bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18346: Transcriptional Characterization of Glo1 Knockdown and Transgenic Mouse Models Implies a Role in Cardiometabolic Diseases
Authors: Shu Le , Davis Richard C , Wu Xiuju , Lusis Aldons J , Palmer Abraham A , Yang Xia
Published: July 2021

Accumulation of advanced glycation end-products (AGEs) has been associated with atherosclerosis and diabetes. As the major detoxifying enzyme for AGE precursors, Glyoxalase 1 (Glo1) has been implicated in diabetic complications and more recently in coronary artery disease (CAD). We have recently identified Glo1 as a potential key regulator for an antigen-related gene network that is causal for CAD through an integrative genomics analysis. However, whether Glo1 plays a protective role against cardiometabolic disorders remains controversial. To systematically investigate the impact of Glo1, we performed genome-wide transcriptional profiling of two genetically modified animal models with either Glo1 overexpression in a transgenic (TG) model or Glo1 knockdown (KD), both on C57BL/6J background. For each mouse model, we examined the liver, aorta, adipose and kidney tissues. We found that the Glo1 KD mice which had ~50% reduced Glo1 expression showed much stronger perturbation at transcriptomic level, as compared to Glo1 TG mice. For Glo1 KD mice, significant differential expression was observed across tissues for multiple known cardiometabolic risk genes, including Ide, Cdkn2b and Col4a1, as well as perturbations of lipid metabolic pathways such as PPAR signaling and fatty acid metabolism. We also identified iron transport and collagen formation pathways as specifically enriched in the differentially expressed genes in aorta. When intersected with human GWAS, the Glo1 KD signature genes were found to be enriched for candidate genes associated with lipid levels, type 2 diabetes and coronary heart disease. Lastly, genes perturbed in the Glo1 KD animals had significant overlap with our predicted CAD-antigen gene network in both aorta (p = 0.005) and liver (p = 0.03). This study suggests a functional role of Glo1 in regulating multiple processes relevant to cardiometabolic diseases. Future investigation of these animal models in atherogenesis under diabetic conditions is warranted.
Abstract 18368: Social Network Health Interventions: Can Mayweather and Pacquiao “Knock-out” Health Disparities?
Authors: Cadeiras Martin , Choi Min , Starling Charlotte , Soroya Saad , Bakir Maral , Chang Eleanor , Lim Gene , Mone Tom , Deng Mario , Menezes Ronaldo
Published: July 2021

Background:
A key factor underlying health disparity is the lack of interrelatedness. Social Media has become a very popular form of interaction among both minorities and non-minorities. Any single day millions interact through social media reducing the distance between people from diverse cultural backgrounds. We hypothesized that targeted social network intervention strategies effectively reach minorities to promote cardiovascular disease awareness.

Method:
We used the popular social media platform Twitter to deliver content during regular times or during major events involving people with mixed backgrounds. We first developed a diverse social media community; we then engaged with the audience, identified influencers and delivered different types of content at different moments, linked or unlinked to trending hashtags. We evaluated general social media metrics including impressions, engagement and behavior.

Results:
There was a significant variation in our ability to reach the audience, cause an impression and trigger a behavior. Trending Hashtag targeting was associated with the highest exposure, however with low engagement rates. Influencer-driven content delivery was linked to highest enrichment and intermediate exposure while non-targeted content delivery was associated with the lowest exposure and engagement rates. Other factors including the time of delivery, quality, type and content were also important determinants of effectiveness. The figure shows an example of a single “tweet” during the May 2, 2015 Mayweather-Pacquiao Box event and the exposed network.

Conclusion:
Carefully planned Social Network Health interventions are highly effective to reach and engage mixed audiences and influence peers to increase awareness about cardiovascular health. Social media and big data analytics allows the development of novel strategies responsive to the specific needs of culturally diverse audiences.
Abstract 18463: A Novel Grading System for Post-implant Right Heart Failure Correlates With One-year Survival After Continuous-flow Left Ventricular Assist Device
Authors: Grandin E. Wilson , Mazurek Jeremy A , Zamani Payman , Troutman Gregory S , Birati Edo Y , Atluri Pavan , Margulies Kenneth B , Rame J. Eduardo
Published: July 2021

Introduction:
Right ventricular failure (RVF) is a common complication after continuous-flow left ventricular assist device (cf-LVAD) and carries an increased risk of mortality. There is a spectrum of early RVF and the optimal definition is controversial, hindering efforts to identify relevant risk factors. Correlating the severity of RVF with outcome after LVAD could inform clinical criteria for this important syndrome.

Hypothesis:
Increasing severity of RVF will be associated with worse one-year survival.

Methods:
We identified 196 patients undergoing isolated durable cf-LVAD since 2005 at our center. Post-implant RVF was graded as absent, mild (requiring inotropes for 14-20 days), moderate (requiring inotropes for ≥ 21 days), or severe (requiring unplanned RVAD at any time during the index hospitalization). One-year survival, censored at the time of heart transplant or VAD explant for recovery, was examined using Kaplan-Meier plots, the log-rank test, and Cox proportional-hazard modeling.

Results:
Seventy-three patients (37.2%) developed RVF: 35 (17.9%) mild, 24 (12.2%) moderate, and 14 (7.1%) severe. The median follow-up time was 266 days (IQR: 81-761), and 51 patients (26%) died within one year. Compared to patients without RVF, those with mild RVF had similar one-year survival (HR 0.69, 95%CI:0.26-1.80, p=0.45) while the risk of death was substantially increased in patients with moderate (HR 2.65, 95%CI:1.27-5.54, p=0.009) and severe RVF (HR 8.16, 95%CI:3.97-16.76, p<0.0001). The severity of RVF was strongly associated with one-year mortality, which persisted in multivariate modeling (Figure).

