bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13196: The Prevalence and Prediction of Significant Coronary Artery Disease in Patients Referred for Valvular Heart Surgery
Authors: Lappe Jason M , Grodin Justin L , Wu Yuping , Bott-Silverman Corinne , Cho Leslie
Published: July 2021

Background:
The guidelines recommend preoperative diagnostic coronary angiography (DCA) prior to valvular heart surgery (VHS) in men ≥35 years, premenopausal women with CAD risk factors ≥35 years, and postmenopausal women.

Objectives:
To determine the prevalence and risk factors for significant CAD in patients, without a prior history, undergoing DCA as a part of a preoperative evaluation for VHS. To create a risk prediction model to identify very-low risk patients.

Methods:
Patients undergoing DCA between 2/1/2004 and 10/1/2013 as a part of a preoperative evaluation for VHS were included. Significant CAD was defined as either ≥50% stenosis on DCA or the use of bypass grafting at the time of VHS. Multivariate analyses were used to determine risk factors for CAD. Patients were randomly split into derivation and validation cohorts. A nomogram was created to predict the risk of significant CAD, and the performance was assessed using a ROC curve.

Results:
We identified 5,360 patients (age 63±14 years, male 57%, diabetic 16%, hypertension 50%, hyperlipidemia 39%), of which 1,035 (19.3%) were found to have significant CAD. In multivariate analysis, age, gender, diabetes, renal dysfunction, hyperlipidemia and a family history of CAD were related to the presence of CAD (p<0.001 for all). After multivariate adjustment, the specific dysfunctional valve was not associated with the presence of significant CAD. The risk prediction nomogram (Figure) performed well in predicting the presence of significant CAD in the validation group (AUC 75.7%).

Conclusions:
In patients undergoing DCA prior to VHS, the prevalence of significant CAD is associated with demographics and traditional risk-factors, but not the specific dysfunctional valve. This data suggests there is a group with sufficiently low risk of significant CAD to merit non-invasive testing instead of DCA. The risk prediction nomogram created in this study can be used to identify patients with a very-low risk of significant CAD.
Abstract 132: Compliance Changes in the Aorta Following Chest Compressions in a Standard and High Impulse Model
Authors: Sundermann Matthew , Salcido David , Menegazzi James
Published: July 2021

Introduction:
In cardiopulmonary resuscitation (CPR), chest compressions eject blood from the aorta and into the circulation. Following return of spontaneous circulation (ROSC), the circulation generated by the heart may be hemodynamically compromised, notably in its aortic compliance, or the aorta’s ability to resist blood pressure changes in response to blood volume changes. We investigated the relationship between CPR force delivery and relative change in aortic compliance in standard and high impulse chest compression models.

Hypothesis:
We hypothesized that average compliance would increase following chest compressions and that high impulse CPR would yield larger compliance changes than compliance changes in standard CPR.

Methods:
Central aortic pressure (CAP) waveforms were retrospectively analyzed via Millar catheters in female swine separated into standard CPR (n=4) and high impulse CPR (n=5). Ventricular fibrillation was induced and left untreated for 8 minutes, followed by 5 minutes of CPR and drugs. Rescue shocks were then delivered. Compliance was defined as stroke volume divided by the pressure difference between the dicrotic notch and end diastole. Stroke volume was estimated by using a previously validated model, which defined stroke volume as the area beneath the systolic portion of the CAP waveform multiplied by both a calibration constant and a ratio of time in diastole over time in systole. Compliances were calculated from CAP waveforms in ten consecutive beats before and after CPR with custom software built using MATLAB. A 2-way ANOVA was performed on average compliance across ten beats before and after chest compressions in both standard and high impulse CPR.

Results:
The average compliance (mL/mmHg) at baseline or pre-CPR (203), was significantly different from the average compliance post-CPR (335) (p=.03). The compliance change in standard CPR (151) did not significantly differ from compliance change in high impulse CPR (116) (p=.27).

Conclusion:
We observed a significant compliance increase in beats post-CPR compared to beats pre-CPR in both standard and high impulse groups. A significant difference in compliance change was not found when comparing standard vs. high impulse CPR.
Abstract 13221: Family Caregivers’ Perceptions of Illness Severity in Heart Failure Patients with Limited Life Expectancy
Authors: Kitko Lisa , Hupcey Judith , Palese Maureen
Published: July 2021

Introduction:
End-of-life (EOL) services, such as hospice and palliative care are often lacking even for the sickest heart failure (HF) patients. Use of these services have been hampered by the lack of availability, lack of referrals due to the unpredictable course in HF, and refusal of services by patients and caregivers due to a lack of understanding of the terminality of HF. The purpose of this study was to determine whether caregivers of HF patients with a predicted survival of less than 2 years, understood disease terminality prior to and after the patient’s death.

Methods:
As part of a longitudinal study of 100 patient-caregiver dyads, caregivers were interviewed monthly until the patient’s death and then twice post-death. Caregiver interviews immediately preceding and post-patient death were analyzed to determine caregivers’ perceptions of the terminality of heart failure.

Results:
There were 49 caregivers of patients who died. Patients died an average of 8 months after study enrollment. Most caregivers did not understand the severity of the patient’s disease and 51% (25/49) viewed the death as unexpected. When caregivers retrospectively reflected on the patient’s illness trajectory, they recounted downward trends in patient’s health, but were not aware of the terminality of the patient until after death occurred. Those few caregivers who perceived the illness severity prior to death came to this realization late in the disease trajectory. At the point of recognition, advanced treatments were limited or withdrawn and the short-term use of EOL services such as palliative care or hospice was instituted.

