bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14765: Exosome Shuttled VEGFR Promotes Angiogenesis in Peripheral Vascular Disease
Authors: Shi Ao , Arrell D Kent K , Peterson Timothy E , Witt Tyra A , Nagel Mary , Li Jialun , Moran Steven , Terzic Andre , Behfar Atta
Published: May 2021

Introduction:
Counteracting the pandemic of peripheral vascular disease necessitates development of proangiogenic treatments. As stem cell benefit has increasingly been associated with paracrine influence on diseased tissue, a purified extracellular vesicle population (PEP) was established to promote tissue regeneration and neovascularization. The mechanistic basis for PEP-induced proangiogenic effects was here probed and validated in two separate in vivo models of vascular ischemia.

Hypothesis:
PEP drives pro-angiogenic effects though donation of VEGFR.

Methods:
Nanosight and immunoblotting were utilized to characterize PEP purity and identity. OMICs profiling identified VEGFR as highly prioritized, with downstream signaling was tested in human umbilical vascular endothelial cells using Matrigel assay, qPCR and immunoblotting. In vivo, blood perfusion (Fluorescent imaging - SPY) was quantified in a rodent model of hind-limb ischemia and in a rabbit model of critical ischemic ear, each treated with sham or PEP. Rabbit tissues were next examined by whole transcriptome analysis to assess PEP-induced proangiogenic signaling. Immunohistochemical staining with smooth muscle actin and von Willebrand factor probed de novo blood vessel formation.

Results:
PEP was characterized by size (mean: 128.6 +/-1 nm) and VEGFR expression. VEGFR knock-down diminished endothelial cell angiogenic activity in vitro, rescued with PEP (5.3x1010+/-109 vesicles/ml) was sufficient enhance total and phosphor-VEGFR expression, along with amplification of downstream VEGFR targets (MAPK, AKT, CXCL8, NOTCH4, MMP9) and enhanced tube formation. In both hind-limb (n=5) and critical ear (n=4) ischemia models, local delivery of PEP to ischemic tissue resulted in restoration of blood perfusion and prioritized proangiogenic signaling in tissue transcriptome pathway analysis, further confirmed by immunohistochemistry.

Conclusions:
Taken together, our study establishes a new regenerative paradigm documenting exosome-based delivery of VEGFR as a key driver for angiogenesis. This PEP-based platform broadens potential options available for treatment of peripheral vascular disease and may have therapeutic implications in restoration of microvasculature.
Abstract 14778: Watchman Associated With Lower Risk of Stroke and Mortality in Patients With Atrial Fibrillation and Difficulties Taking Anticoagulation
Authors: Yao Xiaoxi , Van Houten Holly K , Sangaralingham Lindsey R , Henk Henry , Graff-Radford Jonathan , Gersh Bernard J , Holmes David R , Noseworthy Peter A
Published: May 2021

Introduction:
Watchman has been increasingly used in AF patients who have difficulties taking anticoagulation, but the RCTs only compared Watchman to warfarin. There was also a signal of increased ischemic stroke with Watchman in comparison to warfarin in RCTs, which made some clinicians question the fundamental premise that Watchman can reduce stroke. We aimed to compare Watchman to no anticoagulation in a large national cohort of patients in the US.

Methods:
We identified AF patients treated with Watchman (N=7,309) or no anticoagulation (N=1,234,543) between 2015-2017 from the OptumLabs Data Warehouse, which is the first to link private insurance, Medicare Advantage, and Medicare Fee-for-Service records at patient level longitudinally. One-to-one propensity score matching was used to balance patients on demographics and medical history. The primary outcomes were ischemic stroke or systemic embolism (hereafter referred to as stroke) and major bleeding. Secondary outcomes included all-cause mortality and intracranial bleeding.

Results:
In the unmatched cohort, the mean age was 76.6±6.4 yr in the Watchman group and 76.6 ±8.5 yr in the no anticoagulation group, but Watchman patients were more likely to have a history of bleeding (44.9% vs 13.7%) and intracranial bleeding (9.5% vs 2.6%). After matching, the two groups were similar on 18 baseline characteristics. Watchman was associated with a lower risk of stroke and mortality, but a higher risk of major bleeding and a similar risk of intracranial bleeding. The associations were largely consistent across subgroups, including those with relative contraindications to anticoagulation (Figure).

Conclusions:
In AF patients who had difficulties taking anticoagulation, Watchman offers an alternative approach to reduce stroke and mortality. The results provide important evidence to inform clinical decision making in the absence of RCTs, since 40% of AF patients in routine practice are not on anticoagulation.
Abstract 14790: Prospective Evaluation of the Effect of Smartphone Electrocardiogram Usage on Anticoagulant Medication Compliance: Results of the Better Outcomes of Anticoagulation Therapy by Observation of Atrial Rhythm (BOAT OART) Study
Authors: Gupta Sanjaya K , Tran Andy T , Steinhaus Daniel , Yousuf Omair , Giocondo Michael , Ramza Brian M , Wimmer Alan P
Published: May 2021

Introduction:
Compliance with anticoagulation treatment for atrial fibrillation is variable. Smartphone electrocardiograms that provide accurate arrhythmia diagnosis may allow patients to have greater insight into their arrhythmia burden.

Hypothesis:
Our hypothesis was that regular use of a smartphone electrocardiogram would improve anticoagulant compliance.

Methods:
Patients were enrolled if they had atrial fibrillation with a CHA2DS2-VASc score of 2 or more, were eligible for anticoagulation and had a smartphone. Participants were randomly assigned to receive a smartphone electrocardiogram (AliveCor Kardia) or to the control group. All patients received 6 months of anticoagulant (apixaban) dispensed as 1-month pre-loaded pill boxes. Patients returned monthly to assess medication compliance and receive subsequent month medication. Monitor patients were encouraged to record their electrocardiogram 5 times a week.

