bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9294: Spironolactone Reduces Galectin-3 Levels in Mildly Symptomatic Systolic Heart Failure Patients
Authors: Gucuk Ipek Esra , Akin Suljevic Senay , Demirel Haydar , Karalok Neslihan , Guray Yesim
Published: April 2024

Background:
Galectin-3, is a biomarker believed to reflect cardiac remodeling and fibrosis in patients with heart failure. Spironolactone, has been reported to reduce fibrosis, improve cardiac function and survival in heart failure patients. Whether spironolactone improves remodeling process by altering galectin-3 is unknown.

Methods:
14 patients (ejection fraction ≤35, NYHA class II) being treated with guideline base treatments were enrolled to the study. Baseline echocardiographic measurements were noted and serum samples were obtained for galectin-3 levels. After excluding renal failure and hyperkalemia they were prescribed spironolactone, 25 mg daily. Patients were followed during 3 months for side effects. After the third month of follow up, echocardiographic measurements were repeated and serum samples were recollected for galectin-3 levels.

Results:
The mean age of the patients was 67±11, 64% of the patients were male. Most of the patients (93%) had ischemic cardiomyopathy. Of all, 14% had diabetes, 71% had hypertension. There was no significant change in left atrial diameter, left atrial volume, left ventricular end systolic diameters and myocardial performance indexes. Comparing to baseline measurements, there were significant improvements in left ventricular ejection fraction (30.3±4.6 vs. 31.3±4.5, p=0.04), left ventricular end diastolic diameter (58.9±0.5 vs. 58.2±0.6, p=0.03), left ventricular end diastolic volume (137.2±16.4 vs. 127.8±20.4, p=0.002), left ventricular end systolic volume (95.4±15.3 vs. 88±16.9, p=0.002). Galectin-3 levels decreased significantly after commencing spironolactone treatment (1.49±0.58 vs. 0.98±0.29 p=0.01). Decrease in galectin-3 levels were significantly correlated with the improvements in the left ventricular end diastolic and end systolic volumes (p=0.01 and p=0.02 respectively).

Conclusions:
Administration of spironolactone to patients with mildly symptomatic heart failure has beneficial effects on left ventricular remodeling and has a correlation with a significant decrease in serum galectin-3 levels. Spironolactone may improve remodeling by altering galectin-3 levels. Larger studies are necessary to evaluate whether these findings have clinical implications.
Abstract 9313: Progression of Coronary Plaque Burden In Patients With Familial Hypercholesterolaemia: Assessment With Coronary CT
Authors: Tada Hayato , Kawashiri Masa-aki , Nakanishi Chiaki , Konno Tetsuo , Sakata Kenji , Hayashi Kenshi , Yoshimuta Tsuyoshi , Nohara Atsushi , Inazu Akihiro , Mabuchi Hiroshi , Yamagishi Masakazu
Published: April 2024

Background:
It is well known that patients with familial hypercholesterolemia (FH) exhibit markedly elevated LDL-C levels resulting premature coronary artery disease. Statins have been shown to be effective in delaying the onset of coronary artery disease even in patients with FH. However, the optimal timing for initiation of lipid-lowering therapy for heterozygous FH patients still remains unclear. The aim of our study was to determine the optimal timing for initiation of lipid-lowering therapy for heterozygous FH.

Methods and Results:
Genetically determined 42 heterozygous FH patients were included in this study (mean age 54±13, male=23, initial mean LDL-C=250±40mg/dl). All patients underwent contrast-enhanced 64-slice coronary CT using the standard protocol. We evaluated coronary plaque burden assigning score (0 to 5) to each of 15 coronary artery segments according to the Society Cardiovascular Computed Tomography guideline. Almost all FH patients were treated with statins during a period of 8±4 years before coronary CT. From the regression equations between age (X) and stenosis index (Y) (Figure), we can assume that coronary artery stenosis detectable by coronary CT will occur after 17 years of age in male, and 28 years in female heterozygotes FH patients, respectively even under the statin uses .

Conclusions:
These data suggest that coronary artery stenosis detectable by coronary CT will occur after 17 and 28 years of age in male and female heterozygous FH, respectively, even in the strong statin era. We suggest that the lipid-lowering therapy for heterozygous FH should start at least by these early ages in terms of prevention from coronary plaque burden.
Abstract 9368: Long QT Syndrome and Therapy for Attention Deficit/Hyperactivity Disorder
Authors: Zhang Claire , Moss Arthur J , McNitt Scott , Zareba Wojciech , Kaufman Elizabeth S
Published: April 2024

Objective:
This study was designed to investigate the clinical course of patients with long QT syndrome (LQTS) who are treated for attention deficit/hyperactivity disorder (ADHD) with medications.

Background:
Current literature on the effect of ADHD treatment on the clinical outcome of LQTS patients is limited. We hypothesized that LQTS patients on ADHD pharmacotherapy, which has known adrenergic side effects, would be at increased risk for cardiac events.

Methods:
Patients in this study were from the Rochester-based LQTS Registry. LQTS patients being treated with stimulant or non-stimulant ADHD medications (n=48) were compared to a 2:1 age-, gender-, and QTc-duration matched LQTS control group not exposed to ADHD medications (n=96). Kaplan-Meier and Cox proportional hazards regression analyses were used to evaluate risk of cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) in LQTS patients treated with ADHD medications compared to those who were not.

Results:
During a mean follow-up of 7.9 ±5.4 years of follow-up after initiation of ADHD medication at a mean age 10.7 ±7.3 years, there was a 62% cumulative probability of cardiac events in the ADHD treatment group compared to 28% in the matched LQTS control group (p<0.001 [Figure]). Time-dependent use of stimulant and non-stimulant ADHD medication was associated with an increased risk for cardiac events dominated by syncope (HR=3.07; 95% CI 1.09-8.64; p=0.03) in the multivariate Cox model adjusted for time-dependent β-blocker use and prior cardiac events. Subgroup gender analyses showed that time-dependent ADHD medication was associated with an increased risk in male LQTS patients (HR=6.80, p=0.04).