Conclusions:
A simple grading system for the severity of early RVF is strongly associated with one-year survival after cf-LVAD, supporting the notion that there is a spectrum of post-implant RVF. If confirmed in other cohorts, targeting risk-prediction and risk-mitigation strategies for moderate and severe RVF could improve post-LVAD survival.
Abstract 18494: WNT Mediated Regulation Signals IN Chamber-Specific Neonatal Heart Maturation and Disease
Authors: Touma Marlin , Kang Xuedong , Zhao Yan , Cass Ashley , Biniwale Reshma , Xiao Xinshu , Reemtsen Brian , Wang Yibin
Published: July 2021

Background:
Chamber-specific and temporally orchestrated perinatal cardiac growth and maturation is critical to functional adaptation of heart to the dramatic changes in hemodynamic load and nutrient environment, and perturbation of this process may have major implications in congenital heart defects (CHDs). However, the responsible molecular regulatory mechanisms are still poorly understood.

Objective:
To determine the factors that control chamber specificity of neonatal heart growth during perinatal maturation

Methods:
Total transcriptome was analyzed from deep RNA-seq in male newborn mouse (C57BL) left ventricle (LV) and right ventricle (RV) at postnatal day 0, 3 and 7. Functional validation was performed in Neonatal Rat Ventricular Myocytes (NRVMs) and intact neonatal mice.

Results:
Chamber specific- regulation of cell cycle genes was correlated with chamber specific- expression of the non-canonical Wnt11. Exogenous expression of Wnt11 induced maturation markers and suppressed cell cycle genes in myocytes. In contrast, targeted Wnt11 inhibition induced myocyte proliferation associated with upregulated cell cycle genes both in cultured NRVMs and in the intact heart. Notably, Wnt inhibition also significantly enhanced β-catenin phosphorylation without impacting JNK, PKCα, or p38- activities. Remarkably, both Wnt mediated signals and cell cycle markers were altered in heart samples from infants cyanotic CHDs. Furthermore, hypoxia exposure suppressed Wnt11 and induced cell cycle genes in cultured cardiomyocytes.

Conclusions:
Differential expression of Wnt11 and downstream cell cycle genes are novel molecular basis for chamber specific maturation. Wnt11 mediated-signaling has potential impact on cyanotic CHDs. Differential role of Wnt signaling in chamber specific post-natal heart maturation can lead to potential chamber-specific diagnoses and therapies for congenital heart diseases.
Abstract 18600: Very Long-term Clinical Outcome After Sirolimus-eluting Stent Implantation
Authors: Kuramitsu Shoichi , Matsuda Hiroaki , Jinnouchi Hiroyuki , Hiromasa Takashi , Domei Takenori , Soga Yoshimitsu , Shirai Shinichi , Ando Kenji
Published: July 2021

Background:
Late adverse events such as stent thrombosis (ST) or late target-lesion revascularization (TLR) after sirolimus-eluting stents (SES) implantation remain an important concern. However, there is little data regarding clinical outcome beyond 5 years after SES implantation. We sought to assess very long-term clinical outcome after SES implantation.

Methods:
Between April 2004 and December 2006, a total of 686 patients with 894 lesions underwent percutaneous coronary intervention only with SES. We assessed the major adverse cardiac events (MACE), defined as a composite of cardiac death, TLR, definite ST.

Results:
At 10 years, cumulative incidence of MACE and cardiac death were 50.8% and 8.2%, respectively. Cumulative incidence of TLR within 1 year was 12.6%. However, late TLR beyond 1 year continued to occur without attenuation up to 10 years (2.3%/year) (5 years, 22.8%; 10 years, 33.3%). Cumulative incidence of definite ST was low (30 days, 0.3%; 1 year, 0.9%; 5 years, 1.8%; and 10 years, 3.3%), whereas definite ST also continued to occur without attenuation (0.27%/year). The predictors of MACE were hemodialysis (hazard ratio [HR] 2.87, 95% confidence intervals [CI]:1.76-4.53, p <0.001) and age ≥75 years (HR 1.72, 95% CI: 1.31-2.26, p <0.001).

Conclusions:
Late catch-up phenomenon regarding ST and TLR continued up to 10 years without attenuation. Careful clinical follow-up is required in patients treated with SES beyond 5 years.
Abstract 18637: Recurrence Quantification Analysis to Distinguish Active From Passive Mechanisms of CFAEs During Catheter Ablation of Atrial Fibrillation
Authors: Baher Alex , Gehi Anil K , Kumar Prabhat , Chung Eugene , Buck Benjamin H , Mounsey John P , Akar Joe G , Hummel James P
Published: July 2021

Background:
Ablation of complex fractionated atrial electrograms (CFAEs) is controversial, primarily because of difficulty in visually distinguishing CFAEs representing an active site of driver activity from a passive site of double potentials, wave break, and/or slow conduction. We hypothesized that CFAEs within rotors in atrial fibrillation (AF) would exhibit highly recurrent behavior compared with CFAEs remote from these driver regions.

Methods:
Active and passive mechanisms of CFAE formation were simulated in several 2D 7.5 x 7.5 cm modified Luo-Rudy 1 models. CFAEs within areas of rotors were considered active, while those caused by wave break, slow conduction or double potentials remote from rotors were considered passive. Clinical signals were also collected during catheter ablation of paroxysmal AF (n=8 patients). An active driver CFAE site was defined by termination of AF with ablation followed by non-inducibility. A passive site was defined as CFAE occurring remotely. Detection of CFAEs was based on mean cycle length (MCL) calculated from 4 second windows using -dV/dt for detection (40ms refractory period/10ms maximum EGM width for simulations; 45ms/15ms respectively for clinical signals). Recurrence quantification analysis (RQA) was performed on discrete time series of simulated and clinical CFAE activations.

