bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15273: Estimating Coronary Heart Disease Risk and Treatment Benefit in Patients With Familial Hypercholesterolemia to Enable Shared Decision Making
Authors: Bangash Hana , Saadatagah Seyedmohammad , Hargraves Ian , Gundelach Justin , Dikilitas Ozan , Montori Victor M , Kullo Iftikhar J
Published: May 2021

Introduction:
Current risk equations for coronary heart disease (CHD) do not take into account family history or cumulative exposure to LDL-C. We modified CHD risk equations for use in familial hypercholesterolemia (FH) patients and developed a decision aid (DA) for FH to facilitate shared decision making (SDM).

Methods:
Literature review, evidence synthesis and expert input were used to adapt the 30-year Framingham Risk Score (FRS) and 10-year ACC/AHA pooled cohort equations to calculate the CHD risk in individuals with FH aged 20-39 years and ≥40 years, respectively. Based on published data, estimated risk was multiplied by 2 for family history of early CHD or 3 in the presence of a pathogenic variant. Treatment benefit of lipid lowering was estimated based on the ‘cumulative exposure to LDL-C’ model (
JACC 2012; 60
) using the following equations:
Post-treatment 30-yr risk in those aged 20-39 years
= Baseline Risk
(FRS)
x 0.54
delta LDL-C (mmol/L)
Post-treatment 10-yr risk in those aged ≥40 years
= Baseline Risk
(ACC/AHA Pooled Cohort)
x 0.72
delta LDL-C (mmol/L)
To convey CHD risk and treatment benefit, we developed a DA using an iterative, patient-centered design process for use in FH encounters.

Results:
Using the DA, providers can discuss baseline CHD risk estimates, lipid lowering drug (LLD) options and the expected post-treatment risk reduction with FH patients. The estimated % LDL-C reduction for each LLD and the predicted risk reduction per mmol/L of LDL-C lowered were obtained from literature review. Lowering LDL-C by 1 mmol/L (39 mg/dL) was associated with a 28% CHD risk reduction over 10 years and a 46% reduction over 30 years (
Eur Heart J 2017; 38
). We describe 2 examples of estimating CHD risk and treatment benefit in FH cases in
Table 1
.

Conclusion:
We adapted CHD risk prediction equations to account for family history of CHD and presence of a pathogenic FH variant and designed a DA to convey personalized CHD risk estimates and treatment benefit to facilitate SDM with FH patients.
Abstract 15291: ‘Heart Rate Deficit’ From Dysautonomia in a Bariatric Surgery Patient - An Unusual Cause of Recurrent Syncope
Authors: Akella Krishna , Murtaza Ghulam , Ahmed iftekhar , Couchonnal LUIS , Krauthammer Yoaav , Olshansky Brian , Atkins Donita , Lakkireddy Dhanunjaya , Gopinathannair Rakesh
Published: May 2021

Background:
Patients undergoing bariatric surgery are prone to develop symptomatic dysautonomia but the mechanisms remain unclear.

Methods:
N/A

Results:
A 61-year-old female with hyperlipidemia, fibromyalgia, morbid obesity status post gastric sleeve 2 years prior, was transferred to our institution after an unremarkable initial cardiac workup for recurrent syncope and bradycardia. Patient had significant weight loss (180 lbs) post-surgery over this 2-year period but began noticing increasing fatigue, and exercise intolerance in the last four months preceding recent syncopal episodes. Syncopal spells happened while trying to lift her head >60 degrees/sit up from a recumbent position. Baseline heart rate (HR) was 36-42 bpm (Figure lower Panel) while it was 75-90 bpm immediately following bariatric surgery (Figure upper panel). Blood pressure was normal. During witnessed syncopal episodes, HR remained in the 35-40 bpm range with no asystolic pauses and normal blood pressure. Video EEG showed loss of brain electrical activity during syncope; no seizure activity was noted. Progressive decline in HR and baseline bradycardia was suspected as the cause and she underwent permanent pacemaker implantation, which resulted in complete resolution of symptoms and no recurrence of syncope at 6-mo follow-up.

Conclusion:
We describe a unique case where marked decline in resting HR occurred in association with significant weight loss following bariatric surgery. This ‘HR deficit’ and resting bradycardia, likely due to dysautonomia, resulted in recurrent syncope without asystole or vasodepression, and completely resolved with permanent pacemaker implantation.
Abstract 15294: 24-hour Levosimendan Infusion Decreases Biventricular Filling Pressures and Increases Cardiac Output at Rest and Exercise in PH-HFpEF
Authors: Burkhoff Daniel , Borlaug Barry A , Shah Sanjiv J , Rich Stuart ,   HELP Study Investigators
Published: May 2021

Background:
There are no specific treatments for patients with HFpEF and pulmonary hypertension (PH-HFpEF). Increased central and pulmonary venous pressures (CVP, PCWP) are believed to contribute importantly to symptoms at rest and during exercise. Levosimendan (LEVO), a calcium sensitizer/KATP channel activator, is known to reduce CVP and PCWP in patients with reduced LVEF. We hypothesized that LEVO would have similar effects in PH-HFpEF.

Methods:
44 PH-HFpEF patients with mean pulmonary artery (mPAP) ≥35 mmHg, PCWP ≥20 mmHg, LVEF ≥40% and NYHA II or III symptoms underwent hemodynamic measurements at rest, during passive leg raise (PLR) and during supine bicycle exercise for 3 minutes at 25 Watts (EX) at baseline and following a continuous 24-hour infusion of LEVO (0.1 μg/kg/min) as part of a multicenter clinical trial. Measurements included CVP, mPAP, PCWP, mean arterial pressure (MAP) and cardiac index (CI); pulmonary and systemic vascular resistances (PVR, SVR) were calculated. Hemodynamic tracings were analyzed in a core lab blinded to condition and timepoint. The primary endpoint was the change of PCWP at 25 Watts.

