Yoshiki , Miyata Hiroaki
Published: November 2020

Introduction:
Recent large-scale clinical trials have shown that the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduces the risk of cardiovascular (CV) events, particularly heart failure (HF) hospitalizations, in type 2 diabetes mellitus (T2DM) patients with established CV disease. We aimed to assess (1) the incidence of HF admissions, and (2) the potential reduction in HF admissions with the further introduction of SGLT2i, in a contemporary large administrative claims database in Japan.

Methods:
We selected patients aged ≥40 years, without previous HF diagnosis, who newly initiated oral antidiabetics in Shizuoka Kokuho Database between 2013 and 2018. We estimated the 5-year cumulative incidence of hospitalization for HF, myocardial infarction (MI), and stroke, treating death as a competing risk. Among the subgroup of patients with laboratory data, we identified patients meeting the inclusion criteria for EMPA-REG OUTCOME (EMPA-REG) or DECLARE-TIMI 58 (DECLARE) regarding HbA1c, eGFR, and CV disease. We estimated the number of events that can be reduced if they benefited the same risk reduction from the trials.

Results:
Among 23,340 oral antidiabetic drug initiators (46.0% women, 21.9% ≥75 years old) included, 2.6% were initiated on SGLT2i. The 5-year cumulative incidences of hospitalization for HF, MI, and stroke were 5.4% (95% confidence interval: 4.9-5.9%), 1.9% (1.7-2.2%), and 6.1% (5.7-6.6%), respectively. Among 6192 patients with laboratory data, 651 (10.5%) and 2680 (43.3%) patients met the EMPA-REG-like and DECLARE-like criteria, respectively (Figure). The 5-year cumulative incidence among the 2849 patients meeting either of the criteria was estimated to decrease from 97.1 to 75.2 events via 75% adoption of SGLT2i.

Conclusion:
The burden of HF among Japanese T2DM patients was high, almost equivalent to stroke. Increased use of SGLT2i among patients with high CV risk may significantly reduce its disease burden.
Abstract 13603: Utility of the 6-minute Walk Test in Coronary Artery Disease Screening Before Kidney Transplant
Authors: Cheng Xingxing , Watford Daniel J , Arashi Hiroyuki , Tan Jane C , Fearon William F
Published: November 2020

Introduction:
Coronary artery disease (CAD) screening is a cornerstone of kidney transplant (KTx) evaluation, but existing approaches result in excess testing and low intervention rate.

Hypothesis:
We hypothesize that aerobic performance, based on a simple office test (the 6-minute walk test, 6MWT), may help risk stratify KTx candidates.

Methods:
We performed 6MWT in waitlisted patients who were nearing KTx. Results were used for frailty counselling and not for cardiac evaluation. CAD screening was done according to our center protocol: invasive angiogram for patients with long-standing diabetes mellitus (DM) and non-invasive testing for other patients with risk factors and at the evaluating transplant nephrologist’s discretion. We used subdistribution Cox regression and time-dependent receiver operator curve to evaluate time to CAD event (revascularization, myocardial infarction, waitlist removal for CAD, or cardiac death), treating waitlist removal for non-CAD and non-cardiac death as competing events.

Results:
Of the 360 patients, 200 and 161 patients had 6MWT results <400 meters and ≥400 meters (~4 metabolic equivalents), respectively. Patients with lower 6MWT results were older (59±10 vs 50±12 years) and more likely to be female (54% vs 34%), have DM (61% vs 33%) or known atherosclerotic disease (44% vs 22%), and have had prior cardiac evaluation (72% vs 61%). They were also more likely to exhibit cardiac symptom during 6MWT (36% vs 6%) and more likely to be censored due to waitlist removal for non-CAD reasons (follow-up 391±337 vs 541±277 days). 6MWT was not associated with CAD event (subdistribution hazard ratio 1.00 [0.90-1.10], 1-year area under the curve [AUC] 0.54). 196 patients had invasive (52%) or non-invasive (48%) CAD testing within 6 months of 6MWT: 6MWT did not predict the CAD test result (odds ratio 0.96 [0.81-1.14], AUC 0.54). Of the 94 patients who had concurrent non-invasive CAD testing, the 1-year AUC of 6MWT, symptom (at rest or during 6MWT), AST guidelines, or non-invasive testing for CAD event were 0.64, 0.52, 0.46 and 0.66 respectively.

