bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14148: Local Aldosterone Production via StAR in PAH and in Human IPS Cell-derived Cardiomyocytes: Efficacy of Spironolactone in Cardiac Remodeling and Mitochondrial Dynamics Under Hypoxic Stress
Authors: Murai Itsumi , Kaiami Anyu , Kato Ryuji , Imano Hideki , Morihara Hirofumi , Tomoda Kiichiro , Asahi Michio , Ijiri Yoshio , Yamaguchi Takehiro , Izumi Yasukatsu , Yoshiyama Minoru , Ohta-Ogo Keiko , Ishibashi-Ueda Hatsue , Hayashi Tetsuya
Published: November 2020

Objective:
Pulmonary arterial hypertension (PAH) is a progressive disease that frequently leads to right ventricular (RV) remodeling. Increased plasma aldosterone levels have been reported in patients with PAH. The aim of this study was to examine the expression of steroidogenic acute regulatory protein (StAR) in patients and animal model of PAH, and in the human iPS cell-derived cardiomyocytes (hiPSC-CMs). Furthermore, we evaluated therapeutic effects of mineralocorticoid receptor (MR) antagonist, spironolactone (SPL) on mitochondrial dynamics in the RV myocardium.

Methods:
Autopsied heart samples (n=20) were obtained from patients with or without PAH. PAH model rats (n=46) were injected with Sugen5416 (20 mg/kg) and then exposed to hypoxia and reoxygenation for 4 weeks with/without treatment with SPL (25 mg/kg/day). Human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs were cultured under hypoxic conditions (37 °C, 1% O
2
, 5% CO
2
) with/without treatment with SPL (10 μM). In addition, we applied the Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) technology and repressed StAR gene expression in hiPSC-CMs under hypoxic conditions.

Results:
In PAH patients, the expression of StAR and MR was significantly increased in cardiomyocytes and endothelial cells in the RV myocardium. In PAH rats, RV systolic pressure elevated over 60 mm Hg with deteriorated RV function. Under electron microscopy, severe degeneration of mitochondria and capillaries with myofibrillar lysis in the RV myocardium were observed, which were compatible with those findings in PAH patients. Hypoxic stress significantly increased the StAR and phosphorylated JNK, ERK-1/2, and NF-kB proteins in hiPSC-CMs as well as in HUVECs. Furthermore, we established the CRISPRi-hiPSC cell lines where StAR gene was successfully knockdown. Treatment with SPL decreased the phosphorylation of JNK, ERK-1/2, NF-kB, and Smad3 in HUVECs and hiPSC-CMs. Strikingly, SPL attenuated mitochondrial degeneration and increased mitophagy, suppressing the RV remodeling under hypoxic stress.

Conclusion:
SPL might regulate mitochondrial dynamics and attenuates RV remodeling in PAH via StAR/JNK signaling pathway.
Abstract 14173: Emailing is an Economical Way to Recruit Participants
Authors: Raby Kirsten , Blinson Karen , Herrington David M , Zhao David X , Rosenthal Gary , Jones Schuyler , Zhou Li
Published: November 2020

Introduction:
To produce results from clinical trials that are statistically significant, researchers must enroll enough participants; however, it is difficult to recruit sufficient participants. The ADAPTABLE trial is a pragmatic randomized controlled trial designed to compare two aspirin doses in patients with cardiovascular disease.

Methods:
We used eligibility criteria set forth by the ADAPTABLE study protocol. We then put patients into two groups. Patients with email addresses were group one, and sent an email weekly. Patients without an email address were in group two, and a letter was mailed to their home address. Eligible patients who had a clinic appointment scheduled were also recruited approached in clinic. Most of these patients had already been stratified into the email or letter group, but there was the possibility that they had a new diagnosis and had not been contacted. All were given a link to the ADAPTABLE trial portal with an access code to enroll. An explanatory video about the study and electronic informed consent were on the trial website.

Results:
As shown in Table 1, four hundred and nine patients enrolled in our trial over a 10-month period. Three hundred and ninety-seven (97.06%) patients enrolled in the study via email. Letters were sent to 7,226 patients and four (0.98%) enrolled in the study. Eight (1.96%) of the patients who were approached in person enrolled in the study. The cost of email campaign was $1.44/patient and the cost per enrollment was the least expensive, at $95.71. In person enrollment cost $23.34/patient and the total cost per enrollment was $417.12. The letter recruitment cost $0.30/patient, however, the cost per enrollment was the highest, at $542.26.

Conclusion:
Email is an effective and economical way to recruit patients for clinical trials. Email allows researchers to contact more patients about proposed studies promptly and facilitates pragmatic research trials that achieve results in a timely and cost-efficient manner.
Abstract 14181: Impact of Prehospital Mobile Cloud Electrocardiogram Transmission System to Reduce Door to Balloon Time and Onset to Recanalization Time in ST-elevation Myocardial Infarction
Authors: Kametani Motoko , Unoki Takashi , Takagi Daisuke , Tamura Yudai , Nakayama Tomoko , Konami Yutaka , Suzuyama Hiroto , Inoue Masayuki , Yufu Tetsuo , Kodama Kazuhisa , Taguchi Eiji , Sawamura Tadashi , Maehara Junichi , NAKAO KOICHI , Sakamoto Tomohiro
Published: November 2020

Background:
Guidelines strongly recommend patients with ST-elevation myocardial infarction (STEMI) receive timely mechanical reperfusion, defined as door-to-balloon time (DTBT) ≤90 minutes.

Objective:
To evaluate the impact of the prehospital mobile cloud ECG transmission system (C-ECG) on DTBT and mortality in patients with STEMI.