Conclusions:
The lack of perceived illness severity/terminality has profound implications for patients, caregivers, and healthcare providers. Patients and caregivers who do not understand the seriousness of the illness are less likely to accept EOL services, if offered. Clinicians need to understand the HF EOL trajectory and that EOL discussions and advance care planning help patients and caregivers make informed choices and receive quality care at EOL. We also need to educate all healthcare providers about having these discussions, so palliative care becomes a philosophy of care not merely a referral service immediately preceding death.
Abstract 13237: Impact of Pain and Heart Failure Symptom Severity on Physical Performance
Authors: Wingate Suzanne , Patel Kushang V , Guralnik Jack , Goodlin Sarah
Published: July 2021

Introduction:
The purpose was to determine whether pain and heart failure (HF) symptom severity are associated with physical performance in patients with advanced HF.

Methods:
Cross-sectional data were analyzed on 160 adults with advanced HF (dyspnea or fatigue at rest or with minimal exertion despite optimal medical therapy). Demographics, comorbidity (Charlson), pain (Brief Pain Inventory), HF symptom severity (Kansas City Cardiomyopathy Questionnaire), and depression (Patient Health Questionnaire-9) data were obtained. Physical function was assessed with the Short Physical Performance Battery (SPPB), a measure of lower extremity function (timed walking speed, standing balance, chair rises). Scores range 0-12 (higher scores=better). Multivariable linear regression assessed the associations of pain and HF symptom severity with SPPB scores.

Results:
Subjects had a mean (standard deviation [SD]) age of 67.0 (15.9) years, 43% were women, and 19.6% were non-white. The mean (SD) SPPB score was 6.4 (3.6), indicating limited mobility function. Subjects in the highest quartile of pain (severe), as compared to those in the lowest quartile, had clinically significant decreased SPPB scores (b coefficient = -2.1; p<0.01), adjusting for demographics, comorbidity, and depression. However, this association was no longer significant when adjusting for HF symptom severity. For every SD increase in HF symptom severity, SPPB scores decreased 1.2 points (p<0.01). The combined effect of pain and HF symptom severity on SPPB scores (Table) suggests that pain exacerbates the impact of HF symptom severity on physical performance.

Conclusions:
Among patients with advanced HF, symptom severity was strongly associated with decreased physical performance. Pain may exacerbate HF symptom severity and contribute to decline in mobility function.
Abstract 13253: Cost-effectiveness of CABG vs PCI for Treatment of Multivessel Coronary Disease among Unstable Angina Patients---A Secondary Analysis from ASCERT
Authors: Zhang Zugui , Kolm Paul , Grau-Sepulveda Maria V , Ponirakis Angelo , O’Brien Sean M , Klein Lloyd W , Shaw Richard E , McKay Charles , Shahian David M , Grover Frederick L , Mayer John E , Garratt Kirk N , Hlatky Mark , Edwards Fred H , Weintraub William S
Published: July 2021

Background:
The American College of Cardiology Foundation and The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies (ASCERT) has demonstrated that coronary artery bypass graft (CABG) surgery was associated with reduced mortality compared to percutaneous coronary intervention (PCI) at 4 years. In this study, we examined the cost-effectiveness of CABG versus PCI for treatment of multivessel coronary artery disease (CAD) patients among unstable angina patients.

Methods:
Unstable angina age ≥65 year-old patients with stable 2 and 3-vessel disease undergoing revascularization from 2004 through 2008 were evaluated. Costs were assessed at index, study period from years 2004 to 2008 by Diagnosis Related Group for hospitalizations. The average Medicare participant per capita expenditure in 2004 was used to estimate cost beyond the study period. Effectiveness during the study period was measured via mortality rate. Costs and effectiveness comparisons were adjusted using propensity scores bin bootstrapping (PSBB) method. The incremental cost-effectiveness ratio (ICER) was expressed as cost per quality adjusted life year (QALY) gained. Analyses were also conducted for 1-to-1 matched analytic population.

Results:
Among unstable angina patients (24,630 of 86,244 in CABG group and 48,261 of 103,549 in PCI group) at least 65 years old with two or three vessel CAD, results from both matched analytic population (16,500 in each group) and PSBB adjusted approach were similar. Costs were higher for CABG by $10,389 (95% CI: $10,269 to $10,509) during the index hospitalization. Over the period from 2004 through 2008, average total costs were $69,476 for CABG versus $57, 037 for PCI, a difference of $12,439 (95% CI: $11,038 to $13,751); patients undergoing CABG gained an average of 0.4066 life-years relative to PCI; the ICER of CABG compared to PCI, was $30, 484 per LYG, with 37%, 100%, and 100% of bootstrap-derived estimates <$30,000/ QALY, <$50,000/ QALY , and <$100,000/ QALY, respectively.

Conclusions:
Recognizing the limitations of an observational study, this study shows that over a period of 4 years or longer, CABG is associated with better outcomes but at higher cost than PCI in patients with unstable angina.
Abstract 13271: Incidence of Stent Complications detected by Optical Coherence Tomography and their Clinical Significance: One Year Follow up Study
Authors: Soeda Tsunenari , Park Seung-Jung , Jang Yangsoo , Lee Stephen , Raffel Owen C , Choi So-Yeon , Chia Stanley , Itoh Tomonori , Toma Catalin , Jia Haibo , Minami Yoshiyasu , Vergallo Rocco , Tian Jinwey , Hu Sining , Lee Hang , Yu Bo , Uemura Shiro , Saito Yoshihiko , Jang Ik-Kyung
Published: July 2021

Introduction:
Optical coherence tomography (OCT) was introduced to optimize percutaneous coronary intervention (PCI). Due to its unprecedented resolution, complications are frequently visualized. The exact incidence and clinical significance of these OCT detected complications are unknown.

