bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19070: Hispanic/Latino Knowledge, Attitudes and Behaviors About Tobacco Use: Results of Focus Groups in 4 US Cities
Authors: Giachello Aida L , Robertson Rose M , Payne Thomas J , Rodriguez Carlos J , Walker Kandi L , Hart Joy , Groom Allison , Quiroz Cristina , Navas Elena , Kesh Anshula
Published: March 2022

Despite the reduction in the overall prevalence of cigarette smoking in the US, use has remained high among Hispanics/Latinos (H/Ls), particularly Puerto Ricans (33.7%) and Cuban/Cuban Americans (27.2%) (HCHS/SOL Databook, 2013). There is limited understanding about H/Ls knowledge, attitudes and behaviors (KAB) toward the use of other tobacco products such as e-cigs and hookah and how they may differ across diverse ethnic backgrounds, SES and acculturation.

Objective:
To assess KAB and perception of risk about the use of tobacco products among H/Ls that can inform the development of a culturally appropriate campaign to reduce prevalence.

Methods:
During the summer of 2014, 26 English and Spanish-speaking focus groups (6-10 persons per group, N = 182) were conducted among smokers and non-smokers, young (18-35) and old (36-65), men and women, of different SES and acculturation levels in: Chicago (Central and South Americans), New York City (Puerto Ricans and Dominicans), San Diego (Mexican/Mexican Americans) and Miami (Cubans). During 1 ½ hrs. discussion, participants were asked about: tobacco use problem in the community, type of tobacco use, health consequences of tobacco use, tobacco industry policy, second hand smoke, efforts to quit cigarette use, and channels of communication, including information technology. Data were analyzed using Atlas.ti for prevalent themes, perceptions and KAB.

Results:
Regardless of ethnic background, Latino smokers were most likely to use regular cigarettes, e-cigs and hookah. Older H/Ls (36+) and Spanish-speaking immigrants were most likely to use regular cigarettes while younger adults (women and men), US-born or more acculturated, were most likely to report using e-cigarette and/or hookah. Users stated that easy access, appeal of the different flavored tobacco taste & smell, no restrictions in their use, and socializing with others, made these products attractive. Differences did emerge in KAB and perceptions of tobacco risk by specific H/L group, smoking status, city, SES and acculturation.

Conclusion:
Tobacco use continues to be a serious problem in the H/L communities with growing use and acceptance of e-cigarettes and hookah among younger and more acculturated H/Ls.
Abstract 19076: ATAC-seq Implicates Epigenome-wide CTCF Dissociation in the Progression of Cardiac Ischemia
Authors: Lee Jonathan D , Lin Shin , Snyder Michael P
Published: March 2022

Introduction:
Heart disease is currently the most common cause of death in the United States. In 2010 alone, over 375,000 people died of coronary heart disease, of which over 120,000 were from myocardial infarction. Due to technical challenges associated with current techniques, profiling epigenome changes due to myocardial infarction has been limited. We have optimized an assay for transposase-accessible chromatin with sequencing (ATAC-seq) protocol that circumvents these challenges and works well with frozen tissue.

Hypothesis:
We assessed the hypothesis that ATAC-seq would enable the identification of novel chromatin remodeling and transcription factor binding events in a murine model of cardiac ischemia.

Methods:
Six 10 ± 2 week old C57BL/6J mice were paired by same gender, age, and litter, and mice from these pairs were selected for either mid left anterior descending artery ligation or sham surgery, both for 30 minutes. Successful ligation was confirmed by blanching of the tissue and representative electrocardiography changes. We performed our ATAC-seq protocol on left ventricular tissues, and regions of open chromatin were determined using the Hotspot algorithm at a false detection rate of 0.5%. Gene ontology was performed with the Genomic Regions Enrichment of Annotations Tool (GREAT), and motif discovery was performed with the Multiple Em for Motif Elicitation (MEME) Suite.

Results:
From stringent overlap criteria were obtained 159 loci that became “open” due to ischemia and 782 loci that became “closed”. Downregulation of growth and signaling processes was determined by GREAT. MEME strongly implicated the dissociation of CCCTC-binding Factor (CTCF) due to ischemia (MEME E-score = 8.10e-235; motif identification
p
-value = 1.88e-18; 262/782 of “closed” loci). CTCF ChIP-seq data and footprint analysis enabled the further identification of a robust set of 189 CTCF differential binding events.

Conclusions:
ATAC-seq was able to identify widespread chromatin remodeling due to cardiac ischemia alone. We identified a robust set of 189 gene loci from which CTCF binding is attenuated in response to this disease state. To our knowledge, this represents the first study that has examined chromatin accessibility changes in the setting of cardiac ischemia.
Abstract 19087: Left Atrial Appendage Thrombus is not an Independent Predictor of Mortality in Patients With Atrial Fibrillation
Authors: Johal Gurpreet S , Qazi Abdul H , Reddy Preetham , House John A , Main Michael L
Published: March 2022

Background:
Atrial fibrillation (AF) is an independent predictor of mortality. It is hypothesized that an increase in mortality in patients with AF is due to the presence of a thrombus in the left atrial appendage (LAA). However, data supporting this is limited. The purpose of this study was to determine if the presence of a LAA thrombus in patients with AF is associated with an increase in all cause mortality and whether or not it is an independent predictor of mortality.

Methods:
A total of 2918 patients with AF underwent trans-esophageal echocardiography (TEE) prior to cardioversion at a tertiary care hospital from 1999 to 2012. Subjects with history of a LAA ligation or resection, rheumatic heart disease, cardiac transplant, watchman device, and prosthetic valve were excluded. Patients who had multiple TEE studies, only the first TEE study was included. Subjects were then classified based on presence or absence of a LAA thrombus and followed for all cause mortality.

