bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18471: A Teachable Moment: Clinically Stable Emergency Department Patients and Their Companions are Willing to Learn Compression-only Cardiopulmonary Resuscitation
Authors: Goyal Munish , Dall Tanya , Tainsh Valerie , Konieczny Jaime , Garcia Olga E , Carlberg David
Published: July 2021

Introduction:
Bystander CPR is uncommonly performed in out of hospital cardiac arrest patients transported to our Emergency Department (ED). ED visits are brief and complex, but represent a valuable opportunity to teach CPR to members of our community. Our objective was to determine what percentage of ED patients and their companions are willing to learn compression-only CPR.

Hypothesis:
The majority of ED patients and their companions are willing to learn compression-only CPR.

Methods:
A convenience sample of clinically stable adults age 18-70 from two urban, academic EDs with socioeconomically diverse patient populations was recruited. Patients in hallways and non-english speakers were excluded. Subjects were asked to complete a pre-video survey to assess baseline knowledge and willingness to perform CPR, watch a 60-second previously validated CPR instructional video, and then complete a post-training CPR survey. Consenting patients were asked if they thought their ED visit was related to their heart. All study subjects were categorized as: 1. patient or companion, and 2. cardiovascular or non-cardiovascular complaint. Subjects who did not consent were asked to share reasons for not participating. Data were entered into a REDCap database.

Results:
Between 1/1/15 to 6/7/15, 281 patients and their companions were approached about study participation. Mean age was 47, 66% female, 68% African American, and 69% had a college education. 73 believed their visit was related to their heart. 70% were patients, and the remainder were their companions. Overall, 229 (82%) were willing to learn compression-only CPR. 51 of 52 shared reasons for not participating. Reasons included: not feeling well (29%), already CPR trained (16%), and not interested (16%). Patients who thought their ED visit was related to their heart and their companions were equally likely to participate than those who did not (80% vs 83%).

Conclusion:
In two diverse, academic EDs, 82% of medically stable adult patients and their companions were willing to learn compression-only CPR.
Abstract 18482: Impact of Tricuspid Regurgitation and Tricuspid Annulus Dilation on Mortality After Transcatheter Aortic Valve Replacement
Authors: Mongrut Vilchez Carmen , Toubal Oumhanie , Magne Julien , LeVen Florent , Dahou Abdellaziz , Clavel Marie-Annick , Thebault Christophe , Rodes-Cabau Josep , Pibarot Philippe
Published: July 2021

Background and Objetives:
According to the guidelines a concomitant tricuspid annuloplasty should be performed at the time of mitral or aortic valve surgery in presence of: i) severe tricuspid regurgitation (TR) or ii) mild-to-moderate TR with significant tricuspid annulus dilation (TAD, i.e. diameter>40 mm by echo). In patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), no tricuspid annuloplasty or replacement is performed. The objective of this study was to determine the prevalence of TR and TAD and their impact on mortality following TAVR.

Methods:
TR and TAD were assessed by transthoracic echocardiography in 227 consecutive patients who underwent TAVR at our institution. The primary end-point was all-cause mortality.

Results:
Figure 1 shows the distribution of the patients according to TR severity and presence of TAD. Overall, very few patients had none or trace TR, 88% had mild or moderate TR, and 7% had severe TR. Furthermore, 73% had TAD. After a mean follow-up of 1.5± 1.2 years, 73 patients died. Two-year survival rate was 52±8% in patients with severe TR, 65±5% in patients with mild/moderate TR and TAD, and 87± 7% in patients with mild/moderate TR and no significant TAD (Figure 2). After adjustment for sex, EuroSCORE, creatinine and other risk factors, mild/moderate TR with TAD had higher risk of mortality (HR : 2.88; 95% CI :1.3-8.9; p=0.025) compared to mild/moderate TR without TAD and similar risk (HR : 1.34; 95% CI :0.6-3.7; p=0.53) compared to severe TR

Conclusion:
Both TR and TAD are highly prevalent in the patients with severe AS undergoing TAVR. Among patients with mild/moderate TR, those with significant TAD have worse outcomes compared to those with no TAD and similar outcomes compared to those with severe TR. Further studies are needed to determine if concomitant or subsequent transcatheter tricuspid annuloplasty or replacement would improve outcomes of patients undergoing TAVR.
Abstract 18515: Forward Flow Ejection Fraction as a Major Determinant of Outcome in Organic Mitral Regurgitation
Authors: Dupuis Marlène , Clavel Marie-Annick , Mahjoub Haïfa , O’Connor Kim , Sénéchal Mario , Pibarot Philippe
Published: July 2021

Introduction:
The optimal timing of mitral valve (MV) surgery in patients with organic mitral regurgitation (OMR) is controversial. The objective of this study was to determine independent predictors of cardiac events in patients with OMR and no triggers for mitral valve surgery.

Hypothesis:
We hypothesized that forward LV ejection fraction (LVEF) calculated by the Dumesnil’s method (i.e. stroke volume measured in LV outflow tract divided by left ventricular end diastolic volume) is superior to the LVEF measured by the biplane Simpson’s method.

Methods:
Two hundred seventy eight patients with OMR (i.e. severity grade ≥1/4) and Doppler echocardiography exam at least 6 months before MV surgery or death were included. Clinical and echocardiographic data of 278 patients with OMR were analyzed retrospectively. The study end-point was the composite of death or need for mitral valve surgery.