Conclusions:
The 6MWT did not perform better in risk stratification for CAD events compared to a symptom- or risk factor-based approach.
Abstract 13621: Predictors of Short-term and Long-term Clinical Outcomes After an Acute Atrial Fibrillation or Flutter Admission
Authors: Ne Jia Yi Anna , Nguyen Tu , Thomas Stuart , Han Joanne , Charlston Emma , Chow Clara K
Published: November 2020

Introduction:
Atrial fibrillation (AF) is a major cause of mortality and morbidity globally. This study aims to identify predictors of AF-related rehospitalization following an acute AF/flutter admission.

Methods:
Patients admitted to Westmead Hospital with a primary diagnosis of AF/flutter from 1 May 2014 to 31 May 2018 were included and followed up until 31 May 2019. We defined AF-related rehospitalization as an admission due to recurrent AF/flutter, congestive heart failure, stroke and/or myocardial infarction. Multivariable logistic regression was used to identify independent predictors of 30-day outcomes. Cox regression was used to identify independent predictors of long-term outcomes: first AF-related rehospitalization or all-cause mortality.

Results:
Of 1664 consecutive patients admitted with AF/flutter, 55.8% were male and the median age was 68.0. At 30 days, 123 (7.4%) had an AF-related readmission (110 for AF/flutter and 13 for other cardiovascular outcomes). During a mean follow-up period of 2.1 ± 1.5 years, 683 (41.0%) of patients had at least one AF-related rehospitalization (38.1%, n=634) or died (2.9%, n=49). Chronic kidney disease (CKD) (OR 1.94, 95% CI 1.07 - 3.50) was an independent predictor of 30-day AF-related rehospitalization. Age (HR 1.01, 95% CI 1.01 - 1.02 for each additional year), initial admission via emergency (HR 1.29, 95% CI 1.08 - 1.54), CKD (HR 1.64, 95% CI 1.24 - 2.18), chronic obstructive pulmonary disease (HR 1.42, 95% CI 1.09 - 1.83) and the presence of additional comorbidities (HR 1.38, 95% CI 1.04 - 1.83) were independent predictors of first AF-related rehospitalization or death (all p <0.05).

Conclusion:
AF-related rehospitalization is common following an acute AF/flutter admission. AF/flutter patients with comorbidities, particularly renal and pulmonary diseases, are at high risk of readmission. Such patients could be targeted for increased surveillance and additional post-discharge support to prevent readmission.
Abstract 13633: Predictors of Mental and Physical Health Outcomes of Patients Undergoing an Appointment-based Cardiac Rehabilitation Program
Authors: Xie Catherine , Fournier Sean , Hiller Susan , Oen Hsiao Joyce , Dreyer Rachel P
Published: November 2020

Introduction:
Cardiac rehabilitation (CR) is an evidence-based program to improve secondary prevention outcomes for patients with cardiovascular disease (CVD). Lower health-related quality of life is a known risk factor for worse CVD outcomes. We examined the effects of a patient-driven appointment-based CR program on health-related quality of life.

Methods:
We utilized data from the Yale New-Haven Health (YNHH) CR program over a 6-year period (2012-2017). Data was collected on patient demographics, clinical characteristics and socioeconomic status. The Medical Outcome Short-Form General Health Survey (SF-36) was used to measure general health status. We evaluated SF-36 score changes pre and post CR with paired T-tests and conducted logistic regression analysis to examine predictors of improvements in health-related quality of life.

Results:
Over the 6-year study period, a total of 2,135 patients (27.9% women, mean age 65±12 years) were enrolled in the CR program. Patients demonstrated significant improvements in both the SF-36 physical, mental and health transition components (P<0.001)
(Table)
. In particular, patients had significant improvement in the social functioning domain (measures limitations patients see in their ability to participate in social activities due to physical/emotional issues), with an increase of 23.3 points out of 100. Physician-reported patient stress and/or depression on intake medical exam were significant negative predictors for improvement in the total SF-36 score (OR 0.23, 95% CI 0.08-0.80, P=0.021), with the effect driven largely by its impact on the physical component of SF-36 (OR 0.27, 95% CI 0.09-0.83, P=0.022).

