bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16923: Healthy Lifestyle is Inversely Associated With All-Cause Mortality Irrespective of Medication Burden
Authors: Kelly Neil , Soroka Orysya , Onyebeke Chukwuma , Pinheiro Laura , Banerjee Samprit , Safford Monika M , Goyal Parag
Published: May 2021

Introduction:
The benefits of a healthy lifestyle in the context of a high disease and medication burden are not clear.

Hypothesis:
Healthy lifestyle is inversely associated with all-cause mortality among adults with high medication burden.

Methods:
We examined participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Exposure variables were 4 healthy behaviors: adherence to a Mediterranean diet, physical activity, smoking abstinence, and sedentary lifestyle avoidance (low TV time). Each behavior was scored from 0-2, where 0 indicated low adherence and 2 indicated high adherence. We also examined a cumulative Health Behavior Score (HBS) based on the sum of individual behavior scores (range 0-8). The main outcome was all-cause mortality. To examine the association between each behavior and mortality, we estimated Cox proportional hazards models for each medication burden stratum (no polypharmacy: 0-4 medications at baseline; polypharmacy: 5-9; hyperpolypharmacy: ≥ 10), adjusting for socio-demographics, health status, comorbid conditions, and medication adherence.

Results:
Among 20,417 participants (9.8 ± 3.8 years followup), mean age was 64.8 ± 9.2 years, and 56% were women. At baseline, 44% had no polypharmacy, 39% had polypharmacy, and 17% had hyperpolypharmacy. Mortality increased with increasing medication burden (no polypharmacy: 19.1%; polypharmacy: 29.7%; hyperpolypharmacy: 41.3%). The highest score for each behavior was inversely associated with all-cause mortality in all 3 strata. The highest HBS for each stratum conferred substantial benefit (no polypharmacy: HR 0.52 (95% CI 0.45-0.61); polypharmacy: HR 0.55 (95% CI 0.49-0.63); hyperpolypharmacy HR 0.69 (95% CI 0.58-0.82)) (Table).

Conclusions:
Healthy lifestyle was inversely associated with all-cause mortality irrespective of medication burden, supporting the value of healthy lifestyle counseling even among adults with high medication burden.
Abstract 16958: Comparison of Clinical and Hemodynamic Outcomes Between Redo Surgical Aortic Valve Replacement versus Transcatheter Valve in Valve in Patient With Failed Aortic Bioprostheses
Authors: Hecht Sebastien , Bernard Jeremy , Tastet Lionel , cote nancy , Salaun Erwan , Guimaraes Leonardo , Dumont Eric , Mohammadi Siamak , Rodés-Cabau Josep , Pibarot Philippe
Published: May 2021

Introduction:
Transcatheter valve-in-valve implantation (ViV) has emerged as an alternative to redo surgery (REDO) for the treatment of failed surgical aortic bioprostheses. However, there are few studies comparing clinical and hemodynamic outcomes between REDO and ViV in both the short- and long- term follow-up.

Objective:
The aim of this study was to compare hemodynamic and clinical outcomes between REDO and ViV.

Methods:
A total of 184 patients who underwent REDO or ViV at our institution between 2003 and 2017 were included in this study. Clinical and transthoracic echocardiography (TTE) data were collected for each patient. TTE was performed prior and after the reintervention and were retrospectively analyzed in an echocardiography core laboratory. An inverse propensity treatment weighting (IPTW) was used to compare outcomes between groups.

Results:
104 patients underwent REDO and 80 underwent ViV. Prevalence of suboptimal valve hemodynamics (mean gradient ≥ 20 mmHg and/or ≥ moderate aortic regurgitation) following reintervention was higher in ViV group (29.8% vs. 61.3%, p<0.001), the rate of novel permanent pacemaker tended to be higher with REDO (10.6% vs. 3.8%, p=0.08). During a median follow-up of 5.0 (3.7-7.5) years, 60 patients died. There was a trend toward higher rate of 30-day mortality in the REDO vs. ViV group (8.6% vs. 2.5%, OR [95% CI]: 3.70[0.77-17.6], p=0.10) and a trend toward lower risk of long-term mortality in REDO (HR [95% CI]: 0.61[0.33-1.14], p=0.12). In multivariate cox proportional analysis adjusted for age, sex, EuroSCORE 2, ViV was significantly associated with increased risk of long-term mortality (HR [95% CI]: 2.28[1.25-4.15], p=0.03). Results were confirmed in IPTW analyses (30-day mortality in REDO vs. ViV: 3.39[3.25-3.53], p<0.001; long-term mortality: 0.70[0.69-0.71], p<0.001).

Conclusions:
ViV was associated with lower risk of 30-day but higher risk of long-term mortality compared to REDO.
Abstract 16970: Prognostic Utility of High-Sensitivity Troponin I Among Hospitalized COVID-19 Positive Patients in Michigan - A Retrospective Analysis
Authors: Altibi Ahmed M , Sheth Radhika , LeDuc Allison , Al Jebbawi Lama , Masri Ahmad , Slota Alexander , Liaqat Hassan , George Matthew , Jain Saniya , Abdallah Enas , Russell Luke , Shirvanian Narine , Patel Brijesh D , Bhargava Pallavi , Kak Vivek
Published: May 2021

Introduction:
Cardiac injury, evidenced by elevated troponin levels, had been proposed as a prognostic marker in COVID-19 patients.

Hypothesis:
We conducted a retrospective analysis to investigate whether high-sensitivity troponin I (hs-TNI) predicts mortality in hospitalized COVID-19 patients.

Methods:
Medical records for all COVID-19 positive patients hospitalized between March 1 and May 10, 2020 were reviewed retrospectively (n= 708). Patients with no available hs-TNI data (n=22) were excluded. Elevated hs-TNI was defined as values >18 ng/L. Multivariate logistic regression and Cox proportional-hazard model were used to investigate association between hs-TNI and in-hospital and 30-day mortality. Adjustment in both models was for age, gender, and race. Kaplan-Meier curve was plotted to compare mortality in patients with and without cardiac injury.