Object: The aims of this study were 1) to evaluate the incidence of acute stent complications by OCT, 2) to correlate these complications with clinical outcome at 1 year, and 3) to identify the OCT predictors for major adverse cardiac events (MACE) including death, acute myocardial infarction (AMI), stent thrombosis, and target lesion revascularizations (TLR).

Methods and Results:
A total of 409 patients with 473 drug eluting stents (DES) who had post stent OCT imaging were included in this study. The incidence of stent edge dissection was 36.4% and of intra stent dissection was 72.3%. Incomplete stent apposition was detected in 36.4% of stents. The incidence of smooth protrusion, fibrous flap or disrupted fibrous plaque, irregular protrusion and thrombus were 93.7%, 56.0%, 55.2%, and 33.4%, respectively. Minimal stent underexpansion defined by minimal stent area (MSA) < 1.0 of reference area and severe stent underexpansion defined by MSA< 0.8 of reference area were observed in 84.8% and 37.8% of stents. MACE occurred in 3.7% of cases at 1 year follow up. There was no death. AMI, stent thrombosis, and TLR occurred in 0.7%, 0.2%, and 3.2%. Univariate analysis showed small MSA (MSA< 5 mm2) and irregular protrusion were correlated with MACE at 1year follow up (P=0.003 and P=0.044). Following adjustment of stent edge dissection, incomplete stent apposition, irregular protrusion, small MSA, stent type, and clinical presentations, small MSA and irregular protrusion remain as independent predictors of MACE (P=0.004 and P=0.037).

Conclusions:
OCT-detected stent complication rate is high. Small MSA and irregular protrusion are independent predictors of MACE at 1 year.
Abstract 13272: High Density Lipoprotein Subclasses Predict Non-Cardiovascular Disease, Non-Cancer Chronic Inflammatory-Related Death and Hospitalization More Strongly than Cardiovascular Disease Events in the Multi-Ethnic Study of Atherosclerosis
Authors: Duprez Daniel , Otvos James , Feingold Kenneth , Greenland Philip , Gross Myron D , Lima Jao , Neaton James D , Sanchez Otto A , Tracy Russel , Jacobs David
Published: July 2021

In vitro studies have demonstrated that high density lipoprotein particles (HDL-P) antagonize inflammatory processes. We studied the predictive value of HDL-P and inflammatory markers for incident cardiovascular disease (CVD) and non-CVD, non-cancer, chronic inflammatory-related events.

Methods:
In the Multi-Ethnic Study of Atherosclerosis, we studied 6475 men and women free of overt CVD, baseline age 45-84 years, who had fasting venous samples for lipid profile, lipoprotein particles, and inflammatory markers Interleukin-6 (IL-6), hs-CRP and D-dimer at baseline. Median follow-up was 10.1 years. Poisson regression models predicted non-CVD, non-cancer, chronic inflammatory-related events (death and hospitalization), based on diagnostic codes, n=1054) and CVD events due to coronary heart disease, myocardial infarction, coronary artery disease requiring revascularization, stroke, peripheral arterial disease, congestive heart failure and CVD or unwitnessed death (adjudicated, n=756). Adjustment was for age, race, gender, clinic, heart rate, smoking, body mass index, blood pressure, blood pressure and lipid lowering medication, diabetes mellitus, plus all lipid, lipoprotein particle and inflammatory variables.

Results:
Non-CVD, non-cancer, chronic inflammatory-related events were inversely associated with the sum of small+medium HDL-P independent of covariates (relative risk (RR) per standard deviation (95% confidence limits), RR: 0.85 (0.79-0.91, P < 0.0001). Non-CVD, non-cancer, chronic inflammatory-related events were positively associated with IL-6, RR:1.19 (1.11-1.27, P < 0.0001) and D-dimer, RR: 1.10 (1.05-1.16, P < 0.0001). CVD was associated with small+medium HDL-P, RR: 0.90 (0.82-0.99, P < 0.03) and IL-6, RR:1.15 (1.06-1.25 P < 0.0001). hsCRP was unrelated to either outcome after adjustment for other inflammatory markers.

Conclusion:
The long-term inverse association of small+medium HDL-P with non-CVD, non-cancer, chronic inflammatory-related death and hospitalization was stronger than with fatal and non-fatal CVD in subjects initially free of overt CVD. These findings provide clinical evidence that small+medium HDL-P have anti-inflammatory properties and may rethink the importance of HDL-P beyond CVD.
Abstract 13274: Frailty is an Independent Prognostic Factor when Added to Existing Acute Ischemic Stroke Mortality Models
Authors: Reeves Mathew J , Sucharew Heidi , Khoury Jane , Alwell Kathleen , Moomaw Charles , Kissela Brett , Woo Daniel , Flaherty Matthew , Adeoye Opeolu , Khatri Pooja , Ferioli Simona , Kleindorfer Dawn
Published: July 2021

Introduction:
Frailty is a state of decreased reserve and cumulative decline in multiple physiologic systems. Several frailty measures have been developed but have not been considered in existing stroke mortality prediction models. We sought to determine whether frailty is an independent predictor when added to existing stroke mortality models.

Methods:
Clinical data from incident ischemic stroke admissions in the Cincinnati/ Northern Kentucky Stroke Study during 2005 were abstracted by research nurses. Using established methods, we developed a frailty index using 35 age-related deficits that included pre-stroke function, comorbidities, symptoms, and clinical and lab values at admission. The index was specified as the total number of deficits or frailty score (range 0 to 35). Two established stroke mortality prediction models - one for in-hospital mortality and one for 1-year mortality, were identified and applied to the data. The independent contribution of the frailty score (expressed as a 1 deficit increase) to these existing models was determined from the logistic regression models.

