bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18653: Outcomes After Induction Immunosuppression in Heart Transplant Patients
Authors: Ambur Vishnu , Taghavi Sharven , Furuya Yuka , Jayarajan Senthil , Shiose Akira , Leotta Eros , Gomez-Abraham Jesus , Toyoda Yoshiya
Published: March 2022

Introduction:
Outcomes after induction immunosuppression in heart transplant patients have not been investigated since the heart allocation policy was changed in 2006. The optimal induction therapy continues to be controversial with many centers continuing to use none at all. We evaluated the outcomes after modern induction immunosuppression agents with the primary end points being survival and rejection.

Methods:
The United Network for Organ Sharing (UNOS) database was examined for all heart transplants from January 2006 to December 2012. Patients receiving induction therapy were compared to those receiving no induction agent. Additional subgroup analysis was performed on the induction group including those patients receiving either basiliximab (Simulect), thymoglobulin, or alemtuzumab (Campath). Kaplan Meier survival curves and multivariate cox regression analysis were utilized to evaluate outcomes.

Results:
Of the 14,210 heart transplants performed during this time period, 5905 (41%) received no induction while 8605 (59%) received induction therapy. Interestingly, the no induction group had a lower incidence of acute rejection (15.5% vs. 36.8%, p = 0.005). However, Kaplan Meier analysis revealed no difference in survival between the two cohorts (6.36 vs. 6.23 years; p = 0.59). On multivariate analysis, induction was not associated with a survival advantage (HR: 0.95; 0.88 - 1.03, p = 0.23). Subgroup analysis revealed that patients receiving Campath had the highest incidence of acute rejection (29.5% vs. 19.3% vs. 9.6%, p < 0.0001) and highest panel reactive antibody (7.6 vs 4.3 vs. 4.9, p = 0.002) while those receiving thymoglobulin had the lowest. However, Simulect (HR: 1.08; 0.97 - 1.19, p = 0.16), Campath (HR: 0.87; 0.69 - 1.09, p = 0.22), and Thymoglobulin (HR: 0.94; 0.77 - 1.14, p = 0.50) did not provide a survival benefit on multivariate or Kaplan Meier analysis (6.26 vs. 5.59 vs. 6.26 years; p = 0.21).

Conclusions:
This analysis of induction agents on outcomes after heart transplantation since the change in allocation policy in 2006 shows that induction does not affect survival when compared to no induction. Furthermore, there is no difference in survival when comparing the three most commonly used agents: Simulect, Campath, and thymoglobulin.
Abstract 18660: CVSN Best Abstract Award: Genome-wide Candidates Unique to Females With Coronary Artery Disease Significantly Predict Mortality Risk
Authors: Dungan Jennifer R , Qin Xue , Hurdle Melissa , Haynes Carol , Burns Elizabeth , Craig Damian , Gregory Simon G , Hauser Elizabeth R , Shah Svati H , Kraus William E
Published: March 2022

Introduction:
Women are disproportionately affected by coronary artery disease (CAD). Among major factors such as age and anatomical differences, biologic contributions are purported; yet, little is understood about the underlying genomic architecture that may contribute to female-specific disparities. We explored whether genome-wide variants could predict survival in females with clinically-appreciable CAD, unique to that of male cases.

Methods:
A sex-stratified genome-wide association analysis was conducted for survivorship in Caucasian patients with CAD in a discovery cohort (
N
=1,099; 589 females) and a replication cohort (
N
= 404; 198 females), selected from a cardiovascular biorepository consisting of sequential patients referred for cardiac catheterization. CAD cases were defined as having a CAD index >32 (at least one vessel CAD) and indication for catheterization was concern for ischemic heart disease. GWAS genotyping was done using the Illumina Omni Quad v1.0 GWAS chip with stringent QC metrics. Sex-stratified, Cox multivariable regression models for each SNP (additive), adjusted for age and four Eigenstrat-defined principal components, were constructed (R statistical package), with models censored on time from cardiac catheterization to all-cause mortality/last follow-up (med 5.2 yrs).

Results:
Fourteen SNPs met nominal significance (p<10
-5
) for increased hazards of all-cause mortality in women; none of these SNPs or genes were even nominally significant at p<0.05 in male cases. Three top SNPs were biologically relevant: rs17591646 (
SLC9A9
;
HR
6.2,
95%CI
2.9-13.3,

p
discovery
=3.2x10
-6
,
p

replication

=0.68,
p

male

=0.87); rs12145981 (
NEK2/LPGAT1
;
HR
3.3,
95%CI
2.0-5.6,
p

d

=4.2x10
-6
,
p

r

=0.05,
p

m

=0.92); and rs7217169 (
RAP1GAP2
;
HR
4.1,
95%CI
2.3-7.5,
p

d

=4.3x10
-6
,
p
r
=0.02,
p
m
=0.44),

as they are involved in endosome recycling (
SLC9A9
), cardiolipin synthesis (
LPGAT1
), and regulating dense granule secretion from platelets at endothelial damage sites (
RAP1GAP2
).

Conclusions:
We present preliminary evidence of genome-wide candidates that appear to uniquely predict mortality risk in women with CAD. Further investigation of genomic variation may help improve understanding of sex differences in CAD disparities.
Abstract 18674: Predicting Long Term Outcome in Patients Treated With Continuous Flow Left Ventricular Assist Device - The Penn - Columbia Risk Score
Authors: Birati Edo Y , Hanff Thomas C , Maldonado Dawn , Grandin E. Wilson , Kennel Peter , Mazurek Jeremy A , Vorovich Esther , Phillips Emily , Acker Michael A , Naka Yoshifumi , Wald Joyce , Goldberg Lee R , Jessup Mariell , Atluri Pavan , Margulies Kenneth B , Schulze P. Christian , Rame J. Eduardo
Published: March 2022

Mechanical assist devices have emerged as an established therapeutic option for patients with end-stage heart failure. Predicting which patients are unlikely to benefit from continuous flow left ventricular assist device (cf-LVAD) treatment is crucial for the identification of appropriate patients while excluding those considered futile. Previously developed scoring systems are limited to prior eras of device and medical support or restricted to specific devices.