Results:
RQA was performed on 20 simulated EGMs. MCL was similar in both active and passive CFAEs (74±11ms and 78±6ms respectively, p=NS), but recurrence was significantly higher in active compared to passive sites (%recurrence: 61±22% active, 4±6% passive, p<0.01). In patients with AF, the driver sites were all located within the pulmonary vein antra while passive CFAEs were remote. The MCL of CFAEs at active driver sites was similar to that of passive sites (100±13ms active, 98±17ms passive, p=NS), but recurrence was significantly higher in the active driver sites (%recurrence: 18±15% active, 2±1% passive, p=0.02).

Conclusion:
CFAEs may occur due to either active or passive mechanisms. Sites within rotors or focal drivers of AF are more likely to exhibit recurrent patterns. RQA may be a powerful tool to differentiate driver from bystander CFAEs enabling more efficient targeting for ablation.
Abstract 18836: Integrative Pathway Analysis of Genome-wide Association Studies of Carotid Plaque Phenotypes
Authors: Zhao Yuqi , van der Laan Sander M , den Ruijter Hester M , Haitjema Saskia , Pasterkamp Gerard , Yang Xia
Published: July 2021

Introduction:
The composition of atherosclerotic plaques differs between individuals and contributes to the incidence of cardiovascular events. A better understanding of the biology underlying variability in plaque composition will provide insights into the progression of cardiovascular diseases. We carried out genome-wide association studies (GWAS) to investigate the genetic underpinnings of the plaque.

Methods:
We included carotid endarterectomy patients from the Athero-Express Biobank Study (n = 1,439). We quantified the percentage of macrophages and smooth muscle cells, the number of intraplaque vessels, the amount of collagen and calcification, the atheroma size, and the presence of plaque hemorrhage. GWAS was performed for all 9 plaque traits, and combined with summary level from GWAS consortia data on coronary artery disease (CAD), and ischemic stroke. Next, these data were integrated with data from human expression quantitative trait loci analyses, and pathway analyses of the plaque traits.

Results:
No individual locus reached genome-wide significance, likely due to the moderate sample size involved. However, it is plausible that perturbations of diverse pathways by a large number of genetic loci with small effects together contribute to the regulation of plaque composition. We identified 42-97 pathways significantly associated with each plaque phenotype, with many specific to each trait, supporting the presence of unique genetic components of individual plaque phenotypes. We also detected 39 pathways associated with at least four plaque phenotypes, among which were CAD-associated processes such as “extracellular matrix”, “complement and coagulation cascades” and stroke-associated pathways such as “Toll-like receptor signaling”. Interestingly, we found that smooth muscle cell percentage and atheroma size shared more genetic loci and pathways with intraplaque hemorrhage (such as “Sphingolipid metabolism”); the latter trait is associated with secondary cardiovascular events.

Conclusion:
There are genetic correlations among plaque phenotypes as well as between plaque phenotypes that provide mechanistic insight into the composition of the plaque and progression to secondary events.
Abstract 18844: Diagnosis of Thin-capped Fibroatheromas in Intravascular Optical Coherence Tomography Images: Effects of Light Scattering
Authors: Hoyt Taylor , Phipps Jennifer , Vela Deborah , Wang Tianyi , Buja Maximillian , Jang Ik-Kyung , Milner Thomas , Feldman Marc
Published: July 2021

Objectives:
Intravascular optical coherence tomography (IVOCT) images are recorded by detecting light backscattered within coronary arteries. We hypothesize that non- thin-cap fibroatheroma (TCFA) etiologies may scatter light to create the false appearance of IVOCT TCFA.

Background:
Conflicting reports are recognized about the accuracy of IVOCT for TCFA detection.

Methods:
Ten human cadaver hearts were imaged with IVOCT (N=14 arteries). Coronary arteries were sectioned at 120 μm intervals. IVOCT and histologic TCFA were co-registered and compared.

Results:
Of 21 IVOCT TCFAs identified by two independent IVOCT core labs (fibrous cap <65 μm, lipid arc >90°), only 8 were true histologic TCFA. Foam cell infiltration was responsible for 62% of cases in which either thick-capped fibroatheromas (ThKFAs) appeared like TCFAs or arterial tissue appeared like TCFAs when no lipid core was present. Other false IVOCT TCFA etiologies included SMC-rich fibrous tissue (15%) and loose connective tissue (8%). If the lipid arc >90° criterion was disregarded, 45 IVOCT TCFAs were identified, and sensitivity of IVOCT TCFA detection increased from 53% to 88%; specificity remained high at 93%, and the presence of a new IVOCT image feature called “bright streaks” increased positive predictive value (PPV) to 53%. New mechanisms for light scattering are proposed to explain the low PPV of IVOCT to identify true TCFA (44%), and explain why other plaque components can masquerade as IVOCT TCFA.

Conclusions:
IVOCT can exhibit up to 88% sensitivity and 98% specificity to detect TCFA, but PPV is limited due to multiple etiologies that cause light scattering similar to true TCFA. Disregarding the lipid arc >90° IVOCT TCFA requirement, and the identification of a new feature, bright steaks, can enhance the ability of IVOCT to detect TCFA. Combining IVOCT with another imaging modality that more specifically recognizes lipid will be important for increasing PPV in the future.
Abstract 18893: ADP Receptor Inhibitor Therapy Use Beyond 12 Months in Community Practice: Results From the Translate-ACS Registry
Authors: Hansen Jonathan D , McCoy Lisa A , Cohen David J , Henry Timothy D , Fonarow Gregg , Effron Mark B , Zettler Marjorie E , Baker Brian A , Peterson Eric D , Wang Tracy Y
Published: July 2021

Background:
Prolonged use of ADP receptor inhibitors (ADPri) beyond 1 year following myocardial infarction (MI) and percutaneous coronary intervention (PCI) is supported by recent studies such as DAPT and PEGASUS. In community practice, how often and in which patients prolonged ADPri therapy is used is poorly understood.