Results:
A total of 100 patients were enrolled from July 2017 to August 2019, but 4 patients in the monitor arm withdrew prematurely. The monitor and control groups did not differ in age, gender, CHA2DS2-VASc score, comorbidities or atrial fibrillation burden. Medication compliance was 99.1%, with greater compliance in the monitor group (99.5 ± 0.86%) than the control group (98.8% ± 2.19%; p=0.03). In the monitor group, there was no association between missed doses and use or nonuse of the smartphone monitor on a given day. Overall monitor compliance was 87.0±14% with an average of 4.35 recorded electrocardiograms per week. Monitor group patients with 100% medication compliance had a higher average monitor compliance than those patients who missed doses (90.3±11% vs 83.5±15.8%; p=0.05). There were no major adverse events related to anticoagulation.

Conclusions:
Despite excellent overall anticoagulant medication compliance, this study indicates that smartphone electrocardiogram usage is associated with higher medication compliance. Greater monitor compliance was also associated with greater medication compliance. Future studies are necessary to determine if smartphone electrocardiograms can be used to maintain anticoagulant compliance long-term or improve compliance at onset of anticoagulation treatment.
Abstract 14793: Association Between Cardiac Ejection Fraction and the Size of Stroke
Authors: Alvi Muhammad M , Ranasinghe Tamra , Kabbani Yasser , Alkhouli Mohamad Adnan , Tarabishy Abdul Rahman
Published: May 2021

Introduction:
Heart failure with low ejection fraction (EF) is a known risk factor for stroke. Low EF is associated with increased risk of thrombus formation and is accompanied with 2 to 3 fold increased risk of stroke. This can happen even in the absence of atrial fibrillation.

Hypothesis:
Our hypothesis was that size of the stroke will be larger in patients with reduction in EF as compared with cardioembolic strokes in preserved EF. The worse the EF, the more stagnation of blood and poor cardiac output leading higher risk of thrombus formation. It’s also likely that the group with reduced EF form a larger thrombus leading to larger stroke as compared to the group with preserved EF.

Methods:
For our analysis, we retrospectively reviewed charts for 49 acute ischemic stroke patients without atrial fibrillation. We used transthoracic echocardiogram to determine the EF. There are 25 patients with preserved EF, cutoff > 50%. There were 24 patients in reduced EF group. Both groups were matched for age and cardiovascular risk factors. Infarct volume was manually calculated from T1 MRI using BrainLab software.

Results:
There is an inverse correlation between EF and infarct volume (r=-.283, p=.048) meaning patients with reduced EF had greater infarct volume. Median infarct volume is higher in reduced EF group (median volume = 36 cm
3
) compared to patients with preserved EF (median volume = 11 cm
3
) (p=.117).

Conclusions:
In our patient’s sample, there seems to be an inverse correlation between EF and size of stroke. Patients with reduced EF were associated with larger strokes. Larger studies need to be performed to establish a correlation.
Abstract 14795: Oral Anticoagulation Associated With Lower Risk of Stroke in Patients With Post-operative Atrial Fibrillation
Authors: Yao Xiaoxi , Van Houten Holly , Siontis Konstantinos , Gersh Bernard J , Noseworthy Peter A
Published: May 2021

Introduction:
Recent studies showed post-operative atrial fibrillation (POAF) is associated with increased stroke risk - even approaching that of unprovoked AF. This raises the question of whether patients with POAF should receive anticoagulation. We aim to compare different anticoagulation strategies in patients with POAF after cardiac and non-cardiac surgeries.

Methods:
Using a large national administrative database (OptumLabs Data Warehouse), we identified 33,981 patients with POAF between 1/1/2013-9/30/2019. Patients were divided to four groups based on the initial treatment within 30 days of POAF: (1) no anticoagulation (N=28,807) (2) apixaban (N=2178) (3) rivaroxaban (N=1320) (4) warfarin (N=1676). Follow up started at the 30
th
day after POAF to exclude patients who died shortly after surgery and minimize immortal time bias. The follow up continued until patients changed treatment strategies, insurance, or died. 1:1 propensity score matching was performed between each anticoagulant to no treatment to balance on 86 baseline characteristics.

Results:
The mean age was 71.1±11.2 yr; mean CHA
2
DS
2
-VASc was 4.1±1.8; 29.1% received cardiac surgeries; 15.2% received anticoagulation within 30 days of POAF. The event rate per 100 person years was 1.58 for stroke in no-anticoagulation group, and 1.29 for anticoagulation group; 2.86 for major bleeding in no-anticoagulation group and 4.50 for anticoagulation group. After matching, apixaban and rivaroxaban were associated with a lower risk of stroke, but a higher risk of major bleeding; warfarin was not associated with a lower risk of stroke, but a higher risk of major bleeding (Figure). The effect was consistent across subgroups, e.g., age and surgery type.

Conclusions:
In patients with POAF, the stroke rate was lower than what was typically observed in clinical AF. Treatment with apixaban and rivaroxaban immediately after POAF was associated with a reduced risk of stroke but an increased risk of major bleeding.
Abstract 14802: Relation of Non-exercise Walking Activity With Exercise Performance in Patients With Peripheral Artery Disease
Authors: Mays Ryan J , Kahnke Rachel , Schorr Erica N , Treat-jacobson Diane J
Published: May 2021

Introduction:
Structured exercise programs in home settings are beneficial for patients with peripheral artery disease (PAD). However, the impact of lower levels of walking activity accumulated separately from formal home exercise in PAD is unclear. The aim of this study was to determine the relation of non-exercise walking (NEW) activity with exercise performance in PAD.

