bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13046: Treatment of Highly Sensitized Patients Before Heart Transplant Associated With Long-term Post-transplant Benefit
Authors: Ho Timothy , Patel Jignesh K , Nishihara Keith , Kittleson Michelle M , Chang David H , Kransdorf Evan P , Czer Lawrence S , Zhang Xiaohai , Kobashigawa Jon A
Published: May 2021

Introduction:
Highly sensitized patients awaiting heart transplantation (HTx) are disadvantaged by a narrow donor pool due to incompatible potential donors. Desensitization therapy has been demonstrated to be effective in lowering antibodies and thereby enlarging the donor pool. By desensitization, the calculated panel reactive antibody (cPRA) has been reported to decrease and result in a shorter waitlist time. It has not been established whether desensitization before transplant can have impact after HTx outcomes.

Methods:
Between 2010 and 2015, we assessed 34 patients awaiting HTx who had a PRA >50% and underwent desensitization therapy. Desensitization therapy included combinations of IVIG, rituximab, plasmapheresis, and bortezomib. These patients who underwent HTx were then assessed for outcomes, which included 5-year survival, freedom from cardiac allograft vasculopathy (CAV), freedom from non-fatal major adverse cardiac events (NF-MACE), and freedom from donor specific antibody (DSA) development and 1-year freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody mediated rejection (AMR)). Patients who underwent desensitization were compared to a similar group of patients with PRA >50% who did not undergo desensitization and underwent HTx.

Results:
Patients who underwent desensitization compared to those who did not had significantly greater freedom from 5-year development of CAV (94.1 vs 78.8%, p=0.039). There was no significant difference in 5-year survival, 5-year freedom from NF-MACE or DSA development, and 1-year freedom from ATR, ACR, AMR.

Conclusions:
Desensitization in highly sensitized patients awaiting HTx appears to have long ranging effects to modulate the immune system after HTx, resulting in less development of CAV. Further investigation should be pursued to understand the mechanism of this intervention.
Abstract 13079: An Increase in Circulating Cardiomyocyte-specific Cell-free DNA in Heart Failure
Authors: Misaka Tomofumi , Yokokawa Tetsuro , KIMISHIMA Yusuke , Takeshi Shimizu , Kaneshiro Takashi , Takeishi Yasuchika
Published: May 2021

Introduction:
Cardiomyocyte cell death is closely linked with the pathophysiology of heart failure. Cell-free DNA (cfDNA) is found in circulating blood as fragmented double-strand DNA, which is released from dying cells. However, the clinical significance of cfDNA in heart failure has not been elucidated.

Methods and Results:
The present study enrolled 32 heart failure patients and 28 control subjects. Circulating cfDNA was isolated from plasma samples in peripheral blood. The levels of total cfDNA assessed by quantitative PCR using LINE1-specific primers were not different between the two groups (P=0.343). Next, cfDNA was subjected to bisulfite conversion to identify cardiomyocyte-derived cfDNA, based on that FAM101A locus is unmethylated in a cardiac-specific manner. Digital PCR targeting the unmethylated FAM101A locus demonstrated that the copy numbers of cardiomyocyte-specific cfDNA were significantly elevated in heart failure patients compared to controls (0.99 [0.77 - 1.98] vs 0 [0 - 0.91] copies/mL, P=0.003,
Figure A
). The receiver operating characteristic curve revealed that cardiomyocyte-specific cfDNA significantly discriminated heart failure patients from control subjects (AUC, 0.716, P=0.003). Correlation analysis showed that the levels of cardiomyocyte-specific cfDNA were significantly correlated with serum levels of high-sensitivity cardiac troponin I (r = 0.438, P = 0.012,
Figure B
), but not with BNP (r = 0.275, P = 0.058), suggesting that the elevated cardiomyocyte-specific cfDNA might be associated with enhanced cardiomyocyte death but not with high ventricular filling pressure.

Conclusions:
A newly developed bisulfite-digital PCR system identified an increase in cardiomyocyte-specific cfDNA in heart failure patients. cfDNA may be a novel biomarker to measure the actual numbers of cardiomyocyte death in heart failure.
Abstract 13080: Clinical Significance of Clonal Hematopoiesis With JAK2V617F in Patients With Cardiovascular Diseases
Authors: Wada Kento , Misaka Tomofumi , Yokokawa Tetsuro , KIMISHIMA Yusuke , Minakawa Keiji , Kaneshiro Takashi , YOSHIHISA Akiomi , Ikeda Kazuhiko , Takeishi Yasuchika
Published: May 2021

Background:
It becomes increasingly clear that age-related clonal hematopoiesis (CH) is associated with cardiovascular diseases. However, CH with a driver mutation that causes myeloproliferative neoplasm (MPN) is not fully understood.

Objective:
To determine the clinical relevance of CH with MPN-driving mutations on cardiovascular diseases.

Methods:
This study prospectively enrolled 832 patients with cardiovascular diseases who did not show any hematological disorders. We examined the presence of the known MPN-driving mutations including JAK2V617F, CALRdel52, CALRins5, MPLW515L, and MPLW515K by an allele-specific polymerase chain reaction.

Results:
Out of 832 patients, 16 patients (1.9%) exhibited MPN-driving mutations including 15 patients with JAK2V617F (1.8%) and 1 patient with CALRins5 (0.1%). We divided the patients into two groups: vascular diseases including coronary artery disease, stroke, aortic aneurysm, aortic dissection, peripheral artery disease, deep vein thrombosis, and pulmonary thromboembolism (n=462, 55%) and non-vascular diseases (n=370, 45%). The prevalence of JAK2V617F-positive CH was significantly higher in patients with vascular diseases than in those with non-vascular diseases (2.8% vs. 0.5%, P = 0.014). In a multivariable analysis adjusted for known classic-atherosclerotic risk factors (age, male, obesity, smoking, hypertension, diabetes mellitus, dyslipidemia), the presence of JAK2V617F-positive CH was independently associated with vascular diseases (odds ratio, 5.448; P = 0.043). Additionally, peripheral leukocyte IL1B mRNA expressions as well as plasma interleukin-1β concentrations were significantly increased in patients with JAK2V617F-positive CH compared to those without JAK2V617F (P = 0.040 and P = 0.030, respectively).