Results:
During a mean follow-up of 5.4 ± 3.2 years, there were 147 (53%) events: 96 (35%) mitral surgeries and 66 (24%) deaths. There was no difference in the Simpson LVEF (65 ± 6% vs 65 ± 4%; p=0.86) and global longitudinal strain (-21.18 ± 3.26 % vs -21.26 ± 2.44 %; p=0.86) between patients who had an event versus those who were event-free during follow-up. However, LVEF calculated by Dumesnil’s method at baseline was lower in the event-group (47 ± 15%vs 59 ± 15%; p<0.0001) compared to the non-event group. After adjustment for age, sex, Charlson’s probability, coronary artery disease, ACE inhibitors, β-blockers, diuretics, AF and MR grade, forward LVEF by Dumesnil’s method remained an independent predictor of the occurrence of cardiac events (adjusted hazard ratio: 1.09, 95% interval confidence: 1.02-1.17; p=0.01).

Conclusion:
This study shows that the forward LVEF calculated by the Dumesnil’s method is superior to the standard LVEF or to longitudinal strain to predict outcomes in OMR. These results could help to improve risk stratification of patients with OMR and thereby individualized the treatment’s strategy. Further prospective studies are needed to confirm these findings.
Abstract 18654: Expert Adjudication of Device Electrograms: Is an Atrial Channel More Important than Gray Hair?
Authors: Orlov Michael V , Houde-Walter Haley , Swiryn Steven , Qu Fujian , Waldo Albert , Olshansky Brian
Published: July 2021

Background:
The diagnosis of a tachycardia from ICD recordings ultimately depends upon analysis of captured electrograms (EGMs). While atrial EGM may improve tachycardia discrimination, the degree of benefit has not been evaluated in medical professionals with different level of expertise.

Methods:
Expert-adjudicated supraventricular tachycardia (SVT) and ventricular tachycardia (VT) EGMs from the RATE Registry were given to EP Specialists (EPS), EP Fellows (EPF), and Nurse Practitioners or Physician Assistants (NPPA). Each participant diagnosed 112 EGMs (61 VTs, 51 SVTs) as SVT, VT, or Uncertain in two stages. First, participants made diagnosis based on ventricular EGM (VEGM) alone (Atrial Channel covered). Then the EGMs were re-randomized with atrial EGM exposed and diagnosis was made again. The accuracy of diagnosis by EPS, EPF, and NPPA in the use of VEGM alone vs dual-chamber EGM was assessed.

Results:
Fifteen participants (5 in each group) completed diagnosis. All 3 groups significantly improved diagnosis accuracy (>20% for VTs, >15% for SVTs, all p values < 0.02) when dual-chamber EGM was provided. EPS diagnosed VTs more accurately than NPPA (VEGM: 73.1±7.6% vs 56.1±14.1%, p = 0.03; dual-chamber EGM: 98.0±2.7% vs 80.3±7.4%, p = 0.001). EPF diagnosed VTs better than NPPA but worse than EPS (not statistically significant). There was no significant intergroup difference in SVT diagnosis.

Conclusion:
These results suggest that atrial EGMs help rhythm discrimination at all levels of expertise. However, experience seems to improve diagnosis accuracy with and w/o atrial EGM.
Abstract 18673: JNK Inhibition Restores Endothelial Function in Type 2 Diabetes Mellitus
Authors: Breton-Romero Rosa , Feng Bihua , Holbrook Monika , Farb Melissa G , Fetterman Jessica L , Linder Erika A , Berk Brittany D , Masaki Nobuyuki , Weisbrod Robert M , Inagaki Elica , Gokce Noyan , Fuster Jose J , Walsh Kenneth , Hamburg Naomi M
Published: July 2021

Introduction:
Diabetes mellitus type 2 is an increasingly public health problem and it is a major cause in the development of cardiovascular diseases. Endothelial dysfunction is a key mechanism that contributes to the pathogenesis of cardiovascular diseases and is a well-known feature of clinical diabetes. Prior studies have demonstrated an impaired nitric oxide bioavailability and a reduced endothelium-dependent vasodilation under diabetic conditions and in animal models, JNK activity has been widely described to be involved in systemic insulin resistance.

Hypothesis:
Our study aimed to evaluate the involvement of JNK in endothelial dysfunction, studying its potential role in altered eNOS activation and NO synthesis in diabetic patients.

Methods:
We measured endothelial function and JNK activity in freshly isolated endothelial cells from diabetic patients (n=38) and nondiabetic controls (n=40).

Results:
ECs from diabetic patients displayed impaired eNOS activation and reduced NO release after insulin and A23187 stimulation, consistent with the presence of endothelial dysfunction. JNK activation was higher in diabetic (**P=0.003), and was associated with lower flow-mediated dilation (r=-0.53, *P=0.02). In endothelial cells from diabetic patients, treatment with JNK chemical inhibitor (SP600125) restored eNOS activation and insulin response (***P<0.001). Nitric oxide bioactivity after A23187 stimuli with diabetes was also recovered in endothelial cells from patients with diabetes.

Conclusions:
In summary, our data suggest that JNK activation contributes to vascular insulin resistance and endothelial dysfunction in patients with type 2 diabetes and may represent a target in novel therapeutic opportunities.
Abstract 18692: Evolution of Diastolic Parameters and Their Relationship to Heart Rate in the 7-15 Week Human Fetus
Authors: Bohun Claudine M , Howley Lisa , Serrano Lomelin Jesus , Savard Winnie , Mills Lindsay , McBrien Angela , Gyenes Dora , Motan Tarek , Jain Venu , Hornberger Lisa K
Published: July 2021

Objectives:
Fetal echo offers a unique opportunity to investigate cardiac function in humans from the 1st trimester. We sought to explore the evolution left ventricular (LV) diastolic parameters and their relationship to fetal heart rate (HR) from 7-15 weeks gestational age (GA).

Methods:
We prospectively performed fetal echo in 137 healthy pregnancies recruited from 7+0 to 15+0 (mean 11.5±2.1) weeks GA. From Doppler studies we measured LV isovolumic relaxation time (IRT), mitral valve (MV) inflow patterns,and duration, diastolic time (IRT+inflow duration), LV ejection time (ET) and systolic time interval (isovolumic contraction time+ET). All variables were compared to GA and HR and were assessed as a proportion of the cardiac cycle length (R-R). Data were analyzed by regression and correlation analyses.