Methods:
We performed a retrospective analysis of all patients implanted with a cf-LVAD (Heartmate II or HVAD) at our institution between 2005 and 2014. From all plausible pre-operative covariates, we performed univariate Cox regression analysis for covariates affecting the odds of 1yr post implantation survival (p<0.4). These variables were included in a multivariable model and dropped if significance rose above p=0.4. From this base model, we performed stepwise forward and backward selection for other covariates that improved power by minimizing Akaike Information Criteria while maximizing the Harrell Concordance Index. We then used Kaplan-Meier curves, the log rank test, and Cox proportional hazard models to assess internal validity of the scoring system and its ability to stratify survival. The risk score was validated in another VAD center.

Results:
A total of 204 patients (male 78%; mean age 57+15, mean follow up 465+486 days). After stepwise selection for variables that increased predictive power, a final optimized model was identified (Figure). One yr survival was significantly lower in patients with higher risk score (HR 2.48, p=<0.001, figure). The validation cohort of 260 patients confirmed the prognostic utility of this risk score (p=0.0237).

Conclusion:
We present a novel risk score and its validation for prediction of long-term survival in patients on cf-LVAD support. This score may prove useful for patient selection and identification of patients requiring adjuvant therapies
Abstract 18677: Disease Progression in Human Heart Failure is Associated With Leptin Deficiency and Ketosis
Authors: Rame J. Eduardo , Cappola Anne R , French Benjamin C , Bedi Kenneth C , Wu Alan , Margulies Kenneth B , Cappola Thomas P
Published: March 2022

Introduction:
Dysregulation of the adipocyte hormone leptin has been implicated in insulin resistance and metabolic syndromes of excess non-esterified free-fatty acids (NEFAs). We have recently identified a reliance on ketones in the human end-stage failing heart, and described a metabolic signature of decreased myocardial acylcarnitines, disrupted Krebs cycling, and
increased
circulating NEFAs.

We hypothesize that the progression to end-stage heart failure is marked by loss of circulating leptin, as cachexia and increased lipolysis deplete the adipocyte mass sustaining the utilization of peripheral ketones by the heart.

Methods:
Leptin was measured for 1159 subjects in the Penn Heart Failure Study (R&D Systems ELISA). Circulating β-hydroxybutyrate (β-HB) was assayed utilizing a commercially available colorimetric assay (Caymen) in 16 lean, non-diabetic patients with end-stage heart failure at the time of cardiac transplantation and 18 non-failing, non-diabetic donors as controls.

Results:
Over a median follow-up time of 4.2 years, there were 337 events: 218 deaths, 92 transplants, and 27 LVAD placements. The figure below presents Kaplan-Meier curves for survival free from transplant or LVAD implantation by leptin tertiles (Logrank p=0.0003). After adjustment for covariates including BMI lower leptin levels remained associated with worsening survival (third versus first tertile of leptin: HR 0.73, p=0.04). In the patients with end-stage heart failure we found a significant increase in circulating β-HB (mean 145 μM versus 19 μM in non-failing, p=0.02) and NEFAs (mean 1.03mM versus 0.56mM in non-failing, p=0.01)

Conclusion:
Decreased circulating leptin is associated with worsening survival in human heart failure, while serum β-hydroxybutyrate is increased in advanced heart disease. Future studies will explore the mechanistic link between ketogenesis and dysregulated leptin in the emerging metabolic syndrome of heart failure.
Abstract 18682: Increased Oxidative Stress is Associated With Vascular Endothelial Dysfunction and Central and Peripheral Arterial Stiffening in Patients With Fontan Circulation
Authors: Kurishima Clara , Kuwata Seiko , Iwamoto Yoichi , Ishido Hirotaka , Masutani Satoshi , Senzaki Hideaki
Published: March 2022

Background:
It is well recognized that oxidative stress is responsible for fat accumulation and tissue inflammation, and causes endothelial cell damage that leads to the initiation of atherosclerosis. We and others have previously reported that vascular stiffness is increased with impaired vascular endothelial function in patients after Fontan operation. We hypothesized that increased oxidative stress is associated with vascular endothelial dysfunction and arterial stiffening in patients with Fontan circulation

Methods:
Relationship of oxidative stress with endothelial function and arterial stiffness was examined in 16 Fontan patients. Endothelial function and arterial stiffness of forearm artery was measured by flow mediated dilatation. We also measured central arterial stiffness by calculating aortic pulse wave velocity (PWV) during catheter drawback from the ascending aorta to the iliac bifurcation at the time of cardiac catheterization. Oxidative stress was estimated by measuring serum levels of oxidized low-density lipoprotein (LDL) and superoxide dismutase (SOD) activity in the urine as an anti-oxidant.

Results:
PWV of the ascending aorta but not of the descending aorta was significantly and positively correlated with oxidized LDL level (P<0.05). Ratio of oxidized LDL level and SOD activity, a balance between oxidative stress and antioxidant activity, was also significantly and positively correlated with the ascending aortic PWV. This was also the case even after controlling for age of the patients by multivariate analysis. Vascular stiffness and endothelial function of the forearm artery were correlated with the balance between oxidative stress and antioxidant activity. Enhanced oxidative stress was related to increased central venous pressure and age.

Conclusion:
Increased oxidative stress is associated with vascular endothelial dysfunction and central and peripheral arterial stiffening in patients with Fontan circulation. Antioxidant therapy may improve vascular health and thereby patient’s outcome after Fontan operation.
Abstract 18690: Risk Factors of Cardiovascular Fatal Events: 10 Year Follow up Cohort of 8,224 Subjects in Chile
Authors: Lira Maria Teresa , Kunstmann Sonia , Icaza Gloria , Nunez Loreto
Published: March 2022

Introduction:
Understanding the contribution of cardiovascular risk factors (CVRF) of cardiovascular fatal events incidence in different populations is crucial to identify susceptible individuals more accurately.