Conclusions:
CH with JAK2V617F, but not CALR or MPL mutations, was significantly associated with vascular diseases independently on classic-atherosclerotic risk factors, in relation to interleukin-1β-related inflammatory mechanisms. JAK2V617F is a potential diagnostic and therapeutic target for vascular diseases.
Abstract 13081: Predictive Value of Visceral-to-subcutaneous Fat Ratio for Long-term Clinical Outcomes in Patients With Suspected Coronary Artery Disease
Authors: Machida Keisuke , Otagiri Kyuhachi , Itagaki Tadashi , Takeuchi Takahiro , Kitabayashi Hiroshi
Published: May 2021

Introduction:
Although visceral fat accumulation is an important risk factor for coronary artery diseases (CAD), the relationship between visceral fat accumulation and its long-term outcomes has not been extensively investigated.

Hypothesis:
In patients with suspected CAD, the distribution of subcutaneous fat and visceral fat is associated with cardiovascular events.

Methods:
Computed tomography (CT) angiographies (CTA) were performed on 945 consecutive patients with suspected CAD. Plain abdominal CT scanning was performed to measure the patients’ visceral fat area (VFA) and subcutaneous fat area (SFA). The VFA/SFA (V/S) ratios were calculated to assess the visceral fat accumulation. Based on the results of the CTA, the prevalence of CAD was assessed. The patients were classified into low (<0.627), and high (≥0.627) V/S ratio groups, based on their median value, and the association between V/S ratio and long-term outcomes was evaluated. The primary endpoints were major cardiac adverse events (MACE), including all-cause death, new-onset acute coronary syndrome (ACS), emergent hospitalization due to cardiovascular disease, and any coronary revascularization.

Results:
The average follow-up period was 845.3 days. The baseline characteristics for patients in the high V/S ratio group were worse than those for patients in the low high V/S ratio group. As compared to the low V/S ratio group, a higher incidence of MACE and ACS, and a higher tendency of mortality was observed in the high V/S ratio group. After adjusting for traditional coronary risk factors, the V/S ratio was independently associated with incidence of MACE, ACS, and increase of mortality (table).

Conclusions:
The present study suggests that the V/S ratio is an independent predictor of long-term outcomes in patients with suspected CAD. The visceral fat accumulation indicated by high V/S ratio signifies a potential risk and may contribute to the future cardiovascular events in patients with suspected CAD.
Abstract 13116: Ventilatory Gas Exchange in Stable Coronary Artery Disease
Authors: Ganesananthan Sashiananthan , Rajkumar Christopher , Shun-Shin Matthew , Nowbar Alexandra , Foley Michael , Seligman Henry , Wensel Roland , Davies John , Francis Darrel , Al-Lamee Rasha K
Published: May 2021

Introduction:
Cardiopulmonary exercise testing (CPET) provides a non-invasive evaluation of exercise physiology via ventilatory gas exchange (VGE). We do not know how these assessments correlate with myocardial ischemia or angina symptoms in patients with stable single-vessel coronary artery disease (CAD). In this analysis, we use randomised, blinded data from the ORBITA trial to investigate the association between VGE, ischemia and symptoms in patients with severe single-vessel CAD.

Methods:
Patients underwent treadmill CPET using the smoothed-modified Bruce protocol, after a 6-week medical optimisation phase during which antianginals were uptitrated. Symptoms were assessed using the Seattle Angina Questionnaire (SAQ), EuroQOL 5 and Canadian Cardiovascular Society (CCS) angina class. Ischemia was quantified using fractional flow reserve (FFR), instantaneous wave-free ratio (iFR) and dobutamine stress echocardiography (DSE).

Results:
We assessed 195 patients [mean age 66.1±9.1, 143 (73.3%) male]. We found a significant association between peak oxygen uptake (VO
2
) and minute ventilation to carbon dioxide (VE/VCO
2
) slope, and physician assessed CCS class [P
correlation(cor)
<0.0001(Figure 1), P
cor
<0.0001, respectively], patient-reported SAQ angina frequency score [P
cor
<0.011(Figure 1), P
cor
<0.0001], physical limitation (P
cor
<0.0001, P
cor
=0.0001) and EuroQOL 5 visual analogue score (P
cor
= 0.0011, P
cor
=0.0019). There was no detectable relationship between peak VO
2
or VE/VCO
2
slope, and FFR, iFR or DSE (p>0.05, for all). Patients with an oxygen pulse plateau however, had higher dobutamine stress echo score compared to those without (+0.71; 95%CI 0.22-1.21, p=0.0049).

Conclusions:
The association between VGE and angina symptoms is stronger than its ability to detect severity of myocardial ischemia. This analysis highlights the complexity of the relationship between symptoms, functional capacity and myocardial ischemia.
Abstract 13122: Sensor-controlled Digital Game May Improve Weight Monitoring Among Older Adults With Heart Failure
Authors: Radhakrishnan Kavita , Julien Christine , O'Hair Matthew , Baranowski Thomas , Lee Grace , Sagna Atami , Allen Catherine , Thomaz Edison , Kim Miyong T
Published: May 2021

Introduction:
Poor self-management of heart failure (HF) has contributed to poor health outcomes with an annual loss of $32 billion. Our innovative sensor controlled digital game (SCDG) integrates data from weight scale and physical activity sensors to trigger rewards, progress, changes in avatar’s health status and feedback based on HF individuals’ real-time behaviors (Fig1).

Hypothesis:
Weight monitoring and physical activity by participants receiving both the SCDG app and sensors will be higher than participants receiving only the sensors (CG).

Methods:
English-speaking HF adults aged >55 years, own a smartphone, and walk unassisted were recruited from cardiac settings in Texas. Both SCDG and CG participants were given ‘Withings’ activity tracker and smart weight scale sensors to track behaviors for 12 weeks. Physical activity goal was tailored to the participant’s ability.