Methods:
On June 2018, eight mobile C-ECG systems (SCUNA®, MEHERGEN GROUP) were implemented into the Uki and Kamimashiki fire departments in Kumamoto, Japan. Within two years, 428 ECGs of patients complaining of chest pain, difficulty in breathing and any other symptom that the emergency staff deemed necessary were transmitted to our hospital. 119 patients were diagnosed with ACS, 93 received emergency CAG and 69 were diagnosed with STEMI. After excluding eight patients with onset to arrival over 24 hours, a total of 137 consecutive STEMI patients received emergency PCI during the study period. Among them, 68 received PCI during the pre-C-ECG period (Pre: from June 2016 to May 2018), whereas 69 were received during the post-C-ECG period (Post: June 2018 to May 2020). We compared the DTBT, Onset to Recanalization time (OTRT), and in-hospital mortality between the two periods.

Results:
There was no significant difference in age, gender, Killip classification, and number of diseased coronary lesion between the two periods. The door to Cath-Lab time (DTCT) and DTBT were significantly shorter in the post-C-ECG period compared to the pre-C-ECG period (Pre: 34 min [IQR; 23-44] vs. Post: 24 min [IQR; 18-38]; P=0.01, Pre: 66 min [IQR; 48-80] vs. Post: 49 min [IQR; 42-71]; P=0.02, respectively). Furthermore, OTRT was also significantly shorter in the post-C-ECG period compared to the pre-C-ECG period (Pre: 190 min [IQR; 137-343] vs. Post: 153 min [IQR; 110-247]; P=0.02). However, peak-CPK and in-hospital mortality were not significantly different between the two periods (Pre: 2254 IU/L [IQR; 1153-4257] vs. Post: 1985 IU/L [IQR; 740-4021]; P=0.2, Pre: 5.9% vs. Post: 4.4%; P=0.7, respectively).

Conclusion:
Prehospital mobile cloud ECG transmission system reduced not only the DTBT but also OTRT.
Abstract 14185: Targeting Lower Oxygen Saturation Parameters in Premature Infants Does Not Increase Incidence of Pulmonary Hypertension in the Neonatal Intensive Care Unit
Authors: Niccum Maria , Spyropoulos Fotios , Levin Jonathan , Petty Carter , Mullen Mary P , christou helen
Published: November 2020

Introduction:
Lower oxygen saturation targets in preterm infants have been associated with decreased incidence of bronchopulmonary dysplasia (BPD) but increased risk of pulmonary hypertension (PH). Studies have shown that targets of <90% are associated with higher incidence of PH, however data on the optimal saturation target >90% are lacking. In this study, we compared the rate of BPD and PH in two cohorts with saturation targets of 94-98% and 92-97%. We hypothesized that BPD rate would be lower and PH rate would be unchanged at the lower saturation target.

Methods:
We performed a retrospective cohort study comparing PH and BPD rates among two cohorts of infants born at ≤32 weeks gestation at Brigham and Women’s Hospital: cohort 1 with saturation target of 94-98% (n = 129, July 2017-July 2018), cohort 2 with saturation target of 92-97% (n = 124, July 2018-July 2019). PH was defined by echocardiographic evidence of systolic septal flattening or right ventricular pressure ≥35 mmHg (estimated by tricuspid regurgitant jet velocity or shunt velocity) at gestational age (GA) ≥36 weeks. Comparisons between groups were carried out by Chi-square test, t-test, and multivariable logistic regression.

Results:
Subjects had a GA of 23-32 weeks; 46% were female. Groups did not differ with respect to GA, sex, or birth weight. There was no difference in rate of PH (2.4% vs. 4.2%, p = 0.12) or BPD (25% vs. 20%, p = 0.31) between cohort 1 and cohort 2. Other clinical parameters were not different between groups, including presence of patent ductus arteriosus, presence of atrial septal defect, use of diuretics, or use of steroids. After controlling for GA, birth weight, sex, and diagnosis of BPD using logistic regression, there was no difference in rate of PH between groups (p = 0.47), but there was a positive association of BPD with PH (OR 3.45; 95% CI, 1.18-10.09; p = 0.02).

Conclusions:
A lower oxygen saturation target was not associated with a higher rate of PH or lower rate of BPD in preterm infants. The overall rate of PH was much lower than rates previously reported at saturation targets <90%. Given our low incidence of PH, and the lack of a significant difference in rate of PH between groups, a saturation target of 92-97% may be safe while also minimizing need for supplemental oxygen in this population.
Abstract 14197: C14a Mutation Abolishes Mg53-Aggravated Glucose Metabolic Dysfunction and Exerts a Dominant Therapeutic Target for Ischemia and Reperfusion (i/r) Injury in Diabetic Heart
Authors: Feng Han , Shen Hao , Robeson Matthew J , Wu Hongkun , Chen Gengjia , Zhang Shuo , Lv Fengxiang , Hu Xinli , Zhang Yan , Xiao Ruiping
Published: November 2020

Introduction:
MG53, essential for cardiac ischemic protection, negatively regulates insulin receptor (IR) to trigger globular metabolic dysfunction, which makes up a big obstacle for its clinical use. In vitro evidence shows that C14A site of MG53 might be a promising target both to abolish MG53 regulation on IR and to keep as much protective function. However, in vivo effect on C14A mutation of MG53 is urgent to be explored.

Results:
Here, we found C14A knock-in mice exerted relieved insulin resistance, blood glucose, and metabolic phenotype in high fat diet-induced pre-diabetic model. C14A mutation did NOT lessen the protective effect of MG53 by either intracellular knock-in or extracellular addition of mutant protein against ischemia/reperfusion(I/R) injury in db/+ mice. Consistent with our previous study, we found that administration of MG53 on diabetic mice showed aggravated blood glucose, insulin resistance, and unstable cardiac function to induce a higher risk under I/R attack. C14A mutation reduced the affinity between IR ECD and MG53 to block recombinant human (rh) MG53-WT-triggered acute hyperglycemia, increased heart infarct area and death rate on db/db mice during I/R injury. Post-conditioning of rhMG53-C14A stabilized intra-operative blood glucose and showed stronger anti-I/R ability than MG53-WT protein on db/db mice.