Conclusion:
LQTS patients treated with ADHD medications have an increased risk for cardiac events during follow-up, and this risk is augmented in males.
Abstract 9441: Three-Dimensional Speckle Tracking Echocardiography for Evaluating Left Ventricular Rotation: An in vitro Validation Study using a Rotational Phantom Model
Authors: Park Austin , Zhu Meihua , Kimura Sumito , Bleck Rosie , Amacher Kacie , Streiff Cole , Ravi Sreyas , Ashraf Shahryar , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
Left ventricular (LV) rotation provides an index of regional and global LV function. Two-dimensional (2D) speckle tracking imaging (STI) has been used to calculate rotation, but is subject to computational errors due to through plane myocardial motion; 3D STI is not subject to such limitations. We qualitatively evaluated the accuracy of a new 3D wall-motion tracking program (3D-WMT) in terms of physiologically relevant degrees of LV rotation in a digitally controlled phantom.

Methods:
Eleven pig hearts with a fixed left ventricular volume of 60mL were passively rotated using a custom apparatus in a water bath. Each heart was mounted on a rotary actuator with the apex externally fixed to optimize the imaging angle and rotated at 0°, 3°, 5°, 7°, 10°, and 15°. Full-volume 3D image loops were acquired on a Toshiba Applio Artida™ ultrasound system. 3D-WMT values were compared to the angle of rotation of the phantom as defined by the actuator.

Results:
Linear regression between phantom rotation and 3D-WMT derived values demonstrated a strong correlation as rotation increased (R
2
= 0.93, P < 0.001). The mean and standard deviation for 3D-WMT derived rotation for 0° was 0.020° ± 0.016°, 3° was 0.228° ± 0.298°, 5° was 2.073° ± 1.031°, 7° was 4.590° ± 1.391°, 10° was 8.142° ± 1.173°, 12° was 10.289° ± 0.934°, and 15° was 13.059° ± 0.647°. Bland-Altman analysis showed 98% of data points within 95% CI.

Conclusion:
The Toshiba 3D-WMT program may be able to track LV rotation at physiologically relevant degrees of rotation.
Abstract 9457: Determining Three-Dimensional Catheter Location Using Single-Plane Fluoroscopy Only
Authors: Sra Jasbir , Belanger Barry , Palma Mark , Krum David
Published: April 2024

Introduction:
Catheter ablation of cardiac arrhythmias requires accurate navigation of a catheter in the heart. Biplane fluoroscopy is expensive and significantly increases radiation exposure. Single-plane fluoroscopy, although available in all interventional laboratories, does not provide three-dimensional (3D) catheter visualization. Thus, in a typical X-ray image seen during ablation, it is only possible to view the x-y axes; the actual depth of the cardiac catheter is not discernible.

Hypothesis:
We tested whether a set of digital image processing techniques and mathematical algorithms (APN Algorithm) could accurately construct 3D spatial orientation of an ablation catheter from single-plane fluoroscopy.

Methods:
Algorithms were designed to automatically determine 3D position and orientation of a radio-opaque mapping and ablation catheter using single-plane fluoroscopy only. Design consisted of: 1) capturing a stream of digital images from a single-plane fluoroscope; 2) detecting the image of the catheter in a subset of fluoroscopic images; and 3) applying pixel-level geometric calculations to the catheter image. The algorithms further included identifying the edges of the catheter at a subpixel level and determining the x-y-z location of the catheter. The 3D location of the catheter tip using single-plane images alone was then compared with 3D location as determined by two current gold standards: a 3D magnetic navigation system (CARTO, Biosense Webster Inc., Diamond Bar, CA), and biplane images taken in back projection technique (Ground Truth).

Results:
In a hexagonal phantom model (see figure), APN Algorithm revealed catheter location within 0.99 mm of Ground Truth.

Conclusion:
It is possible to determine the exact location of ablation catheters in three dimensions from single-plane fluoroscopic images without the need for biplane fluoroscopy. This approach could be extended to create 3D maps for catheter navigation and ablation.
Abstract 9468: Exploring the Missing Heritability of Complex Traits: Multiple Associated Variants Increase the Heritability Explained for Plasma Lipids and Coronary Artery Disease
Authors: Tada Hayato , Won Hong-Hee , Yang Jian , Peloso Gina M , Do Ron , Kathiresan Sekar
Published: April 2024

Background:
Plasma lipid levels as well as coronary artery disease (CAD) have been shown to be highly heritable-estimates range from 40%-60%. However, top variants detected by large-scale genome-wide association studies (GWAS) could explain only a fraction of the total variance in these phenotypes, raising the challenge for “missing heritability” to which multiple variants at a loci may contribute. Recently, a conditional and joint association analysis tool using summary-level statistics has been developed.

Methods and Results:
We performed a conditional and joint association analysis using GWAS summary-level statistics from two large consortiums: (1). the Global Lipids Genetics Consortium (GLGC) study, and (2). the CAD from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) study. These studies included up to 100,184 individuals from 46 studies for lipids, and 22,233 cases and 64,762 controls from 14 studies for CAD, respectively. We detected a number of loci which represent multiple associated independent SNPs with lipid traits within a locus (12 at 33 loci for high-density lipoprotein cholesterol [HDL-C], 10 at 35 loci for low-density lipoprotein cholesterol [LDL-C], 13 at 44 loci for total cholesterol [TC], and 8 at 28 loci for triglycerides [TG]) with genome-wide significance (p < 5x10
-8
), nearly doubling the heritability explained by the previous GWAS results (3.6% to 7.6% for HDL-C, 4.9% to 8.8% for LDL-C, 5.4% to 8.8% for TC, and 5.7% to 8.5% for TG). Multiple SNPs were also associated with CAD (3 at 15 loci, 9.6% to 11.4% of increased heritability). Among them, 9 SNPs in the CETP locus could explain as much as 2.6% of variance explained in HDL-C, 9 SNPs in the APOE locus explained 2.1% of that in LDL-C, 6 SNPs in the APOE locus explained 1.1% of that in TC, 7 SNPs in the LPL locus explained 1.7% in that of TG, and 2 SNPs in the CDKN2A/CDKN2B locus explained 2.8% of that in CAD trait. The prediction analysis validated our results.