Results:
In early results over six weeks on 12 participants (58% women, white, and 65+ years age), the mean days with weight monitoring in the SCDG group was 34 and 27 in the CG. Daily average steps were 2195 (53% of goal) in SCDG group and 3187 in CG (75% of goal). 100% of participants found the SCDG easy and enjoyable to play. Study adaptations in response to the COVID19 crisis will allow us to present results on 30 participants at conference time.

Conclusion:
SCDG had trends of higher weight monitoring but lower physical activity among older adults with HF. Participants in the study continue to engage in weight-monitoring and physical activity even during the COVID19 crisis. This presents opportunities to tailor digital health interventions to remotely motivate self-management behaviors.
Abstract 13140: Right Ventricular Remodeling and Changes in Tissue Biomechanics in Healthy Aging
Authors: Sharifikia Danial , Shen Yuanjun , Bachman Timothy , Goncharova Elena , Kim Kang , Simon Marc A
Published: May 2021

Introduction:
Normal aging in healthy adults has been associated with pulmonary vasculature remodeling and alterations in right ventricular (RV) systolic and diastolic function, which may lead to increased RV afterload and pulmonary hypertension (PH). Previous studies have found a close link between RV biomechanics and function. While current findings suggest a connection between aging and survival rates of PH patients, limited data exist on age-associated differences in the biomechanical properties of RV myocardium.

Hypothesis:
Aging results in increased RV afterload, hypertrophy, and myocardial stiffening.

Methods:
Two groups of control (11 weeks) and aging (80 weeks) Sprague-Dawley rats were studied via terminal invasive hemodynamic measurements (n=5/group), quantitative transmural histological analysis (n=3/group; Masson’s trichrome), biaxial mechanical testing (n=6/group) and constitutive modeling (n=6/group) for a comprehensive multi-scale study on the effects of aging on RV biomechanics.

Results:
Aging increased RV peak pressures by 15% (26.79±0.87 vs. 23.28±0.83 mmHg for aging vs. control; p=0.020). Increased RV wall thickness (0.89±0.06 vs. 0.66±0.04 mm for aging vs. control; p=0.010) and cardiomyocyte width (25.42±0.34 vs. 14.94±0.64 μm for aging vs. control; p<0.001) were observed in the aging group, while not showing any effects on the Fulton index. Histological analyses showed transmural realignment of RV collagen and myofibers towards the apex-to-base direction by 14.6° (p=0.017). This was accompanied by transmural loss of cardiomyocytes (cardiomyocyte area fraction: 88.4%±0.4% vs. 95.3%±0.7% for aging vs. control; p<0.001) and increased myofiber stiffness (169.9±20.6 vs. 65.8±4.7 kPa for aging vs. control; p<0.001). While aging resulted in RV fibrosis (collagen area fraction: 5.1%±0.5% vs. 3.8%±0.1% for aging vs. control; p=0.049), collagen fibers in the aging myocardium showed decreased effective intrinsic stiffness compared to young controls (23.9±3.8 vs. 73.1±15.4 MPa for aging vs. control; p=0.031).

Conclusions:
Healthy aging has the potential to modulate RV dysfunction via increased myofiber stiffness, fiber reorientation, loss of ventricular cardiomyocytes, RV hypertrophy and fibrosis.
Abstract 13143: Safety Evaluation of Therapeutic Angiogenesis With Adipose-derived Regenerative Cells for Ischemic Limb in a Tumor Bearing Model
Authors: Suzuki Junya , Shimizu Yuuki , Tsuzuki Kazuhito , Pu Zhongyue , Yamaguchi Shukuro , Shibata Rei , Murohara Toyoaki
Published: May 2021

Introduction:
Implantation of adipose-derived regenerative cells (ADRC) is a promising novel strategy to augment angiogenesis and blood perfusion recovery in ischemic diseases with no other therapeutic option. However, there is a clinical concern underlying therapeutic angiogenesis that implantation of ADRC may promote tumor growth and metastasis via remote angiogenesis. Accordingly, we tested whether therapeutic angiogenesis with ADRC against hindlimb ischemia (HLI) would affect remote tumor growth and angiogenesis in a tumor-bearing mouse ischemic hindlimb model.

Methods and results:
B16F10-Luc (murine melanoma cells expressing luciferase, 1x106 cells/animal) were implanted to C57BL/6J mice’s (male, 8-10 weeks old, n=10) back. Mice were subjected to unilateral HLI surgery one day after tumor implantation. Then, mice were randomly assigned to the control group or the ADRC group (n=5 for each). ADRC (1x106 cells/animal) or PBS were implanted/injected into ischemic hindlimb muscles one day after the surgery. Blood perfusion recovery in HLI by laser Doppler perfusion imaging system and tumor size by a caliper were measured every week up to 21 days after surgery. At POD 21, tumor weight and luciferase activity in primary tumors obtained by in vivo bioluminescence imaging system were also evaluated. Immunohistochemistry by CD31 or LYVE1 staining was performed to detect feeder arteries or outflow lymphatic vessels in tumors. The results demonstrated that better blood perfusion recovery and more capillary density in HLI was observed in the ADRC group than in the control group (p<0.05, respectively). However, there were no significant differences in terms of tumor volume (p=0.95), tumor weight (p=0.88) and luciferase activity of primary tumor (p=0.92) between those two groups. No sign of distant metastasis was detected by macroscopic and pathological examination, and by in vivo bioluminescence imaging system in both groups. Further study also revealed that capillary density of peritumoral blood vessels or lymphatic vessels was not augmented by ADRC implantation into remote HLI.

