bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P366: Fasting Glucose and Insulin Resistance Trajectories in Young Adulthood and Cognitive Function in Middle Adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Bancks Michael P , Carnethon Mercedes , Jacobs David R , Launer Lenore , Reis Jared , Schreiner Pamela J , Shah Ravi , Sidney Steve , Yaffe Kristine , Yano Yuichiro , Allen Norrina B
Published: March 2022

Introduction:
Whether multiple unique trajectories in fasting glucose (FG) and insulin resistance (HOMA-IR) are present during young adulthood and if such trajectories are associated with cognitive function in middle adulthood is unclear.

Hypothesis:
We hypothesized that a high-increasing trajectory of FG and HOMA-IR in the absence of diabetes during young adulthood would be associated with lower level of cognitive function in midlife compared to a low trajectory.

Methods:
We studied 2,650 CARDIA participants, age 18 to 30 years (1985-1986) to determine FG and HOMA-IR at baseline and 7, 10, 15, and 20 year follow-up exams (≥ 8 hours fasting and not pregnant). Using latent class analysis (SAS Proc Traj), we determined trajectory groups for FG and HOMA-IR through year 20. Cognitive function was assessed at year 25 (2010-2011) with three cognitive tests including the Digit Symbol Substitution Test (DSST; a test of sustained attention, psychomotor speed, working memory, and executive function), Rey-Auditory Verbal Learning Test (RAVLT; verbal memory), and Stroop Test (executive function). We used multivariable linear regression to estimate adjusted means for each cognitive test according to trajectory group for both FG and HOMA-IR for individuals free from diabetes during follow-up, after adjustment for potential confounding factors.

Results:
We identified three trajectory groups for FG and HOMA-IR for individuals free from diabetes in middle adulthood, qualitatively low-stable to increasing, moderate-increasing, and high-increasing. Compared to the low FG trajectory group, the high FG trajectory group had significantly lower mean score for the RAVLT, shown in the
Table
. Otherwise, cognitive test scores generally did not differ according to FG or HOMA-IR trajectory group.

Conclusion:
In this community-based sample of individuals free from diabetes, a high-increasing FG trajectory through young adulthood was associated with worse memory in midlife.
Abstract P379: Leg Length, Marker of Environmental Exposition During Early Lifetime, and Subclinical Cardiovascular Disease
Authors: Alba Xiomara , Stern Dalia , Puchner Karl , Ortiz Eduardo , Yunes Elsa , Cantú-Brito Carlos , Zuñiga Jorge , Lajous Martin , L. Ridaura Ruy
Published: March 2022

Introduction:
Intrauterine and early life factors such as low birth weight, not being breastfed, smoking parents, and other socioeconomic conditions have been associated with later predisposition to chronic diseases. Although there still exists controversy in which is the best marker for environmental exposition during early lifetime, leg length has been one of the most accepted.

Hypothesis:
There is an inverse relationship between leg length and subclinical cardiovascular disease (sCVD).

Methods:
We conducted a cross-sectional analysis of a sub sample of 2,038 women from the Mexican Teacher’s Cohort. Participants underwent anthropometry during clinical assessments. Trunk length was calculated as the height measured in seated position minus the height of the stool participants were sitting on. Leg length was defined as height minus trunk length. Carotid intima media thickness(CIMT) was measured by trained neurologists through standardized ultrasound and log-transformed. We defined sCVD as CIMT ≥0.8 mm or the presence of plaque. We used multivariable linear and logistic regression models to estimate the association between leg length quartiles with CIMT and sCVD respectively.

Results:
Mean height was 153.8 cm and mean leg length was 72 cm. The prevalence of sCVD was 23%(469 of 2038). Participants with shorter legs were likely to report low birthweight, indigenous origin, rural residence, and low socioeconomic environment. We observed an inverse relationship between leg length and mean IMT when we compared the lowest(median 67cm) to the highest quartile(median 77.1 cm) (
multivariable-adjusted mean % difference= -2.93; 95% CI-5.53,-0.32
). In contrast to the lowest quartile, the multiple-adjusted odds ratio for sCVD in the highest quartile was 0.58(
95% CI 0.34, 0.98
). Additional analysis controlling for mediators such as weight, diabetes, hypertension and hypercholesterolemia weakened the association but remained significant.

Conclusion:
We found a significant association between leg length, CIMT and sCVD in a population of middle-aged Mexican women.
Abstract 20898: The Value of Sensing Optimization During Exercise After S-ICD Implantation
Authors: Kooiman Kirsten M , Baalman Sarah W , Brouwer Tom F , Quast Anne Floor B , Knops Reinoud E
Published: March 2022

Introduction:
T-wave oversensing (TWOS) is the main cause of inappropriate shocks (IAS) in patients with a subcutaneous ICD (S-ICD). Sensing optimization during exercise post S-ICD implantation may prevent IAS caused by TWOS. In our tertiary center, sensing optimization after S-ICD implantation has been used as standard of care since 2014. Improved detection and sensing algorithms, like high pass filter designs, are expected to overcome the problem of TWOS, but the value of sensing optimization during exercise is unknown.

Hypothesis:
Sensing optimization during exercise prevents TWOS-related IAS in patients implanted with an S-ICD.

Methods:
Sensing optimization was performed within two months in all patients who underwent S-ICD implantation or replacement. Sensing was evaluated during maximal exercise and a new QRS morphology template was stored. The optimal sensing vector was determined based on absence of TWOS and optimal R-T ratio. Follow-up data on IAS was divided into a group before and a group after introduction of the high pass filter, and compared with data of S-ICD patients and IAS in our institution before 2014.