Results:
Patients averaged 69±9.1 years old, 61.4% were female and had a mPAP of 41.0±9.3 mmHg at rest. LEVO decreased mPAP at rest, CVP and PCWP at rest and EX, and increased CI with EX; there were no significant changes in mPAP, PVR or SVR. Resting and EX hemodynamic data are summarized in the Table. 37 of the 44 patients (84%) were considered hemodynamic “responders” based on a pre-specified ≥4 mmHg decrease of EX PCWP.

Conclusions:
In patients with PH-HFpEF, a 24 hour levosimendan infusion at 0.1 μg/kg/min decreased CVP and PCWP and increased CI at rest and EX, despite no significant effect on SVR or PVR. A majority of patients exhibited acute hemodynamic response. While the underlying mechanism(s) remain to be clarified, LEVO’s effects on CVP and PCWP warrant further study of this drug as a treatment for PH-HFpEF.
Abstract 15295: Clinical Characteristics, Treatment Patterns, and Short-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis
Authors: Caraballo Cesar , Bikdeli Behnood , Trujillo-Santos Javier , Galanaud Jean-Philippe , di Micco Pierpaolo , Rosa Vladimir , Vidal-Cusidó Gemma , Schellong Sebastian , Mellado Meritxell , Morales Maria del Valle , Gavin Olga , Krumholz Harlan M , Monreal Manuel
Published: May 2021

Background:
Isolated distal deep vein thrombosis (IDDVT) is a common form of venous thromboembolism (VTE). Limited data exist about the clinical characteristics, initial treatment, and short-term outcomes of these patients.

Methods:
Using the data from the RIETE registry (05/2001-02/2019), we identified patients with IDDVT without pulmonary embolism (PE). We determined the clinical presentation, initial treatment, and 30-day and 90-day outcomes. We compared the findings with patients with proximal DVT without PE.

Results:
We identified 5,359 patients with IDDVT (mean age 61±17 years, 50% women). The most prevalent comorbidities were hypertension (39%), anemia (28%), prior VTE (14%), active cancer (12%), heart failure (6.7%), and diabetes (6.6%). Recent surgery was reported in 16%. Most participants received anticoagulation (99%), most commonly with low-molecular-weight heparin (88%). No patient received thrombolytics and use of vena cava filters was rare (0.4%). At 30 days, 59 patients (1.1% [99% CI, 0.8%-1.5%]) died, including only 3 from PE (0.1% [99% CI, 0.01%-0.2%]), 44 (0.8% [99% CI, 0.5%-1.2%]) had nonfatal VTE recurrence, and 31 (0.6% [99% CI, 0.4%-0.9%]) had major bleeding. At 90 days, 2.9% (99% CI, 2.4%-3.6%) died (no additional death from PE), 1.5% (99% CI, 1.1%-2.0%) had nonfatal VTE recurrence, and 0.9% (99% CI, 0.6%-1.3%) had major bleeding. When compared with 25,420 individuals with proximal DVT without PE, those with IDDVT had lower co-morbidity burden including diabetes, heart failure, and cancer, but were more likely to have had recent surgery (P<0.001 for all). Patients with IDDVT also had lower odds of 30-day and 90-day death and major bleeding in bivariate and multivariable analyses (Figure).

Conclusions:
In a large multinational study, IDDVT occurred in patients with low comorbidity burden. Most patients with IDDVT received anticoagulation. Fatal PE was rare, and patients had a more benign prognosis compared with those with proximal DVT.
Abstract 15299: Outpatient Intravenous Lasix Trial in Reducing Hospitalization for Acute Decompensated Heart Failure (OUTLAST)
Authors: Hamo Carine E , Abdelmoneim Sahar S , Han Seol Young , Chandy Elizabeth , Muntean Cornelia , Khan Saadat A , Sunkesula Prasanthi , Meykler Marcella , Vidhya Ramachandran , Emelie Rosenberg , Klem Igor , Sacchi Terrence , Heitner John F
Published: May 2021

Introduction:
Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. While previous studies have shown outpatient intravenous (IV) diuretic therapy to be safe and cost-effective, there have been no randomized controlled trials to evaluate the utilization of continued outpatient IV furosemide diuretic maintenance treatment in patients with HF following hospitalization for ADHF.

Hypothesis:
We hypothesized that 30-day hospital readmission from ADHF would be lower with routine, standardized outpatient IV diuretic treatment along with a comprehensive HF care approach vs standard treatment.

Methods:
In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3 hours, biweekly for a one-month period following hospitalization for ADHF. Patients in Groups 2 and 3 also received a comprehensive HF care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment, laboratory, weight, and blood pressure-monitoring, and education during infusion visits. Echocardiography, Kansas City Cardiomyopathy Questionnaire (KCCQ) and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF.

Results:
Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American, 70% HF reduced ejection fraction). There were a total of 14 (15%) readmissions for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p=0.11; p=0.037 comparing Group 2 and Group 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores.

Conclusions:
The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.
Abstract 15339: Prediction of Severe Right Ventricular Failure After Left Ventricle Assist Device Using Echocardiographic Right Ventricular Dp/dt
Authors: Li Dan L , Agrawal Vineet , Hernandez Gabriel , Sandhaus Emily M , Womack Sara , Kim Eun-jeong , Brittain Evan , Shah Ashish S , Mendes Lisa , Zalawadiya Sandip K , Lindenfeld Joann
Published: May 2021

Introduction:
Right ventricular failure (RVF) remains a major cause of morbidity and mortality after continuous flow Left Ventricle Assist Device (CF-LVAD) implantation. Previous risk assessments using pre-operative data to predict RVF have performed only modestly well.