Results:
In 684 included patients, mean age was 66.9±15.6, 57.6% were males, and 47.7% were Caucasians. Prevalence of comorbidities: hypertension 74.3%, dyslipidemia 57.8%, type 2 diabetes 33.9%, coronary artery disease 19.6%, prior myocardial infarction 9.2%, and heart failure 16.2%. hs-TNI was elevated in 36.6% of included patients. 30-day mortality was higher in patients with elevated hs-TIN (46.8% vs. 14.3%). Unadjusted OR of in-hospital death was 5.0 (95% CI: 3.36-7.31, p-value <0.001) and adjusted OR was 2.97 (95% CI: 1.93-4.55, p-value <0.001). Unadjusted HR of 30-day mortality was 4.1 (95% CI 3.0-5.6, p-value <0.001), and adjusted HR was 2.10 (95% CI: 1.49-2.95, p-value <0.001).

Conclusions:
Elevated troponin levels in hospitalized COVID-19 patients is associated with significant increase in risk of in-hospital and 30-day mortality.
Abstract 16993: Impact of Donor and Recipient Cytomegalovirus Immune Status on Long-Term Graft Survival in Pediatric Heart Transplantation
Authors: Rabbani Naveed , Kronmal Richard , Albers Erin L , Friedland-Little Joshua , Hong Borah , Kemna Mariska , Law Yuk M
Published: May 2021

Introduction:
While CMV infection has been associated with graft loss in adult heart transplants, its role in children is less understood. We aim to better understand the effect of donor and recipient CMV immune status at transplant on survival in pediatric recipients.

Methods:
We analyzed 6,951 pediatric heart-only transplants in the Scientific Registry of Transplant Recipients (1987-2019). Patients were stratified by recipient and donor CMV status at transplant. The primary endpoint was freedom from graft loss.

Results:
Of the various donor and recipient CMV statuses, only CMV-positive recipients had decreased graft survival compared to CMV-negative ones (at 15-yrs: 47% vs. 53%, HR 1.14). However, when fully adjusted by Cox regression, recipient status was no longer a risk factor (
p
= 0.12). In this model, anti-CMV treatment with ganciclovir or valganciclovir was associated with a lower risk of graft loss (HR 0.80, CI 0.71 - 0.90,
p
< 0.005). When stratified by the four donor-recipient CMV status combinations, antiviral use was associated with improved survival in both donor-positive groups: most strongly in donor-positive/recipient-positive transplants (at 15-yrs: 51% vs. 39%,
p
< 0.005) and to a lesser extent in donor-positive/recipient-negative transplants (at 15-yrs: 53% vs. 51%,
p
< 0.005). The association is maintained when examined by era, such as with more frequent use of anti-CMV therapy after 1995. No association with antiviral use was observed in either donor-negative transplant group.

Conclusion:
CMV-positive recipients had greater long-term graft loss, although this may be confounded by other transplant characteristics. Anti-CMV therapy is associated with improved long-term graft survival in transplants with CMV-positive donors. This finding may explain the lack of association between donor CMV status and graft loss in that an association may be masked by antiviral use. Further investigation of anti-CMV therapy may mitigate risk of graft loss.
Abstract 16995: Anti-Inflammatory and Immuno-Modulatory Properties of Neonatal MSC
Authors: Sharma Sudhish , Mishra Rachana , Saha Progyaparamita , Gunasekaran Muthukumar , Shah Aakash , Abdullah Mohamed , Kaushal Sunjay
Published: May 2021

Background:
Anti-inflammatory and immunomodulatory properties are prerequisites for the success of cell therapy as shown by adult Mesenchymal Stem cells (MSC) by reducing both B- and T-lymphocyte proliferation, in a paracrine dependent manner. Proteomics of neonatal MSCs (nMSCs) has identified the superior quality of secretome containing a significantly higher number of anti-inflammatory (68 vs 21 in aMSCs) molecules.

Hypothesis:
nMSCs have potent anti-inflammatory and immunomodulatory characteristics as compared to other cell types currently being used as cell therapy.

Methods:
nMSC were tested and compared to other cell types for: a) Hypo-immunogenicity (expression of MHCII in the presence of IFN-gamma), b) immunogenicity (reduce proliferation of human CD4+ T-cells in a co-culture mixed lymphocyte reaction (MLR), c) anti-inflammatory properties (reduce IL-8 secretion of macrophages in the presence of Nigericin, d) systematic immune response (using rat myocardial infarction (MI) model (IL10, TNF-a and IL12)) and e) Immunomodulation (CD4+ cells to T
reg
CD4
+
/CD25
+
/FoxP3
+
).

Results:
Expression of MHCII on nMSCs, after 72 hours of exposure to IFN-gamma and proliferation of CD4
+
cells in MLR was significantly (40±3.8% and 55±4.3%, n=5) reduced as compared to aMSC or CDC. IL8 was measured in the supernatants of nMSC derived secretome reduced the secretion of IL8 from activated macrophages in a dose dependent manner (150 ug protein/ml). Intravenous injection of nMSCs in a rat MI model significantly reduced serum levels of of TNF-α and IL-12 while upregulated IL-10 and improving myocardial function. While BM-MSCs and aMSCs failed to significantly modulate immune system, nMSC significantly increased the number of Treg cells as compared to CDC. Similar results were observed with Pig IRI model.

