bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18302: Left Ventricular Structure by Echocardiography is Associated With Vasopressor Requirements and Severity of Organ Failure After Cardiac Arrest
Authors: Chonde Meshe , Jentzer Jacob C , Abu-Daya Hussein , Shafton Asher , Chalhoub Didier , Althouse Andrew , Rittenberger Jon
Published: March 2022

Introduction:
Patients resuscitated from cardiac arrest (CA) often require vasopressors for hemodynamic support and frequently have cardiac dysfunction identified on transthoracic echocardiography (TTE). The association between TTE parameters and vasopressor requirements is not well-described.

Hypothesis:
Echocardiographic findings early after resuscitation from CA will predict vasopressor requirements.

Methods:
Prospective registry of patients resuscitated from CA underwent TTE within 24 hours after CA. We determined 2D measurements, LVEF, spectral Doppler of mitral inflow (E) and LV outflow and systolic and early diastolic (e’) tissue Doppler of the mitral annulus. Using Pearson correlation coefficients, we examined the association between TTE parameters and number of vasopressor drugs, cumulative vasopressor index (CVI) and Sequential Organ Failure Assessment (SOFA) score. Mean values of TTE parameters were compared in patients with high and low cardiovascular SOFA subscores using t-tests.

Results:
Among the 55 patients, LV end-diastolic diameter (LVEDD, r = -0.498 to -0.569, p = 0.0001 to 0.0003), LV end-systolic diameter (LVESD, r = -0.392 to -0.463, p = 0.0008 to 0.0053) and LV relative wall thickness (RWT, r = 0.452 to 0.503, p = 0.0002 to 0.0011) correlated significantly with admission and peak 24 hour number of vasopressor drugs and CVI. LVEDD (r = -0.324, p = 0.0229), LVESD (r = -0.290, p = 0.0431), RWT (0.429, p = 0.0021) and septal e’ velocity (r = -0.344, p = 0.037) correlated with admission SOFA score. Other TTE parameters including LVEF did not correlate with vasopressor requirements or SOFA score. Patients with cardiovascular SOFA subscore = 4 had lower LVEDD (4.16cm vs. 5.0cm, p = 0.0008), lower LVESD (3.07cm vs. 4.03cm, p = 0.0008), higher RWT (0.48 vs. 0.65, p = 0.0026) and lower E/e’ ratio (10.84 vs. 18.91, p = 0.0169) compared with patients with cardiovascular SOFA subscore < 4.

Conclusions:
A smaller, thicker LV cavity by echocardiography at 24 hours after CA is associated with higher vasopressor requirements and more severe organ failure. Patients who required more vasopressor support had smaller, thicker LV cavities and a lower E/e’ ratio. LV systolic dysfunction was not a significant predictor of vasopressor requirements.
Abstract 18342: Development of Fibrotic Substrate for Atrial Fibrillation in Advanced Heart Failure is Driven Not by Inflammation but by Smad2/3 Dependent Replacement Fibrosis
Authors: Yoo Shin , Thorp Edward B , Kunamalla Aaron , Aistrup Gary L , Ng Jason , Gordon David , Knight Bradley , Passman Rod , Goldberger Jeffrey , Arora Rishi
Published: March 2022

Introduction:
Fibrosis is an important contributor to atrial fibrillation (AF) substrate in heart failure, with TGF-β signaling generating atrial fibrosis. Inflammation is also known to contribute to AF. However, it is not known: a) if inflammation underlies the development of atrial fibrosis, b) if TGF-β signaling is involved in the generation of atrial inflammation and c) what is the relative role of canonical SMAD2/3 versus non-canonical TGF-β-activated kinase 1 (TAK) signaling in the creation of atrial inflammation/fibrosis.

Methods:
21 dogs underwent transfection in the posterior left atria of either a plasmid expressing a dominant negative TGF-β type II receptor (pUBC-TGFβ-DN-RII) (N=9) or control vector (pUBC-LacZ) (N=12), followed by 3-4 weeks of right ventricular tachypacing (VTP) (240 bpm). After 3-4 weeks of VTP, the following were assessed: AF by open-chest mapping. Atrial tissue was assessed for signaling (pSMAD2/3 and pTAK) by western blot, fibrosis by trichrome staining and iflammation by CD68 staining.

Results:
The interstitial fibrosis in LacZ atria was replacement in character (Fig 1A). TGFβ-RII-DN dogs had a significant decrease in replacement fibrosis leading to a decrease in duration of inducible AF (LacZ 63.64 ± 12.12 s vs. TGFβ 26.52 ± 3.79 s, p < 0.05). While both groups demonstrated evidence of inflammation (CD68 staining), there was no difference in inflammation between the groups (Fig 1B). TGFβ-RII-DN dogs had a significant decrease in pSMAD2/3 but not pTAK, compared to pUBC-LacZ dogs.

Conclusion:
The development of fibrotic substrate for AF in advanced HF is driven not by inflammation but primarily by SMAD2/3 mediated myocardial replacement fibrosis. These findings may have important implications for mechanism-guided therapies for AF, with canonical TGF-β signaling appearing to be an attractive therapeutic target in AF.
Abstract 18349: Molecular Classification of the Heart Transplant Endomyocardial Biopsy
Authors: Chang Eleanor , Fishbein Gregory , Bakir Maral , Bondar Galyna , Jackson Nicholas , Liem David , Litovsky Silvio , Tallaj Jose , Starling Charlotte , Ping Peipei , Reed Elaine , Deng Mario , Tabak Esteban , Cadeiras Martin
Published: March 2022

Background:
Endomyocardial Biopsy
(
EMB) is the standard method to diagnose allograft rejection post HTx. While it is used to support medical decisions, insufficient diagnostic accuracy constitutes a fundamental limitation. The aim of this study is to develop a methodology that improves the classification of the EMB through a non-supervised evaluation of intramyocardial gene expression.