Results:
Results: From 7+0-15+0 weeks, HR and GA showed a non-linear relationship (R2=0.55, p<0.001) with low HRs at 7-8 weeks, peaking between 8-9 weeks, then falling thereafter. Diastolic time linearly increased with GA (R2=0.65, p<0.001) and inversely correlated with HR (r=0.77, p<0.001). IRT showed a nonlinear inverse relationship with GA (R2= 0.70, p<0.001), but did not correlate with HR, and IRT/RR increased linearly with GA (R2=0.71, p<0.001). Both inflow duration and inflow duration/R-R linearly increased with GA (R2=0.81,p<0.001). Inflow duration inversely correlated with HR (r=-0.70) and with IRT (r=-0.71) and IRT/R-R (r=-0.83, p<0.001 for all 3). A uniphasic MV atrial systolic inflow signal was present in 20/21 fetuses at 7+1-9+0 weeks, whereas, biphasic MV inflow was seen in 45% at 9+1-10+0 , 76% at 10+1-11+0 , 95% at 11+1-13+0 and 100% after 13+1 weeks GA. Inflow duration was significantly longer (146.9±25.4 vs 85.2±12.6ms, p<0.001) and HR was lower (160±9 vs 170±10 bpm, p<0.001) in fetuses with a biphasic flow pattern. ET demonstrated a weak relationship with GA (R2=0.41) and no relationship with HR, IVRT,or IVRT/R-R, and the systolic time showed a nonlinear trend of decreasing with GA (R2=0.46).

Conclusions:
In the 7-15 week fetus, improvements in relaxation suggested by decreasing IRT, decreasing HR, and, to a lesser extent, decreasing systolic time likely contribute to increasing inflow duration and to early ventricular filling.
Abstract 18700: Impact of Gender on Clinical Outcomes in Adults With In-hospital Cardiac Arrest
Authors: Garry Jonah , Nguyen Robert , Schoenfeld Elinor , Parnia Sam , Patel Jignesh
Published: July 2021

Background:
Despite numerous advances in the delivery of resuscitative care, in-hospital cardiac arrest (IHCA) continues to be associated with high morbidity and mortality. We sought to study the impact of gender on return of spontaneous circulation (ROSC) and survival to discharge in patients with IHCA.

Methods:
The study population included 255 consecutive patients who underwent ACLS-guided resuscitation from January 2012- December2013 for IHCA at an academic tertiary medical center. Baseline demographic, clinical, laboratory, and clinical outcome data were recorded. Outcomes of interest included presence of sustained ROSC (defined as ROSC > 20 minutes) and survival to discharge.

Results:
Of the 255 patients studied, 96 (37.6%) were women and 159 (62.4%) were men. No difference in age, race, or ethnicity was noted between men and women. Women were shorter (160cm vs 174cm, p<0.001) and had lower weight (78kg vs 89kg, p<0.001), but had a trend towards higher body mass index (31.4 kg/m2 vs 29.4kg/m2, p=0.087). Women had lower rates of peripheral vascular disease (15.6% vs 27.0%, p=0.035) and hyperlipidemia (26.4% vs 41.6%, p=0.017). Rates of other comorbidities, including cardiovascular disease, chronic obstructive pulmonary disease, congestive heart failure, stroke, diabetes mellitus, chronic kidney disease, and hypertension were similar in men and women. Clinical presentation of IHCA, in particular, the initial rhythm, location of IHCA, duration of cardiopulmonary resuscitation, and laboratory results at the time of IHCA was similar in both men and women. With respect to outcomes, women were noted to have a trend toward lower rates of sustained ROSC (45.8% vs 57.9%, p=0.062) but no difference in survival to discharge (22.9% vs 27.0%, p=0.464). In multivariate analysis, gender was not an independent predictor of sustained ROSC or survival to discharge.

Conclusion:
Gender is not independently predictive of ROSC or survival to discharge in adults with IHCA.
Abstract 18708: Vascular Dysfunction in Hyperhomocysteinemia: In vitro Evidence for Endoplasmic Reticulum Stress-mediated Calcium-activated Potassium Channel Dysfunction
Authors: Sun Wen-Tao , Wang Xiang-Chong , Yu Cheuk-Man , Pun Shun-Hay , Yang Qin
Published: July 2021

Objectives:
KCa channels play an important role in the control of vascular tone. Opening of IKCa and SKCa in endothelial cells underlies the classic EDHF pathway and promotes NO production. Smooth muscle BKCa provides a negative feedback mechanism opposing vasoconstriction and is an effector of NO and EDHF. Previous studies demonstrated homocysteine (Hcy), a risk factor for atherosclerosis, compromises NO and EDHF function, however, whether KCa is involved is poorly studied and the underlying mechanisms remain unknown. We studied the effect of Hcy on vascular KCa with the role of endoplasmic reticulum (ER) stress explored.

Methods:
In vitro studies were performed in porcine coronary arteries and primary cultured porcine coronary endothelial (PCECs) and smooth muscle cells (PCSMCs). IKCa and SKCa-, and BKCa-mediated relaxations were studied in endothelium-intact and -denuded arteries in a myograph. IKCa and SKCa currents in PCECs and BKCa current in PCSMCs were analyzed by whole-cell patch clamp and channel expressions were examined by western blot.

Results:
Hcy impairs the role of IKCa and SKCa, and BKCa in vasorelaxation. Relaxant responses to channel activators NS309 and NS1619 were attenuated and EDHF-type response was inhibited. Hcy suppressed IKCa and SKCa currents in PCECs and BKCa currents in PCSMCs. Inhibition of ER stress enhanced KCa currents and improved EDHF-type and channel activators-induced responses. Whole-cell protein levels of IKCa and SKCa remained unchanged in Hcy-exposed PCECs whereas IKCa and SKCa at cell surface were significantly decreased. Hcy lowered protein of β1 but not α subunit of BKCa in PCSMCs. The decrease in cell surface IKCa and SKCa and reduction of BKCa β1 were restored by ER stress inhibition. Further, inhibition of PERK increased BKCa β1 protein and enhanced BKCa current.