Results:
We analyzed 65 patients (69% male, mean age 45 years, ischemic cardiomyopathy in 25%, genetic arrhythmia disease in 37%). Mean maximal heart rate (maxHR) was 142 bpm. A new template was stored in 61 patients (94%). TWOS was observed in 12 patient (18%), but not in the programmed sensing vector selected by the post implant automatic setup. The sensing vector was changed in nine patients (14%) (mean age 35 years, maxHR 163 bpm) based on drop in QRS amplitude in five patients, variable QRS amplitudes in two, an inferior R-T ratio in one and sensing of myopotentials in one. The IAS incidence caused by TWOS declined from 11.6% in 2012 to 2.0% and 0% before and after the introduction of the high pass filter, respectively.

Conclusions:
There is a decrease in TWOS-related IAS. Sensing optimization during exercise may be an additional tool to overcome TWOS-related IAS in S-ICD patients. Future studies may identify patients, such as those capable of reaching high heart rates, who are most likely to benefit from sensing optimization during exercise.
Abstract 20905: The Force-Displacement Relationship in Commonly Used Resuscitation Manikins: Not Very Human
Authors: Thomsen Jakob E , Stærk Mathilde , Løfgren Bo
Published: March 2022

Introduction:
Manikins are widely used for CPR training and designed to simulate a human in cardiac arrest. Previous studies show a non-linear force-displacement relationship in the human chest. This may not be the case for resuscitation manikins. The aim of this study was to investigate the force-displacement relationship in commonly used resuscitation manikins.

Methods:
Commonly used infant and adult manikins for resuscitation training were included in the study. Manikins were tested by placing them in a material testing machine (ProLine Z050, Zwick/Roell, Ulm, Germany). A piston was placed on lower half of the sternum of the manikin. The testing machine applied a constant growing force downwards on the manikin chest while recording the force-displacement relationship. The test was stopped when either the manikin was nearly fully compressed or the displacement exceeded 7 cm. On manikins with adjustable compliance of the thorax, the medium setting was used. The force needed to achieve the recommended compression depth i.e. 3 cm and 5 cm were compared for infant and adult manikins respectively.

Results:
Seven different resuscitation manikins were included in the study; two infant manikins: Resusci Infant (Laerdal) and CPR Anytime® Infant (inflatable; American Heart Association) and five adult manikins: Mini Anne (inflatable), Little Anne®, Resusci Anne, Resusci Anne Advanced(Laerdal) and Ambu® Man (Ambu). Infant manikins required a force of 57 N and 34 N to compress the chest 3 cm. The force required to compress the adult manikins to a depth of 5 cm ranged from 195 N to 543 N. The force-displacement curve is shown in the Figure.

Conclusions:
Four out of five adult resuscitation manikins and one infant manikin had a nearly linear force-displacement curve different from the human chest. The Mini Anne and Resusci Infant showed a non-linear curve more like the human chest. The force needed to compress the chest to the recommended chest compression depth varied between manikins.
Abstract 20910: Alpha-Ketoglutarate Metabolism Regulates Oncometabolic Adaptation in the Heart
Authors: Karlstaedt Anja , Khanna Radhika , McNavish Daniel , Taegtmeyer Heinrich
Published: March 2022

Introduction:
The term “cancer and the heart” traditionally refers to the cardiotoxic effects of chemotherapeutic agents. However, independent of any cytostatic treatment cancer survivors have a five-fold higher risk for developing heart failure. Therefore, new therapeutic strategies must consider tumor biology when aiming at protecting the heart. In isocitrate dehydrogenase (IDH)1 and 2 mutant tumors, the elevated production of the oncometabolite D-2-hydroxyglutarate (D2-HG) is associated with systemic effects, including dilated cardiomyopathy. About 20% of acute myeloid leukemia cases harbor mutations of the IDH, which leads to reduced patient survival and causes metabolic dysfunction through production of the oncometabolite D2-HG. Recent findings have shown that D2-HG impairs oxidative decarboxylation of α-KG, which in turn increases ATP citrate lyase activity.

Hypothesis:
Based on these findings we are now proposing that modulation of ACL activity reverses D2-HG mediated metabolic changes.

Methods:
As models we used isolated working rat hearts; and combined C13-tracer studies with computational flux analysis.

Results:
Wild type rat hearts were perfused with the ACL inhibitor BMS303141 (0.5 μM; BMS) or D2-HG (1 mM). Cardiac power rapidly declined by 25% in the presence of BMS or D2-HG alone. Simultaneous perfusion with D2-HG and BMS, improved cardiac power, suggesting that modulation of ACL improves cardiac function only in presence of D2-HG. Further, α-KG dehydrogenase (α-KGDH) activity increased with ACL inhibition, reflecting an inverse relationship between these enzymes. Computational flux analysis using the metabolic genome-scale network CardioNet revealed that D2-HG-dependent inhibition by α-KGDH shifts cardiac metabolism towards increased reductive carboxylation of α-KG.

Conclusions:
Our findings suggest an “oncometabolic axis” in the heart and underscore the potential application of ACL inhibitors to protect the heart from failing in IDH-mutant tumors.
Abstract 20918: Cytokines Involved in Arterial Wall Inflammation Are Transported by High Density Lipoprotein Particles
Authors: Creasy Kate Townsend , Stock Eveline O , Tian Xiaoli , Prakash Arun , Pullinger Clive R , Malloy Mary J , Kane John P
Published: March 2022

Introduction:
Inflammation plays an important role in the induction of CAD and the progression to deadly coronary syndromes. Cytokines are key mediators of inflammation, both in pro- and anti-inflammatory capacities. HDL has a vital role in the maintenance of cardiovascular health, and recent discoveries highlight the diversity of HDL functions to include the transport of lipid signaling molecules, microRNAs, and other effectors of metabolic regulation. Given the importance of HDL in transporting molecules involved in cardiovascular health, we questioned if HDL has a direct role in transporting cytokines and effecting inflammatory responses in CAD.