Conclusions:
A portion of the missing heritability for lipid traits and CAD could be explained by joint effects from multiple variants at each locus. There should be multiple causal variants within a single locus, providing deeper understanding for various complex heritable traits.
Abstract 9545: Airway Management and Outcomes After Out of Hospital Cardiac Arrest in the CARES Network
Authors: McMullan Jason T , McNally Bryan , Gerecht Ryan , Bonomo Jordan , Robb Rachel , Wang Henry E ,   CARES Surveillance Group
Published: April 2024

Introduction:
While commonly performed during out of hospital cardiac arrest (OHCA) resuscitation, the optimal airway management strategy [endotracheal intubation (ETI), supraglottic airway (SGA), or no advanced airway device] remains unclear.

Hypothesis:
We tested the following hypotheses: 1) ETI and SGA result in similar rates of neurologically intact OHCA survival, and 2) compared with [ETI or SGA], the use of no advanced airway device results in similar rates of neurologically intact OHCA survival.

Methods:
We studied adult OHCA cases from 2011 with airway management information in the Cardiac Arrest Registry to Enhance Survival (CARES), a large multicenter North American OHCA registry. Primary exposures were: 1) ETI, 2) SGA, 3) no advanced airway. Primary outcomes were: 1) sustained ROSC, 2) ED survival, 3) survival to hospital discharge, 4) neurologically intact survival to hospital discharge (cerebral performance category 1-2). We defined propensity scores to characterize the probability of receiving ETI, SGA or no advanced airway. Using multivariable random effects regression to account for clustering by EMS agency, we compared outcomes between 1) ETI vs. SGA, and 2) [no advanced airway] vs. [ETI or SGA]. We adjusted for Utstein confounders (age, sex, race, witnessed arrest, use of AED initial rhythm, public location, response time) and propensity score.

Results:
Of 10,691 OHCA, there were 5591 (52.6%) ETI, 3110 (29.3%) SGA, and 1929 (18.2%) with no advanced airway. Unadjusted neurologically intact survival was: ETI 5.4%, SGA 5.2% and no advanced airway 18.6%. Compared with SGA, patients receiving ETI achieved higher sustained ROSC (OR 1.35; 95% CI 1.19-1.54), ED survival (1.36; 1.19-1.55), hospital survival (1.41; 1.14-1.76) and hospital discharge with good neurologic outcome (1.44; 1.10-1.88). Compared with [ETI or SGA], patients receiving no advanced airway attained higher ED survival (1.31; 1.16-1.49), hospital survival (2.96; 2.50-3.51) and hospital discharge with good neurologic outcome (4.24; 3.46-5.20).

Conclusions:
OHCA in the CARES network receiving no advanced airway exhibited superior outcomes than those receiving ETI or SGA. When an advanced airway was used, ETI was associated with improved outcomes compared to SGA.
Abstract 9547: AMPKa2 Deletion Promotes Vascular Smooth Muscle Cell Migration via Skp2 Upregulation and E-cadherin Downregulation
Authors: Song Ping , Zhou Yanhong , Coughlan Kathleen A , Dai Xiaoyan , Wu Yue , Xu Hairong , Wang Qilong , Zhu Huaiping , Zhang Wencheng , Viollet Benoit , Zou Ming-Hui
Published: April 2024

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are critical events in the progression of several vasculopathologies. Adenosine monophosphate-activated protein kinase (AMPK) has been shown to play a pivotal role in cellular proliferation and migration. However, the exact role of AMPK in VSMCs migration and its underlying molecular mechanisms remain elusive. We cultured mouse VSMCs isolated from wild-type (WT) C57BL/6J mice and either AMPKα2 or AMPKα1 homozygous-deficient (AMPKα2
-/-
, AMPKα1
-/-
) mice to investigate the molecular mechanisms of VSMCs migration. Deletion of AMPKα2, but not AMPKα1, led to increased phosphorylation of IκB kinase α (IκKα) and its downstream target nuclear factor κB2 (NFκB2)/p100 at serine 866/870. This resulted in pp100-S866/870 association with E3 ubiquitin ligase β-transducin repeat-containing protein (β-TrCP), which contributed to NFκB2/p52 induction from the proteolytic processing of the p100 precursor. Interestingly, acetylation of histone H3 at lysine 56 (AcH3-K56) resulted in association with histone deacetylase 3 (HDAC3) which was significantly enhanced in AMPKα2
-/-
VSMCs compared with either WT or AMPKα1
-/-
VSMCs. Moreover, the augmented association of p52/AcH3-K56 with the promoter of ubiquitin E3 ligase S-phase kinase-associated protein 2 (Skp2) was shown in AMPKa2
-/-
VSMCs by ChIP assay. Furthermore, AMPKα2 deletion caused E-cadherin downregulation, which is mediated by Skp2 and the ubiquitin-proteasome system. Skp2 siRNA abolished the increased migration of AMPKα2
-/-
VSMCs via E-cadherin upregulation. Finally, neointima formation after ligation of carotid artery was increased in AMPKα2
-/-
, but not AMPKα1
-/-
, mice and was associated with increased AcH3-K56 as well as reduction of both HDAC3 and E-cadherin. This compelling evidence indicates that deletion of AMPKα2, rather than AMPKα1, mediates VSMCs migration and the resultant neointimal formation after vascular injury. These events appear to occur via the NFκB2/Skp2/E-cadherin pathway.
Abstract 9565: Left Atrial “Reservoir” and “Passive Emptying” Reserve During Dobutamine Stress Have Prognostic Relevance for Patients With Dilated Cardiomyopathy
Authors: Matsumoto Kensuke , Tanaka Hidekazu , Tatsumi Kazuhiro , Yamadori Yoshiki , Sawa Takuma , Mochizuki Yasuhide , Miyoshi Tatsuya , Motoji Yoshiki , Fukuda Yuko , Kawai Hiroya , Hirata Ken-ichi
Published: April 2024

Background:
Left atrial (LA) structural and functional remodeling has been proposed as a predictor of cardiovascular outcomes. However, the importance of LA functional reserve for patients with depressed left ventricular (LV) function remains unclear. The objective of this study was thus to test the hypothesis that diminished augmentation of LA function during dobutamine stress may be associated with adverse cardiovascular events in patients with dilated cardiomyopathy (DCM).