Conclusion:
We demonstrated that a novel appointment-based CR program produced improvements in patient-reported health-related quality of life. Appointment-based CR could be a viable alternative for patients who prefer more scheduling flexibility, to optimize health status improvement and CVD outcomes.
Abstract 13648: Sex Differences in Modifiable Risk Factors and Severity of Coronary Artery Disease
Authors: Cenko Edina , MANFRINI Olivia , Yoon Jinsung , van der Schaar Mihaela , Kedev Sasko , vavlukis Marija , Stankovic Goran , Milicic Davor , Vasiljevic Zorana , Badimon Lina , Bugiardini Raffaele
Published: November 2020

Introduction:
It is still unknown whether traditional risk factors may have a sex specific impact on coronary artery disease (CAD) burden.

Hypothesis:
We sought to investigate at individual level whether there are sex differences in the four modifiable traditional cardiovascular risk factors and how these differences may impact the CAD and outcomes in ACS.

Methods:
We identified 14,793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC registry (NCT01218776) from 2010 to 2019. Main outcome measure was the association between traditional risk factors and severity of CAD and its relationship with 30-day mortality. The relative risk (RR) ratios and 95% CI were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Estimates were compared by test of interaction on the log scale. Severity of CAD was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD.

Results:
The RR ratios for obstructive CAD in women versus men among nondiabetic people was 0.49 (95%CI 0.41-0.60) and diabetic people was 0.89 (95%CI 0.62-1.29); interaction by diabetes status: p=0.018. Exposure to smoking shifted the RR ratios from 0.50 (95%CI 0.4 -0.61) in nonsmokers to 0.75 (95%CI 0.54-1.03) in current smokers; interaction by smoking status: p=0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR 1.75, 95%CI 1.48-2.07). No sex differences in mortality were observed in patients with nonobstructive CAD.

Conclusions:
Obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still require intensive efforts toward further implementation of lifestyle and treatment interventions.
Abstract 13669: Slow Conduction Zone of Left Atrium is a Precursor to Low Voltage Area in Patients With Atrial Fibrillation
Authors: Kishima Hideyuki , Mine Takanao , Kitagaki Ryo , Fukuhara Eiji , Ishihara Masaharu
Published: November 2020

Introduction:
The slow conduction zone (SCZ) in the left atrium (LA) has attracted attention as an arrhythmia substrate of atrial fibrillation (AF). However, the occurrence mechanism of SCZ remains unclear.

Hypothesis:
The SCZ is related to the low voltage area (LVA) or the LA anatomical contact areas (CoAs) with other organs in patients with AF.

Methods:
We studied 100 patients (49 non-paroxysmal AF, 66 males, 67.9 ± 9.9 years) who received catheter ablation for AF. High-density LA mapping during right atrial appendage pacing at a rate of 100 bpm after pulmonary vein isolation were constructed. Isochronal activation maps were created at 5-ms interval setting, and the SCZ was identified on the activation map by finding a site with isochronal crowding of ≥3 isochrones, which are calculated as ≤27 cm/s (Figure). The LVA was defined as the following; mild (<1.3 mV), moderate (<1.0 mV), and severe LVA (<0.5 mV). The CoAs (ascending aorta-anterior LA, descending aorta-posterior LA, and vertebrae-posterior LA) were assessed using computed tomography.

Results:
The SCZ was distributed linearly (Figure), and observed in 95 of 100 patients (95%). The SCZ was most frequently observed in the anterior wall region (77%). A longer SCZ was significantly associated with a larger LA size and a prevalence of non-PAF. The 51.2±36.2% of SCZ overlapped with mild LVA, 32.9±32.8% of SCZ with moderate LVA, and 14.6±22.0% of SCZ with severe LVA. In contrast, only 25.6±28.0 % of SCZ matched with the CoAs.

Conclusion:
The slow conduction zone reflects LA electrical remodeling and may be a precursor finding of the low voltage zone, not LA contact areas in patients with atrial fibrillation.
Abstract 13680: Icosapent Ethyl Therapy for Patients With an Established Cardiovascular Disease Provides Significantly More Value for Money Than When Prescribed as Primary Prevention
Authors: Arbel Ronen , Aboalhasan Enis , Hammerman Ariel , Azuri Joseph
Published: November 2020

Introduction:
Icosapent ethyl is currently the only drug approved for the prevention of major adverse cardiovascular events (MACE) in patients with hypertriglyceridemia, who are already on statin therapy. The approved use is both for secondary prevention in patients with established cardiovascular disease (CVD) or primary prevention for patients with diabetes and multiple risk factors. Despite its’ proven clinical benefits, the addition of icosapent ethyl to patient’s current treatment regimens may impose a significant cost burden on healthcare systems.