Conclusion:
ER stress mediates Hcy-induced vascular dysfunction through inhibition of KCa. Suppression of cell surface expression underlies ER stress-mediated IKCa and SKCa inhibition. Downregulation of BKCa β1 by PERK-ER stress pathway plays a key role in the loss of BKCa function. This study provides new mechanistic insights into the role of ER stress in vascular dysfunction.

Supported by RGC GRF CUHK4774/12M & CUHK14118414, and NSFC 81200123.
Abstract 18713: Quantification of Cortical Recovery After Cardiac Arrest With Continuous Somatosensory Evoked Potentials
Authors: Werner Nicole L , Mergos Joshua , Sun Liqun , Tooley Trevor , Alghanem Fares , Chulski Nick , Villa Christy , Stacey William , Bartlett Robert H , Rojas-Pena Alvaro , Neumar Robert W
Published: July 2021

Objective:
Reliable early prognostication of neurologic recovery in comatose cardiac arrest (CA) survivors remains a major clinical challenge. We hypothesized that continuous somatosensory evoked potentials (SSEP) in the immediate post-CA period could enable early quantification of cortical recovery.

Methods:
Pigs were instrumented for hemodynamic and SSEP monitoring. For SSEP, stimulation was applied to the right median nerve and electrodes in the brachial plexus and scalp acquired recordings. The primary cortical signal was the N20. Animals were then subjected to ventricular fibrillation CA that was left untreated for up to 4 minutes and followed by advanced cardiac life support until return of spontaneous circulation (ROSC). SSEP monitoring started before CA and continued after ROSC until SSEPs were unchanged for 60 minutes.

Results:
Six experiments were performed. In all animals, peripheral, subcortical, and cortical SSEPs were acquired prior to CA, demonstrating morphology similar to that of humans. Cortical potentials completely disappeared during CA. Average arrest duration was 6.9 ± 3.0 min. After ROSC, the N20 signal returned but with variable recovery rate and amplitude. The final N20 amplitude inversely trended with total duration of arrest (Figure 1). The N20 amplitude recovery over time took a logarithmic shape and ranged from 5 to 180 minutes to reach maximum (Figure 2).

Conclusions:
Continuous SSEP monitoring allows for quantification of cortical recovery within hours of short duration CA in a porcine model. The maximum N20 amplitude and rate of increase may be useful tools for quantifying recovery of cortical function in comatose cardiac arrest survivors.
Abstract 18749: Body Mass Index, Leptin, and Recovery in Peripartum Cardiomyopathy: Results of the Multicenter IPAC Study
Authors: Davis Esa , Damp Julie , Alharethi Rami , Ewald Gregory , Givertz Michael , Bozkurt Biykem , Boehmer John , Skopicki Hal , Felker Michael , Semigran Marc , Hanley-Yanez Karen , McNamara Dennis M ,   for the IPAC Investigators
Published: July 2021

Introduction:
The contribution of obesity and metabolic syndrome to the development of peripartum cardiomyopathy (PPCM) remains unknown. Leptin is a peptide hormone released by adipose tissue which may mediate impact of the obesity on cardiovascular function. We sought to evaluate their effect on myocardial recovery in PPCM in the multicenter Investigation of Pregnancy Associated Cardiomyopathy (IPAC) study.

Methods:
100 women with new onset of PPCM were enrolled and serum obtained for biomarker analysis at entry. Myocardial function was assessed by echocardiography at entry, 2 months, 6 months and 12 months postpartum and LVEF calculated at a core lab. Leptin levels were measured by ELISA and the correlation of leptin with body mass index (BMI) and days post-partum evaluated. LVEF over the first year postpartum was compared by BMI at study entry (BMI >30 versus<=) and then compared by of Leptin levels (median).

Results:
The cohort was 30% black 65% white 5% other,age 30
+
6, mean BMI was 28.9
+
7.4 and LVEF 0.34
+
0.10 at study entry 31
+
25 days post-partum.Compared to those with a BMI<=30 women with a BMI > 30 had a similar LVEF at entry (LVEF BMI>30 vs
<
: 0.35
+
0.09 vs 0.34
+
0.10, p=0.60), but a lower LVEF at 2 month (0.39
+
0.12 vs 0.45
+
0.12, p=0.02), 6months (0.38
+
0.12 vs 0.53
+
0.09, p=0.02) and 12 months (0.50
+
0.13 vs 0.55
+
0.08, p=0.03). Leptin levels (mean 23.4
+
21.1 ng/ml, median 15.26 ng/ml) correlated with BMI (r=0.57, p<0.001). Higher leptin levels were associated with more remodeling (LVEDD for high/low leptin= 5.8
+
0.7/5.4
+
0.6, p=0.02) at entry and lower LVEF 2months (high/low= 0.40
+
0.12/ 0.46
+
0.11, p=0.02) which persisted at 12 months (high/low= 0.51
+
0.11/0.56
+
0.08, p=0.03). Leptin levels were significantly lower at entry in subjects who subsequently recovered to an LVEF>=0.50 (19.2
+
19.1 vs 31.8
+
22.9, p=0.006), and were higher in diabetics (p=0.01) and in blacks (p=0.03).