Results:
Of the 1900 patients included, 146 (7.7%) were found to have a LAA thrombus. Kaplan Meier mortality analysis showed a significantly higher all cause mortality rate in patients with a LAA thrombus (n=67, 45.9%) compared to those without a LAA thrombus (n=458, 26.1%) (p<0.0001). Multivariate analysis confirmed that a LAA thrombus is not predictive of independent mortality (hazard ratio (HR), 1.079; 95% confidence interval (CI), 0.823-1.415; p=0.58). The greater mortality is attributable to age (p<0.001), congestive heart failure (p<0.001), stroke (p<0.001), diabetes mellitus (p=0.0015), vascular disease (p=0.0119), ischemic cardiomyopathy (p=0.0218), pulmonary disease (p<0.001), dyslipidemia (p=0.0178), and chronic kidney disease (p<0.001). Data was reassessed considering the possibility that thrombus size was the cause of this increase in mortality; however, that was also shown not to be an independent predictor of mortality (HR, 1.085; 95% CI, 0.9-1.308; p=0.393).

Conclusion:
In a large cohort of patients with AF undergoing TEE prior to cardioversion, we concluded that the presence of a thrombus in the LAA was associated with a higher degree of mortality. However, after adjusting for coexisting conditions it was found not to be an independent predictor of mortality.
Abstract 19154: Emergency Department Overcrowding is Not Associated With Outcome of Out-of-hospital Cardiac Arrest
Authors: Jung Euigi , Kang Jiwon , Hwang Ji eun , Lee Jungyoup , Kim Joonghee , Lee Jae Hyuk , Jo You Hwan , Kim Taeyun , Kim Kyuseok
Published: March 2022

Aim of the study:
Emergency department (ED) overcrowding is a worldwide problem associated with adverse outcomes. This study was performed to investigate the association between ED overcrowding and outcome and quality of cardiopulmonary resuscitation for out-of-hospital cardiac arrest (OHCA).

Methods:
Prospectively collected data including patient demographics, Utstein factors and outcomes on 608 consecutive OHCA patients at a single ED from January 2008 to December 2012 were retrospectively analyzed. The patients were categorized into 4 groups according to ED occupancy rate. The primary outcome was resuscitation outcome, a composite of rates of return of spontaneous circulation (ROSC), survival at discharge and neurological outcome at 6 months. The secondary outcome was resuscitation quality assessed by time to advanced airway, time to first drug administration, resuscitation duration in refractory cases and rate of initiation of therapeutic hypothermia after ROSC in the ED.

Results:
There was no significant difference in rates of ROSC, survival at discharge and good neurological outcome according to ED occupancy rate in the univariate and multivariate analyses (p > 0.05). In addition, ED overcrowding was not associated with resuscitation quality (p > 0.05).

Conclusion:
ED overcrowding was not associated with outcome of OHCA or resuscitation quality.
Abstract 19155: Quantification of Progressive Pulmonary Valvular Insufficiency Using 4-Dimensional Flow Magnetic Resonance Imaging in an Ovine Model
Authors: Oquendo Yousi A , Han Joyce , Dori Yoav , Harris Matthew A , Zsido Gerald A , McGarvey Jeremy , Aoki Chikashi , Takebayashi Satoshi , Witschey Walter R , Jackson Benjamin M , Gorman Joseph H , Gorman Robert C , Gillespie Matthew J
Published: March 2022

Introduction:
Chronic postoperative pulmonary insufficiency (PPI) is the major cause of long-term morbidity and mortality in patients (pts) with tetralogy of Fallot (TOF). Pulmonary valve replacement (PVR) can mitigate the risk, but optimal timing for PVR remains controversial. Time-resolved 3D phase-contrast MRI (4DF) provides insight into complex intracardiac flow patterns. 4DF may help inform management decisions regarding timing of PVR. We describe the first quantitative serial 4DF analysis in an ovine model of PPI.

Methods:
A baseline cardiac MRI (CMRI) was performed on four Dorsett sheep (36-39kg) on a 3-Tesla Siemens scanner. Following baseline MRI, animals underwent pulmonary valvectomy and transannular patch (TAP) placement yielding PPI. Follow-up CMRI were obtained at 5mo and 7mo post-valvectomy (PoVa). Pathlines were emitted from a circular region of interest (ROI) representing the pulmonary valve annulus. Velocities, flow rate, and stresses were obtained throughout a complete cardiac cycle and compared across time.

Results:
Systolic max velocity, average velocity, and flow rate normal to the ROI plane decreased over time. Diastolic velocities increased at 5mo before decreasing at 7mo PoVa. Regurgitant flow was observed in diastole PoVa , and regurgitant flow rate increased with time. The max and average component of shear stress (viscosity = 3 cP) along the pulmonary artery wall decreased over time in systole. In diastole, shear stress increased at 5mo and decreased at 7mo. Parameters plotted in Figure 1.

Conclusion:
4DF provides a new method for visualization and quantification of alterations in blood flow patterns in the right side of the heart in an ovine model of PPI. Alterations in above parameters may indicate myocardial and pulmonary vascular deterioration precedent to morphological changes. Characterization of altered flow patterns in human pts with TOF may help to ultimately inform decisions regarding timing of PVR.
Abstract 19163: Rapid Progressive Thoracic and Abdominal Aneurysm Model in Fbn1C1039G/+ Mice Treated With Angiotensin Ii
Authors: Arakawa Mamoru , Koyano Tiffnay K , Emrich Fabian , Pedroza Albert J , Magavern Emma , Sato Tetsuya , Penov Kiril , Adachi Hideo , Fischbein Michael P
Published: March 2022

Rationale:
Marfan syndrome patients typically develop aortic root aneurysms with ensuing aortic dissection remaining the leading cause of death. Although losartan (Angiotensin 1 receptor blocker) has been shown to reduce aneurysms in mice, the role Angiotensin II (AngII) plays during aneurysm formation in MFS remains unknown.