Hypothesis:
Prioritizing icosapent ethyl therapy for patients with an established CVD may provide significantly more value for money than when prescribed as primary prevention.

Methods:
We performed an analysis of the cost required for icosapent ethyl per achieved outcome when prescribed either for primary or for secondary prevention of MACE. The cost needed to treat (CNT) to prevent one MACE in the REDUCE-IT trial was estimated by multiplying the annualized number needed to treat to prevent one event, by the annual cost of therapy. The market price of icosapent ethyl in the US was estimated as 75% of the US national average drug acquisition cost listing.

Results:
In the REDUCE-IT population, the figured CNT of Icosapent ethyl provided as primary prevention was $874,500 (95% CI: $349,800-∞) vs. $206,965 (95% CI: $160,325-$294,415) for secondary prevention; P<0.001.

Conclusions:
The CNT for patients receiving the drug for primary prevention of MACE was four-fold higher than when provided as secondary prevention. Our findings suggest that icosapent ethyl therapy for patients with an established CVD provides significantly more value for money.
Abstract 13690: Association of Serum Fatty Acids With Age at the Onset of Acute Ischemic Stroke in Patients Aged 50 Years or Older
Authors: Mori Takahisa , Yoshioka Kazuhiro
Published: November 2020

Introduction:
There are few reports about the association of concentrations and proportions of serum fatty acids with age at the onset of acute ischemic stroke (AIS) in elderly patients.

Hypothesis:
A higher level of saturated FA (SFA) and n-6 polyunsaturated FA (PUFA) cause a younger onset of AIS, and a higher level of n-3 PUFA causes an older onset of AIS.

Methods:
For the retrospective cross-sectional study, we included patients aged 50 years or older who: 1) were admitted to our institution between August 2016 and July 2019 within 24 hours of AIS onset, and 2) underwent an examination of serum fatty acids. We evaluated concentrations of palmitic acid (PA) and stearic acid (SA) as SFA, oleic acid (OlA) as n-9 PUFA, linoleic acid (LiA), dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA) as n-6 PUFA on admission. We evaluated the concentration of alpha-linolenic acid (AlA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) as n-3 PUFA on admission. We evaluated the proportion of PA, SA, OlA, LiA, DGLA, AA, AlA, EPA, and DHA on admission. Furthermore, we evaluated their correlations with age at the AIS onset.

Results:
Three hundred sixty-six patients met our inclusion criteria. Their median average age was 75 years. Age at the onset was negatively correlated with concentrations of PA, SA, OlA, LiA, DGLA, AA, and AlA. Age at the onset was negatively correlated with the proportion of SA, OlA, and DGLA and positively correlated with the proportion of EPA and DHA. Multiple regression analysis showed that DGLA was an independent factor for the younger onset of AIS. Multiple regression analysis showed that DHA proportion was an independent factor for the older onset and that proportions of SA and DGLA were independent factors for the younger onset of AIS.

Conclusions:
The higher proportion of SA (SFA) and higher concentration and proportion of DGLA (n-6 PUFA) were significantly correlated with the younger onset of AIS, and the higher proportion of DHA (n-3 PUFA) was significantly correlated with the older onset of AIS.
Abstract 13706: Differences in the Distribution of Systolic Blood Pressure by Rural and Urban Residence
Authors: Heindl Brittain , Howard George , Jackson Elizabeth A
Published: November 2020

Introduction:
The incidence of stroke is higher in rural areas. Hypertension is the leading risk factor for stroke, but the difference in systolic blood pressure (SBP) for those living in rural and urban areas is unknown.

Hypothesis:
We hypothesized that rural residence is associated with higher SBP levels, and this difference is modified by race, sex, and United States (US) division.

Methods:
We analyzed 26,113 participants enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, recruited between 2003 and 2007. Participants were grouped based on the Rural-Urban Commuting Area (RUCA) scheme into urban, large-rural, and small-isolated rural groups. Resting SBP was measured during the initial home visit. Differences in percentiles of SBP distribution were compared using multivariate models with adjustment for age, race, sex, and US Census Bureau division.