Methods:
Using data from the TRANSLATE-ACS observational study, we examined prevalence of ADPri continuation beyond 1 year post-MI in routine US practice (2010-2012) and used multivariable logistic regression to identify patient characteristics associated with ADPri use beyond 1 year.

Results:
Of 8,749 patients alive and still on ADPri at 12 months post-MI, 6,627 (76%) were still on ADPri at the 15-month interview. ADPri use beyond 1 year occurred more frequently among black vs. white patients (82.7% vs. 75.1%), patients with prior PCI (85.4% vs. 73.2%) or prior CABG (87.0% vs. 74.5%), and those with multivessel disease (78.8% vs. 72.7%, p<0.001 for all). Use of drug eluting stents did not affect likelihood of prolonged ADPri use, 77% in both groups (p= 0.98). Patients discharged on prasugrel/ticagrelor were less likely to continue their ADPri beyond 1 year than those discharged on clopidogrel (71.1% vs. 77.9%, p<0.001). Unplanned coronary revascularization occurred more commonly within the first 1 year post-MI among patients who continued on ADPri beyond 1 year (14.3% vs. 4.6%, p<0.001), but the rate of BARC 2+ bleeding was lower (19.9% vs. 22.3%, p=0.02) than those who stopped ADPri at 1 year. These variables remained independent factors associated with post-1 year ADPri continuation in multivariable modeling (Figure).

Conclusion:
In routine US practice, the majority of MI patients who underwent PCI were already receiving prolonged ADPri therapy beyond 1 year even before DAPT and PEGASUS trials. Post-discharge unplanned revascularization and bleeding appear to be the strongest predictors for and against prolonged ADPri use, respectively.
Abstract 18942: Inhibition of β-arrestin 1 Prevents post-MI Maladaptive Ventricular Remodeling
Authors: Razzaque Md Abdur , Xu Xianyao , Badami Abbasali , Klepacz Peter , Han Mei , Philip Jennifer L , Akhter Shahab A
Published: July 2021

Remote (non-infarct) territory fibrosis is a significant cause of post-myocardial infarction (MI) heart failure (HF). We have previously shown that increased activity of β-arrestin 1 in adult human cardiac fibroblasts (CF) isolated from failing hearts is an important mechanism of cardiac fibrosis. This study investigates the potential therapeutic role of β-arrestin 1 inhibition on CF biology in vivo. Adult male rats underwent LAD ligation to induce post-MI HF. β-arrestin 1 was inhibited by intra-coronary adenoviral-mediated delivery of a β-arrestin 1 inhibitor (Ad-Barr1ct) immediately following LAD ligation (n=11). Ad-Barr1ct contains a rat β-arrestin 1 C-terminal fragment (aa. 369-418). Control rats received a null adenovirus (n=10). Animals were studied prior to and up to 8 weeks (wks) post-MI and adenoviral delivery. There was a significant decline in LV function at 8 wks post-MI in Ad-null rats vs. pre-MI. Remote territory (non-infarct area) fibrosis increased by 8 wks post-MI consistent with adverse remodeling. Intra-coronary delivery of Ad-Barr1ct following LAD ligation significantly inhibited post-MI LV dysfunction vs. Ad-Null as measured by improved fractional shortening and ejection fraction. Ad-Barr1ct also decreased peri-infarct and remote territory fibrosis. Consistent with these findings, Ad-arr1ct resulted in decreased α-SMA, collagen I, collegen III and fibronectin expression in CF isolated 8 wks post-MI vs. Ad-Null providing evidence of decreased post-MI CF activation and myofibroblast transformation with Ad-Barr1ct. Targeted inhibition of β-arrestin 1 in the heart may represent a novel therapeutic approach to prevent pathological fibrosis and maladaptive remodeling post-MI.
Abstract 18996: Impact of Infarct Size on Left Ventricular Diastolic Function Following Acute Myocardial Infarction
Authors: Lin Andrew , Kwan Christopher , Guppy-Coles Kristyan , Sippel Joanne , Atherton John , Prasad Sandhir
Published: July 2021

Introduction:
Severe left ventricular diastolic dysfunction is associated with worse prognosis after acute myocardial infarction (MI). Twenty percent of patients have a restrictive filling pattern (RFP) following MI, and this is associated with a fourfold increase in mortality. The determinants of diastolic function in this setting are not well defined.

Aim:
We sought to determine the correlation between enzymatic infarct size and RFP in patients with a first ever MI. We hypothesized that a larger infarct size would result in greater impairment of left ventricular diastolic function.

Methods:
Data analysis was performed on consecutive patients admitted with first ever non-ST elevation MI (NSTEMI) or ST-elevation MI (STEMI) to a single large tertiary referral hospital from January 2013 to December 2014. All patients underwent coronary angiography during the index admission. Infarct size was determined by peak troponin I. Doppler transmitral flow pattern was obtained from the initial transthoracic echocardiogram performed within 48 hours of admission. RFP was defined as: E/A ratio >2.0 and/or E-wave deceleration time <160ms (American Society of Echocardiography Guidelines 2009).