Objective:
We hypothesized that AngII may exacerbate aneurysm growth in Fbn1
C1039G/+
mice. Moreover, we predicted AngII would induce abdominal aneurysms, creating a novel model to study the pathophysiology of aneurysm formation with two different embryonic origins.

Method and results:
Fbn1
C1039G/+
mice (n = 7) were treated with either (a) AngII (500 ng/min/kg) or (b) vehicle control and compared to ApoE-/- mice treated with Ang II (1000 ng/min/kg). Aortic root, ascending and abdominal diameters are measured with echo on POD 3, 7 and 14. Following dose-response curve experiments, optimal survival rate is 70%, 14 days after treatment. The average aortic root/ascending (AS) aortic diameter in Ang II Fbn1
C1039G/+
mice was 2.08 ± 0.31 mm, compared to 1.48 ± 0.25 mm in vehicle control Fbn1
C1039G/+
mice (p<.05). Interestingly, in addition to AS aortic aneurysms, 50% developed abdominal aneurysms. Cause of death in Ang II Fbn1
C1039G/+
mice were due to either AS or abdominal aneurysm dissection. Immunohistochemistry on POD 14 showed severe elastic layer disruption in aneurysmal tissue from both aneurysms. Quantitative PCR was performed to measure the expression of matrix-metalloproteinase (MMP) gene expression. When comparing AS and abdominal aneurysms in AngII Fbn1
C1039G/+
mice, MMP-2 was highly up-regulated in AS aneurysms (Fold change: 3.03 ± 0.69, p<0.05), whereas MMP-9 was up-regulated in abdominal aneurysms (Fold change: 1.86 ± 0.15, p<0.05). In contrast, MMP-9 was down-regulated in abdominal aneurysms in AngII ApoE-/- mice (Fold change: 0.18 ± 0.13, p<0.05).

Conclusions:
Fbn1
C1039G/+
mice treated with AngII develop severe aortic root/ascending aortic aneurysms. Ang II treatment results in abdominal aneurysm formation. Interestingly, gene expression analyses suggest different mechanisms of aneurysm development in aortic segments of different embryonic origin.
Abstract 19221: Low Mortality and Rate of Cardiac Events in Patients After Acute Coronary Syndrome Systematically Managed by Office-based Cardiologists in Germany: 1-year Outcomes of the ProAcor Study
Authors: Goss Franz , Haerer Winfried , Brachmann Johannes , Hamm Christian W , Reifart Nicolaus , Levenson Benny
Published: March 2022

Background/Introduction:
The ProAcor Study assessed the effectiveness of a structured patient management program over 12 months in patients who were discharged from hospital after an acute coronary syndrome (ACS) into ambulatory cardiology care (36 hospitals, 56 office-based cardiologists).

Methods:
The program comprised patient documentation with a specific instrument (BNK cardiac pass with visit scheduling) done jointly by the hospital physician and the office-based cardiologists, the definition of treatment targets and the structured information of patients in order to optimise adherence to therapy.

Results:
992 patients with ACS were included (STEMI 44.3%, NSTEMI 39.5%, unstable angina pectoris UA 15.2%). In these groups, acute intervention PTCA was performed in 98.0%, 91.9% and 81.6% of patients, stent implantation in 98.6%, 95.6% and 92.7%, and coronary artery bypass graft in 0.7%, 2.5% and 3.3%, respectively. Mean hospital stay due to ACS was 6 days (median).

At 12 months, 18 patients (1.8%) had died (among these, 9 due to cardiac event), while for 51 the status was unknown (5.1%). Based on a conservative approach that considered patients with unknown status as dead, 1-year mortality was 6.9%. Further data on non-fatal cardiac events, medication and quality of life (QoL) were collected from 796 patients (79.4%). Recurrent cardiac events were noted in 119 patients (14.9%), with an about equal distribution across STEMI and NSTEMI patients. On the EQ-5D visual analogue scale (0= worst, 100 best state of health) at 3 months as well as 12 months the median value was 80 points with little differences between subgroups. The EQ-5D index score was 0.91 ± 0.18 points at inclusion (STEMI 0.92, NSTEMI 0.90, UA 0.89) and was unchanged at 12 months.

Conclusion:
Compared to data based on usual care (e.g. German MONICA registry 13.3%), the 1-year mortality after ACS of only 6.9% in the structured ProAcor patients management program is remarkably low.
Abstract 19224: Fibrinogen And Neopterin Predict Future Myocardial Infarction Events In Patients With Stable Coronary Heart Disease
Authors: Mjelva Øistein R , Svingen Gard F , Pedersen Eva K , Seifert Reinhard , Ueland Per M , Nordrehaug Jan E , Nilsen Dennis W , Nygård Ottar
Published: March 2022

Background:
Fibrinogen is synthesized by hepatocytes. It is a precursor of fibrin and forms bridges between platelets during thrombus formation, but it is also a marker of ongoing inflammation. Neopterin is released by monocyte/ macrophage activation associated with atherosclerosis. Whether these markers interact or act independently among patients with suspected stable coronary heart disease has previously not been given much attention.

Methods:
We included 3526 patients undergoing elective coronary angiography at two university hospitals in Norway during 2000-2004, with a median follow-up of 7.3 years. Cox regression analysis was used to obtain hazard ratios (HR) and 95% confidence intervals (CI) for incident AMI of fibrinogen and neopterin levels in a crude model and a model adjusted for age, gender, diabetes, current smoking, hypertension and serum apoA1 and apoB. Potential effect modifications were investigated according to strata of fibrinogen or neopterin below or above the median, as well as across subgroups of age, gender, smoking status, diabetes, serum apoA1 and apoB. A p-value <0.05 was considered significant.