Hypothesis:
HDL plays an important role in the transport of cytokines involved in CAD.

Methods:
To explore the role of HDL in arterial inflammation, we profiled the abundance of 35 cytokines in plasma and HDL of men and women with and without CAD. We analyzed whole plasma and native HDL isolated using a selected-affinity immunosorption technique from patients who suffered myocardial infarction at an early age (<60 years, male n=19; female n=20) and control patients (male n=10, female n=10). Samples were assayed by multiplex array technology for quantification of cytokines.

Results:
Of 35 cytokines analyzed, 25 appear to be significantly transported in HDL. Three cytokines (IL-12, MCP-1, and IL-RA) are excluded from HDL and are only detectable in plasma. IL-3 and IL-7 are predominately associated with HDL and are elevated in both males and females with MI. There are differences in several HDL-associated cytokines that appear to be sex-dependent.

Conclusions:
We have discovered that a number of cytokines are transported in HDL complexes. Significant elevations or decreases in a number of these cytokines are observed in patients with CAD, and vary in abundance between males and females.
Abstract 20927: Use of a Novel Pre-Shaped Nitinol Esophageal Deviator (EsoSure®) to Successfully Ablate the Left Atrium Without Esophageal Temperature Rise During Atrial Fibrillation Ablation: The DEFLECT GUT Study
Authors: Lakkireddy Dhanunjaya , Parikh Valay , Reddy Madhu , Swarup Vijay , Hantla Jacob , Di Biase Luigi , Al-Ahmed Amin , Natale Andrea
Published: March 2022

Background:
Esophageal injury is a feared complication of atrial fibrillation (AF) ablation. Esophageal temperature monitoring has been used as a surrogate marker for potential esophageal thermal injury. Often times, rise in esophageal temperature during radiofrequency ablation (RFA) for AF limits the ability to deliver RF energy.

Objective:
The aim of this study was to evaluate the safety and efficacy of the EsoSure® (Northeast Scientific, Inc., Waterbury, CT), a mechanical esophageal deviation tool, during RFA for AF.

Methods:
In this prospective observational series, we evaluated 135 consecutive patients from 4 centers in whom luminal esophageal temperature (LET) rise or likely rise was limiting RFA lesion delivery on the posterior wall of the LA. EsoSure® was used to deflect the esophagus away from the ablation site in the LA. Light Barium was used to visualize and confirm esophageal displacement in all patients. Baseline demographics, procedural variables and complication rates were collected and evaluated. Patients were followed up to 3 months for clinical signs and symptoms of esophageal injury.

Results:
The mean age of our sample was 64 ± 10 years and 77 (57%) patients were males. Mean CHA2DS2-VASc score was 2.72 ± 1 and 97 (74 %) patients had paroxysmal AF. The mean deviation of the trailing edge of the esophagus with EsoSure® was 2.6 ± 1 cm (range: 0.8 - 4.5 cm). Successful intra-procedural end point, defined as successful pulmonary vein isolation, was achieved in 100% of patients. Among the 96 (71%) patients in whom EsoSure® was used after an increase in LET, the mean peak rise of LET was 1.3 ± 0.2° C prior to the EsoSure® use and 0.2 ± 0.1° C after the EsoSure® use (p<0.001). There were no complications related to the EsoSure® use through 3-month follow-up. No symptoms suggestive of esophageal injury were noted related to AF ablation.

Conclusions:
Mechanical displacement of the esophagus with EsoSure® device appears to be safe and efficacious in enabling adequate RF energy delivery to the posterior wall of the LA during RFA for AF without significant luminal temperature rise and obvious clinical signs or symptoms of esophageal injury up to 3 months of follow up.
Abstract 20929: Impact of Complete Revascularization on Long-Term Clinical Outcomes in Patients With Multi-Vessel Disease Including Chronic Total Occlusion
Authors: Kim Ji Bak , Choi Byoung Geol , Rha Seung-Woon , Jang Ho-Jun , Choi Rak-Kyeong , Choi Young Jin , Oh Dong Joo
Published: March 2022

Introduction:
Chronic total occlusion (CTO) intervention is still challenging because of the limited procedural success rate and higher recurrence. Also, it is not clear whether the complete revascularization will significantly improve the angiographic and clinical outcomes in patients with multi-vessel disease (MVD) including CTO.

Hypothesis:
We assessed that the impact of complete revascularization on long-term clinical outcomes in patients with MVD including CTO.

Methods:
A total of 559 CTO patients with MVD who underwent percutaneous coronary intervention (PCI) for CTO lesion at Sejong General Hospital and Korea University Guro Hospital were enrolled and divided into two groups according to complete revascularization (CTO-PCI; n=325) or not (optimal medial therapy for non-CTO lesion, CTO-OMT; n=234). To adjust potential confounders, a propensity score matching (PSM) analysis was performed. The individual and composite major clinical outcomes were compared between the two groups up to 5 years.

Results:
After PSM analysis, two PSM groups (186 pairs, total=372) were generated and the baseline characteristics were balanced. Although the CTO-PCI group showed a higher incidence of target lesion and vessel revascularization (TLR and TVR) on CTO, there was a trend toward lower incidence of myocardial infarction (MI) and the incidence of total death or myocardial infarction (MI) was lower in the CTO-PCI group compared with the CTO-OMT group up to 5 years (Table).