Methods:
This was a post-hoc analysis from twenty patients with PAD enrolled in a 12-week structured home-based walking exercise program using diaries and accelerometry. Formal exercise sessions (3 sessions·week
-1
) were detected using patient-reported diary entries that corresponded with accelerometer step data. NEW activity was characterized as steps completed over five days each week, excluding steps during formal exercise sessions. The primary outcome for the intent-to-treat analysis was peak walking time (PWT) assessed on a graded treadmill. Secondary outcomes were claudication onset time (COT) from the graded treadmill test and maximal distance achieved during the six-minute walk test (6MWT). Pearson correlations evaluated the relation between NEW activity (step·week
-1
) and exercise performance outcomes using intensity (step·week
-1
) and duration (min·week
-1
) from formal exercise sessions as covariates.

Results:
NEW activity demonstrated a strong, positive correlation with change in PWT (r=0.50, p=0.04) when controlling for exercise intensity and duration during the 12-week intervention. Other exercise performance outcomes were not significantly related to NEW activity (COT: r=0.14; 6MWT maximal distance: r=0.27).

Conclusions:
A positive association was demonstrated between NEW activity and the primary outcome of PWT following 12 weeks of structured home-based walking exercise. Interventions to improve physical activity outside of formal exercise sessions may be beneficial for patients with PAD.
Abstract 14810: Gender Differences in the Prevalence of Physical Frailty in Heart Failure
Authors: Davis Mary C , Lee Christopher S , Corcoran Amy , Gupta Nandita , Uchmanowicz Izabella , Denfeld Quin E
Published: May 2021

Introduction:
The intersection of frailty and heart failure (HF) continues to garner interest. Almost half of patients with HF are frail; however, gender differences in the prevalence of frailty in HF are poorly understood. The objective of this study was to quantify gender differences in the prevalence of frailty in HF.

Methods:
Data from a subset of studies from a previous meta-analysis were analyzed if they included prevalence of frailty by gender. We performed a random-effects meta-analysis to quantify the relative and absolute risk of frailty in women compared to men with HF overall, and divided into Physical and Multidimensional Frailty measures. Risk ratios (RR) along with their confidence intervals (CI) were estimated.

Results:
Thirteen studies involving 3,662 women and men with HF were included in this meta-analysis. The estimated prevalence of frailty in HF was 51.4% for women and 33.9% for men. The overall absolute risk increase for women compared to men with HF being frail was 14% (z = 3.92, p < 0.001). Overall, women with HF had a 42.1% higher risk of being frail (RR = 1.42 (CI = 1.19-1.69), p < 0.001) compared to men with HF, and there was significant heterogeneity in RRs across studies (
I
2
= 81.7%). Among studies that used Physical Frailty measures, women with HF had a 43.7% higher risk of being frail (RR = 1.44 (CI = 1.20-1.73), p < 0.001) compared with men. Among studies that used Multidimensional Frailty measures, there was no significant difference in risk of frailty between women and men (RR = 1.36 (CI = 0.94,1.96), p = 0.105).

Conclusions:
In HF, frailty affects women significantly more than men, although this was only noted among studies that measured physical frailty, and there was significant heterogeneity across studies. Future work should focus on elucidating potential causes of gender differences in frailty in HF.
Abstract 14813:
Cardiovascular Stroke Nursing Best Abstract Award:
Heterogeneity of Cardiovascular Disease Risk Factors Among Asian Immigrants: Insights From the 2010 - 2018 National Health Interview Survey
Authors: Koirala Binu , Commodore-mensah Yvonne , Turkson Ocran Ruth Alma , Baptiste Diana , Davidson Patricia , Dennison Himmelfarb Cheryl R
Published: May 2021

Introduction:
Cardiovascular disease (CVD) is the leading cause of death in the US. Asians are the fastest-growing immigrant group in the US and are disproportionately affected by CVD risk factors, compared to Whites. Studies on CVD risk aggregate Asians into a homogenous group. It is unclear how Asian immigrants (Indian subcontinent, Southeast Asia, Asia) differ with respect to CVD risks and in comparison, to Whites.

Hypothesis:
We hypothesize that there will be significant heterogeneity in CVD risk factors among Asian immigrant subgroups as compared to Non-Hispanics Whites.

Methods:
A cross-sectional comparative analysis of the 2010 to 2018 National Health Interview Survey was conducted among 508,941 participants. A generalized linear model using Poisson distribution was fitted to compare the prevalence of self-reported hypertension, overweight/obesity, diabetes, high cholesterol, physical inactivity, and smoking among Asian immigrants to Whites, adjusting for known confounders.

Results:
In this sample, 33,973 were Asian immigrants (26% Indian subcontinent; 45% Southeast Asia; 29% Asia) and 474,968 Whites; Indian subcontinent were the youngest (39 years; SE: 0.36). Compared to Whites, the Indian subcontinent had the highest prevalence of overweight/obesity (PR:1.22; 95% CI:1.19-1.25) and Southeast Asian had highest in high cholesterol (PR:1.16; 95% CI:1.10-1.23). Both, the Indian subcontinent (PR:1.69; 95% CI:1.49 - 1.93) and Southeast Asian (PR:1.38; 95%:1.26-1.52), reported a higher prevalence of diabetes. All Asian subgroups were more likely to be physically inactive and less likely to smoke than Whites (Table).