Methods:
Sixty-four heart tissues from 47 HTx recipients were subjected to genome wide mRNA sequencing. An unsupervised algorithm using optimal transport to mitigate batch effects and to filter confounding sources of variability was developed to identify molecular signatures of rejection. Linear Mixed Model identified genes statistically significant among the histology defined rejection groups. Weighted Gene Correlation Network Analysis (WGCNA) was used to establish 13 eigengene modules and module-clinical phenotype relationships. Gene Ontology was used for interpretation of the modules in their biological context.

Results:
O
ur algorithm best classified the EMBs into 4 unsupervised clusters solely based on their gene expression. Statistical analysis showed a set of genes differentially expressed among groups defined by histology criteria. Top ranked genes were CLNK, TNFRSF10A, TRADD, CD2, and HLA-A. WGCNA revealed best trait-module correlation was observed between the classes defined by the unsupervised algorithm developed in this study followed by Histology. Figure 1 shows Module-Trait relationships, strength of association, significance and enriched biological process.

Conclusion:
We have developed an unsupervised algorithm that classifies the EMBs into 4 functionally distinctive categories. These categories are highly correlated with genomic modules defined by WGCNA and with the clinical phenotypes. To our knowledge, this is the first unsupervised classification of the EMBs. Further validation and performance will be provided at the time of presentation.
Abstract 18350: Impact of Amount vs Duration of Smoking on Incident Heart Failure and Mortality Among Community-dwelling Older Adults: Need to Reassess the Role of Pack-years as a Tool to Estimate Smoking
Authors: Ahmed Amiya A , Bittner Vera , Morgan Charity , Zhang Sijian , Fonarow Gregg C , Deedwania Prakash , Butler Javed , Wu Wen-Chih , Allman Richard M , White Michel , Fletcher Ross D , Howard George , Bonow Robert O , Aronow Wilbert S , Ahmed Ali
Published: March 2022

Background:
Clinicians and public health professionals often use pack-years (PY) to quantify amount and duration of smoking. Thus, 40 PY of smoking may mean 1 pack of cigarette a day for 40 years or 4 packs a day for 10 years. However, it is unknown if the impact of smoking as measured by PY may vary by amount and duration.

Methods:
Of the 3185 community-dwelling adults ≥65 years without prevalent heart failure (HF) in the Cardiovascular Health Study (CHS), 2556 were never-smokers. The 629 current smokers smoked a median of 1 (20 cigarettes) pack a day (PPD) for a median of 51 years resulting in a median of 42 PYs of smoking. Of 319 smoking ≥1 PPD, 125 smoked <51 years (higher-amount-“shorter”-duration; median 49 PY) and of 336 smoking ≥51 years, 142 smoked <1 PPD (lower-amount-longer-duration; median 27 PY). Age-sex-race-adjusted hazard ratios (aHR) and 95% CI for centrally-adjudicated incident HF and all-cause mortality during 13 (mean, 10) years of follow-up for the two smoker groups (vs. never smokers) were estimated in Cox regression models.

Results:
Patients (N=2823) had a mean (±SD) age of 74 (±6) years, 70% were women, and 16% African American. Incident HF occurred in 21%, 24% and 28% of never smokers, higher-amount-“shorter”-duration (aHR, 1.32; 95% CI, 0.91-1.91) and lower-amount-longer-duration smokers (aHR, 1.60; 95% CI, 1.14-2.16), respectively (Figure; left panel). Respective rates for all-cause mortality were 39%, 48% (aHR, 1.34; 95% CI, 1.04-1.74) and 58% (aHR, 1.73; 95% CI, 1.39-2.17; Figure; right panel). .

Conclusions:
Smokers who survived into older age and smoked larger amount for “shorter” duration appear to have numerically higher risk for incident HF and death than those who smoked smaller amount for longer duration, despite the fact that former group had lower pack-year estimates. These findings suggest that the use of pack-year to estimate smoking may underestimate the risk of prolonged smoking.
Abstract 18376: Long-term Atherosclerotic Cardiovascular Disease Outcomes Associated With Coronary Artery Calcium
Authors: Mitchell Joshua D , Paisley Robert , Moon Patrick , Villines Todd C
Published: March 2022

Introduction:
Current risk assessment guidelines focus on prevention of atherosclerotic cardiovascular disease (ASCVD), which includes stroke as a primary outcome variable. The long-term (>10 year) relationship of coronary artery calcium (CAC) scoring with stroke has not been previously reported, a limitation cited by the guidelines. Further, large-scale, long-term outcomes studies following CAC are limited. We sought to define the long-term relationship of CAC for stroke and myocardial infarction (MI) in a large screening cohort.

Methods:
We retrospectively identified 24,246 subjects (mean age 50±8; 70.5% men) without ASCVD or malignancy who underwent CAC scoring (Agatston) at Walter Reed Medical Center from 1997-2009. Subjects were assessed for the primary outcomes of MI and stroke and the secondary outcome of late (>90 days post CAC) coronary revascularization. Outcomes were extracted from the military data repository, a comprehensive healthcare database that captures care provided within and outside of the military healthcare system, and then analyzed using Cox proportional hazard multivariate stepwise regression controlling for baseline risk factors.

Results:
With a mean follow-up of 11.3±3.6 years there were 546 MI, 947 strokes and 843 late coronary revascularizations. Compared to subjects with no CAC, the adjusted hazard ratios (aHR) for MI were 2.09 (95% CI, 1.68-2.60), 2.01 (1.78-2.28) and 1.91 (1.72-2.11) for CAC scores of 1-100, 101-400 and >400, respectively. CAC of 1-100 was not predictive of stroke compared to no CAC. The aHRs of incident stroke were 1.15 (1.03-1.28) and 1.23 (1.13-1.33) for CAC scores of 101-400 and >400. CAC was strongly associated with late coronary revascularizations. CAC explained the most variance in models for MI and late revascularization and was the third most important predictor for stroke behind age and hypertension.