Conclusions:
In women with PPCM, obesity was associated with a lower LVEF at 6 and 12 months. Leptin levels correlated with BMI and were associated with greater LV remodeling at presentation and lower LVEF at 12 months. The impact of obesity and leptin on the development of cardiomyopathy warrants further investigation.
Abstract 18760: Evaluation of a Web-based Cardiac Pain Knowledge Dissemination Platform Fueled by Social Media
Authors: McGillion Michael , Carroll Sandra L , Jolicoeur E Marc , O'Keefe-McCarthy Sheila , Pilote Louise , Arthur Heather
Published: July 2021

Introduction:
The prevalence of persistent cardiac pain-related conditions is on the rise. Increasingly prevalent forms of persistent cardiac pain include refractory angina, cardiac syndrome X and functional cardiac pain syndromes. Our aim was to disseminate a web-based, multi-media resource centre, CardiacPain.Net, as a prototype for large-scale knowledge dissemination and educational outreach in partnership with Elsevier.

Methods:
Multi-media design features included open access published resources, narrated video, roundtable discussions, downloadable fact sheets, and an asynchronous discussion forum. Accreditation for continuing medical education (Canada and United States) was secured to maximize incentive for end-user uptake. Dissemination strategies included opt-in email blasts to Elsevier subscribers (n= 27,000) every 3 months, e-banner advertising, and mass social media via Twitter. Standard dissemination metrics included total site visits and components visited and downloaded. Customized metrics included unique and return visitor rates, bounce rate, stream views, and geo-targeting. All metrics were analyzed in aggregate and examined for outliers and monthly trends. Interrupted time series analysis with an autoregressive structure was used to examine immediate impact of social media on 12-month dissemination metrics.

Results:
CardiacPain.Net reached end users in 132 countries across 5 continents. A total of 7,066 unique visitors were engaged and resources were viewed and downloaded 13,629 times. The monthly return visitor and bounce rates were 30% and 50%, respectively. Average time spent on multi-media presentations was 14.5 minutes. Twitter constituted 66% of all total social media engagement; 62% of Twitter users were female. Interrupted time series analyses revealed that Twitter outreach significantly increased end user sessions, number of users, and page views (p< 0.001). Twitter did not affect proportion of new users monthly or website navigation behavior. Conclusions: Results suggest that as a large-scale knowledge dissemination and online cardiac educational outreach prototype, CardiacPain.Net is far reaching and capable of sustained engagement of an international-scale audience.
Abstract 18774: Increased Epicardial Fat After Fontan Palliation Associated With Decreased Cardiac Output
Authors: Lubert Adam M , Lu Jimmy C , Rocchini Albert P , Norris Mark D , Yu Sunkyung , Agarwal Prachi P , Ghadimi Mahani Maryam , Dorfman Adam L
Published: July 2021

Introduction:
Epicardial fat produces multiple proinflammatory and proatherogenic cytokines and is associated with adverse cardiovascular events. Inflammation and resultant endothelial dysfunction may play a role in progressive myocardial dysfunction among adults with single ventricle physiology status post Fontan, but the potential impact of epicardial fat volume (EFV) has not been studied. This study aimed to quantify EFV in Fontan patients compared to a control group of repaired tetralogy of Fallot patients (rTOF) and to evaluate its association with ventricular ejection fraction and cardiac index.

Methods:
We retrospectively measured EFV on all patients post Fontan, 15 years or older, with cardiac magnetic resonance performed at the University of Michigan from 2007-2014, and 1:1 age, sex, and body mass index (BMI) matched patients with rTOF. EFV was measured manually on cine, steady-state free precession, short-axis images and was indexed to body surface area (BSA). Cardiac index was calculated as the sum of flow in the superior vena cava and inferior vena cava, indexed to BSA. A random subset of studies was re-measured >1 week after initial measurement to assess intraobserver variability.

Results:
Fontan patients (n=63, mean age 22.3±6.0, 52% male) had a larger indexed EFV compared to rTOF (mean age 22.2±5.8, 52% male) measuring 75.6±29.2 vs. 60.0±19.9 ml/m
2
(p= 0.0003). There was no difference in BMI between the two groups (24.2±5.2 vs 24.2±5.6, p= 0.81). In Fontan patients, indexed EFV was inversely correlated with ventricular ejection fraction (r = -0.26, p = 0.03) and cardiac index (r = -0.34, p = 0.01). Intraobserver variability of the indexed EFV measurements in both groups was excellent (intraclass correlation coefficient of 0.95 and 0.93 in the Fontan group and rTOF group, respectively).

Conclusions:
Indexed EFV is higher in individuals post Fontan compared to patients with rTOF and is associated with lower ventricular ejection fraction and cardiac index. Increased epicardial fat could play a role in progressive myocardial dysfunction in this population, but longitudinal studies are necessary to establish any causative role.
Abstract 18789: BRCA2 is a Novel Regulator of Endothelial Cell Function and Apoptosis Following Hyperglycemia
Authors: Matkar Pratiek N , Al-Omran Mohammed , Verma Subodh , Leong-Poi Howard , Singh Krishna K
Published: July 2021

Background:
Germ-line mutations in the tumor suppressor gene BRCA2 (breast cancer 2, early onset) predispose carriers mostly to breast cancer, and BRCA2 mutation carriers also face a 2-fold increase in the risk of developing diabetes.Hyperglycemia, the hallmark of diabetes, is a major risk factor for endothelial dysfunction leading to vascular complications. The relationship linking role of BRCA2 in the development of diabetes and endothelial dysfunction remains mainly unexplored.

Methods:
To elucidate the role of BRCA2 in diabetes and endothelial apoptosis/dysfunction in vitro, we silenced BRCA2 in human umbilical vein endothelial cells (ECs) and evaluated the markers of EC function and apoptosis following hyperglycemia.