Methods:
We retrospectively studied the potential of echocardiographic RV dP/dt - a non-invasive measure of right ventricular contractility derived from the Doppler signal of tricuspid regurgitation, to predict post-LVAD RVF in patients who were inotrope-independent and those who were on inotropic therapy prior to LVAD. Sixty-five consecutive CF-LVAD recipients at Vanderbilt University Medical Center from 2013-2019 who had a baseline echocardiogram without inotrope support within 3 months prior to LVAD implantation were included. Forty patients from the cohort were started on inotropes prior to LVAD implantation. Baseline off-inotrope and on-inotrope RV dP/dt data were analyzed. Severity of post-LVAD RVF was defined by INTERMACS criteria.

Results:
Of the 65 studied patients, 30 patients had none or mild RVF, 17 had moderate RVF, and 18 had severe RVF. Patients with severe RVF had markedly poorer survival outcome than no/mild and moderate RVF patients. Baseline RV dP/dt was significantly lower in patients who developed post-LVAD severe RVF. A baseline off-inotrope, or on-inotrope RV dP/dt ≥ 300 mmHg/s predicted a low risk of severe RVF with high sensitivity (89% and 80%, respectively) and negative predictive value (91% and 88% respectively); while the presence of both off-inotrope and on-inotrope RV dP/dt < 300 mmHg/s was associated with a high likelihood of post-LVAD RVF (OR 10.5, 95% 1.8-59.4 compared to the rest of the cohort on inotrope therapy).

Conclusion:
Echocardiographic RV dP/dt may be a valuable adjunct tool for prediction of post-LVAD severe RVF in patients undergoing evaluation for LVAD implantation.
Abstract 15340: Reducing Unnecessary Preoperative Cardiology Referral and Cost in Patients Undergoing Bariatric Surgery
Authors: Ibrahim Kaitlyn , Soans Rohit , Tragesser Lauren , Haddad Abdullah , Dalsania Raj , Eddy Vikram J , Zhang Liti , McComb Joseph , Keane Martin G , Whitman Isaac R
Published: May 2021

Introduction:
Candidates for bariatric surgery are at increased risk for cardiovascular disease, which may increase surgical risk. Currently, there are no society guidelines indicating which patients are appropriate for preoperative cardiovascular evaluation and risk stratification.

Hypothesis:
We hypothesized that applying a standardized surgical risk calculator with a novel multidisciplinary internal referral algorithm to stratify patients for preoperative cardiovascular evaluation would decrease unnecessary referrals and cost.

Methods:
All patients undergoing bariatric surgery at our institution between 2014-2018 were identified. After assessing baseline patient characteristics, referral patterns to cardiology, prevalence of cardiac testing ordered, and surgical outcomes were measured. The Revised Cardiac Risk Index (RCRI) score was retrospectively calculated for each patient and grouped as low versus increased risk (RCRI score of 0 versus ≥ 1). Imputing a
post hoc
referral algorithm requiring an RCRI ≥ 1, age ≥ 65, METS ≤ 4, and/or ever smoking history for cardiology referral, we calculated how referral pattern would be affected and the resultant change in referral costs.

Results:
A total of 797 patients underwent bariatric surgery during the study period, of which 68% (n=540) were referred to cardiology preoperatively. Those referred had more hypertension, hyperlipidemia, diabetes, smoking history, and were more likely to have BMI >50 kg/m
2
. Of those referred, 81% (n=438), 15% (n=81), 3% (n=17), and 1% (n=4) had RCRI scores of 0, 1, 2, and ≥ 3, respectively. Of those patients with an RCRI score of 0, 53% (n=234) underwent further cardiac testing. Strictly applying our standardized internal referral algorithm, of the 540 patients referred to cardiology, only 45% (n=199) were appropriately referred. Based on Medicare reimbursement for Level 4 outpatient consults, this would have resulted in a savings of approximately $86,000.

Conclusions:
Among candidates for bariatric surgery, a novel referral algorithm based on RCRI and other cardiovascular risk factors may reduce unnecessary preoperative cardiology referrals, with resultant reduction in resource utilization and overall cost savings.
Abstract 15360: Coronary Artery Dominance, Anatomical Variants and Anomalies in African American Population
Authors: Gonzalez Bonilla Hilda M , Ganta Nitheesha , Awan Ahmad A , Opoku Asare Isaac
Published: May 2021

Introduction:
Coronary arterial dominance is defined by the vessel which gives rise to the posterior descending artery (PDA). The prevalence of right dominance is 80- 85%, left dominance is 8% and codominance is 7% among the general population. The coronary dominance in African Americans is not well known. The aim of this study was to investigate the coronary dominance in African Americans. Previous studies showed that left dominance and codominance are associated with increased post-percutaneous coronary intervention (PCI) in-hospital mortality in patients with acute coronary syndrome (ACS).

Methods:
A retrospective analysis of coronary angiograms performed in our facility was done. A total of 556 cases were reviewed from 2018 to 2019. All the data was collected from the electronic medical records. Patients were categorized by race, gender, age, and comorbidities. Angiograms were reviewed and coronary dominance was determined by the vessel which supplied the PDA.

Results:
From the 556 charts reviewed, 430(77%) cases were performed in African Americans. Of the 430 patients, 220(51%) were male and 210(49%) were female. Mean age was 62.6 years. 370(86%) patients had hypertension, 171(39.7%) had diabetes, 28(6.5%) had peripheral vascular disease, 149(34.6%) had heart failure, 33(7.6%) had history of stroke. 28(6.5%) were on dialysis, 201(46.7%) had dyslipidemia, 14(3.2%) had HIV, 43 (10%) had atrial arrhythmias, 237(55.1%) had history of tobacco use and 21(4.8%) had history of cocaine use. In 390(90.7%) patients, left main coronary artery bifurcated into left anterior descending coronary artery (LAD) and left circumflex artery (LCX). In 40(9.3%) patients, left main coronary artery trifurcated into LAD, LCX and ramus intermedius artery. Among these patients, 303(70.4%) had right coronary dominance, 38(8.8%) had left coronary dominance and 89(20.7%) had codominance. 7 patients had ectasia of the coronary vessels and 8 patients had anomalous origin of coronary vessels.