Methods:
Sixty-seven DCM patients with ejection fractions of 35±9% were recruited, and LA strain was determined as the averaged global speckle-tracking longitudinal strain from apical 4- and 2-chamber views during dobutamine stress (20μg/kg/min). The systolic component of LA strain (S-LAs) was considered to reflect reservoir function, whereas the passive (S-LApass) and active emptying components (S-LAa) were considered to reflect conduit and booster-pump function, respectively. Event-free survival was tracked over a 17-month period.

Results:
Both relative increases in the LA reservoir (cut-off ≤10.9%; 71% sensitivity and 89% specificity, p<0.001) and in passive emptying function(cut-off ≤12.3%; 93% sensitivity and 85% specificity, p<0.001) during dobutamine stress were significantly predictive of adverse cardiovascular events. The patients with good LA “reservoir reserve” (ΔS-LAs >24.7% [median]) and “passive emptying reserve” (ΔS-LApass >32.5% [median]) had a significantly better prognosis than those with poor functional reserve (log rank p<0.001, respectively). Of particular importance was that the absence of “reservoir reserve” and “passive emptying reserve” was associated with the worst outcome (event rate: 90.0%), whereas the reverse condition was associated with the lowest adverse event rate (2.4%; p<0.001).

Conclusions:
Diminished augmentation of LA reservoir and passive emptying function is closely associated with adverse cardiovascular event.
Abstract 9569: Assessment of Bi-ventricular Functional Reserve During Dobutamine Stress Offers a Significant Prognostic Impact for Patients With Dilated Cardiomyopathy
Authors: Matsumoto Kensuke , Tanaka Hidekazu , Tatsumi Kazuhiro , Yamadori Yoshiki , Sawa Takuma , Mochizuki Yasuhide , Motoji Yoshiki , Miyoshi Tatsuya , Fukuda Yuko , Hirata Ken-ichi
Published: April 2024

Background:
Right ventricular (RV) function has been increasingly recognized as an important prognostic factor for heart failure patients as well as left ventricular (LV) function. The objective of this study was thus to investigate the prognostic importance of RV functional reserve in patients with dilated cardiomyopathy (DCM), and whether combined assessment of bi-ventricles can further enhance the prognostic evaluation.

Methods:
Seventy-three DCM patients with ejection fractions of 32±9% were recruited, and speckle-tracking echocardiography was used to assess both RV and LV functional reserve under dobutamine stress (20 mg/kg/min). RV contractile function was determined as peak global longitudinal strain from RV free wall (RV-free), whereas LV contractile function was calculated by averaging of peak global longitudinal strain from standard apical views (GLS). Event-free survival was tracked over an 18-month.

Results:
Multivariate Cox proportional-hazards analysis revealed that RV-free during dobutamine stress (ΔRV-free) as well as that in GLS (ΔGLS) were the two major independent predictors of cardiovascular events (p<0.001 and p=002, respectively). The Kaplan-Meier curve analysis disclosed that patients with RV reserve (ΔRV-free ≥16.5%) and with LV reserve (ΔGLS ≥10.0%) had a significantly better prognosis than those without (log rank p<0.01, respectively). Of special interest was that a pattern of both RV and LV functional reserve was associated with favorable outcome, whereas a pattern of neither RV nor LV functional reserve was associated with poor outcome (event rate: 2.3% vs. 82%, p<0.001). Patients with heterogeneous pattern of either RV or LV functional reserve had an intermediate risk of cardiac events (26.3%).

Conclusions:
RV functional reserve as well as LV was associated with prognostic impact in patients with DCM. Combined assessment of bi-ventricular functional reserve may play a key role for better management of such patients.
Abstract 96: Normalization of Left Ventricle Ejection Fraction, Not Initial Left Ventricle Ejection Fraction, is Associated with Outcomes After Cardiac Arrest
Authors: Grossestreuer Anne V , Perman Sarah M , Seder David B , Riker Richard R , Yao Yuan , Gaieski David F
Published: April 2024

Background:
Many patients with cardiac arrest are initially resuscitated but far fewer survive to hospital discharge. Post-arrest myocardial dysfunction is common and associated with higher mortality. We describe myocardial dysfunction and its association with outcome at 4 hospitals.

Objectives:
To discover the prevalence of left ventricle (LV) dysfunction in the first 24 hours post-arrest, the normalization of LV ejection fraction (LVEF) post-arrest, and determine their relationship to functional outcome at hospital discharge.

Methods:
A multicenter retrospective study of 464 patients who underwent post-arrest echocardiography at 4 hospitals with aggressive post-arrest protocols including therapeutic hypothermia. Abnormal LVEF was defined as <50%.

Results:
357/464 (77%) patients had an echo within the 1
st
24 hours post-arrest (mean age: 59±16 years, 62% male, 37% VT/VF, and 70% out-of-hospital). 206/357 (58%) had an abnormal LVEF within 24 hours. Analysis of survival and neurologic outcome of patients with an echo in the 1
st
24 hours as well as a subsequent echo prior to discharge (180/357; 50%) showed patients with an abnormal LVEF that recovered had the best outcomes, while patients who had an initially normal LVEF had the worst outcomes, regardless of whether their LVEF changed (Table 1).