Objective:
To analyze the 10 year follow up survival of this population with and without CVRF, and to estimate their attributable risk of CV fatal events.

Method:
A single cohort of 8,224 subjects (35-74y) free from CV disease was screened for CVRF in 2002-2003 using standard methods. From them, 114 suffered a CV fatal event. Comparison of survival and incidence, between exposed/non exposed to CVRF, Preventable Fraction (PF), Population Attributable Fraction (PPF) were estimated (Kaplan Meier, Log Rank, Z statistic).

Results:
A total of 3,975 men (48.3%) and 4,249 women (51.7%) mean age 50.3 ± 10.1 were follow-up. (mean 10.9y. 89,825 y/person observation). CVRF prevalence was Sedentarism (68,7%), Hypercholesterolemia (55,1%), Abnormal Waist Circumference IDF cutpoint (53,0%) Smoking (40,6%), Hypertension (35,3%), Diabetes M II (5,5%). Survival analysis showed that Hypertension (p<0.0001), Diabetes (p<0.0001), Men (p=0.004) and IDF abnormal Waist Circumference (p=0.02) were associated with higher risk of suffering a fatal CV event in the studied period. Sedentarism, Hypercholesterolemia and Smoking, evidenced no event risk difference (p values 0.4, 0.69 and 0.67, respectively). PF of Diabetes was 73% IC (56.2-82.7) p<0.0001 and the PPF for Hypertension was 60.9% (51.8-68.2) p<0.0001

Conclusions:
In this population Hypertension and Diabetes add significant risk of suffering a fatal CV event in a 10y follow-up. 73% of events could be prevented in Diabetics II and up to 61% of CV fatal events incidence may be reduced with Hypertension control. Sedentarism, Hypercholesterolemia and Smoking are highly prevalent but evidenced no difference in survival rates. Identifying local attributable risk of CVRF aids to tailor preventive policies in different countries.
Abstract 18717: The Pro-osteogenic Phenotype of Interstitial Cells of Calcified Human Aortic Valves is Due to Altered Expression of Mir-486 and -204
Authors: Song Rui , Fullerton David A. , Ao Lihua , Zhao Kesen , Reece T. Brett , Cleveland Jr Joseph C. , Meng Xianzhong
Published: March 2022

The transition of aortic valve interstitial cells (AVICs) to myofibroblastic and osteoblast-like phenotypes plays a critical role in the progression of calcific aortic valve disease (CAVD). Understanding of the mechanism underlying AVIC phenotypic transition may lead to the development of therapeutic approaches for prevention of CAVD progression. Several microRNAs (miRs) have been implicated in stem cell differentiation into osteoblast. We
hypothesized
that an epigenetic mechanism regulates the myofibroblastic and osteoblast-like transition in AVICs. This study is to examine miR profile in diseased AVICs and to identify miRs responsible for cell phenotypic transition.

Methods and results:
AVICs were isolated from normal and diseased human aortic valves. MiR array analysis revealed 16 up-regulated and 14 down-regulated miRs in diseased AVICs, and increased miR-486 and decreased miR-204 were prominent and associated with higher levels of myofibroblastic biomarker α-smooth muscle actin (α-SMA) and osteogenic transcription factors Runx2 and Osx. MiR-486 antagomir and miR-204 mimic reduced the ability of diseased cells to form calcium deposits. While miR-486 antagomir suppressed α-SMA expression in diseased AVICs, miR-204 mimic suppressed the expression of Runx2 and Osx. MiR-486 mimic up-regulated α-SMA expression in normal AVICs through the PTEN-Akt pathway, and miR-204 antagomir up-regulated Runx2 and Osx levels by post-transcriptional modulation. Interestingly, miR-486 mimic and miR-204 antagomir synergistically up-regulated Runx2 and Osx in normal AVICs, resulting in greater calcium deposition. Knockdown of α-SMA attenuated the effect of miR-486 on osteogenic activities.

Conclusions:
In AVICs of diseased aortic valves, increased expression of miR-486 mediates myofibroblastic transition through the PTEN-Akt pathway, and decreased expression of miR-204 is responsible for the elevated osteogenic activity. MiR-486 also promotes AVIC osteogenic activity by inducing myofibroblastic transition. These novel findings indicate that modulation of the epigenetic mechanism underlying AVIC phenotypic transition and osteogenic activity has therapeutic potential for slowing down CAVD progression.
Abstract 18723: In vivo Tissue Engineered Small Diamiter Vascular Graft “Biotube”; Application to Off-pump CABG in the Porcine Model
Authors: Watanabe Taiji , Kanda Keiichi , Yamanami Masashi , Yaku Hitoshi , Nakayama Yasuhide
Published: March 2022

Objective:
In spite of the great labor and fund for the development of the small diameter vascular prostheses applicable to the coronary arterial bypass grafting (CABG), the only available grafts are still autologous arteries and veins. Aiming for the application to CABG and below knee distal arterial bypass grafting, we have developed autologous small diameter grafts (ID; 1.5 ~ 5 mm) “Biotubes” constructed in the recipient bodies. In AHA 2006, we have already reported that "BIOTUBEs" could be ideal small-caliber vascular grafts in rabbit model. In this study, we evaluate the feasibility of Biotubes to the off-pump CABG using an acute xenogeneic porcine model.

Materials & Methods:
Silicon rod molds (diameter; 3 mm, length; 15 cm) were embedded in the subcutaneous pouches of beagle dogs for 4 weeks to obtain Biotubes. They were xenogenically implanted to swine using conventional off-pump CABG technique (n=5). Top-end anastomosis of each Biotube was placed on innominate artery using 8-0 polypropylene sutures. Its distal end was anastomosed to the side of left anterior descending coronary artery (LAD) with 8-0 sutures using cardiac stabilizer.