Conclusion:
In patients without ASCVD, CAC was a stronger independent predictor of incident MI and late coronary artery revascularization as compared to stroke over one of the longest follow-up intervals reported to date. Advanced CAC (>100) was a modest independent predictor of stroke during the study period. These results support the role of CAC for the prediction of incident ASCVD outcomes.
Abstract 18378: Comparsion of Cerebral Protection Strategies on Immediate And Longterm Outcome of Patients With Stanford Type a Aortic Dissection
Authors: Stelzmueller Marie-Elisabeth , Wiedemann Dominik , Ogrodny Philipp , Urban Michael , Obrovsky Paul , Mahr Stephane , Kocher Alfred , Laufer Guenther , Ehrlich Marek
Published: March 2022

Introduction:
The optimal protection strategy for use during acute type A aortic dissection surgery is controversial.

Hypothesis:
To assess the efficacy and immediate and long-term results of different cerebral protection techniques in the treatment of acute type A aortic dissection.

Methods:
Between April 1987 and January 2015, 400 patients (270 male patients; mean age 58 years; range 15-88) with acute type A dissection underwent surgical aortic repair with an open distal anastomosis. Either hypothermic circulatory arrest alone at 18 °C (n = 111; 28%) or combined with retrograde cerebral perfusion (n = 117; 29%) or antegrade cerebral perfusion at 25 °C (n = 172; 43%) was used for cerebral protection.

Results:
The median circulatory arrest time was 35 minutes. The overall 30-day mortality was 16% (63 of 400). The 30-day mortality stratified by group was 20% (22 patients) in the hypothermic circulatory arrest group, 17% in the retrograde cerebral perfusion group (20 patients), and 12% (21 patients) in the antegrade cerebral perfusion group (P = .021). Permanent neurologic dysfunction occurred in 53 patients (14%), with statistically significant differences among the 3 groups (25% for hypothermic circulatory arrest, 13% for retrograde cerebral perfusion, and 7% for antegrade cerebral perfusion; P = 0.01). Univariate analysis showed a significant effect of the cerebral protection strategies on 30-day mortality and neurologic outcome. Kaplan-Meier analysis showed differences among the 3 groups with a 1-, 2-, and 5-year survival rate of 85%, 82%, and 77% with antegrade cerebral perfusion, 75%, 72%, and 66% with retrograde cerebral perfusion, and 65%, 64%, and 62% with hypothermic circulatory arrest alone (p=0.19).

Conclusion:
Antegrade cerebral perfusion group had a superior 30 day as well as midterm survival and inferior rate of PND. During the study period, several significant improvements in surgical as well anaesthesiological in treatment and management of acute type A aortic dissection were achieved. However, postoperative outcome of patients with type A dissection is multifactorial and independent predictors of mortality and permanent neurologic dysfunction were difficult to identify
Abstract 18391: The Effect of Targeted Temperature Management on the Neurologic Outcome of In-hospital Cardiac Arrest Survivors
Authors: Lundbye Justin , Sawyer Kelly N , Bergman Leah , Nair Sanjeev , Fernandez Antonio
Published: March 2022

Introduction:
Cooling patients that have been resuscitated from out-of-hospital cardiac arrest (OHCA) using targeted temperature management (TTM) is standard of care. However the role of TTM in patients after in-hospital cardiac arrest (IHCA) is presently unclear.

Hypothesis:
We evaluated the effect of TTM on neurologic outcome of patients after successful resuscitation from IHCA

Methods:
A retrospective analysis was performed on prospectively collected data from 112 consecutive, adult IHCA patients admitted to a tertiary cardiac intensive care unit between January 1, 2004, and June 1, 2013. Patients were categorized into the hypothermia group (underwent TTM) and the control group (did not undergo TTM). Univariable as well as multivariable analyses by binomial logistic regression were performed on the collected data. The primary outcome was defined as neurologic outcome at hospital discharge using the cerebral performance categories (CPC) (Good= CPC 1-2 and Bad= CPC 3-5 respectively).

Results:
Of the 112 patients who formed the study cohort, 84 patients formed the hypothermia group and 28 patients formed the control group. The two groups were similar with respect to age, gender, ethnicity, past medical history, smoking, rate of witnessed cardiac arrest, and time to return of spontaneous circulation(P>0.05). On univariable analysis 34(41%) patients in the hypothermia group had good neurologic outcome as compared to 5 (18%) patients in the control group (p=0.03). On multivariable analysis the use of TTM was the only independent predictor of good neurologic outcome (OR=3.79, 95 % CI: 1.18-12.79, P=0.024).(Figure)

Conclusions:
The use of TTM in patients resuscitated from IHCA is associated with significantly better neurologic outcome as compared to similar patients who did not undergo TTM. Larger studies are required to corroborate this finding.
Abstract 18410: Prescriptions for and Use of β-Blocker Following Heart Failure Hospitalization: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Levitan Emily B , Van Dyke Melissa K , Chen Ligong , Durant Raegan W , Brown Todd M , Rhodes J D , Olubowale Olusola , Muyiwa Oluwole A , Kilgore Meredith L , Blackburn Justin , Albright Karen C , Safford Monika M
Published: March 2022

Introduction:
In heart failure (HF) with reduced ejection fraction (HFrEF), there is evidence that the β-blockers metoprolol succinate, bisoprolol and carvedilol improve prognosis.

Objective:
To examine β-blocker prescriptions and fills after HF hospitalization.

Methods:
In 2006-2011, we identified 344 HF hospitalizations (147 HFrEF, 152 with preserved ejection fraction, 45 unknown) with linked Medicare claims among 201 participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a cohort of 30,239 black and white adults. Comorbidities and prescriptions were abstracted from medical records. Claims were used to assess prescription fills. Risk ratios (RR) and confidence intervals (CI) for β-blocker prescriptions and fills were calculated using generalized estimating equations adjusted for age, race and sex.