Results:
We first confirmed the basal expression of BRCA2 in ECs at transcript and protein levels by qPCR and immunoblotting, respectively. Interestingly, hyperglycemia significantly induced BRCA2 expression after 48 hours of treatment. We then silenced BRCA2 in ECs and confirmed successful silencing at transcript and protein levels. Hyperglycemia significantly increased the reactive oxygen species (ROS) production in the BRCA2-deficient ECs in comparison to control ECs. Increased ROS production was associated with exacerbated DNA-damage in BRCA2-silenced ECs as evidenced by increased expression and activation of DNA double-stranded breaks (DSBs) marker H2A.X and reduced RAD51-foci formation, an essential regulator of DSB repair. Increased DSBs were associated with significantly increased activation of p53. Elevated levels of DNA-damage and activated-p53 were further associated with significantly increased hyperglycemia-induced apoptosis in BRCA2-silenced ECs as measured by immunoblotting for cleaved-caspase-3, Bax and by TUNEL-staining.Key indices of endothelial function, including tube formation and NO production, were significantly reduced following hyperglycemia-treatment in BRCA2-deficient ECs.

Conclusion:
Our data for the first time, show an entirely novel role of BRCA2 as a regulator of endothelium in the setting of hyperglycemia, and provide important clues regarding the potential susceptibility of BRCA2 mutation carriers to hyperglycemia-induced cardiovascular complications.
Abstract 18792: Beclin-1 Haploinsufficiency Protects Against Obesity-induced Cardiac Dysfunction Through Compensatory Mitophagy and Alternative Autophagy
Authors: Liu Xiangwei , Xu Xihui , Zhang Yingmei , Ren Jun
Published: July 2021

Background:
Though autophagy including the selective mitophagy is essential for cellular homeostasis, its role in obese heart function remains controversial. Beclin-1 plays a cardinal role in conventional autophagy and has recently been implicated in alternative autophagy and mitophagy. This study was designed to examine the impact of Beclin-1 haploinsufficiency using heterozygous deletion of Beclin-1 (BCN-KO) on high fat diet (HFD)-induced cardiac anomalies.

Methods and Results:
Adult wild type (WT) and BCN-KO mice were fed low fat diet (LFD) or HFD for 12 weeks. HFD triggered comparable body weight gain in WT and BCN-KO mice. However, BCN-KO improved HFD-induced glucose intolerance and countered against HFD-induced cardiomyocyte contractile dysfunction manifested as decreased peak shortening, +dL/dt, -dL/dt and prolonged TR
90
. Levels of Beclin-1 were downregulated following HFD feeding although such effect was masked by BCN haploinsufficiency. Levels of autophagy markers LC3B-II/I and Atg5 were downregulated in a comparable manner in both HFD groups. Interestingly, Rab9, an essential regulator for alternative autophagy, was upregulated in HFD groups with a more pronounced effect in BCN-KO mice. Level of p62 was increased by HFD in WT but not BCN-KO group. Furthermore, the mitochondrial coupling protein for LC3B Bnip3 (also a key molecule for alternative autophagy-induced mitophagy) was upregulated in HFD groups with a more pronounced effect in BCN-KO mice. Moreover, Pink1 and AMPK phosphorylation, two key regulators in mitophagy were decreased by HFD in WT but not BCN-KO group. In line with these results, PGC-1
a
(a marker of mitochondrial biogenesis) was downregulated by HFD, the effect of which was rescued by BCN-KO.

Conclusion:
Taken together, our data revealed that HFD led to cardiac contractile defect accompanied with dampened conventional autophagy and facilitated alternative autophagy. Our data suggested that adaptive mitophagy may play a pivotal role in BCN haploinsufficiency-induced beneficial effect. Such as beneficial effect was achieved through promoting HFD-induced alternative autophagy, which may contribute to increased mitophagy under HFD intake possibly via AMPK, Rab9 and Bnip3-mediated signaling pathways.
Abstract 18815: High Dose Aspirin is Associated With Decrease of Hemoglobin and Do Not Affect the Disease Outcome in Acute Stage of Kawasaki Disease
Authors: Kuo Ho-Chang , Hsieh Kai-Sheng
Published: July 2021

Introduction:
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Although intravenous immunoglobulin (IVIG) has been shown to reduce the incidence of coronary artery lesions (CAL) effectively, the role and appropriate dose of aspirin during acute phase is still unclear. Thus, this study was conducted to evaluate the effect of treatment and the change of serum hepcidin with or without high dose aspirin in the acute stage of KD.

Hypothesis:
High dose aspirin is not benefit for acute stage of KD.

Methods:
Retrospective analysis of KD patients from two medical centers during 1999-2009 in Taiwan. All patients were initially treated with a single dose of IVIG (2 g/kg) during a 12-h period. High dose aspirin was given (> 50 mg/kg/day) until the fever subsided then low-dose aspirin (3-5 mg/kg/day) was prescribed until all signs of inflammation resolved at group 1. Low-dose aspirin was prescribed without high-dose aspirin at group 2. A total of 851 KD patients (group 1, N= 305, group 2, N= 546) were enrolled in this study. patients.

Results:
There were no significant difference between group 1 and group 2 including gender distribution (p=0.51), IVIG resistant rate (31/305 vs. 38/546, p=0.07), CAL formation rate (52/305 vs. 84/546, p=0.67), and total hospital days (6.3 ± 0.2 vs. 6.7 ± 0.2, p=0.13). There were also no significant difference between total white blood counts, hemoglobin levels, platelet counts, CRP and serum hepcidin levels before IVIG treatment between group 1 and group 2 (all p>0.1). After IVIG treatment, there were significant lower hemoglobin and higher CRP as well as lower decrease of CRP levels in group 1 than in group 2 (p=0.006, <0.001 and =0.012, respectively). Furthermore, there were also high serum hepcidin and lower decrease of hepcidin levels in group 1 than in group 2 (p=0.04, and =0.02, respectively).