Conclusions:
Together, in a head-to-head comparison, nMSCs outperformed all other competitive cell types currently under investigation for their tissue repairing role, including CDCs and BM-MSCs to achieve the highest clinical efficacy.
Abstract 16996: Relationship of Paravalvular Leak and Mean Platelet Volume With Stroke Risk Following Transcatheter Aortic Valve Replacement
Authors: Rahgozar Kusha , Hasani Aliaskar , Kargoli Faraj , Latib Azeem , Jorde Ulrich P
Published: May 2021

Introduction:
Stroke remains a major complication patients may face following Transcatheter Aortic Valve Replacement (TAVR). It has been hypothesized that turbulent flow across persistent paravalvular leak (PVL) may lead to low level hemolysis, a state known to heighten serum thrombotic potential and increase stroke risk. We hypothesized that the presence of paravalvular leak would lead to elevations in serum mean platelet volume (MPV), a marker of platelet activation and aggregation, and thus would heighten stroke risk after TAVR.

Methods/Results:
We retrospectively reviewed the charts of 322 patients who underwent TAVR at Montefiore Medical Center from January 2015 to January 2019. Stroke was seen in 24 patients (7%) following TAVR and was associated with higher overall mortality (p=<0.001). PVL was recorded in scaling severity of “none”, “trace”, “mild”, “moderate”, and “severe”. “Significant PVL”, defined as the presence of “mild” or greater PVL on initial post-op transthoracic echocardiogram, was found in 72 patients (22.4%). No associations were seen between the presence of significant PVL and stroke after TAVR. Serum MPV values after TAVR were not associated with the presence of significant PVL, nor with an increase in the observed rate of stroke or death on follow-up.

Conclusions:
Stroke after TAVR is significantly associated with increased mortality. In our dataset, the presence of significant PVL was not associated with increased rate of stroke or elevated serum MPV levels post-TAVR. Moderate and severe PVL are known to generate the greatest amount of hemolysis and were rare in our dataset (combined 1.5%), likely contributing to the lack of significant findings.
Abstract 17008: Cardiologist Adherence to Physical Activity Guidelines: Failure to Walk the Walk
Authors: Gualano Sarah K , Theriot Paul , Mehta Laxmi S , Duvernoy Claire S
Published: May 2021

Introduction:
The 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease recommends adults engage in ≥ 150 minutes of moderate or ≥75 minutes of vigorous intensity aerobic activity per week to reduce cardiovascular risk. Cardiologist adherence to these guidelines is unknown.

Methods:
Electronic surveys were sent to 437 ACC CardioSurve cardiologists, a representative sample of current ACC members. Demographic data was collected. Respondents were asked to quantify and rate intensity of exercise in an average week.

Results:
Between February and March 2020, a total of 189 panelists completed the survey for a response rate of 43%, of which 13% were women. There was even representation in number of years in practice: 33% early career, 27% mid-career, and 35% late career. Cardiologists across all career stages were evenly represented; 33% early career, 27% mid-career, and 35% late career. Overall only 56% of cardiologists met exercise guidelines (Figure). Less than half participated in vigorous activity (46%) with higher prevalence among mid versus early career (58% vs 38%, p=0.035). Interventional cardiologists were less likely to meet the standards for exercise intensity compared to general cardiology (44% vs. 59%, p=0.09). Early career respondents were less likely to adhere to activity recommendations (39% vs 59%, p=0.018). Those who reported vigorous activity were more likely to strength train at least twice per week (43% vs. 15%, p < 0.001).

Conclusions:
Nearly half of cardiologists are not adherent to the ACC recommended guidelines for aerobic activity. The impact on cardiologists’ health was not quantified, but this study suggests there is room for improvement in prevention behaviors. Since physicians are known to serve as role models for their patients, we hypothesize lack of adherence to activity guidelines may also negatively impact our patients.
Abstract 17023: Adipose Tissue Specific Temporal Deletion of
Ager
Induces Weight Loss in Diet Induced Obese Mice and Improves Glucose Homeostasis
Authors: Wilson Robin , Arivazhagan Lakshmi , Ruiz Henry , Pendse Jay , Frye Laura , Mangar Kaamashri , Ramasamy Ravichandran , SCHMIDT Ann Marie
Published: May 2021

Introduction:
The incidence of obesity and its comorbidities is increasing at an alarming rate in US and around the globe. Our previous studies showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance (IR), as global
Ager
(gene encoding RAGE) and adipocyte-specific
Ager-
deleted mice fed a high fat diet (HFD) showed protection from weight gain and IR. However, the role of
Ager
deletion in mice with established obesity, switched to low fat diet has not been tested. We hypothesize that temporal adipocyte-specific deletion of
Ager
in obese mice could enhance weight loss and improves glucose homeostasis.

Methods:
Mice with conditional adipocyte-specific
Ager
deletion were generated by breeding Ager

flox/flox

mice with AdipoQ ERT2 Cre recombinase mice resulting in

Ager
flox/flox

/ AdipoQ ERT2 Cre (+) and Cre (-) animals. Mice were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity and were then treated with tamoxifen (TAM) (75 mg/kg per day x 3 alternative days) to induce deletion of
Ager
. After 4 weeks of TAM treatment, mice were switched to standard chow for 7 weeks and body weight was monitored regularly. Fasting glucose, insulin and glucose tolerance was measured.

Results:
After 7 weeks of switching to standard chow following TAM, Cre (+) lost significantly more body weight whereas Cre (-) mice showed no significant weight loss over 7 weeks. Furthermore, Cre (+) mice exhibited significantly higher food intake, lower fasting glucose, lower epididymal and inguinal white adipose tissue weights, and improved glucose and insulin tolerance compared to Cre (-) mice.