Results:
Data were available on 645 consecutive patients who underwent coronary angiography for MI. We excluded 160 patients with a previous MI. Of the remaining 485 patients (mean age 62±13 years; mean left ventricular ejection fraction (LVEF) 53±12%), there were 338 NSTEMIs (70%) and 147 STEMIs (30%). PCI was performed in 360 (74%) patients (single vessel (82%), ≥2 vessels (18%)); coronary artery bypass surgery in 58 (13%); and medical management in 67 (13%). Sixty-nine patients (14.4%) had RFP; 52% of these had a LVEF ≥45%. Peak troponin I levels were higher in the RFP group (31.8±30.9μg/L vs 16.8±25.2μg/L, p=<0.001). On multivariate analysis, infarct size by peak troponin I (OR 1.02, 95%CI 1.00-1.03, p=0.026) and low LVEF (OR 0.95, 95%CI 0.91-0.99, p=0.015) were the only independent predictors of RFP.

Conclusion:
Infarct size was a major determinant of diastolic dysfunction following first ever MI. Whilst LV systolic dysfunction was strongly associated with impaired diastolic function, 52% of patients with severe diastolic dysfunction had relatively preserved LVEF.
Abstract 19013: Longitudinal Changes in Ankle and Brachial Pressures in a Community Dwelling Population: Results From the Baltimore Longitudinal Study of Aging
Authors: AlGhatrif Majd , Oberdier Matt T , Lakatta Edward , Studenski Stephani , Ferrucci Luigi
Published: July 2021

Reduction in ankle-brachial index (ABI) is a marker of peripheral arterial disease (PAD) and is attributed to flow limiting lesions. It is unclear whether the major changes in blood pressure with aging affect ankle and brachial pressures differently and result in changes in ABI with advancing age. We studies 719 participants (2176 observations) from the Baltimore Longitudinal Study of Aging who were free of clinical cardiovascular (CV) disease at baseline. Ankle and brachial systolic blood pressures (SBP) and their index (ABI) were measured in both sides using oscillometric device (Colin VP2000) and averages of both sides were calculated. Linear mixed effects models were used with age expressed as Entry-Age and Follow up Time (Time) to test for non-linear longitudinal changes in these parameters. About 15% of the sample had diabetes at baseline, 3.5% were current and 38% were former smokers. Adjusting for diabetes, smoking status and anti-hypertensive medications, men had greater ABI than women (B= 0.02, P=<0.001) with no statistically significant differences in trajectories. ABI changed with aging with statistically significant Entry-age X Time terms (P<0.01). Model predicted values (Figure 1) shows a longitudinal decline in ABI after the age of 65. In men, this decline was a result of a longitudinal decline in ankle SBP vs plateauing brachial SBP. In women, the decline in ABI was a result of a greater increase in brachial SBP compared to ankle SBP. In conclusion, aging is independently associated with a decline in ABI in a healthy population free of clinical C disease. There were gender different in the pressure profiles yielding this reduction in ABI. A pathological reduction in ABI could represent an exaggerated age-associated hemodynamic alterations and not exclusively due to flow limiting lesions. Further studies are needed to understand the underlying alterations in arterial properties and the clinical significance of this subclinical reduction in ABI.
Abstract 19091: Prognosis of Patients With Out-of-hospital Refractory Cardiac Arrest Referred for Extracorporeal Life Support: An Observational Study
Authors: Ursat Cecile , Tilliette Marie-Ange , Groizard Charles , Cassuto Margot , Ozguler Anna , Baer Michel , Loeb Thomas
Published: July 2021

Introduction:
In case of no return of spontaneous circulation (ROSC) after conventional cardio-pulmonary resuscitation (CPR), out-of-hospital cardiac arrest (OHCA) patients could be referred for extracorporeal life support (ECLS). Guidelines have been published concerning this specific situation (1). The aim of our study was to describe the prognosis of OHCA patients and verify if referral to ECLS was compliant with these recommendations mainly studying time intervals (no-flow < 5 min, low-flow < 100 min).

Methods:
A prospective survey on OHCA referred to ECLS was implemented from 03/01/12 until 06/11/15 in an Emergency Medical Service (EMS) located in Paris area (France). This survey included 43 patients referred to hospital for ECLS. Variables were given as means and percentages.

Results:
Patients referred to ECLS were more often men (77%), with a mean age of 51 years old. Most of 43 OHCA occurred at home (51%), although 26% occurred on public area and 16% at workplace. In 40% of cases, CPR was performed by a witness and in 33% by a health professional.

A first Basic Life Support ambulance arrived on scene within 7 min 50 sec, whereas EMS ambulance arrived on scene within 18 min 27 sec after OHCA. At EMS arrival on scene, patients were on asystole (44%), ventricular fibrillation (37%), and on spontaneous circulation (12%). The no-flow time interval was 4 min 10 sec on average (6 patients had a no-flow over 5 min) with 43% of patients with no no-flow. Low-flow time-interval was 44 min.

External electric shock was delivered before EMS arrival on 21% of cases, and EMS itself delivered a shock in 40% of cases. Epinephrine was used for all patients, 10.35 mg on average.

No patient survived OHCA after referral to ECLS.

Discussion:
Although this is a small series of 43 patients, no OHCA patient referred to ECLS survived. These results are mainly due to a non-shockable initial condition or too long no-flow time intervals.