Results:
Of the participants, 20,976 (80.3%) were classified as urban, 3,020 (11.6%) as large-rural, and 2,137 (8.2%) as small-isolated rural, reflecting the distribution of the population. The large-rural group had a 0.09 mmHg higher mean SBP compared to the urban group (95% CI, 0.33 to 1.52 mmHg, p = 0.0023), but the difference in SBP at the 95th percentile between these groups was 3.23 mmHg (95% CI, 1.43 to 4.73 mmHg, p = 0.0006). A similar difference was present between the small-isolated rural and urban groups at the highest percentiles. No urban-rural interaction was observed by race, sex, or US division. However, large SBP differences were present between US divisions, especially at the highest percentiles. To illustrate, SBP at the 95th percentile was 9.51 mmHg higher in the East North Central division than in the Pacific (95% CI, 6.41 to 12.61 mmHg, p < 0.0001).

Conclusions:
Residence in a rural area is associated with higher SBP, with larger differences at the highest percentiles of distribution. SBP differences are present between US divisions, independent of urban-rural status.
Abstract 13718: Automatic Microvolt-level Measurement of ST Level at J-point on 12-lead Electrocardiography Can Distinguish Takotsubo Syndrome and Acute Anterior Myocardial Infarction
Authors: Shimizu Masato , cho shummo , Misu Yoshiki , Ohmori Mari , Tateishi Ryo , Kaneda Toshio , Yamakami Yosuke , Shimada Hiroshi , Manno Tomoko , Isshiki Ami , Kimura Shigeki , Fujii Hiroyuki , Suzuki Makoto , Nishizaki Mitsuhiro , Sasano Tetsuo
Published: November 2020

Introduction:
ST elevation/depression on 12-leads electrocardiography (ECG) at onset was recognized difficult to distinguish Takotsubo syndrome (TTS) and acute anterior myocardial infarction (ant AMI). Diagnostic performance of automatic microvolt-level measurement of the ST levels was not elucidated.

Hypothesis:
Microvolt-level differences of ST level at J-point on ECG can distinguish TTS and ant AMI in acute phase.

Methods:
We firstly enrolled consecutive 40 patients of TTS, and among 500 ant AMI patients, one to two random matching was done by their age and gender. Finally, 40+80 patients (74.5±11.2 years, 87 females) were enrolled. ECG at onset of both group was measured by automated system (ECAPs12c: Nihon-Koden).

Results:
ST level of TTS at J-point in I/II/V4-6 lead was significantly elevated comparing to that of ant AMI. Conversely, Conversely, significant ST depression in aVR and no ST elevation in V1 of TTS was observed in TTS. Logistic regression analysis revealed that ST elevation in I lead and no ST elevation in V1 lead showed high odds ratio and low P value.

Conclusions:
Automated measurement of microvolt-level difference of ST level at J-point was a powerful tool to distinguish TTS and ant AMI at onset.
Abstract 13719: Long Qt Associated Ventricular Tachycardia Caused by Sex Hormone Therapy
Authors: Kviatkovsky Bina , abureesh mohammad , Saouma Samer , Cinelli Michael P , Akhrass Philippe , Shah Rina , Kowalski Marcin , Bekheit Soad
Published: November 2020

Introduction:
Increasing number of patients are currently receiving hormonal therapies for a variety of conditions. Modulation of cardiac repolarization by sex hormones resulting in VT remains controversial. Anastrozole is an aromatase inhibitor (ANI), used as an anti-estrogen medication in women with breast cancer or as replacement therapy for hypogonadism. Arrhythmias associated with ANI are extremely rare and hence ANI is considered relatively safe to use.

Case Presentation:
We report two cases receiving ANI who presented with VT and long QT (LQT). Case 1, 71 year old female with breast cancer on ANI recently started on levofloxacin 750 mg qd, presented with monomorphic VT. Post-conversion ECG showed sinus rhythm (SR) QT 0.48s/QTc 0.56s. Case 2, 50 year old male with hypogonadism on ANI and clomiphene (CL) presented with monomorphic VT, post conversion ECG showed SR with QT 0.65s/QTc 0.59s. Both patients had normal electrolytes and coronaries.

Discussion:
Studies have shown that levofloxacin is not associated with significant LQT, however, a relationship between its concentration and the extent of LQT has been demonstrated. LQT in our first case can be explained by an increase in levofloxacin level resulting from inhibition of CYP by ANI. CL is a HERG inhibitor however has not been shown to prolong QT. ANI lower the estradiol level which blocks the membrane trafficking of KCNH2 channels, potentially lengthening the QT. LQT in the second case can be explained by the additive effect of both HERG and KCNH2 inhibition.

Conclusion:
Although reported as safe, ANI hormone therapy can be arrhythmogenic if combined with agents that potentially affect potassium currents. We recommend QT monitoring in such patients to prevent lethal arrhythmias.