Results:
The obtained Biotubes had very thin wall (less than 0.1 mm) mainly consisting of fibroblasts and collagen fibers as previously reported. However, anastomoses of Biotubes to native arteries were possible even under off-pump surgery with a little difficulty. Postoperative angiography and doppler flow meter confirmed their patency and durability without rupturing or aneurysm formation.

Conclusion:
Application of Biotubes to the off-pump CABG was technically feasible in an acute swine model. Long-term animal CABG implantation study using auto-grafts is planed in the next stage for clinical use.
Abstract 18727: Predictors of Health-related Quality of Life After Isolated CABG Surgery
Authors: Fornaresio Lisa M , Holmes Sari D , Shuman Deborah J , Pritchard Graciela , Ali Rabia , Armstrong Katherine , Ad Niv
Published: March 2022

Introduction:
The purpose of this study was to determine which factors were important in predicting HRQL scores at 6 months after isolated CABG surgery.

Methods:
Study includes patients who had isolated CABG from Sept 2005 to Sept 2014 and completed HRQL surveys (SF-12) before and 6 months postsurgery (
N
=818). Patients were categorized into 3 groups given 6 month course of General Health (GH) scores: decreased (
n
=153), no change (
n
=351), increased (
n
=314). Multivariate linear regressions were used to examine predictors for 6 month HRQL adjusting for baseline HRQL.

Results:
Baseline and 6 month scores on 10 SF-12 subscales are shown (FIGURE). Patients with no change or decreased GH had higher presurgery HRQL, but at 6 months, those with increased GH had the highest HRQL. In univariate analyses, lower operative risk (EuroSCORE II) presurgery correlated with greater GH (
P
<0.001) and physical composite score (PCS;
P
<0.001) improvement from before to 6 months after surgery. Independent predictors for greater GH at 6 months were: no peripheral vascular disease (
P
=0.029), no lung disease (
P
=0.001), no MI history (
P
=0.001), no blood product transfusion (
P
=0.027), and shorter LOS (
P
=0.004). Independent predictors for greater PCS at 6 months were: younger age (
P
=0.002), no lung disease (
P
<0.001), no MI history (
P
=0.001), no diabetes (
P
=0.005), no blood transfusion (
P
=0.001), and shorter LOS (
P
=0.002). Predictors for greater mental composite score at 6 months were older age (
P
<0.001) and no lung disease (
P
=0.003).

Conclusions:
Even patients who present with lower HRQL can see significant HRQL improvement after surgery. Comorbid conditions present before surgery impacted HRQL postsurgery and should be managed to minimize effects on HRQL improvements. Blood transfusion was associated with lower HRQL. Given previous literature on negative implications of blood transfusion after cardiac surgery and these results, more conservative blood transfusion protocols are warranted.
Abstract 18730: Impact of Hospital Volume on Outcomes of Endovascular Stenting for Adult Aortic Coarctation: A 12-year US Experience
Authors: Bhatt Parth , Sonani Rajesh , Patel Aashay , Thakkar Badal , Patel Achint , Savani Chirag , Dave Abhishek , Patel Samir , Patel Nilay , Arora Shilpkumar , Bhimani Ronak , Lahewala Sopan , Panaich Sidakpal , Jhamnani Sunny , Singh Vikas , Deshmukh Abhishek , Patel Nileshkumar J , Badheka Apurva O
Published: March 2022

Introduction:
Use of transcatheter endovascular stenting has been increasing in the treatment of Coarctation of Aorta (CoA). The present study was undertaken on adults with CoA undergoing stent placement from the period of 2000 to 2011 to analyze the relationship of hospital volume to the outcomes of stenting in adults with CoA.

Methods:
We queried Healthcare Cost and Utilization Project (HCUP)’s Nationwide Inpatient Sample (NIS) database from 2000 to 2011. Patients with CoA were identified using ICD-9-CM diagnosis code of 747.10. Patients≥18 years of age undergoing endovascular stenting were identified using ICD-9-CM procedure code of 39.90. Hospital volume was divided into two groups with ≥3 and <3 procedures annually. The outcomes studied were procedure-related complications, length of stay (LOS), and cost in relation to the hospital volume. Complications were coded using specific patient safety indicator codes released by HCUP. Length of stay (≤1 and >1 days) and cost (≤ $13,830 and > $13,830) were divided at median and included in regression analysis.

Results:
No in-hospital death was reported in either group. Hospitals with ≥3 procedures annually had significantly lower incidence of complications (9.50% vs. 23.01%) compared to the hospitals with <3 procedures annually (p=0.002). After multivariate regression analysis, compared to hospitals with <3 procedures annually, the hospitals with ≥3 procedures annually had odds ratio (OR) of 0.40 (95% CI: 0.19-0.82, p=0.013) for having any complications, OR of 0.67 (95% CI: 0.39-1.17, p=0.15) for having LOS>1 day, and OR of 0.72 (95% CI: 0.45-1.13, p=0.15) for having cost>$13,830.

Conclusion:
Stenting in adults for aortic coarctation is remarkably safe and the outcomes of the procedure have improved in centers with annual hospital volume of ≥3 procedures, and there is also decreasing trend of procedure-related complications, shorter hospital stay, and lower costs compared to centers with annual volume <3 procedures.
Abstract 18758: Hypertrophy of Neonatal Cardiomyocytes in 3D Engineered Cardiac Tissue Induced by Activation of mTOR Signaling
Authors: Jackman Christopher , Bursac Nenad
Published: March 2022

Introduction:
An in vitro system inducing robust hypertrophy of neonatal cardiomyocytes (CM) is highly useful for studying cardiac development and improving function of engineered cardiac tissues. Our objective was to establish a methodologically simple way to hypertrophy CMs in densely-packed engineered 3D tissues, and to identify signaling pathways involved.