Conclusions:
Our data indicated that therapeutic angiogenesis with ADRC implantation against HLI did not promote remote tumor growth, angiogenesis and metastasis.
Abstract 13174: Coronary Origin Patterns: Utility in Echocardiographic Diagnosis of Forme Fruste Right-left Bicuspid Aortic Valve
Authors: Beauchamp Daniel N , Ramaciotti Claudio , Brown Paul , Thankavel Poonam
Published: May 2021

Introduction:
Bicuspid aortic valve (BAV) is a common congenital heart defect associated with coronary artery (CA) variants, including higher incidence of left CA dominance and shorter left main CA length. In patients with right-left fusion (R/L) BAV, we observed that the origins of left and right coronaries are in closer proximity than in normal patients. ‘Forme fruste’ types of R/L BAV are subtle and difficult to diagnose, hence this coronary pattern can aid in diagnosis. We defined intercoronary distance as the angle separating the left and right coronary ostia relative to the aortic valve center.

Hypothesis:
The coronary angle is more acute in R/L BAV than in normal aortic valves.

Methods:
A retrospective review of pediatric echocardiograms with R/L BAV at a single institution (12/2010-11/2018) was performed; coronary angles were measured and compared to age-matched controls. Those with inadequate images or anomalous coronary origins were excluded.

Results:
We identified 193 patients with R/L BAV (64% male) and 136 patients with normal aortic valves (57% male). Coronary angle was significantly more acute in R/L BAV than in controls (117.7°±16.8° vs 139.0°±10.1°, p<0.0001). This was independent of age, gender, or other cardiac defects. This relationship remained when BAV patients with abnormal aortic Z-scores were removed from analysis (119.2°±15.3° vs 139.0°±10.1°, p<0.0001), ruling out an effect of abnormal aortic annulus or root.

Conclusions:
Coronary origins are in closer proximity in R/L BAV independent of annulus/root geometry, associated cardiac defects, age, or gender. This new finding may assist in echocardiographic diagnosis of subtle subtypes of BAV.
Abstract 13175: Social Jet Lag in Eating Patterns as a Marker of Meal Timing Variability is Associated With Elevated Cardiometabolic Risk in the AHA Go Red for Women Strategically Focused Research Network
Authors: Makarem Nour , Sears Dorothy D , St-Onge Marie-Pierre , Zuraikat Faris M , Gallo Linda , Talavera Gregory A , Castaneda Sheila , Xi Huaqing , Aggarwal Brooke A
Published: May 2021

Introduction:
Social jet lag, typically defined as the difference in sleep timing on work vs. free days, is related to elevated cardiovascular disease (CVD) risk, via circadian disruption. Irregular meal timing may also lead to circadian disruption, but the role of social jet lag in eating patterns in CVD risk has not been examined.

Hypothesis:
Social jet lag in eating patterns, a measure of meal timing variability, will be associated with elevated cardiometabolic risk in women.

Methods:
Women from the AHA Go Red for Women SFRN at Columbia (n=116, mean age: 33 y, 45% Hispanic) completed a 1-wk food record using the web-based NIH Automated Self-Administered 24-h Dietary Assessment Tool. Social jet lag in eating patterns was evaluated using the difference between weekday vs. weekend: 1) nightly fasting duration (NFD), 2) time of first meal, and 3) time of last meal. Standard deviation (SD) of % kcal consumed after 5PM and 8PM was used to capture variability in nighttime eating. Cardiovascular health (CVH) was assessed with the AHA Life Simple 7 (LS7) score. Linear regression models adjusted for age, socioeconomic status, and sleep were used to examine associations with CVH, BMI, waist circumference (WC), systolic blood pressure (SBP), diastolic BP (DBP), and fasting glucose.

Results:
The average time of first meal and NFD on weekdays vs. weekends was 8:54AM vs. 10:11AM and 12.5 h vs. 13.7 h, respectively; average time of last meal was similar (8:27PM). Each 1-h increase in the difference between first meal time on weekdays vs. weekends was associated with higher BMI (β=0.81, p=0.018), WC (β=0.67, p=0.029), DBP (β=1.34, p=0.049), and SBP (β=1.45, p=0.062). Each 1-h increase in the difference between weekday vs. weekend NFD was associated with higher BMI (β=0.55, p=0.045), fasting glucose (β=2.46, p=0.028), and SBP (β=1.17, p=0.058) and lower LS7 score (β=-0.24, p=0.014). Greater variability in nighttime eating (higher %kcal after 5PM and 8PM SD) was associated with higher WC (β=0.014, p=0.020 and β=0.030, p=0.040).

Conclusions:
Greater meal timing variability was related to poorer CVH and higher BMI, WC, BP, and fasting glucose. Results suggest that stabilizing meal timing patterns should be considered for lowering CVD risk and warrant confirmation in a larger sample.
Abstract 13184: A New Intraprocedural Automated System for Localizing Idiopathic Ventricular Arrhythmia Origin Sites
Authors: Zhou Shijie , AbdelWahab Amir , Sapp John L , Sung Eric , Aronis Konstantinos , Warren James , MacInnis Paul , Shah Rushil , Horacek Bohumil Milan , Berger Ronald D , Tandri Harikrishna S , Trayanova Natalia , Chrispin Jonathan
Published: May 2021

Introduction:
Few intraprocedural localization systems have been developed to predict idiopathic ventricular arrhythmia (IVA) source sites. However, an accurate and bi-ventricular patient-specific automated site of origin localization system remains elusive. To address this issue, we have developed a new automatic arrhythmia origin localization (AAOL) system that determines the sites of earliest activation in both ventricles and provides superior accuracy.

Hypothesis:
We hypothesized that the AAOL system can use electroanatomic mapping (EAM) geometry and accurately localize IVA source sites on patient-specific geometry of LV, RV and neighboring vessels using 3-lead ECGs.

Methods:
Twenty patients undergoing IVA catheter ablation had a 12-lead ECG recorded during clinical arrhythmia and during pacing at various locations identified on EAM geometries. The AAOL system combined 3-lead (III, V2, V6) 120-ms QRS integrals and patient-specific EAM geometry with intracardiac pacing to predict the site of earliest ventricular activation. The predicted site was projected onto the EAM geometry using the EAM triangular-mesh site nearest to the tip of the predicted site.

Results:
Twenty-three IVA source sites were clinically identified by activation mapping and/or pace mapping (8 RV, 15 LV, including 8 from the posteromedial papillary muscle; 2 from the aortic root; and 1 from the distal coronary sinus). The new system achieved a mean localization accuracy of 3.6 mm for the 23 mapped IVAs (Figure 1D), better than that achieved by previous systems.