Conclusions:
More than half of successfully resuscitated post-arrest patients had an abnormal LVEF in the 24 hours post arrest. An abnormal LVEF in the first 24 hours post-arrest did not predict negative outcome, and normalization of LVEF predicted good outcome. Prospective studies with echocardiography obtained at predetermined time points post-arrest are needed to further elucidate these findings.
Abstract 9615: PP1-12, a Novel Protein Phosphatase-1 Inhibitor, Ameliorates Ventricular Function After Myocardial Infarction in Rats
Authors: He Kunlun
Published: April 2024

Objectives:
Myocardial apoptosis has been known to induce heart function damage after myocardial infarction(MI).PP1-12 was designed to inhibit endoplasmic reticulum stress (ERS)-related apoptosis. In this study, we tested the effect of PP1-12 on cardiomyocyte apoptosis as well as on heart function after MI in rats.

Methods:
In vitro, neonatal rat cardiomyocytes were cultured and exposed to different concentrations of PP1-12 (0.3, 1, and 3 μg/mL) for 30 min followed by tunicamycin, which can induce ERS, for 36h. Apoptosis was measured using multiparameter high content screening. Phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α) and C/EBP homologous protein (CHOP) were determined by western blotting. In vivo, rats that survived MI were divided into six groups: Normal; Vehicle; Perindopril (2mg/kg/d) and PP1-12 (1,3 and10 mg/kg/d). After 4 weeks, transthoracic echocardiographic and hemodynamic parameters were evaluated. The cardiac tissue sections were subjected to TUNEL to assess the level of apoptosis.

Results:
In vitro, compared with the vehicle group, PP1-12 suppressed cell apoptosis with maximum protection at a concentration of 3μg/mL. Western blotting showed that PP1-12 protected cardiomyocytes against apoptosis by inducing eIF2α phosphorylation and down-regulating CHOP. In vivo, the LVEDD and LVESD were significantly decreased while the EF and FS were greatest increased by PP1-12 at 10mg/kg/d. The hemodynamic parameters including LVEDP, +dp/dtmax and -dp/dtmax were ameliorated by PP1-12. By calculating the apoptotic index, we found that PP1-12 at 10 mg/kg/d had a great anti-apoptotic effect.

Conclusions:
PP1-12 can efficiently inhibit apoptosis and improve heart function. The mechanism was proved to be associated with its ability to depress myocardial apoptosis induced by ERS.

Molecular structure of PP1-12:
Abstract 9618: Real-World Effectiveness of ICDs Implanted During Unplanned Medicare Hospitalizations
Authors: Chen Chih-Ying , Stewart Garrick C , Stevenson Lynne W , Bhatt Deepak L , Desai Manisha , Seeger John D , Williams Lauren , Jalbert Jessica J , Setoguchi Soko
Published: April 2024

Background:
Benefits of ICDs for primary prevention are well established in ambulatory HF population.

Aim:
To examine clinical effectiveness of primary ICDs in Medicare patients(pts) receiving the device during unplanned hospitalizations for HF or other acute conditions.

Methods:
Linking data from the CMS/National Cardiovascular Data Registry (NCDR®) ICD Registry™, a national HF registry, and the Medicare files (04-09), we identified 23,111 hospitalized pts ≥ 66 yrs with EF ≤35% who were eligible for primary ICDs from the ICD registry (ICD recipients) or the HF registry (non-ICD recipients). To account for potential bias due to ICD recipients being healthier, we employed latency analysis conditioning on the 1st 6 months survival and adjusted for high-dimension propensity score (hdPS). Cox models were used to derive adjusted hazard ratios (HRs) for all-cause mortality and sudden cardiac death (SCD).

Results:
The mean follow-up was 2.8 yrs. ICD recipients were younger, had lower EF, more prior cardiac hospitalizations, yet, non-ICD recipients had lower eGFR, more prior non-cardiac hospitalizations and non-CV comorbidities. ICD recipients had lower crude mortality than non-ICD recipients (Figure), but, the difference was most notable within the 1st 3-6 months of follow-up, likely reflecting selection of healthier pts for ICDs. Conditioning on the 1st 6-month survival and with hdPS adjustment, ICD use was not associated with a significant decrease in mortality (HR=0.91 95% CI=0.81, 1.00) or SCD (HR=0.95, 95% CI=0.78, 1.17). No significant treatment heterogeneity was observed among various demographic subgroups.

Conclusion:
ICD use did not appear to be associated with a lower mortality risk among non-ambulatory Medicare patients receiving primary ICD during unplanned hospitalization for HF or other acute conditions after accounting for selection bias and confounding. The effectiveness of primary ICD therapy likely did not differ among demographic subgroups.
Abstract 9685: Circulating Osteoglycin and NGAL/MMP9 Complex Concentrations are Associated With 1-year Major Adverse Cardiovascular Events After Coronary Angiography
Authors: Cheng Jin M , Akkerhuis Martijn , Oemrawsingh Rohit , Garcia-Garcia Hector M , van Geuns Robert-Jan , Meilhac Olivier , Malaud Eric , Piquer Dominique , Merle Delphine , Serruys Patrick W , Boersma Eric , Fareh Jeannette , Kardys Isabella
Published: April 2024

Background:
In previous proteomics experiments, we have found several proteins to be differentially expressed in human hemorrhagic carotid atherosclerotic plaques, which are considered as unstable, when compared to fibrotic plaques. Circulating concentrations of these proteins may predict cardiovascular outcome in patients with coronary artery disease.