Results:
Women accounted for 59% of HF hospitalizations and blacks 54%; 90% had prior HF. β-blockers were prescribed for 78% (87% with HFrEF); 58% (74% with HFrEF) of β-blocker prescriptions were metoprolol succinate, bisoprolol or carvedilol. Prescriptions were filled within 30 days of discharge for 46%. There was evidence of β-blocker up-titration for 9% (21% with HFrEF). HFrEF was more strongly associated with prescriptions and fills of metoprolol succinate, bisoprolol or carvedilol (RR 1.82 [95% CI 1.32, 2.53] and 1.73 [95% CI 1.12, 2.68], respectively) than any β-blocker (RR 1.12 [95% CI 0.99, 1.27] and 1.06 [95% CI 0.82, 1.36], respectively). After HFrEF hospitalization, black race and β-blockers at admission were positively associated with β-blocker prescriptions, female sex was positively associated with fills and chronic obstructive pulmonary disease was inversely, but not significantly, associated with prescriptions and fills (
Table
).

Conclusions:
β-blockers were prescribed at discharge for most HF hospitalizations, but many prescriptions do not appear to have been filled and up-titration was rare.
Abstract 18449: Apolipoprotein B/Apolipoprotein A-I Ratio and Progression of Aortic Valve Stenosis - Results From the PROGRESSA Study
Authors: Tastet Lionel , Capoulade Romain , Shen Mylene , Dahou Abdellaziz , Clavel Marie-Annick A , Mathieu Patrick , Arsenault Marie , Bédard Élisabeth , Dumesnil Jean-Gaston G , Després Jean-Pierre P , Pibarot Philippe
Published: March 2022

Introduction:
Calcific aortic stenosis (AS) is an active and complex disorder, which involves atherosclerotic-like processes. However, previous studies reported that the association between atherosclerotic risk factors and AS progression appears to be stronger in younger middle-aged patients compared to elderly ones.

Hypothesis:
Apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio reflects the balance between proatherogenic versus antiatherogenic lipid profile. The objective of this study was to examine the association between apoB/apoA-I ratio and progression of AS according to patient’s age.

Methods:
One hundred sixty five patients with AS were prospectively recruited in the PROGRESSA study. AS progression was assessed by increase in peak aortic jet velocity (Vpeak) measured by Doppler echocardiography between baseline and 2-year follow-up. Blood samples were collected to measure plasma levels of apoB and apoA-I.

Results:
The mean age was 66±13 years and 72% were male. During the 2-year follow-up, AS progression was similar in younger patients (age <69 y.o. [median age for the whole cohort]; n=82) and older patients (Vpeak: +0.24±0.04 vs +0.25±0.03 m/s; p=0.82). There was a significant interaction (p<0.01) between patient’s age and baseline apoB/apoA-I ratio for AS progression. Younger patients with high baseline apoB/apoA-I ratio (i.e. apoB/apoA-I ≥0.53; n=41) had faster AS progression compared to those with lower apoB/apoA-I ratio (Vpeak: +0.32±0.06 vs +0.16±0.04 m/s; p=0.03). In older patients, there was no significant association between apoB/apoA-I ratio and AS progression (Vpeak: +0.23±0.05 vs +0.27±0.04 m/s; p=0.55). After adjustment for sex, hypertension, dyslipidemia, diabetes, metabolic syndrome, creatinine level, degree of aortic valve calcification and baseline Vpeak, higher apoB/apoA-I ratio remained independently associated with faster progression of AS in younger patients (p=0.003).

Conclusions:
This prospective study shows for the first time that higher apoB/apoA-I ratio is a powerful and independent predictor of faster AS progression in younger patients. These findings suggest that the pathological processes involved in the progression of AS are different in younger versus older patients.
Abstract 18480: Mortality Risk in Married and Unmarried ICD and CRT-D Patients With Mild Heart Failure: A MADIT-CRT Sub-study
Authors: Aktas Mehmet K , Biton Yitschak , Zareba Wojciech , Polonsky Slava , McNitt Scott , Moss Arthur J , Kutyifa Valentina
Published: March 2022

Background:
Married patients have been shown to have a lower risk for adverse cardiovascular outcomes. However, the risk of heart failure or death, and death alone in married versus unmarried patients with left ventricular (LV) dysfunction and an implantable cardioverter defibrillator (ICD), and the effect of cardiac resynchronization therapy with defibrillator (CRT-D) are unknown.

Methods:
In MADIT-CRT, we evaluated the long-term clinical outcomes of all-cause mortality, and heart failure (HF) or death in married and common law patients compared to the unmarried (single/divorced/widowed) with left bundle branch block (LBBB) and CRT-D vs. an ICD-only.

Results:
There were 937 married patients and 344 unmarried patients with LBBB. Married patients were more likely to be men, white, smokers, and heavier. During a median follow-up of 5.6 years, married/common law ICD patients had a significantly lower incidence of death compared to unmarried patients (p=0.004) (Figure). In multivariate analysis in the ICD-only sub-group, married or common-law patients had a 39% lower risk of all-cause mortality (HR 0.46, 95% CI 0.30 - 0.71, p<0.001) when compared to the unmarried. However, in the CRT-D group, the survival benefit was attenuated in married/common-law patients (HR 0.74, 95% CI 0.51 - 1.06, p=0.10) compared to the unmarried (HR 0.40, 95% CI 0.23 - 0.69, p<0.001, interaction p=0.07). There were no differences in clinical outcomes of HF or death in married and unmarried patients with an implanted CRT-D vs. ICD-only, or in patients with non-LBBB ECG pattern.

Conclusions:
During long-term follow-up of mild HF patients with LV dysfunction, married/common-law patients were at a significantly lower risk for death compared to those not married. In married patients, CRT-D was associated with an attenuated survival benefit when compared to their unmarried counterparts.
Abstract 18502: Mass and Genetic Polymorphism of Group IIA Secretory Phospholipase A2, Rosuvastatin Therapy, and Risk of Cardiovascular Events: An Analysis From the JUPITER Trial
Authors: Akinkuolie Akintunde O , Chu Audrey Y , Caulfield Michael , Mu Jianying , Eva Hurt-Camejo , Ding Bo , Nyberg Fredrik , Glynn Robert J , Ridker Paul M , Chasman Daniel I , Mora Samia
Published: March 2022

Background:
Although group IIA secretory phospholipase A2 (sPLA2-IIA) is well appraised for its involvement in atherosclerosis by modifying LDL, its role in managing CVD risk in a primary prevention setting with low LDL-C is unknown. Furthermore, the utility of sPLA2-IIA mass for assessing future CVD risk relative to statin therapy in a population free of CVD is unknown.