Results:
During follow-up, 580 patients experienced an AMI. In the unadjusted model, both fibrinogen and neopterin predicted future AMI [HR = 1.32; 95% CI 1.22-1.43; p<0.001 and HR = 1.31; 95% CI 1.23-1.40; p<0.001, respectively]. The estimates were only slightly attenuated in the multivariate model, and still associated with incident AMI when both biomarkers were added simultaneously [HR = 1.15; 95% CI 1.05-1.25; p<0.001 and HR = 1.20; 95% CI 1.12-1.28; p<0.001, respectively]. Baseline fibrinogen and neopterin levels were modestly correlated (Spearman’s rho = 0.18, p-value <0.001). There were no statistically significant interaction across subgroups (p for interaction fibrinogen and high/ low neopterin = 0.26, neopterin and high/low fibrinogen = 0.46, respectively).

Conclusion:
Patients with increased levels of fibrinogen or neopterin are at increased risk of future AMI. Neopterin levels did not significantly interact with the prognostic utility of fibrinogen. This suggests that circulating fibrinogen and neopterin may reflect different pathophysiological mechanisms.
Abstract 19227: Weight History Influences the Likelihood of Subclinical Myocardial Injury
Authors: Ndumele Chiadi , Cobb Laura , Lazo Mariana , Bello Natalie , Shah Amil , Nambi Vijay , Blumenthal Roger S , Gerstenblith Gary , Solomon Scott D , Ballantyne Christie M , Selvin Elizabeth , Coresh Josef
Published: March 2022

Introduction:
Obesity is associated with myocardial injury as reflected by levels of high-sensitivity cardiac troponin T (hs-cTnT), and the combination of obesity and elevated hs-cTnT is linked to markedly increased heart failure risk. The association of weight history with myocardial injury is unknown.

Hypothesis:
We hypothesized that prior obesity increases the likelihood of myocardial injury among individuals without clinical cardiovascular disease (CVD).

Methods:
We evaluated 9,472 participants (mean age 63 years) at ARIC Visit 4 (1996-99) with BMI ≥ 18.5 kg/m2 and without prior CVD. BMI (kg/m2) at Visit 4 and BMI calculated from self-reported weight at age 25 were categorized as normal weight (18.5-24.9), overweight (25-29.9) and obese (≥30). We then cross-tabulated BMI categories at Visit 4 and at age 25. A cumulative weight measure of “BMI years” was also calculated by taking the average of the BMI values at ARIC visits 1-4 and at age 25 (with BMI centered at 25 kg/m2) and multiplying the average by the number of years from age 25 to visit 4. The primary outcome was elevated hs-cTnT (≥14 ng/L) at Visit 4. Logistic regression was used to estimate the associations of cross-categories of BMI at the two time points and of BMI years with elevated hs-cTnT.

Results:
Within each Visit 4 BMI category, a higher BMI category at age 25 was associated with increased odds of elevated hs-cTnT, with the highest odds seen among those with obesity at both time points (OR 4.97 [95% CI: 3.39-7.29]) compared to those with normal weight at both time points. BMI years ranged from -307 to 1,205 ((kg/m2) x years). A graded positive association was seen between BMI years and myocardial injury (Figure), with each 100 higher BMI years linked to a 27% higher likelihood of elevated hs-cTnT.

Conclusions:
Prior obesity and greater cumulative weight from young adulthood increase the likelihood of subclinical myocardial injury, underscoring the importance of long-term weight control for reducing CVD risk.
Abstract 19268: Robust Performance of LpPLA2 Activity in Predicting Cardiovascular Disease Risk in a National, Diverse, Sample
Authors: Judd Suzanne E , Fang Kenneth , Safford Monika , Cushman Mary
Published: March 2022

Introduction:
LpPLA2 activity increases in inflamed plaques associated with atherosclerotic disease. Elevated circulating LpPLA2 is associated with increased risk of cardiovascular disease but it is not known whether this risk is consistent across demographic and risk groups.

Methods:
We developed a case cohort study within the REasons for Geographic and Racial Disparities in Stroke (REGARDS) study. We included a random cohort sample (n=3719) derived from the 23,019 REGARDS participants who were free from stroke and cardiovascular disease at baseline in 2003-7. We used weighted Cox models to study the association between LpPLA2 activity and risk of cardiovascular disease. Acute CHD during complete follow up through 12/31/2010 was adjudicated by an expert committee and defined as definite or probable myocardial infarction (MI) not resulting in death within 28 days (nonfatal acute CHD) or fatal acute CHD. LpPLA2 activity was measured using the PLAC® Activity Test at Diadexus. LpPLA2 activity was dichotomized at the 80th percentile of gender specific activity. The cut-off for men was 250 and for women was 200 nmol/ml/min.

Results:
The cohort included black (46%) and white (54%) participants over age 45 and was 42% male. 565 cases of acute CHD were available for analysis. After controlling for race, age, sex, statin use, income, education, lipid profile, hypertension, diabetes, and history of smoking, elevated LpPLA2 activity was associated with increased risk of cardiovascular disease HR=1.52; 95% CI (1.21, 1.91). This result was consistent and not significantly different across demographic and risk categories (Table).The Net Reclassification Index was 13%, p<0.001.

Conclusions:
LpPLA2 activity is associated with increased risk of cardiovascular disease among black and white men and women. The increased risk is observed even in participants at low risk of cardiovascular disease as defined by the Framingham risk function.
Abstract 19286: Pharmacoinvasive Strategy versus Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction: A Propensity Score Matched Analysis From the Korea Acute Myocardial Infarction Registry
Authors: Sim Doo Sun , Jeong Myung Ho , Ahn Youngkeun , Kim Young Jo , Chae Shung Chull , Hong Taek Jong , Seong In Whan , Chae Jei Keon , Kim Chong Jin , Cho Myeong Chan , Rha Seung-Woon , Bae Jang Ho , Seung Ki Bae , Park Seung Jung
Published: March 2022

Background:
There is a paucity of data comparing pharmacoinvasive treatment (PI) versus primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) in real world patients.