Methods and results:
Blood samples were drawn in 768 patients who underwent coronary angiography for acute coronary syndrome or stable angina pectoris in a prospective biomarker study in a tertiary center between 2008 and 2011. We selected the 88 patients (cases) with major adverse cardiovascular events (MACE) within one year and 176 controls without MACE, matched on age, sex and number of diseased coronary vessels. MACE was defined as all-cause mortality, acute coronary syndrome, unplanned coronary revascularization and stroke. Thirteen circulating protein biomarkers that were previously found to have altered expression in hemorrhagic plaques were evaluated. Univariable conditional logistic regression analyses showed that baseline plasma neutrophil gelatinase-associated lipocalin (NGAL, p=0.038), osteoglycin (OGN, p=0.011), thrombospondin-2 (p=0.066), pro-B-type natriuretic peptide 1-108 (p=0.088), metalloproteinase inhibitor-1 (p=0.020) and NGAL/matrix metalloproteinase-9 complex (NGAL/MMP9, p=0.070) concentrations were higher in patients with MACE during follow-up. After further adjustment for established cardiovascular risk factors, OGN (OR 1.84 per SD of ln-transformed OGN unit, 95%CI 1.10-3.08, p=0.021) and NGAL/MMP9 (OR 1.76, 95%CI 1.04-2.98, p=0.034) were independently associated with MACE.

Conclusions:
Circulating OGN and NGAL/MMP9 complex may be promising biomarkers that are expressed in atherosclerotic plaques and that are independently associated with occurrence of MACE after coronary angiography.
Abstract 9772: Caloric Restriction Enhances Cardiomyocyte Autophagy via AMPK and ULK1 Pathways and Mitigates Postinfarction Cardiac Remodeling and Dysfunction
Authors: Watanabe Takatomo , Takemura Genzou , Kanamori Hiromitsu , Tsujimoto Akiko , Goto Kazuko , Ogino Atsushi , Morishita Kentaro , Fujiwara Hisayoshi , Fujiwara Takako , Mikami Atsushi , Minatoguchi Shinya
Published: April 2024

We previously reported that cardiomyocyte autophagy is an innate mechanism that protects against progression of postinfarction cardiac remodeling. In the present study, we hypothesized that caloric restriction (CR), a potent inducer of autophagy, enhances cardiomyocyte authophagy and mitigates post-infarction cardiac remodeling and dysfunction.Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. After one week of MI, mice were randomly divided into the following four groups. The control group was fed ad libitum (100%; n=6). Others were fed restricted diet respectively 80%, 60%, and 40% of the control mice’s total calorie (n=6 each). Three weeks later, we evaluated the left ventricular (LV) function. The dilatation and hypofunction of the LV were apparent in the control group: LV diastolic dimension (LVDd) = 4.9±0.1 mm; LV ejection fraction (LVEF) = 27±3.3%; and +dP/dt = 4677±277 mmHg/s. However, both dilatation and hypofunction were significantly mitigated in groups undergoing CR: in 80%, 60%, and 40%CR, respectively, LVDd = 4.0±0.1 mm, 3.4±0.2 mm and 4.0±0.1 mm; LVEF = 36±2.8%, 51±4.3% and 43±1.5%; and +dP/dt = 6849±221 mmHg/s, 7758±638 mmHg/s and 6923±553mmHg/s, among which the 60% CR group showed the strongest therapeutic effect on postinfarction cardiac remodeling (control vs. 60% CR: p<0.001). Cardiomyocyte autophagy was markedly activated in CR groups as evidenced by the overexpressed microtubule-associated protein 1 light chain 3-II (LC3-II) and specific ultrastructural findings including autophagosome formation. Myocardial ATP contents were found significantly increased in the 60% CR group compared with other groups. The activities of AMP-activated protein kinase (AMPK), ULK1 (a homolog of yeast Atg1) and silent information regulator-1 (Sirt1) were enhanced in hearts of the CR groups. Chloroquine, an inhibitor of autophagy, brought about deleterious outcomes, accompanying inactivation of AMPK-ULK1 but not influencing Sirt1 activity.In conclusion, caloric restriction enhances cardiomyocyte autophagy via AMPK-ULK1 pathway to enhance energy status and ameliorates left ventricular remodeling in the postinfarction heart; the optimal caloric restriction is suggested to be 60%.
Abstract 9782: Sudden Death in U.S. College Athletes: Incidence, Causes, and Implications for Preparticipation Screening
Authors: Maron Barry J , Haas Tammy S , Murphy Caleb J , Ahluwalia Aneesha , Rutten-Ramos Stephanie
Published: April 2024

Introduction:
Frequency with which cardiovascular-related sudden deaths (SD) occur in competitive athletes importantly impacts considerations for the most appropriate preparticipation screening strategy, particularly the potential value of incorporating the12-lead ECG.

Hypothesis:
Unsuspected cardiovascular disease may not be the predominant cause of sudden death in college athletes.

Methods:
We assessed databases (including autopsy reports) from both the U.S. National Sudden Death in Young Athletes Registry and National Collegiate Athletic Association (NCAA) (2002-2011) to define the incidence and causes of SD in college student-athletes.

Results:
Over the 10 year period, 182 SDs occurred (ages 20 ± 1.7; 85% males; 64% white): 52 resulting from suicide (n = 31) or drug abuse (n = 21), and 64 probably or likely attributable to cardiovascular causes. Of the 64 athletes, 47 had a confirmed post-mortem diagnosis, most commonly hypertrophic cardiomyopathy in 21, and congenital coronary anomalies in 8. The 4,052,369 athlete participations (in 30 sports over 10 years) incurred mortality risks of: suicide and drugs combined, 1.3/100,000 athlete participation-years (5 deaths/year); documented cardiovascular disease, 1.2/100,000 (4 deaths/year); and cardiovascular diseases judged reliably detectable by screening ECGs, 0.7/100,000 (2-3/year). Notably, cardiovascular deaths were significantly (5-fold) more common in African-American athletes than whites (3.8 vs. 0.7 100,000; p <0.01), but were less frequent in NCAA college athletes than in the general population of the same age (p < 0.01).