Hypothesis:
We hypothesized that hypertrophy could be induced by enhancing mass transport of nutrients to CMs in degradable hydrogel, and this effect would act through mTOR signaling pathway.

Methods:
Neonatal rat CMs were embedded in fibrin-based hydrogel to form cardiac microbundles, which were cultured for 2 weeks on either a static or dynamic platform.

Results:
Dynamic culture increases the volume occupied by CMs (Fig 1A), quantified as 2.3-fold increase in CM cross-sectional area (Fig 1B). The amount of sarcomeric proteins was increased by 2.4 to 4.6 fold in dynamically cultured tissues (Fig 1C). mTOR phosphorylation was increased by 51% upon transfer to dynamic culture, and decreased by 42% upon transfer to static culture (Fig 1D). Dynamic cultures generated higher contractile force (2.09 +/- 0.10 mN vs. 0.65 +/- 0.11 mN), and inhibition of mTOR with rapamycin attenuated the effect (1.27 +/- 0.07 mN, Fig 1E, n=12). Conduction velocity of action potentials was increased from 38.1 +/- 2.2 cm/s in static cultures to 51.7 +/- 2.8 cm/s in dynamic cultures (n=19).

Conclusions:
Dynamic culture of 3D cardiac microtissues results in significant mTOR-mediated CM hypertrophy and contractile force increase without the need for biophysical or growth factor stimulation. For the first time, we show optimized cardiac microtissues with diameter and specific contractile forces similar to trabecular muscle of the adult myocardium (~200 um diameter, 61.5 mN/mm2).
Abstract 18761: Mechanical CPR associated With Decreased Survival From Out-of-hospital Cardiac Arrest
Authors: Buckler David , Li Kam Ching , Heisler Elizabeth , Kupas Douglas , Leary Marion , Abella Benjamin , Becker Lance
Published: March 2022

Background:
Randomized trials have shown mechanical CPR yields equivalent outcomes when compared to manual CPR for out-of-hospital cardiac arrest (OHCA). Many Emergency Medical Services (EMS) agencies have adopted mechanical CPR but data are lacking on the association of mechanical CPR with survival in real-world clinical practice.

Objective:
To assess the utilization of mechanical CPR and its association with survival to hospital discharge among adult cardiac arrest patients in Pennsylvania.

Methods:
Utilizing data from Pennsylvania within the Cardiac Arrest Registry to Enhance Survival, we identified all resuscitation events in which mechanical CPR was used and compared these to all other manual CPR cases. Events where ROSC occurred before mechanical CPR would have arrived on scene were excluded. Demographic and survival data were analyzed using chi-squared testing for categorical variables and t-test for continuous variables. Multivariable regression was used to control for confounding, including: age, witnessed arrest, arrest location, bystander CPR, arrest rhythm, and no flow time.

Results:
From 1/2012 to 12/2014, 10,457 cardiac arrests met inclusion criteria. Of those 1955 (19%) received mechanical CPR. Mean age was 66.7 ±15.9 years, and 34% received bystander CPR. Survival to hospital discharge was lower in the cohort receiving mechanical CPR compared to the cohort receiving manual CPR (106/1836 [5.8%] vs. 583/8048[7.2%], p=0.02). Good neurologic outcome was similarly reduced (80/1836[4.4%] vs. 453/8046[5.6%], p=0.02). In the adjusted model, use of mechanical CPR corresponded to reduced odds of survival to discharge (OR 0.75; CI 0.59-0.95; p=0.02) and good neurologic recovery (OR 0.75; CI 0.57-0.98; p=0.04). In this population, race or ethnicity were not associated with survival. We were unable to control for hospital and EMS agency characteristics or duration of resuscitation as possible confounders.

Conclusions:
Mechanical CPR is associated with a 25% lower likelihood of survival from OHCA in Pennsylvania, even after adjustments for patient and arrest characteristics. Further research needs to be conducted to understand factors associated with mechanical CPR use and OHCA outcomes, including possible unmeasured confounders.
Abstract 18808: Higher Short Term Mortality in Sickle Cell Patients Presenting With ST Elevation Myocardial Infarction
Authors: Rahman Riaz , Hajjali Raef
Published: March 2022

Introduction:
Sickle cell disease (SCD) has been shown in multiple studies worldwide to be associated with considerable morbidity and mortality, including a higher risk for acute myocardial infarction (AMI). However, the effect of SCD on outcome in patients with myocardial infarction remains unclear. We sought to investigate the in-hospital mortality in patients with SCD presenting with acute ST elevation myocardial infarction (STEMI) compared to the general population.

Hypothesis:
Short term mortality in patients with SCD presenting with STEMI is higher when compared to the general population.

Methods:
The National Inpatient Sample (NIS), part of the Healthcare Cost and Utilization Project (HCUP), is the largest publicly available inpatient database designed to provide information on characteristics and outcomes of patients discharged from US hospitals. Using the NIS database, we identified 879,108 adult patients with a primary diagnosis of STEMI in the period between 1998 and 2012. Among this patient population, 52 patients also had a diagnosis of SCD.

Results:
Compared to the general population, patients with SCD were significantly younger (55 years vs. 66 years, p<0.001), were more likely to be female (60% vs. 37%, p=0.001), and had a lower prevalence of hypertension (35% vs. 47%, p=0.06) and dyslipidemia (2% vs. 13%, p=0.02). They were less likely to undergo revascularization procedures compared to the general population (38% vs. 53%, p=0.04). The in-hospital mortality for patients with STEMI and SCD was 19.2% compared to 10.0% in patients without SCD (p=0.03). After adjusting for pertinent covariates using logistic regression analysis, SCD remained an independent predictor of higher in-hospital mortality (p=0.02, OR 2.4; 95% CI 1.1-5.1).