Results:
A total of 2092 ischemic strokes were included. The median age was 72 years, 22% black, 56% female, median NIHSS 4 (IQR 2, 7). In-hospital and 1-year mortality were 8.8% and 26%, respectively. The median frailty score was 6 (IQR 4, 9). Both existing models fit the data well; the model c-statistics were both high (0.877 and 0.808, respectively) (Table). The frailty score was independently associated with higher mortality in both models; a 1 unit increase in age-related deficits was associated with a 20% and 17% increase in the adjusted odds ratio of in-hospital and 1-year mortality, respectively.

Conclusions:
When added to existing mortality prediction models, a frailty score showed strong independent associations with mortality. These data suggest that adding frailty to stroke mortality prediction models could improve their predictive accuracy and clinical utility.
Abstract 13301: Methylome-wide Association With Soluble Cell Adhesion Molecules Among Monozygotic Twins
Authors: Sun Yan , Goldberg Jack , Jones Dean P , Vaccarino Viola
Published: July 2021

Introduction:
Inflammation plays a critical role in the pathogenesis of cardiovascular disease. Epigenetic mechanisms, including DNA methylation (DNAm), is critical in the regulation of inflammatory genes, and can be influenced by inflammation. The soluble form of cell adhesion molecules, including vascular adhesion molecule 1 (sVCAM1), intercellular adhesion molecule 1 (sICAM1), and P-selectin (sP-selectin), are established biomarkers for inflammation and endothelial function, and are linked to cardiovascular events.

Methods:
To identify epigenetic markers associated with inflammation and endothelial function, we conducted a methylome-wide association study and investigated over 480,000 DNAm sites of peripheral blood cells from 140 monozygotic (MZ) middle-aged male twins from the Emory Twin Study.

Results:
Using two randomly selected subsets consisting of unrelated subjects, we identified and replicated 69 and 23 DNAm sites significantly associated with sVCAM1, and sICAM1 respectively, adjusted for multiple testing, but none for sP-selectin. All 23 sICAM1-associated DNAm sites were also associated with sVCAM1, including sites on gene ANKRD11 (P=1.51х10-21, 2.62х10-20), KDM2B (P=1.52х10-21, 9.13х10-17), CAPS (P=2.81х10-20, 3.17х10-18), and CUX1 (P=7.63х10-20, 2.84х10-19). They jointly explained 54% and 40% of variance in sVCAM1 and sICAM1 respectively. Two DNAm sites, located on UNC5D and TMEM125, were also significant comparing MZ twins who were phenotypically discordant for both sICAM1 (P=1.79х10-7, 2.78х10-6) and sVCAM1 (P=1.70х10-9, 1.71х10-7).

Conclusions:
These results suggest that sVCAM1 and sICAM1, but not sP-selectin, may share common pathophysiology in inflammation and endothelial function via an epigenetic mechanism in leukocytes. In addition, the epigenetic association with inflammation may be driven by unshared environmental exposures.
Abstract 13308: The Transcriptome of Kawasaki Disease Arteritis Reveals Activation of T Lymphocyte and Natural Killer Cell Function, Antigen Presentation, Immunoglobulin Production, and Interferon Response
Authors: Rowley Anne H , Wylie Kristine , Pink Adam , Reindel Rebecca , Baker Susan , Shulman Stanford , Orenstein Jan , Perlman Elizabeth , Lingen Mark , Weinstock George , Wylie Todd
Published: July 2021

Introduction:
We recently published the new information that necrotizing arteritis, subacute/chronic vasculitis and luminal myofibroblastic proliferation are the three linked pathologic processes of Kawasaki Disease (KD) vasculopathy, which critically affects the coronary arteries (CA). The specific dysregulated immune pathways in KD CA have been unknown, and controversy exists as to whether immune dysregulation is primarily macrophage or T and B lymphocyte-driven.

Hypothesis:
We hypothesized that the immune transcriptome of KD arteritis was primarily one of T and B lymphocyte rather than macrophage activation.

Methods:
RNA was isolated from paraffin-embedded CA tissues. RNA samples passing quality control assays were subjected to ribosomal RNA subtraction, and Illumina HiSeq 2000 RNA sequencing (101 nt paired-end reads, 40-100million reads/sample) was performed. Reads were aligned to the human genome, and Cuffdiff used to test for differential gene expression in CA tissues from 8 KD children (median age=7 mo, median 4 wks from onset) compared to 7 controls who had normal CA pathology (median age=5 mo). Pathways analysis was performed using Ingenuity iReport™.

Results:
1057 differentially expressed transcripts were identified with >1.5-fold change and q-value <0.05. The most significantly upregulated pathways included T lymphocyte, dendritic cell and natural killer cell signaling, antigen presentation, and toll-like receptor (TLR) signaling (p values 1e-18 to 5e-05). Immunoglobulin A, G, and M genes and at least 50 type I interferon-stimulated genes were significantly upregulated. Tumor necrosis factor α (TNFα) receptor and transforming growth factor β signaling pathways were not significantly altered (p-value >0.1). 50 immune response genes encoding secreted proteins were upregulated and are candidate biomarkers of KD arteritis.

Conclusions:
The host transcriptional response in target CA tissues in KD demonstrates a prominent innate and acquired immune response to antigen. Genes related to T and B lymphocyte activation were upregulated but macrophage responses were not prominent. This first report of the CA transcriptome of KD could lead to identification of new therapeutic targets and biomarkers for KD arteriopathy.
Abstract 13312: Risk Factors for the Development of Tachyarrhythmia Following the Norwood Procedure in the Single Ventricle Reconstruction Trial
Authors: Oster Matthew , Chen Shan , Pober David , Bar-Cohen Yaniv , Brothers Matthew , Cain Nicole , Colan Steve , Czosek Richard , Decker Jamie , Gamboa David , Idriss Salim , Kirsh Joel , LaPage Martin , Ohye Richard , Radojewski Elizabeth , Shah Maully , Silver Eric , Singh Anoop , Temple Joel , Triedman John , Kaltman Jonathan
Published: July 2021

Background:
Tachyarrhythmias are an important contributor to morbidity following the Norwood procedure for single ventricle congenital heart disease. The purpose of this study was to determine what demographic, preoperative, or operative factors may be associated with the development of postoperative tachyarrhythmias in this population.