Methods:
We employed the Korea Acute Myocardial Infarction Registry to identify patients with STEMI who received either PI defined as fibrinolysis followed by PCI (rescue/urgent or elective) or PPCI. Patients receiving facilitated PCI within 3 hours from fibrinolysis were excluded. Propensity-matched 12-month clinical outcome was compared between the 2 groups.

Results:
In all patients (n = 9,586), PI group (n = 708) was younger, more often male, smokers, more likely to have typical chest pain and off-hour hospital arrival. PPCI group (n = 8,878) was more likely to have diabetes, lower blood pressure, higher Killip class and to receive glycoprotein IIb/IIIa inhibitors. PI group had shorter symptom-to-first medical contact (FMC) time (60 min vs. 80 min, p < 0.001), symptom-to-reperfusion time (165 min vs. 255 min, p < 0.001), and higher rate of pre-PCI Thrombolysis In Myocardial Infarction (TIMI) 3 (50.6% vs. 13.6%, p < 0.001). However, rate of post-PCI TIMI 3 was similar between the 2 groups. After propensity matching (n = 708 for each group), PI group had similar symptom-to-FMC time but had shorter symptom-to-reperfusion time (165 min vs. 240 min, p < 0.001), higher pre-PCI TIMI 3 rate (15.8% vs. 50.6%, p < 0.001) with similar post-PCI TIMI 3 rate. In all patients, PI group had lower rates of 12-month death (4.4% vs. 6.4%, hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.44 to 0.92, p = 0.015) and major adverse cardiac events (MACE: composite of death, recurrent myocardial infarction, repeat revascularization) (7.5% vs. 9.5%, HR: 0.69, 95% CI: 0.52 to 0.92, p = 0.010). In propensity-matched cohorts, 12-month mortality and MACE were similar between PI and PPCI: 4.4% vs. 2.8%, HR: 1.60, 95% CI: 0.91 to 2.84, p = 0.105 and 7.5% vs. 7.6%, HR: 0.96, 95% CI: 0.65 to 1.41, p = 0.827, respectively.

Conclusions:
In this large observational study with propensity-matched analysis, STEMI patients receiving PI, compared to PPCI, had shorter symptom-to-reperfusion time, higher culprit-vessel patency, and similar 12-month clinical outcome.
Abstract 19301: Blood Pressure Trajectories From Age 7 To 31 are Associated With Augmentation Index at Age 31 in Young Adults: The Kangwha Study
Authors: Lee Ju-Mi , Allen Norrina B , Yano Yuichiro , Kim Hyeon Chang , Lee Joo Young , Greenland Philip , Suh Il
Published: March 2022

Introduction:
Longterm blood pressure (BP) trajectories have been associated with subsequent subclinical atherosclerosis in early adulthood. However the association of BP trajectories at earlier age with subsequent arterial stiffness have not been studied.

Objectives:
Are BP trajectories from early childhood to adulthood associated with augmentation index (AIx) in young adults?

Methods:
The Kangwha Study is a community-based prospective cohort study that started in 1986 in Kangwha County, South Korea. Study participants were recruited at age 7 years, and 15 follow-up examinations have been conducted until age 31 (every year from age 7 to 18, and at age 20, 26, and 31 years). The current analysis includes 239 (male 110, female 129) participants whose BP were measured at least 3 times (on average 10 times) over 25 years. Augmentation index (AIx) as a measure of arterial stiffness was determined using radial artery tonometry by (Second peak systolic BP- diastolic BP) / (first peak SBP- DBP)*100 at the age 31 examination and adjusted for heart rate 75 were used. Latent mixture modeling was used to identify trajectories in mid-BP ((SBP+DBP)/2) over time. The associations of BP trajectories with AIx were assessed by linear regression.

Results:
We identified 5 mid-BP trajectories: low-stable (Group 1; 18.9%), continuously increasing (Group 2; 27.3%), increased slow and remain lower (Group 3; 29.9%), increasing moderately and remain lower (Group 4; 18.6%), and increasing fast and remain (Group 5; 5.3%). When we adjusted for sex and age, group 2 (β=6.05, p=0.01) and group 4 (β=6.72, p<0.01) showed higher AIx than group 1. With additional adjustment for obesity, high fasting glucose, high cholesterol, cigarette smoking, alcoholic drinks, and exercise, group 2 (β=6.53, p=0.01), and group 4 (β=7.47, p<0.01) showed higher AIx than group1.

Conclusions:
Longterm BP trajectories from early childhood had increased associations with arterial stiffness in early adulthood.
Abstract 19312: Multiplexed Images of the Heart Provide Novel Functional Information to Guide Invasive Procedures: A Review of the Initial Case Series
Authors: Ernst Sabine , Underwood Richard S , Ben-Haim Simona
Published: March 2022

Introduction:
The novel, high sensitivity and dedicated cardiac camera (D-SPECT, Spectrum Dynamics) allows single or dual tracer studies to add functional information to 3D DICOM image information from CT or CMR. Information consists of either perfusion information (from (technetium-99m (Tc-99m) methoxyisobutylisonitrile (MIBI, for perfusion) and/or sympathetic nnervation information using meta-iodobenzylguanidine (mIBG). Merging these 3D images with invasive 3D electroanatomical maps (EAM) offers image integration on a function rather than geometrical level alone. These fused 3D images can be combined with EAM to guide ablation procedures for either atrial or ventricular arrhythmias.

Methods:
A total of 23 patients (15 male, mean age 59.9 yrs) underwent either single iodine-123 mIBG (n=10, for sympathetic innervation) or dual tracer (n= 13, mIBG+MIBI, for perfusion) imaging and the acquired information was fused with the 3D cCT or CMR using a custom-made software.