Methods:
We analyzed data from JUPITER (NCT00239681) in which participants with LDL cholesterol <130 mg/dL and hsCRP≥2 mg/L were randomized to rosuvastatin 20mg/day vs placebo. sPLA2-IIA was quantified by sandwich-type ELISA (Cayman) in 11269 participants before and 1 year after randomization. Cox regression was used to examine the association of sPLA2-IIA with CVD. The impact of lifelong reduction in sPLA2-IIA on CVD risk was assessed by Mendelian randomization analysis in 6692 participants.

Results:
313 first CVD events occurred during maximum follow-up of 5.0 (median, 1.9) years. Baseline sPLA2-IIA levels (median, 25th-75th percentile: 3.81, 2.49-6.03 ng/ml) were associated with increased risk of CVD: after adjusting for age, sex, race, treatment, smoking, family history, BMI, blood pressure, glucose, HDL-C, LDL-C, and triglycerides, HR (95%CI, p-value) per SD in sPLA2-IIA was 1.22 (1.08-1.38; p= 0.002). This association was slightly attenuated after additionally adjusting for hsCRP (1.18, 1.04-1.35; p=0.01) and there was no statistical heterogeneity by rosuvastatin therapy. In the rosuvastatin arm, on-treatment sPLA2-IIA levels trended towards an increased residual risk of CVD; HR 1.19 (0.97-1.45; p=0.09) in multivariable adjusted model, this was attenuated after additionally adjusting for hsCRP (HR: 1.08 95% CI 0.87-1.34; p=0.50). rs11573156C in PLA2G2A (encoding sPLA2-IIA) had the strongest effect on sPLA2-IIA levels, median (25th-75th percentile) for the CC and GG genotype were 2.79 (1.97-4.01 ng/mL) and 7.38 (5.38-10.19 ng/mL), respectively; but showed a non-significant association with CVD risk (HR: 1.11, 95% CI 0.89-1.38, p=0.34).

Conclusion:
While sPLA2-IIA may be a measurable biomarker to assess the prognostic impact of inflammation on baseline and residual CVD risk, this result do not support sPLA2-IIA as a viable pharmacological target for reducing CVD risk.
Abstract 18547: Utilization of Percutaneous Coronary Intervention in Cancer Patients With Acute Coronary Syndrome - A Nationwide Analysis
Authors: Shah Nishi N , Pothineni Naga Venkata K , Rochlani Yogita , Bhatti Sabah , Iliescu Cesar , Marmagkiolis Konstantinos , Hakeem Abdul
Published: March 2022

Background:
Patients with active cancer represent an increasingly significant subset of patients presenting with acute coronary syndromes (ST elevation and Non ST elevation myocardial infarction). These patients are underrepresented in clinical trials. We sought to identify utilization of percutaneous coronary intervention (PCI) in patients with various cancers.

Methods:
We used the Nationwide inpatient sample to identify all patients that presented with STEMI and NSTEMI from the years 2002-2012. Patients with various cancers were identified with appropriate ICD-9 codes.

Results:
There were an estimated 3,120,957 STEMI admissions during the study period, of which 4.9% (140,008) had an associated cancer diagnosis. PCI was done in 48.3% of STEMI patients without cancer, but only in 32.9% of patients with cancer. We identified a total of 5,422,406 NSTEMI admissions during the same period. 5.6% (303,751) of NSTEMI patients had cancer. PCI utilization in NSTEMI patients without cancer was 27.8% and 19% in patients with cancer. Among individual cancers, patients with pancreatic, liver and gastric cancers had the lowest rates of PCI (table)

Conclusion:
Our study demonstrates significantly lower rates of PCI in patients with various cancers. Malignancies with a poor overall survival seem to be associated with lower PCI rates. With lack of clinical trial data on management of ACS in patients with various cancers and with improvements in cancer survivors overall, further studies are required to identify gaps in knowledge in appropriate selection of cancer patients for PCI.
Abstract 18556: Renal Sympathetic Denervation Modulates Cardiac Repolarization in a Post Myocardial Infarction Pig Model
Authors: Krishna Kumar Nair Govind , Gizurarson Sigfus , Jackson Nicholas , King Benjamin , Hu Xudong , Ramadeen Andrew , Zamiri Nima , Porta-Sanchez Andreu , Kusha Marjan , Massé Stéphane , Lai Patrick F , Al-Hesayen Abdul , Graham John J , Dorian Paul , Nanthakumar Kumaraswamy
Published: March 2022

Introduction:
Changes in cardiac repolarization parameters such as QT interval and QT dispersion have been implicated in cardiac arrhythmogenesis following acute myocardial infarction (AMI). These parameters are susceptible to sympathetic modulation. We therefore hypothesized that renal sympathetic denervation (RDN) may produce potential anti-arrhythmic actions through its effects on cardiac repolarization.

Methods:
Fifteen pigs randomized to AMI & RDN (6 pigs), AMI & sham RDN (6 pigs) and sham MI & sham RDN (3 pigs) underwent percutaneous occlusion of the mid to distal LAD to achieve AMI. 2 weeks after infarction, the St. Jude EnligHTN® basket catheter was used to perform RDN bilaterally. Cardiac repolarization parameters were measured at 3 time points over the course of the 3 week study: baseline (immediately before MI), midpoint (2 weeks post MI; at time of RDN) and end (1 week post RDN). ECG data were acquired from limb leads.