Conclusion:
Significant heterogeneity in CVD risk factors among Asian immigrants was observed compared to Whites. Providers caring for Asians should consider health behaviors and cultural beliefs influencing health outcomes and provide tailored and culturally informed care to improve the cardiovascular health of diverse populations.
Abstract 14819: Excess Epicardial Fat Volume is Associated With Increased Cardiovascular Structural and Functional Abnormalities in Menopausal Women Regardless of Body Weight: The Higher the Epicardial Fat Volume, the Higher the Abnormalities
Authors: EL SHAHAWY Mahfouz , Tucker Susan , Izadi Lillee , Sabatini Antonella
Published: May 2021

Background:
It has been reported that an increase in epicardial fat volume (EFV) has been associated with an increase in cardiovascular structural and functional abnormalities (CVSFA).

Purpose:
The purpose of this study is to assess whether a step-wise increase in EFV is associated with a proportional increase in CVSFA.

Methods:
We screened 2,756 asymptomatic subjects, ages 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System (ECVDRS), which consists of 10 tests; 7 are vascular and 3 are cardiac. The vascular tests are: large (C1) and small (C2) artery stiffness, blood pressure (BP) at rest and post-mild protocol exercise (PME), CIMT, abdominal aorta ultrasound, retinal photography, and microalbuminuria. The 3 cardiac tests are: Pro-BNP, ECG, and LV ultrasound. Additional tests are waist circumference, BMI, fasting blood sugar, lipid profile, and CRP. 596 out of the total subjects were asymptomatic, and out of these 220 (37%) underwent cardiac CT for coronary artery calcium scoring (CACS) and EFV determination using Siemens Somatom Definition Dual source CT scanner 64x2. 107 out of the 220 were females (48%). These females were divided into 5 groups based on their EFV: 24 with < 69cm
3
; 33 between 70cm
3
and 94cm
3
; 16 between 95cm
3
and 119cm
3
; 20 between 120cm
3
and 144cm
3
; and 14 >145cm
3
.

Results:
As noted in the table, a step-wise increase in EFV was associated with proportional increases in CVSFA, specifically CACS, resting BP, abnormal rise in BP-PME, CRP, and triglycerides. An increase in EFV was noticeably associated with an increase in resting blood BP by a 10mmHg difference between the group whose EFV < 120cm
3
and those whose EFV is > 120cm
3
.

Conclusions:
Based on our data, we feel that excess EFV appears to be the villain for most CVSFA. Accordingly, we urge all healthcare professionals that it is time to focus on early and accurate assessment of this significant risk marker, which is the culprit for many CVD risk factors.

Early detect to protect.
Abstract 14820: Hypertensive Patients’ Perceptions of the Food Environment
Authors: Hines Anika L , Brody Rebecca , Zhou Zehui , Collins Sarach V , Omenyi Chiazam , Miller Edgar R , Cooper Lisa A , Crews Deidra
Published: May 2021

Introduction:
Poor food environment and disproportionate food insecurity among African Americans represent determinants of chronic disease disparities by race/ethnicity. The presence of a supermarket could lead to a 32 percent increase in fruit and vegetable consumption among AAs, yet a complex set of barriers may make it difficult to participate in healthy nutrition. We examined the food environment in Baltimore, MD, through the perspectives of African Americans with hypertension.

Methods:
Photovoice is a community-based participatory research tool that uses photography to engage participants in reflection and dialogue regarding their community's strengths, needs, and capacity for social change. We recruited 24 residents of Baltimore who met initial demographic—age (21 years or older), race (African American), and clinical criteria (hypertension) for the
Five Plus Nuts and Beans for Kidneys
study—a randomized control trial of a dietary intervention, but were ultimately found ineligible. After photography training, participants responded to “Photograph everything related to food in your neighborhood” and discussed their images over 4 sessions. Audiotaped conversations were analyzed for common themes.

Results:
Through this formative, community-engaged process, residents deemed the food environment reflective of the race of the neighborhood’s occupants with low-income Blacks consistently situated at the disadvantaged end. Participants expressed the lack of access to food—a resource that they deemed should be accessible to all—as a catalyst of crime, a point of racial injustice, and a stumbling block in improving their health. Residents identified both individual- and system-level barriers and facilitators to eating healthy foods.

Conclusions:
Engaging community voices and taking stock of the nuances of the food environment, including its construction and subsequent impact on residents’ outcomes, may inform clinical practice and health policy. Photos will be exhibited and used during a moderated conversation on the food environment among multiple stakeholders in Baltimore, including viable solutions to the “food desert” conditions and opportunities to address racial disparities in chronic disease.
Abstract 14825: Efficacy and Safety of Dabigatran, Rivaroxaban, and Apixaban Compared to Warfarin in Asian Patients With Non-valvular Atrial Fibrillation: A Systemic Review and Meta-analysis
Authors: Li Weijia , Kokkinidis Damianos , Wang Yu Chiang
Published: May 2021

Background:
Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF) originated from western countries. We aimed to systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.

Methods:
Medline and Cochrane databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. The primary outcome was ischemic stroke. The secondary outcomes were all-cause mortality, major bleeding, intracranial hemorrhage, and gastrointestinal bleeding.

Results:
Twelve studies from East Asia or Southeast Asia and 429496 patients in total were included. Dabigatran, rivaroxaban, and apixaban were associated with a significant reduction in the incidence of ischemic stroke (HR=0.78, 95% CI, 0.65-0.94; HR=0.79, 95% CI, 0.74-0.85, HR=0.70, 95% CI, 0.62-0.78; respectively), all-cause mortality (HR=0.68, 95% CI, 0.56-0.83; HR=0.66, 95% CI, 0.52-0.84; HR=0.66, 95% CI, 0.49-0.90; respectively), and major bleeding (HR=0.61, 95%CI, 0.54-0.69; HR=0.70, 95% CI, 0.54-0.90; HR=0.58, 95% CI, 0.43-0.78; respectively) compared to warfarin.