Conclusions:
In the present study, successful CTO-PCI was associated with a lower trend of MI as well as reduction of the risk of total death or MI up to 5-year in CTO patients with MVD regardless of treatment strategy for the non-CTO target vessel.
Abstract 20933: Regulation of Hypoxia Induced Cardiac Cell Death by the Intrinsic Circadian Clock
Authors: Kirshenbaum Lorrie A , Rabinovich-Nikitin Inna , Gang Hongying , Margulets Victoria , Aguilar Floribeth
Published: March 2022

Circadian rhythms play a fundamental role in cell metabolism and tissue homeostasis and are influenced by the diurnal oscillation of cellular circadian clock genes. Zeitgebers influence the activation of the circadian rhythm by serving as molecular switches for the intrinsic cellular clock. Herein, we provide new evidence that hypoxia is a Zietgeber for the circadian rhythm and regulator of
clock
gene expression in cardiac myocytes. We further show that clock gene regulation promotes survival of cardiac myocytes by a mechanism that bi-directionally influences the inducible death protein Bnip3. Cardiac myocytes exhibited phasic oscillations in
clock
gene expression under basal conditions. Interestingly, in contrast to control cells, a marked time dependent decline in
clock
gene transcription was observed in cardiac myocytes subjected to hypoxia with maximal decline occurring at 18hrs. This coincided with a reciprocal increase in the expression of the mitochondrial autophagy protein Bnip3 and cell death. Given that Bnip3 is transcriptionally repressed under basal conditions, we reasoned that
clock
may promote cell survival by negatively regulating Bnip3 gene transcription. While Bnip3 transcription was markedly increased in cardiac myocytes subjected to hypoxia, gain of function of clock suppressed Bnip3 gene activation and cell death of cardiac myocytes. Hence, the findings of the present study provide the first direct evidence that hypoxia is a circadian Zeitgeber for circadian rhythm in cardiac myocytes. We further show that circadian protein Clock regulates cell survival during hypoxic injury by a mechanism that involves the transcriptional repression of Bnip3.
Abstract 20935: Improving Spinal Cord Protection During the Frozen Elephant Trunk Technique: Effect of a Dedicated Neuroprotection Protocol
Authors: Iafrancesco Mauro , Ranasinghe Aaron , Adam Donald , Claridge Martin , McCafferty Ian , Riley Peter , Clift Paul , Mascaro Jorge
Published: March 2022

Introduction:
The frozen elephant trunk (FET) technique may be complicated by a risk of spinal cord injury (SCI) which has been reported as high as 10%.Precise mechanisms responsible for SCI after FET are still unclear and so the best protection strategy to avoid it.

Hypothesis:
We aim to review our experience with a specific protocol developed to reduce the risk of SCI during open surgery of the descending aorta applied to patients operated with FET in order to increase spinal cord protection

Methods:
Spinal cord protection protocol included: 1.Careful preoperative planning to deploy of stent above the level of the 10th thoracic vertebra and preserving the patency of the left subclavian artery; 2.Postoperative management with goal directed therapy aimed to achieve mean systemic blood pressure between 85 and 105 mmHg, cardiac index >2.4 l/min/m2, urine output >1 ml/Kg/min, a base excess of 0±5, a pH>7.3 and haemoglobin level >10 g/dl; 3.Cerebrospinal fluid (CSF) drainage was used in 4 patients (5.8%) only

Results:
From April 2006 to December 2015 69 patients underwent aortic repair with the FET at our Institution.There were 31 males (51.7%). Median [IQR] age was 69 [59-75] years and median [IQR] Log EuroSCORE was 20.3 [13.9-36.2].

There were 19 (27.5%) reoperations. Operative times and outcomes are reported in Table 1.

Conclusions:
SCI remains the Achilles’ heel of the FET procedure.Elevated blood pressure in the preoperative period may reduce the risk of SCI by increasing the collateral network remodeling.Careful preoperarative planning and avoidance of sacrifice of all thoracic segmental arteries and preservation of left subclavian artery patency may reduce the risk of SCI maintaining good collateralization of the spinal cord perfusion network.Attention to all haemodynamic and metabolic parameters may avoid further ischemic insults to the spinal cord. CSF drainage may not be necessary in all cases of FET
Abstract 20942: Non-Invasive Isolation of the Pulmonary Veins in an Animal Model
Authors: Van Langenhove Glenn , Boussy Tim
Published: March 2022

Introduction:
Pulmonary vein isolation (PVI) is well established as the preferred treatment for symptomatic paroxsysmal atrial fibrillation (pAF). We introduce a novel technique in which PVI is aimed for in a pig model, by non invasive heating of the proximal ring of an implant inserted in the pulmonary veins.

Hypothesis:
Non-invasive heating of an implant in the PV is feasible and safe

Methods:
A self-expanding nitinol-based implant was positioned in the common inferior pulmonary vein of 11 pigs, using a fluoroscopy guided transatrial approach. In a second part of the experiment, implants were positioned in the superior caval vein through a transfemoral approach of another 6 animals. Ablation was performed through a contactless energytransfer from a primary extracorporal coil to a secondary heatring (HR) embedded in the proximal part of the implant. Electrophysiological properties were assessed prior to and post ablation. Histological samples were obtained after 3 months.

Results:
In total, eightteen PV-implants were succesfully positioned. Ablation was performed in a safe manner, without injury of adjacent structures. PVI and bidirectional block was confirmed in all PV cases, and bidirectional block in 5 of the 6 caval vein implants (entry block shown in the figure-the heatring is at the level of the white arrow). Only mild neointimal proliferation was observed 3 months post ablation.