Conclusions:
Our study showed that African Americans have higher prevalence of codominance compared to general population. It is important to identify it at the time of coronary angiogram since it has been associated with increased post PCI in-hospital mortality in patients with ACS.
Abstract 15368: Index Admission and Thirty-day Readmission Outcomes of Cancer Patients Presenting With Stemi
Authors: Osman Mohammed , Benjamin Mina M , Balla Sudarshan , Kheiri Babikir , Bianco Christopher , sengupta Partho , Daggubati Ramesh , malla midhun , Liu Stephen , Mamas Mamas , Patel Brijesh
Published: May 2021

Introduction:
National-level data of cancer patients’ readmissions after a ST-segment elevation myocardial infarction (STEMI) are lacking.

Objectives:
The primary aim of this study was to describe rates and causes of 30-day readmissions in this population.

Methods:
Among patients who were admitted with STEMI in the United States National Readmission Database (NRD) from October 2015-December 2017, we identified patients with the diagnosis of active breast, colorectal, lung or prostate cancer. The primary endpoint was 30-day unplanned readmission rate. Secondary endpoints included in-hospital outcomes during the index admission and causes of readmissions. A propensity score model was used to compare the outcomes of cancer and no cancer patients.

Results:
A total of 385,522 patients were included in the current analysis (Cancer= 5,956, No Cancer=379,566). After propensity score matching, 23,880 patients were compared (Cancer=5,949, No Cancer=17,931). Cancer patients had higher 30-day readmission (19% vs 14%, p<0.01). The most common causes for readmission among cancer patients were cardiac (31%), followed by infectious (21%), hematological and oncological (17%), respiratory (4%), stroke (4%) and renal (3%). During the first readmission, cancer patients had higher in-hospital mortality (15% vs 7%; p<0.01) and bleeding complications (31% vs 21%; p<0.01). In multivariate logistic regression, cancer status (OR 1.5, 95% CI 1.2-1.6, p<0.01) was an independent predictor for 30-day readmission.

Conclusions:
About one in five cancer patients presenting with STEMI will be readmitted within 30 days. Cancer patients’ 30-day readmissions are still predominantly cardiac-related but with a higher proportion of admissions for infectious, cancer-related and bleeding and than those without cancer.
Abstract 15378: Impact of Delirium on Mortality in Patients Hospitalized for Heart Failure: A National Inpatient Sample Study
Authors: Ritchie Charlotte , Walters Ryan , Ramaswamy Sriram , Alla Venkata M
Published: May 2021

Introduction:
Heart Failure (HF) is one of the leading causes of hospitalization in USA accounting for ≈ 800,000 hospital discharges and $11 billion annually. Delirium is a common problem in the elderly hospitalized patients and can occur in 30-80%.

Hypothesis:
Given the increasing age of the HF population, we hypothesized that rate of delirium in HF hospitalizations is increasing and that delirium is associated adverse outcomes in HF hospitalizations.

Methods:
We queried the 2001-2014 Nationwide Inpatient Sample to identify hospitalizations that included a primary discharge diagnosis of HF (ICD-9-CM: 428.xx) stratified by presence or absence of delirium (ICD-9-CM: 239.0, 290.41, 293.0, 293.1, 348.31). The delirium trend was evaluated using orthogonal polynomial contrasts, whereas differences between delirium and non-delirium for in-hospital mortality, length of stay (LOS), and hospital costs were evaluated using propensity-score matched cohorts; match robustness was evaluated via propensity distributions and standardized mean differences.

Results:
Of the 12.8 million hospitalizations with HF, 89,489 (0.7%) had a diagnosis of delirium. The rate of delirium increased slightly from 0.3% in 2001 to 0.4% in 2007 and increased significantly to 1.6% by 2014 (quadratic p trend < .001). Major predictors of delirium included advanced age, Caucasian race, underlying dementia or psychiatric diagnoses, higher Elixhauser Comorbidity Index, renal failure, cardiogenic shock, and coronary artery bypass surgery. In the propensity-score matched analysis of 76,411 hospitalization with delirium compared to 76,612 without delirium, in-hospital mortality (odds ratio: 1.67, 95% CI: 1.51-1.77), LOS (rate ratio [RR]: 1.47, 95% CI: 1.45-1.51), and hospital costs (RR: 1.44, 95% CI: 1.41-1.48) were all statistically higher in the presence of delirium (all p < 0.001).

Conclusions:
In patients hospitalized with HF, delirium is an independent predictor of increased in-hospital mortality, longer LOS, and excess hospital costs despite adjustment for baseline characteristics. Whether interventions targeting prevention, early recognition, and treatment of delirium will mitigate this excess risk requires evaluation in future studies.
Abstract 15379: A Novel Acoustic Biomarker of Quality of Life in Left Ventricular Assist Device Recipients
Authors: Mainsah Boyla O , Patel Priyesh A , Chen Xinlin , Olsen Cameron , Collins Leslie , Karra Ravi -
Published: May 2021

Introduction:
Left ventricular assist device (LVAD) recipients experience variable improvements in quality of life (QoL). Methods for optimizing LVAD support to improve QoL are needed.

Hypothesis:
We hypothesized that acoustic signatures obtained from digital stethoscopes can predict patient-centered outcomes in LVAD recipients.

Methods:
Subjects were recruited from the LVAD clinic at Duke University Medical Center. Subjects were trained to use a digital stethoscope and recorded their precordial sounds weekly for 6 months. Subjects also completed a Kansas City Cardiomyopathy Questionnaire (KCCQ) weekly. The primary outcome for this study was QoL, as measured by the KCCQ summary score.