Conclusions:
Temporal adipocyte-specific deletion of
Ager
in mice with established obesity promotes weight loss and improves glucose homeostasis. RAGE may act as a novel therapeutic target in obesity.
Abstract 17034: The AKT/AMPK/FOXO3 Axis in Pulmonary Arterial Hypertension
Authors: Grobs Yann , romanet Charlotte , Nadeau Valerie , Omura Junichi , Orcholski Mark , Shimauchi Tsukasa , Toro Victoria , Tremblay Eve , Bourgeois Alice , Paulin Roxane , BOUCHERAT Olivier , Bonnet Sebastien , Provencher Steeve
Published: May 2021

Like cancer, pulmonary arterial hypertension (PAH) is characterized by exaggerated proliferation and resistance to apoptosis related to metabolic alterations (Warburg effect) of pulmonary smooth muscle cells (PASMCs). These anomalies result in a progressive narrowing of the pulmonary arteries, increasing pulmonary resistance and leading to right heart failure and premature death. In cancer cells, unphosphorylated and nuclear FOXO3 has been extensively studied as a crucial protein that functions as a tumor suppressor by regulating expression of genes involved in apoptosis and cell cycle arrest. These functions combined with other FOXO3 attributes, including its key role in communicating mitochondrial-nuclear signals, make the FOXO3 a suitable candidate for controlling the cancer-like phenotype of PAH-PASMCs. Interestingly, AKT and AMPK known to be implicated in PAH exert antagonistic effects on FOXO3; AKT promoting its nuclear exclusion while AMPK favors its nuclear and mitochondrial accumulation. The thus made the hypothesis that FOXO3’s nuclear exclusion (secondary to AKT/AMPK imbalance) promotes metabolic reprogramming towards glycolysis leading to enhanced proliferation/resistance to apoptosis of PAH-PASMCs and vascular remodeling. Using Western blot and immunofluorescence in isolated PASMCs from both PAH and control patients (n=10), we found that nuclear and mitochondrial exclusion of FOXO3 due to its phosphorylation is a feature of PAH-PASMCs. In vitro, we demonstrated that nuclear localization of FOXO3 using an adenovirus expressing a constitutively active, non-phosphorylable form of FOXO3 or trifluoperazine (TFP) resulted in reduced PAH-PASMC proliferation (Ki67 labeling, p<0,0005) and resistance to apoptosis (Annexin V assay, p<0,05). These effects were accompanied by increased expression of P27 and SOD2 and diminished expression of Survivin (p<0,05). In vivo, we showed that FOXO3 activation using TPF improved established PAH in the monocrotaline rats (reduced RVSP and increased Sv and CO, by right catheterization, p<0,01, n=29) without any sign of toxicity. We showed that FOXO3 is implicated in pulmonary vascular remodeling. Pharmacological activation of FOXO3 may represent a novel avenue to improve PAH.
Abstract 17060: Machine Learning and Video Recognition for Automated Detection of Fluid Status in Heart Failure Patients
Authors: Doshi Pratik , Tanaka John , Wosik Jedrek , Gil Natalia M , Bertran Martin , Russell Stuart D , Sapiro Guillermo
Published: May 2021

Introduction:
There is a need for innovative solutions to better screen and diagnose the 7 million patients with chronic heart failure. A key component of assessing these patients is monitoring fluid status by evaluating for the presence and height of jugular venous distension (JVD). We hypothesize that video analysis of a patient’s neck using machine learning algorithms and image recognition can identify the amount of JVD. We propose the use of high fidelity video recordings taken using a mobile device camera to determine the presence or absence of JVD, which we will use to develop a point of care testing tool for early detection of acute exacerbation of heart failure.

Methods:
In this feasibility study, patients in the Duke cardiac catheterization lab undergoing right heart catheterization were enrolled. RGB and infrared videos were captured of the patient’s neck to detect JVD and correlated with right atrial pressure on the heart catheterization. We designed an adaptive filter based on biological priors that enhances spatially consistent frequency anomalies and detects jugular vein distention, with implementation done on Python.

Results:
We captured and analyzed footage for six patients using our model. Four of these six patients shared a similar strong signal outliner within the frequency band of 95bpm – 200bpm when using a conservative threshold, indicating the presence of JVD. We did not use statistical analysis given the small nature of our cohort, but in those we detected a positive JVD signal the RA mean was 20.25 mmHg and PCWP mean was 24.3 mmHg.

Conclusions:
We have demonstrated the ability to evaluate for JVD via infrared video and found a relationship with RHC values. Our project is innovative because it uses video recognition and allows for novel patient interactions using a non-invasive screening technique for heart failure. This tool can become a non-invasive standard to both screen for and help manage heart failure patients.
Abstract 17077: Functional Class, Biomarker Stability, and Clinical Outcomes of Patients With Transthyretin Cardiac Amyloidosis Treated With Tafamidis
Authors: Chandrashekar Pranav , Dale Zack , Rashdan Lana , Elman Miriam , Nazer Babak , Heitner Stephen B , Masri Ahmad
Published: May 2021

Introduction:
Tafamidis has been shown to improve survival and decrease heart failure (CHF) hospitalizations in transthyretin cardiac amyloidosis (ATTR-CM). In the ATTR-ACT trial, survival benefit emerged after approximately 18 months of treatment, with less clear benefit in those with NYHA class III symptoms. We sought to evaluate the short-term changes in NYHA class, biomarkers, and clinical outcomes in a real-world cohort of patients treated with tafamidis.

Methods:
A single center retrospective observational study of patients with ATTR-CM who were prescribed tafamidis since its FDA approval in May 2019. We collected data on prospectively assessed NYHA class, NTproBNP, Troponin I, and outcomes of CHF hospitalizations and death.