Conclusion:
Dabigatran, rivaroxaban, and apixaban appear to be superior to warfarin in both efficacy and safety in Asian patients with non-valvular AF.
Abstract 14826: Increased Risk of Coronary Artery Disease Among South Asians in a National Biobank
Authors: Patel Aniruddh P , Wang Minxian , Kartoun Uri , Ng Kenney , Khera Amit V
Published: May 2021

Background:
Individuals of South Asian ancestry represent 23% of the world population and experience substantially increased risk of coronary artery disease (CAD) compared to most other ethnicities. AHA/ACC practice guidelines recognize South Asian ancestry as an important ‘risk-enhancing’ factor. The magnitude of increased risk despite contemporary care, extent to which it is captured by existing risk estimators, and its potential mechanisms warrant further study.

Methods:
We studied 9,310 individuals of South Asian ancestry and 456,454 individuals of European ancestry free of baseline CAD from the UK Biobank prospective cohort study.

Results:
Over a median follow-up of 8.1 years, we confirm a striking increase in incident CAD events in individuals of South Asian ancestry, occurring in 352 (3.8%) of South Asians versus 10,165 (2.2%) of European ancestry individuals. After adjusting for age, sex, and enrollment site, this corresponded to a hazard ratio of 2.25 (95% CI 2.02 - 2.52; p<0.001). Importantly, this increased risk was not predicted by the AHA/ACC Pooled Cohorts Equation, which estimates similar 10-year risk for South Asians and European ancestry individuals. Adjustment for a broad range of clinical, anthropometric, and lifestyle risk factors led to modest attenuation of the hazard ratio to 1.73 (95% CI 1.43 - 2.09; p<0.001). By analyzing the population attributable fractions (PAF) of various risk factors, we observe that diabetes accounts for an outsized proportion of risk in South Asians (PAF 0.20, 95% CI 0.14 - 0.25 vs. 0.07, 95% CI 0.06 - 0.08 in European ancestry individuals) and current smoking accounted for a higher proportion of risk in individuals of European ancestry (PAF of 0.08, 95% CI 0.07 - 0.09 vs. 0.02, 95% CI -0.02 - 0.05 in South Asians).

Conclusion:
In the largest prospective study to date, we confirm and extend prior observations of a substantially increased risk of CAD among South Asians that is not captured by current clinical risk estimators.
Abstract 14835: Corona Virus Disease 2019 (covid-19) Myocarditis: Where and What is the Evidence?
Authors: Das Bibhuti B , Deshpande Shriprasad R
Published: May 2021

Background and Objectives:
Cardiac complications due to COVID-19 can occur either directly (myopericaridal involvement) or indirectly by the profound systemic inflammatory response and cytokine storm leading to cardiac dysfunction. No virus RNA has been detected in cardiac myocytes in patients with COVID-19 from China. Our objective is to analyze the COVID-19 myocarditis cases reported in literature to-date.

Methods:
We used terms COVID-19, myocarditis, and cardiac involvement in COVID-19 to perform a search for myocarditis cases due to COVID-19 in PUBMED. We found a total of 8 cases with a diagnosis of COVID-19 myocarditis and analyzed their clinical data as summarized in Table.

Results:
Age ranged from 21-69 years and 75% were male. Of eight COVID-19 myocarditis patients, 3/8(38%) had pre-existing cardiac issues, 5/7(71%) had abnormal electrocardiograms and decreased function by echocardiograms. Troponin and BNP levels were elevated in all cases. CMR was performed in 5 cases and showed myocardial edema in T2 mapping and late gadolinium enhancement suggesting scar/fibrosis in 100% cases. No endomyocardial biopsy or autopsy was performed except one case, who was dead on arrival and autopsy study showed eosinophilic myocarditis, not a typical finding of viral myocarditis. Overall outcomes were 2 deaths and 6 patients recovered.

Conclusions:
COVID-19 can cause direct myocardial injury but the evidence is extremely limited at this stage. Although serum markers and imaging suggest cardiac involvement, the pathogenesis and long term impact of COVID-19 on cardiovascular system is unknown. Evaluation for myocarditis by endomyocardial biopsies may be appropriate in selected cases when a treatable type of myocarditis is suspected (e.g. giant cell myocarditis) or unexplained severe bi-ventircular dysfunction or arhrhythmia with normal coronaries to confirm a definitive diagnosis of myocarditis and identify its cause to enable possible etiology-directed therapy.
Abstract 14851: Under Pressure: Hemodynamics Bringing the Right "fix" to Heart Failure
Authors: Oliveros Estefania , Correa Ashish A , Parikh Aditya , Leber Robert , Talebi Soheila , Brailovsky Yevgeniy , Lala Anu , Contreras Johanna P
Published: May 2021

Introduction:
High-output heart failure (HF) develops in the setting of excessive cardiac output.