Results:
Twenty-four subjects, 8 supported by a HeartWare LVAD and 16 supported by a HeartMate3 (HM3) LVAD, were enrolled. We developed a novel algorithm to filter LVAD sounds from recordings. Unsupervised clustering of LVAD-mitigated sounds revealed discrete groups of acoustic features. Six out of 16 [38%] HM3 recipients made up a unique cluster and shared a common acoustic feature that we have termed the pulse synchronized sound (PSS) based on its temporal association to the artificial pulse of the HM3. Subjects with the PSS had significantly better KCCQ scores at baseline (median, 89.1 [IQR, 86.2-90.4] vs 66.1 [IQR, 31.1-73.7],
P
= 0.03) and over the 6 months of the study (mean = 79.67 [95% CI, 74.55 - 84.78] vs 60.57 [95% CI, 55.58 - 65.55],
P
< .001). Mechanistically, the PSS shares acoustic features with patient-derived intrinsic sounds. Because the PSS cannot be detected by routine auscultation, we developed a robust machine learning algorithm to detect the PSS in precordial sound recordings (AUC = 0.95 by leave-one-subject out cross-validation).

Conclusions:
We have identified a novel acoustic feature associated with better QoL in HM3 recipients. This novel biomarker is the first of its kind in LVAD recipients and may provide a method for assaying optimized LVAD support.
Abstract 15386: Integrated Phosphoproteome and Transcriptome Analysis of Biased Agonists at CXCR3 Reveals Differential Cellular Outputs of Inflammation
Authors: Zheng Kevin Z , Eiger Dylan , Smith Jeffrey S , Warman Anmol , Tsai Chia-Feng , Jacobs John M , Shi Tujin , Rajagopal Sudarshan
Published: May 2021

Background and Objective:
G-protein-coupled receptors (GPCRs) are the most common cell surface receptor class and are known to influence nearly every biological process. GPCRs signal through downstream effectors such as G proteins and β-arrestins. Certain ligands drive activation of G protein over β-arrestin signaling, or vice versa - a phenomenon known as biased agonism. To investigate the mechanisms and implications of biased agonism, we studied CXCR3, a chemokine receptor expressed on T cells, which binds three biased endogenous ligands, CXCL9, CXCL10, and CXCL11. Importantly, CXCR3 has been implicated in atherosclerosis and other inflammatory diseases.

Methods:
To obtain a broad view of biased signaling at CXCR3, we performed global phosphoproteomic and transcriptomic analyses of CXCR3-transfected HEK 293 cells and activated human CD8+ T-cells, respectively, treated with CXCL9, CXCL10, and CXCL11. To assess the phosphoproteome, we utilized an antibody-free mass spectrometry approach with high-pressure, high-resolution separation and intelligent selection. RNA-seq was performed to assess transcriptomic changes in activated CD8+ T-cells.

Results:
Our analyses revealed 1532 phosphosites and 887 transcripts differentially regulated between treatment groups. Gene Set Enrichment Analysis (GSEA) of CXCL11-treated cells revealed enrichment of pro-inflammatory targets including the Myc and TNF-α pathways via NFKB not observed in CXCL10- or CXCL9-treated cells. GSEA of CXCL10- and CXCL11-treated cells also revealed enrichment of the IL6-JAK-STAT3 pathway, linked to chronic inflammatory conditions. Kinase-Substrate Enrichment Analysis (KSEA) revealed differential phosphorylation activity associated with multiple kinases including AURKB (CXCL9), ROCK1 (CXCL9, 10, 11), CDK9 (CXCL10), and ATM (CXCL10, 11) - all known to regulate pro-inflammatory targets. Several phosphoproteins were transcription factors, including p53, known to mediate IL-6 production and atherosclerosis pathogenesis.

Conclusion:
Together, our integrated analysis of phosproteomic and transcriptomic data reveal the extent of differential cellular outputs produced by biased agonists at CXCR3 in modulating targets implicated in inflammatory diseases.
Abstract 15507: Trajectories of Point of Care B-type Natriuretic Peptide (bnp) and Its Role as a Predictor of All-cause Mortality Among Hiv and Non-hiv Heart Failure Patients in Uganda
Authors: Okello Samson , Abeya Fardous C
Published: May 2021

Introduction:
The usefulness of serial measurement of BNP to reduce hospitalization or mortality in patients with HIV and heartfailure is unknown.

Hypothesis:
We sought to describe changes in B-type natriuretic peptide (BNP) and estimate the effect of HIV on BNP over a week of observation in an acute heart failure cohort of 40 HIV-infected adults (≥18 years) on antiretroviral therapy (ART) and 175 HIV-uninfected hospitalized patients in Uganda.

Methods:
We measured BNP using i-STAT BNP (Abbott point of care, Princeton, New Jersey) and compared changes by HIV serostatus, and evaluated BNP as a predictor of all-cause mortality at 30 days from hospitalization using multilevel mixed and competitive risk regression models respectively.

Results:
Overall HIV-infected participants had a higher mean BNP than HIV-uninfected counterparts. After initial declines in BNP in both groups between day 0 and day 3, BNP moderately increased among the HIV-infected on day 7 and continued to decline in the HIV-uninfected group. Each 1 pg/mL increase in baseline BNP from 400 pg/mL increased the risk of all-cause mortality within 30 days by 1% (adjusted standardized hazard ratio (aSHR) 1.01, 95%CI 1.01, 1.01). Other predictors of increased 30-day all-cause mortality included smoking (aSHR 1.99, 95%CI 1.04, 3.84), hypotension (aSHR 1.69, 95%CI 1.26, 2.26) and renal failure stage 3 (aSHR 2.06, 95%CI 1.34, 3.18), and renal failure stage 5 (aSHR 2.02, 95%CI 1.30, 3.13). We found a lower risk of 30-day all-cause mortality of 38% (95%CI 20%, 73%) for those receiving loop diuretics and 74% (95%CI 56%, 99%) for antiplatelet agents.