Results:
In a ten beat span, the range in the durations of the QT interval was seen to increase from 18+/-7ms to 19+/-11ms in the real AMI & sham RDN group while in the real AMI & real RDN group it decreased from 17+/-5ms to 14+/-5ms (p=0.11). The mean QT interval which increased by 25% in the real AMI & sham RDN group saw only an 11% increase in the real AMI & real RDN group (p=0.048). The standard deviation of the average QT intervals post AMI, which quantifies the reduction in global dispersion of repolarization, saw a 41% decrease with RDN compared to an 8% decrease with sham RDN. The temporal dispersion of repolarization was also diminished by RDN. The dispersion of T wave peak to T wave end durations which increased in the real AMI & sham RDN group (from 15+/-6ms to 22+/-10ms), was decreased in the real AMI & real RDN group (from 19+/-7ms to 16+/-6ms) (p=0.05). T wave alternans values displayed no significant response to RDN (p=0.977).

Conclusions:
Adverse changes in cardiac repolarization parameters were attenuated via renal denervation in this post infarct pig model. These effects may mitigate post infarct arrhythmogenesis but require further study to evaluate the influence of local, reflex and circulating mediators.
Abstract 18590: Hypoxic Liver Injury at Admission as a Predictor of In-hospital Death in Patients With ST-Elevation Myocardial Infarction Undergone Primary Percutaneous Coronary Intervention: Data From the INTERSTELLAR Cohort
Authors: Park Hyun Woo , Suh Jon , Moon Jeonggeun , Oh Pyung Chun , Jang Ho-Jun , Kim Tae-Hoon , Park Sang-Don , Kwon Sung Woo , Kang Woong Chol
Published: March 2022

Introduction:
Recently, hypoxic liver injury (HLI) has been proposed as a novel prognostic marker for ST-elevation myocardial infarction (STEMI) in small study. So, we evaluated the prognostic implication of HLI at admission in patients with STEMI who underwent primary percutaneous coronary intervention (PCI) in large cohort.

Methods:
From 2007 to 2014, a total of 1540 consecutive patients (1221 males, mean age 61±13 years old) with STEMI underwent primary PCI were analyzed retrospectively. HLI was defined as ≥ 2-fold increase of serum alanine aminotransferase (ALT) above upper normal limit at the time of presentation. Primary endpoint was in-hospital death.

Results:
Of all patients, the HLI was noted in 7.7% patients. Compared to patients without HLI, the patients with HLI were younger (58±14 vs. 61±13 years, p=0.043), had lower ejection fraction (43±15 vs. 48±17%, p=0.002). A total of 89 in-hospital death (5.8%) were occurred. Compared to patients without in-hospital death, those patients were older (69±11 vs. 60±13 years old, p<0.001), had higher ALT (65±69 vs. 36±40 IU/L, p<0.001) at the time of presentation and had lower left ventricular ejection fraction (49±12 vs. 27±19, p<0.001). The HLI at the presentation was associated with high in-hospital death (p <0.001) and was an independent predictor of in-hospital death (HR 5.69, CI 3.12-10.38, p<0.001) after adjusted by age, diabetes, sex and shock.

Conclusions:
The HLI is an independent predictor of in-hospital death in patients with STEMI underwent primary PCI.
Abstract 18614: Rheumatic Heart Disease Screening in Schools Through Portable Echocardiography: Data From the PROVAR Study
Authors: Nascimento Bruno R , Beaton Andrea Z , Nunes Maria do Carmo P , Webb Catherine L , Diamantino Adriana C , Bruno Kaciane K , Miri Cassio O , Pereira Gabriel T , Lopes Eduardo L , Ferreira Camila G , Lafeta Luciana C , Ribeiro Antonio Luiz P , Sable Craig
Published: March 2022

Introduction:
The accuracy of clinical examination is limited for early diagnosis of Rheumatic Heart Disease (RHD). The 2012 World Heart Federation (WHF) Criteria provides standardized echocardiographic (echo) guidelines for diagnosis of RHD. There is sparse data on echo prevalence of RHD in Brazil.

Objective:
Assess the prevalence of RHD in students (6-18 years) from public schools in low-income areas in Belo Horizonte, Brazil.

Methods:
Over 4-days, experts used standard portable echo machines (GE, Vivid-Q) and the 2012 WHF Criteria to determine RHD prevalence. All consented and present children at the visited schools were eligible for participation. Studies identified as abnormal were blindly read by a second cardiologist, with non-agreement adjudicated by a third. RHD prevalence by gender and age (5-11 & 12-18) were compared using Fisher’s Exact Test.

Results:
A total of 1381 students were screened across four schools in urban Belo Horizonte, Brazil. The mean age was 13.6±2.8 years, range 5-18 years; 59.3% were female. The prevalence of RHD was 3.8% (53/1381): 3.4% borderline RHD (n=47) and 0.4% definite RHD (n=6). Of these cases, 46 (86.8%) had pathologic mitral regurgitation (≥2cm, seen in 2-views, pan-systolic, and velocity ≥3m/sec) and 7 had pathologic aortic regurgitation (≥1cm, seen in 2-views, pan-diastolic, and velocity ≥3m/sec). One child had mixed mitral and aortic valve disease. There were no cases of mitral or aortic stenosis. There was no difference in RHD prevalence between males and females (p=0.57), but older children had a higher prevalence rate (5-11 years 1.3% vs. 12-18 years 4.5%, p=0.01). Minor congenital heart disease was detected in 8 additional children (5.8%), including one large ASD that was referred for closure.

Conclusions:
WHF Criteria make it possible to obtain and accurately compare echo prevalence of RHD among different regions of the world. The PROVAR study shows that, among children living in low-socioeconomic conditions in urban Brazil, RHD remains a significant health burden, comparable to that in other low-resource communities. Screening older children has higher yield. Contemporary data such as these provide justification for investing in comprehensive RHD control programs both in Brazil, and around the globe.
Abstract 18619: All Advanced Lipid Tests are Not Equal: Prospective Analysis of Discordance Between LDL-P, Small Dense LDL (or Subfractions), and HDL-P (or Subfractions) as Determined by NMR, Ion Mobility, and VAP in Treated Patients
Authors: Mukai Kanae , Rolph Kellie , McCauley Julie C , Triffon Douglas W
Published: March 2022

Introduction:
LDL-P has been shown to be a better predictor of cardiovascular risk than LDL-C (Framingham Offspring, Jupiter, and MESA). HDL-P has been reported as a better predictor than HDL-C (Jupiter and MESA) and small dense LDL measurements have been reported as more predictive of cardiovascular disease progression than LDL-C (HATS). Clinicians rely on these markers to assess residual risk in treated patients.