Results:
Twenty out of 23 patients underwent invasive electrophysiology studies which targeted either atrial or ventricular arrhythmias. During the atrial arrhythmia procedures, high uptake sites for mIBG was correlated to positive effect of high frequency stimulation (=transient prolongation of AV nodal conduction) and thereby confirming ganglionated plexi which were targeted in addition to the standard ablation. Patients with ventricular arrhythmia, low amplitude voltage mapping showed good correlation to the perfusion scar imaging, thereby serving as a substrate map even in patients with implantable devices. Interestingly, regions of mismatch where identified which proved to be pro-arrhythmogenic during EP study in the 4/6 patients who underwent ventricular tachycardia (VT) ablation.

Conclusion:
The combination of innervation (by mIBG) and perfusion (by MIBI) nuclear imaging in addition to the 3D cCT or CMR imaging provides a novel type of “road map” information for complex arrhythmia ablation by providing a region of mismatch of innervation and perfusion. This provides a novel substrate information even in the presence of implantable devices.
Abstract 19364: C-Kit
+
Cardiac Progenitor Cells are Important in Cardiomyocytes Generation i
n vivo
in Response to Sfrp2
Authors: Gomez Jose , Hodgkinson Conrad , Payne Alan , Scmeckpeper Jeffrey , Zhang Lunan , Mao Lan , Dzau Victor
Published: March 2022

Introduction:
Resident c-Kit
+
cardiac progenitor cells (CPCs) differentiation into cardiomyocytes
in vivo
is controversial. Using lineage tracing and gene ablation techniques we documented that the Wnt signaling modulator Sfrp2 substantially increased differentiation of c-Kit
+
CPCs into cardiomyocytes in post-MI heart and restored cardiac function.

Methods:
c-Kit-CreERT2/mTeG mice were used where the c-Kit promoter drives expression of a tamoxifen (TX)-inducible Cre. Upon TX treatment Cre-mediated recombination drives expression of eGFP exclusively in c-Kit cells. Mice were crossed with a Diphtheria toxin receptor (DT) strain to selectively ablate heart c-Kit cells. Mice were subjected to myocardial infarction. 2 days later, mice were injected with Sfrp2 (0.5 μg) or saline at the infarct border zone. Heart tissue was analyzed 2 months post-MI for eGFP expression and various markers by microscopy.

Results:
c-Kit-CreERT2/mTeG model was tested. eGFP expression had no effect on in vitro c-Kit CPC differentiation or proliferation. In TX treated mice, >90% of c-Kit+ cells were eGFP+. No eGFP+ c-Kit+ cells were seen in vehicle-only mice (N=6, p<0.001). c-Kit negative cells, such as cardiomyocytes, endothelial cells, and smooth muscle cells, did not express eGFP following TX treatment. In sham animals, eGFP was localized to small c-Kit+ cells. In the vehicle MI group eGFP+ cardiomyocytes were rare (0.08% in infarct border zone. N=8, P=0.005). In contrast, the number of eGFP+ cardiomyocytes was significantly higher in the Sfrp2 treated group (15% in infarct border zone, N=10, P=0.0002). Co-localization of eGFP with blood vessels (0.77%, N=10) was infrequent. Induction of c-Kit CPC differentiation into cardiomyocytes by Sfrp2 was associated with lower fibrosis (15%, N=10, P=0.01), higher LV mass (58mg, N=10, P=0.01) and increased ejection fraction (16%, N=10, P=0.02). DT treatment ablated c-Kit cells (>95% N=4, P=0.01). Sfrp2 induction of c-Kit differentiation to cardiomyocytes and functional improvements were completely ablated by DT.

Conclusion:
Using c-Kit lineage-tracing and genetic ablation we have identified that these cells are important in cardiomyocyte generation
in vivo
in response to Sfrp2 and improves cardiac function following MI.
Abstract 19373: Glycemic Variability Determined by Continuous Glucose Monitoring System Predicts Rapid Progression of Non-culprit Lesions in Patients With Acute Coronary Syndromes
Authors: Kataoka Shunsuke , Gohbara Masaomi , Iwahashi Noriaki , Akiyama Eiichi , Maejima Nobuhiko , Tsukahara Kengo , Ebina Toshiaki , Umemura Satoshi , Kimura Kazuo
Published: March 2022

Backgounds:
Rapid progression (RP) of coronary artery disease (CAD) has been shown to be a powerful predictor of cardiovascular events. However, the predictor of RP in patients with acute coronary syndromes (ACS) remains to be fully elucidated.

Methods
We prospectively investigated the clinical impact of glycemic variability (GV) as determined by a continuous glucose monitoring system (CGMS) on RP of non-culprit lesions in 107 patients with ACS. All patients underwent emergent and follow up angiography 11 months after the initial angiography repeatedly. Patients with type 1 DM, an inflammatory disease, or CKD stage G4 and G5 were excluded.

RP was defined as a ≥10% diameter reduction in a preexisting stenosis of ≥50%, a ≥30% diameter reduction in a stenosis of <50%, development of a new stenosis of ≥30% in a previously normal segment, or progression of any stenosis to total occlusion. Patients were classified into 2 groups according to the presence (progressor, n = 21) or absence (non-progressor, n = 86) of RP. 4 cases out 110 patients had ACS during their follow up (Figure).All patients were equipped with a CGMS during the stable phase, and mean amplitude of glycemic excursion (MAGE) levels were calculated as a marker of GV.

Results:
The mean value of MAGE was significantly higher in progressor than in non-progressor (52 ± 19 mg/dL vs. 40 ± 21 mg/dL, P = 0.02). (Table) Multiple logistic regression analysis showed that the value of MAGE was an independent predictor of RP (odds ratio, 1.06 per 1 mg/dL; P <0.01).

Conclusions:
In prediction of RP, the value of MAGE was superior to that of HbA1c.