Methods:
We performed a retrospective analysis of data collected prospectively through the multicenter Pediatric Heart Network Single Ventricle Reconstruction Trial for infants undergoing a Norwood procedure in 2005-2008. Our primary outcome of interest was any documented tachyarrhythmia requiring treatment or intervention during the inpatient postoperative stay. Subjects with a documented preoperative tachyarrhythmia (n=15) were excluded. After performing univariate chi-square analyses on a variety of candidate factors, we conducted multivariate stepwise logistic regression, including spline terms for nonlinearly associated variables, to calculate the adjusted odds ratios for the final variables.

Results:
Of 529 subjects, 108 (20%) had at least one documented tachyarrhythmia, with 11 having more than one. Tachyarrhythmias included: 77 supraventricular tachycardia, 23 junctional ectopic tachycardia, 10 atrial flutter, 7 ventricular tachycardia, and 2 atrial fibrillation. In the final multivariate model (c-statistic=0.65), significant factors associated with arrhythmia included receiving a modified Blalock-Taussig shunt, use of ultrafiltration, and age. (Table)

Conclusions:
Tachyarrhythmias are common following the Norwood procedure and are associated with the modifiable risk factors of shunt type and use of ultrafiltration. In addition, when surgery is performed between 8 and 20 days of age, older age is associated with a decreasing risk for tachyarrhythmia.
Abstract 13352: Work Absenteeism, Short Term Disability and Related Indirect Costs Associated with Cardiovascular Events and Related Clinical Procedures
Authors: Song Xue , Quek Ruben G , Gandra Shravanthi R , Cappell Katherine , Fowler Robert , Cong Ze
Published: July 2021

Objectives:
To examine work absenteeism (WA) and short-term disability (STD) hours and related indirect costs associated with cardiovascular events and related procedures (CVERP): myocardial infarction (MI), ischemic stroke (IS), unstable angina (UA), heart failure (HF), transient ischemic attack (TIA), coronary artery bypass graft (CABG), and percutaneous coronary intervention (PCI).

Methods:
Full-time employees aged 18-64, with WA or STD benefits, hyperlipidemia or lipid-lowering therapy, and ≥1 CVERP in 2003-2011 were extracted from a large claims and productivity database. Index date was the date of the first CVERP. All patients had data for ≥1 year pre-index and ≥1 month post-index. Per patient per month (PPPM) WA and STD hours were measured during the acute 1 month and 1 year post-index periods. Indirect costs associated with these hours were calculated using the Bureau of Labor Statistics wage rates (in 2013 $).

Results:
A total of 5,803 patients were included in the WA analysis (mean age 53, 86% male, mean Charlson comorbidity index [CCI] 0.6) and 21,074 in the STD analysis (mean age 53, 82% male, mean CCI 0.7). Patients with CABG as the first CVERP type had the highest mean PPPM costs and hours during the acute 1 month and the 1 year post-index periods (Fig. 1), followed by MI (for WA acute 1 month and 1 year, for STD acute 1 month) and HF (for STD 1 year). Mean PPPM WA hours ranged between 31 - 61 (indirect cost: $998 - $1842) and STD hours between 31- 121 (indirect cost: $532 - $2154) during the acute 1 month post-index period. Compared with the mean PPPM hours lost from work in the pre-index period, mean PPPM WA hours went up by 22.5 hours (indirect cost by $647) in the acute 1 month post-index period, and STD went up by 53 hours ($916).

Conclusions:
CVERP were associated with substantial work loss and related indirect costs, especially in the acute first month period following CVERP. Prevention of CVERP could result in potential WA and STD related cost savings for employers.
Abstract 13383: Atrial Fibrillation Alters Both Left and Right Atrial 3D Hemodynamics
Authors: Carr Maria , Ng Jason , Lee Dan , Jarvis Kelly , Schnell Susanne , Carr James , Goldberger Jeffrey J , Markl Michael
Published: July 2021

Introduction:
In patients with atrial fibrillation, pulmonary embolism and right atrial (RA) thrombus are less common than stroke and left atrial (LA) thrombus. Prior studies have linked thrombus formation to decreased blood flow velocity (stasis) promoting blood clotting. We hypothesized LA stasis is more evident than RA stasis.

Methods:
Whole heart 4D flow MRI was performed in n=70 subjects: 33 AF patients in sinus rhythm (SR) during imaging (AF-SR, age = 62±10 years), 29 AF patients in AF (AF-afib, age = 67±12 years), and 8 age-matched controls (age = 59±5 years). 3D segmentation (MIMICS, Materialise, USA) of the LA and RA geometry was performed to calculate the flow velocity distribution for all atrial voxels and cardiac time frames. Velocity histograms normalized by the total number of entries (figure 1A) were used to assess mean and median atrial velocities and the % of LA and RA with velocities <0.2m/s (stasis).

Results:
Compared to controls (LA = 0.20±0.2m/s, RA = 0.19±0.02m/s), both LA and RA velocities were significantly reduced in AF-SR (LA = 0.16±0.03m/s, RA = 0.16±0.04m/s, p<0.03) and even further in AF-afib patients (LA = 0.13±0.03m/s, RA = 0.13±0.04m/s, p<0.001). Atrial stasis was more pronounced in AF-afib (LA = 82±13%, RA = 80±16%, p<0.001) and AF-SR (LA = 72±15%, RA = 69±20%, p<0.04) than in controls (LA = 53±10%, RA = 53±13%). No significant RA vs LA differences were noted, Figure 1 shows significant associations (p<0.01) between LA and RA mean velocity (R2=0.40) and stasis (R2=0.36) in figure 1B. RA/LA mean velocity ratio (1.0±0.2, range=0.6-2.0) and RA/LA stasis ratio (1.0±0.3, range=0.3-2.2) were not significantly different.