Hypothesis:
NMR, ion mobility (IM), and VAP tests will report discordant results for LDL-P, HDL-P (or subfraction), and small dense LDL (or subfraction) in treated patients.

Methods:
This is a prospective study (#SCIML001 on ClinicalTrials.gov), approved by the Scripps Clinic (#IRB-14-6458). We aimed to determine the discordance between Liposcience NMR, Quest CardioIQ, and Atherotech VAP Plus. 102 patients older than 18 years on therapy for at least 30 days were included. A one-time fasting lab draw was obtained with all 3 lipid tests performed simultaneously on fresh samples. Concordance and discordance analysis was performed with the cut-off between normal and abnormal ranges.

Results:
Pearson correlations between LDL-P by VAP and NMR, NMR and IM, and VAP and IM were 0.886, 0.785, and 0.762, respectively.

All 3 tests were concordant 63% and discordant 37% of the time.

IM reported an abnormal LDL-P more commonly (28% of time vs NMR and 20% of the time vs VAP) when using the same cutoff value of 1000 as NMR. When using the cutoff of 1260 for LDL-P for IM, NMR was abnormal 15.6% of the time vs IM and VAP was abnormal 24% of the time vs IM. VAP more frequently reported an abnormal LDL-P vs NMR (27% of the time) and vs IM (32% of the time). VAP small LDL sub-fractions were more commonly reported as abnormal vs NMR and IM (27% and 32% respectively). Ion mobility more consistently reported a lower large HDL-P (48% of the time vs VAP and vs NMR).

Conclusions:
Correlations between advanced markers of residual risk were low and would give discordant signals on decisions to intensify therapy.
Abstract 18631: PKA Inhibition Ameliorates Cardiac Dysfunction In High-fat Feeding Induced Type II Diabetic Mice
Authors: Zhang Xiaoxiao , Zhang Xiaoying M , Zhang Chen , Zhang Haohui , Cai Angela , Chen Xiongwen
Published: March 2022

Background:
In type 2 diabetic (T2D) patients, the sympathoadrenergic system (SAS) is chronically activated, resulting in chronic protein kinase A (PKA) activation. T2D causes cardiac dysfunction.

Objective:
To test the hypothesis that PKA plays an important role in diabetic cardiac dysfunction.

Methods:
PKA inhibition (PKI) transgenic (TG, n=18) and nontransgenic littermate control (NLC, n=20) mice (3-month old) were fed with high fat food (D12451, Research Diet) for 6 months. The body weight (BW) was measured twice a week. Intra-LV hemodynamic, heart weight, liver weight, lung weight, and tibia length were determined at the end point. Myocyte contraction was analyzed. The lean body weight was measured after removing water and fat content of the entire carcass. Inflammatory cell infiltration and fibrosis were determined with MAO staining and Masson’s trichrome staining respectively.

Results:
1. The BW of both groups was increased similarly (NLC: from 23.8±3.6g to 45.8±5.6g; TG: from 24.2±3.9g to 46.4±5.6g). Lean body weight and fat composition were not different. 2. The PKI TG group had better cardiac function when examined with intra-LV hemodynamic measurements: (1). The maximal systolic pressure (mmHg) of TG (107.8±4.49) was significantly higher than that of NLC (83.0±8.1) mice. (2). The end diastolic pressure (EDP, mmHg) of TG (2.7 ± 2.2) was significantly lower compared to WT mice (11.5 ± 3.3); (3). Maximum dp/dt (mmHg/s) was significantly higher in PKI TG (7628.0 ± 537.5) than in NLC mice (5021.4 ± 806.2); (4). The relaxation rate of the heart (minimum -dp/dt in mmHg/s) was significantly better in TG (-7159.5 ± 543.0) than in NLC mice (-5334.7 ± 516.2); (5). The HW/BW (mg/g) was significantly less in TG mice (4.6 ± 0.2) than in control mice (5.2 ± 0.2). (6). The lung weight/BW and liver Weight/BW were also reduced in TG mice. (7). At the myocyte level, myocyte contraction amplitude was slightly but significantly greater in TG myocytes than in NLC myocytes. Myocyte relaxation rate was significantly faster in TG myocytes. (8). TG hearts had less inflammatory cell infiltration and fibrosis than control hearts.

Conclusion:
PKA inhibition ameliorates cardiac remodeling and preserves cardiac function in high fat feeding-induced diabetic mice.
Abstract 18651: Proteomic Discovery of Pulmonary Hypertension Biomarker Hepatoma Derived Growth Factor
Authors: Nies Melanie K , Yang Jun , Fu Zongming , Damico Rachel L , Hassoun Paul M , Korley Frederick K , Everett Allen D
Published: March 2022

Introduction:
A non-cardiac blood based biomarker could enhance treatment monitoring and prognostication for pulmonary hypertension (PH). We investigated the diagnostic and prognostic value of hepatoma derived growth factor (HDGF), a pulmonary angiogenic factor in PH.

Methods:
Using a cohort of Johns Hopkins Pulmonary Hypertension Clinic patients (JHPH, n=73; 49% idiopathic PAH, 51% PAH associated with scleroderma), a healthy control group (n=30) and Johns Hopkins Emergency Department (ED) patients with left sided heart failure (N=55) or chronic illnesses (DM, hypertension, hypercholesterolemia, or smoking, N=66), we investigated the association of HDGF and NT-proBNP and the diagnosis of PH, PH survival, left sided heart failure and chronic disease.