Conclusions:
Non-invasive ablation using self-expanding stents in the PV is safe and feasible, bidirectional isolation can be demonstrated in almost all cases, whilst no significant neointimal formation is observed:
Abstract 20946: Decreasing Mortality and Hospital Costs: Trends in Congestive Heart Failure Exacerbation Admissions From 2004 to 2014
Authors: Ahsan Syed A , Hosseini Dehkordi Seyed Hamed , Gholitabar Farid , Lee Shawn , Lemor Alejandro , Gholitabar Navid , Herzog Eyal
Published: March 2022

Introduction:
Congestive Heart Failure (CHF) exacerbations are associated with high mortality rates and exact significant costs on the health care system. New guidelines, innovations in technology and novel pharmacological agents for treatment of patients admitted with CHF have been developed in the last decade. While they have been shown to improve outcomes independently, data is limited on the cumulative effects of these interventions. We investigated the impacts of these therapeutic modalities over 10 years, and hypothesized improved outcomes of in-hospital admission for CHF exacerbation.

Methods:
This is a retrospective cohort study using the 2004-2014 National Inpatient Sample, the largest publicly available inpatient database in the United States. We included women and men >18 years of age admitted between 2004 and 2014 with a primary diagnosis of CHF (using ICD-9 CM codes). The primary outcome was all-cause in-hospital mortality and the secondary outcomes were mean total hospital cost and mean length of stay (LOS). STATA 13.0 was used for data analysis; costs were adjusted for inflation using the Bureau of Labor Statistics calculator.

Results:
2,254,286 patients were included in this study. The mean age was 72.6 years, and 1,142,923 patients were female (50.7%). The inpatient mortality rate was 3.9% in 2004 and decreased with statistical significance to 2.9% in 2014 (p-trend <0.001) [Figure 1]. Mean hospital cost adjusted for inflation was $11605 in 2004 and decreased to $11,272 in 2014 [Figure 2]. Mean LOS decreased from 5.4 days in 2004 to 5.2 days in 2014.

Conclusions:
Over the course of 10 years, advances in care for patients with CHF have led to improvements in inpatient mortality rates, with marginally decreased hospital costs when inflation is taken into account. This likely reflects advances in comprehensive cardiovascular care, increasing use of evidence based guidelines, and introduction of novel medications and new therapeutic modalities.
Abstract 20956: Acute Kidney Injury Following Angiography and Endovascular Therapy for Lower Extremity Peripheral Arterial Disease: An Analysis From the National Inpatient Sample
Authors: Hughston Haley K , Michalek Joel , Martinez John P , Hoang Dale T , Trevino Aron , Gupta Kamal , Masoomi Reza , Prasad Anand
Published: March 2022

Introduction:
Patients undergoing endovascular therapy (EVT) for lower extremity peripheral arterial disease (PAD) are at risk for acute kidney injury (AKI). The purpose of this study was to determine the incidence, risk factors, and outcomes of AKI in the context of EVT from the National Inpatient Sample (NIS).

Methods:
Patient admissions in the NIS were queried from 2003-2012. The admissions were limited to non-dialysis patients with either critical limb ischemia (CLI) or claudication undergoing either EVT and/or angiography. AKI was defined using a composite of ICD-9 codes which have been previously validated in this context. Available comorbidity data, demographics, and inpatient outcomes (AKI, mortality) were analyzed using multivariable logistic regression models with age expressed in decades.

Results:
552,484 admissions for CLI and 441,736 for claudication were included. The incidence of AKI is shown in the figure. The multivariate predictors of AKI in patients with claudication undergoing EVT only included age (OR 1.05, CI [1.02-1.09], P<0.001), female gender (OR 1.1, CI [1.01-1.15], P=0.03), heart failure (OR 2.8, CI [2.6-3.1], P<0.001), chronic kidney disease (CKD) (OR 6.5, CI [6.0-7.1], P<0.001), and diabetes (OR 1.1, CI [1.05-1.2], P=0.001). A similar analysis for CLI patients revealed the following predictors: age (OR 1.1, CI [1.09-1.12], P<0.001), heart failure (OR 2.1, CI [2.05-2.22], P<0.001), CKD (OR 2.8, CI [2.7-2.9], P<0.001), diabetes (OR 1.2, CI [1.1-1.2], P<0.001), and stroke (OR 1.6, CI [1.45-1.7], P<0.001). AKI was an independent predictor of mortality in patients undergoing EVT with either claudication (OR 17.8 [15.5, 20.5], P<0.001) or CLI (OR 4.6 [4.2, 4.9], P<0.001).

Conclusions:
AKI occurs in approximately 3.5% of patients undergoing endovascular procedures for claudication and 10.9% in CLI patients. CKD and heart failure are the strongest risk factors for AKI. AKI is an independent predictor of inpatient mortality.
Abstract 20958: Smyd1a Overexpression Suppresses Functional Decline in the Adult Myocardium
Authors: Szulik Marta , Wang Li , Garcia-Llana June , Tracy Christopher , Franklin Sarah
Published: March 2022

Heart disease is the leading cause of death in the United States. This chronic condition affects the heart so it can no longer sufficiently pump blood to vital organs in the body. While heart disease can manifest in many different ways the general pathophysiology is conserved: the heart compensates for an increased workload by undergoing hypertrophic growth, accompanied by transcriptional reprogramming, and progresses into heart failure. Although many epigenetic factors have been identified which influence these underlying changes in transcription during disease, we still know very little about how this process is regulated in the cardiomyocyte. Smyd1, a unique histone methyltransferase that regulates gene expression in the cardiomyocyte, was originally shown to play a crucial role in early cardiac development. More recently, we have shown that loss of Smyd1 in the adult mouse heart leads to pro-hypertrophic signaling resulting in cardiomyocyte growth, fibrosis and functional decline. In addition, we examined the two Smyd1 isoforms (Smyd1a and Smy1b) in isolated myocytes and showed that Smyd1a (but not Smyd1b) overexpression (OE) was capable of inhibiting phenylephrine-induced hypertrophy. To further characterize the role of Smyd1 in the myocardium and determine if Smyd1a is capable of inhibiting hypertrophic growth in adult heart we generated transgenic mice capable of inducible, cardiac-specific OE of Smyd1a using a Tet-On system. Mice were fed doxycycline-laced chow for 2 weeks to achieve Smyd1a-OE at which time we characterized their cardiac phenotype under basal conditions and after stress (permanent occlusion). Interestingly, transgenic mice showed no observable difference under basal conditions, however, 3 weeks after permanent occlusion of the LAD, the EF of wild type animals decreased to ~37%, while transgenic mice maintained an EF of ~61% . In addition, transgenic mice exhibited exacerbated growth (12% increase in HW/BW ratio) with no change in expression of the hypertrophic marker ANF, in contrast to wild type animals (4 fold increase). These exciting results suggest that Smyd1a is capable of preserving cardiac function in adult mice, however, this mechanism appears to be independent of hypertrophic signaling.
Abstract 20966: Increasing Cav1.2 in Smooth Muscle Cells Has Different Effects on Vascular Remodeling Dependent of Insults
Authors: Zhang Ying , Zhou Jian , Zhang Xioaying , Zhang Chen , Shen Ying H , Chen Xiongwen
Published: March 2022