Results:
Fifty-one patients with ATTR-CM (mean age 73.3±7 years, 100.0% male) were prescribed tafamidis. Forty-five patients had wild-type and 6 had hereditary ATTR-CM. At the visit when tafamidis was initiated 6 (11.8%) patients were NYHA Class I, 24 (47.1%) Class II, 20 (39.2%) Class III, and 1 (2%) Class IV. Over a median follow up of 8 (IQR 6.0-11) months after starting tafamidis, there were no significant differences before and after tafamidis treatment in time-averaged median NYHA functional class (paired Wilcoxon test, p=0.1610; Figure 1A), time-averaged median NTproBNP (paired exact Wilcoxon test, p > 0.9999; Figure 1B), and time-averaged median troponin I (paired exact Wilcoxon test, p=0.9400; Figure 1C). Following initiation of tafamidis, 13 patients (25.5%) were admitted for CHF hospitalization. A total of 8 patients (15.7%) died a median of 9.5 (IQR 2.5-12.5) months after initiation of tafamidis.

Conclusions:
ATTR-CM patients taking tafamidis were observed to have stable functional status and biomarkers, including those with NYHA class III symptoms. Despite a higher proportion of worse NYHA functional class, the rate of death at 10 months appears comparable to the ATTR-ACT trial in this real-world population.
Abstract 17094: A New Grading of Tricuspid Regurgitation Beyond Severe and Its Clinical Importance
Authors: Taku Omori , Uno Goki , Shimada Shunsuke , Rader Florian , Siegel Robert J , Shiota Takahiro
Published: May 2021

Introduction:
Recently a new grading system for tricuspid regurgitation (TR) beyond severe has been proposed. However, few studies assessing the validity of the new grade of TR has been conducted. We evaluated the new grading system of TR by comparing it with patient hemodynamics and outcome.

Methods:
We retrospectively reviewed patients who underwent 2 dimensional echocardiography and had severe TR in 2014. According to the vena contracta width (VC) of TR jet, the patients were classified into 3 groups: VC<11mm, 11<=VC<14 and VC >=14mm (160,113 and 86 patients respectively). Stroke volume (SV), cardiac index (CI) and right atrial pressure (RAP) were estimated by echocardiography. Cardiac events were defined as cardiac death or admission for heart failure (HF).

Results:
376 patients were diagnosed as severe TR. We excluded 15 patients on mechanical respiratory support and 2 with missing clinical data. Remaining 359 severe TR patients (75 ± 16 years, 204 (57%) female) were investigated. TR patients with VC >=14mm had significantly lower SV and CI compared to the other groups, though there was no difference in SV and CI between those with VC<11 and those with 11<=VC<14 (Figure). Compared to TR patients with VC<11, those with VC >=14 had a significantly higher frequency of RAP >=15mmHg (Odds ratio (OR) 1.30; 95% Confidence Interval (CI), 1.01 to 3.08;
p=0.047
), though those with 11<=VC<14 had no significant difference (OR 1.30; 95% CI 0.79 to 1.37;
p=0.31
) (Figure). During a follow-up period (median, 205 days; range, 36 to 1032 days), 124 (35%) patients experienced cardiac events (30 cardiac death and 94 HF admission). The Kaplan-Meier curves showed that TR patients with VC>=14 was at higher risk for cardiac events (Figure).

Conclusion:
TR patients with VC >=14mm showed significantly worse hemodynamics and outcome than those with VC<14mm. TR with VC >=14mm should be considered to clinical grade of TR that is beyond severe.
Abstract 17099: Implementation of a High Sensitivity Troponin-I Assay in an Academic Medical Center: A Qualitative and Quantitative Assessment
Authors: Winchester David , Betageri Omkar , Perche Patrick , Allen Brandon , Theis Ryan
Published: May 2021

Background:
High sensitivity troponin assays (hsTn) have received regulatory approval for use in the United States and health care facilities are beginning to adopt these new assays. Questions remain about how to implement these assays and what affect they may have on demand for cardiovascular services.

Methods and Results:
We conducted a mixed-methods implementation science-based investigation of hsTn adoption at a single academic medical center. We designed the investigation based on the Consolidated Framework for Implementation Research, exploring clinicians’ perspectives on intervention characteristics, inner setting, individual characteristics, and process of implementation domains. Focus groups were conducted with clinicians from multiple service lines. Participants reported that the new hsTn assay did not fundamentally change processes of care such as cardiology consultations or inpatient admissions. Implementation was facilitated by leveraging the electronic medical record to provide useful suggestions for hsTn management at the point-of-care. Participants expressed satisfaction with the multidisciplinary and collaborative approach taken to educating clinicians prior to implementation. The use of case-based teaching was considered most effective. Emergency department clinicians expressed greater confidence about decisions to discharge to home with the hsTn assay, compared to the older assay. Areas of ongoing concern included management of high risk patients, outpatient follow-up, and feasibility of accelerated diagnostic protocols for early discharge from the emergency department. Deidentified quantitative data on cardiovascular service use were gathered from administrative sources and analyzed on runcharts. A decrease in the number of hsTn assays ordered was observed; no change was noted for admissions, cardiology consultations, or noninvasive cardiac imaging.

Conclusions:
A comprehensive educational campaign, based on multidisciplinary collaboration can effectively prepare clinicians for implementation of hsTn. New hsTn assays may not have any substantial effect of acute management of patients with cardiac complaints. Many questions remain about best clinical practices for hsTn assays.
Abstract 17253: The Late Sodium Current Contributes to Electromechanical Defects Occurring With Aging
Authors: Cervantes Daniel O , Pizzo Emanuele , Comelli Martina , Plosker Aaron , Faltas Bridget , Cianflone Eleonora , Mohler Peter J , Hund Thomas J , Jacobson Jason T , Rota Marcello
Published: May 2021