Conclusions:
In both controls and AF patients, there was no evidence for increased stasis in the LA vs RA. Although stasis likely contributes to clot formation, other factors such as atrial geometry in combination with individual LA vs. RA flow differences may account for the more prevalent formations in the LA vs. the RA.
Abstract 13426: Percent Time With a Supratherapeutic Inr in Atrial Fibrillation Patients Using an Antiplatelet Agent is Associated With Long-term Risk of Dementia
Authors: Bunch Thomas J , May Heidi T , Bair Tami L , Jacobs Victoria , Crandall Brian G , Weiss J P , Osborn Jeffrey S , Mallendar Charles , Day John D , Anderson Jeffrey L , Olson Jeffrey L , Johanning Katie , Long Yenh Long , Stevens Scott M , Woller Scott C
Published: July 2021

Background:
Patients with atrial fibrillation (AF) are at higher risk of developing all forms of dementia. The mechanisms behind the association of AF and dementia are unknown. One possibility is that exposure to chronic microbleeds results in repetitive cerebral injury that is manifest by cognitive decline. We hypothesize that AF patients receiving antiplatelet therapy will display higher rates of dementia if coupled with a higher percentage of time exposed to over-anticoagulation.

Methods:
Chronically anticoagulated patients receiving warfarin (target INR 2-3) for AF and managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service (CPAS) with no history of dementia or stroke/TIA and receiving antiplatelet therapy were included. The primary outcome was the presence of dementia defined by neurology determined ICD-9 codes. Percent time with an INR above 3.0 was determined. Multivariable Cox hazard regression was utilized to determine dementia incidence by percentage categories of supratherapeutic INR.

Results:
A total of 1031 patients were studied. Of these, the categories of the mean percent time with an INR >3.0 were 25% (n=240). Patients with a higher percent of time with supratherapeutic INRs were more likely to have valvular heart disease, renal failure (Cr>2.0), a higher percent of CHADS 3-6 scores, and a prior bleed. Dementia was diagnosed in 2.7% of patients with supratherapeutic INR levels 25%, p=0.05. Those with a supratherapeutic INR >25% of the time were at an increased dementia risk throughout follow-up. After multivariate adjustment, those with levels >25% had significantly higher rates of dementia compared to those with levels <10% (HR 2.40, p=0.04).

Discussion:
In AF patients receiving antiplatelet and anticoagulant therapies, the percent of time exposed to over anticoagulation increases risk of dementia. These data support the possibility of chronic cerebral injury from microbleeds as a mechanism that underlies the association of AF and dementia.
Abstract 13433: Angiotensin II Type 2 Receptor Regulates Skeletal Myoblast Differentiation: Implications for treatment of Cachexia and Skeletal Muscle Wasting
Authors: Yoshida Tadashi , Delafontaine Patrice
Published: July 2021

Patients with advanced congestive heart failure (CHF) or chronic kidney disease (CKD) often have increased angiotensin II (Ang II) levels and cachexia. We previously demonstrated that Ang II infusion in rodents causes skeletal muscle wasting and decreases muscle regenerative potential via Ang II type 1 receptor (AT1R) signaling, likely contributing to cachexia in CHF and CKD. However, the potential role of Ang II type 2 receptor (AT2R) signaling in skeletal muscle physiology remains unknown. We found that AT2R expression was robustly increased in mouse skeletal myoblasts during differentiation, suggesting that the AT2R plays an important role in skeletal muscle regeneration. To test this hypothesis, we infused mice with AT2R antagonist PD123319 (PD, 30 mg/kg/d) or agonist CGP123319 (CGP, 1 μg/kg/min) during cardiotoxin (CTX)-induced muscle injury and regeneration. PD reduced the size of regenerating myofibers (727.5±54.6 and 516.0±37.0 μm2 in sham and PD, respectively, p<0.05) and expression of the myoblast differentiation markers myogenin and eMyHC (56.9% and 40.2% decrease in PD, respectively. p<0.01), whereas CGP had the opposite effects. siRNA mediated AT2R knockdown in mouse primary myoblasts suppressed the increase of myogenin and desmin, resulting in lowered differentiation. We analyzed changes in phosphoprotein levels in myoblasts after AT2R knockdown by phosphoprotein array and identified multiple changes, including increased phospho-ERK1/2 levels. Importantly, inhibition of ERK1/2 restored normal myoblast differentiation in the setting of AT2R knockdown, suggesting the AT2R positively regulates myoblast differentiation by reducing ERK1/2 activity. Furthermore, we found that skeletal muscle regeneration was reduced (decreased regenerating myofiber size and myogenin/desmin expression) in a mouse myocardial infarction model of CHF, concomitantly with markedly blunted increase of AT2R expression, strongly suggesting that the AT2R plays an important role in the reduction of skeletal muscle function in CHF. These data indicate that AT2R signaling positively regulates myoblast differentiation and potentiates skeletal muscle regeneration, providing a new therapeutic target in wasting disorders such as CHF and CKD.
Abstract 13464: Underutilization of Invasive Coronary Angiography Post Out of Hospital Cardiac Arrest: is a Paradigm Shift Needed?
Authors: Ramanathan Krishnan , Cheung Christopher , Grunau Brian , Habibi Mona , Deyell Marc W , Taylor Carolyn M , Stub Dion , Fordyce Christopher B , Kaila Kendeep , Christenson Jim , Wong Graham C , Farkouh Michael E
Published: July 2021

BACKGROUND:
The immediate post-resuscitation 12-lead electrocardiogram (ECG) aids in the diagnosis of an acute coronary syndrome (ACS) following an out-of-hospital cardiac arrest (OHCA). Guidelines support immediate coronary angiography (CA) for a finding of acute ST-elevation (STE), no such recommendations exist for ST-depression (STD) post-OHCA. We aimed to assess the relationship of STE and STD on the post-resuscitation ECG with diagnostic CA findings.