Conclusions:
Sickle cell patients have a higher in-hospital mortality compared to the general population when presenting with STEMI.
Abstract 18847: Impact of Coronary Artery Aneurysms in Myocardial Deformation of Convalescent Kawasaki Disease Patients
Authors: Sanchez Mejia Aura , Sexson Tejtel Kristen , Almeida-Jones Myriam , Feagin Douglas , Altman Carolyn , Pignatelli Ricardo
Published: March 2022

Background:
Abnormal strain, independent of coronary involvement, has been reported in the acute phase of KD. However, there is limited data about the impact of coronary aneurysms in myocardial deformation during the convalescent phase of KD.

Objective:
To perform a comprehensive assessment of myocardial deformation in patients with KD during the convalescent phase and assess for the effect of coronary artery aneurysms.

Methods:
KD patients with echocardiograms performed during the convalescent phase (>42 days from fever onset to study date) between 8/2013 -11/2014, and with adequate images for analysis with two-dimensional speckle tracking echocardiography (2DSTE) were included. Demographic, clinical, 2D and 2DSTE parameters were measured, including left ventricular global longitudinal strain (GLS), global circumferential strain (GCS) and strain rate (SR), torsion and right ventricular longitudinal strain (RLS) and SR. The patients with and without aneurysms were compared using Chi-square and T-test. Linear regression was used to assess association between variables.

Results:
A total of 67 patients were included. Table 1 shows the demographic, clinical and echocardiographic data. The groups differ in heart rate (HR) and body surface area (BSA). Treatment resistance and coronary involvement at presentation were more frequent in the aneurysms group. The myocardial deformation values were within normal limits for age. However, the aneurysms group had significantly lower GLSR and GCSR relative to the group without aneurysms. GLSR was associated with BSA and HR and GCSR with age, p<0.05 for all.

Conclusions:
Convalescent KD patients with aneurysms have subtle decrease in LV longitudinal and circumferential myocardial deformation. This data suggests potential impact of chronic coronary involvement in the myocardial function of KD patients that warrants follow-up. BSA, HR and age should be considered when evaluating GLSR and GCSR.
Abstract 18849: Molecular Signature of Early Cardiovascular Lineages Revealed by Single Cell Transcriptomics
Authors: Gong Wuming , Das Satyabrata , Pan Wei , Koyano-Nakagawa Naoko , Garry Daniel J
Published: March 2022

Background:
The molecular definition of the differentiation process of cardiovascular lineages is of intense interest for developmental biologists. Recent studies have demonstrated that multipotent cardiac progenitors are capable of giving rise to multiple cardiovascular lineages such as endothelium, endocardium, epicardium and myocardium. Moreover, Nkx2-5 and Etv2 are two of the key genes that regulate the specification of the cardiac lineage. Understanding the global gene expression pattern and ontogeny of Nkx2-5 and Etv2 positive cells are critical steps for the decoding of the signaling cascade and the molecular mechanisms that govern mesodermal lineage differentiation.

Methods:
Using Etv2- and Nkx2-5-EYFP transgenic embryos, from which progenitors of cardiovascular/circulatory lineages can be isolated with high purity, we performed single cell transcriptome analysis. We used our recently developed single cell RNA-seq analysis pipeline,
dpath,
to decompose the transcriptome into seven major metagenes. Each gene and each cell was assigned the “metagene signature” based on its unique and robust features, which successfully captured their molecular dynamics and global expression patterns.

Results:
An unbiased clustering analysis using the metagene signature of 459 Etv2- and Nkx2-5 EYFP positive cells from E7.75 and E8.25 embryos revealed 16 mesodermal cell populations with distinct global gene expression patterns. The metagene entropy analysis revealed distinct differentiation potential and mesodermal lineage coverage among Etv2-EYFP
+
and Nkx2-5-EYFP
+
cells. Two major Nkx2-5
+
cell populations were significantly associated with the first and second heart fields and novel gene markers for each heart fields were identified. We also discovered multiple types of endocardial populations from different sources and with distinct global gene expression patterns.

Conclusions:
We report the analysis of complete gene expression profiles during mesodermal lineage specification at a single cell resolution. These results demonstrate the power of combining machine learning algorithms and single cell RNA-seq for discovering hidden cell types from mixed cell population and novel lineage markers.
Abstract 18858: Assessment of Coronary Artery Aneurysms Caused by Kawasaki Disease Using Transluminal Attenuation Gradient Analysis of Coronary CT Angiograms
Authors: Grande Gutierrez Noelia , Shirinsky Olga , Gagarina Nina V , Lyskina Galina A , Fukazawa Ryuji , Ogawa Shunichi , Burns Jane C , Marsden Alison L , Kahn Andrew M
Published: March 2022

Introduction:
Patients with coronary artery aneurysms (CAA) resulting from Kawasaki Disease (KD) are at risk for thrombosis and myocardial infarction. Current guidelines recommend using CAA diameter >8mm as the criterion for initiating systemic anticoagulation, but this is not based on outcome or simulation data. Transluminal Attenuation Gradient (TAG) has been proposed as a non-invasive method for evaluating the functional significance of coronary stenoses from CT Angiography (CTA). However TAG has not been previously used for the assessment of CAA.

Hypothesis:
We hypothesized that abnormal flow conditions in CAA caused by KD could be quantified using TAG.

Methods:
We studied 23 patients with a history of KD who had undergone clinically indicated CTA. We quantified TAG in the major coronary arteries by performing linear regression of the average lumen intensity as a function of vessel length. Aneurysm geometry was characterized using maximum aneurysm diameter, aneurysm shape index (ASI) and sphericity index.

Results:
A total of 41 arteries were analyzed, 22 of which had at least one aneurysmal region. TAG of aneurysmal arteries was significantly lower than in normal arteries (-22.4±10.5 vs. -9.3±10, p=0.0003). Differences were also significant in aneurysmal vs. normal LAD and RCA sub-groups (-26.7±9.7 vs. -16.5±9.0, p=0.02; -14.7±8.2 vs. -0.1±4.4, p=0.001). Aneurysm diameter, ASI, and sphericity index showed little to no correlation with TAG (r2=0.04, r2=0.18, r2=0.17).