To establish the contribution of the late sodium current (I
NaL
) on cardiovascular defects occurring with aging, mice with phosphomimetic mutation of Na
+
channel Nav1.5 at Ser571 (S571E), which causes I
NaL
enhancement in cardiomyocytes (I
NaL
gain-of-function), and mice with ablation of the Nav1.5 Ser571 (S571A), preventing CaMKII-mediated I
NaL
increase under stress condition (I
NaL
loss-of-function) were studied together with C57Bl/6 mice (wild-type, WT). Male mice at 2-6 (~4 m), 10-16 (~12 m), 17-20 (~18 m), and 20-27 (~24 m) months of age underwent electrocardiographic and echocardiographic evaluation. In WT mice, the QT interval duration of the ECG in the anesthetized state was similar at ~4 and ~12 months (56±5 ms and 58±5 ms, respectively) and was prolonged at ~18 and ~24 months (66±4 ms and 67±3 ms, respectively). In S571E mice, QT interval at ~4 months was prolonged with respect to WT animals (67±4 ms) and remained protracted at ~12, ~18, and ~24 months (65±3 ms, 68±6 ms, and 69±5 ms). S571A animals at ~4 months presented intermediate QT interval duration with respect to the other two strains (61±3 ms), and remained unchanged at ~12, ~18, and ~24 months (63±4 ms, 62±4 ms, and 64±4 ms). Ejection fraction was not altered with age and was comparable for the three mouse groups. In contrast, by transmitral flow Doppler echocardiography diastolic function, quantified here by the isovolumic relaxation time, was normal in WT mice at ~4 (17.4±1.6 ms) and ~12 months (16.8±1.6 ms) and became depressed at ~18 (21.5±2.5 ms) and ~24 months (21.4±1.7 ms). Defective diastolic function was apparent in S571E mice at ~4 months (19.7±2.9 ms) and persisted at ~12, ~18, and ~24 months (19.1±1.7 ms, 21.0±1.9 ms, and 22.1±2.2 ms, respectively). Interestingly, S571A mice at ~4 months had normal diastolic function (16.2±2.2 ms) and minor alterations were observed at ~12, ~18, and ~24 months (17.1±1.5 ms, 18.4±1.6 ms, and 19.3±3.3 ms, respectively). Overall, collected results suggest that I
NaL
enhancement in S571E mice is associated with premature appearance of prolonged electrical recovery and defective diastolic function, with respect to aging WT animals. In contrast, S571A mice, with inability to increase I
NaL
, are protected from electromechanical defects occurring with aging.
Abstract 17256: Utility of Echocardiography in Acute and Recurrent Pericarditis
Authors: Furqan Muhammad M , Tabucanon Ray , Khayata Mohamed , Verma Beni R , Ayoub Chadi , Klein Allan L
Published: May 2021

Background:
Pericarditis usually presents with sharp chest pain, and other diagnostic features include pericardial rub, typical EKG changes (diffuse ST elevation and PR depression), and the presence of pericardial effusion (PEff). Echocardiography (ECHO) is the first-line imaging modality in pericarditis. It helps to identify PEff, constrictive physiology, and wall motion abnormalities. We sought to characterize ECHO features in a large cohort of patients with acute (AP) and recurrent pericarditis (RP).

Methods:
Data were collected retrospectively for patients with acute and recurrent pericarditis. Pericarditis was diagnosed based on the European Society of Cardiology pericardial disease guidelines. ECHOs were reviewed for relevant features and findings. Chi-square test statistics were used to compare AP and RP.

Results:
A total of 323 consecutive patients with RP (68%) and AP (32%) was identified from January 2015 to December 2018. The median age was 52 years 56% were female. Of the total patients, the most common finding on ECHO was PEff (42%). Of the patients having PEff, 65 (20%) had trivial, 42 (13%) small, 19 (6%) moderate, and 6 (2%) had large effusion. Other findings included constrictive physiology (20%), thickened pericardium (4%), and echo wall motion abnormality (3%). AP patients had higher number of PEff compared to RP (51% vs 38%; [X
2
=4.1, p=0.043]. Increased pericardial thickness was only found in patients with RP (6% in RP vs 0% in AP; [X
2
=6, p=0.014]. All the other findings were similar across RP and AP

Conclusion:
The most common echocardiographic finding in acute and recurrent pericarditis patients is pericardial effusion followed by constrictive physiology and thickened pericardium. Pericardial effusion appears to be more frequent in AP patients as compared to RP. These findings may be useful in the diagnostic workup of pericarditis.
Abstract 17303: Longitudinal Cerebral Oxygen Metabolism in Congenital Heart Disease
Authors: Lim Jessie Mei , Marini Davide , Saini Amandeep , Au-Young Stephanie , Fan Steven , Chau Vann , Miller Steven , Seed Mike
Published: May 2021

Background:
Brain growth differences are apparent between different types of cyanotic congenital heart disease, but the underlying mechanism remains unclear. Here, we explored and characterized longitudinal cerebral hemodynamic and oxygen metabolism profiles and their relationships to brain growth patterns in infants with single ventricle physiologies (SV) and transposition of the great arteries (TGA). We hypothesized that there are marked differences in cerebral oxygen metabolism in those with SV compared with TGA.

Methods:
Cerebral blood flow (CBF), oxygen delivery (CDO2) and consumption (CVO2) and brain growth were measured in 103 term newborns with SV and TGA using MRI at pre- and post-surgery and at follow-up. We measured whole brain size by segmenting a 3D steady state free precession acquisition. Cerebral blood flow was measured using phase contrast imaging of the neck vessels and cerebral venous blood oxygen saturation was derived from T2 oximetry of the superior sagittal sinus. TGAs were divided into those with and without ventricular septums.

Results:
CBF profiles were similar between the 3 lesion groups. Cerebral oxygen delivery trends increased but were not significantly different between cardiac groups. We observed that this may be mediated by different mechanisms: an increase in arterial saturation in TGAs, and an increase in hemoglobin concentration in SVs. Cerebral oxygen consumption in SV infants remained low (p = 0.54) while that of TGA increased over time (TGA IVS p < 0.001; TGA VSD p <0.001) (Fig. 1), mediated by an unchanging oxygen extraction fraction in SVs (p = 0.59). The SV cerebral oxygen consumption profile aligned with their declining brain weight z-score trajectory.