Introduction:
Increasing Calcium (Ca
2+
) influx through the L-type Ca
2+
channel (Cav1.2) increases smooth muscle cell (SMC) contractility while the loss of Cav1.2 is associated with enhanced SMC remodeling. However, increasing Ca
2+
influx into SMCs through non-Cav1.2 routes is often associated with enhanced vascular remodeling under pathological conditions. Whether increasing Cav1.2 in SMCs may inhibit or promote SMC remodeling is unclear.

Hypothesis:
Increasing Cav1.2 in SMC protects SMCs from remodeling.

Methods:
Transgenic mice with SMC-specific overexpression of Cavβ2a and control mice were subjected to carotid artery ligation or aneurysm induction (high fat feeding for 2 months and then HFD+AngII infusion for 1 month) to study vascular remodeling.

Results:
1. The Cav1.2 current in SMCs from middle cerebral artery was increased by 98.5±5.4%; 2. The left common carotid artery (LCCA) close to the internal and external arterial bifurcation were completely ligated. After ligation for 3 weeks, there were less thickening of the media and less neointima formation in LCCA region proximal to the ligation in TG (n=8) than in control (n=8) mice; in accordance, there were less EdU labelled cells in TG. The surface area of TG SMCs was not increased as such as in the control. 3. HFD+AngII induces higher frequency (10/10 in TG vs. 4/13 in control) of aneurysm/aortic dilation segments. Among the mice with aortic aneurysm/dilation, the average number of segments of aneurysm/arotic dilation in each mouse was higher in TG (2.7±0.2) than in control (1.3±0.2) mice. The TG mice had thinner vascular wall, larger aneurysmal area accompanied with more severe elastin and middle layer degradation, and more inflammatory cell infiltration in the aortic aneurysm/dilation region than control mice. 4. Rat smooth muscle cells in culture infected with Cavβ2a-GFP adenoviruses (MOI=10) had less proliferation (both total number of cells and EdU
+
cells) but more death (LDH and TUNEL+) than rat SMCs infected with AdGFP (MOI=10). Less collagen synthesis was observed in rat SMCs infected with Ad Cavβ2a-GFP.

Conclusions:
Increased Cav1.2 in SMCs may inhibit or promote vascular smooth muscle remodeling depending on the injury nature.
Abstract 20981: Use of Intrathoracic Pressure Regulation Therapy in Breathing Patients for the Treatment of Hypotension Secondary to Trauma
Authors: Convertino Victor A , Parquette Brent A , Wampler David A , Manifold Craig A , Lindstrom David A , Boland Lori L , Burkhart Nathan , Segal Nicolas , Lurie Keith G , Lick Charles J
Published: March 2022

Objectives:
Intrathoracic pressure regulation therapy (IPRT) has been shown to increase blood pressure in hypotensive patients. The potential value of this therapy in patients with hypotension secondary to trauma with bleeding is not well understood.

Hypothesis:
We hypothesized that IPRT would non-invasively and safely enhance blood pressure in spontaneously breathing patients with trauma-induced hypotension.

Methods:
This prospective observational cohort study assessed vital signs from hypotensive patients with a systolic blood pressure (SBP) ≤90 mmHg secondary to trauma treated by pre-hospital emergency medical personnel with IPRT (ResQGARD) in three large US metropolitan areas. Upon determination of hypotension, facemask-based IPRT was initiated as long as bleeding was controlled. Vital signs were recorded before, during, and after IPRT. An increased SBP with IPRT use was the primary study endpoint. Device tolerance and ease of use were also reported.

Results:
A total of 54 patients with hypotension secondary to trauma were treated from 2009 to 2016. The mean (± SD) SBP increased from 81 ± 12 mmHg to 107 ± 19 with IPRT (p < 0.0001) and mean arterial pressures (MAP) increased from 62 ± 11 mmHg to 82 ± 17 (p < 0.0001). There were no significant changes in mean heart rate or oxygen saturation. Approximately 75% of patients reported moderate to easy tolerance of the device. There were no safety concerns or reported adverse events.