Conclusions:
C14A mutation is a potential target for MG53 treatment on diabetic heart. This potential therapeutic approach for the treatment of patients within type 2 diabetes provides a strategy of gene engineering optimizing well-known target to draw on advantages and avoid pitfalls.
Abstract 14507: Suboptimal Blood Pressure Control Increases the Risk of Non-alcoholic Fatty Liver Disease
Authors: Saeed Gul , Aneni Ehimen , Abraham Bincy , Bittencourt Marcio S , Cainzos Achirica Miguel , Santos Raul D , Nasir Khurram
Published: November 2020

Introduction:
Recent blood pressure (BP) guidelines recommend aggressive control of BP to prevent target organ damage, however, no population-level studies have assessed the impact of aggressive BP control on the incidence of Nonalcoholic Fatty Liver Disease (NAFLD). In this study, we investigate the implications of suboptimal BP control for incident NAFLD.

Methods:
We analyzed data from 6,252 consecutive participants in an employer-mandated routine health evaluation at Hospital Israelita Albert Einstein (São Paulo, Brazil) collected between 2004 to 2016 who were free of NAFLD at baseline. NAFLD was defined as liver ultrasound detected hepatic steatosis among individuals with an alcohol use disorder identification test (AUDIT) score <8. Hypertension was defined as either self-reported history and/or use of BP-lowering medications. Suboptimal BP control was defined per the 2018 ACC/AHA criteria as systolic BP >/= 130mmHg and/or diastolic BP >/= 80 mmHg. Multivariate analysis was conducted adjusting for possible confounders as noted in the figure.

Results:
Over a median follow-up period of 2.9 years (range: 0.6 - 10.6 years), the incidence of NAFLD was 25.8% among individuals with hypertension (N=473) compared to 15.2% among non-hypertensive individuals (N=5,779; p<0.001). Amongst individuals with known hypertension and suboptimal BP control, the incidence was 29.7% compared to 14.3% among those with optimal BP (adjusted RR 1.80 [95%CI: 1.12 - 2.90]). Similarly, the risk of NAFLD was 18% greater among those without known hypertension but whose BP was suboptimal (adjusted RR: 1.18 [95% CI: 1.05 - 1.33]; figure).

Conclusions:
Among persons with known hypertension, suboptimal BP is an independent risk of NAFLD. In addition, among those without known hypertension, suboptimal BP is an independent predictor of future NAFLD. Intervention studies are needed to investigate the role of BP control in the prevention of NAFLD.
Abstract 14510: Post-traumatic Stress Disorder and Traumatic Brian Injury Are Associated With Increased Incidence of Myocardial Infarction in US Veterans
Authors: Derbas Laith , Singh Vikas , ONI OLURINDE , Thakkar Garima , Thakur Hemant , Sharma Mukut , Sharma Ram , SHARMA Rishi
Published: November 2020

Background:
We have recently shown that PTSD/TBI takes an especially devastating toll on America’s veterans and their families with mental, physical and financial ramifications and poor clinical outcomes (Thakur et al. Epidemiology (Sunnyvale) 2018; 8:353). Patients with PTSD were found to have higher rates of cardiovascular symptoms, hospitalizations and mortality. Whereas electrocardiographic abnormalities, arrhythmias and ventricular dysfunction have been reported in patients with TBI. Association of PTSD/TBI with Myocardial Infarction (MI) is not well studied; the objective of this study was to examine the relationship between PTSD/TBI and MI in a large patient population.

Methods:
This retrospective study used national data from Veterans Administrations Informatics and Computing Infrastructure (VINCI). Propensity score analysis was performed to obtain matched pairs of (1) Non-PTSD/TBI vs. PTSD (2) Non-PTSD/TBI vs. TBI. Confounding variables used for matching were patients’ demographics and co-morbidities. Cox proportional hazard regression analysis was conducted on matched pairs to determine the relationship between PTSD, TBI and incidence of MI. Kaplan-Meier curves were plotted to compare the time to development of incident MI among the groups. Relationships between variables were examined using chi-square tests, t-tests and non-parametric tests.

Results:
The risk of new-onset MI was significantly higher for patients with PTSD/TBI when compared with their counterparts without PTSD/TBI. Risk of MI with TBI (HR=2.687, CI 2.546-2.835, P<0.0001) was higher than with PTSD (HR=1.618, CI 1.574-1.662, P<0.0001).

Conclusion:
There is a significant increase in the incidence of MI in patients with a diagnosis of PTSD or TBI. Further studies are needed to formulate clinical guidelines to risk stratify and intervene to help reduce the incidence of MI in this patient population.
Abstract 14518: Effects of 1-year of High Intensity Interval Training and Omega-3 Fatty Acid Supplementation in Stage A HFpEF: A Randomized Controlled Trial
Authors: Hearon Christopher M , Dias Katrin , Samels Mitchel , morris margot , Palmer Dean , Livingston Sheryl A , Macnamara James P , LEVINE Benjamin D , Sarma Satyam
Published: November 2020

Background:
There are no proven pharmacologic strategies for HFpEF; therefore, lifestyle interventions must be developed to prevent disease progression in those at high risk for developing HFpEF (Stage A). We performed a randomized, double blind, placebo controlled trial evaluating the effect of 1-year of high intensity interval training (HIIT) and polyunsaturated fatty acid supplementation (PUFA) on key risk factors in Stage A HFpEF.

Hypothesis:
Long duration (1-year) HIIT and PUFA (1.6g/daily Omega-3-Acid Ethyl Esters) will reduce visceral adiposity, improve aerobic fitness, and reverse vascular stiffness in middle-aged subjects with cardio-metabolic risk factors.