In order to improve the outcome and bring benefit to the proper expected patients through a cost-effective pathway, we released a reminder of the right recommendations in our EMS. (1) Riou B., Adnet F., Baud F et al. A. Recommandation sur les indications de l’assistance circulatoire dans le traitement des arrêts cardiaques réfractaires. Ann Fr Anesth Réanim 2009 ; 28 : 182-6.
Abstract 19104: Impact of the Ross Procedure on Long Term Survival in Adults: A 25-year Single-center Follow-up Study
Authors: Martin Elisabeth , Mohammadi Siamak , Jacques Frederic , Voisine Pierre , Doyle Daniel , Perron Jean
Published: July 2021

Introduction:
It has been accepted that early and mid-term survival of patients who underwent the Ross procedure is comparable to that of the general population. We reviewed our 25-year experience with the Ross procedure with the aim of defining long-term survival rates and freedom from reintervention.

Hypothesis:
We assessed the hypothesis that long-term survival following the Ross procedure was comparable to the general population when matched on age and gender.

Methods:
Between 1990 and 2015, the Ross procedure was performed on 310 consecutive adult patients in a single center. All patients were prospectively added in a dedicated cardiac surgery registry and every patient was included in the analysis. Complete postoperative clinical examination and history were obtained and transthoracic echocardiogram was performed according to a standardized protocol or when clinically indicated. There was no loss to follow-up. Median follow-up duration was 12.4 years and ranged up to 25 years. Approximately 58% of the study population was followed for more than 10 years.

Results:
The mean age of our cohort was 40.3 years and included 187 (60.3%) male patients. Congenital aortic valve disease was diagnosed in 77.1%. Indications for surgery were aortic stenosis in 64.6%, aortic insufficiency in 23.4% and mixed aortic disease in 12%. There were 4 (1.3%) hospital deaths and 26 (8.4%) late deaths. Survival at 10 and 25 years was 92.5% and 79.7% respectively. Freedom from pulmonary autograft reintervention was 97.5% and 48% at 10 and 25 years. Freedom from homograft-related reoperation was 99.1% and 69.9% at 10 and 25 years. Ross-related reoperation did not reduce long-term survival in our study population. However, compared to the general population, survival rate was significantly lower in patients following the Ross procedure when matched on age and gender.

Conclusions:
In conclusion, the Ross procedure is associated with excellent long-term survival, regardless of the need for surgical reintervention. However, long-term survival rates are lower in these patients when compared to matched individuals.
Abstract 19147: Fast, Free-breathing, Heart-rate Independent Quantitative Myocardial Oxygenation MRI at 3T for Detecting Ischemic Heart Disease Without Contrast Agents With Simultaneous 13N-Ammonia PET Validation
Authors: Yang Hsin-Jung , Dey Damini , Syskes Jane , Butler John , Bi Xiaoming , Kali Avinash , Cokic Ivan , Sharif Behzad , Tsaftaris Sotirios , Li Debiao , Slomka Piotr , Prato Frank , Dharmakumar Rohan
Published: July 2021

Introduction:
Myocardial BOLD MRI is an emerging non-contrast approach for the assessment of ischemic heart disease. Current BOLD MR methods are limited in part by poor spatial coverage, heart rate dependency and image artifacts, particularly at 3T. To address these limitations, we developed a heart-rate independent, free-breathing 3D T2 mapping technique at 3T that utilizes near perfect imaging efficiency, which can be completed within 3 minutes. We tested our approach in a canine model and validated our findings with simultaneously acquired 13N-ammonia PET perfusion data in a clinical hybrid PET-MR system.

Methods:
Healthy dogs (n=8) were studied with a state of the art PET-MR system (Siemens Healthcare). For validation, dynamic 13N-ammonia PET scans were simultaneously acquired with BOLD MR data. PET images were analyzed using qPET (Cedars-Sinai Medical Center). T2 values were measured from basal, mid and apical slices at rest and adenosine stress in BOLD images. Myocardial BOLD reserve (T2(stress):T2(rest)) and perfusion reserve (Q(stress):Q(rest)) were computed on a slice basis and regressed.

Results:
A representative set of BOLD and PET images acquired at rest and adenosine stress are shown in Fig. 2. T2 measures at stress were significantly greater than at rest (T2: 39.5±2.5 ms (rest) vs. 44.0±3.3 ms (stress), p<0.05)); similar results were observed for Q (Q: 0.8±0.1 ml/mg/min (rest) vs. 2.0±0.9 ml/mg/min (stress); p<0.05). Linear regression of BOLD and perfusion reserves showed high correlation (R2=0.6, p<0.05).

Conclusions:
This is the first study to examine myocardial BOLD MRI with simultaneously acquired PET perfusion data. Our findings showed that BOLD response is highly correlated with PET perfusion suggesting that the proposed BOLD MR method is a viable non-contrast approach for imaging myocardial perfusion. Further studies are required to examine its utility in the setting of ischemic heart disease.
Abstract 19218: Complete Intimal Healing of the Renal Arteries After Radio-frequency Renal Denervation in Long-term Follow-up by Optical Coherence Tomography
Authors: Roleder Tomasz , Skowerski Mariusz , Wiecek Andrzej , Adamczak Marcin , Czerwienska Beata , Wanha Wojciech , Jadczyk Tomasz , Partyka Lukasz , Smolka Grzegorz , Ochala Andrzej , Dudek Dariusz , Tendera Michal , Gasior Zbigniew , Wojakowski Wojciech
Published: July 2021

Intoduction:
Although radiofrequency renal denervation (RF-RND) may cause acute spasm, intimal injury and thrombus formation, there are no data on long-term renal artery (RA) healing.

Hypothesis:
Aim of this study was to assess the RA healing after RF-RND by optical coherence tomography (OCT) imaging and quantitative contrast angiography (QCA) at long-term follow-up.

Methods:
A single center registry enrolled 12 patients (22 RA) with refractory hypertension previously treated with RF-RND (Symplicity, Medtronic). Imaging studies (QCA and OCT) were done at (mean±SD) 18.41±5.83 months after RF-RND.