Conclusions:
This study is the first application of TAG in CAA from KD, and demonstrates significantly different TAG values in aneurysmal compared to normal arteries. Lack of correlation between TAG and CAA geometry suggests that TAG may provide information on hemodynamic conditions not available from anatomy alone. The use of TAG in KD patients represents a possible extension to standard CTA that could aid in clinical decision-making and help to better evaluate the risk of thrombus formation.
Abstract 18861: Effects of Class III Antiarrhythmics on ICD Therapies and Clinical Outcomes: A Meta-analysis of Randomized Controlled Trials
Authors: Kancharla Krishna , Oktay Ahmet A , Kumar Shashi , Kaddaha Firas , Pamidimukala Chaithanya , El Hayek Georges , Benjo Cezar , Molina Marcos , Kanaan Salim , Herzog Eyal , Aziz Emad , Benjo Alexandre M
Published: March 2022

Introduction:
Implantable cardioverter defibrillators (ICD) prolong survival in patients with heart failure, reduced left ventricular ejection fraction (LVEF <= 35%) and/or sustained ventricular arrhythmias (VA) by terminating VA with either anti-tachycardia pacing (ATP) or shock. However, ICD therapies are associated with significant pain, psychological distress, and increased risk for hospitalization and mortality. Antiarrhythmic drugs are commonly used to reduce frequency of VA in patients with ICD. We attempt to study the effects of class III antiarrhythmics on the frequency of ICD therapies, hospitalization and mortality.

Methods:
PubMed database was queried to identify prospective randomized controlled trials comparing class III antiarrhytmics to placebo on a standard background medical therapy in patients with an ICD and prior history of sustained VA (spontaneous/ treated/ induced) and/or sudden cardiac death. Information on appropriate ICD therapy, hospitalization and mortality was extracted. Fixed effect analysis was used when I2 ≤ 25% and p >0.1, otherwise random effect analysis was performed.

Results:
After reviewing 2931 articles, seven trials that studied Amiodarone, Sotalol, Azimilide or Celivarone were included. A total of 2117 patients (87% males, mean age 63.8 years, mean LVEF 32.8%) were analyzed. 50.6% of the patients had at least one appropriate ICD therapy delivered and 4.5% died during the follow up. Antiarrhythmic drug usage significantly reduced the number of patients receiving ICD therapy by 55% (OR=0.45, 95% confidence interval [CI] 0.26-0.77, P=.004). There was no significant difference in mortality between treatment and placebo arms. Only 2 of the 7 trials reported number of hospitalizations and the sample size was insufficient for analysis.

Conclusions:
Class III antiarrhythmics significantly reduced ICD therapy for VA with no significant change in mortality.
Abstract 18870: Impact of Atherectomy on Length of Stay and Cost of Care for Lower Extremity Arterial Intervention - A Cross-sectional US Experience
Authors: Patel Nilay , Arora Shilpkumar , Lahewala Sopan , Panaich Sidakpal S , Patel Nileshkumar , Savani Chirag , Dave Abhishek , Thakkar Badal , Patel Achint , Bhatt Parth , Patel Sanskruti , Patel Samir V , Sonani Rajesh , Agnihotri Kanishk , Patel Aashay , Singh Vikas , Jhamnani Sunny , Deshmukh Abhishek , Badheka Apurva O
Published: March 2022

Background:
There is lack of data regarding impact of atherectomy on the length of stay (LOS) and cost of hospitalization in lower extremity arterial revascularization.

Methods:
HCUP’s Nationwide Inpatient Sample (NIS) 2012 was queried using the ICD-9- CM code for peripheral vascular disease and procedural codes 39.90 (bare metal stent - BMS), 00.55 (drug eluting stent - DES), 17.56 (peripheral atherectomy) and 39.50 for angioplasty. Only procedures performed in patients ≥18 years of age were included. Hierarchical mixed effects linear regression models were generated to evaluate multivariate predictors of LOS and hospitalization costs.

Results:
A total of 13,206 (weighted: 66,030) lower extremity arterial revascularizations were identified (43.8% female & 65.5% white). Out of these, atherectomy was utilized in 23.2%. Atherectomy utilization was associated with significant reduction in LOS (4.96 ± 0.11 days vs. 5.78 ± 0.07 days, p <0.001) but higher hospitalization cost ($ 25196 ± 359 vs. $ 23408 ± 185, p < 0.001). Multivariate analysis showed similar results with decrease in LOS (-0.71 days, -1.00 - - 0.43; p < 0.001) but higher hospitalization cost (+1875 $, +811 - +2940; p = 0.001) with atherectomy, which was matched by propensity score analysis. Additionally, emergent/urgent & weekend admissions and Charlson score ≥2 were further associated with increased LOS and hospitalization costs. (Figure)

Conclusion:
Our study demonstrates that atherectomy utilization is associated with significant reduction in length of stay, which was counterbalanced by a slight increase in hospitalization costs following lower extremity arterial revascularization.
Abstract 18898: Long Non-coding RNA Fingerprint Regulated by Stretch and Cyclic Strain in Vascular Smooth Muscle Cells: Implications for Aortic Aneurysms
Authors: Mantella Laura-Eve , Kantores Crystal , Singh Krishna K , Quan Adrian , Al-Omran Mohammed , Jankov Robert P , Verma Subodh
Published: March 2022

Background:
Alterations in the characteristics of vascular smooth muscle cells (VSMCs), triggered largely by changes in mechanical stress, play a critical role in the pathophysiology of aneurysms and hypertension. Understanding the molecular determinants that link altered rheology to aberrant VSM remodeling may uncover novel approaches to treat vascular diseases. Long noncoding RNAs (lncRNAs) are a new class of noncoding RNA and emerging evidence suggest that they not only have a key role in the regulation of various biological processes but also represent a cellular hub for coordination of various cellular, inflammatory, and immune reactions involved in health and disease. In the present study, we report for the first time the lncRNA fingerprint regulated by cyclic strain in VSMCs.