Case Presentation:
65-year-old male with HF (EF 40%), severe right ventricular dysfunction, and emphysema presented with dyspnea and anasarca. On admission, physical examination showed a BP 97/66mmHg, heart rate 109bpm, temperature 97.2F, respiratory rate of 19rpm, 93% on 2-Liters of oxygen. Jugular venous pressure was 20 cm H20 with large V waves. The rhythm was irregular, with a loud second heart sound, audible third heart sound, parasternal heave, and left lower sternal border murmur. Lung exam demonstrated basilar crackles and prolonged expiratory phase. The abdomen was distended with a pulsatile liver and the lower extremities were cool with 3+ pitting edema. There was an audible bruit with thrill at the right groin. Laboratory testing showed sodium=123mEq/L, creatinine=1.25mg/dL, bilirubin=2.2, ALT=135U/L, AST=146u/L, troponin-I=0.097ng/mL, BNP=1528pg/mL. CT and VQ scan were negative for acute/chronic pulmonary embolism. Lower extremity Doppler ultrasound revealed a right common femoral arteriovenous (AV) fistula (Fig.1). After diuretics and milrinone, a left heart catheterization demonstrated known three vessel disease, but without limitations in instant flow reserve. Right heart catheterization demonstrated RA=15mmHg, RV=50/16mmHg, PA=50/24(34)mmHg, PCWP=11mmHg, CO=5.4L/min, PVR=4.25WU, after which the fistula was ligated. On post-op day 2, repeat hemodynamics off inotropes showed an RA=4mmHg, PA=40/18mmHg, PCWP=18 mmHg, CO=4.4L/min and normalization of end-organ function. He was maximized on GDMT. Echocardiogram 5 months later showed improvement of RV function and he was able to go back to work with minimal symptoms.

Conclusion:
AV fistulas can lead to high-output HF if undiagnosed. A multidisciplinary approach and comprehensive hemodynamic assessment proved essential in allowing improvement of symptoms and resulting outcomes.
Abstract 14858: Conditional Deletion of Lysyl Oxidase Improves Vascular Function in Apoe
-/-
Mice
Authors: Stoyell Conti Filipe F , Hernandez Diana , Rojas Miguel , Martinez Laisel , Vazquez-Padron Roberto I
Published: May 2021

Introduction:
Lysyl oxidase (LOX) is a copper-dependent amino-oxidase that initiates covalent cross-linking of collagen and elastin, modifies growth factor action and controls gene expression. LOX upregulation is associated with cardiovascular diseases. Because embryonic LOX knockout (KO) mice die perinatally of aortic aneurysms and cardiovascular dysfunction, the studies about LOX function in cardiovascular disease has relied mostly on the use of beta-aminopropionitrile. However, this irreversible inhibitor also inhibits other members of LOX family.

Hypothesis:
To overcome this limitation, we hypothesized that conditional inactivation of lysyl oxidase would improve vascular function in apoE
-/-
mice.

Methods:
We developed, for the first time, a global (LOX
f/f
CAG-CreERT2 ApoE
-/-
) and a smooth muscle cell (SMC) specific (LOX
f/f
Myh11-CreERT2 ApoE
-/-
) LOX conditional knockout mice.

Results:
LOX inactivation in SMC decreased immature collagen crosslinking in the aorta, carotid pulse wave velocity and blood pressure. It led to a significant reduction in atherosclerotic plaque deposition in the aorta after 16 weeks of high-fat diet (HFD). Global inactivation of LOX, on the other hand, also reduced the systolic blood pressure and prevented vascular stiffness after 4 weeks of HFD. In in-vitro studies, we found that LOX is present in the extracellular space and the nucleus of SMC. Bulk RNA-seq revealed that LOX deletion elevated the expression of SMC alpha-actin, transgelin, and filamin A genes, which are typically present in the contractile phenotype.

Conclusion:
Our data show that conditional deletion of LOX is atheroprotective and improved vascular and hemodynamic function in ApoE KO mice.
Abstract 14859: Mesenchymal Stem Cells Rescue Patient-Specific Cardiomyocyte Viability and Function Following Doxorubicin Injury via Microvesicle Mediated Mitochondrial Transfer to Recapitulate Human Clinical Trial Results
Authors: OBrien Connor G , Ozen Mehmet O , Vaskova Evgeniya , Jung Jihye , Santoso Michelle , Shi Liye , Wahlquist Christine A , Jiang Zewen , Jung Yunshin , Ikeda Gentaro , Zeng Yitian , Sinclair Robert , Gee Adrian , Witteles Ronald M , Mercola Mark , Svensson Katrin , Demirci Utkan , Yang Phillip C
Published: May 2021

Introduction:
Anthracyclines are effective chemotherapeutic agents associated with cardiac toxicity. Anthracycline induced cardiomyopathy (AIC) carries a mortality of 20% at four years. Effective therapies for AIC have not been established. The NIH-sponsored Stem Cell Injection for Cancer Survivors (SENECA) Trial examined the role of allogeneic mesenchymal stem cells (MSC) to treat AIC. To predict the efficacy of MSC in the SENECA patients, we performed an
in vitro
clinical trial to study the restorative effects of MSC on patient-specific iPSC-derived cardiomyocytes (iCM) by assessing the effects
in vitro
following doxorubicin (dox) exposure.

Hypothesis:
MSC secretome will rescue SENECA Trial patient-specific iCM from dox injury.

Methods and Results:
We generated three SENECA patient-specific iPSC lines.
In vitro
iCM dox sensitivity was shown to be comparable to published values. iCM were cultured in 1μM dox for 24hrs, treated with MSC or MSC-secretome, and assessed for viability and apoptosis. Co-culture of MSC with iCM using a 1μm trans-well system improved iCM viability by 43% (p-value < 0.005) and reduced apoptosis (p-value = 0.013). To better define the paracrine mechanism, MSC-secretome was divided into microvesicles >200nm (MV) and exosomes <200nm (Ex) using a novel filtration system. MV recapitulated the effect of co-culture, improving iCM viability by 87.8% (p-value = 0.006) and reducing apoptosis by 60% (p-value = 0.013). Treatment with Ex had no effect. MV restore contractility and calcium transients in the dox-injured iCM. MV were found to contain mitochondria (MT), which are taken up by iCM. Treated iCM demonstrate increased MT-copy number and augmented MT-biogenesis. Inhibition of MT function in MV attenuated therapeutic efficacy. We were unblinded to SENECA outcomes. In our cohort, the MSC-treated patient improved across all endpoints while placebo treated patients did not consistent with our
in vitro
findings.