Conclusions:
Over a week of observation, HIV-infected people hospitalized with acute heart failure in Uganda have higher BNP levels than HIV-uninfected counterparts. Increases in BNP above the upper bound of the normal predicted heightened risk of all-cause mortality within 30 days of hospitalization.
Abstract 15509:
SYNE2
Expression Regulates Calcium Cycling and Mitochondria Function in Cardiomyocytes: Implications for Association With Atrial Fibrillation
Authors: Liu Nana , Witherow Conner , Prasad Sathyamangla V , Barnard John , Van Wagoner David , Chung Mina K , SMITH Jonathan D
Published: May 2021

Introduction:
SYNE2
encodes a nuclear membrane protein that connects the nucleus with the cytoskeleton. rs1152591 is a common SNP in the
SYNE2
gene that is associated with atrial fibrillation (AF) and with reduced expression of
SYNE2α1
, a short isoform, in human left atrial appendage tissue. We previously found that
SYNE2α1
over expression (OE) acts as a dominant negative for the nuclear phenotype, similar to the
SYNE2
knockdown (KD), leading to enlarged nuclear size and decreased nuclear stiffness.

Objectives:
To determine if GFP-
SYNE2α1
(OE) and KD of all
SYNE2
isoforms show similar effects on gene expression and cell physiology in human induced pluripotent stem cell-derived cardiomyocytes (iCMs).

Methods and Results:
RNAseq after
SYNE2α1
OE or
SYNE2
KD revealed both congruent changes in expression of specific genes, supporting the dominant negative role of
SYNE2α1
, but also divergent changes in expression of some genes, showing specific effects of the
SYNE2α1
short isoform. We identified both mitochondrial function and sarcoplasmic reticulum (SR) function as differentially expressed pathways comparing OE vs. KD iCMs. Fura-2 photometry was used to study Ca
2+
cycling in beating iCMs, and revealed delayed calcium reuptake in the
SYNE2
KD cells (15.9% increase in reuptake time as % of each contraction, p<0.0001), but not in the GFP-
SYNE2α1
OE cells (not significant). Flow cytometry showed significantly lower
SERCA2
expression in the
SYNE2
KD cells but not in the
SYNE2α1
OE cells (12% decrease, p=0.029). Immunofluorescence microscopy revealed that GFP-SYNE2α1 not only localized to the nuclear membrane but also to the SR, stained with anti-SERCA2. Flow cytometry after MitoTracker Orange staining, to monitor the cellular volume of functional mitochondria, was significantly increased in both the
SYNE2α1
OE and
SYNE2
KD iCMs vs. their respective controls. Thus, despite differential expression of mitochondrial pathway genes,
SYNE2α1
mimics the KD of all SYNE2 isoforms in regard to mitochondrial function.

Conclusions:
SYNE2α1
OE, unlike KD of all SYNE2 isoforms, preserves SR Ca
2+
reuptake activity, and this may contribute to the mechanism by which the AF risk allele in the SYNE2 gene, associated with decreased expression of SYNE2α1, predisposes carriers to AF.
Abstract 15514: Ace Inhibitors, Angiotensin Receptor Blockers, and Outcomes in Hospitalized Patients With Severe Covid-19 Pneumonia
Authors: Grewal Prabhjot , Yoo Jeanwoo , Papamanoli Aikaterini , Mojahedi Azad , Dhaliwal Simrat , Nakamura Jacquelyn , Abata Joshua , Robin Jacob , Fung Jenny , Hotelling Jessica , Rawal Sahil , Karkala Nikitha , Tsui Stella T , Coritsidis Alexandra , Marcos Luis , Bloom Michelle E , Skopicki Hal , Kalogeropoulos Andreas P
Published: May 2021

Introduction:
Angiotensin converting enzyme (ACE) 2, is a co-receptor for the entry of SARS-CoV-2 into target cells. The impact of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with coronavirus disease 19 (COVID-19) is under investigation.

Hypothesis:
ACEIs/ARBs are associated with worse outcomes in patients hospitalized with COVID-19.

Methods:
We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O2). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of previous (home) use of ACEIs or ARBs with mortality and the composite of death or MV.

Results: Table 1
summarizes the patient characteristics according to ACEI/ARB use (ACEI: 73; ARB: 73; 146/469 patients, 31.1%). After a median of 13 days (8-22), 123 patients (26.2%) died and 105 patients (22.4%) required MV and survived. In models adjusting for age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, heart failure, atrial fibrillation, chronic lung disease, chronic kidney disease, and baseline 0
2
saturation, ACEIs/ARBs were not associated with mortality (HR 1.00; 95%CI 0.62-1.61; P=0.99). There was no difference between classes in mortality (ACEI vs. ARB: HR 1.14; 95%CI 0.61-2.15; P=0.68). However, there was a trend towards lower rates of death or MV with ACEI/ARB (HR 0.75; 95%CI 0.54-1.05; P=0.095), mainly because of lower MV rates. The protective effect of ARBs on the composite was significant (HR 0.66; 95%CI 0.44-0.99; P=0.046) whereas that of ACEIs was not (HR 0.87; 95%CI 0.57-1.31; P=0.50), albeit difference was not significant (P=0.28).