Results:
No adverse events or complications were noted during the follow-up. Ten patients (83%) achieved significant reductions of blood pressure by ≥10 mmHg on 4.50 ± 1.08 medications per patient. OCT analysis involved 518 mm of pullbacks and 518 cross-sections. There were 26 spots of focal intimal thickening found in 10 (83%) patients in 14 (64%) arteries and calcifications in 2 (9%) of treated RA. The mean area of focal intimal thickening was 0.054±0.033 mm2 and it was limited to the intimal layer. No vessel dissection, thrombus, intimal tear or acute vasospasms were observed during the OCT analysis. The QCA revealed that minimal lumen and proximal lumen diameter were smaller after the RND and this difference was persistent at follow-up, as compared to measurements obtained before RND [6.21±1.01 vs. 5.61 ± 0.60, p=0.005 and 5.53±0.99 vs. 5.15±0.67, p=0.034, respectively].

Conclusions:
There is a favorable long-term vessel healing after RF-RND without significant RA stenosis. Only focal intimal thickening and a modest reduction of the minimal lumen diameter may be observed in long-term and their relation to the RND procedure needs further studies.
Abstract 19288: Acute and Chronic Affects of Indoor Air Pollution on Endothelial Function
Authors: Miele Catherine H , Iantorno Micaela , Weiss Robert G , Gilman Robert H , Valdivia Guelki , Wise Robert A , Davila-Roman Victor G , Checkley William
Published: July 2021

Objective:
Pollution exposure has been linked to accelerated atherosclerosis. Endothelial dysfunction is a reversible indicator for early atherosclerosis, but it is unknown if indoor air pollution from biomass fuel cookstoves is associated with acute and chronic endothelial dysfunction.

Methods:
We enrolled 76 adults in Puno, Peru (3825 m above sea level); 56 from a rural community that almost exclusively use biomass fuels for cooking (biomass fuel users) and 20 from urban communities that use clean fuels for cooking (clean fuel users). We measured flow-mediated dilatation (FMD) of the brachial artery before and after cooking. We compared baseline FMD in biomass vs. clean fuel users and evaluated for acute effects of cooking by looking and changes in FMD before and after cooking with biomass vs. clean fuels

Results:
Mean age was 53 ± 9.1 years with 54% male. Biomass fuel users had similar age, blood pressure, and BMI but had lower LDL-cholesterol compared to clean fuel users (p<0.05). Mean baseline FMD was 5.2 ± 2.3% vs. 6.3 ± 3.2% in clean vs. biomass fuel users respectively (p=0.22). Adjusting for age, sex, blood pressure, BMI, and LDL-cholesterol demonstrated no difference in baseline FMD between biomass and clean fuel users (p=0.92). Among biomass fuel users, mean FMD dropped to 3.8 ± 3.0% after one hour of biomass fuel smoke exposure from cooking (p<0.001). This did not occur when FMD was repeated in clean fuel users one hour after baseline exam (FMD: 4.9 ± 2.9%, p=0.29).

Conclusion:
Biomass fuel smoke exposure causes acute decrease in endothelial function in this population with already abnormal function. However, we found no differences in baseline endothelial function in these two heterogeneous populations. Larger studies are needed to determine if biomass fuel exposure is associated with chronic endothelial dysfunction and if interventions aimed to decrease biomass fuel smoke exposure can improve endothelial function and thus cardiovascular mortality.
Abstract 19315: Geometry, Reintervention, and Growth Patterns in the Reconstructed Aortic Arch With Interdigitating Technique in Patients With Hypoplastic Left Heart Syndrome and Variants
Authors: Haller Christoph , Chetan Devin , Doyle Matthew , Saedi Arezou , Parker Rachel , Van Arsdell Glen , Honjo Osami
Published: July 2021

Objectives:
The interdigitating technique in aortic arch reconstruction in hypoplastic left heart syndrome and variants (HLHS) is very effective to minimize the recoarctation rate. Little is known on the aortic arch’s growth characteristics and the resulting clinical impact.

Methods:
139 patients with HLHS underwent staged palliation between 2007 and 2014. 72 patients who underwent Norwood arch reconstruction with the interdigitating technique were included. Dimensions of the ascending aorta (AA), transverse arch (TA), isthmus (IA) and descending aorta (DA) in pre-stage II (P1, n=50) and pre-Fontan (P2, n=21) angiograms were measured and geometry and growth characteristics of the aortic arches were analyzed. Correlations between the aortic dimensions and clinical outcomes were assessed.

Results:
There were significant increases in diameters in all segments between P1 and P2 (p < .0005). The z-scores in AA, TA and IA were unchanged between P1 and P2 (p = .931/.425/.121), but increased significantly in DA at P2 (p = .039). The percent increase in diameters were comparable among 4 segments (mean, 146% in IA, 144 in DA, p=.648). There were correlations in dimensions and z-scores between P1 and P2 in AA (p = .029/.013) and TA (p = .001/ < .0005), but no correlations were found in IA (p = .140/.747) and DA (p = .075/.432). The most significant tapering in the arch dimension occurred between TA and IA in both time points (P1, 67.3% vs. P2, 61.1%, p=.303). The reverse coarctation index (TA/IA ratio) at P1 (r = .381, p = .042), but not coarctation index (CoAI, IA/DA ratio) at P1 (p = .774) had a significant correlation with post-stage II ventricular function. Balloon dilatation for recoarctation was needed in 2 (2.7%) patients prior to stage II palliation. CoAI at P1 was a predictor for ventricular dysfunction at latest follow-up (p=.017).