Conclusions:
The new AAOL system offers highly accurate localization of IVA source sites in both ventricles and neighboring vessels, which could facilitate ablation procedures for patients with IVAs.
Abstract 13192:
Xbp1s - Foxo1
Axis Governs Lipid Accumulation and Cardiac Performance in Heart Failure With Preserved Ejection Fraction
Authors: Schiattarella Gabriele G , Altamirano Francisco J , Tong Dan , Kim Esther , Ferdous Anwarul , Piristine Hande , Dasgupta Subhajit , Wang Xuliang , French Kristin , Villalobos Elisa , Spurgin Stephen B , Hotiner Waldman Mayaan , Jiang Nan , May Herman , Hill Theodore M , Zaha Vlad G , Lavandero Sergio , Gillette Thomas G , Hill Joseph A
Published: May 2021

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is now the dominant form of heart failure (HF). Limited insight into underlying mechanisms has culminated in the longstanding absence of evidence-based therapies capable of mitigating the substantial morbidity and mortality associated with the syndrome. Existing clinical and epidemiological evidence suggests that excessive body fat and lipid mishandling contribute to HFpEF. However, molecular mechanism(s) governing metabolic alterations and perturbations in lipid homeostasis in HFpEF are unknown. We recently developed a novel, clinically relevant, murine model of HFpEF, uncovering suppression of the Xbp1s (spliced form of the X-box-binding protein 1) arm of the UPR (unfolded protein response) signaling pathway as a critical driver of HFpEF pathogenesis.

Objectives:
To define and manipulate mechanisms downstream of Xbp1s in HFpEF and decipher its cardioprotective actions.

Methods and Results:
In the myocardium of experimental HFpEF, we detected cardiomyocyte steatosis coupled with increases in the abundance and activity of FoxO1 (Forkhead box protein O1), a conserved transcription factor involved in cell metabolism. FoxO1 depletion, as well as Xbp1s over-expression, in cardiomyocytes each ameliorated the HFpEF phenotype and reduced myocardial lipid accumulation. Strikingly, forced expression of Xbp1s in cardiomyocytes triggered proteasomal degradation of FoxO1. Furthermore, we discovered that FoxO1 is ubiquitinated upon Xbp1s over-expression, and Xbp1s-induced proteasomal degradation of FoxO1 occurs, in large part, through activation of the E3 ubiquitin ligase STUB1 (STIP1 homology and U-Box-containing protein 1), a protein we identified as a novel and direct transcriptional target of Xbp1s.

Conclusions:
Our findings uncover the Xbp1s-FoxO1 axis as a pivotal mechanism in the pathogenesis of HFpEF and unveil previously unrecognized mechanisms whereby the UPR governs metabolic alterations in cardiomyocytes.
Abstract 13300: Hepatocyte Growth Factor and 10-year Change in Left Ventricular Structure: The Multi-Ethnic Study of Atherosclerosis
Authors: Ferraro Richard A , Ogunmoroti Oluseye , Zhao Di , Ndumele Chiadi E , Ac Lima Joao A , Subramanya Vinita , Pandey Ambarish , Larson Nicholas B , Bielinski Suzette J , Michos Erin D
Published: May 2021

Introduction:
Hepatocyte Growth Factor (HGF) is a mesenchymal cytokine linked to incident heart failure (HF), with recent data from our group showing a strong and independent association with HF with preserved ejection fraction (HFpEF). Cardiac MRI (cMRI) allows for precise analysis of morphologic changes in left ventricular (LV) structure. Increasing LV mass and concentric remodeling (defined by an increasing mass:volume ratio) are imaging markers of HFpEF risk. Whether HGF is associated with adverse LV remodeling over time is unknown.

Hypothesis:
Higher HGF will be associated with increasing LV mass, decreasing LV volume and increasing mass:volume ratio over 10 yrs.

Methods:
We studied 4762 participants of the MESA cohort, free of cardiovascular disease (CVD) and HF at baseline, who completed both HGF measurement and cMRI at baseline. Participants with LV EF<50% were excluded. Of these, 2855 completed a 2
nd
cMRI at 10 yrs. We examined the cross-sectional and longitudinal associations of HGF and LV parameters using multivariable-adjusted linear mixed effect models.

Results:
The mean (SD) for age was 61 (10) yrs. Median (IQR) for HGF level was 888 pg/mL (745-1066); 53% women. At baseline, the 3
rd
HGF tertile, compared to the 1
st
, was associated with greater mass:volume ratio [relative difference 1.66 (0.43, 2.89)] and lower LV end diastolic volume [-1.87 mL (-3.45, -0.28)], after adjustment for CVD risk factors and NT- proBNP (model 2)
[Table]
. In longitudinal analysis, the 3
rd
HGF tertile was also associated with increasing mass:volume ratio [difference in 10-yr change: 4.79 (2.73, 6.85)] and decreasing LV end diastolic volume [-4.97 (-7.10, -2.85)].

Conclusions:
In a community cohort, higher HGF levels were independently associated with a concentric LV remodeling pattern of increasing mass:volume ratio and decreasing LV end diastolic volume over 10 yrs. This association may suggest an intermediate phenotype explaining the association of HGF with HFpEF risk.
Abstract 13302: The Depression and Anxiety Paradox Following Percutaneous Coronary Intervention: A National Inpatient Sample Analysis
Authors: Abu Hawa O , Igbinomwanhia Efehi , Olagoke Olakanmi , Lukan Abdulkareem O , Diala Chiamaka S , Sanni Habeeb , Aibangbee Keziah E , Fasanmi Oluwafisayo , Eromosele Oseiwe B , Chukwuma Vivian , Ogunsua Adedotun A
Published: May 2021

Introduction:
Depression and Anxiety are prevalent among patients with cardiovascular diseases. However, their impact on important clinical outcomes, such as length of hospital stay (LOS) and mortality, is incompletely understood.