Conclusion:
In patients with hypotension secondary to trauma IPRT increased blood pressure to levels known to provide near normal or normal vital organ blood flow in the vast majority of patients. Patients were treated safely and not over resuscitated with this intervention. These findings support the use of IPRT to treat trauma-induced hypotension as long as bleeding has been controlled.
Abstract 20984: Transfer of Functional Properties From the Two-Domain Apolipoprotein E3 to a Single Domain 5-Helix Bundle Apolipoprotein
Authors: Horn James V , Kakutani Leesa M , Kiss Robert S , Narayanaswami Vasanthy , Weers Paul M
Published: March 2022

Apolipoprotein E3 (apoE3) is a 34 kDa exchangeable apolipoprotein critical for lipid transport and associates with chylomicrons, VLDL, and a subclass of HDL. The protein contains two independently folded domains: a 22 kDa N-terminal domain and a 10 kDa C-terminal domain. The N-terminal domain contains LDL receptor binding sites and is tightly folded into a 4-helix bundle. The smaller C-terminal (CT) domain contains helical segments that: (i) promote protein-protein interaction and apoE3 self-association, (ii) bear high lipid binding affinity, and, (iii) facilitate cholesterol efflux from macrophages. In contrast, insect apolipophorin III (apoLp-III) is a one-domain protein bearing a 5-helix bundle, does not self-associate and binds to diacylglycerol enriched lipoproteins. To better understand the domain organization of apolipoproteins, a chimeric protein was constructed of apoLp-III and the CT domain of apoE3 (residues 201-299). The structure and function of the 28 kDa apoLp-III/CT-apoE3 chimera was determined and compared to that of parent proteins apoLp-III and apoE3. The novel chimeric construct was expressed in
E. coli
and purified using an N-terminal poly-histidine tag. Electrophoresis and Western blot analysis showed that the apoLp-III/CT-apoE3 chimera was of the expected size and reacted with apoE3 specific antibodies. Circular dichroism demonstrated that the chimera was α-helical, similar to both parent proteins. While apoLp-III was monomeric, the chimera formed tetramers similar to apoE3. Probing for hydrophobic pockets on the protein surface with anilinonaphthalene-8-sulfonic acid demonstrated that the CT domain provided increased binding sites for the probe. Addition of the CT domain to apoLp-III conferred an increased ability to promote cholesterol efflux from J774 macrophages, comparable to that of parent apoE3. Thus, the fold of apoLp-III/CT-apoE3 chimera was similar to that of apoE3, promoted self-association and cholesterol efflux. This demonstrated that functional characteristics of CT domain of apoE3 can be transferred independently to another apolipoprotein, allowing us to further increase our understanding of apolipoprotein domains.
Abstract 20993: Role of Noncoding scaRNA20 in Differentiation of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: Rajasingh Sheeja , Bittel Douglas C , Samanta Saheli , Zhou Zhigang , Barani Bahar , Drosos Nicholas , Dawn Buddhadeb , Rajasingh Johnson
Published: March 2022

Introduction:
Studies have shown that mRNA splicing is regulated by scaRNAs and plays a significant role in mammalian cardiac development and differentiation, but the potential contribution to human in vitro differentiation of iPSCs into CMCs remains unknown. In this study, the comparison of scaRNA20 modified and unmodified iPSCs derived-CMCs (iCMCs) will allow us to understand the role of scaRNAs in cardiac differentiation.

Hypothesis:
We hypothesize that CMCs modulated with scaRNA20 plays an important role in iPSCs-derived CMC differentiation.

Methods and Results:
Recently, our RNA sequencing analysis of iCMCs indicated that scaRNA20 plays an important role in CMC differentiation. We observed that si-scaRNA20 knockdown iPSCs underwent CMCs differentiation. They failed to grow as mature functional CMCs (
Fig. A
) and the number of beating clusters were reduced compared to the scrambled control cells
(Fig. B).
Our FACS data showed that there was a significant reduction in the expression of Gata4 and CTT in the CMC-derived from iPSCs kockdown with si-scaRNA20-1 but not in those with si-scaRNA-2
(Fig. C)
. Similarly, our FACS data from scaRNA20 overexpressing iPSCs differentiated into CMCs showed a significant increase in the number of Gata4- and CTT-expressing cells, suggesting the role of scaRNA20 in CMC differentiation.

Conclusions:
We report for the first time the role scaRNA20 in the regulation of in-vitro cardiac development.
Abstract 20999: Cardiac Implantable Electrical Device Related Procedures and Associated Complications in Continuous Flow LVAD Recipients: A Multicenter Experience
Authors: Gopinathannair Rakesh , Dhawan Rahul , Trivedi Jaimin , Roukoz Henri , Bhan Adarsh , Ahmed Mustafa M , Bhat Geeta , Cowger Jennifer , Slaughter Mark S , Ravichandran Ashwin
Published: March 2022

Introduction:
Patients with continuous flow Left Ventricular Assist Devices (LVAD) and concomitant Cardiac Implantable Electrical Devices (CIED) are prone for device and lead-related complications requiring intervention.

Hypothesis:
We evaluated the incidence and characteristics of CIED-related procedures and complications and their association with survival in a multicenter LVAD cohort.

Methods:
We retrospectively reviewed data on 480 LVAD patients with a CIED from 5 centers. Of the 480, 235 patients had accurate long-term CIED follow-up data and were used for this analysis. Kaplan Meier analysis was used to assess survival differences between patients with CIED-related complications versus those who did not.

Results:
Of 235 patients with an LVAD and a CIED (Age 58±13, 80% male), 130 had a CRT-D and 105 had ICD only. During a median LVAD follow-up of 692 days, 103 patients required a CIED generator replacement with CRT-D patients having a significantly higher rate of generator replacement compared to the ICD only group (68[52%] vs 35[33%], p=0.003). A CIED or lead-related complication occurred in 36 (28%) of CRT-D patients and 16 (15%) of the ICD patients (p=0.06). 20 (15%) patients in the CRT-D group and 14 (13%) in the ICD group underwent lead removal or extraction during follow-up (p=0.5). Both the CRT-D and ICD groups had comparable incidences of pocket hematoma (8% vs 5%), pocket and/or lead infection (9% vs 4%), and lead malfunction (8% vs 9%). Kaplan Meier analysis showed no significant survival difference between those who had a CIED-related complication versus those who did not (log rank p= 0.7).