Conclusions:
Aortic arch growth after interdigitating reconstruction in HLHS is substantial and relatively constant. The isthmus growth is proportional to other segments. Overall reintervention rate for recoarctation is exceptionally low. CoAI prior to stage II palliation may be associated with long-term ventricular function.
Abstract 19496: A New Exercise Testing Model Performs Better than the Duke Treadmill Score to Identify Patients at Increased Risk for All-cause Mortality
Authors: Cremer Paul C , Wu Yuping , Pierson Lee , Brennan Danielle , Cho Leslie
Published: July 2021

Background:
Cardiovascular mortality has declined with advances in primary and secondary prevention, yet risk assessment for patients undergoing exercise treadmill testing is generally still based upon the Duke Treadmill Score (DTS). We hypothesized that a new risk score would perform better than the DTS.

Methods:
We studied 59,877 consecutive patients who had exercise testing between Januray 1, 2000 and October 27, 2011 with the sample divided equally into derivation and validation cohorts. The primary outcome was all-cause mortality. Risk scores for men and women were developed from Cox proportional hazards models. The DTS was compared to new risk scores in the validation cohort with C-statistics, category-free net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results:
Over a median follow-up of 8 years, there were 2,521 deaths. In the multivariable model, age, exercise capacity, heart rate recovery, weight, and renal disease were associated with mortality in men and women. Diabetes mellitus and history of smoking were associated with mortality in women whereas heart failure, current smoking, and hypertension were associated with mortality in men. C-statistics, NRI, and IDI were all improved with the new risk scores (Table). In particular, the new risk scores correctly reclassified patients with events, especially in women. Patients in the highest tertile of risk score also had substantial mortality during follow-up (Figure).

Conclusions:
We have developed new risk scores for men and women that perform better than the DTS, particularly in patients at the highest risk for all-cause mortality.
Abstract 19542: A North American Survey of Public Opinion on the Acceptability of Crowdsourcing Basic Life Support for Out-of-hospital Cardiac Arrest
Authors: Dainty Katie N , Brooks Steven
Published: July 2021

Introduction:
Performance of bystander CPR and early defibrillation following out-of-hospital cardiac arrest (OHCA) have been shown to increase the odds of survival to hospital discharge more than 3-fold. The PulsePoint Respond™ Application (App) is a novel system that can be implemented by EMS to crowdsource basic life support for victims of OHCA. The system sends cardiac arrest notifications to a user’s mobile device which includes the location of the emergency and nearby public access defibrillators to facilitate bystander CPR and AED use while EMS personnel are en route. We conducted a North American survey to evaluate public perceptions of such an application, including acceptability and willingness to respond to alerts.

Methods:
The web-based survey was conducted in Canada and the USA by an established external polling vendor, Ipsos Reid. Sampling was designed to ensure broad representation of gender, age, geography, and spoken language following recent census statistics. Respondents were presented with a short concept description of cardiac arrest and the Pulsepoint app in text format followed by 6 closed-ended and 4 open-ended questions.

Results:
A random sample of 2,415 total surveys were collected (1106 from Canada and 1309 from the US). 70% of Canadian respondents but only 47% of US respondents had been trained in CPR at some point. On average, 79.5% of respondents agreed that Pulsepoint is something they would like to see in their community and 59.5% said they would download the App. 80% of Canadians and 77% of Americans were comfortable with receiving help in a public setting (street, office, etc) and 72 and 68% respectively, indicated they would be comfortable with receiving help in a private setting (home). Less than 40% of respondents identified concerns; as expected those identified included training concerns and trust issues. An average of 89% of the sample from both countries felt it was important that responders have up-to-date CPR certification.

Conclusions:
Overall, the North American public find the concept of the Pulsepoint application and crowdsourcing basic life support for OHCA acceptable and would be willing to respond. This is encouraging insight to support the use of social media to increasing bystander CPR rates in North America.
Abstract 19585: Overestimation of Functional Cardiomyopathy Disease Variants in the Human Gene Mutation Database
Authors: Lim Kian Huat , Aplenc Richard , Rossano Joseph
Published: July 2021

Introduction:
Dilated cardiomyopathy (DM), hypertrophic cardiomyopathy (HCM), and arryhmogenic right ventricular dysplasia (ARVD) have been associated with germline genetic variants. However, uncertainty exists regarding the functional impact of specific variants described in the literature.

Hypothesis:
We hypothesized that a substantial fraction of presumed casual variants would be identified as non-disease causing in a normal patient population.

Methods:
Missense variants associated with three main subtypes of cardiomyopathy were extracted from Human Gene Mutation Database Professional (HGMD). To assess the prevalence and pathogenicity of these potential disease-causing alleles, the population frequency of each variant was screened in a recently published large-scale exome database of over 60,000 whole exomes (ExAC). In addition, PolyPhen-2 was used to predict the functional impact of amino acid substitution for each missense variant.

Results:
In the HGMD, 1,405 missense variants were associated with cardiomyopathy, of which 25% were found in 2 or more samples in the ExAC database. Specifically 121 of 422 (28.7%) DM associated variants, 201 variants of 900 (22.3%) HCM associated variant, and 40 of 83 ARVD (48.2%) associated variants were observed in the ExAC database. Polyphen predicted 331 (23.9%) of variants as benign, 290 (20.6%) as possibly damaging, and 784 (55.8%) as probably damaging. Table 1 presents disease specific Polyphen results.

Conclusions:
We observed that a large proportion (25-45%) of cardiomyopathy-associated missense variants predicted as being damaging were indistinguishable from the background in ExAC. Using stringent cutoffs derived from these observations, we estimated more than 50% of previously associated cardiomyopathy variants may be non-functional or non-monogenic causes of cardiomyopathy.