Objective:
Examine the magnitude and impact of major depressive disorder (MDD) and anxiety on LOS and in-hospital mortality in patients with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI).

Hypothesis:
Patients with MDD or anxiety will have poorer clinical outcomes after PCI.

Methods:
Data were obtained from the National Inpatient Survey (NIS). Admissions in 2017 with a primary diagnosis of ACS and undergoing PCI were identified based on ICD10 codes. Patients with MDD or anxiety were further delineated with ICD10 codes. The association between MDD or anxiety and LOS and in-hospital mortality was analyzed using linear and logistic regression models, respectively. Various sociodemographic (age, race, sex, income), clinical (history of hypertension, hyperlipidemia, stroke, peripheral artery disease, valvular heart disease, chronic kidney disease, anemia, obesity, smoking) and hospital-level (region, location, payer type) factors were adjusted for in the analysis.

Results:
Among 130,712 patients admitted for ACS who underwent PCI, the prevalence of MDD and anxiety were 8.7% (n=11,303) and 10.8% (n=14,066), respectively. Patients were on average aged 67 years (SD=13.5), 38% were females, and 73% non-Hispanic White. Overall, the mean LOS was 4.4 days (SD=5.4) and 4.7% of patients died while hospitalized. Patients with MDD (4.6 vs 4.4, p=0.001) or anxiety (4.7 vs 4.4, p=0.001) had longer LOS than those without these conditions. Contrary to our hypothesis, patients with MDD (OR: 0.82; 95% CI: 0.73-0.91) or anxiety (OR: 0.72; 95% CI: 0.64-0.79) had significantly lower odds of mortality than those without MDD or anxiety after adjusting for several factors of prognostic importance.

Conclusions:
Among ACS patients who underwent PCI, MDD and anxiety were associated with increased LOS but paradoxically lower in-hospital mortality. These findings reinforce the need for future investigations to evaluate the impact of psychological factors on clinical outcomes in ACS patients who undergo PCI.
Abstract 13313: Venous Thromboembolism as a Presenting Finding and Complication of Covid-19: A Case Series
Authors: Celli Diego , Plate Thomas , Alarcon-Calderon Amarilys , Galo Jason , Alvarez Roger A
Published: May 2021

Background:
Although not yet fully understood, the pathogenesis of the novel RNA betacoronavirus2 currently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is thought to involve thrombotic microangiopathy, as evidenced by autopsy. To date, the number of pulmonary embolism (PE) reports in the setting of COVID-19 is increasing, with many presenting in acute cor pulmonale. In this case series, we aim to describe our center’s experience with COVID-19 and PE.

Methods:
A total of 10 patients with a diagnosis of PE in the setting of positive qualitative SARS-CoV-2 through RT-PCR were identified and managed by our service.

Results:
The mean age was 58 years old with 60% being males. The majority of the population was Hispanic (70%) with 30% self-identifying as black. All of our patients were middle-aged except for one elder and one young adult, and they had other risk factors for thromboembolism, (e.g. obesity, heart failure, COPD, and HIV). The mean time from presentation to diagnosis of PE was 100 hours. Hemodynamic instability was present in 30% of the cases. There was a whole spectrum of PE involvement, the vast majority of which were segmental and subsegmental (60%) compared to distal main arteries (20%) and saddle PE (20%). Mortality rate was 10% and the rest of the patients were successfully discharged on oral anticoagulation. Although our cohort comprised low-to-intermediate pretest probability for PE per Wells criteria (1.5-3), high clinical suspicion prompted further imaging studies with computed tomography angiography and 2D-echocardiogram. Currently, many hospital systems are avoiding advanced imaging for concerns of infection control, which likely contributes to the underdiagnosis of VTE in patients with COVID-19.

Conclusion:
As we continue to understand the pathophysiology of this emerging disease, clinicians should maintain a high degree of suspicion to differentiate causes of hypoxemic respiratory failure and hemodynamic instability in the setting of COVID-19. Overt PE may increase inpatient mortality and post-discharge mobility due to the burden of pulmonary hypertension in this population. Further research is required to elucidate the relationship between these entities and the best management approach.
Abstract 13320: Direct Cardiac Actions of Empagliflozin Improve Mitochondrial Oxidative Phosphorylation and Attenuate Pressure-overload Heart Failure
Authors: Li Xuan , do Carmo Jussara M , Wang Zhen , da Sivla Alexandre A , Mouton Alan J , Omoto Ana M , Hall Michael E , Hall John E
Published: May 2021

Introduction:
The underlying mechanisms by which empagliflozin (EMPA) and other sodium glucose co-transporter 2 (SGLT2) inhibitors attenuate heart failure (HF) are still poorly understood. However, this protection does not appear to be fully explained by their antihyperglycemic or diuretic effects.

Hypothesis:
EMPA attenuates HF by direct effects on the heart to improve its metabolism and function.

Methods:
C57BL/6J mice (4-6 months) were subjected to transverse aortic constriction (TAC) or sham surgeries. Two weeks after TAC, EMPA (10 mg/kg/day) or vehicle was administered daily for 4 additional weeks. Cardiac function was assessed by echocardiography and cardiac substrate metabolism measured in isolated perfused hearts. Transmission electron microscopy was used to evaluate mitochondrial morphology and molecular docking analysis to predict potential cardiac targets of EMPA.

Results:
EMPA increased survival and attenuated adverse left ventricle remodeling and cardiac fibrosis after TAC. EMPA also attenuated left ventricular systolic dysfunction (ejection fraction 51.6 vs. 40.2% p<0.05; fraction shortening 28.8 vs 18.4% p<0.05). EMPA rescued impaired glucose and fatty acid oxidation in failing hearts, while reducing glycolysis. Molecular docking analysis and isolated perfused heart experiments indicated that EMPA can directly bind glucose transporters in the heart to reduce glycolysis, and enhance AMP-activated protein kinase. EMPA treatment enhanced mitochondrial biogenesis, restored mitochondria cristae integrity, increased expression of endogenous antioxidants, and reduced cellular apoptosis caused by leakage of cytochrome C from mitochondria into the cytosol. These beneficial cardiac effects of EMPA occurred despite no alterations in fasting blood glucose, body weight, or daily urine volume.