Conclusion:
Allogeneic MSC attenuate apoptosis and restore contractility following dox injury in patient-specific iCM. MV and MT-transfer appear to be the putative mechanism. Our findings correlate with the SENECA results, demonstrating proof-of-concept that iPSC-derivatives can be used to predict trial outcomes.
Abstract 14861: Premature Menopause and Mid-life Subclinical Atherosclerosis: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Mehta Priya P , Petito Lucia , Colangelo Laura A , Lewis Cora E , SCHREINER Pamela , Terry James G , Wellons Melissa , Kim Catherine , Rana Jamal S , Lloyd-jones Donald M , Allen Norrina B , Khan Sadiya S
Published: May 2021

Introduction:
Women who experience premature menopause are known to have higher rates of long-term atherosclerotic cardiovascular disease (ASCVD). Specifically, menopause prior to age of 40 years has been identified as a risk enhancer by the 2019 AHA/ACC Primary Prevention guidelines. Coronary artery calcium (CAC) may have clinical utility for refinement of risk stratification in this high-risk group of women for the primary prevention of ASCVD.

Methods:
We included women from the Coronary Artery Risk Development in Young Adults (CARDIA) study who completed a coronary-gated CT scan at a baseline age of 43-55 years. We excluded women who had a myocardial infarction prior to CAC assessment. Menopausal status was self-reported as before the age of 40 years, at 40 years or older, or pre-menopausal. No significant interaction by race was observed. We performed multinomial logistic regression analysis to examine the association between premature menopause and 3 categories of CAC (0, 1-99, and ≥100 Agatston units). In separate multivariable models, we adjusted for demographic and cardiovascular risk factors at the time of CAC measurement.

Results:
Of 1786 women, 167 (9.4%) experienced premature menopause, 1175 (65.8%) reached menopause after the age of 40 years, and 444 (24.9%) were pre-menopausal at the time of CT. Presence of any CAC in these 3 groups was 18.0%, 19.6%, and 11.3% for premature menopause, ≥40 menopausal, and the pre-menopausal groups, respectively (FIGURE). Premature menopause was not associated with higher odds of non-zero CAC in unadjusted or adjusted analyses.

Conclusions:
Premature menopause was not associated with prevalent CAC score in these women in mid-life. Consideration of alternative approaches or biomarkers for risk stratification for ASCVD should be evaluated in this high-risk group.
Abstract 14868: Promises of Transcatheter Tricuspid Valvular Interventions in Patients With Clinically Significant Tricuspid Regurgitation: A Meta-analysis
Authors: Rezaei Bookani Kaveh , Nso Nso , Radparvar Farshid , Ricciardi Mark
Published: May 2021

Introduction:
Clinically significant tricuspid regurgitation is common especially in patients with structural heart disease and is independently associated with poor outcomes. Several transcatheter interventions for tricuspid valve repair are under investigation. We aimed to illustrate and summarize the efficacy and safety of these interventions.

Methods:
We conducted a literature search for relevant clinical registries and trials published until April 2020. We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL. We performed the analysis of continuous outcomes using the mean difference (MD) while used the risk ratio (RR) for analysis of dichotomous outcomes. We included the following outcomes: Tricuspid annular plane systolic excursion (TAPSE), Vena Contracta (VC), Tricuspid Annulus diameter (TAD), Tricuspid regurgitation volume (TRV), Left ventricular ejection fraction (LVEF), and mortality rates. The random-effects model was used for the analysis of heterogeneous data, while homogeneous data were analyzed under the fixed-effects model.

Results:
We obtained fifteen clinical registries/trials and included a total of 1329 patients. We found that tricuspid valve interventional devices improved LVEF (MD = 1.46%, 95% CI [0.45, 2.47], p=0.005), led to smaller VC (MD = -4.69, 95% CI [-5.50, -3.88], p=0.005), lower TRV (MD = -11.68, 95% CI [-21.25, -2.11], p=0.02), and smaller TAD (MD = -3.78mm, 95% CI [-5.09, -2.47], p<0.001). No significant difference was noted regarding TAPSE (MD=0.07mm, 95% CI [-0.29, 0.44], p=0.7). Results of the six minutes walking test showed that patients could walk 40 more meters after intervention (MD = 40.64, 95% CI [23.89, 57.40], p<0.001). Pooled mortality rate was 8.2%, stroke 1%, and bleeding 5% during the mean 12 months follow up.

Conclusions:
Transcatheter tricuspid valve repair devices prove to be effective interventions in decreasing regurgitation and improving functional capacity in patients with clinically significant TR. Mortality (8% during mean 12 months follow up) seems to be related to underlying cardiovascular disease.
Abstract 14878: Exosomes From Induced Pluripotent Stem Cell-Derived Cardiomyocytes vs Mesenchymal Stem Cells Demonstrate Differential Restoration of Myocardial Function in a Porcine Ischemia Reperfusion Injury Model
Authors: OBrien Connor G , Vaskova Evgeniya , Tada Yuko , Jung Jihye , Ikeda Gentaro , Santoso Michelle , Yang Phillip C
Published: May 2021

Introduction:
Coronary artery disease is a leading cause of death worldwide. Ischemic injury leads to myocardial dysfunction, resulting in heart failure. Exosomes have emerged as a promising therapeutic for restoring the failing heart. Fundamental questions such as cell of origin and molecular cargo for optimal therapeutic effect are areas of intense research. Our lab has shown that the exosomes from bone marrow derived mesenchymal stem cells (MSC-Ex) and induced pluripotent stem cell derived cardiomyocytes (iCM-Ex) both restore injured murine myocardium. These results led us to compare the therapeutic effects of MSC-Ex vs. iCM-Ex in a porcine myocardial ischemia reperfusion (IR) injury model, a step toward predicting efficacy in humans.