Methods:
Individuals with stage A HFpEF (n= 73; 40-55 years; BMI>30 kg/m
2
; visceral fat > 2 kg; NT-proBNP>40pg/ml or hscTnT>3.0 pg/ml) were randomized to HIIT + PUFA (n=22)/placebo (n=24) or yoga + PUFA (n=15)/placebo (n=19). We assessed visceral fat (DEXA), aerobic fitness (VO
2
max), cardiac output (Q
C
, acetylene rebreathe), peripheral oxygen extraction (a-vO
2
-difference), and arterial stiffness (pulse wave velocity and augmentation index; tonometry). Data are presented as mean change and 95% CI.

Results:
1-year of HIIT decreased body fat (-1.26%, CI: -2.43 to -0.58; p=0.036) and had a similar but less consistent effect on visceral fat (-0.28 kg, CI: -0.62 to 0.04; p=0.083). Aerobic capacity increased by ~24% (ΔVO
2
: 4.41 mL/kg/min, CI: 3.22 to 5.61; p<0.0001), due to improved peak Q
C
(1.84 L/min, CI: 0.34 to 2.24; p=0.017) and a-vO
2
-difference (1.31 mL/100mL, CI: 0.13 to 2.49; p=0.031). While large elastic arterial stiffness was unchanged (PWV: -21 cm/s, CI: -61 to 19; p=0.299), augmentation index was reduced (-5.23%, CI: -9.18 to -1.35; p=0.009) indicative of improved ventricular-arterial coupling. There was no independent effect of PUFA, or interaction between HIIT and PUFA for any outcomes.

Conclusions:
1-year HIIT improved leanness, aerobic fitness, peak Q
C
and a-vO
2
-difference, and ventricular-arterial coupling in middle-aged Stage A HFpEF. There was no independent or additive effect of PUFA administration. This is the first randomized trial to demonstrate that regular HIIT can reverse cardiometabolic impairments in Stage A HFpEF.
Abstract 14520: Differences in Left Atrial Size and Function and Supraventricular Arrhythmias Between Blacks and Whites in the Atherosclerosis Risk in Communities (ARIC) Study: Implications for AF Pathogenesis
Authors: Wang Wendy , Inciardi Riccardo M , Norby Faye L , Zhang Michael J , Reyes Jorge L , Shah Amil M , Soliman Elsayed Z , Lutsey Pamela L , Alonso Alvaro , Solomon Scott , Chen Lin Y
Published: November 2020

Introduction:
Black Americans have more atrial fibrillation (AF) risk factors but lower AF risk than whites. Left atrial (LA) enlargement, impaired LA function, frequent premature atrial contractions (PAC), and atrial tachycardia (AT) are risk factors for AF. Racial differences in LA size and function, PAC, or AT may exist that could explain the difference in AF risk.

Hypothesis:
Whites have higher PAC and AT frequency than blacks. Additionally, whites have larger LA size and lower LA function than blacks, which may contribute to the racial difference in AF.

Methods:
We included 1,623 ARIC participants free of AF who had 2D-echocardiograms at visit 5 (2011-2013) and wore a 2-week continuous heart monitor, the Zio
®
XT Patch, at visit 6 (2016-2017). Weighted linear regression was used to analyze the association of race with LA size and function, as well as runs of AT per day and PAC per hour.

Results:
At visit 5, participants were 74 (4) years old, 58% were female, and 26% were black. AT runs were detected in 87% of blacks and 92% of whites, respectively (p=0.002). Among participants with >0 runs of AT per day (n=1480), blacks had 48% (95% CI: 21%-66%) fewer runs of AT per day than whites after adjustment for cardiovascular (CV) risk factors
†
. There was no significant difference in PAC frequency between blacks and whites. After adjusting for age and sex, blacks had greater LA size and lower LA function than whites; these differences attenuated after adjusting for CV risk factors (Table).

Conclusion:
Blacks have greater age and sex-adjusted abnormality in LA size and function than whites, likely due to higher prevalence of CV risk factors. Yet, blacks have lower propensity for AT. More research is needed to elucidate the mechanisms underlying the resistance to atrial arrhythmogenesis in blacks despite greater adverse LA remodeling.
Abstract 14532: Computational Drug Repurposing Identifies a Piperlongumine Analog That Controls a Gstp1-iscu Pathogenic Axis in Pulmonary Hypertension
Authors: Yang Jimin
Published: November 2020

Background and Hypothesis:
Pulmonary arterial hypertension (PAH) is an incurable vascular disease for which chemotherapies are being considered for therapeutic development. There is no method reported to date for effective computational screening of these drugs for this disease. Big data analyses that leverage the molecular parallels between cancer and PH may define novel pathogenic mechanisms and facilitate repurposing of chemotherapies for PAH. More specifically, while functional deficiency of the iron-sulfur (Fe-S) biogenesis gene ISCU and oxidative metabolism in human pulmonary arterial endothelial cells (PAECs) is known to drive PAH, the pathogenic regulation of ISCU is not fully defined, and no tailored drugs have been identified to bolster ISCU activity.

Methods and Results:
We applied a computational algorithm EDDY (Evaluating Differential DependencY), which analyzes RNA sequencing data from 810 cancer cell lines exposed to 368 small molecules, in order to identify chemotherapeutics that depended upon rewired PH-related gene clusters. The top ranked drug was a piperlongumine (PL) analog (BRD2889) that was predicted to extensively rewire dependencies across PH gene clusters, mediated by ISCU. In vitro, coupling gain- and loss-of-function analyses of GSTP1 with BRD2889 exposure in PAECs, we found that BRD2889 inhibits glutathione S-transferase P1 (GSTP1), an enzyme which in turn catalyzes ISCU glutathionylation and increases its stability in hypoxia. Consequently, BRD2889 and GSTP1 knockdown phenocopy one another by increasing Fe-S-dependent Complex I activity and mitochondrial oxygen consumption while ameliorating pathogenic apoptosis. Consistent with these computational and in vitro results, in a mouse model of PAH (IL-6 transgenic mice in hypoxia), BRD2889 improved hemodynamic and molecular disease manifestations in vivo.