Conclusions.
Our study demonstrated that EMPA may directly bind glucose transporters and reduce excessive glycolysis in failing hearts. EMPA enhanced mitochondrial biogenesis, improved mitochondrial oxidative phosphorylation, and reduced mitochondria-mediated apoptosis, thereby attenuating cardiac dysfunction and progression of HF.
Abstract 13322: Association Between Allergic Diseases and Development of Kawasaki Disease Among Children: A Systematic Review and Meta-analysis
Authors: Ramachandra Ramya , Rafael John , Tsou Po Yang , Lee Chien Chang
Published: May 2021

Introduction:
Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. It is the leading cause of pediatric acquired heart disease in developed countries. Growing evidence points to the role of immunoregulatory abnormalities for its causation.

Hypothesis:
It is hypothesized that a history of allergic diseases is associated with the development of KD in children.

Methods:
A systematic review and meta-analysis of observational studies was performed to ascertain the association between history of allergic diseases and KD. Major electronic databases were searched from inception through March 2020 using pre-defined index terms such as “allergic disease”, “Kawasaki disease” and “children”. Random effects model was used to derive pooled estimates of odds ratios (OR) and 95% confidence intervals (CI). The Newcastle-Ottawa Scale was used for qualitative assessment. This study was reported according to MOOSE (Meta-analyses Of Observational Studies in Epidemiology).

Results:
Of 854 articles identified, 8 studies were considered eligible. History of allergic diseases was significantly associated with the development of KD (OR 1.99; 95% CI 1.26-2.73). On subgroup analysis of case-control studies (n=6), allergic diseases remained significantly associated with KD (OR 1.61; 95% CI 1.10-2.12). However, subgroup analysis with allergic diseases limited to asthma (n=5) revealed no significant association with KD (OR 1.17; 95% CI 0.45-1.90). Qualitative assessment found minimal concerns for bias.

Conclusions:
The available evidence suggests a strong association between history of allergic diseases and development of Kawasaki disease among children.
Abstract 13327: Worse Cerebral Blood Flow in Single Right verses Left Ventricle After Fontan Completion
Authors: PIKE Nancy A , Roy Bhaswati , Halnon Nancy J , Lewis Alan B , Woo Mary A , Wang Danny JJ , Kumar Rajesh
Published: May 2021

Introduction:
Single ventricle heart disease (SVHD) adolescents with a single right ventricle (RV) have worse cognition and mood function compared to single left ventricle (LV) which may result from variability in ventricular function or structure related sequela after Fontan completion. However, it is unclear whether RV SVHD has worse cerebral blood flow (CBF) in cognitive and mood regulatory areas over LV SVHD compared to healthy controls.

Methods:
Cross-sectional, comparative design, 14 adolescents with RV SVHD (age 16.1±1.5 years; 7 male), 6 LV SVHD (age, 16.3±1.0 years; 4 male), and 25 healthy controls (age, 15.9±1.4 years; 13 male) were studied. SVHD participants were recruited who have undergone surgical palliation with Fontan completion from local pediatric cardiology clinics. Self-reported healthy controls were recruited from the community. Brain MRI studies were performed using a 3.0-Tesla MRI scanner and 3D pseudo-continuous arterial spin labelling data were collected. We calculated whole-brain CBF maps, normalized to a common space, and assessed brain changes between RV and LV SVHD and controls [ANCOVA; covariates, age and sex; p<0.005]. Region of interest analyses were performed in cognitive and mood control brain sites.

Results:
Regional brain CBF was reduced in single RV over LV SVHD. Multiple brain sites showed more widespread reduced CBF values in RV over LV SVHD compared to controls (Figure 1, p<0.005), including the prefrontal cortices, caudate, insula (a, f), anterior (b, g), mid (c, h), and posterior (d, i) cingulate, and hippocampus (e, j).

Conclusion:
Single RV adolescents show more widespread reduced CBF than single LV in cognitive and mood regulatory sites, which may result from variable function or structure related sequela between ventricle types. The findings indicate that the therapeutic approach should recognize the differences in CBF based on ventricle type and investigate interventions to optimize CBF in single RV SVHD.
Abstract 13332: Platelet Distribution Width is Associated With Adverse Prognosis in Patients With Heart Failure
Authors: Watanabe Koichiro , Sato Yu , YOSHIHISA Akiomi , Ichijo Yasuhiro , Hotsuki Yu , KIMISHIMA Yusuke , Yokokawa Tetsuro , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , KOBAYASHI ATSUSHI , Takeishi Yasuchika
Published: May 2021

Backgrounds:
The associations between red blood cell distribution width and prognosis in patients with heart failure (HF) have been reported. However, the prognostic impact of platelet distribution width (PDW) has been unclear in HF patients.

Methods:
We conducted a prospective observational study. We analyzed data on 1,746 hospitalized patients with HF who discharged alive and measured PDW at stable condition in prior to discharge. Patients were divided into tertiles based on levels of PDW: 1
st
(PDW < 15.9 fL, n = 586), 2
nd
(PDW 15.9-16.8 fL, n = 617), and 3
rd
(PDW ≥ 16.9, n = 543) tertiles. We compared baseline patients’ characteristics and their post-discharge prognosis such as all-cause death, cardiac death, and cardiac events including cardiac death and re-hospitalization due to worsening HF.