Hypothesis:
iCM-Ex is superior to MSC-Ex in restoring the injured porcine myocardium.

Methods and Results:
Pigs underwent ischemia reperfusion (IR) injury, consisting of 1 hour percutaneous balloon occlusion of the proximal left anterior descending artery immediately distal to the first septal artery. Following IR injury, 5 x 10
11
exosomes were delivered in ten, 500μL intramyocardial injections using a BioCardio Helix™ catheter. Biplane ventriculography was used to target the peri-infarct region. At 2- and 4-weeks post-infarct, pigs underwent cardiac MRI (cMRI) with ciné, delayed-enhanced (DEMRI) and manganese-enhanced (MEMRI) MRI. Pigs treated with iCM-Ex (n = 5) demonstrated a 41% improvement in left ventricular ejection fraction (LVEF, p = 0.004) and 35% reduction in indexed left ventricular end diastolic volume (p = 0.008) compared to controls while MSC-Ex (N = 5) did not demonstrate significant functional improvement. Furthermore, DEMRI and MEMRI showed a 21% reduction in myocardial scar (p = 0.14) in iCM-Ex treated animals compared to control while MSC-Ex group showed no difference. RNA-seq of the exosomes and transcriptomic analysis of the
ex vivo
myocardium will delineate the molecular mechanism of action and the putative intracellular pathway.

Conclusion:
iCM-Ex is superior to MSC-Ex in improving LVEF and reducing myocardial scar formation following ischemic insult. Comparative analysis between iCM-Ex and MSC-Ex is underway to identify the molecular targets that restore the failing heart.
Abstract 14882: Outcomes of Heart Failure in Hypoplastic Left Heart Syndrome and the Impact of Recovery
Authors: Lynch Aine , Jeewa Aamir , Minn Sunghoon , Arathoon Katelyn , Ashkanase Jenna , Honjo Osami , Floh Alejandro , Jean-st-michel Emilie M
Published: May 2021

Introduction:
Survival for children with hypoplastic left heart syndrome (HLHS) and right ventricular (RV) dysfunction (dysfxn) remain poor. We describe outcomes of HLHS patients with RV dysfxn and the long-term impact of interval normalization.

Methods:
The SickKids Heart Failure (HF) Database is a retrospective cohort of HF patients from 2001 to 2017. We included patients with HLHS and at least mild RV dysfxn on echocardiogram lasting >30 days, or death or transplant within 30 days of onset of dysfxn. We defined normalization as normal RV function (fxn) lasting > 30 days after dysfxn onset. The primary endpoint was death or transplant. Descriptive statistics and time to event analysis were used.

Results:
We identified 99 patients with a median (IQR) age at onset of dysfxn of 2.6 (1 - 5.3) months. Of these, 51 (52%) had normalization of RV fxn for a median (IQR) duration of 3.5 (0.8 - 9.1) years and 28 (55%) had multiple periods of normal fxn. Of those who normalized, 4 (8%) normalized within a few months post Glenn procedure and 6 (13%) had normal fxn at last follow up. Patients with and without normalization had similar frequency of severe dysfxn (41 vs 52%, p=0.6). Normalization of RV fxn correlated with improved transplant free survival (78 % vs. 14 %, p<0.001, Figure 1C) independent of surgical stage (p=0.03, figure 1D). Table 1 shows risk factors independently associated with transplant-free survival, including angiotensin converting enzyme inhibition.

Conclusions:
HLHS patients with RV dysfxn have poor transplant-free survival, especially those at interstage, but outcomes improve in those with persistent normalization of fxn. Factors predicting normalization need further study
Abstract 14883: The Role of Obstructive Sleep Apnea in Hospitalization in Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus
Authors: Hashmath Zeba , Bose Abhishek , Chevli Parag A , Sherif Akil , Avinashsingheswarsingh Fnu , Pandey Shubhi , Shah Tanvi , Kirkpatrick Joseph
Published: May 2021

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disease with diverse etiologies. Obstructive sleep apnea (OSA) is known to increase the risk of diastolic dysfunction and heart failure. OSA also increases the risk and severity of type 2 diabetes (DM2) independent of age and obesity. However, its role in patients with HFpEF and concomitant DM2 is unclear.

Hypothesis:
Our aim was to study the role of OSA in hospitalizations in patients with HFpEF and concomitant DM2.

Methods:
We did a retrospective chart analysis of 142 patients age (72 ± 11, 54.9% women) with HFpEF and known DM2 for five years after the initial diagnosis of HFpEF. Presence of OSA at the time of initial HFpEF diagnosis was noted based on the results of a documented sleep study. A multivariable cox-proportional hazard model was used to assess whether the presence of OSA had any significant impact on the risk of future HFpEF hospitalization. Kaplan-Meier analysis was used to calculate if OSA predicted time to future HFpEF hospitalization.

Results:
After a five year follow up, 63 (44.3%) participants developed HFpEF exacerbation. Patients were dichotomized based on presence (n=40, 28.1%) or absence (n=102, 71.8%) of OSA. In a multivariable model adjusted for baseline demographics, risk factors and medications, presence of OSA did not predict risk for a future HFpEF hospitalization (p=0.57, Table). Additionally, on Kaplan-Meier analysis, presence of OSA was not a significant predictor for HFpEF hospitalization (p=0.77, Figure).

Conclusion:
In patients with HFpEF and concomitant DM2, presence of OSA was not a predictor for future heart failure hospitalizations.