Conclusions:
These results provide evidence supporting high dose aspirin in acute phase of KD may affect the improvement of inflammatory markers. It also caused lower hemoglobin level that was associated with higher hepcidin level after IVIG treatment. It seems unneeded of high dose aspirin in acute phase of KD.
Abstract 18819: Adverse Pregnancy Outcomes and Their Prediction of Future Heart Disease
Authors: Green Paul-Ann , Fridman Dmitry , Smith Heather , Rosser Mary
Published: July 2021

Objective:
Pregnancy provides an opportunity for a natural stress test, with the physiological demands of pregnancy acting as a maternal stress test that can predict a woman’s health later in life. The 2011 Update of the American Heart Association’s Evidence-Based Guidelines for the Prevention of Cardiovascular Disease in Women identifies many complications of pregnancy as relevant in the determination of cardiovascular disease (CVD) risk. This is important because CVD is the leading cause of death in women worldwide. The purpose of this research was to determine if, in our diverse inner city population, pregnancies complicated by hypertensive disorders, gestational diabetes, intrauterine growth restriction, or abruption were associated with future development of CVD.

Methods:
We identified women who delivered at a large, urban hospital in Bronx, NY from 1997-2001 who were treated for gestational diabetes, hypertensive disorders of pregnancy, intrauterine growth restriction, and placental abruption (n=183). A hospital database was used to identify our cohort and electronic medical records were reviewed to determine if these patients developed CVD over 10 years since the index pregnancy. The end points were subsequent Hypertension, Myocardial Infarction, Cerebrovascular disease, Type 2 Diabetes Mellitus, and Thromboembolic events. The cohort was compared to controls delivered at the same institution.

Results:
The relative risk (RR) of subsequent type 2 diabetes mellitus was 1.93 [CI 1.00-3.75], if the exposed population was older than 35 at the time of the index pregnancy. The RR of subsequent hypertension was 2.21 [CI 1.3-3.77] in African Americans at any age of index pregnancy, regardless of exposure. When comparing all exposed population to our controls; there is an increased risk in our population of CVD with a RR of 1.58 (CI 1.12-.2.23), and a p value of 0.01.

Conclusions:
In our large, diverse, urban population, age or the presence of preeclampsia were associated with an increased risk for adverse CVD. These women may be appropriate for early CVD risk screening and intervention at younger ages than previously identified. Women with adverse pregnancy outcomes should be targeted for risk factor modification and prevention programs.
Abstract 18831: Utilization of Palliative Care Consultation During Therapeutic Hypothermia Following Cardiac Arrest
Authors: Zern Emily K , Young Michael N , Xu Meng , Triana Taylor S , Holmes Benjamin B , Borges Nyal , McPherson John A , Karlekar Mohana B
Published: July 2021

Background:
Palliative care (PC) is integral in the care of patients with advanced medical illnesses. The significant morbidity and mortality associated with therapeutic hypothermia (TH) after cardiac arrest calls for improved end-of-life care. The goal of this descriptive study was to review our institutional experience with PC consultation in this critically ill population.

Methods:
We conducted a retrospective study of 319 consecutive patients undergoing TH post-cardiac arrest at Vanderbilt University Medical Center from May 2007 to April 2014. We compared intensive care unit characteristics of patients who received PC consultation (n=125) to those who did not (n=194). We performed Wilcoxon rank sum analyses for time on mechanical ventilation and vasopressor support and Pearson chi-square analyses for inpatient mortality, placement of a Do Not Resuscitate (DNR) order and withdrawal of life support.

Results:
The number of TH patients and PC consultations in this population increased over time (Figure 1). In the overall cohort, the mean age was 57.3 years (+/- 15.3), and 61% of patients were male. The PC group was mechanically ventilated longer (mean 5.18 vs. 3.45 days, p<0.001) with a trend toward longer vasopressor support (47.2 vs. 40.8 hours, p=0.055) and higher inpatient mortality (68% vs. 49%, p=0.001). PC consultation was also associated with a higher frequency of DNR order placement during hospitalization (75% vs. 36%, p<0.001) and increased frequency of withdrawal of life support (64% vs. 42%, p<0.001).

Conclusions:
In our TH population, PC consultation increased over time, corresponding to our institution’s expansion of staffing, opening of a PC unit and integration of this service into our published TH protocol. Future studies may delineate the appropriate patient selection for PC consultation to better facilitate goals of care and medical decision-making.
Abstract 18842: Prognostic Impacts of Metabolic Syndrome in Patients With Chronic Heart Failure -A Multicenter Prospective Cohort Study
Authors: Tadaki Soichiro , Sakata Yasuhiko , Miyata Satoshi , Asakura Masanori , Shimada Kazunori , Yamamoto Takeshi , Kadokami Toshiaki , Yasuda Satoshi , Miura Toshiro , Ando Shin-ichi , Yano Masafumi , Kitakaze Masafumi , Daida Hiroyuki , Shimokawa Hiroaki
Published: July 2021

Background:
Metabolic syndrome (MetS) is a pathological condition with a clustering of metabolic components and is substantially associated with increased risk of atherosclerotic cardiovascular diseases. However, prognostic impacts of MetS in patients with chronic heart failure (CHF) remain to be fully elucidated.

Methods and Results:
From the database of our nationwide, multicenter observational study with 10,464 CHF patients in stage A/B/C/D in Japan, 4,764 patients with Stage C/D CHF were enrolled. The prevalence of MetS, according to the Japanese standard diagnostic criteria, was 39.6% (48.7% in males and 20.5% in females), which was almost twice higher as compared with the general population in Japan. CHF patients with MetS were characterized by higher prevalence of male, obesity and lifestyle-related diseases, including diabetes mellitus, hypertension and hyperlipidemia. Although univariate Cox proportional hazard analysis revealed that MetS was not associated with increased incidence of composite of all-cause death and atherosclerotic cardiovascular events (unadjusted HR 0.92; 95% CI 0.81-1.04, P=0.177), multivariate analysis adjusted with body mass index (BMI) alone or fully adjusted with clinical backgrounds showed that MetS was associated with increased incidence of the composite endpoint (BMI-adjusted HR 1.33; 95% CI 1.15-1.55, P<0.001 and full-adjusted HR 1.24; 95% CI 1.05-1.46, P=0.013), particularly in males (BMI-adjusted HR 1.36; 95% CI 1.14-1.62, P<0.001, full-adjusted HR 1.31; 95% CI 1.08-1.59, P=0.005), but not in females (BMI-adjusted HR 1.20; 95% CI 0.86-1.67, P=0.287, full-adjusted HR 1.15; 95% CI 0.80-1.64, P=0.456). Interestingly, the adverse prognostic impacts of MetS were evident in males with BMI<25.0kg/m
2
, but not in those with BMI≥25.0kg/m
2
(
Table
).