Conclusions:
In college student-athletes, SD risk due to cardiovascular disease is relatively low, with mortality rates similar to that of suicide and drug abuse, significantly less than expected in the general population, but highest in African-Americans. About 40% of confirmed cardiovascular deaths may not have been reliably detected by preparticipation screening, even with 12-lead ECGs.
Abstract 9788: Exosomes Released From GATA-4 Overexpressed Mesenchymal Stem Cells Enrich Anti-apoptotic microRNAs and Mediate Cardioprotection
Authors: Yu Bin , Gong Min , Wang Jingcai , Wang Yigang , Millard Ronald W. , Ashraf Muhammad , Xu Meifeng
Published: April 2024

Increased evidences indicate that exosomes play an important role in cell to cell communication and exert regulatory function by shuttling bioactive molecules. We have previously reported that overexpression of GATA-4 in mesenchymal stem cells (MSC) (MSC
GATA-4
) increased cardioprotection. In this study, we investigated if this action was associated with microRNAs (miRs) carried by exosomes. Our studies indicated: 1) Exosomes isolated from MSC increased cultured neonatal cardiomyocyte (CM) survival under hypoxic environment for 48 hours in a concentration-dependent manner (Fig. A). The cardioprotection was partially attenuated by treating MSC with GW4869 (10μM), an exosome release inhibitor and enhanced in the exosomes obtained from MSC
GATA-4
(Exo
GATA-4
) (Fig. B). 2) Exo
GATA-4
well maintained mitochondria membrane potential of CM assessed by JC-1 staining and expressed as a ratio of aggregate to monomer fluorescence (Fig. C). 3) The expression of pro-apoptotic miR-15b, miR-34c in CM was up-regulated, and anti-apoptotic miR-19a, miR-451 was down-regulated following exposure to hypoxia (Fig. D). 4) The expression of miR-19a and miR-451 was higher in MSC
GATA-4
(Fig. E) and Exo
GATA-4
(Fig. F). 5) Treatment CM with Exo
GATA-4
dramatically reversed the alteration of these miRs in CM which was induced by exposure to hypoxia and resulted in an increase of expression of miR-19a and miR-451 (Fig. G). It is
concluded
that GATA-4 enhanced MSC mediated cardioproteciton, which was associated with a transfer of exosomes enriched anti-apoptotic miRs from MSC to CM.
Abstract 9795: Deficiency of Phospholipase A
2
Receptor Exacerbates Airway Inflammation and Pulmonary Vessel Remodeling After Ovalbumin Treatment Through Impaired Clearance of Secretory Phospholipase A
2
Authors: Tamaru Shun , Mishina Hideto , Watanabe Yosuke , Watanabe Kazuhiro , Fujioka Daisuke , Takahashi Soichiro , Suzuki Koji , Nakamura Takamitsu , Obata Jun-ei , Kawabata Kenichi , Yokota Yasunori , Hanasaki Kohji , Kugiyama Kiyotaka
Published: April 2024

Secretory phospholipase A
2
(sPLA
2
) plays a critical role in the genesis of various inflammatory diseases through pro-inflammatory eicosanoids. We previously discovered a cell surface receptor for sPLA
2
(PLA
2
R) and showed that PLA
2
R as well as its ligands, sPLA
2
groups IB and X, were expressed in the lung, but the pathogenic role of PLA
2
R in the lung is unknown. This study examined the role of PLA
2
R in the pathogenesis of inflammation of the airway and pulmonary vessels using PLA
2
R knockout (KO) mice.

Methods and Results:
Allergic lung inflammation was induced by immuno-sensitization with ovalbumin (OVA). In immunohistochemical analysis, PLA
2
R was detected in airway smooth muscle cells in PLA
2
R wild type (WT) lung. PLA
2
R KO mice showed a significantly greater infiltration of inflammatory cells around the airways and blood vessels (1.7 fold greater than WT mice) and a greater wall thickness of blood vessels (1.3 fold greater than WT mice) after OVA-treatment. PLA
2
R KO mice had significantly higher levels of sPLA
2
-IB and -X in bronchoalveolar lavage fluid (BALF) after OVA treatment than WT mice (sPLA
2
-IB, 34.4 ± 3.2 pg/mL vs. 13.5 ± 1.8 pg/mL; sPLA
2
-X, 9.8 ± 2.4 pg/mL vs. 3.9 ± 0.9 pg/mL; respectively, p < 0.05 for both). This difference was associated with greater levels of eicosanoids (LTB
4
, CysLTs and PGD
2
), and Th2 cytokines (IL-4 and IL-5) and higher numbers of eosinophils and neutrophils in OVA-treated BALF of PLA
2
R KO mice than WT mice. When
125
I-labeled sPLA
2
-IB was endotracheally instilled into the lung,
125
I-sPLA
2
-IB was cleared much more slowly from BALF of PLA
2
R KO mice than from WT mice (instilled
125
I-sPLA
2
-IB remaining in BALF at 2 hrs; 40% vs. 10%, respectively). Degradation of instilled
125
I-sPLA
2
-IB, assessed by TCA-soluble radioactivity in BALF, was lower in PLA
2
R KO mice (70% of WT mice at 4 hr). In experiments using cultures of airway smooth muscle cells, binding, internalization and degradation of
125
I-sPLA
2
-IB were lower in PLA
2
R KO cells than WT cells, supporting the impaired clearance of sPLA
2
from lungs of PLA
2
R KO mice.

Conclusions:
PLA
2
R-deficiency increased sPLA
2
-IB and -X levels in the lungs due to impaired clearance from the lung, leading to exaggeration of airway inflammation and pulmonary vessel remodeling after OVA treatment in a mouse model.
Abstract 9841: Expression of Mitochondrial Fusion Proteins is Increased in Hibernating Hearts Following Bypass Surgery
Authors: Long Eric K , Butterick Tammy A , Duffy Cayla , Cabrera Jesús A , Lindsey Meghan , Holley Christopher T , Ward Herbert B , McFalls Edward O , Kelly Rosemary F
Published: April 2024

Background:
Based on clinical studies, regional function within hibernating myocardium may not return to normal immediately following successful bypass surgery (CABG). We hypothesized that the mitochondrial proteome within chronically ischemic hibernating hearts does not fully recover early post-CABG and may in part, contribute to submaximal myocardial oxygen expenditure.