Conclusions:
Using a novel computational platform, we identified a coordinated connection between BRD342289 and GSTP1-ISCU axis, crucial to PAEC metabolism. This study offers insight to fundamental PH pathobiology and sets the stage for accelerated repurposing of chemotherapies such as BRD342289 in PH.
Abstract 14541: Incidence, Risk Factors, and Outcomes of Heart Failure in Patients With Graves’ Disease
Authors: Naser Jwan A , Pislaru Sorin , Stan Marius N , Lin Grace
Published: November 2020

Background:
Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF). Due to the rarity of thyrotoxic HF, population-based studies are lacking, and data from smaller studies are widely variable.

Methods:
We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. HF was defined according to Framingham criteria. GD-related HFrEF was defined by left ventricular ejection fraction of <50%, while HFpEF was defined according to the Heart Failure Association of the European Society of Cardiology. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were analyzed with adjustments for age, gender, and history of coronary artery disease (CAD). 1:1 matching with controls (age, gender, and CAD) was additionally done.

Results:
HF occurred in 74 patients (31 HFrEF; 43 HFpEF). Incidence of GD-related HF, HFrEF, and HFpEF was 5.4%, 2.3%, and 3.1%, respectively. In HFrEF, atrial fibrillation (AF) (RR 10.05, p <0.001) and thyrotropin receptor antibodies (TRAb) level (RR 1.05 per unit, p=0.005) were independent predisposing factors. In HFpEF, independent risk factors were COPD (RR 5.78, p < 0.001), older age (RR 1.48 per 10 years, p = 0.003), overt hyperthyroidism (RR 5.37, p = 0.021), higher BMI (1.06 per unit, p = 0.003), and HTN (RR 3.03, p = 0.011). Rates of cardiac hospitalizations were higher in HFrEF (41.9% vs 3.2%, p <0.001) and HFpEF (44.2% vs 4.7%, p < 0.001) compared to controls. Furthermore, while both increased risk of strokes (HFrEF: RR 4.12, p = 0.027; HFpEF: RR 4.64, p = 0.009), only HFrEF increased risk of all-cause mortality (RR 3.78, p = 0.045).

Conclusion:
De novo HF occurs in 5.4% of patients with GD and increases the rate of cardiovascular events. HF occurs more frequently in GD patients with AF, higher TRAb, higher BMI, and overt hyperthyroidism, suggesting that these may be targets for treatment to prevent cardiovascular complications, especially in older multimorbid patients.
Abstract 14543: Diminished Aortic Flow in Fetus and Its Implications in Development of Aortic Coarctation and Arch Interruption: A 3d/4d Fetal Echocardiography and Computational Fluid Dynamics Study
Authors: Chen Zhuo , Zhao Hongkai , Zhao Ying , Han Jiancheng , Do-Nguyen Chi chi , Wei Zhenglun , He Yihua , Ge Shuping
Published: November 2020

Background and Objectives:
During critical windows of cardiac morphogenesis and remodeling, altered intrauterine hemodynamics may lead to congenital heart defects, such as aortic arch abnormalities. We sought to investigate the effects of diminished flow in the fetal aorta to understand the cause, improved diagnosis, and prognosis of coarctation of aorta (CoA) and interrupted aortic arch (IAA).

Methods:
Computational fluid dynamics (CFD) model of aortic and ductal arches was built based on dynamic 3D/4D spatiotemporal image correlation (STIC) fetal echocardiography (FE) and Doppler images from a normal fetus. Pulsatile hemodynamics, including velocity, pressure gradient, and wall shear stress (WSS), were stimulated as aortic flow decreased from 100% to 80%, 60%, 40%, and 20% by CFD, with accompanying ductal flow increased proportionally to maintain combined cardiac output (Figure).

Results:
As aortic flow diminished from 100% to 20% progressively, velocity, pressure, and WSS decreased in systole and diastole in aortic arch and isthmus. As aortic flow decreased, the flow structures changed, resulting in a reduction of WSS in the aortic isthmus, especially on the posterior wall. There was a “zero flow zone” between the left carotid and subclavian arteries when aortic flow decreased to 40% of baseline, and another one between innominate and left carotid arteries when it decreased to 20%. Pearson correlation analysis showed significant correlations between aortic flow, pressure, velocity, and WSS (r=0.883 - 1.000, P=0.047 - 0.001) at aortic isthmus.

Conclusions:
It is feasible to create a hemodynamic model of human fetal aortic arch using 3D/4D FE and CFD. The alterations of flow variables, especially WSS, and the “zero flow zones" in the aorta from progressive aortic flow reduction suggest the "flow-dependency” of the fetal aortic arch development and a unifying hypothesis of diminished flow in the pathogenesis of CoA and IAA.
Abstract 14554: Angiogenic Agent Ono-1301 Enhanced Cardiac Contractile Proteins in Hipsc Derived Cardiac Tissue-like Construct With Functional Angiogenesis
Authors: Qu Xiang , Li Junjun , Suzuki Kota , Harada Akima , Miyagawa Shigeru , Liu Li , sakai yoshiki , Sawa Yoshiki
Published: November 2020

Introduction:
Transplantation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) into myocardial infarcted areas has shown potential in healing myocardial infarction (MI). However, the survival rate of transplanted cells is yet considered limited, restricting the therapeutic effects of the transplantation. We assumed that adding angiogenic agent ONO-1301 could promote early stage angiogenesis between host and graft, and benefit the therapeutic effects of hiPSC-CM transplantation.