Conclusions:
These results indicate that MetS is associated with worse prognosis in patients with Stage C/D CHF, particularly in male patients without obesity.
Abstract 18845: Induced Cardiac Progenitor Cells Differentiate Into Cardiac Lineage Cells in vivo and Improve Survival in Mice post Myocardial Infarction
Authors: Lalit Pratik A , Salick Max R , Nelson Daryl O , Squirrell Jayne M , Shafer Christina M , Shmuck Eric G , Markandeya Yogananda S , Eliceiri Kevin W , Hacker Timothy A , Crone Wendy C , Kyba Michael , Garry Daniel J , Stewart Ron , Thomson James A , Downs Karen M , Lyons Gary E , Kamp Timothy J
Published: July 2021

Several studies have reported reprogramming of fibroblasts (Fibs) to induced cardiomyocytes, and we have recently reprogrammed mouse Fibs to induced cardiac progenitor cells (iCPCs), which may be more favorable for cardiac repair because of their expandability and multipotency. Adult cardiac (AC), lung and tail-tip Fibs from an Nkx2.5-EYFP reporter mouse were reprogrammed using a combination of five defined factors into iCPCs. Transcriptome and immunocytochemistry analysis revealed that iCPCs were cardiac mesoderm-restricted progenitors that expressed CPC markers including Nkx2.5, Gata4, Irx4, Tbx5, Cxcr4, Flk1 etc. iCPCs could be extensively expanded (over 30 passages) while maintaining multipotency to differentiate in vitro into cardiac lineage cells including cardiomyocytes (CMs), smooth muscle cells and endothelial cells. iCPC derived CMs upon co-culture with mESC-derived CMs formed intercellular gap junctions, exhibited calcium transients, and contractions. The purpose of this study was to determine the in vivo potency of iCPCs. Given that the Nkx2.5-EYFP reporter identifies embryonic CPCs, we first tested the embryonic potency of iCPCs using an ex vivo whole embryo culture model injecting cells into the cardiac crescent (CC) of E8.5 mouse embryos and culturing for 24 to 48 hours. GFP labeled AC Fibs were first tested and live imaging revealed that after 24 hours these cells were rejected from the embryo proper and localized to the ecto-placental cone. In contrast, iCPCs reprogrammed from AC Fibs when injected into the CC localized to the developing heart tube and differentiated into MLC2v, αMHC and cardiac actin expressing CMs. Further we injected iCPCs into infarcted adult mouse hearts and determined their regenerative potential after 1-4 wks. The iCPCs significantly improved survival (p<0.01 Mantel-Cox test) in treated animals (75%) as compared to control (11%). Immunohistochemistry revealed that injected iCPCs localized to the scar area and differentiated into cardiac lineage cells including CMs (cardiac actin). These results indicate that lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for cardiac regenerative therapy as well as drug discovery and disease modeling.
Abstract 18889: Circulating microRNA Implicated in the TGF-β Signalling Pathway are Altered in Marfan Syndrome
Authors: Robertson Elizabeth N , Lu Yaxin , Sahagian Alex , Lai Donna , Kekic Murat , Hambly Brett , Jeremy Richmond
Published: July 2021

Thoracic aortic aneurysms in Marfan Syndrome (MFS) caused by mutations in FBN1 are associated with altered TGF-β signaling. Regulation of gene expression can occur at the level of microRNA, which can modify signaling pathways.

We hypothesized that there would be altered microRNA expression in MFS that may alter the expression of signaling proteins.

Total RNA was isolated from whole blood collected in PAXgene® tubes (PreAnalytiX), from 13 MFS patients with aortic dilatation (6F, 7M; Ao Diameter 44.4±6.0mm; Age 39±12yrs) and 10 normal controls (5F, 5M; Ao Diameter 32.3±5mm; Age 34±10yrs). The RNA was reverse transcribed with Human Pool A & B primers and qPCR was performed on the subsequent cDNA using TaqMan® OpenArray® Human miRNA Panels (2454 targets) (ThermoFisher). microRNA expression was considered to be significantly altered if there was >2 fold change (p<0.05) compared to controls. microRNA that were identified as significantly altered were then validated with qPCR using targeted primers on an additional 33 MFS patients (15F, 21M; Ao Diameter 44.2±5.0mm; Age 37±13yrs).

In MFS patients, the OpenArray® identified 30 microRNA were significantly altered (22 up regulated, 8 down regulated). Of these, 12 were confirmed to be altered using targeted qPCR (Graph 1). Three of these have previously been identified as modifiers of the TGF-β signaling pathway (miR 17, miR 93, miR 93*). Three were from the let-7 family (let-7e, let-7f, let-7g), which are involved in terminal cell differentiation and have been implicated in several cardiovascular disease processes. Another three have been shown to be dysregulated in various cardiovascular disease states including atherosclerotic thoracic aortic aneurysm and left ventricular hypertrophy (miR 208, miR 486, miR 378).

This study provides novel evidence for adaptive responses at the post-transcriptional level of gene expression that may modulate aneurysm development in Marfan syndrome.