METHODS:
A retrospective analysis of consecutive patients admitted to a Vancouver Hospital with CA capability post-OHCA, between November 2009 and December 2011. Patients were identified using the Resuscitation Outcomes Consortium Cardiac Arrest Registry and included if they had an interpretable post-resuscitation ECG. ST-segment changes >0.1mV in 2 contiguous leads were deemed significant. A stenosis ≤70% (or ≤50% for left main) was defined as obstructive coronary artery disease (CAD).

RESULTS:
Our cohort of n=231 pts had a mean age of 65±17y and 74% were males. The presenting rhythm was ventricular tachycardia/fibrillation (49%), pulseless electrical activity (19%), asystole (17%), and unspecified (15%). The post-resuscitation ECG demonstrated STE in 33%, STD in 27% and no ST abnormality in 40%. The QRS morphology included narrow complex (42%), intraventricular conduction delay (25%), RBBB (27%), and LBBB (6%). The rate of CA was 41% (n=94), with a mean LVEF of 42%. In
Table 1
below the odd ratios describe the association of STE and STD with CA findings compared to patients with no ST abnormality.

CONCLUSIONS:
A high proportion of patients with OHCA demonstrated ST-segment abnormalities on the post-resuscitation ECG. The association with obstructive CAD was greatest with STE, the presence of STD showed a trend towards an association with both, occlusive and obstructive CAD. A randomized clinical trial is needed to assess the utility of diagnostic CA in OHCA patients with STD on the post-resuscitation ECG.
Abstract 13469: Drp1 Accumulates in Mitochondria and Plays a Protective Role in the Heart in Response to Pressure Overload
Authors: Shirakabe Akihiro , Ikeda Yoshiyuki , Zai Peiyong , Sadoshima Junichi
Published: July 2021

Dynamin-related protein 1 (Drp1) plays an essential role in maintaining the quality control of mitochondria through mitochondrial (Mt) fission and mitophagy. We investigated how Mt function, autophagy and Drp1 are regulated in the heart during pressure overload (PO) and whether endogenous Drp1 plays an important role in regulating cardiac function. Mice were subjected to transverse aortic constriction (TAC) at multiple time points between 6 hours and 30 days. Left ventricular (LV) weight/tibial length (LVW/TL) was significantly elevated at Day 7 (TAC vs sham; 5.92 ± 0.27 vs 4.22 ± 0.12, p<0.05). Ejection fraction (EF) was maintained at Day 7, but gradually decreased thereafter (at 30 days; 65±9 vs 83±9 %, p<0.05). LC3-II was decreased (-45.7%, p<0.05) while p62 accumulated (1.17 fold, p<0.05) significantly at Day 7. Both Mt ATP content (-65.6%, p<0.05) and production (-90.3%, p<0.05) were reduced significantly at Days 7 and 14, respectively, and thereafter. Mt mass, evaluated by electron microscopy, was also reduced (-19.9%, p<0.05) at Day 7. Drp1 accumulated in mitochondria at Day 7, and S616 phosphorylation of Drp1, associated with increased activity, was increased at Day 7. Thus, PO suppresses autophagy and induces Mt dysfunction by Day 7, at which time Drp1 accumulates in mitochondria and Mt mass is decreased. To examine the functional significance of endogenous Drp1 during PO, cardiac-specific heterozygous Drp1 knock out (Drp-hetCKO) mice were subjected to TAC. At Day 7, decreases in EF (61± 2 vs 84 ± 7%, p<0.05) and increases in LVW/TL (7.22 ± 0.26 vs 5.86 ± 0.65, p<0.05) and lung weight/TL (12.01 ± 1.10 vs 6.31 ± 1.19, p<0.05) were exacerbated in Drp-hetCKO compared to in control mice. LV end diastolic pressure was significantly higher (22.0 ± 2.8 vs 5.7 ± 2.9 mmHg, p<0.05) and myocardial fibrosis (14.1 ± 2.5 vs 6.2 ± 4.3 %, p<0.05) was greater in Drp-hetCKO than in control mice. Mt mass was also significantly greater in Drp-hetCKO than in control mice (relative Mt mass, 1.21 ± 0.46 vs 1.00 ± 0.02, p<0.05). These results suggest that PO inhibits autophagy and induces mitochondrial dysfunction by Day7, which coincides with Mt accumulation of Drp1. Drp1 plays an adaptive role in this condition, mediating decreases in Mt mass and protecting the heart from dysfunction.
Abstract 13474: Incremental Value of Left Atrial Conduction Time for Predicting Atrial Fibrillation in Patients Receiving Cardiac Pacing
Authors: Saito Makoto , Negishi Kazuaki , Kosmala Wojciech , Kaye Gerry , Marwick Thomas H
Published: July 2021

Background:
Atrial fibrillation (AF) is a relatively common complication of cardiac pacing. Prolonged LA electromechanical conduction time (EMT) has been proposed for prediction of new- onset AF. We sought to investigate the incremental benefit of EMT for predicting AF over conventional predictors in pts undergoing pacing.