Conclusions:
In conclusion, there are characteristic differences in hemodynamic adaptations between SVs and TGAs. Changes in oxygen metabolism may be facilitating brain growth trajectories. This informs us of possible mechanisms involved during a time of critical brain development.
Abstract 17306: Primary Prevention Aspirin Use Trends and Associations With Health Beliefs Among African Americans, 2015-2019
Authors: Vant Hof Jeremy R , Misialek Jeffrey , Oldenburg Niki C , Luepker Russell V , Eder Milton , Duval Sue
Published: May 2021

Introduction:
Cardiovascular disease (CVD) disproportionately affects African Americans. Aspirin has long been recommended as an option to reduce cardiovascular events. However, recent clinical trials involving primary prevention aspirin have prompted changes in national guidelines restricting the aspirin recommended population.

Hypothesis:
Primary prevention aspirin use will decline over the 5 year period 2015-2019.

Methods:
Using 3 cross-sectional surveys, data were collected from self-identified African Americans in 2015, 2017 and 2019, querying information on CVD risk factors, health behaviors and beliefs, and aspirin use. Poisson regression modeling was used to estimate age- and risk-factor adjusted aspirin prevalence, trends and associations.

Results:
A total of 1,491 African Americans adults, ages 45-79, 61% women and no prior CVD completed surveys and were included in this analysis. There was no change in age- and risk factor-adjusted aspirin use over the 3 surveys for women (37%, 34% and 35% respectively) or men (27%, 25%, 30% respectively). However, fewer participants believed aspirin was helpful in 2019--75% vs 84% in 2015 (p<0.05). In the total sample (n=1,491) aspirin discussions with a health care practitioner were highly associated with aspirin use (aRR 2.97, 95% CI 2.49-3.54), as were several health beliefs and social norms that affirm preventive behaviors and aspirin use (Figure).

Conclusion:
Despite major changes in national guidelines and negative perceptions of aspirin effectiveness in the media, overall primary prevention aspirin use did not significantly change in this African American sample from 2015 to 2019.
Abstract 17308: Unsupervised K-means Clustering to Identify Signatures of Right Ventricle Dysfunction in Patients With Pulmonary Hypertension
Authors: Janowski Alexandra M , Ravellette Keeley S , Garcia Joe G , Rischard Franz , Vanderpool Rebecca R
Published: May 2021

Introduction:
Right ventricular (RV) function is a determinant of mortality in patients with pulmonary hypertension but current assessments are based on individual variables. Unsupervised k-means clustering can be used as an unbiased approach to determine distinct patient groups based on RV dysfunction. The aim of the study was to use unsupervised clustering to identify clinically meaningful RV phenotypes.

Methods:
Participants were identified from the University of Arizona PH registry (n=213). Patients with missing hemodynamic RV function data were excluded (n=23). Unsupervised clustering (k-means) was applied to variables of systolic and diastolic ventricular function including: max dP/dt/RVSP, Ees, Ea, Ees/Ea, max dP/dt, min dP/dt, RV EDP, β and Eed. Linear discriminant analysis (LDA) was performed to determine the weight of variables in cluster assignment.

Results:
Participants without PH (n=41) and World Symposium Pulmonary Hypertension (WSPH) Groups 1 (n=104), 2 (n=22), 3 (n=28), 4 (n=12), 5 (n=2) were assigned to four clusters based on the elbow method (Figure 1A). Two major determinants of cluster assignment were arterial elastance (Ea) and end systolic elastance (Ees). Participants with WSPH Group 1 were distributed across clusters (Figure 1B). Degree of RV dysfunction was highest in cluster 4 with increased Ees and Ea compared to other clusters (Figure 1C). Eed, Ees/Ea and mPAP (61 ± 22 mmHg) were increased compared to clusters 1 and 3. Sex, Ethnicity, BMI and cardiac output were not significant between clusters. Cluster 4 had increased PVR (11.1 ± 5.5 WU), and decreased PA compliance (1.2 ± 0.6 mmHg/ml) compared to other clusters.

Conclusions:
Unsupervised k-means clustering based on hemodynamic measures of RV function identified four distinct RV dysfunction phenotypes ranging from mild to severe.
Abstract 17311: Ventricular Arrhythmias and Fibrosis in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Cuk Natasha , Cho Jae H , Han Donghee , Ebinger Joseph E , Cingolani Eugenio
Published: May 2021

Introduction:
Sudden death due to ventricular arrhythmias (VA) is one of the main causes of mortality in patients with heart failure and preserved ejection fraction (HFpEF). Ventricular fibrosis in HFpEF has been suspected as a substrate of VA, but the degree of fibrosis has not been well characterized.

Hypothesis:
HFpEF patients with increased degree of fibrosis will manifest more VA.

Methods:
Cedars-Sinai medical records were probed using Deep 6 artificial intelligence data extraction software to identify patients with HFpEF who underwent cardiac magnetic resonance imaging (MRI). MRI of identified patients were reviewed to measure extra-cellular volume (ECV) and degree of fibrosis. Ambulatory ECG monitoring (Ziopatch) of those patients were also reviewed to study the prevalence of arrhythmias.

Results:
A total of 12 HFpEF patients who underwent cardiac MRI were identified. Patients were elderly (mean age 70.3 ± 7.1), predominantly female (83%), and overweight (mean BMI 32 ± 9). Comorbidities included hypertension (83%), dyslipidemia (75%), and coronary artery disease (67%). Mean left ventricular ejection fraction by echocardiogram was 63 ± 8.7%. QTc as measured on ECG was not significantly prolonged (432 ± 15 ms). ECV was normal in those patients for whom it was available (24.2 ± 3.1, n = 9) with 3/12 patients (25%) demonstrating ventricular fibrosis by MRI (average burden of 9.6 ± 5.9%). Ziopatch was obtained in 8/12 patients (including all 3 patients with fibrosis) and non-sustained ventricular tachycardia (NSVT) was identified in 5/8 (62.5%). One patient with NSVT and without fibrosis on MRI also had a sustained VA recorded. In those patients who had Ziopatch monitoring, there was no association between presence of fibrosis and NSVT (X2 = 0.035, p = 0.85).