The value of MAGE early after the onset of ACS is a predictor of RP of non-culprit lesions.
Abstract 19386: The Mitochondrial Deacetylase Sirtuin 3 (sirt3) is Important in the Pathogenesis of Both Pulmonary Hypertension and Pulmonary Fibrosis: Potential for an “Overlap Syndrome” and a Common Therapy?
Authors: Paulin Roxane , Zang Hengjia , Boukouris Aristeidis , Gurtu Vikram , Haromy Alois , Michelakis Evangelos D
Published: March 2022

Introduction:
Pulmonary arterial hypertension (PAH) is often associated with interstitial lung disease, like idiopathic pulmonary fibrosis (IPF). IPF pulmonary fibroblasts have a very similar pro-proliferative and anti-apoptotic phenotype similar to PAH vascular smooth muscle cells (SMC). As this phenotype is often associated with a cancer-like mitochondrial suppression, we hypothesized that a common mitochondria abnormality may underlie both PAH and IPF. We speculated that the loss of the mitochondrial deacetylase Sirt3, which we recently showed promotes PAH, will also promote IPF.

Results:
SIRT3 expression was decreased in human IPF-PH lungs (transplant recipients, n=7) and in Sirt3 wild type (Sirt3WT)+ bleomycin BLEO lungs (n=15 for each) and fibroblasts compared to healthy lungs (unused transplant tissue, n=3) and Sirt3WT. Sirt3 knockout (Sirt3KO) fibroblasts, like Sirt3WT+BLEO, had decreased mitochondrial function assessed by decreased pyruvate dehydrogenase activity, decreased respiration (Seahorse Assay) and increased mitochondrial membrane potential (TMRM dye in live cell imaging). Sirt3KO and Sirt3WT+BLEO fibroblasts had increased collagen production and smooth muscle actin expression (immunoblot). All of these findings are very similar to those in pulmonary artery SMCs from the same Sirt3KO animals, which develop spontaneous PAH.

In vivo, Sirt3KO mice treated with BLEO developed worse IPF than Sirt3WT+BLEO (dynamic resistance 2±0.5 vs 1.4±0.2cmH2O.s/mL, dynamic elastance 20±3 vs 38±10cmH2O/mL). Intra-tracheal delivery of an adenovirus overexpressing SIRT3 improved both Sirt3KO+BLEO and Sirt3WT+BLEO compared to GFP-only adenovirus. We have previously showed that the same virus reverses PAH in rodents.

Conclusion:
Sirt3 downregulation plays an important role in the development of IPF. While the exact mechanisms by which Sirt3 is downregulated remains to be established, this work opens new perspectives for the treatment of IPF. Given the frequent overlap of IPF and pulmonary hypertension in the same patients, our data suggest the intriguing possibility that they both represent aspects of an “overlap syndrome”, which may benefit from similar therapeutic approaches, despite the differences in the “cell of origin”.
Abstract 19415: Temperature Management After Aortic Arch Surgery With Deep Hypothermic Circulatory Arrest Affects Survival and Neurologic Outcome
Authors: Rungatscher Alessio , Luciani Giovanni Battista , Linardi Daniele , Milani Elisabetta , Gottin Leonardo , Walpoth Beat , Faggian Giuseppe
Published: March 2022

Introduction:
Therapeutic hypothermia is recommended by international guidelines after cardio-circulatory arrest. However the effect of different temperature during first 24 h after deep hypothermic circulatory arrest (DHCA) for aortic arch surgery on survival and neurologic outcome are undefined.

Hypothesis:
We hypothesize that target temperature management after aortic arch surgery could affect survival and neurologic outcome.

Methods:
In the period 2010-2014, a total of 210 consecutive patients undergoing aortic arch surgery with DHCA were included. They were retrospectively divided in three groups by median peak nasopharyngeal temperature within 24 h after rewarming: hypothermia (<36°C; n = 65), normothermia (36-37°C; n = 110), hyperpyrexia (>37°C; n = 35). Multivariate stepwise logistic and linear regressions were performed to determine whether different temperature independently predicted 30-day mortality, stroke incidence and neurologic outcome assessed by Cerebral Performance Category (CPC) at hospital discharge.

Results:
Compared with hypothermia and normothermia, hyperpyrexia was associated independently with a higher risk of 30-day mortality (35.7% vs 6.5%; odds ratio [OR], 9.4; 95% confidence interval [CI], 1.1-81.6; P= .005), stroke incidence (64.3% vs 13.3%; OR 9.3; 95% CI, 2.9-92.3; P= .002) and poor neurologic outcome (CPC 3-5) (85.7% vs 36.9%; OR 4.5; 95% CI, 0.9- 87.6; P= .01). No significant differences were demonstrated between hypothermia and normothermia.

Conclusions:
Post-operative hypothermia is not associated with better outcome after aortic arch surgery with DHCA. However post-operative fever (>37°C) is associated with high stroke incidence, poor neurologic outcome and increased 30-day mortality. Target temperature management in the first 24 h after surgery should be evaluated in prospective randomized trials.
Abstract 19422: Origin of Ventricular Fibrillation in Bileaflet Mitral Valve Prolapse Syndrome
Authors: Syed Faisal F , Ackerman Michael , McLeod Christopher J , Kapa Suraj , Mulpuru Siva K , Sriram Chenni S , Cannon Bryan C , Asirvatham Samuel J , Noseworthy Peter A
Published: March 2022

Introduction:
Although most patients with mitral valve prolapse (MVP) have a benign prognosis, there is a subgroup with bileaflet MVP syndrome (biMVPS) at increased risk of idiopathic ventricular fibrillation (VF). The phenotypic features of this syndrome include myxomatous bileaflet prolapse, complex ventricular ectopy (VE), T-wave inversion in inferolateral ECG leads, and female predominance. The mechanism of ventricular arrhythmia in these patients is unknown.

Methods:
We reviewed our center’s ablation experience of 14 consecutive patients with biMVPS patients between February 2007 and October 2013 (n=13 female, median [range] age at index ablation 33.8 [21.0 - 58.7] years, left ventricular ejection fraction [EF] 60 [45-67] %, all ≤ moderate mitral regurgitation [MR]). We compared findings from 6 with prior sudden cardiac arrest (SCA) and recurrent ICD shocks for drug refractory VF with 8 who had symptomatic drug-refractory complex VE but without prior SCA.