Methods:
This study is based on our former study of Cardiac Tissue-Like Construct (CTLC), where 5 x10e6 of hiPSC-CM was seeded on a 1x1cm poly(lactic-co-glycolic acid) (PLGA) nano fiber (Figure A). In addition, angiogenic agent ONO-1301 was mixed into the fibers. After 24h culture in vitro, 3 layers of CTLCs were transplanted into Nude rat MI models with or without ONO-1301. The rats were raised for another 4 or 8 weeks before sacrifice.

Results:
In vitro experiments have shown that supernatant of iPS-CM with ONO-1301 underwent a rise in VEGF during a 3 to 6 day culture (Figure B). The VEGF concentration in ONO-1301 positive group is much higer than ONO-1301 negative group (P=0.022) on day3. This difference narrows down over time. In vivo experiments on nude rat have shown that capillary density on MI border zone of ONO fiber+iPS-CM group is 29.95% higher than that of PLGA fiber+iPS-CM group (P=0.004) (figure C). HE and immunofluorescence staining shows remaining transplanted hiPSC-CMs in ONO fiber+iPS-CM group shows more significant TNT2 and human nuclear antigen(HNA) expression than that of PLGA fiber+iPS-CM group (Figure D and E). Also ONO fiber+iPS-CM group showed functional recovery compared to the sham.
Abstract 14555: Trends, and Impact of Atrial Fibrillation in Patients With Cardiac Amyloidosis
Authors: Abe Temidayo , Ghali Jalal K , Khoury Mtanis , Effoe Valery S , Olaosebikan Kikelomo , Hayes Dolphurs , abe Tolulope
Published: November 2020

Introduction:
The prevalence of atrial fibrillation (AF) in patients with cardiac amyloidosis (CA) can be as high as 40%, depending on the amyloid protein involved. There is a lack of data, however, concerning the temporal trends and prognostic implications of AF in these patients.

Hypothesis:
AF is associated with worse outcomes in patients with CA

Methods:
We identified 21,661 patients with the primary diagnosis of CA from the 2006 to 2014 National Inpatient Sample, of which 5,279 (25%) had AF. We used trend analysis to assess the temporal trends in the prevalence of AF from 2006 to 2014. We compared overall mortality, stroke, length of stay (LOS), and total cost in patients with those without AF.

Results:
The prevalence of AF increased from 1.3% in 2006 to 17.7% in 2014 (p<0.0001). Patients with AF were older and had more comorbidities. After propensity matching, overall mortality (8.7% vs 7.5%; p= 0.027) and rates of stroke (21.0% vs 18.0%; p<0.0001) were significantly higher in patients with CA and AF, compared to those with CA alone. There was no difference in median LOS (5 (3,9) vs 5(3,10); p= 0.065) and median total hospital cost ($36163 vs $34706; p= 0.114). The strongest predictors for overall mortality were hemodialysis, stroke, cardiac arrest, and congestive heart failure.

Conclusions:
Over a decade period, the prevalence of AF increased among CA patients and was associated with a higher risk of stroke and overall mortality.
Abstract 14614: The Automatically Assessed P-wave Notch Predicts Cardiovascular Events in Patients With Cardiovascular Risks: The Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi
Published: November 2020

Background:
The notched P-wave characteristics is associated with atrial remodeling. However, the relationship between notched P-wave characteristics and long-term cardiovascular events remains unclear.

Hypothesis:
We hypothesized that the notched P-wave would be associated with cardiovascular events.

Methods:
We enrolled 810 subjects from the J-HOP Study who had ≥1 of four cardiovascular risk factors. Twelve-lead electrocardiography was conducted, and the peak-to-peak distance in the M-shape was calculated automatically using a 12-lead ECG Analysis system (Fukuda Denshi, Tokyo). We compared two definitions: P waves were defined as "notched" if the peak-to-peak distance in the M-shape was ≥20 msec or ≥40 msec in lead II. The primary endpoints were fatal/nonfatal cardiovascular events: myocardial infarction, stroke, hospitalization for heart failure, and aortic dissection. We assessed the left atrial diameter and left ventricular mass index (LVMI) by echocardiography.

Results:
The mean follow-up period was 101±34 months, and 85 cardiovascular events occurred. When we defined a notched P wave as ≥20msec in the M shape (n=92), a notched P wave was a significant predictor of cardiovascular events after adjustment for age, gender, and comorbidity (hazard ratio 1.80, 95%CI: 1.06-3.05). When we defined a notched P wave as ≥40msec in the M shape (n=25), the hazard ratio of cardiovascular events in the notched P-wave group was significantly borderline after adjustment for covariates (hazard ratio 2.23, 95%CI: 0.90-5.56). The left atrial diameter and LVMI in the patients in the notched P-wave group (≥20 msec in the M shape) were significantly higher than those in the control group (left atrial dia. 38.8±5.9 vs. 36.8±5.0 mm, p=0.001; LVMI 103.9±27.7 vs. 96.3±25.7 g/m
2
, p=0.010).

Conclusion:
The automatically assessed notched P wave was associated with cardiovascular events, left atrial enlargement and left ventricular hypertrophy.
Abstract 14618: Bicuspid Aortic Valve Morphology and Risk Factors of Abnormal Hemodynamics: An Experimental Investigation of Velocity, Vorticity and Eccentricity of Systolic Jet Stream, Using a Magnetic Resonance Imaging Compatible Pulsatile Flow Circulation System
Authors: Hattori Kaoru , Nakama Natsuki , Takada Jumpei , Nishimura Gohki , Moriwaki Ryo , Kawasaki Eita , Nagao Michinobu , Goto Yasuhiro , Niinami Hiroshi , Iwasaki Kiyotaka
Published: November 2020

Introduction:
Abnormal hemodynamics with bicuspid aortic valve (BAV) is influenced by the BAV morphology. However, due to the morphological variety, the relationship between BAV morphology and hemodynamics has not been well clarified. We experimentally investigated influences of BAV morphology on hemodynamics.