Conclusions:
Ventricular fibrosis was present in 25% of HFpEF patients in this study and NSVT was observed in 62.5% of those patients with HFpEF who had Ziopatch monitoring. The presence of fibrosis by Cardiac MRI was not associated with NSVT in this study; however, the size of the cohort precludes broadly generalizable conclusions about this association. Further investigation is required to better understand the relationship between ventricular fibrosis by MRI and VA in patients with HFpEF.
Abstract 17318: Cardioprotective Microbes and Restorative Sleep Are Reduced and Blood Pressure During Sleep is Increased When Rats Have Fragmented Sleep
Authors: Maki Katherine A , Barb Jennifer J , Bronas Ulf G , Calik Michael W , Green Stefan , Fink Anne M
Published: May 2021

Introduction:
Sleep that is restless and fragmented impairs cardiovascular (CV) health. Using a rat model, we measured sleep characteristics and assessed bacterial communities in the gut microbiome. We hypothesized poor quality sleep to be associated with a reduction in cardioprotective microbiomes and adverse CV outcomes.

Methods:
Wistar Kyoto rats had normal sleep (n= 7, controls) or 8-hrs of fragmented sleep (n = 8) for 28 days. Implanted telemetry transmitters recorded blood pressure (BP), heart rate (HR), and cortical electroencephalogram (EEG) signals continuously. Fecal samples were collected daily; microbial composition was determined by 16S rRNA amplicon sequencing.

Results:
The sleep fragmented (SF) rats could not achieve deep slow-wave sleep (SWS) for 8-hrs each day—compared with controls, relative EEG delta power (a marker of the depth of sleep) was significantly lower (29±3% versus 39±3%,
P
= 0.04). In addition, SF was associated with a rise in BP and HR. The relative abundance of
Parabacteroides
(classified to genus level) and Tannerellaceae (classified to family level), both gram-negative anaerobic bacteria from the phylum Bacteroidetes, were decreased in SF rats during late-SF (intervention days 20 & 27), relative to controls. Elevated
Parabacteroides
levels (%) were significantly and inversely correlated with systolic (R= -0.002,
P
<0.001) and diastolic (R= -0.003,
P
<0.001) BP levels recorded during sleep in both groups of rats.

Conclusions:
Parabacteroides
levels in the gut microbiome may contribute to changes in BP. Undesirable changes in sleep from SF are associated with reduced levels of
Parabacteroides
during the late-SF period in the gut microbiome, compared with controls. The
Parabacteroides
-BP associations and reactivity of this bacterium to disrupted sleep support
Parabacteroides
as an exciting cardioprotective biomarker to stratify and prevent negative CV outcomes provoked by SF.
Abstract 17326: Blockade of Thrombospondin1 Attenuates Tgfβ Signaling and Enhances the Automaticity of Tbx18-Induced Pacemaker Cells
Authors: Fernandez Natasha , Fan Jinqi , Cho Hee
Published: May 2021

Introduction:
Transcription factor Tbx18 can reprogram chamber cardiomyocytes to induced pacemaker cells (iPMs). Transcriptomic analysis of Tbx18-iPMs identified Tgfβ pathway as a prominent signaling cascade in this transition. The activity of Tgfβ1 is regulated primarily in the extracellular domain where the secreted latent form must be modified to expose the active ligand. We hypothesize that thrombospondin1 (Tsp1) mediates the activation of the Tgfβ signaling by Tbx18.

Methods:
Neonatal rat ventricular myocytes (NRVMs) were transduced with adenoviral constructs expressing either human TBX18 or GFP.

Results:
Tsp1 transcript (Thbs1) level was higher in TBX18 iPMs compared to GFP-NRVMs (1.5±1.3 vs 0.6±0.6, p<0.05, n=4). Tsp1 concentration was higher in the conditioned media of TBX18 iPMs than in GFP-NRVMs (1220±794 vs 138±178 pg/mL, p<0.05, n=20). The population of Tsp1+ fibroblasts were significantly higher within TBX18 iPMs compared to GFP-NRVMs (45±7% vs 9±10%, p<0.05, n=3). We tested for cause-and-effect relationship between Tsp1 and Tgfβ signaling. Treatment of TBX18 iPMs with 20μM LSKL, a peptide inhibitor of Tsp1, attenuated secreted Tgfβ1 ligand concentration compared to DMSO-treated TBX18 iPMs (127±70 vs 214±44 pg/mL, p<0.05, n=20). Similarly, LSKL treatment reduced αSMA+ myofibroblast population in TBX18 iPMs at day 4 compared to untreated iPMs (10±6 vs 21±5%, p<0.05, n=3). Transcript levels of key Tgfβ signaling genes such as of Cola1, Tgfβ1, and Thbs1 were downregulated in LSKL-treated TBX18 iPMs compared to DMSO-treated iPMs. Functionally, LSKL treatment increased rates of single cell automaticity (125±13 vs 61±6 bpm) and the percentage of spontaneously beating cells (95±7 vs 62±17%, n=6, p<0.05) in TBX18-iPMs compared to DMSO-treated TBX18 iPMs at day 16 after gene transfer. The enhanced automaticity was evident by day 7 and remained stable for two weeks.

Conclusions:
Our data identify Tsp1 as the key mediator through which Tbx18 activates the Tgfβ pathway during iPM reprogramming. Inhibition of Tgfβ pathway may serve as a solution to attain durable pacing from TBX18-iPMs.