Results:
All patients with prior SCA had a predominant VE trigger for the VF. There was no difference between the two groups in EF, MR severity, VE burden, and number of different VE morphologies or foci ablated. Sites of successful VE ablation at index procedure were the LV papillary muscles (PM, n=6 anterior, 6 posterior), fascicular system (n=5 anterior, 4 posterior), mitral annulus (n=2), outflow tracts (3 RVOT, 1 LVOT), and coronary sinus (n=1). All patients had at least one LV papillary or fascicular VE focus. Purkinje origin VE was identified as the VF trigger in 6/6 SCA patients (3 from PM, 3 from LV fascicles) and only 4/8 (none from PM) non-SCA patients (p=0.04). Acute success was seen in 17/19 procedures with no complications. VF storm occurred within 24 hours of ablation in a single patient. At 310 (39 - 2099) days follow-up, 1 SCA patient received a single shock (p=0.031 compared to pre-ablation), and symptoms from VE were reduced in 12/14.

Conclusions:
BiMVPS is characterized by VE from the LV fascicles and papillary muscles that trigger VF. The VE is invariably multifocal and may also involve the outflow tracts and mitral annulus. Ablation of clinically dominant VE foci alleviates symptoms and reduces the number of VF-terminating ICD shocks.
Abstract 19432: Neuronal Isoform of Nitric Oxide Synthase is Upregulated in Cardiac Intrinsic, and Extrinsic Sympathetic Afferent and Efferent Ganglia Following Myocardial Infarction
Authors: Nakamura Keijiro , Ajijola Olujimi A , Irie Tadanobu , Yamakawa Kentaro , Ardell Jeffrey , Shivkumar Kalyanam
Published: March 2022

Objective:
The impact of myocardial infarction (MI) on neuronal nitric oxide synthase (nNOS), an important mediator of cardiac neurotransmission is not well understood.

Methods:
Yorkshire pigs (n=10) underwent anterior MI by LAD occlusion. After 6-8 weeks, bilateral stellate ganglia (SG), T1 dorsal root ganglia (DRG), right atrial (RAGP) and ventral inter-ventricular ganglionated plexi (VIVGP)were extracted, formalin-fixed, paraffin-embedded, and sectioned. Immno-staining for nNOS was performed on representative slides through the middle of the ganglia, and for calcitonin-gene related peptide (CGRP), a marker of sensory afferent neurons. The percentage of immunoreactive (IR) neurons was quantified.

Results:
An average of 63.1±40.7, 169.7±55.5, and 448.1±204.5 neurons were counted in the GPs, DRG, and SG respectively. There was no significant difference in the number of neurons counted in controls vs MIs. In the GPs, nNOS was differentially altered by MI, with significant upregulation in VIVGP but not RAGP of MI (13.8±2.8% vs 46.6±5.3%, p<0.001; and 12.1±3.6% vs 12.5±2.9%, p=NS, respectively) compared to control animals. In the DRG, IR of both CGRP and nNOS was increased (36.3±6.2% vs 65.3±4.8%, p<0,001 for nNOS; and 64.1±6.2% vs 85.2±5.6%, p<0.001 for CGRP), with increased co-expression of both CGRP and nNOS in approximately 20% of DRG neurons. In the SG, the number of neurons demonstrating strong IR for nNOS was approximately 0.4% in control animals. After MI, this increased 8-fold to 3.12% (P<0.01).

Conclusions:
nNOS expression is upregulated differentially following MI in the GPs, with increased expression in the ventricular GP innervating the region of MI, but not in the RAGP. Both cardiac sympathetic afferent (DRG) neurons, and efferent (SG) neurons increase expression of nNOS following MI. The impact of nNOS in these different sites warrants further investigation.
Abstract 19468: Timing of Atrial Fibrillaiton-related Stroke and the Risk of All-cause Mortality
Authors: Patel Parin J , Katz Ronit , Liang Jackson J , Dixit Sanjay , Callans David J , Epstein Andrew E , Marchlinski Francis E , Deo Rajat
Published: March 2022

Introduction:
Strokes that occur after the onset of atrial fibrillation (AF) have a worse prognosis than strokes that do not occur in the setting of AF. Recent studies suggest that strokes that occur within several months prior to an AF diagnosis may be related to underlying, silent AF. Limited studies have evaluated survival differences between AF-related strokes that occur prior versus after AF diagnosis.

Objective:
We evaluated differences in the risk of all-cause death between patients that develop stroke in the 6 months before compared to any time after the diagnosis of AF.

Methods:
We utilized the University of Pennsylvania AF Free study to create an inception cohort of patients with incident stroke and AF. We assessed ECGs, clinical records, and administrative data within the health system over a 5 year period to identify individuals that had a first diagnosis of stroke or AF. Cox proportional hazards models evaluated associations between stroke subtypes and death.

Results:
We identified 3,616 individuals that developed stroke (323 had stroke after AF diagnosis, 292 patients had stroke within 6 months preceding AF diagnosis, and 2795 patients had stroke without an AF diagnosis). Of these patients, there were 319 all-cause mortality events over a median 4.6 [3.8, 5.5] years follow-up. The overall mortality rate was highest in patients that had a stroke within 6 months prior to AF (Table 1) and was almost 2-fold higher than those that had a stroke after an AF diagnosis (p<0.001). After multivariable adjustment, patients with an AF-related stroke that occurred within 6-months prior to the diagnosis of AF had a significantly higher risk of death than those with stroke that occurred after an AF diagnosis or those with stroke but no AF (Table 1).

Conclusions:
Stroke that occurs prior to the diagnosis of AF was associated with a significantly higher risk of all-cause death. This increased mortality risk is not explained by the presence of other comorbid conditions.