Results:
Prevalence of diabetes mellitus, anemia, and chronic kidney disease was highest in the 3
rd
tertile than in the 1
st
and 2
nd
tertiles (diabetes mellitus, 42.7% vs. 40.3% and 30.5%, P < 0.001; anemia, 52.5% vs. 48.3% and 41.2%, P < 0.001; chronic kidney disease, 57.5% vs. 49.0% and 49.3%, P = 0.005). Age was oldest and B-type natriuretic peptide levels were highest in the 3
rd
tertile compared to the 1
st
and 2
nd
tertiles (age, 70.0, vs. 69.0 and 68.0 years old, P = 0.038; B-type natriuretic peptide, 241.0 vs. 235.2 and 171.9 pg/mL, P < 0.001). In contrast, sex and left ventricular ejection fraction did not differ among the groups. The Kaplan-Meier analysis (
Figure
) demonstrated that rates of all endpoints were the highest in the 3
rd
tertile among the groups (log-rank P < 0.001, respectively). The Cox proportional hazard analysis adjusted for potential confounding factors revealed that the 3
rd
tertile was independently associated with adverse prognosis (all-cause death, hazard ratio [HR] 1.312, P = 0.042; cardiac death, HR 1.422, P = 0.046; cardiac event, HR 1.283, P = 0.041).

Conclusion:
PDW is a novel independent predictor of adverse prognosis in patients with HF.
Abstract 13349: An Investigation Into the Association Between Inflammatory Bowel Disease and Cardiac Arrhythmias an Examination of the United States National Inpatient Sample Database
Authors: Mubasher Mahmood , Syed Tausif , Hanafi Amir , Yu Zhao , Yusuf Ibrahim , Abdullah Abdullah S , Mohamed Mouhand F , Alweis Richard , Danjuma Mohammed , Rao Mohan C , Hoefen Ryan
Published: May 2021

Introduction:
A growing evidence depicted the role of systemic inflammation in the pathogenesis of cardiac Arrhythmias (CA). However, uncertainty remains as to the exact relationship between Inflammatory Bowel Disease (IBD) and CA. So far, most of the studies had centered on the implication of inflammatory mechanisms in the development of atrial fibrillation (AF) in IBD. The association between IBD and other arrhythmias is not well elucidated.

Hypothesis:
We hypothesized that IBD might be associated with a higher burden of CA.

Methods:
We queried the national inpatient sample (NIS) from 2012 to 2014. Discharges associated with IBD (Chron's or ulcerative colitis), cardiac arrhythmias including AF, Atrial flutter, SVT, VT, VF were identified using ICD-9-CM codes 555.xx, 556.xx, 427.3, 427.32, 427.0, 427.1, 427.41, respectively. We divided patients into two groups, IBD Vs. Non-IBD. Outcomes are the prevalence of CA (AF, A.flutter, SVT, VT, V.fib) amongst both groups, as well as the correlation between CA and demographic of patient cohorts. Multivariable logistic regression (MLR) was utilized to adjust for differences in baseline characteristics.

Results:
We identified 847,235 weighted hospitalizations among patients with IBD and 84,757,349 hospitalizations among the general population, ≥18 years of age. Overall, IBD patients were less likely to be admitted with cardiac arrhythmias than the non-IBD population (9.7% versus 14.2%, P, <0.001). On MLR, IBD Group had lower odds of CA during hospitalization (OR, 0.87; 95% CI 0.85-0.88), AF (OR, 086; 95%CI 0.85-0.88) A.flutter (OR,0.78; 95% CI 0.74-0.83), VF (OR, 0.69; 95% CI 0.59-0.79). While the prevalence of SVT and VT was not different between the two groups. Male sex, age of more than 60 years, and white Race were risk factors for Arrhythmias.

Conclusions:
In conclusion NIS analysis revealed lower rates of hospitalization-associated arrhythmias in the IBD population compared to the general population.
Abstract 13359: Acute Phase Predictors for In-hospital Mortality and Chronic Thromboembolic Pulmonary Hypertension in Acute Pulmonary Embolism Patients
Authors: Yamamuro Megumi , Nakayama Tomoko , Tamura Yudai , Unoki Takashi , Taguchi Eiji , Sawamura Tadashi , Koyama Jyunjiroh , NAKAO KOICHI , Sakamoto Tomohiro
Published: May 2021

Background:
Various predictors in patients with acute pulmonary embolism (PE) have been reported for in-hospital mortality and chronic thromboembolic pulmonary hypertension (CTEPH), but none have been established conclusively.

Methods and Results:
We retrospectively analyzed data that might be associated with in-hospital mortality and CTEPH from patients with acute PE who were admitted to our hospital. Among 163 patients (aged 69.3± 14.6 years) with acute PE, 11 patients (6.7%) died in the hospital. We examined the following acute and chronic-phase data: vital signs, echocardiography values, medications, laboratory test results, blood gas data and heparin infusion time. Multivariate logistic regression analysis showed that the acute-phase levels of plasma B-type natriuretic peptide (BNP) (odds ratio (OR), 1.003; 95% confidence interval (CI), 1.0004-1.0053;
P
= 0.034,) and arterial blood gas lactate (OR, 1.306; 95% CI, 1.056-1.615;
P
= 0.014) were significant independent predictors of in-hospital mortality. The area under the receiver operating characteristic (AUROC) curves of BNP and arterial blood lactate levels for in-hospital mortality were 0.846 and 0.921, respectively. (BNP, 400.65 pg/mL [sensitivity 77.8%, specificity 84.6%]; lactate 7.9 mmol/L [sensitivity 81.8%, specificity 89.5%]). In univariate logistic regression analysis, the plasma BNP level > 400.65 pg/mL and lactate level > 7.9 mmol/L on admission were significant predictors for in-hospital mortality (OR 62.5, 95% CI 10.0-390.3;
P
= 0.0001). Among 152 patients (aged 68.9±14.6 years) with acute PE who did not die in-hospital, 15 (9.8%) patients progressed to CTEPH. Multivariate logistic regression analysis showed that right ventricular systolic pressure (RVSP) at admission was an independent and significant predictor for CTEPH (OR, 1.183; 95% CI, 1.090-1.285;
P
= 0.0001). The AUROC curve of RVSP for developing CTEPH was 0.944. (RVSP, 51.4 mm Hg [sensitivity 86.7%, specificity 83.8%]).

Conclusions:
In patients with acute PE, the acute-phase BNP and arterial blood lactate levels are effective predictors of in-hospital mortality. And RVSP during the acute phase, but not during the chronic phase is an effective predictor of progression to CTEPH.