Results:
HDGF concentrations were significantly elevated in PH versus healthy controls (p=0.013), left sided heart failure (p=0.0026) or chronic disease (p=0.0002), but were not significantly different between healthy controls versus left sided heart failure (P=0.70) or chronic disease (P=0.29). Among PH subjects, the area under the receiver operator curve (AUC) for discriminating survival was 0.71 (p=0.001) for HDGF, with no significant difference between the survival AUC for HDGF and NT-proBNP (p=0.66). The hazard ratio of survival for a HDGF concentration of >0.426 ng/mL was 3.7 (95% CI: 1.5-8.7, P=0.02) and when adjusted for NT-proBNP increased to 4.5 (95% CI: 1.0-20.1, P <0.05) (figure 1). HDGF concentrations were significantly associated with decreased six minute walk distance (6MWD; p=0.04) but not mean PA pressure (p=0.8) or PVR (p=0.4).

Conclusion:
HDGF is a novel non-cardiac PH biomarker equivalent to NT-proBNP, not confounded by left sided heart failure and significantly associated with 6MWD, the single most important clinical functional measure in PH. Thus, HDGF may add additional value in PH risk stratification for clinical trials as well as future PH drug development.
Abstract 18680: Skap2 Regulates the Inflammatory Macrophage Response in Atherogenesis
Authors: Hyatt Danielle , Alenghat Francis J
Published: March 2022

Background:
Macrophages are central to atherosclerosis. A macrophage-specific, integrin-stimulated signaling pathway acts through the adaptor protein Skap2 to drive actin reorganization and migration. Absence of this pathway yields accelerated atherosclerosis, but the manner in which Skap2 governs macrophage behavior in atherogenesis is undefined.

Results:
We have previously shown that

Skap2
-/-
;apoE
-/-

mice have increased atherosclerotic plaque in their aortic roots compared to their

Skap2
+/+
;apoE
-/-

counterparts on a standard diet, and there is no difference in weight, lipid profile, development, or other organ pathology. Here, we find that despite
in vitro
defects in chemotaxis and migration, Skap2-deficient

apoE
-/-

mice have intact macrophage content (F4/80 stain) in their atheromata. M1 and M2 polarized bone marrow-derived macrophages express canonical mRNA markers:
Tnfa
and
Nos2
for M1 and
Ym1
and
Arg1
for M2. In this system, compared to polarized wild-type (WT) cells,

Skap2
-/-

M1s express higher levels of inflammatory M1 markers [
Nos2
: 1.0 +/- 0.005 a.u. for

Skap2
-/-

vs. 0.22 +/- 0.02 a.u. for WT; p < 0.05], and

Skap2
-/-

M2s express lower levels of M2 markers [
Arg1
: 0.66 +/- 0.15 a.u. for

Skap2
-/-

vs. 1.0 +/- 0.02 a.u. for WT;
Nos2
: 0.38 +/- 0.04 a.u for

Skap2
-/-

vs. 1.0 +/- 0.006 a.u. for WT; p < 0.05]. Compared to WT M2s,

Skap2
-/-

M2s also express lower levels of the M2 marker CD206 by Western blot analysis. There is also higher Skap2 protein expression in wild-type M2s compared to wild-type M1s by Western analysis and immunofluorescence staining. In

apoE
-/-

mice, Skap2+ atheromata have commingled CD86 and CD206 expression, whereas

Skap2
-/-

lesions predominantly express the M1 marker CD86 such that the ratio of CD86:CD206 is skewed away from M2 in Skap2-deficient lesions. In an
in vitro
system of efferocytosis,

Skap2
-/-

macrophages show impaired uptake of apoptotic foam cells.

Conclusions:
Overall, we find that a Skap2-dependent pathway contributes to regulation of atherogenesis through maintenance of normal lesional macrophage homeostasis. Taken together, our findings support a model in which Skap2 does this by driving macrophages toward a regulatory, efferocytic phenotype.
Abstract 18696: Regional Distribution of Cerebral White Matter Hyperintensities in HFrEF and HFpEF
Authors: Melah Kelsey , Moon Chooza , Johnson Sterling C , Bratzke Lisa C
Published: March 2022

Introduction:
Patients with heart failure (HF) commonly suffer from cognitive impairment. White matter hyperintensities (WMHs) are associated with cognitive decline, cardiovascular risk in healthy aging and CNS disorders. Studies have shown that patients with heart failure with reduced ejection fraction (HFrEF) have greater volume of WMHs compared to controls. However, little is known about the distribution and size of WMHs in patients with heart failure with preserved ejection fraction (HFpEF). This study utilizes quantitative neuroimaging analysis to examine volume and regional distribution of WMHs between patients with HFrEF, HFpEF, and controls.

Methods:
Thirty-nine HF patients (mean age=68.2) and 28 controls (mean age=67.4) underwent high-resolution T-2 weighted fluid attenuated inversion recovery imaging. Volume of WMHs was calculated using the Lesion Segmentation Tool in Statistical Parametric Mapping 8 (SPM8). Total volume of WMHs was divided by intracranial volume to calculate WMH ratio (WMHr). Regional analysis of WMHs was performed using a multiple regression analysis of lesion probability maps in SPM8. Imaging results were family wise error corrected for multiple comparisons.

Results:
One-way ANCOVA revealed that individuals with HF had greater WMHr compared to controls, controlling for age, sex, and comorbid burden (p=0.001). Further analysis revealed that there was no significant difference in WMHr between HFrEF and HFpEF, although both groups had significantly greater WMHr compared to controls (p=0.005). Individuals with HF were more likely to have WMHs in the right cingulum (p<0.001) and right genu (p=0.001) of the corpus callosum. There were no differences in distribution of WMHs between patients with HRrEF or HFpEF.

Conclusion:
Patients with HFrEF or HFpEF have greater WMHr compared to controls and WMHs are likely to be located in the right cingulum and genu. The cingulum and genu are white matter tracts that are essential for memory and cognitive control. In patients with HF, the damage to these areas caused by WMHs may be associated changes in cognition. Future studies are needed to further examine the relationship between cognition and WMHs in HF patients and the mechanistic relationship between HF and WMHs.