Methods:
An MRI compatible pulsatile flow circulation system incorporating an aortic valve model and morphologically relevant aortic arch model was developed. Two types of BAV models with cusp angles of 240-120 (asymmetric BAV) and 180-180 (symmetric BAV) were prepared using bovine aorta and pericardium. The vorticity and eccentricity of jet in the aortic arch model in systolic phase were assessed using 4D-flow MRI. Streamlines at peak systole were compared among 5 BAV morphologies defined based on the symmetry and the position of leaflets (Fig).

Results:
Eccentric supra-valvular jets directed to the aortic wall faced to the smaller leaflet were present in the 3 asymmetric BAVs. In the ABAV-1, a markedly eccentric jet impinging on the aortic outer curvature was present. In the ABAV-2, a left-posterior directed jet shifting to the outer curvature of proximal arch was present. The asymmetric BAVs induced larger flow vorticity in the ascending aorta than the symmetric BAVs (ABAV-1 vs -2 vs -3 vs SBAV-1 vs -2, 0.018 vs 0.019 vs 0.014 vs 0.010 vs 0.011 m
2
/s). The ABAV-2 had a larger vortex in the middle arch than the ABAV-1 (ABAV-2 vs -1, 0.010 vs 0.005 m
2
/s).

Conclusion:
Our study indicated that the angles and orientations of the BAV impacted on the locations of jets impinging on the aortic wall and magnitudes of vorticities in systole. In the asymmetric BAVs, the direction of jet was influenced by the position of smaller leaflet. Our data suggests that the ABAV-1 morphology may be a risk factor inducing asymmetric aneurysm bulged toward the aortic outer curvature, while the ABAV-2 morphology may be a risk factor of an aortic aneurysm involving the transvers arch.
Abstract 14903: Single Center STEMI Experience in New York During COVID-19 Pandemic
Authors: Medranda Giorgio A , Brahmbhatt Kunal , Marzo Kevin P , Schwartz Richard K , Green Stephen J
Published: November 2020

Background:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged the highly contagious and lethal virus, devastating healthcare systems throughout the world. The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to rapidly evolve, as does our understanding of its implications on the cardiovascular system. The purpose of our study was to describe a single center STEMI experience at the epicenter of the COVID-19 pandemic.

Methods:
This was a retrospective, observational study, which included consecutive suspected STEMI patients from March 1 2020 through May 31 2020 compared to with the same time period in 2019, at a tertiary referral center in New York. Cohort 1 (2019 pre-pandemic period) included all patients with suspected STEMI from March 1 2019 to May 31 2019. Cohort 2 (2020 pandemic period) included all patients with suspected STEMI from March 1 2020 to May 31 2020. Statistical analysis was performed using t-test and chi-squared test.

Results:
Cohort 2 saw a similar number (n=46) of acute myocardial infarction (AMI) team activations when compared to cohort 1 (n=42) (Figure 1). As expected during the pandemic, infection control measures and additional investigation were required to clarify the diagnosis in cohort 2 resulting in significantly longer door to balloon times (96.3 minutes vs. 72.7 minutes, p=0.0307). Despite this, we observed similar inpatient length of stay (4.3 days vs. 4.9 days, p=0.1807) and mortality (11.1% vs. 12.1%, p=0.5141).

Conclusions:
Our single center study, at the epicenter of the pandemic, demonstrated similar AMI team activations compared to 2019, but longer door-to-balloon time. Despite this, inpatient length of stay and mortality remained unchanged. As we continue to manage these patients amidst this dynamic pandemic, our approach should continue to focus on the safety of healthcare workers with an understanding that primary PCI remains the standard of care for patients with STEMI.
Abstract 14906: Predictors and Outcome Impact of Mitral Regurgitation in Transcatheter Aortic Valve Replacement
Authors: Medranda Giorgio A , Brahmbhatt Kunal , Salhab Khaled , Schwartz Richard K , Green Stephen
Published: November 2020

Background:
Mitral regurgitation (MR) frequently accompanies aortic stenosis (AS). Several studies have reported that certain patients see improvement in their MR following transcatheter aortic valve replacement (TAVR) alone using earlier generation valves. The purpose of this study was to determine the predictors and short-term outcome impact of MR in patients undergoing TAVR using all generation valves across all risk groups.

Methods:
In this retrospective, study from 2012-2019, we reviewed data on 1,626 low, intermediate and high-risk patients who underwent TAVR. Included were patients with baseline MR who underwent transfemoral TAVR. We excluded prior valve replacement and aborted TAVR. Our primary outcome was persistence or worsening of baseline MR post-TAVR. Additional endpoints included an inpatient composite (intensive care unit length of stay >24 hours, post-TAVR length of stay >2 days and inpatient death), 30-day composite (30-day death or 30-day readmission) and 1-year composite (1-year death or readmission).

Results:
Of the 1,626 patients screened, 552 had significant baseline MR (>moderate), which improved in 79.7% of patients. Female patients, those with higher right ventricular systolic pressures and those who underwent TAVR using earlier generation valves were more likely to have persistence or worsening of significant baseline MR. Patients whose significant baseline MR (>moderate) persisted or worsened, had higher rates (92.2 vs. 84.1%, p=0.0343) of our inpatient composite and higher rates (36.6% vs. 25.5%, p=0.0243) of our 1-year composite when compared to patients whose significant baseline MR (>moderate) improved post-TAVR.