Methods:
Twelve pigs underwent thoracotomy with placement of a constrictor around the LAD artery and had reduced regional function 12 weeks later. Six pigs then underwent sternotomy and off-pump revascularization with a left internal mammary artery graft to the LAD just beyond the chronic stenosis. A patent graft was confirmed by CTA at 4 weeks post-CABG. Five additional pigs underwent a SHAM operation and served as controls. Prior to sacrifice, regional blood flows by μspheres were determined at baseline and during high dose dobutamine (40 μg/kg/min). Post-sacrifice, the content of mitochondrial electron transport chain (ETC) and fusion proteins was determined by western gels.

Results:
In the hibernating regions that underwent CABG, maximal blood flow during dobutamine was lower than Control hearts (2.5±0.2 vs 3.5±0.2 ml/min/g; NS). As shown in the Figure, the content of mitochondrial ETC proteins, when normalized to SHAM hearts, did not recover in hibernating hearts that had undergone CABG. Compared with non-revascularized hibernating hearts however, hearts that had undergone CABG demonstrated increased expression of fusion proteins.

Conclusion:
Despite successful revascularization of hibernating heart tissue, maximal blood flow in response to a catecholamine challenge is submaximal at 4 weeks following CABG, at a time that the expression of ETC proteins has not recovered to normal. Mitochondrial fusion proteins are increased however, and may be an important dynamic mitochondrial process to restore maximal energetics of hibernating hearts following CABG.
Abstract 9869: Collagen-plug based Vascular Closure Devices can they Decrease Vascular and Bleeding Complications occurring After Balloon Aortic Valvuloplasty ?
Authors: Leclercq Florence , Delseny Delphine , Nogue Erika , Nagot Nicolas , Gervasoni Richard , Roubille Francois , Macia Jean C
Published: April 2024

Introduction:
Whereas they are controversial after coronary angioplasty, we assessed the hypothesis that the use of vascular closure devices (VCDs) after balloon aortic valvuloplasty (BAV), may decrease vascular and bleeding complications of the procedure.

Methods:
We conducted a prospective analysis of consecutive patients who underwent BAV in our center between 2009 and 2012. BAV was performed by femoral retrograde technique using 8 to 10 French sheaths. Group 1 consists of patients from which femoral puncture hemostasis was obtained with use of a 8 French collagen-plug based VCD (Angio-seal, St Jude Medical), group 2 consists of patients who have manual or mechanical compression (FemoStop, RADI Medical systems) of the femoral puncture site. We collected all major in-hospital adverse events, major bleeding (≥ BARC 3) and serious vascular access complications (pseudoanerysm, arterio venous fistula or acute limb ischemia).

Results:
Overall, 180 patients were included in that study. Indications for performing BAV included bridge to surgery (n=27), bridge to TAVI (n=71), therapy before extra cardiac surgery (n=35) or palliative (n=47). The two groups had similar median age (84 years) and previous lower extremity artery disease (overall n= 47, 26%, p=0.79). Vascular and bleeding complications occurred overall among 11.7% of the patients (n=21) and were more frequent in group 1 (p=0;02; table 1). Five of the 6 patients who suffered acute limb ischemia belonged to this group (p= 0.15). The rate of complications was the same whatever was the size if the sheath used.

In conclusion, this study shows that collagen-plug based vascular closure devices increase vascular and bleeding complications occurring after balloon aortic valvuloplasty. Except in high risk bleeding patients, in whom femoral hemostasis can be difficult to obtain, the systematic use of these devices in a population of elderly patients with often advanced limb atherosclerosis, is questionable.
Abstract 9894: Rho-associated Kinase Activity and Cardiovascular Disease Prediction
Authors: Kajikawa Masato , Maruhashi Tatsuya , Iwamoto Yumiko , Matsumoto Takeshi , Iwamoto Akimichi , Hidaka Takayuki , Kihara Yasuki , Noma Kensuke , Nakashima Ayumu , Liao James K , Higashi Yukihito
Published: April 2024

Background:
Cardiovascular diseases are associated with chronic activation of Rho-associated kinase. Rho-associated kinase activity is significantly correlated with endothelial function and Framingham risk score, but there is no information on the prognostic value on Rho-associated kinase activity.

Methods:
We evaluated Rho-associated kinase activity in peripheral leukocytes by Western blot analysis in 633 subjects who underwent health-screening examination at Hiroshima University Hospital. We assessed the associations between Rho-associated kinase activity and first major cardiovascular events (death from cardiovascular causes, myocardial infarction, and stroke), death from cardiovascular causes, acute myocardial infarction, stroke, revascularization (percutaneous coronary intervention, coronary artery bypass grafting) and hospitalization for heart failure.

Results:
During a median period of 42.0 months (interquartile range, 24.4 to 56.6 months) of follow-up, 29 subjects died (10 from cardiovascular causes), 2 myocardial infarction, 20 revascularization, 15 stroke, and 17 hospitalization for heart failure. After adjustment for age, sex, cardiovascular risk factors and other relevant variables, Rho-associated kinase activity remained a strong independent indicator of first major cardiovascular events (hazard ratio, 2.19; 95 percent confidence interval, 1.35 to 3.70; P=0.002), death from cardiovascular disease (hazard ratio, 2.57; 95 percent confidence interval, 1.18 to 6.60; P=0.002), stroke (hazard ratio, 2.14; 95 percent confidence interval, 1.24 to 3.86; P=0.006) and revascularization (hazard ratio, 2.68; 95 percent confidence interval, 1.60 to 4.66; P<0.001).

Conclusions:
Leukocyte Rho-associated kinase activity may be a new biomarker of cardiovascular events. These findings suggest that inhibition of leukocyte Rho-associated kinase activity may be a therapeutic target for prevention of cardiovascular events.