Conclusions:
CIED related procedures are common in LVAD patients. Compared to ICD only, continued CRT-D post-LVAD resulted in a significantly higher number of generator changes and showed a trend towards higher device or lead related complications. CIED-related complications were not associated with reduced survival.
Abstract 21002: Comparison of Clinical Outcomes of Patients With Acute Heart Failure and Recovered Ejection Fraction versus Preserved or Reduced Ejection Fraction
Authors: Cho Jae Yeong , Kim Kye Hun , Lee Sang Eun , Cho Hyun Jai , Lee Hae-Yeoung , Choi Jin-Oh , Jeon Eun-Seok , Kim Min-Seok , Kim Jae-Joong , Hwang Kyung-Kuk , Chae Shung Chull , Baek Sang Hong , Kang Seok-Min , Choi Dong-Ju , Yoo Byung-Su , Ahn Youngkeun , Park Hyun-Young , Cho Myeong-Chan , Oh Byung-Hee
Published: March 2022

Introduction:
Recent studies showed that patients with chronic heart failure with recovered ejection fraction (HFrecEF) have better clinical outcomes than those with preserved ejection fraction (HFpEF). However, there is lack of data about HF prognosis according to EF change in acute heart failure (AHF). Therefore, the aim of this study was to investigate the prognosis of HFrecEF compared to HFpEF in patients with AHF.

Methods:
A total of 5,625 cohort patients with AHF enrolled in Korean AHF registry (KorAHF). Of them, 2,632 patients underwent follow-up echocardiography with measurement of EF. They were divided into three groups according to EF change: HF with reduced EF (HFrEF) (n=1,522, 68.6±14.5 years, 818 males), HFpEF (n=281, 72.6±13.5 years, 115 males), and HFrecEF (n=829, 67.6±14.2 years, 341 males). HFrEF was defined as AHF patients with EF <50%, HFpEF as EF >=50%, and HFrecEF as EF>=50% with previous EF <50%. Primary end-point was all-cause mortality at 1-year follow up.

Results:
Patients were older (72.6±13.5 vs. 67.6±14.2 vs. 68.6±14.5 years, p<0.001) and more likely to be female (59.1% vs. 41.1% vs. 46.3%, p=0.058) in HFpEF group than in HFrecEF and HFrEF group. Systolic BP was lowest (136.7±31.1 vs. 128.6±29.9 vs. 131.9±29.7 mmHg, p<0.001) in the HFrecEF group. In echocardiographic exam, EF was lowest in the HFrecEF group (60.0±6.4% vs. 30.4±10.1% vs. 37.8±15.8%, p<0.001) and E/e’ was highest (18.7±10.9 vs. 22.0±12.0 vs. 21.2±11.3, p<0.001). Ischemic etiology was less evident in the HFpEF group (22.1% vs. 40.0% vs. 39.0%, p<0.001), but valvular (29.5%), hypertensive (6.8%), and tachycardic etiologies (12.8%) were more frequent in the HFpEF group. In clinical outcomes, 1-year death was highest in the HFrecEF group (13.9% vs. 18.3% vs. 16.6%, p=0.752) and rehospitalization rate was comparable between the groups (42.7% vs. 41.9% vs. 45.5%, 0.141). Kaplan-Meier survival analysis showed that 1-year mortality in the HFrecEF group was marginally higher than that in the HFpEF group (p=0.046 by log rank test).

Conclusions:
AHF patients in HFrecEF group had higher mortality than those in HFpEF group. Recovery from acute depressed LV function may not always warrant favorable clinical outcomes in long-term follow-up.
Abstract 21009: Outcomes of Pregnancy in Young Women With Valvular Dysfunction, 2005-2015
Authors: Batra Jaya , Chikwe Joanna , Itagaki Shinobu , Lee Timothy , Toyoda Nana , Egorova Natalia N
Published: March 2022

Background:
For young women who require cardiac valve replacement, the optimum prosthetic type for successful future pregnancy is not well established. Current data is limited to single-center studies and guidelines offer weak or no recommendations on valve selection. This study compares outcomes of pregnancy in women with mechanical valves (MHVs), bioprosthetic valves (BHVs), and valve repair.

Methods:
This was a retrospective analysis of 268 pregnancies in 222 women with a history of cardiac valve replacement or repair in California and New Jersey between 2005 and 2015. Each pregnancy was treated as a unique event. Patients were identified using state-run mandatory administrative databases which capture all inpatient, emergency department, and ambulatory surgery discharges. A multivariable logistic regression model with clustering by patient was used to identify factors associated with pregnancy loss, defined as spontaneous or induced abortion, fetal death, or maternal death prior to delivery. Covariates included maternal demographic characteristics and baseline comorbidities, time between most recent valve operation and pregnancy, year of pregnancy, and valve characteristics.

Results:
There were 64 pregnancies with MHVs present, 107 with BHVs, and 97 with repair only. Mean age at the time of first valve operation was 27.5 years (SD, 7.9 years; range, 11.2-53.7 years). Mean maternal age was 30.3 years (SD, 6.4 years; range, 15.6-54.9), with no significant difference between the three groups. Rates of spontaneous abortion for MHVs, BHVs, and repair were 32.8%, 8.4%, and 13.4%, respectively (p<0.0001), and rates of total pregnancy loss were 57.8%, 15.0%, and 22.7% (p<0.0001). After adjustment for covariates, the odds ratio for pregnancy loss with MHVs compared to BHVs was 5.3 (95% CI, 3.9-28.3) and 1.2 (95% CI, 0.9-6.2) with repair compared to BHVs. Other risk factors for pregnancy loss included maternal age ≥35 years and maternal hypertension.

Conclusion:
For women in the United States with mechanical heart valves, the risk of pregnancy loss is significant, with less than half of all pregnancies successfully progressing to delivery.