Conclusions:
In patients with severe COVID-19 pneumonia, ACEI/ARB use was not associated with mortality. Especially ARBs may reduce need for MV in this high-risk COVID-19 population.
Abstract 15515: Cardiovascular Phenotyping of the APP23 Overexpressing Mouse Model of Alzheimer’s Disease Reveals Decreased Vascular Contractility
Authors: Hendrickx Jhana O , De Moudt Sofie , Van Dam Debby , De Meyer Guido , Fransen Paul
Published: May 2021

Background and Aim:
Alzheimer’s disease (AD), the most common form of dementia, is characterized by noticeable neuropsychiatric symptoms and cognitive decline. Increasing epidemiological and experimental evidence highlights the occurrence of cardiovascular (CV) disease in the progression of AD. Therefore, we aimed to investigate the cardiovascular phenotype of the APP23
+/-
overexpressing mouse model (APP23
+/-
).

Methods:
The current study presents the CV characterization of APP23
+/-
mice (male, n=10) compared to C57BL/6 (male, n=24) at 6 months of age, including
in vivo
analysis of blood pressure (BP, CODA), aortic pulse wave velocity (aPWV), and echocardiography (high-frequency echocardiography, VEVO2100). Serum corticosterone levels and vascular smooth muscle cell (VSMC) phenotypic markers were ascertained via ELISA and qPCR. Data are presented as mean ± SEM.

Results:
At 6 month of age, APP23
+/-
mice experience a lower survival rate compared to C57BL/6 littermates (39% vs. 100%, p=0.001) and APP23
+/-
mice showed increased corticosterone levels compared to C57BL/6 mice (13.39 ± 5.15 vs. 2.30 ± 2.52 μg/mL, p=0.0025). Peripheral BP was increased (systolic BP: 110 ± 5 vs. 99 ± 3 mmHg, p=0.045; diastolic BP: 81 ± 5 vs. 71 ± 3 mmHg, p=0.09) with unaltered pulse pressure. Echocardiography revealed no differences in systolic and diastolic heart function.
In vivo
arterial stiffness was elevated in APP23
+/-
mice (aPWV: 4.08 ± 0.3 vs. 2.94 ± 0.1 m/s, p=0.0004). Vascular reactivity studies showed decreased (32 %) adrenoreceptor-dependent contractions of the thoracic aorta from APP23
+/-
mice. Endothelial-dependent (acetylcholine) and -independent (diethylamine nonoate) relaxations were unaffected. Contractile VSMC markers remained unchanged.

Conclusion:
In conclusion, APP23
+/-
mice present with high serum corticosterone levels, elevated pulse wave velocity and decreased vascular contractility.
Abstract 15525: Morphology of Calcification on Culprit Site: A Significant Indicator of Plaque Erosion in Acute Coronary Syndrome
Authors: NAGAI Michiaki , Dote Keigo , Kato Masaya , Oda Noboru , Kunita Eiji , Kagawa Eisuke , YAMANE AYA , Kobatake Hiroshi , Shiota Haruko , Osawa Ayano , Ishibashi Naoki , Takahashi Kazuki
Published: May 2021

Introduction:
While clinical predictors of plaque erosion (PE) in patients with acute coronary syndromes (ACS) were reported, PE was more frequently observed in the population with normal kidney function. On the other hand, earlier studies indicated that spotty calcification related to plaque rupture on the culprit site in ACS. However, the morphological features of coronary calcification on culprit site have not been investigated in relation to PE.

Hypothesis:
We assessed the hypothesis that the morphology of calcification on culprit site was associated with PE in ACS patients without chronic kidney disease (CKD).

Methods:
In the 166 ACS patients (66.9±10.7 years old, male 83 %), based on Optical Coherence Tomography/ Optical Frequency Domain Imaging, existence of PE on culprit site was investigated. In the morphological features of coronary calcification, the maximum thickness, maximum area, maximum angle, minimum depth from the lumen in axial sections, and the length in longitudinal image were determined.

Results:
There were the 73 patients with PE, 58 patients with calcification and 38 patients with CKD. A marginal significant difference in thickness (300 vs 190μm, p=0.07) and significant difference in angle (60 vs 23degree, p=0.001), area (0.89 vs 0.43mm
2
, p=0.001) and length (2.34 vs 1.12 mm, p=0.03) were observed between the patients with PE and the patients without PE. In the multiple regression analysis adjustment for age, gender, region location, maximum creatine phosphokinase, STEMI or not, diabetes mellitus, angiotensin receptor blockers use, statin use and systolic blood pressure on admission, angle (OR: 1.01, 95%CI: 1.002 to 1.013, p=0.005) and area (OR: 1.46, 95%CI: 1.02 to 2.1, p=0.04) each had significant associations with PE. Specifically, only in the patients without CKD, thickness (p=0.025), angle (p=0.003) and area (p=0.013) were significant indicators of PE.

Conclusions:
In conclusion, morphology of calcification on culprit site was a significant indicator of PE in the patients with ACS. Specifically, larger calcification might serve as a pathophysiology underlying in the phenotype of plaque vulnerability in ACS patients with normal kidney function.
Abstract 15528: Tafamidis Free Acid 61 Mg in Patients With Transthyretin Amyloid Cardiomyopathy
Authors: Nativi-Nicolau Jose , van der meer peter , Gundapaneni Balarama , Sultan Marla B , Garcia-Pavia Pablo
Published: May 2021

Introduction:
Tafamidis meglumine, available as 20 mg capsules, is approved around the world for the treatment of transthyretin amyloidosis in early stage polyneuropathy (20 mg) and more recently in cardiomyopathy (80 mg). A new formulation, tafamidis free acid 61 mg (a single capsule bioequivalent to tafamidis meglumine 80 mg), was subsequently developed as a more convenient option for patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and further characterization of its safety profile would be of value.

Methods:
Patients who completed the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) were eligible to enroll in a long-term, extension study (LTE). The LTE was subsequently expanded to include ATTR-CM patients not previously enrolled in ATTR-ACT, with all patients receiving tafamidis free acid 61 mg (tafamidis 61 mg). As of 20 July, 2018, patients in the LTE were transitioned to tafamidis free acid 61 mg (data assessed for patients treated with tafamidis 80 mg in the LTE who transitioned to tafamidis free acid 61 mg [tafamidis 80/61 mg]). Adverse events (AEs) during the LTE are described (as of 1 Aug, 2019) and compared with AEs with tafamidis 80 mg in ATTR-ACT.