Conclusions:
Our study identifies certain clinical characteristics, which could help identify the subset of patients who may require closer post-procedural follow-up and warrant possible staged mitral valve intervention post-TAVR across all risk groups.
Abstract 14921: Sulfated Dextran-coated Iron Oxide Nanoparticles Detect Inflammation in the Acute Phase of Myocardialsulfated Dextran-coated Iron Oxide Nanoparticles Detect Inflammation in the Acute Phase of Myocardial Infarction
Authors: Tada Yuko , Ikeda Gentaro , Louie Angelique , Yang Phillip
Published: November 2020

Introduction:
We investigated whether the negatively-charged sulfated dextran-coated iron oxide (SDIO) nanoparticles with higher affinity with macrophage can delineate inflammation more efficiently compared to non-sulfated dextran-coated iron oxide (DIO) nanoparticles in mice LAD ligation model.

Methods:
After mice were induced with LAD ligation, SDIO or DIO nanoparticles (15mg/kg) were injected intravenously at either day 1, day 3, day 5, and day 7. MRI was performed pre- and post-24 hours later. Dephasing signal loss caused by iron-oxide nanoparticles was detected by gradient echo sequence. Iron uptake was quantified by T2* mapping and calculated as delta R2* (=1/T2*(post)-1/T2*(post)) in the region of interest in the infarct, peri-infarct, and remote zones.

Results:
SDIO injection produced clear signal voids in the peri-infarct zone at day 3 (n=8), which extend into the infarct zone at day 5 (n=3) (figure). The signal was remarkably decreased at day 7 (n=7). Iron uptake represented by delta R2* in the peri-infarct (80.6±35.7 s
-1
) was significantly higher than that in the infarct (32.3±32.6 s
-1
, p<0.001) and the remote (5.1±16.7 s
-1
, p<0.0001) at day 3. At day 5, delta R2* in the infarct (91.6±5.4 s
-1
, p<0.001) and the peri-infarct (41.0±33.3 s
-1
,p=0.04) were significantly higher than the remote (4.2±14.1 s
-1
, p<0.001). DIO did not produce significant change in delta R2* in the peri-infarct or infarct at each time phase. The MRI signals of SDIO corresponded with the area of enhanced vascular permeability peaking at day 3-5, which precedes the macrophage infiltration.

Conclusions:
SDIO can detect inflammation in the peri-infarct region in the early phase of acute myocardial infarction.
Abstract 14922: Association of Increase of Serum Albumin Levels During Hospitalization With 1-year Outcomes for Acute Heart Failure
Authors: Kato Takao , Yaku Hidenori , Ozasa Neiko , Yamamoto Erika , INUZUKA YASUTAKA , Tamaki Yodo , Kimura Takeshi
Published: November 2020

Introduction:
Hypoalbuminemia is a well-known prognostic factor in acute heart failure (AHF).

Hypothesis:
We hypothesized that there is an favorable association of the increase in serum albumin levels during hospitalization with 1-year clinical outcomes in patients hospitalized for AHF.

Methods:
Using the data of the consecutive 3717 patients hospitalized for AHF and discharged alive in the Kyoto Congestive Heart Failure registry, we evaluated the baseline and therapeutic factors associated with the increase of serum albumin levels during hospitalization for AHF. Next, we compared the effect of increase of albumin for the primary composite outcome measures compromising all-cause death and HF hospitalization using a Cox proportional hazard model.

Results:
The patients in the increase of albumin group (N=1083, 34%) were younger and less likely to have a larger body mass index and renal dysfunction than those in the non-increase group (N=2077, 66%). Median follow-up was 470 days with 96% 1-year follow-up rate. The risk for the primary outcome measure in the increase group relative to the non-increase group was significantly low (adjusted hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.69-0.90: P=0.0004) after adjusting confounders including baseline albumin levels. When stratified by the quartiles of albumin levels at discharge, the trend was more evident in the lower quartiles of albumin levels but without interaction (interaction P=0.38).

Conclusions:
The increase of albumin was associated with lower 1-year risk for the composite of all-cause death and HF hospitalization in patients with hospitalized AHF, independently of baseline albumin levels.
Abstract 14949: Influence of Myocardial Bridge on Atherosclerotic Plaque Distribution and Characteristics Evaluated by Near Infrared Spectroscopy
Authors: Saito Kan , Kitahara Hideki , Matsuoka Takaaki , Mori Naoto , Tateishi Kazuya , Fujimoto Yoshihide , Kobayashi Yoshio
Published: November 2020

Introduction:
Myocardial bridge (MB) has been reported to be associated with developed atherosclerosis in the segment proximal to MB. Near-Infrared Spectroscopy (NIRS) identify the lipid content of atherosclerotic plaque as lipid core burden index (LCBI) but little is known about the influence of MB on characteristics of atherosclerosis assessed by NIRS imaging.

Methods:
116 consecutive patients who underwent percutaneous coronary intervention using NIRS were included. MB was defined as an echo-lucent band surrounding left anterior descending artery (LAD) which could be detected by gray-scale intravascular ultrasound (IVUS). In MB patients, LAD was divided into 3 segments: proximal segment, MB segment, and distal segment. In non-MB patients, corresponding 3 segments were defined based on the average length of the above segments. Segmental maximum plaque burden and lipid content derived from NIRS-IVUS imaging in the section of maximum plaque burden were evaluated in each segment.

Results:
MB was identified in 42 patients. MB was not associated with maximum plaque burden in the proximal segment. Whereas MB was negatively correlated with both LCBI and max LCBI 4mm in the proximal segment. Multivariable analysis demonstrated both MB and maximum plaque burden in proximal segment to be independent predictors of LCBI or LCBI 4mm in proximal segment.

Conclusions:
MB was negatively correlated with both LCBI and max LCBI 4mm in the proximal segment and could be considered as an independent predictor of lipid content of atherosclerotic plaque assessed by NIRS-IVUS imaging.