Methods:
We prospectively followed 127 pts with preserved ejection fraction, absence of chronic or known paroxismal AF, and a pacemaker implantation because of atrioventricular block in the PROTECT-PACE trial for 2 years. Reliable recognition of AF episodes was based on pacemaker monitoring. Echocardiography was performed just after the implantation. EMT was measured as the time interval from the onset of the P wave to the peak of the late diastolic wave from the septal and lateral mitral annulus on tissue Doppler echocardiography. We also assessed LA volume index (LAVI) and CHADS2 score.

Results:
24 patients (19%) had new onset AF. Septal EMT was significantly longer in pts with AF than that in pts without AF (130±31 vs 112±31 ms, p=0.01). Larger LAVI and prolonged septal EMT were significantly associated with AF. In sequential logisitic models, LAVI added to the model power of CHADS2 score, and the model based on CHADS2 score and LAVI was significantly improved by adding septal EMT (Figure).

Conclusion:
EMT provides incremental value over the conventional risks for predicting a first episode of AF in patients receiving cardiac pacing.
Abstract 13483: Pathological Decline in Incretin Hormone Glucagon-like Peptide-1 Causes Cardiac Apoptosis and Dysfunction in Pressure-overloaded Heart Failure Through Cyclic AMP-dependent Mechanisms. -Distinct Role of Protein Kinase a and EPAC
Authors: Aoyama Morihiko , Bando Yasuko K , Kawase Haruya , Monji Akio , Mitsui Toko , Shimizu Atsuya , Murohara Toyoaki
Published: July 2021

Introduction:
Ample evidence demonstrates cardiovascular protection by incretin hormone glucagon-like peptide-1 (GLP-1) through the cyclic AMP axis. GLP-1 is known for its inotropic effect on heart, however, the role of GLP-1 in heart failure remains uncertain.

Hypothesis:
To explore the pathophysiological role of GLP-1 in heart failure

Methods:
Pressure overload-induced heart failure model was generated by transverse aortic constriction in mice (TAC).

Results:
At 4 week after the operation, TAC exhibited systolic left-ventricular dysfunction, myocardial hypertrophy and augmented apoptosis. Unexpectedly, circulating GLP-1 concentration was markedly decreased in TAC (in pM; 0.86±0.10 for TAC versus 2.13±0.54 for sham) with concomitant reduction of myocardial cyclic AMP concentration (in pmole/mg protein; 33.0±1.4 for TAC versus 42.2±1.5). TAC exhibited pathological changes in signaling molecules of myocardial contractility [SERCA, phospho-phospholamban(Serine16; pPL), β-myosin heavy chain (MYH7)], remodeling (Akt/mTOR/S6K), and cell death markers (procaspase-3/Bcl2 for apoptosis and PINK/PARKIN complex for mitophagy detecting damaged mitochondria). All of these changes observed in TAC heart were reversed selectively by treatment with GLP-1 analog exendin-4 (Ex4; 24nmole/kg/day for 4 weeks) and indirect supplement of GLP-1 by a DPP4 inhibitor alogliptin (ALO; 10mg/kg/day for 4 weeks). In vitro TUNEL assay using cultured cardiomyocytes revealed that Ex-4 reduced myocardial apoptosis in a cAMP/EPAC1-dependent but PKA-independent manner (Figure).

Conclusions:
Pressure-overloaded heart failure exhibits decline in GLP-1, leading to cAMP/EPAC1-dependent impairment in myocardial apoptosis, and cAMP/PKA/pPL/SERCA-dependent myocardial contractile dysfunction. Our data suggest the distinct role of PKA and EPAC in pathophysiology underlying heart failure.
Abstract 13492: Usefulness of Aortic Valve Area Measurement Obtained by Single-Beat Recording of Double-Envelope Technique in Patients With Aortic Stenosis and Atrial Fibrillation
Authors: Oe Hiroki , Watanabe Nobuhisa , Ohno Yuko , Takemoto Rika , Ikeda Madoka , Sakamoto Hitomi , Kohno Kunihisa , Nakamura Kazufumi , Morita Hiroshi , Ito Hiroshi
Published: July 2021

Introduction:
In patients with aortic stenosis (AS) and atrial fibrillation (AF), the conventional continuity equation to evaluate aortic valve area (AVA) is cumbersome, because 5 to 10 cycles are required to ensure accuracy of results. Double-envelope (DE) is obtained by a single continuous-wave Doppler envelope with double density velocity profiles; the inner envelope represents flow across the left ventricular outflow tract and outer envelope represents flow across the aortic valve orifice.

Hypothesis:
The aim of this study to evaluate the usefulness of the AVA calculated from single-beat recorded inner and outer envelopes in patients with AS and AF.

Methods:
Eighteen AS patients (74.6±7.2 years old) with AF were examined by transthoracic echocardiography. The conventional AVA (PW/CW technique) was calculated from nonsimultaneously measured LVOT flow and AVO flow in randomly picked up 8 cardiac cycles, respectively. The AVA (DE technique) was calculated from the inner and outer envelopes simultaneously recorded. A single-beat AVA was calculated from simultaneously recorded inner and outer envelopes (by DE technique) when the preceding RR interval/pre-preceding RR interval = 1. Bland-Altman analysis was used to compare the results of two techniques and estimate the reproducibility.

Results:
DE profiles were successfully obtained in all patients, and mean AVA (PW/CW technique) was 1.09±0.19 cm2. AVA by Single-beat DE technique showed good correlation with that by PW/CW technique (r=0.90), and the mean bias in the AVA measurements between by PW/CW technique and by DE technique was 0.048 cm2. (Figure)

Conclusions:
AVA in patients with AS and AF obtained by Single-beat DE technique was feasible and in good agreement with that by PW/CW technique. We suggest that DE technique should be considered to estimate the subtle temporal change of AVA in patient with AS and AF more simply and accurately.