Results:
There were 164 patients treated with tafamidis 80/61 mg and 715 newly enrolled patients treated with tafamidis 61 mg; with 157 (95.7%) AEs with tafamidis 80/61 mg and 458 (64.1%) with tafamidis 61 mg. The most common AEs by system organ class were cardiac disorders (
Table
). AEs with tafamidis 80/61 mg were broadly similar to those with tafamidis 80 mg in ATTR-ACT (previously shown to be similar to placebo). While there were fewer AEs with tafamidis 61 mg, the notably shorter exposure time in this group limits direct comparisons. Nevertheless, no new safety concerns emerged in patients who transitioned to, or started, tafamidis 61 mg.

Conclusions:
For patients with ATTR-CM, tafamidis free acid 61 mg is a safe treatment which also offers improved patient convenience.
Abstract 15539: Single-cell Analysis of Aortic Tissues From Patients With Marfan Syndrome Reveals Changes in Smooth Muscle Cell Differentiation
Authors: Dawson Ashley , Li Yanming , Ren Pingping , Vasquez Hernan , Zhang Chen , Ageedi Waleed , Luo Wei , Zhang Lin , Li Yang , Sheppard Mary B , Lu Hong S , Cassis Lisa A , Coselli Joseph S , Daugherty Alan , Shen Ying H , Lemaire Scott A
Published: May 2021

Background:
Thoracic aortic aneurysms associated with Marfan syndrome (MFS) carry a high risk of mortality; however, the molecular and cellular processes leading to aortopathy in this population remain poorly understood. We aimed to use single-cell RNA (scRNA) sequencing to define the non-immune cell populations present within the aortic wall in MFS, hypothesizing that these would differ from those of non-aneurysmal control tissue.

Methods:
We performed scRNA sequencing of ascending aortic aneurysm tissues from MFS patients (n=3) undergoing aneurysm repair and of age-matched, non-aneurysmal control tissue from cardiac transplant donors and recipients (n=4). The Seurat package in R was used for analysis. Differentially expressed genes were identified using edgeR.

Results:
Eighteen non-immune cell clusters were identified, with conserved gene expression of the largest of the clusters consistent with smooth muscle cells (SMCs; n=6), fibroblasts (n=3), and endothelial cells (n=3). The SMCs and fibroblasts exhibited graded changes in their expression of contractile and extracellular matrix protein genes, supportive of a phenotypic continuum. Additionally, we identified differences in the proportions of non-immune cells in MFS tissues compared to controls. In control tissues, the most common non-immune cells expressed markers of contractile SMC maturity including
CNN1
,
MYH11
, and
SMTN
. In contrast, the largest clusters in MFS tissue were most closely related to SMCs on correlation analysis, but displayed increased expression of cyclin genes as well as immune, endothelial, and fibroblast genes indicative of de-differentiated, proliferative SMCs. Additionally, expression of genes associated with SMC phenotypic maturity, including
MYH11
and
MYOCD
, were significantly downregulated in several of the MFS SMC clusters.

Conclusion:
Our data demonstrate a phenotypic continuum between fibroblasts and SMCs, with aortas from patients with MFS exhibiting an increased proportion of de-differentiated, proliferative SMCs compared to controls. Additionally, markers of SMC maturity were downregulated in SMCs in MFS compared to controls. This may be due to disruption of signaling pathways that promote differentiation.
Abstract 15542: Late Pulmonary Hypertension in Surgically Palliated D-transposition of the Great Arteries: A 55-year Review
Authors: Suter Blair , Hall Dylan , Ebenroth Eric S , Markham Larry W , Johansen Michael
Published: May 2021

Introduction:
Pulmonary hypertension (PH) has been described following surgical palliation for transposition of the great arteries (D-TGA). While early pulmonary vascular disease is associated with late repair, the increasing prevalence of late PH has been observed following the intra-atrial baffle procedure (ABP), Mustard/Senning. A previous study from our institution identified patients with precapillary PH. More recent studies have described predominately postcapillary PH, suggesting multiple, differing mechanisms for this complication.

Hypothesis:
While heart failure is a common complication following ABP and is associated with postcapillary PH, we hypothesize that precapillary PH can be identified in a subset of patients.

Methods:
A retrospective descriptive study was performed at a single institution. Using 6
th
World Symposium on Pulmonary Hypertension definitions. PH was defined as a mean pulmonary artery pressure >20mmHg. Etiology of PH was defined as precapillary (≥3 Wood units) versus postcapillary (pulmonary artery wedge pressure >15 mmHg).

Results:
We reviewed 157 D-TGA patients following ABP, finding 33 patients with PH. Mean age at last evaluation was 36.6 (14-54) years. Current condition: 22 alive, 7 dead, and 4 lost to follow-up. Etiology of PH: 10 precapillary, 8 postcapillary, 8 mixed, 2 borderline PH, and 2 did not undergo catherization. Additionally, 2 patients had pulmonary venous baffle obstruction and 1 had left lung hypoplasia. Of patients with recent imaging, 21 of 25 had systemic RV systolic dysfunction on echocardiogram or MRI.

Conclusions:
Late-onset PH in D-TGA following ABP is a significant long-term complication and warrants vigilant surveillance. This highlights the limitations of imaging and need for catheterization for complete evaluation. In this study, we observed precapillary PH in a majority of patients with PH, which differs from some previous studies. Identifying the etiology of PH could drastically alter treatment strategies and has implications for transplant consideration. Further studies are needed to identify the clinical attributes that contribute to this process.