Methods and Results:
VSMCs were plated on Bioflex plates, starved, and subjected to 20% elongation (1 Hz) for 24 h (Flexcell® FX4000™). Total RNA was extracted using TRIzol. LncRNAs and mRNAs were profiled with the Arraystar Human LncRNA Microarray V3.0. Of the 30,586 human lncRNAs screened, 580 were differentially expressed (p<0.05) in stretched VSMCs. Amongst the 26,109 protein-coding transcripts evaluated, 26 of those differentially expressed were associated with 28 of the aforementioned differentially expressed lncRNAs (p<0.05). Subsequent KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that the differentially expressed mRNAs chemokine (C-X-C motif) ligand 1/2/3/5 (CXCL1/2/3/5), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) and vascular cell adhesion protein 1 (VCAM1), were largely associated with the tumor necrosis factor (TNF) signaling pathway, which has been previously associated with VSMC stretch-response. Further Gene Ontology analysis indicated that the differentially expressed mRNAs were associated with cell differentiation, stress response, response to external stimuli and cell migration.

Conclusions:
We provide the first global fingerprint of cyclic strain regulated lncRNAs in VSMC cells. This information provides novel insights into the regulatory switches governing aberrant VSMC remodeling, which may have importance in the pathogenesis of aneurysms and hypertension.
Abstract 18926: Metformin is Associated With Improved Skeletal Muscle Glucose Uptake and Improves Skeletal Muscle Energetics. There is Limited Data of the Impact of Metformin Us on Need for Repeat Revascularization in Patients With Symptomatic Peripheral Artery Disease (pad) Treated With Endovascular Revascularization
Authors: Banerjee Avantika , Mohammad Atif , Kocak Denizen , Planchard Kyle , Das Thomas , Brilakis Emmanouil
Published: March 2022

Background:
Metformin is associated with improved skeletal muscle glucose uptake and improves skeletal muscle energetics. There is limited data of the impact of metformin us on need for repeat revascularization in patients with symptomatic peripheral artery disease (PAD) treated with endovascular revascularization.

Methods:
We compared need for vessel revascularization (TLR) rates in patients with diabetes mellitus (DM) treated with metformin and without, to non-DM enrolled in the Excellence in Peripheral Artery Disease (XLPAD) registry (NCT01904851) between 2006 and 2015.

Results:
In the study cohort of 2140 interventional procedures, 57.4% were performed in DM (n=268 on metformin and n=961 not on metformin). Frequency of hypertension, hyperlipidemia and chronic kidney disease was higher in DM not on metformin compared to DM on metformin (p<0.001 for all comparisons). Lesion and stent lengths were similar in both groups. Revascularization free survival compared to the non-DM (control) was similar for DM on metformin (HR=0.95, 95%CI: 0.56-1.60; p=0.85) compared to DM not on metformin (HR=1.84, 95%CI: 0.98-3.45; p=0.06; Figure 1A). Overall survival compared to non-DM (control), was similar for DM on metformin (HR=1.70, 95%CI: 0.64-4.54; p=0.29) and significantly worse for DM not on metformin (HR=4.55, 95%CI: 2.44-8.48; p<0.001; Figure 1B).

Conclusions:
Metformin therapy in symptomatic PAD patients with DM following endovascular revascularization is associated with improved survival and lower need for repeat revascularization compared to diabetics not treated with metformin.
Abstract 18939: Micro RNA-93 Promotes Macrophage M2 Polarization in Experimenal Peripheral Arterial Disease
Authors: Ganta Vijay C , Kutateladze Anna , Annex Brian , Leitinger Norbert
Published: March 2022

Macrophages (MØ) were well known to play vital roles in promoting blood flow by arteriogenic induction in experimental Peripheral Arterial Disease (PAD). MØs depending on the cytokine milieu, exist in M1 or M2 polarization states (two extremes of polarization continuum). While M1-MØs are pro-inflammatory and anti-angiogenic, M2-MØs are anti-inflammatory and pro-angiogenic. We have previously demonstrated that Micro RNA-93 (Mir93) promotes angiogenesis and perfusion recovery in experimental PAD. However, the downstream mechanisms that operate in Mir93 mediated perfusion recovery in ischemic leg are not yet clear. In our current study we investigated the role of Mir93 in MØ polarization in vitro and in animal models of hind limb ischemic (HLI). We hypothesized that “Mir93 induction in ischemic muscle promotes M2-MØ polarization that improves tissue repair, survival and neovascularization in PAD”

Mir93 mimic transfection in Raw264.7 (MØ cell line) significantly induced Arginase-1 (M1 marker) expression and decreased inducible Nitric oxide synthase (iNOS) (M2 marker) expression compared to negative mimic in qPCR analysis. Bone marrow derived macrophages (BMDM) from MCM7-KO (Mir93 deficient mice) express significantly higher levels of iNOS compared to littermates under hypoxia serum starvation. Monocytes isolated from the bone marrow of MCM7-KO ischemic legs express significantly higher levels of iNOS compared to littermates. Conditioned medium from Antagomir-93 treated Raw264.7 MØs and MCM7-KO BMDM significantly decreased HUVEC capillary like tube formation on matrigel compared to negative antagomir treated or littermates. Flow cytometry analysis showed that MCM7-KO mice had significantly higher levels of M1-MØs correlating with decreased capillary density compared to litter mate controls. P<0.05 considered significant

We conclude that Mir93 plays a crucial role in inducing MØ-M2 polarization. Increased Mir93 levels in ischemic hind limb promote M2-MØ polarization that helps in recovery of ischemic leg by tissue repair and neovascularization. Ongoing experiments are aimed to determine whether Mir93 deficient MØs can inhibit perfusion recovery in littermates and the downstream targets of Mir93 that regulate MØ polarization in HLI